National Guideline For Kala-azar Case Management 2016kalacorebd.com/wp-content/uploads/2016/04/Kala-azar-Case-Managmen… · i | P a g e National Guideline For Kala-azar Case Management

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National Guideline For

Kala-azar Case Management 2016 3

rd Edition

National Kala-azar Elimination Program (NKEP)

Communicable Disease Control (CDC)

Disease control Unit

Directorate General of Health Services (DGHS)

Ministry of Health and Family Welfare (MoHFW)

Government of the People’s Republic of Bangladesh

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NAMES OF THE MEMBERS IN UPDATING THE

NATIONAL GUIDELINE FOR KALA-AZAR CASE MANAGEMENT 2016

Chief Adviser:

Prof. Dr. Abul Kalam Azad

Director General

Directorate General of Health Services

Advisor

Prof. Dr. Sanya Tahmina

Director, Disease Control & Line Director, CDC


Chairman Prof. Dr. Md. Ridwanur Rahman

Head Department of Medicine

Shaheed Suhrawardy Medical College Hospital, Dhaka

Member Secretary

Dr. A.F.M. Akhtar Hossain

Deputy Programme Manager, Kala-azar Elimination Program

Communicable Disease Control, Director General of Health Services

Technical Writer

Dr. M. G. Mostafa,

Technical Advisor, NKEP, CDC, DGHS-Dhaka

Board of Editors:

1. Prof. Dr. Baizid Khoorshid Riaz, Director, NIPSOM, Dhaka

2. Prof. Dr. Be-Nazir Ahmed, Dept. of Microbiology, NIPSOM, Dhaka

3. Prof. Dr. Akhtarun Nahar Nira, Dept. of Microbiology, SSMCH, Dhaka

4. Prof. Dr. Abul Khair Mohammad Shamsuzzaman, Dept. of Microbiology, RMCH, Rajshahi

5. Dr. Abdus Sobur, Deputy Director, CDC, DGHS-Dhaka

6. Dr. AKM Manjurul Islam, Deputy Director, M&PDC, CDC, DGHS-Dhaka

7. Dr. Kamar Rezwan, NPO, WHO-Bangladesh, Dhaka

8. Dr. Dinesh Mondal, Senior Scientist, icddr,b, Mohakhali, Dhaka

9. Dr. M. G. Mostafa, Technical Advisor, NKEP, CDC, DGHS-Dhaka

10. Dr. Robed Amin, Associate Professor, Medicine, DMCH, Dhaka

11. Dr. Shahjada Selim, Assistant Professor, Endocrinology, BSMMU, Dhaka

12. Dr. Md. Abdullah Yusuf, Assistant Professor of Microbiology, NINH, Dhaka

13. Dr. Mostafa Kamal, Civil Surgeon, Mymensingh District, Mymensingh

14. Dr. Parikshit Kumar Parh, Deputy Civil Surgeon, Mymensingh District, Mymensingh

15. Dr. Md. Moshihur Rahman, UH&FPO, Trishal UHC, Trishal, Mymensingh

16. Dr. Robiul Islam, RMO, Trishal UHC, Trishal, Mymensingh

17. Dr. Sabera Sultana, NPO, Neglected Tropical Disease, WHO-Bangladesh, Dhaka

18. Dr. Mizanur Rahman, National Consultant, KEP, WHO-Bangladesh, Dhaka

19. Dr. Ariful Basher, In charge of SKKRC, Infectious & Tropical Disease, MMCH, Mymensingh

20. Dr. Md. Mahbubur Rashid, SMO, Kala-azar Elimination Program, CDC, DGHS-Dhaka

21. Dr. AKM Kayum, SMO, Kala-azar Elimination Program, CDC, DGHS-Dhaka

22. M Mamun Huda, Assistant Scientist, icddr,b, Mohakhali, Dhaka

23. Dr. Mohammad Sohel Shomik, Deputy Program Coordinator, KalaCORE, Dhaka

24. Md. Shahadot Hossain, Manager, M&E, KEP, CDC, DGHS-Dhaka

25. Ms. Fahima Yeasmin Lira, Data Manager, KEP, CDC, DGHS-Dhaka

26. Ms. Shyla Faria, Procurement Officer, KEP, CDC, DGHS-Dhaka

27. Mr. Pankaj Kumar Ghose, Data Management Officer, KEP, CDC, DGHS-Dhaka

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ABREVIATIONS

AIDS Acquired Immune Deficiency Syndrome

ARV Anti-retroviral Therapy

BCC Behavior Change Communication

CL Cutaneous Leishmaniasis

DDT Dichloro Diphenyl Trichloroethane

DGHS Directorate General of Health Services

H&FWC Health & Family Welfare Centre

HIV Human Immuno Deficiency Virus

ICT Immune-chromatographic test

IEDCR Institute of Epidemiology Disease Control and Research

IPD Inpatient department

IRS Indoor Residual Spray

IM Intramuscular

ITN Initial Training Network

IV Intravenous

KA Kala-azar

LAmB Liposomal Amphotericin B

MIS Management Information System

MO Medical Officer

MOU Memorandum of Understanding

NGO Non-Government Organization

NKA New Kala-azar

OPD Outpatient department

PCR Polymerase Chain Reaction

PKDL Post Kala-azar Dermal Leishmaniasis

RD Rural Dispensary

RDT Rapid Diagnostic Test

RKA Retreatment Kala-azar

rK39 RDT rK39 Rapid Diagnostic Test

RTAG Regional Technical Advisory Group

SC Sub Centre

SEARO South East Asian Regional Office

SOP Standard Operation Procedure

SSG Sodium Stibogluconate

TB Tubercle Bacillus

UHCs Upazila Health Complexes

UH&FPO Upazila Health and Family Planning Officer

WHO World Health Organization

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Message Bangladesh has successfully accomplished and achieved numbers of targets under Millennium

Development Goal‟s (MDGs) and is committed to achieve ambitious set of targets under “Sustainable

Development Goals (SDGs)” aiming to transform Bangladesh a middle income country by 2030. The

country is committed to achieve “Good Health and Well-being (SDGs-3)” aiming to ensure healthy lives

and promote well-being for all; bring an end of wave of Malaria, Filaria, Kala-azar, Tuberculosis,

HIV/AIDS and other communicable diseases; attain universal health coverage; and provide access to

safe-effective medicines and vaccines for all.

Bangladesh seeks to create conditions whereby the people of the county have the opportunity to reach and

maintain the highest attainable level of health. The Ministry of Health & Family Welfare (MoHFW) being

the responsible ministry ensures health and well-being of the citizens by expanding access to quality and

equitable healthcare; develops people healthier, happier and economically productive; and make

Bangladesh a middle income country by 2021. We are also committed to achieving the universally agreed

goals in specific areas as set out in the declarations of various world summits including SDGs by 2030.

It is indeed very depressing information to learn that Kala-azar, a neglected tropical disease, claims more

than 50,000 lives every year worldwide. The disease being endemic to central and north part of

Bangladesh for many decades has created public health problems and affected poor and the vulnerable

group of people in the community. However, I feel very happy to know that the National Kala-azar

Elimination Program (NKEP) of Disease Control Division, Communicable Disease Control of Directorate

General of Health Services (DGHS) has developed strategies to eliminate the disease from the country.

I am pleased to know that NKEP has updated the existing treatment guideline: „National Guideline for

Kala-azar Case Management 2016‟. I believe this management guideline will provide strategies,

principles, course of actions and recommendations to the concerned health professionals and help them to

improve the approach of treatment, management, and prevention of Kala-azar at all levels of health

facilities in Bangladesh.

I would like to congratulate technical experts, clinicians, doctors, researchers and health managers for

taking active part in the development of „National Guideline for Kala-azar Case Management 2016‟. I

wish every success of National Kala-azar Elimination Program for taking a leadership role in the

elimination of Kala-azar disease from Bangladesh.

Joy Bangla, Joy Bangabandhu.

Long live Bangladesh

Photo

Honourable Prime Minister

Government of the People‟s Republic of

Bangladesh

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Message

Ministry of Health & Family Welfare (MoHFW) is committed to comprehend Vision 2021 by developing

healthier, happier and economically productive citizens of Bangladesh. The MoHFW being the leading

and responsible ministry has been creating conditions whereby the people will be able to achieve and

maintain the highest attainable level of health, and to ensure access to quality healthcare services in

Bangladesh. The MoHFW has been planning to improve quality, equity and efficiency towards universal

health coverage and would like to achieve Sustainable Development Goals (SDGs) by 2030.

The Kala-azar disease load, being very high in South-Asian region especially in Bangladesh, India and

Nepal, comprises more than fifty percent of the total global disease burden. The government of

Bangladesh, India and Nepal, therefore, signed a memorandum of understanding in 2005 and pledged

their commitment to eliminate Kala-azar from the region and reset a target to reduce the incidence rate of

KA less than 1 case per 10 000 populations by the year 2017. This target has been set in a WHO/SEARO

Regional Summit of Health Minister‟s Meeting held on 9 September 2014 in Dhaka, Bangladesh.

Signatories to this MoU were Bangladesh, Bhutan, India, Nepal and Thailand.

The National Kala-azar Elimination Program (NKEP) of Disease Control Division, Communicable

Disease Control (CDC) of Directorate General of Health Services (DGHS) has developed strategies to

eliminate the disease from the country with a goal to improve the health status of the vulnerable groups

and at-risk population living in Kala-azar endemic areas by eliminating the disease and achieving the

regional and national target by the year 2017. I am happy to know that the NKEP has already achieved the

national target in October 2016.

I have the pleasure to know that the NKEP has updated existing treatment guideline titled: “National

Guideline for Kala-azar Case Management 2016”. I believe the concerned health personnel at every

health facility will receive proper guidance from the national guideline in treating, managing and

preventing Kala-azar disease in the endemic areas of Bangladesh.

I would like to extend my sincere thanks and gratitude to all technical experts, clinicians, doctors,

researchers and health managers for taking active part in the development and updating the national

guideline for Kala-azar Case Management 2016‟. Last but not least, I would like to congratulate all the

staffs of NKEP of Disease Control Unit, CDC of DGHS-Dhaka.

Joy Bangla, Joy Bangabandhu.


Photo

Honourable Minister

Ministry of Health & Family Welfare

Govt. of the People‟s Republic of Bangladesh

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Message

The Ministry of Health & Family Welfare (MoHFW) is the responsible ministry for improving quality,

equity and efficiency of health services towards attaining universal health coverage and achieving

sustainable development goals by 2030 through strengthening governance and stewardship of health

sectors; improving equitable access to and utilization of quality health services; and establishing a high

quality health workforce to be available across the health system. The MoHFW through its coordinated

efforts aims to comprehend long term impacts in the improvement of health indicators that are targeting to

reduce the disease mortality rates, improving nutritional situation, and preventing all types of

communicable and non-communicable diseases in Bangladesh. Bangladesh is a hot-humid tropical country providing an excellent breeding environment for the growth

and multiplication of sandflies, the only vector for Kala-azar disease to transmit within the poor

community. Despite high endemicity prevailing for a period of last few decades, the incidence rate of

Kala-azar, however, has been decreasing remarkably since 2005 as a result of coordinated efforts and

effective strategies implemented by the NKEP of Disease Control Division, Communicable Disease

Control (CDC) of Directorate General of Health Services (DGHS); and as of October 2016, the country

has achieved national target of incidence rate of less than 1 case per 10 000 populations. I am glad to know that NKEP of Disease Control Division, CDC of DGHS is going to publish „National

Guideline for Kala-azar Case Management 2016‟ which will be acting as a strategic guiding document for

all level of health facilities and will be using as a resource text for all physicians, clinicians, researchers

and nurses involved in the treatment and management of Kala-azar disease in Bangladesh.

I would like to congratulate and express my heartiest thanks and gratitude to all the staff of NKEP, CDC,

DGHS and all those experts and resource persons who were involved in every endeavor to the

development of this treatment guideline.

I wish every success of NKEP, Disease Control Division, CDC of DGHS for eliminating Kala-azar

disease from Bangladesh.

Joy Bangla, Joy Bangabandhu


Honourable State Minister



Photo

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Message

The Ministry of Health & Family Welfare (MoHFW) has developed 4th Health Nutrition Population

Sector Program (HNPSP: 2017-2022) focusing to increase access to quality healthcare and improve

equity along with efficiency in both service delivery and health systems strengthening. The 4th HNPSP

aims to achieve Vision 2021 by materializing number of Operational Plans (OPs) and CDC‟s OP intends

to reduce the burden of communicable diseases from the country in general and achieve elimination of

Kala-azar, a neglected tropical communicable disease, by 2017.

We have identified number of issues and challenges that need attention to eliminate Kala-azar from the

country. The PKDL patients for example are acting as a potential reservoir and do not always come to the

treatment facilities, therefore, the low coverage of PKDL poses a great challenge; re-emergence of the

disease as a result of resistance to anti-leishmania drug may become a great threat; provisions of the early

diagnosis and prompt treatment may be jeopardized because of the patient‟s low level of health seeking

behavior; quality of integrated vector management will be at stake because of the non-availability of

effective insecticides; asymptomatic cases of Kala-azar may act a sources for transmission of disease in

the community; and cross-border issue may also contribute disease transmission.

We have set some functional activities to make the elimination of kala-azar faster and effective. In order

to able to make elimination successful, we should continue active case search to be done on a six month

interval within the next five years up to 2021; procure effective drugs, diagnostic kits, insecticides and

other logistics for the program; conduct operational research relevant to diagnose, treatment and vector

management; and carry out training and orientations for the clinicians, researchers, nurses, and other

relevant health staff using the “National Guideline for Kala-azar Case Management 2016 as resource

material.

I would like to express my great appreciation to the Disease Control Unit, Communicable Disease

Control (CDC) of DGHS for publishing „National Guideline for Kala-azar Case Management 2016‟ to

improve not only the cases but to prevent and control of Kala-azar from Bangladesh.

Secretary


Photo

Honourable Secretary



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Message

I am pleased to know that National Kala-azar Elimination Program (NKEP) of Disease Control Division,

Communicable Disease Control (CDC) of the Directorate General of Health Services (DGHS) has

developed “National Guideline for Kala-azar Case Management 2016”aming to train the clinicians,

doctors, nurses and other relevant health professional. I am confident that the clinicians will find the

present guideline as a ready reference text for consultation during the course of daily clinical works. I

believe the present guideline articulates the recent and upgraded treatment procedures and will serve as a

standard tool for the treatment and prevention of Kala-azar disease in Bangladesh.

Bangladesh Government is committed to eliminate Kala-azar from country by 2017 and the country has

already achieved national elimination target of less than 1 case of Kala-azar per 10 000 populations

(Incidence rate is 0.28 in October 2016) through implementing National Kala-azar Elimination Program

(NKEP) strategies and activities. Early diagnosis and prompt treatment with vector control are some of

the main approaches targeted for the elimination of the disease. A number of conventional and innovative

interventions including „Active Case Search‟ through index-based approach, camp-based approach, and

blanket house-to-house search applied during the 3rd HPNSD contributed in the achievement.

The production of “National Guideline for Kala-azar Case Management 2016” is regarded as an essential

resource to pursue policies and regulations in the management of drug therapy in all stages of kala-azar

disease recovery. This treatment guideline summarizes recommended treatments for common forms of

New Kala-azar (NKA), Post Kala-azar Dermal Leishmaniasis (PKDL) and Cutaneous Leishmaniasis

(CL); provides information to make the kala-azar treatment standardized throughout the health system;

assists clinicians and patients in making decisions about healthcare for specific clinical circumstances

such as Kala-azar Treatment Failure (KATF), Relapse Kala-azar (RKA) and Adverse Drug Reactions

(ADR); and promotes rational use of anti-leishmania drugs in hospitals, upazila health complexes and

other clinic settings.

I would like to extend my thanks and gratitude to all technical experts including clinicians, researchers,

health managers and other relevant health professional for updating the present guideline, evaluating the

effectiveness of anti-leishmania drug, assessing and controlling the adverse drug reactions, and proposing

the important strategy for improving medicine use in Kala-azar health care management system.

I wish all the members of NKEP a great success.

Prof. Dr. Abul Kalam Azad

Director General

Directorate General of Health services

Photo

Honourable Director General

Directorate General of Health Services Ministry of Health & Family Welfare

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Message

Kala-azar is a major neglected tropical disease and a major public health problem in Bangladesh. The

disease commonly affects the poor members in the community in developing countries and has been

persisting in this sub-continent for quite a long period, and is responsible for number of deaths each year.

As a collateral benefit of blanket DDT spraying during malaria eradication program during 1960s, the

kala-azar disease was controlled to major extent in our country. However, in late 1980s it had re-emerged

and spread quickly in the central and north of Bangladesh.

The National Kala-azar Elimination Program (NKEP) has been initiated in 2007. Three indicators such as

kala-azar detection rate, treatment completion rate and vector control coverage rate have been set. The

early diagnosis and prompt treatment of the disease are ensured, the surveillance and monitoring system is

strengthened, and the indoor residual spraying (IRS) is instituted. We are committed to achieve national

goal by 2017. This optimistic and realistic goal could be apprehended by realizing the most important

favorable factors such as (i) biological factor where the human is only reservoir for Kala-azar parasite and

Phlebotomus argentipes sandfly is probably the only species transmitting disease in Bangladesh.

The Kala-azar eliminate strategies aim to diagnose and treat the cases and control the vector. Kala-azar

case detections and management along with the improvement of treatment outcome indicators are

regarded as the important criteria for monitoring the progress of activities. Moreover, the vector (sandfly)

management with characteristics of sandfly, its life cycle, behavior & bionomics and control measures are

also very important to eliminate the disease from the country. In Bangladesh, India and Nepal, there is

only one type of sandfly found which is very sensitive to all types of insecticides. The Indoor Residual

Spraying (IRS) is confined to only household and cattle shed, and limited to community in a geographical

areas affecting only to 98 upazilas of Bangladesh.

The recent and upgraded „National Guideline for Kala-azar Case Management 2016‟ in Bangladesh is

published with the aim to provide a handy and quick guideline to diagnose and treat a Kala-azar and

PKDL patient as well as effectively handle the IRS program, ensuring a robust and effective disease and

vector surveillance and develop public awareness through community participation.

At the end I would like to thank from my core of heart to all the technical experts, clinicians, researchers,

and health managers providing their kind support and scientific efforts to publish the „National Guideline

for Kala-azar Case Management 2016‟ in Bangladesh.

Dr. A.F.M. Akhtar Hossain

Deputy Program Manager

National Kala-azar Elimination Program

Photo

Deputy Program Manager, KEP, CDC


Govt. of the People’s Republic of Bangladesh

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Message

Diseases Control Division, Communicable Disease Control (CDC) of Directorate General of Health

Services (DGHS) has been implementing National Kala-azar Elimination Program (NKEP) since 2007,

pursuing WHO/SEARO Regional Strategic Framework for Elimination of Kala-azar from the South-East

Asia Region, setting goal to improve the health status of vulnerable groups and at-risk population, and

building target to reduce the annual incidence rate of Kala-azar less than 1 case per 10 000 populations at

all levels of endemic upazilas of Bangladesh by 2017.

The management and control of Kala-azar disease continues to be one of the highest public health

priorities in Bangladesh. The program strategy is aimed to reduce the Kala-azar disease burden and to

achieve national goals and targets. The country has also started a number of target-oriented health

programs to eliminate other communicable diseases like malaria, filaria, soil transmitted disease, rabies,

HIV/AIDS, hepatitis, nipah, avian influenza, etc under the leadership of Disease Control Division,

Communicable Disease Control of Directorate General of Health Services (DGHS).

The NKEP is implemented as a part of CDC OP (Operational Plan) under 3rd

Health, Population and

Nutrition Sector Development Program (HPNSDP: 2011-2015). The strategic objectives of the national

kala-azar elimination program is to ensure early diagnosis and complete management of the cases,

implement integrated kala-azar vector management (IVM), have effective patient and vector surveillance

system, conduct operational research, and build institutional capacity.

The revised WHO/SEARO Regional Framework for Elimination of Kala-azar Strategy: 2016-2020 has

been adopted by the country emphasing key indicators for elimination. The indicators are: (i) detection

rate – tracking all new cases of kala-azar in an endemic area within a given year; (ii) treatment completion

rate – the target for treatment complition rate in any endemic upazila should be above 90% with effective

anti-leishmania drug; and (iii) vector control for coverage rate – the number of households protected

through indoor residual spray (IRS) to be 100 percent.

It is my immense pleasure that the Disease Control Division, Communicable Disease Control (CDC) of

the Directorate General of Health Services (DGHS) is going to publish „National Guideline for Kala-azar

Case Management 2016‟ which will provide the latest treatment and management for Kala-azar patients.

I would like to express my heartiest thanks to all the resource persons, consultants, experts and physicians

who gave their valuable time; provided technical and financial support; and contributed to the revision

and updating the important guideline within the shortest possible time.

Prof. Dr. Sanya Tahmina



Photo



Govt. of the People’s Republic of Bangladesh

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CONTENT PAGE

Abbreviations………………………………………………………………………………………………… iii

Messages……………………………………………………………………………………….………….…… iv

Content Page………………………………………………………………………………….……………… xii

Executive Summary………………………………………………………………………………………… xvii

CHAPTER: ONE……………………………………………………………………………………….…… 1

1. INTRODUCTION ……………………………………………………………………………………. 2

1.1 Background – Kala-azar………….……………………………………………….…………………. 2

1.2 Current Global Burden of Visceral Leishmaniasis……………....…………………….…………...……. 2

1.3 Vector Sandfly – Characteristics, Life Cycle and Control Measures..………………………………….. 4

1.4 Life Cycle of Leishmania Parasite……………………………………………………………………….. 6

1.5 Factors favorable for Elimination of Kala-azar………………………………………………………….. 7

1.6 Present situation of Kala-azar in Bangladesh…………………………………………………………….. 8

1.7 Objectives of National Guideline for Kala-azar Case Management ……………….……………………. 13

1.8 Target Audiences for the National Guideline…………………….…….………………..….………...…. 14

1.9 Kala-azar Elimination Program in Bangladesh……………………………………...…………………… 15

1.10 Challenges for Kala-azar Elimination Program in Bangladesh……………………………………...…... 16

CHAPTER: TWO………………..…………………………………………………………………….…… 18

2. DIAGNOSIS OF KALA-AZAR, PKDL AND CL….……………….……..……………………. 19

2.1 Clinical Diagnosis of New Kala-azar (NKA) ……………………………….……………………...…… 19

2.2 Clinical Diagnosis of Post Kala-azar Dermal Leishmaniasis (PKDL) ……….…….…………...……… 20

2.3 Kala-azar with Co-infections…..……………………………………………….………….………..…… 22

2.4 Diagnosis of Kala-azar using rK39 RDT………………………………………………………………… 24

2.4.1 Types of diagnostic tests available for Kala-azar…………………...……………………...…… 24

2.4.2 Procedures of rK39 RDT…………………………………………………………………..…… 24

2.4.3 Interpretation of test of rK39 RDT……………………………………………………………… 25

2.4.4 Effectiveness of rK39 RDT in detecting Kala-azar………………………………………...…… 25

2.4.5 Advantages and disadvantages of rK39 RDT……………………………………………...…… 25

2.4.6 Use of rK39 RDT in National Kala-azar Elimination Program……………….………………… 26

CHAPTER: THREE……………………….…………………………………………………………….… 28

3. TREATMENT OF KALA-AZAR, PKDL AND CL.………………………………….…….…. 29

3.1 Treatment for New Kala-azar (NKA)……..…………………………………………...………………… 29

3.2 Treatment for Post Kala-azar Dermal Leishmaniasis (PKDL)………………………...………………… 32

3.3 Treatment of Cutaneous Leishmaniasis CL)……………………………………..………………………. 35

3.4 Diagnosis and Treatment of Kala-azar in Special Situation.…..………………………………………… 37

3.5 Complete treatment of Kala-azar…….…………………………………………………………………. 39

3.6 Clinical/treatment outcomes in Kala-azar……………..…………………………………………….…… 43

3.6.1 Monitoring of clinical/treatment outcomes rates ………..……………………………………… 45

3.6.2 Key indicators for treatment compliance rate of kala-azar……………………………………… 45

3.6.3 Monitoring of clinical/treatment outcomes variables…………………………………..………. 46

3.6.4 The clinical/treatment outcomes of PKDL………………………………………..……………. 46

3.6.5 Monitoring treatment of outcomes rates calculations…………………………………………… 47

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3.7 Pharmaco-vigilance Activities……………..……………………………..……………………………… 48

3.7.1 Operational Plan for Pharmaco-vigilance activities……………………………………...……… 48

3.7.2 Indicators of Pharmaco-vigilance activities……………………………………………...……… 49

CHAPTER: FOUR……………………………………………………………..…………………..……… 51

4. KALA-AZAR SURVEILLANCE SYSTEM……...........................……………………………… 52

4.1 Introduction to surveillance…………………………………………………………………….………… 52

4.2 Types of Kala-azar Surveillance….……………………………………………………………………… 53

4.2.1 Passive Case Surveillance…………………………………..…………………………………… 53

4.2.2 Active Case Surveillance………………………………………………………………...……… 56

4.2.2.1 Blanket Approach …………………………………………………………………… 56

4.2.2.2 Camp Based Approach ……………………………………………………………… 56

4.2.2.3 Index Based Approach ……………………………………………………………… 56

4.2.2.4 Incentive Based Approach …………………………………………………………… 56

4.2.2.5 No Kala-azar Transmission Strategy………………………………………….……… 56

4.2.2.6 Approach to Asymptomatic Kala-azar Management…………………………………. 58

4.3 Management of Kala-azar Surveillance………………………………………………………………….. 60

4.3.1 Kala-azar Surveillance Units…………………………………..………………………………… 60

4.3.2 National Rapid Response Team…………………………………………………………………. 61

4.3.3 Surveillance Reporting from UHC………………………………………………………..……. 61

4.3.4 NKA and PKDL Detection from Community……………………………………………...…… 61

4.3.5 Reporting Format For Diagnosis of NKA and PKDL………………………………………...… 63

4.3.6 Reporting of Surveillance Information………………………………………………………..… 64

4.3.7 Web-based Reporting of Surveillance System…………………………………………………... 65

CHAPTER: FIVE…………………………………………………..……………………………….….…… 66

5. MONITORING AND EVALUATION (M&E)………………………….………………...…….. 67

5.1 The Monitoring & Evaluation Framework …………………….…………………………..…………… 67

5.2 Monitoring and Evaluation Team……………………………………………………………………….. 67

5.3 Indicators related to Kala-azar and PKDL Diagnosis……………………………………………………. 68

5.4 Indicators related to Kala-azar and PKDL Treatment……………………………………………………. 69

5.5 Indicators related to Kala-azar and PKDL Surveillance…………………………………………………. 70

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LIST OF TABLES:

Table 1: Health Facilities and Referral System for Kala-azar Treatment in Bangladesh…………………….. 14

Table 2: Clinical Case Definition for New Kala-azar, PKDL & CL.………………………………..………….. 21

Table 3: Diagnosis of Kala-azar in different level of health facilities in Bangladesh………….……………… 23

Table-4: Diagnostic test for suspected cases of KA using rK39 RDT ……………………………………………. 26

Table-5: Drug treatment of New Kala-azar (NKA) ………………………………………………..….…….……… 30

Table-6: Drug Treatment of RKA…………………………………………………………………..…….…….……… 31

Table-7: Treatment regimens for PKDL…………………………………………………………..…….…….……… 34

Table-8: Treatment of Cutaneous Leishmaniasis (CL)..………………………………………..…….…….………. 36

Table-9: The Clinical/Treatment Outcomes with Case Definitions of NKA……………...…….…….…….…… 43

Table-10: Early Treatment Outcomes with Case Definitions………………………………..….…….…….……… 44

Table-11: Final Treatment Outcomes with Case Definition: ………………………………..….…….…….……… 44

Table-12: Monitoring Clinical/treatment Outcomes Rates…………………………..……….…….…….……… 45

Table-13: Treatment Completion Rates…………………………….…….…….……………………………………… 46

Table-14: Treatment Outcomes in PKDL Patients………………………………………………..…….…….……… 46

Table-15: Names of drug with side effects and the types of laboratory tests indicated…………..…………….. 49

Table-16: Indicators and information for Passive Surveillance ………………………………..…….…….…… 54

Table -17: Indicators for Monitoring Passive Case Surveillance………………………………..…….…….…… 55

Table-18: Screening tool for diagnosis of New KA attending UHC (Check list)……….……………..……. 63

Table-19: Screening tool for “Suspected Cases of PKDL” attending UHC (Check List) …………...…………. 63

LIST OF FIGURES:

Figure -1: Life Cycle of Leishmania Parasite……………………………………………………………………… 6

Figure -2: Bangladesh Maps showing Year-wise Endemicity of Kala-azar: 2008-2014…………………. 8

Figure -3: Endemicity of Kala-azar in Bangladesh in 2014 & 2015……………………………………..……….. 10

Figure- 4: Endemicity of Kala-azar in Bangladesh in January – October 2016……………..………...………… 11

Figure-5: Trend of New Kala-azar Cases and Deaths during 2000-2015…………………..………...………… 12

Figure-6: Trend of VL and PKDL from 2010-2015 in Bangladesh………………………………………………. 12

Figuee-7 Procedures to perform RDT rK39 test………….…………..……..………….…………………………. 24

Figure-8 Interpretation rK39 Strip……………………………………………………..……………………………. 25

Figure-9 Diagnosis of Kala-azar……………………………………………..……………………………. 40

Figure- 10: Treatment Chart for NKA…………………………………………..………………….…………. 41

Figure-11: Treatment Chart for RKA, PKDL & CL.………………………..……………...………………. 42

Figure -12: Diagrammatic view of Activities and responsibilities of NRRTK in NKTA……………………… 57

Figure-13 Flow Chart for NKA and PKDL Detection from Community………………………………………… 62

Figure-14 Data Flow and M&E…………….……………………………….…………..….……………….. 71

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ANNEXTURE:

Annex-1: Household Survey Form ………………………………………………………..………………..……… 73

Annex-2: List of Suspected Cases Kala-azar Patient……………………………….………………….………… 74

Annex-3: Field Referral Form …………………………………………………………….……………….….……… 75

Annex-4: Registration and Follow-up Book…………………………………………..…….………..…………… 76

Annex-5: Treatment Card………………………………………………………………..…………….………….… 77

Annex-6: Follow-up Chart……………………………………………………………………………….………….. 79

Annex-7: Monthly Kala-azar Reporting Format………………………………………....………….…………… 80

Annex-8 Description of Drugs used for the Treatment of Kala-azar…………………………………………. 81

Annex-9 Monitoring of Treatment Outcomes Variables………………………………………………………… 85

Annex-10: Indicators of Kala-azar Treatment Effectiveness……………………………………………………… 85

Annex-11: Monthly/Quarterly Report Format on Early Treatment Outcomes…………………………………. 86

Annex-12: Monthly/Quarterly Report Format on Final Treatment Outcomes…………………………………. 87

Annex-13 Indicators showing the pharmacovigilance activities………………………………………………… 88

Annex-14: Web-based Registration of Kala-azar Cases and Follow-up Form………………………………… 89

Annex-15: SOP of AmBisome………………………………………………………………...…..…………………… 95

Annex-16 M&E Form for Facility Observation Checklist….………………………………..………..….……… 103

Annex-17 M&E for Monthly Reporting Format……………………………………………………………………. 104

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EXECUTIVE SUMMARY

The updated version of the “National Guideline for Kala-azar Case Management 2016” is a product of

the National Kala-azar Elimination Program, Bangladesh. It aims to provide health managers, doctors,

clinicians, researchers, nurses and other relevant health professionals with a firsthand guide and tool for

diagnosis, treatment, health education and follow-up of cases with Kala-azar and Post-Kala-azar Dermal

Leishmaniasis (PKDL) in Bangladesh. The guideline was initially developed in 2013 with technical

support from World Health Organization (WHO), Bangladesh. This guideline comprises five chapters

with list of tables, figures and annexure.

Chapter-One describes general information about the New Kala-azar (NKA), Post Kala-azar Dermal

Leishmaniasis (PKDL) and Cutaneous leishmaniasis (CL) with current global burden of Leishmaniasis

and visceral Leishmaniasis as well as present Kala-azar situation in Bangladesh, brief description about

sandfly, the vector of Kala-azar, its characteristics, life cycle and control measures, short accounts of life

cycle of leishmania parasite; factors favourable for elimination of leishmania from Bangladesh, objectives

and target audiences for the national guideline, level of health facilities and referral system for Kala-azar

and PKDL case management; and summary of vision, mission, target, indicators, impact objectives,

elimination strategies and challenges of kala-azar elimination program in Bangladesh.

Chapter-Two deals mainly with clinical and confirmed case definitions of NKA, PKDL and CL. The

value of confirmatory such as microscopic examination of spleen/bone marrow aspirate or skin slit biopsy

or PCR. This chapter also describes the diagnosis of Kala-azar with co-infection such as tuberculosis,

hepatitis, hematological diseases, HIV/AID, diabetes, pregnancy and malaria. The unique diagnostic

services are made available in different level of health facilities such as upazila health complexes, district

hospitals, tertiary hospitals and specialized hospital in the endemic areas of Bangladesh. This chapter ends

by describing the types of diagnostic tests available for kala-azar, procedures of doing rK39 RDT at

simple laboratory setting, interpretation and effectiveness of rK39 RDT in detecting kala-azar, and

advantages and disadvantages of rK39 RDT for mass screening of Kala-azar in the community level.

Chapter-Three describes the treatment of Kala-azar, PKDL and CL using different types of anti-

leishmania drugs as a monotherapy or in combination and highlights the advantages of using single dose

Liposomal Amphotericin B (LAmB) for the attack phase of the National Kala-azar Elimination Program.

The recommended treatment regimens have been described indicating the importance of first line drug

treatment, value of alternative drug of choice, and effectiveness of combinations of drug therapy in New

Kala-azar (NKA), Kala-azar Treatment Failure (KATF), Relapse Kala-azar (RKA), and other form of

disease. This chapter includes the descriptions of anti-leishmania drugs such as Liposomal amphotericin

B (LAmB), Miltefosine, Paromomycin, Amphotericin B deoxycholate and Sodium stibogluconate with

their advantages, disadvantages and possible side effects. The early and final clinical/treatment outcomes

have been defined. Moreover, monitoring of clinical/treatment outcomes rates such as initial cure rate,

final cure rate, treatment failure rate, loss-to-follow up rate, treatment completion rate and mortality rate

have also been defined. The methods of collection of data on pharmacoepidemiology including detection,

assessment, documentation, and prevention of adverse drug reaction have been described along with the

importance of reporting and analyzing of adverse drug reaction caused as a result of treatment of disease.

Chapter-Four explains the importance of Kala-azar surveillance system and the roles of passive and

active surveillance in collecting, reporting, monitoring, evaluating, analyzing and interpreting Kala-azar

data for making empirical decision to improve the program activities. The management and composition

of Kala-azar surveillance units at upazila, district and national levels along with rules and regulations

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have been described. The roles and responsibilities of health managers at different surveillance units have

been highlighted. The sources of surveillance (health facilities) from where the data are generated have

been identified and components of surveillance system are described; for an effective disease

surveillance, the standard methods and frequency of reporting of Kala-azar disease have been organized;

the indicators for passive case detection have been defined and the corresponding reporting criteria have

been identified to document the disease events. The different methods and the criteria of active case

detection such as blanket approach, camp-based, index-based and incentive-based approaches have been

identified in order to play a more dynamic role in active case detection and to facilitate early diagnosis

and complete treatment of Kala-azar and PKDL cases.

The advantages of “No Kala-azar Transmission Activities”, a modified form of index-based case

approach for the acceleration of active case detection, have been described and the benefits of this

approach to implement the activities for stopping further transmission of the disease within the endemic

community are identified. The approaches and strategies to manage asymptomatic Kala-azar carrier have

been described and empirical value of mass screening of family members and immediate neighboring

contacts of the index case have been documented. The chapter ends by describing the advantages of Web-

based Registration of Kala-azar and PKDL Cases and Follow-up, whereby the information generated

from web-based will be used by the program personnel to take immediate actions to prevent the

transmission of the disease in the epidemic and outbreak situation, and help the program managers to

make better decision to improve the Kala-azar elimination program activities in Bangladesh.

Chapter-Five describes monitoring and evaluation (M&E) component of Kala-azar elimination program.

The importance of M&E for the provision of quality of data on the scope, coverage and effectiveness are

described. The uses of M&E data to monitor progress on inputs, process, outputs, outcomes and impacts

levels have been highlighted. The role of routine monitoring, periodic assessment, supervision and

evaluation to ensure effective implementation is described. A set of objectively verifiable indicators used

to measure progress and to assess the achievement of elimination target in line with national Kala-azar

strategy are defined. The checklists or formats have been designed for regular M&E to identify gaps of

the ongoing activities. The importance of M&E Framework and its different elements are described.

Indicators for NKA, PKDL and CL in relation to diagnosis, treatment and surveillance are described

using log frame, a tool for improving the planning, implementation, management, monitoring and

evaluation of the program activities that organize the main elements of Kala-azar elimination program and

systematize the logical linkages between them.

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PHOTOGRAPHS OF KALA-AZAR PATIENTS

Kala-azar Post Kala-azar Dermal Leishmaniasis

Cutaneous Leishmaniasis Post Kala-azar Dermal Leishmaniasis

(PKDL)

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CHAPTER: ONE

INTRODUCTION TO KALA-AZAR

Sandfly, the Vector of Kala-azar

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INTRODUCTION TO KALA-AZAR

1.1 BACKGROUND – KALA-AZAR

Leishmaniasis is a group of neglected tropical disease caused by more than 20 different types of species of

protozoan parasites of Leishmania genus known to be infective to humans and is transmitted by the bite of

infected female phlebotomine sandflies. Leishmaniasis was first identified in 1824 in Jessore District of

Bangladesh. In 1903, a Scottish Physician Professor William Leishman and an Irish Physician Professor

Charles Donovan worked independently in India and identified the causative organism of Kala‐azar from

splenic aspirates. They published their discoveries almost simultaneously in the same year in British

Medical Journal in May 1903 and July 1903 respectively.

The greatest authority on parasitology at the time, Sir Ronald Ross took up investigations on the parasite of

kala‐azar in Kolkata, India. In 1903, he ended all controversy and jointly accredited Professor William

Leishman and Professor Charles Donovan for their discovery of the parasite of kala‐azar. Ronald Ross

named the parasite in honor of the two greatest medical scientists as “Leishmania donovani”. Today, the

name kala‐azar is used interchangeably with the scientific name visceral leishmaniasis for the most acute

form of the disease caused by L. donovani. Clinical manifestations range from cutaneous ulcers to systemic

multi-organ disease. Visceral leishmaniasis (VL) is caused primarily by the two related species Leishmania

donovani and Leishmania infantum (synonym Leishmania chagasi).

1.2 CURRENT GLOBAL BURDEN OF VISCERAL LEISHMANIASIS

There are three main types of leishmaniasis: i) Visceral leishmaniasis, often known as kala-azar and the

most serious form of the disease (VL); ii) Cutaneous leishmaniasis, the most common (CL); and iii)

Mucocutaneous. A recent review shows that over 98 countries and territories are endemic for leishmaniasis.

Visceral leishmaniasis (VL): VL also known as kala‐azar is highly endemic in Indian subcontinent

(Bangladesh, India and Nepal), and in East Africa (North Sudan, Kenya and Ethiopia). An estimated

200 000 to 400 000 new cases of VL occur worldwide each year. Over 90% new cases of VL occur in 6

countries such as Bangladesh, Brazil, Ethiopia, India, Sudan and South Sudan. VL is caused by two

leishmanial species, L. donovani or L. infantum, depending on the geographical area. L. infantum infects

mostly children and immuno-suppressed individuals, whereas L. donovani infects all age group. There are

two types of VL, which differ in their transmission characteristics: (i) Zoonotic VL is transmitted from

animal to vector to human and (ii) Anthroponotic VL is transmitted from human to vector to human. In the

Zoonotic VL, humans are occasional hosts and animals, mainly dogs, are the reservoir of the parasites.

Zoonotic VL is found in areas of L. infantum transmission, whereas Anthroponotic VL is found in areas of

L. donovani transmission.

Cutaneous leishmaniasis (CL): Cutaneous leishmaniasis is more widely distributed, about 90% of CL

cases occurring in each of three epidemiological regions, the Americas, the Mediterranean basin, and

western Asia from the Middle East to Central Asia. Over two-thirds of the new CL cases occur in 6

countries such as Afghanistan, Algeria, Brazil, Colombia, Iran and the Syrian Arab Republic. An estimated

0.7-1.3 million new CL cases occur worldwide annually. CL is the most common form of leishmaniasis and

causes skin lesions; the patient generally presents with one or several ulcer(s), on exposed parts of the

body, leaving life‐long scars and serious disability. Different species of Leishmania can infect the

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macrophages in the dermis, with variable clinical presentations and prognosis. The ulcers heal

spontaneously, although slowly, in immunocompetents individuals, but cause disfiguring scars..

Muco-cutaneous leishmaniasis: Almost 90% of muco-cutaneous leishmaniasis cases occur in the

Plurinational State of Bolivia, Brazil and Peru. In Mucocutaneous leishmaniasis, the patients suffer from

progressively destructive ulcerations of the mucosa, leading to partial or total destruction of mucous

membranes of the nose, mouth and throat including pharynx and larynx. These lessons are not self-healing

and are usually seen months or years after a first episode of cutaneous leishmaniasis, when the macrophage

of the naso-oropharyngeal mucosa become colonized. Leishmania braziliensis is responsible for most cases

of muco-cutaneous leishmaniasis..

Post Kala-azar Dermal Leishmaniasis (PKDL): PKDL is characterized by a macular, maculo-papular or

nodular rash and is a complication of VL that is frequently observed after treatment of VL. It can also occur

in immuno-suppressed individuals in L. infantum-endemic areas. The interval between treated VL and

PKDL is 0-6 months in Sudan and 6 months to 3 years in Bangladesh, Indian and Nepal. PKDL cases are

highly infectious because the nodular lesions contain many parasites and such cases are the presumed

reservoir for Anthroponotic VL between epidemic cycles.

PKDL has been reported sporadically in patients who do not give a past history of VL. In the Indian Sub-

continent, PKDL is not self-healing. PKDL cases are a potential reservoir of the parasite as sand flies get

infected from biting them. In endemic areas, children and young adults are the principal victims. Kala-azar

with TB or HIV or malaria co-infection also has emerged as a health problem in recent years.

Kala-azar is the disease of poverty and mostly affects the socially marginalized and the poorest

communities of the rural population and is recognized as Neglected Tropical Disease (NTD). Nearly 2.4

million Disability-adjusted life years (DALYs) are lost each year due to kala-azar globally. South-East Asia

Region accounts for the loss of about 400 000 DALYs. The economic burden of the disease in the affected

areas is also very large. About 67% of the global disease burden of Kala-azar is harbored in Bangladesh,

India and Nepal. About 200 million populations are at risk of kala-azar in Indian sub-continent.

Visceral leishmaniasisis one of the clinical forms of Leishmania with its complication such as Post Kala-

azar Dermal Leishmaniasis (PKDL), Cutaneous Leishmaniasis (CL) and muco-cutaneous Leishmaniasis

(ML) and is caused by the protozoa Leishmania donovani. In Indian sub-continent it is transmitted by

female sand fly named Phlebotomus argentipes. The disease is characterized by prolonged fever (≥2

weeks) with splenomegaly, anemia, weight loss and darkening of skin. Kala-azar is fatal if not treated

properly.

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1.3 VECTOR: SANDFLY - CHARACTERISTICS, LIFE CYCLE AND

CONTROL MEASURES

Habits of Sandfly: Sandfly that caused visceral leishmaniasis belongs to Phlebotomus genus and the

Phlebotomus argentipes is the common species. The sandfly is most commonly distributed in the warm

countries; only female sandfly can bite in the dwelling at night. The sandfly is characterized by its densely

hairy wings, giving them a moth-like appearance. It takes shelter during day in holes and crevices in wall,

in dark room and store room etc. The eggs are laid in damp and dark places in cattle sheds and poultry.

The species are mostly nocturnal in habit. The range of flight is on average 200 yards from their breeding

places; however, they cannot fly but can only hop and hop only short distance. The average life of

sandfly is about 2 weeks. The males and females feed on nectar and other plant juices, but females require

a blood meal in order to mature a second batch of eggs. The blood meal hosts include white-tailed deer,

horses, donkeys, mules, dog, cattle, swine, raccoons, rodents, birds and humans. Sand flies are active

during the early morning and evening hours when temperatures are cooler and humidity is lower.

General Characteristics of Sandfly: The body of sandfly consists of three parts: (i) The head bears a

pair of long and hairy antenna. Palpi and proboscis and one pair of prominent black eyes are present; (ii)

The thorax bears a pair of wings and three pair of legs. The wings are upright in shape and hairy. The

2nd

longitudinal vein is branched twice. The legs are long and slender and out of proportion to the size of

the body; and (iii) the abdomen has ten segments and is covered with hairs. In the female the tip of

abdomen is rounded while in male claspers are attached to last abdominal segment.

Life Cycle of Sandfly: The life cycle of sandfly is characterized by complete metamorphosis, having 4

developmental stages as flows:

Egg: Adult females require blood meal to develop eggs. The female generally lays eggs in the damp dark places

in the cattle sheds and poultry. The eggs vary from 40-50 in numbers, elongated oval shaped, and

brownish in color. The eggs measure about 0.4 mm in length. Eggs hatch in 1-2 weeks;

Larva: The larva is maggot like structure with pale cream in color, having large head, thorax and abdomen and

two long bristle on last abdominal segment. Caterpillar-like larvae hatch from eggs through a J-shaped

crack. Four different stages, or instars, of larval development occur over a period of around two weeks,

each one larger than the one before. The newly hatched first instar larvae have two rear bristles, or

whiskers, while all later larval developments have four rear bristles. Larvae feed on dead organic matter

and are found living in moist areas, such as in animal burrows. Larva becomes a pupa in about 2 weeks.

Pupa: Pupae are obtect, measuring approximately 2.6 mm in length looking much like a butterfly pupa. To

prepare for the pupal stage, the sand fly larvae attach themselves to a substrate. During this stage, each

larva develops into adults and grows wings. Sand flies are immobile during this life cycle stage and do not

eat. The pupal stage occurs over a period of five to ten days.

Adult: Sand flies emerge from their pupal stage as adults at night, shortly after they develop their wings, which

are a characteristic V shape when erected. Adults are small, on average 2.5 mm in length, silvery-

brownish in color, long-legged flies with narrow bodies. The wings are less than 3 mm long, and are held

erect above the body. Sexual dimorphism is marked between the male and female flies. Males have

conspicuous external terminalia with a relatively small and slender abdomen compared to the female. The

total time from egg to adult takes 5 weeks. The average life of a sandfly is about 2 weeks.

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Behavior and Bionomics: The life cycle of sandfly develops in moist microhabitats rich in organic

matter. They thrive best in alluvial soil, in areas with relatively even temperature, high humidity and

abundance of cattle. They are not aquatic but eggs and larvae can withstand the immersion in water for a

period of 5 days, and the larvae of the fourth stage can withstand the immersion for a period of 14 days.

Thus they can survive even flooding. Breeding places are found within a radius of about 20-50 meters

from a dwelling. There is no information on the life expectancy of sandfly but thought that they can

survive not more than 35 days. Only the female suck blood and they prefer cattle blood because it

required a blood-meal for egg development. The sandfly shifts from cattle to humans only it has

exhausted the option of blood meal from cattle.

Sandflies rest comparatively in cool and humid places including bedrooms; latrines; basements; fissures

in walls, rocks, soil, crakes and crevices; dense vegetation; tree holes and buttresses; burrows of rodent

and other mammals; bird‟s nests. In the cattle sheds, the favorite breeding place is underneath cattle

troughs. Female sandflies of many species are predominantly exophagic (biting outdoor) and exophilic

(resting outdoors during maturation of eggs), and cannot be controlled by spraying internal walls of

houses with insecticide. In contrast, species that are endophilic (resting indoors during maturation of

eggs) can be controlled by spraying.

Control Measures: Sandflies are easily controlled because they do not move long distance from their

breeding places. (i) Insecticide: Deltamethrin, Lindane, some other insecticides have been proved

effective against sandfly. Spraying should be done in the human dwellings, cattle sheds and poultry. Its

residue may remain effective for a period of 3 months; and (ii) Sanitation: Removal of shrubs and

vegetation, filling of cracks and crevices in the wall and floor, and distance of cattle sheds and poultry

from human habitations may improve the sanitation and wipe out the habitats of sandfly.

Adult sandflies are active after dark, while during the day they escape into their resting shelters. The

indoor habitats of sandflies have implications for the effectiveness of control measures. The sandflies can

hop but cannot fly, and can hop only short distances. They cannot reach above a height of six feet. The

highest risk of disease transmission for Bangladesh, India and Nepal is in the months of June to October

when the humidity is high. Susceptibility test have shown that the sandfly continues to be susceptible to

all insecticides.

The vector behavior and bionomics that make interruption of transmission achievable in this subcontinent

include the following: (i) There is probably only one type of sandfly that causes kala-azar in Bangladesh,

India and Nepal, (ii) The vector is so far sensitive to all the insecticides, (iii) The insecticide spraying can

be done with economy since the spraying is required up to a height of about two meters (6 feet) only, (iv)

The operations may be confined to only the households and cattle sheds, (v) The operations of IRS is to

be limited to community in a geographical areas affecting only 98 upazilas of Bangladesh, (vi) The cross-

border collaboration in IRS operations can interrupt the transmission of the disease, and (vii) There is

historical evidence of interruption of transmission as a collateral benefit of malaria eradication program

when kala-azar was virtually eliminated from the subcontinent as a result insecticide spraying.

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1.4 LIFE CYCLE OF LEISHMANIA PARASITE

Leishmaniasis is a vector-borne disease that is transmitted by sandflies and caused by obligate

intracellular protozoa of the genus Leishmania. Human infection is caused by about 21 of 30 species that

infect mammals. The different species are morphologically indistinguishable, but they can be

differentiated by isoenzyme analysis, molecular methods, or monoclonal antibodies.

Figure-1: Life Cycle of Leishmania Parasite:

Diagram Showing the Sandfly and Human Stages of Leishmaniasis1

Human Stages:

Sandfly injects promastigotes into the skin during a blood meal. *infective stage

Promastigotes are phagocytized by neutrophils that are rapidly recruited to the bite site.

Infected neutrophils release the parasites which are then consumed by macrophages.

Promastigotes transform into amastigotes inside macrophages. *diagnostic stage

Amastigotes multiply in cells (including macrophages) of various tissues. *diagnostic stage

Sandfly Stages:

Sand fly ingests infected macrophages when it takes a blood meal.

Ingestion of parasitized cell.

Amastigotes transform into promastigotes in midgut of sandfly.

Promastigotes divide and migrate to the anterior midgut and foregut of the sandfly.

Sandfly injects promastigotes into the skin during a blood meal. *infective stage

1.5 FACTORS FAVORABLE FOR ELIMINATION OF KALA-AZAR

1 National Institute of Allergy and Infectious Disease (NIAID), Last Updated on September 25, 2008

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The morbidity and mortality of VL in Bangladesh, India and Nepal is high about 67% of the global disease

burden, the governments of these countries have declared this disease as a public health problem and have

launched a Regional VL Elimination Program implementing strategies to reduce the annual incidence of

VL. Bangladesh, India and Nepal signed a memorandum of understanding (MoU) in 2005 and pledged

their commitment to eliminate kala-azar from the region by 2015. Thereafter a “Regional Strategic

Framework for Elimination of Kala-azar from the South-East Asia Region: 2011-2015” was adopted with

clear goal, target, indicators and objectives. On 9th September 2014 in Dhaka, the MoU has been extended

including two countries Bhutan and Thailand, with the aim of reducing annual incidence of kala-azar less

than 1 case per 10,000 populations in the endemic areas by 2017. This optimistic and realistic aim could be

apprehended by realizing two most important favorable factors as follows:

1.5.1 Biological Factors: Biological factors favorable for elimination of kala-azar are in the South-East

Asia Region are:

Man is known to be the only reservoir host for kala-azar parasite (Leishmania donovani),

Phlebotomus argentipes sandfly is probably the only species amongst about 50 phlebotomine

species that transmits kala-azar to humans in Bangladesh, India and Nepal.

1.5.2 Technical Factors: The technical factors favorable for elimination of kala-azar are:

rK39 Rapid Diagnostic Test kit: rK39 Rapid Diagnostic Test kit is available for the diagnosis of

kala-azar. , which is very reliable with high sensitivity and specificity, easy-to-use,;

Availibility of Anti-leishmaniasis Drug: The first line drugs such as oral Miltefosine and single

dose injection Liposomal Amphotericin B are available for the treatment of kala-azar. These

drugs are reasonably safe and effective; Alternative effective drug such as Paromomycin is also

available;

Vector Control Measures: Vector control using indoor residual spraying (IRS) with effective

insecticide is available;

Strong political commitment in the three countries including Bhutan and Thailand favors

feasibility of elimination of the disease; and

The disease is limited to only 90 districts in the Indian subcontinent (26 Bangladesh, 52 India and

12 Nepal). Some districts in Bhutan and Thailand are also affected with sporadic cases. Hence,

elimination efforts should be focused in the five endemic countries.

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1.6 PRESENT SITUATION OF KALA-AZAR IN BANGLADESH

Kala-azar is endemic in Bangladesh for many decades causing a major public health problem. During the

Malaria Eradication Program mid 1960s, blanket DDT spraying had controlled Kala-azar transmission to

a great extent. In the late 1970s Kala-azar re-emerged sporadically in the country. During 1981-85 only 8

upazilas (Sub-district) had been reported Kala-azar cases, whereas in 2004 the number of upazilas has

increased to 105 within 25 years. During 1993 to 2005 Kala-azar situations has assumed as epidemic

proportion with the number of reported cases increasing from 3,978 in 1993 to 8,505 in 2005. Though

Kala-azar was reported from 45 districts previously, the number of districts has declined to 26 districts,

and the total number of cases reached to 1068 in 2014 (New Kala-azar- 650, PKDL- 318, Relapse Kala-

azar- 85, Kala-azar Treatment Failure- 11).

Cases were reported from Upazila Health Complex and specialized hospitals to CDC-DGHS Dhaka

Office. At present the Kala-azar burden in Bangladesh has been gradually declining reaching the national

target of less than 1 case per 10 000 population (the incidence rate of Kala-azar is 0.28 in 2015). The

mortality rate is almost zero due to the successful implementation of National Kala-azar Elimination

Program (NKEP) activities complying with WHO/SEARO Regional Strategic Plan for Kala-azar

Elimination 2011-2015, focusing on early diagnosis, prompt complete case management and integrated

vector management.

Figure-2: Bangladesh Maps showing Year-wise Endemicity of Kala-azar: 2008-2014

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Under the current surveillance system, the Upazila Health Complexes (UHCs) and District Hospitals have

been reporting Kala-azar cases to Civil Surgeon Offices (CS Office) and Kala-azar Elimination Program

(KEP). After compilation of kala-azar reports of designated upazila, CS Office sends the reports to KEP

of CDC-Dhaka Office. On the other hand specialized hospitals report directly to KEP at CDC-Dhaka

Office. However, there is an under-reporting of cases in the field level because the private clinics, private

hospitals and private practitioners do not report cases to the nearest designated UHC or District Hospitals.

Figure 3: Endemicity of Kala-azar in Bangladesh in 2014 & 2015

In recent past, a total of 47 Kala-azar cases have been reported from 15 non-endemic districts

from 17 upazila of Bangladesh. The Bangladesh maps below show endemic areas in year 2014

and 2015 where there is gradual declining of incidence rate of Kala-azar. The incidence rate of

Kala-azar was recorded more than 2.5 case per 10 000 population in two hyper-endemic

upazilas (Trishal and Fulbaria) of Mymensingh district in 2014. However, the incidence rate

was declined further and in 2015, only Fulbaria upazila has found to be hyper-endemic

recording more than 2.5 cases per 10 000 population.

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Figure 4: Endemicity of Kala-azar in Bangladesh in January - October 2016

The map above shows that all 100 endemic upazilas of Bangladesh in the year 2016 (January–October)

have achieved national target of Kala-azar elimination program (incidence rate less than 1 case per 10 000

populations). Bangladesh is the first and leading country in Bangla-Indo-Pak subcontinent achieving the

Kala-azar elimination target.

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Figure 5: Trends of New Kala-azar Cases and Deaths during 2000-2015

Figure 6: Trend of VL and PKDL from 2010-2015 in Bangladesh

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2010 2011 2012 2013 2014 2015VL 3351 2874 1902 1103 750 645

PKDL 455 502 158 325 318 217

Death 0 2 0 2 4 4

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Bar Graphs Showing VL and PKDL Cases: 2010-2015

2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015

Case 764 428 811 611 592 689 937 493 482 429 380 337 206 142 106 862

Death 24 6 36 27 23 16 23 17 17 14 0 2 0 2 3 4

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Line Graphs Showing Trend of Kala-azarCases: 2000-2015

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1.7 OBJECTIVES: NATIONAL GUIDELINE FOR KALA-AZAR CASE

MANAGEMENT

With technical support from Technical Working Group (TWG) Bangladesh, Kala-azar Elimination

Programme (KEP) has developed „National Guideline for Kala-azar Case Management‟ with the

following objective and the contents as follows:

Objective: The primary objective of the National Guideline for Kala-azar Case management is to orient

the health care providers with tools for diagnosis, treatment, surveillance and M&E of Kala-azar.

Contents of the guideline: The treatment guideline would content the following topics:

Identification of suspected cases of Kala-azar at community and hospital level

Diagnosis, detection and confirmation of Kala-azar at Upazila Health Complex, District Hospitals,

Medical College Hospital and Specialized Hospital

Provision of treatment modalities, availability of treatment, doses and administration of drugs

Establishment of effective referral system for Kala-azar patients

Institutionalizing supervision, monitoring and evaluation of Kala-azar Elimination Program

Surveillance system with passive and active case detection and activities for Kala-azar

Reporting system of Kala-azar

In 2015 the guideline has been updated with the following purposes:

To include the latest Data of Kala-azar Elimination Program

To orient with new terminology

To update the treatment modalities for Kala-azar, SOPs of Kala-azar drugs and diagnostics

To orient web-based reporting and Pharmaco-vigilance of Kala-azar drugs

To implement supervision, monitoring and evaluation tools for better management of Kala-azar

Elimination Program

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1.8 TARGET AUDIENCE FOR THE NATIONAL GUIDELINE

This would be a first hand document for the Doctors, Clinicians, Nurses, Medical Technologist -

Laboratory (MT-Lab), Statistician, Health Inspectors (HI) and field level health workers as follows.

ProgramHealth Managers at Central, Divisional, District and Upazila level,

Doctors,Clinicians, Researchers, Nurses, MT-Labs and other health care providers,

Supervisors at all levels (Central to local) including Statisticians and Health Inspectors,

All health care providers and volunteers, who are involved and responsible for active case search at

household level and for behavior change communication (BCC) at community level.

This guideline can be used to (i) promote and provide quick diagnostic services if kala-azar is suspected

early, (ii) ensure prompt and complete treatment to the kala-azar patients, and (iii) undertake advocacy

within the endemic areas to guarantee community participation for ensuring complete and uniform

coverage of their households with insecticides spray. This guideline is adopted according to the

WHO/SEARO guidelines.

Table 1: Health Facilities and Referral System for Kala-azar Treatment in Bangladesh

Upazila HealthComplexes District Hospitals Medical College Hospitals

Go

ver

nm

ent

Sec

tors

Community Clinics (CC)

Union Health Facilities:

(H&FWCs),

Rural Dispensary (RD),

Sub-centres (SCs)

District Hospital

Medical College Hospitals

and othe r specialized

hospitals such as Surya Kanta

Kala-azar Research Centre

(SKKRC)

No

n-

go

ver

nm

ent

Sec

tor

Qualified private practitioners

Non-qualified health care

providers including health

volunteers

NGOs, private hospitals

Qualified private

practitioners

NGOs, private

hospitals,

Private Medical College

Hospitals

Qualified private practitioners

NGOs, private hospitals

N.B Treatment of Kala-azar is available in upazila health complex. Other government upazila health

facilities like Community Clinics (CC), Union Health Facilities (Health &Family Welfare Centres, Rural

Dispensaries, sub-centres and non-government sectors(qualified practitioners, non-qualified private

practitioners, NGOs Clinic and private hospitals) will refer patients to UHC. In case of district private

health facilities, qualifies private practitioners, NGOs, private hospitals will refer patients to corresponding

government facilities stated above.

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For the success of the program, it is important to develop referral linkages from community to medical

college hospitals and specialized hospital. The district focal point should be responsible for sustaining the

linkages. The details of collaboration between the public and private sector need to be worked out with

the objective of obtaining uniform standards of practices.

1.9 KALA-AZAR ELIMINATION PROGRAM IN BANGLADESH

Vision: Kala-azar free Bangladesh by 2020.

Goal: To contribute to improving the health status of vulnerable groups and at-risk population living in

Kala-azar endemic areas of Bangladesh by the elimination of Kala-azar.

Target: To reduce the incidence rate of the disease to less than 1 case per 10000 populations at the

upazila level in Bangladesh by the year 2017.

Indicators: Three indicators have been set: (i) Kala-azar Detection Rate should be close to 100%, (ii)

Treatment Completion Rate should be ≥ 90% and (iii) Vector Control Coverage Rate (HH coverage

through IRS) should be close to 100%.

Impact Objectives: To reduce the incidence of New Kala-azar and PKDL to less than 1 case per 10

000 populations at the upazila level in Bangladesh by the end of 2017 by:

Reducing incidence of KA in the poor, vulnerable and un-reached populations in the endemic areas.

Reducing case fatality rates from Kala-azar to negligible level.

Reducing cases of PKDL to interrupt transmission of kala-azar, and

Preventing and treating Kala-azar-HIV-TB co-infections in the endemic areas.

Elimination strategies: A regional strategic framework for elimination of Kala-azar of WHO/SEARO

2011-2015 has been endorsed by the Regional Technical Advisory Group (RTAG). It comprises of the

following components:

1. Early diagnosis and complete treatment: All suspected cases of Kala-azar and PKDL should have

access to recommended diagnosis and treatment.

2. Integrated vector management (IVM): The IVM strategy aims to prevent and decrease vector

(sandfly) spread within the community and reduce human-vector-pathogen contact, and is done by

controlling vector through IRS in households and distributing LLIN within the kala-azar patients.

3. Effective disease surveillance: An effective surveillance system should be strengthen to ensure early

diagnosis, provide prompt treatment, undertake active case detection, and report kala-azar cases from

the public and private sector.

4. Social mobilization and building partnerships: For community participation and social mobilization

for behavioral change communication (BCC) at community level; and partnership building would help

to achieve the goal of Kala-azar elimination program.

5. Operational research: Operational research aims to explore strategies, interventions, tools and

knowledge that can monitor the quality, coverage, effectiveness and performance of the kala-azar

elimination program activities and evaluate the drug efficacy, insecticide resistance, quality of drugs,

treatment compliance, pharmaco-vigilance and LLIN use.

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1.10 CHALLENGES FOR NKEP IN BANGLADESH

The programme activities have contributed to reduce the incidence rate of kaka-azar remarkably over the

years in Bangladesh, however, the following areas need to be addressed and prioritized as follows:

1.6.1 The epidemiological surveillance systems need to be strengthened further at the upazila and

district level with the focus to capture data from all sources including private sector and NGOs.

1.6.2 Health-seeking behaviour: Kala-azar patients seek treatment not only from the government

facilities but also from the private practitioners, Ayurvedhic, Homeopathy, Unany and even form

village quacks. It is indeed a challage to get data from these non-governmane sources.

1.6.3 PKDL patients do not always come to a treatment facility. They act as a potential reservoir in the

community for transmission of the disease.

1.6.4 Emergence of drug resistance in L. donovani:There was a documented 60% failure rate of VL

cases with Antimonials in North Bihar of India, and parasite resistance was established in the

laboratory. Resistance to anti-kala azar drug is not documented in bangladesh.

1.6.5 Increasing relapse rates on miltefosine has been observed in India and Nepal where upto up to

20% after 12 months has been observed in the latter.

1.6.6 Asymptomatic cases of Kalaa-zar: Asysmptomatic cases of Kala-azar may act as sources of

transmission of disease in the community.

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CHAPTER: TWO

DIAGNOSIS OF KALA-AZAR AND PKDL

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2. DIAGNOSIS OF KALA-AZAR, PKDL AND CL

The evolution and advancement of different serological diagnostic tests that have been used to diagnosis

kala-azar and PKDL include globulin content of the blood, globulin ring test, globulin precipitation test,

globulin opacity test, aldehyde test, direct agglutination test both fridge and dried, rK39 rapid diagnostic

test (RDT), and polymerase chain reaction (PCR) to diagnose leishmaniasis. The confirmation of kala-

azar is also done by examination of bone marrow/spleen aspirate for LD bodies.

The KEP is using rK39 RDT, which is the latest diagnostic test with high sensitivity and specificity

suitable for screening mass population within the kala‐azar endemic areas. The rK39 RDT is usually used

in the upazila health complexes (sub‐district hospital of Bangladesh). The parasitological diagnostic tests

are regarded as confirmatory tests identifying for the presence of parasites (LD bodies) in splenic

aspirates, bone marrow biopsy and slit‐skin biopsy. The confirmatory tests are usually done at tertiary

hospitals. Once the case is diagnosed as Kala-azar, the patient is treated with first line of anti‐leishmania

drug. In some complicated cases of kala-azar in which rK39 RDT found to be negative and therefore

splenic puncture for LD bodies or PCR to detect the antibody or culture may be indicated in those cases.

2.1 CLINICALDIAGNOSIS OF NEW KALA-AZAR (NKA)

Case Definition of New Kala-azar (NKA): The most important diagnostic strategy is to describe a

standard case definition for New Kala-azar (NKA). The Technical Members of WHO in a country

consultation meeting formulated kala-azar case definition and the Regional Technical Advisory Group

(RTAG) of WHO endorsed the case definition as follows:

History of prolonged fever more than two weeks,

History of living or travelling in the kala-azar endemic area, and

Splenomegaly (palpable spleen), that is enlarge spleen.

Additional signs include weight loss, anemia and enlarge liver (Table-2).

This case definition is more sensitive than specific, holding the basis of surveillance system in the kala-azar

elimination program, and forming the basis of setting rules for the early diagnosis and complete treatment of

kala-azar cases.

Clinical Diagnosis of NKA: The second most important diagnostic approach is to conduct the screening

test using “rK39 RDT” for all new cases who meet the above case definition with fever of more than two

weeks and/or splenomegaly. If the rK39 RDT is found to be positive and if the patient has no history of

treatment of kala-azar before, the patients should be diagnosed as New Kala-azar (NKA) and should be

treated with effective first line anti-leishmania drug.

In cases with past history of kala-azar or those with high suspicion of KA but with negative rK39 RDT,

confirmation should be done by examining spleen/bone marrow aspirate for LD bodies. Treatment of

kala-azar in these circumstances should only be started after the diagnosis is confirmed.

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2.2 CLINICAL DIAGNOSIS OF PKDL

Case Definition of PKDL: The strategy for case definition of Post Kala-azar Dermal Leishmaniasis

(PDKL has been adopted from WHO/TDR2.The approved clinical indicators for PKDL case definition are

as follows:

History of previous kala-azar,

History of living in the previous kala-azar endemic area, and

Skin manifestation with multiple hypo-pigmented macule, papule and or nodule with skin sensation

(Table-2).

With these above three clinical indicators, the patient is labeled as “Suspected PKDL Case”. The

suspected case of PKDL is further screened with diagnostic test kit rK39 RDT and if the result of rK39

RDT kit is positive along with the above three clinical indicators, the patient is labeled as “Probable

PKDL Case”. The strategy adopted for Probable PKDL Case is to treat them with effective anti Kala-azar

drug. The patient is labeled as “Confirmed PKDL Case” if they meet the criteria for Probable PKDL

along with confirmed parasites (LD Bodies) in slit-skin smear or skin biopsy. In this situation the

Confirmed PKDL Case should also be treated with effective anti-kala-azar drugs.

Skin lesions in PKDL cases have been not been graded in National Kala-azar Elimination Program

(NKEP) in Bangladesh. However, some countries have graded PKDL cases into three major categories as

follows: Grade I includes scattered maculo-papular or nodular rash in the face with or without some

involvement in the upper chest or arm; Grade II includes maculo-papular or nodular rash mostly on face

and extending to the chest, back upper arms, and legs; and Grade III includes maculo-papular or nodular

rash covering most part of the body, including hands and feet.

In some cases of PKDL, there may be a history of NKA and in some cases, there may not be past history.

All suspected cases of PKDL should be subjected to rK39 RDT. A negative test with rK39 RDT in

macular lesions does not rule out the possibility of PKDL. In such cases and also in nodular and papular

lesions, the diagnosis may be confirmed by biopsy or scraping of slit-skin. PCR tests with skin biopsy or

slit-skin smear is much more sensitive. The rK39 RDT is usually positive in both papular and nodular

lesions.

Bangladesh has adopted this case definition of NKA and PKDL and continued implementing this

standard process in its NKEP. Early diagnosis with case detection and prompt treatment will improve the

prognosis of patients and reduce the transmission of the disease in the endemic area.

2 WHO (2010). Indicators for monitoring and evaluation of the kala-azar elimination programme. August 2010, WHO & TDR, p 6-7.

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Table-2: Clinical Case Definition for New Kala-azar (NKA), PKDL and CL

The diagnosis of New Kala-azar (NKA)and Post Kala-azar Dermal Leishmaniasis (PKDL) will be based on the following criteria case as follows:

New Kala-azar (NKA):

Fever for more than 2 weeks Residing/traveling in Kala-azar endemic areas Splenomegaly rK39 RDT (+ve) Additional symptoms: weight loss, anemia, enlarge liver, darkening of skin

Re-treatment Kala-azar (RKA): Both Kala-azar Treatment Failure (KATF) and Relapse KA:

Kala-azar Treatment Failure (KATF)

Diagnosed as New KA having symptoms and signs mentioned in the above case definition. History of treatment for New KA and no improvement of initial treatment within one month

and/or reappearance of symptoms and sign of KA within 6 months will be defined as KATF.

Relapse Kala-azar (Relapse KA):

Diagnosed as New KA having symptoms & signs mentioned in the above case definition. History of treatment for NKA and considerable degree of improvement through initial treatment

within one month is noted. Relapse: Any reappearance of symptoms and sign of KA within after 6 months after the end of

treatment will be defined as Relapse KA.

All efforts should be made to diagnose KATF or Relapse KA parasitologically by splenic smear or bone marrow examination or PCR. N.B: Splenomegaly may be present for a longer period of time after initial treatment. In that case diagnosis should be based on other clinical features and all effort should be made for parasitological diagnosis of KA.

Post Kala-azar Dermal Leishmaniasis (PKDL):

Residing/travelling in the endemic areas History of treatment for Kala-azar any time in the past

1.

Suggestive skin lesion without loss of sensation, which may be hypomelanotic, macular, papular, nodular or mixed.

Exclusion of other causes of skin disease: leprosy, vitiligo, pityriasis, ring worm, arsenicosis. rK39 (+ve)

2 or slit skin smear positive or PCR positive.

1 H/o treatment of Kala-azar may be absent in some cases of PKDL.

2RDT rk39 may be negative in some instance and should be diagnosed by slit skin smear.

* In some cases PKDL may coexist with KA (Para-Kala-azar Dermal Leishmaniasis)

Cutaneous Leishmaniasis (CL):

CL should be suspected in a person or a case of single or multiple skin ulcer (granulomatous) who travelled in an endemic areas of CL (Middle East, South America, Africa etc.).

CL should always be confirmed by demonstration of parasite from the lesion by slit skin smear, skin biopsy or parasite DNA in tissue specimen.

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2.3 KALA-AZAR WITH CO-INFECTIONS

The most frequent causes of death of Kala azar patients are due to presence of co-morbidities. The

common co-morbid illness are Kala-azar-TB co-infection, Kala-azar hepatitis co-infection, Kala-azar with

hematological diseases, Kala-azar-HIV co-infection, Kala-azar with Diabetes, Kala-azar in pregnancy,

Kala-azar Malaria co-infection, etc. All efforts should be made to diagnose KA with co-morbid illness by

parasitological examination of splenic smear or bone marrow or PCR. In cases of Kala-azar HIV co-

infection 'rK39' test may be negative. Patients with Kala-azar in special situations should be referred to

the required level of health facilities as appropriate.

Bangladesh is a country where both TB and Kala-azar exist. SK-KRC, a specialized research centre, had

diagnosed four cases of NKA having pulmonary tuberculosis, two cases of NKA with malaria, and six

cases NKA with Hepatitis in 2014 (Dr. Ariful Basher, SK-KRC). Hasnain et al (2013) reported a first case

of Kala-azar TB co-infection from a village of Trishal Upazila, one of the hyper-endemic areas of

Mymensingh District. The case was first identified as TB and was treated with TB drug according to the

National TB Guideline of Bangladesh. After taking 5-week of anti-TB drug the patient was diagnosed as

Kala-azar and was treated with AmBisome. With completion of successful treatment, the patient

recovered fully from TB and Kala-azar.3

Kala-azar HIV/AIDS co-infection has been appeared to be an increasing problem in countries such as

Ethiopia, Sudan and Brazil where both infections are becoming more and more prevalent. In Asia, co-

infections are increasingly being reported in India, which also has the highest global burden of Kala-azar.

KA-HIV coinfection is currently reported for 2-9% of all cases in given countries of endemicity. In India,

the first case of KA-HIV coinfection was reported in 1999; the KA-HIV coinfection rate has increased

from 0.88% in 2000 to 2.18% in 2006. In a case series from India, rate of HIV positive among PKDL

patients ranged from 1.5% to 6.3%. One hospital-based study in India reported a KA prevalence of 2.84%

among HIV-positive patients in 2006.

In Nepal, a study conducted for a period of one year from June 2003 to May 2004 in 39 hospitals showed

that 140 of 854 febrile patients had New Kala-azar and 8 of these were HIV positive (5.7%). Both NKA

and PKDL patients co-infected with any type of infection may act as an important reservoir of parasites

with high potential to maintain infection rates.

In Bangladesh, no case of Kala-azar HIV/AIDS co-infection has been reported so far. The diagnosis of

Kala-azar HIV co-infection is difficult because the clinical signs and symptoms are non-specific, and

splenomegaly is less frequent and most of these patients have other associated opportunistic infections

with similar symptoms, which usually complicate the clinical diagnosis.

3 Hasnain MG, et al (2013). Clinical Case Reports: First case of pulmonary tuberculosis and visceral leishmaniasis co-infection

successfully treated with anti-TB drug and AmBisome. Center for nutrition and food security, icddrb, Dhaka, Bangladesh.

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Table 3: Diagnosis of Kala-azar in different level of health facilities in Bangladesh

I. UHC, Union Sub Centre, Community Clinic:

Union Sub Centres, Community Clinic or others 1. Identify cases with fever for more than 2 weeks of duration 2. Identify cases having hypomelanotic, macular, papular or nodular skin lesions but no other signs 3. Refer the patients with above problems to UHC for evaluation, testing and treatment for NKA/PKDL Upazila Health Complex (UHC) 1. Check patients with fever for more than 2 weeks associated with splenomegaly 2. Check patients with hypomelanotic, macular, nodular or mixed lesions without loss of sensation 3. Perform ‘rK39’ RDT:

- On all patients with fever for more than 2 weeks and have splenomegaly - Patients with macular, papular or nodular or mixed lesions and no loss of sensation.

4. Treat NKA and PKDL patients with first line drugs

5. Refer complicated NKA, PKDL andsuspected RKA cases for tissue biopsy and unresponsive cases of Kala-azar to District Hospital

II. District Hospital

1. Check patients with fever for more than 2 weeks associated with splenomegaly 2. Check patients with hypomelanotic, macular, nodular or mixed lesions without loss of sensation 3. Perform ‘rK39’ RDT:

- On all patients with fever for more than 2 weeks and have splenomegaly - Patients with hypomelanotic, macular or nodular or mixed lesions and no loss of sensation

4. Treat NKA and PKDL patients with first line drugs

5. Refer complicated NKA, PKDL and RKA cases for parasitological confirmation to tertiary hospital

III. Tertiary Hospital

1. Treat unresponsive New Kala-azar, RKA or PKDL 2. Perform slit skin smear/biopsy in suspected cases of PKDL that are ‘rK39’ test negative or previously treated

as a PKDL cases 3. Perform bone marrow/splenic aspiration in patients where these are indicated, as a part of drug monitoring

studies or as a part of quality assessment

4. Treat any complications associated with bone marrow/splenic aspirate

IV. Specialized Centers: Surya Kanta Kala-azar Research Centre (SKKRC)

1. Perform PCR and other diagnostic tools like Elisa, IFA and other tests for establishing the diagnosis of NKA and PKDL in cases that are suspected to have the disease but ‘rK39’test is negative

2. Diagnosis and management of RKA

3. Diagnosis and management of Kala-azar with co-infection/co-morbid disease/any complications.

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2.4 DIAGNOSIS OF KALA-AZAR USING rK39 RDT:

2.4.1 Types of diagnostic tests available for Kala-azar:

Kala-azar diagnosis is confirmed through microscopic examination by identifying parasite (LD bodies) in

tissue aspirates from spleen, bone marrow or lymph nodes. The sensitivity and specificity of splenic

aspirate is 100%, but this procedure carries a risk of fatal internal bleeding (~1 in 1000 procedures). Bone

marrow and lymph nodes aspiration are safer but less sensitive. The confirmation can also be done by

culture of parasite or PCR. The PCR of skin specimens is the most sensitive (but not 100%) diagnostic

tool for PKDL cases and therefore, PCR should be encouraged for the diagnosis of PKDL cases. Slit-skin

smear or skin biopsy is another diagnostic tests used for patients with skin involvement. These techniques

require technical expertise which is often not available in field settings.

Antibody detection tests, such as the enzyme linked immuno-sorbent assay (ELIZA) and immuno-

fluorescent antibody test (IFAT) have been developed for the diagnosis of VL. Their utility in the field is

limited because they require a well-equipped laboratory and skilled personnel. However, two serological

tests have been specifically developed for field use and they have been extensively evaluated in both the

laboratory and the field setting: (i) the direct agglutination test (DAT) using freeze dried antigen and (ii)

the rK39 immuno-chromato-graphic test generally referred to as the „rK39 RDT‟ (Figure-1). The test

procedures, interpretation of test, how to read the test result, and effectiveness of the test result and

advantages of rK39 RDT are described in details bellow:

2.4.2 Procedures of rK39 RDT:

The usefulness and effectiveness of a VL RDT lies in its simplicity. Medical Technologist (operator)

should always read the package insert carefully and follow the manufacturer‟s instructions. This is

especially important when whole blood is collected by finger prick. The test strip‟s membrane is pre-

coated with a recombinant rK39 on the test line region and chicken anti-protein A on the control line

region. The Figure-4 below shows the procedures to perform rK39 RDT test.

Figure 7: Procedures to perform RDT rK39 test1

In general, the rK39 test procedure is as follows:

Allow the blood or serum to reach room temperature prior to testing.

Remove the test strip from the pouch and place it on a flat surface so that the end of the strip is

facing downward as indicated by the arrows on the strip,

Add patient‟s specimen (serum/finger prick blood) to the absorbent pad on the strip,

Add 2-3 drops of the chase buffer solution provided with test kit,

Read the result after 10-20 minutes (according to manufacturer‟s instructions).

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2.4.3 Interpretation of test of rK39 RDT:

The test reading is:

Positive result: Both control and test lines appear. The sample tested has antibodies against

recombinant K39 antigen of Leishmania. Faint line should be considered positive.

Negative result: Only control line appears. There are no antibodies against recombinant K39 antigen

of Leishmania.

Invalid result: No control line appears. In this situation, re-testing a fresh patient sample with a new

strip is mandatry.

Readings of rK39 RDT: The Figure-5 shows the interpretation of rK39 Strip.

Figure 8: Interpretation of rK39 Strip

2.4.4 Effectiveness of rK39 RDT in detecting Kala-azar:

rK39 RDT is effective for the detection of only new kala-azar cases. When used according to the

manufacturer‟s instructions, the rK39 RDT is highly effective in detecting VL especially in new kala-

azar. A comprehensive scientific review of published studies estimated the followings:

Sensitivity of rK39 RDT: 93.9% (87.7% - 97.1%) compared to parasitology. Sensitivity appeared higher

and more homogeneous in the studies conducted in South-Asia.

Specificity of rK39 RDT: 90.6% (66.8% - 97.9%) compared to parasitology. Cunningham J et al (2012)

documented the sensitivity range of rK39 RDT was 92.8% - 100% and its specificity range 96% - 100%.4

2.4.5 Advantages and disadvantages of rK39 RDT:

The rK39 RDT is simple to perform with minimal training; the test can be performed both at UHC and in

the field setting allowing the patients to be diagnosed closer to their homes; the test can be performed

with simple finger-prick whole blood, serum or plasma; the rK39 RDT kit can be transported and stored

at ambient temperature up to 300C; and most importantly the results are available within 10-20 minutes.

4Cunningham J, Hasker E, Das P, et al. A Global Comparative Evaluation of Commercial Immunochromatographic Rapid Diagnostic Tests

for Visceral Leishmaniasis. Clinical Infectious Diseases Advance Access Published in September 20, 2012.

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With all these good advantages, the rK39 RDT cannot separate the active cases from the relapse cases of

kala-azar, the cases which have been treated previously; therefore the interpretation must be accompanied

by clinical case definition. In patients with advanced HIV infection or tuberculosis, a negative result with

rK39 RDT should not rule out the diagnosis of NKA or PKDL cases.

2.4.6 Use of rK39 RDT in National Kala-azar Elimination Program:

The table-4 below shows the comparison of results of laboratory diagnostic tests using rK39 RDT in three

consecutive years (2014, 2015 and Jan-Oct 2016) in five hyper-endemic upazila of Mymensingh District,

Bangladesh. In 2014, a total of 5337 suspected cases of Kala-azar were identified and all were tested with

rK39 RDT; among them a total of 466 cases had been found positive with rK39 RDT. In 2015, a total of

6568 suspected cases were identified (23% more compared to the previous year in 2014) with 406 cases

(12.9% less than 2014) were positive with rK39 RDT. In year 2016 (Jan-Oct = 10 months), the number of

suspected cases of Kala-azar has been dropped to half with positive case was only 83

Table-4: Diagnostic test for suspected cases of KA using rK39 RDT5

SN Upazila Health Complexes (UHC)

YR - 2014 YR - 2015 YR – Oct 2016

rK39 Done

rK39 Positive

rK39 Done

rK39 Positive

rK39 Done

rK39 Positive

n n % n n % n n %

1 Fulbaria UHC 2333 169 7.2 2776 150 5.4 1380 17 1.2

2 Trishal UHC 779 137 17.6 648 107 16.5 237 32 13.5

3 Gafargaon UHC 990 79 8.0 1922 62 3.2 349 15 4.3

4 Bhaluka UHC 694 57 8.2 599 49 8.2 783 8 1.0

5 Muktagacha UHC 541 24 4.4 623 38 6.1 437 11 2.5

5337 466 8.7 6568 406 6.2 3186 83 2.6

The table above shows the number of positive case in Fulbaria and Trishal upazila was much higher

compared to other three upazilas (Gafargaon, Bhaluka and Muktagacha) in 2014-2015. In 2016, the

number of positive cases was less indicating the program effectiveness. The average kala-azar detection

rates are 2.02 in 2014; 1.76 in 2015 and 0.36 in Oct 2016.

The most complicated kala-azar cases were referred to SK-KRC from different hyper-endemic upazilas of

Bangladesh. The SK-KRC (Kala-azar Research Centre) has a specialized laboratory diagnostic facilities

carrying out splenic aspiration, slit-skin smear/biopsy, polymerase chain reaction (PCR), bone marrow

aspiration and rK39 RDT. In 2014 the SK-KRC carried out laboratory diagnostic tests of 604 suspected

new cases of kala-azar using rK39 RDT and a total of 320 (53.0%) patients had been found positive with

rK39 RDT.

5 Dr. M G Mostafa (2015). Review of National Kala-azar Elimination Program, Bangladesh (2011-2015). Disease Control Division, CDC,

Directorate General of Health Services (DGHS), Dhaka, Bangladesh. p-14

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CHAPTER: THREE

TREATMENT OF NEW KALA-AZAR (NKA),

POST KALA-AZAR DERMAL LEISHMANIASIS (PKDL)

AND CUTANEOUS LEISHMANISIS (CL)

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3. TREATMENT OF KALA-AZAR, PKDL AND CL

The primary objective of treatment for Kala-azar is to cure the patient, prevent complications of the

disease, minimize side effects of medicines, prevent emergence of drug resistance, and reduce the risk of

spread of kala-azar from the country. The secondary objective is to diagnose and treat appropriately the

complications and concomitant disease conditions if any arises.

3.1 TREATMENT OF NEW KALA-AZAR (NKA):

The Regional Technical Advisory Group (RTAG) of WHO/SEARO at its meeting in Dhaka in 2009

recommended introducing single dose Liposomal Amphotericin B (LAmB), which is safe, highly

effective and guarantee 100 percent treatment compliance. The NKEP of Bangladesh has sorted out

several issues while including LAmB (AmBisome) in the program and ensured maintenance cold chain

and space for drug storage; ensure supply of electricity round the clock or availability of generator;

conduction of training of doctors, nurses and other health care delivery workers for treatment of kala-azar

with AmBisome ensuring knowledge of Good Clinical and Laboratory Practices.

The NKEP has accepted the recommendation of RTAG and has approved the policy of introducing

LAmB (AmBisome) single dose as the drug of choice for the 1st line of treatment. Evidence obtained

from the randomized controlled trial shows that a total dose of ≥ 10 mg/kg body weight results in a cure

rate of more than 95% in Bangladesh, India and Nepal. In India, a 90% cure rate was found with a single

dose of 5 mg/kg body weight, and a 98% cure rate was achieved with a single dose of 10 mg/kg.

In case of drug reaction with LAmB (AmBisome), alternative choice to 1st line of treatment is

Miltefosine, the dose of which is depended on age and body weight of the patients to be administered for

28 days. On the other hand, Paromomycin 15 mg/kg body weight in intramuscular form is another

alternative choice to 1st line of treatment to be dispensed daily for 21 days. Three different combination

of drug, which are alternative choice to 1st line treatment, are available, these are: (i) Miltefosine and

Paromomycin daily for 10 days; or (ii) LAmB (AmBisome) in single dose and Miltefosine daily for 7

days; or (iii) LAmB (AmBisome) in single dose and Paromomycin daily for 10 days (Table-6).

It has been reported that various combination regimens of LAmB (AmBisome), Miltefosine and

Paromomycin are highly effective and safe, all are above 95% efficacious; the program‟s choice can

depend on cost and availability. Combination therapy is expected to prevent or delay the development of

resistance of Leishmania donovani. The choice between monotherapy or combination therapy is a

complex one, and the context should be very carefully considered.

When we compare the efficacy of single dose infusions of LAmB (AmBisome) with that of combination

therapy, we found a single-dose infusion has a clear advantage over other drugs. However, it should be

administered in a safe and correct way, monitored and evaluated patients during infusion, maintained

quality, ensured cold chain, and stored the drug in a safe space with round the clock electricity supply. In

the absence of the above criteria a choice for a combination regimen seems the better option.

30 | P a g e

Table-5: Drug treatment of New Kala-azar (NKA)

Recommended Treatment Regimens for NKA:

First Line of Treatment (Ranked by preference)

1.

First Drug of Choice - First Line of Treatment:(Annex: SOP of Single Doses of AmBisome)

Liposomal Amphotericin B (LAmB):

10 mg/kg as a single dose by IV infusion with 5% dextrose solution over a period of 3-4 hours

2.

Alternative Drug of Choice - First Line of Treatment:

Miltefosine: (Recommended dose schedule)

Age 2-11 years: 2.5 mg/kg twice daily with meal x 28 days (Not exceeding 50 mg/day)

Age ≥ 12 years & wt < 25 kg: 50 mg daily in the morning with meal x 28 days (Total 50 mg/day)

Age ≥12 years & wt 25-50 kg: 50 mgtwice daily with meal x 28 days (Total 100 mg/day)

Adult > 50 kg: 75 mg twice daily with meal x 28 days (Total 150 mg/day)

In case of missed doses, treatment should be continued up to 35 days to complete the full course. The daily dose should never exceed the recommended doses. If the exact doses cannot administered, the closet 10 mg increment will be chosen at the dose. Rounding will be done as follows: If the calculation comes to <5 – to round the dose down If the calculation comes to >5 – to round the dose up

3.

Combination Therapy6 to First Line of Treatment

First Drug of Choice:

LAmB: 5 mg/kg as a single dose IV plus Paromomycin: 15 mg/kg/day IM for 10 days

Alternate Drug of Choice:

Miltefosine plus Paromomycin: Daily for 10 days, the daily doses/route should be as above OR

LAmB: 5 mg/kg as a single dose IV infusion plus Miltefosine: Daily orally from day 2 to day 8

2nd Line of Treatment (Ranked by preference)

1.

Amphotericin B deoxycholate:

0.75-1.0 mg/kg/day by infusion, daily or on alternate days for 15-20 doses.

2. Sodium Stibogluconate (Pentavalent antimonials):

20 mg Sb5+

/kg/day IM or IV for 30 days.

Note: The 2nd line of treatment including Amphotericin B Deoxycholate and Sodium Stibogluconate (SSG) are no longer used in NKEP of Bangladesh since the 1st line of treatment is found much more superior and effective.

Indications of 2nd Line Drugs: When 1rst Line Drugs are not available or not tolerated or previously used in case of retreatment cases.

6Three separate combinations showed 98-99% cure rate. Control of the Leishmaniasis: WHO Technical Report Series-949. P-59

31 | P a g e

Table-6: Drug Treatment of Retreatment Kala-azar (RKA) (including Kala-azar Treatment Failure and Relapse Kala-azar)

Recommended Treatment Regimens for RKA:

Combination Therapy – First choice of treatment for RKA

1.

LAmB single dose + Paromomycin for 10 days in combination as follows:

LAmB: 5 mg/kg as a single dose by infusion on 1st

day plus Paromomycin: 15 mg/kg/day IM from 2

nd day to 11

th day for 10 days

Combination Therapy – Second choice of treatment for RKA

1.

Miltefosine plus Paromomycin:

Daily doses and duration are same as described for the treatment of NKA for 10 days

2. LAmB plus Miltefosine:

LAmB: 5 mg/kg as a single dose by IV infusion on 1st

day plus Miltefosine: Daily orally from 2

nd day to 8

th day for 7 days

Note: The second choice of combination therapy is only recommended when the first choice of combination therapy

cannot be administered because of intolerance, hypersensitivity or for any other contraindication.

In RKA cases, if combination treatment fails, then the standard Liposomal Amphotericin B should be given as follows: Inj. LAmB- 3 mg/kg/day total 15 mg/kg in 5 divided dose in alternative days or 5mg/kg/day in 3 divided dose in alternate days

Assessment of cure at 1st month (Initial cure):

• Improvement of all clinical parameters including absence of fever

• Reduction of spleen size.

• Gain in body weight.

Assessment of cure at 6 months (Definitive cure):

• No fever.

• Substantially reduced spleen size or not palpable.

• Feeling of general wellbeing.

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3.2 TREATMENT OF POST KALA-AZAR DERMAL LEISHMANIASIS

Pathogenesis: The pathogenesis of Post Kala-azar Dermal Leishmaniasis (PKDL) occurs usually after the

treatment of visceral leishmaniasis (VL) in a proportion of patients, and is considered to be triggered

immunologically7. In VL the predominant immune response is a Th2 response; whereas in PKDL there is

a mixed Th1 and Th2 response with persistence of interleukin 10 (IL-10). It is difficult to predict who will

develop PKDL. Inadequate treatment for VL for example, treatment with a low dose of medicine or for a

short/incomplete duration, young age generally 5-17 years, malnutrition, HIV infection and antiretroviral

treatment may play a part in the development of PKDL. There are no proven predictors of PKDL, such as

the degree of splenomegaly or hepatomegaly during VL. PKDL occurs almost exclusively in patients with

VL caused by L. donovani. In biopsy samples, PKDL in India shows a diffuse dermal infiltrate of

macrophages, lymphocytes and plasma cells.

The inflammatory cells are mainly CD3+ cells; IL-10 is predominant in the lesions; interferon-gamma is

found uniformly; and IL-4 is present in varying amounts. Diminished expression of Th1-Type Cytokines

(interferon-gamma) receptor 1 (R-1) and tumour necrosing factor R1 and R2 receptors during PKDL may

interfere with an effective host response. IL-10 expressing CD3+CD8+ lymphocytes are prominent, and

their level decreases with treatment. Patients with PKDL present raised levels of immunoglobulins (G3

and G1) and increased serum levels of IL-10. High serum concentrations of IL-10 during visceral

leishmaniasis correlate with subsequent development of PKDL. Anti-retroviral treatment during

HIV/AIDS co-infection can lead to PKDL. Favorable outcomes for patients with PKDL are predicted by a

positive leishmanin skin test or when levels of interferon-gamma (pro-inflammatory responses) are higher

than levels of IL-10 (anti-inflammatory response).

Clinical Manifestation: PKDL patients with their mild skin rash do not normally present to a health

facility. They do not have fever, and the physical examination is usually normal with no splenomegaly.

But in course of the disease, the skin manifestations may cause significant social and clinical discomfort.

Sometimes the lesions of PKDL are extensive covering mucosa of the lips and palate. In PKDL cases,

sensation over the lesions is preserved in contrast to leprosy where lesions have no sensations.

In Indian subcontinent, most of the patients have a polymorphic presentation comprising macular, papular

or nodular skin lesions, with prediction for the area around the chin and mouth. This presentation can be

subdivided into different forms as monomorphic (macular and nodular), polymorphic or mixed (both

macules and indurated lesions such as papules are present) and rare presentations (for example,

erythrodermic). The severity may be described as: mild with few skin lesions usually on the face;

moderate with lesions easily visible and generalized; and sever with dense coverage with lesions and little

normal skin remains.

Diagnosis: The cases of PKDL usually do not have any signs of kala-azar like fever, splenomegaly, or

anemia because 85-90% of them appear after the cure of kala-azar. It is documented that 15% of cases of

PKDL occur without the preceding history of kala-azar. Therefore, PKDL should be suspected in patients

7 T-Lymphocytes (T helper cells) are regarded as being the most prolific cytokine producers. T helper cells are subdivided into Th1 and

Th2, and the cytokines they produce are known as “Th1-Type Cytokines (interferon gamma)” and “Th2-Type Cytokines (interleukins 5, 9, 10, & 13)”. Cytokines (Th1-Type Cytokines and Th2-Type Cytokines) are the hormonal messengers responsible for most of the biological effects in the immune system, such as cell mediated immunity and allergic type of responses. The optimal scenario is that humans will produce well balanced Th1 and Th2 response, suited to the immune challenge.

33 | P a g e

in endemic areas who present with a skin rash combined with previous or concomitant visceral

leishmaniasis. The diagnosis can be made using clinical criteria or by identifying parasite, or both.

Clinical diagnosis is made by assessing the presence of the typical rash, its distribution, whether the

patient has a history of VL, or PKDL can also occur without previous VL; whether the patient lives in an

endemic area or has a recent history of travel to endemic area.

The rK39 RDT is usually positive in both papular and nodular lesions. A negative diagnostic test with

rK39 RDT in macular lesions does not rule out the possibility of PKDL. In such cases and also in nodular

and papular lesions, the diagnosis may be confirmed by biopsy or scraping of slit-skin in which the

smears are more likely to show amastigotes form of parasites; samples are least likely to show

amastigotes if taken from macular lesions. Culture can be attempted but it takes time and contamination is

common. Skin biopsies may also be examined by histopathology and immuno-histo-chemistry.

Polymerase chain reaction (PCR) tests performed with skin biopsy samples or slit-skin smear is much

more sensitive. The sensitivity of this test varies depending on the PCR method used and the type of

lesions. Quantitative PCR used to assess slit-skin specimens has been shown to be highly sensitive.

Treatment: The PKDL, a primary complication of NKA, is acting as potential reservoir for transmission

of visceral leishmaniasis. PKDL develops within a median time of 21 months (range, 0-120 months) after

VL, and most often is untreated. A severe form of the PKDL disease is very difficult to treat in some

patients. The most important challenges for the clinicians for the treatment of PKDL cases are the reliable

estimates of the burden of infection, infectiousness, pathogenesis, clinical presentations, determination of

the most infective types of PKDL lesions, effective treatment and control. The incidence of PKDL is

reducing in Bangladesh and India after introduction of Liposomal Amphotericin B (LAmB) and

Miltefosine for the treatment of NKA. An initial cure rate of 95% has been achieved with miltefosine for

the treatment of PKDL. However, the efficacy of combination therapy should be explored to reduce the

treatment duration and hence to improve treatment compliance. Younis BM, et al (2015) documented that

Paromomycin and SSG combination therapy was effective, time-saving and safe in treating PKDL cases

within 30 days8 (Table-8).

The objective of treatment of PKDL is the disappearance of all skin lesions of the patients; however, there

is no self-healing of the lesions in the Indian subcontinent. The treatment of PKDL at present is

unsatisfactory, although various regimens have been tried with variable success. There is no standard

treatment of PKDL approved by the national programme. In Bangladesh the number of VL cases are

decreasing, however, true PKDL rates are not known because of the inadequate and losses to follow-up of

PKDL cases. The frequent adverse effects of Miltefosine, 12 week long duration of drug treatment,

potential for emergence of resistance, compliance to Miltefosine treatment, and losses to follow-up are

some of the great concern for the treatment of PKDL patients in Bangladesh.

Treatment of PKDL requires long courses of therapy and very few clinical trials have been conducted to

compare the different regimens. The NKEP of Bangladesh has adopted and approved the policy to treat

PKDL patients with oral Miltefosine for a period of 12 weeks. The dose of Miltefosine is depended on

age and body weight and should be dispensed in divided doses with meal (Table-8).

8 Younis BM, et al (2015). Cure of post kala-azar dermal leishmaniasis with paromomycin/sodium stibogluconate combination: a proof of concept. Int J Res Med Sci. 2015; 3(1):16-21.

34 | P a g e

Table-7: Treatment regimens for PKDL

Recommended Treatment Regimens for PKDL:

First Line of Treatment: Drug of Choice – Miltefosine for 12 weeks duration

1.

Miltefosine: (First Line of Treatment –Drug of Choice)9

Age 2-11 years: 2.5 mg/kg twice daily with meal x 12 weeks (Not exceeding 50 mg/day)

Age ≥ 12 years & wt < 25 kg: 50 mg daily in the morning with meal x 12 weeks (Total 50 mg/day)

Age ≥12 years & wt 25-50 kg: 50 mg twice daily with meal x 12 weeks (Total 100 mg/day)

Adult > 50 kg: 75 mg twice daily with meal x 12 weeks (Total 150 mg/day)

In case of missed doses, treatment should be continued up to 16 weeks to complete the full course.

Second Line of Treatment: Alternative Drug of Choice

1.

Liposomal Amphotericin B (LAmB) 3-5 mg/kg/body weight/dose for maximum of 21 mg/kg total dose, not more than 10mg/kg body weight/week (Total dose should be given over 2-4 weeks) OR

2.

Sodium Stibogluconate (Pentavalent antimonials): 20 mg Sb

5+/kg/day IM or IV for 20 days/cycle. (Total 6 cycles, 10 days gap between cycles). OR

3.

Amphotericin B deoxycholate: 0.75-1.0 mg/kg/day by IV infusion in 5% dextrose daily or on alternate days 4 hours for 15-20 doses.

4 courses of 20 injections over a period of 5-6 months; 20 injections preferably should be given every alternate day dose. One course should be followed by a day course of drug free period.

This above treatment schedule reduces the severity of skin lesions by the end of treatment and it takes an

additional 4-6 months for lesions to heal completely. In some cases, the lesions subside but the glandular

swelling remains.

The NKEP of Bangladesh has discarded drugs such as Amphotericin B deoxycholate and Sodium

Stibogluconate which are considered as the 2nd line of treatment for PKDL. Because of SSG‟s length and

associated toxicity, patients have difficulty tolerating the treatment. High doses of Amphotericin B

deoxycholate are needed to treat PKDL; total doses of up to 4.5 g are given as 1-1.5 mg/kg/day

intravenous or alternate day for 15 doses per cycle; 6 cycles to be followed within 10 days gaps after each

cycle. Amphotericin B deoxycholate is highly phlebotoxic, cardiotoxic and nephrotoxic and hence are no

longer used in Bangladesh. However, Miltefosine has a clear advantage of being an oral drug.

9In the treatment of PKDL, Miltefosine has shown a cure rate in immunocompetents patients of 94% in India. The evidence is obtained from at least one properly designed randomized controlled trial.

35 | P a g e

Cure Assessment of PKDL: Skin lesions are considered for the cure assessment of PKDL whether the

lesions are disappearing or not. The assessment should be done as follows:

1st assessment should be done at 3 months after completion of the treatment,

(A considerable reduction in the number and size of skin lesion (macules, papules, plaques and nodules)

2nd assessment should be done at 6 months after completion of the treatment, and

3rd assessment should be done at 12 months after completion of the treatment.

(Defined as a complete resolution of macules, papules, plaques and nodules)

3.3 TREATMENT OF CUTANEOUS LEISHMANIASIS (CL):

The clinical spectrum of cutaneous leishmaniasis (CL) is broad and may mimic that of other skin

conditions, such as staphylococcal or streptococcal infection, mycobacterial ulcer, leprosy, fungal

infection, cancer, sarcoidosis and tropical ulcer. As the clinical presentation of CL lacks specificity and

treatment is costly, cumbersome or toxic, diagnostic confirmation is required. The diagnosis of CL can be

broadly divided into two categories: (i) parasitological diagnosis and (ii) immunological diagnosis.

Material for parasitological diagnosis can be obtained by skin scraping, fine-needle aspiration or biopsy

of lesions. The material obtained by any of these methods can be used for microscopic examination,

culture and molecular diagnostic techniques. Detection of parasite nucleic acids by molecular diagnosis,

especially by PCR-based methods, improves the diagnostic sensitivity and allows identification of the

Leishmania species. Immunological diagnosis using leishmanin skin test may be useful in

epidemiological studies but is of little value in the diagnosis of CL. Neither serological tests nor the

leishmanin skin test distinguishes between past and present infections.

CL is not a life-threaten condition, and severe complications are infrequent. In some cases the superficial

secondary infections may complicate ulcerated CL and it is therefore important to clean the lesions. The

treatment approach largely depends in part on the leishmania species/strain and the geographic areas in

which infection was acquired. In general, the first sign of a therapeutic response to adequate treatment is

decreasing indurations (lesion flattening). The healing process for large, ulcerative lesions often continues

after the end of therapy.

The systemic treatment options for CL are: (i) first line of treatment includes Miltefosine or pentavalent

antimonials (sodium stibogluconate); and (ii) second line of treatment are pentamidine (antiprotozoal

agent), paromomycin sulphate, ketoconazole, intraconazole and fluconazole. The table-9 below shows the

recommended treatment regimens for CL in Bangladesh.

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Table-8: Treatment of Cutaneous Leishmaniasis (CL)

Recommended Treatment Regimens for CL:

First Line of Treatment: Drug of Choice

1. Miltefosine:

Age 2-11 years: 2.5 mg/kg twice daily with meal x 28 days (Not exceeding 50 mg/day)

Age ≥ 12 years & wt < 25 kg: 50 mg daily in the morning with meal x 28 days (Total 50 mg/day)

Age ≥12 years & wt 25-50 kg: 50 mg twice daily with meal x 28 days (Total 100 mg/day)

Adult > 50 kg: 75 mg twice daily with meal x 28 days (Total 150 mg/day)

In case of missed doses, treatment should be continued up to 35 days to complete the full course. OR

2. Liposomal Amphotericin B (LAmB)

3-5 mg/kg/body weight/dose for maximum of 21 mg/kg total dose, not more than 10mg/kg body

weight/week (Total dose should be given over 2-4 weeks) OR

3. Sodium Stibogluconate (Pentavalent antimonials)

20 mg Sb5+

/kg/day IM or IV for 20 days.(10 days may suffice based on clinical judgment).

Second Line of Treatment

1. Ketokonazole: 600 mg daily for 28 days, OR

2. Itraconazole: 200 mg twice daily for 28 days, OR

3. Fluconazole:200 mg daily for 6 weeks (for adult)

Note: The description of drugs used for the treatment of Kala-azar is attached in Annex-8.

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3.4 DIAGNOSIS AND TREATMENT OF KALA-AZAR IN SPECIAL

SITUATIONS:

The diagnosis and treatment of Kala-azar can be difficult in the following special situations such as:

children under 2 years old, pregnancy, married women of reproductive age who are not using

contraceptives regularly, women who are breast feeding their babies, and severe anemia (Hemoglobin

less than 5 g/dl).

Under the above special circumstances, the diagnosis and treatment should be decided cautiously.

Patients with Kala-azar in special situations should be referred to the required level of facility as

appropriate. The patient‟s treatment outcomes should be closely monitored.

The diagnosis and treatment of Kala-azar in special situations is recommended in centers where

appropriate clinical expertise and health facilities are available. The following conditions can be

considered as special situations:

Pregnancy:

In pregnancy, rK39 RDT may be negative due to altered immunity in pregnancy. The confirmation of

diagnosis can be done by either PCR or parasitological diagnosis through spleen puncture or bone

marrow aspiration in specialized centre. Risk of treatment should be weighed against benefit.

Treatment should be prioritized according to the severity. If a pregnant mother is diagnosed as NKA

during 1st trimester, she should be treated at 2

nd trimester, or if she diagnosed as NKA during 3

rd

trimester then she should be treated after delivery. Kala-azar with pregnancy should be treated with

LAmB as there is proven safety profile for using LAmB in pregnancy in SKKRC. Preferable doses

for Liposomal Amphotericin B will be 5 mg/kg body weight on alternate days for 3 doses or 3mg/kg

body weight for 5 doses in alternate days. Miltefosine and Sodium Stibogluconate are contraindicated

in case of pregnancy.

In Bangladesh a total of 4 cases of New Kala-azar (NKA) in pregnancy have been reported and

treated in SK-KRC in 2014. All four cases of NKA have been found positive with rK39 RDT and

treated with Injection AmBisome. The encouraging result is that all pregnant women delivered

healthy babies. One of 4 women developed PKDL after one year of treatment but the child was found

free from kala-azar. However, one of 4 babies was positive with rK39 RDT and has splenomegaly at

the age of one and half month (Dr. Ariful Basher of SK-KRC).

Rahman KM, et al (2014) described Kala-azar in pregnancy, a case identified from Fulbaria Upazila

of Mymensingh, using a method of social autopsy.10

Miah MT, et al (2010) in their retrospective

study conducted during 2005 to 2009 and documented a total of 16 Kala-azar cases in pregnancy, of

which 11 cases experienced miscarriage with no maternal deaths.11

The abortion took place mostly

between 22 to 24th day of treatment with Sodium Antimony Gluconate (SAG). The researchers in

their conclusion suggested that the kala-azar in pregnancy cases should not be treated with SAG in

early or mid-pregnancy.

10

Rahman KM, et al (2010). Kala-azar in Pregnancy in Mymensingh, BD: A Social Autopsy. PloS, Negl Trop Dis. 2014 May; 8(5) e2710. 11

Miah MT, Ayaz FM, Maniruzzaman M, et al (2010). Kala-azar in Pregnancy. Mymensingh Med J 19: 529-532 PubMed.

38 | P a g e

Married women of reproductive age who are not using contraceptives regularly:

The diagnosis in this situation will be as usual for KA or other patients. The rK39 based diagnosis

will be sufficient for case definition. The drug of choice is single dose Liposomal Amphotericin B

(Miltefosine is contraindicated).

Women who are breast feeding their babies:

The diagnosis in this situation will be as usual for KA or other patients. The rK39 based diagnosis

will be sufficient for case definition .The drug of choice is Liposomal Amphotericin B but temporary

discontinuation of breast feeding for 2 weeks should be advised.

Kala-azar with severe anemia (Hemoglobin less than 5 g/dl):

The diagnosis in this situation will be as usual for KA or other patient .There should be transfusion of

whole blood to raise hemoglobin ≥6 gm/dl prior to commencement of treatment.

Kala-azar with TB:

The diagnosis in this situation will be as usual for KA or other patients. Only disseminated

tuberculosis may need confirmed diagnosis through PCR or parasitological confirmation through

bone marrow aspiration or spleen puncture. Treatment of both diseases should be continued

simultaneously and KA will be treated as NKA or RKA as per case definition.

Kala-azar HIV/AIDS co-infection:

In HIV/AIDS, rK39 may be negative due to immmunosuppression. The confirmation of diagnosis can

be done by either PCR or parasitological diagnosis through Spleen puncture or bone marrow

aspiration in specialized centre. It will be treated with Liposomal Amphotericin B with multiple

doses. ARV should be continued for HIV/AIDS.

Kala-azar in a patient suffering from another serious disease:

In serious diseases, rK39 may be negative due to altered immune reaction. The confirmation of

diagnosis can be done by either PCR or parasitological diagnosis through spleen puncture or bone

marrow aspiration in specialized centre. All the cases of Kala-azar with serious co-morbidities should

be treated under specialized supervision. Liposomal Amphotericin B will be the drug of choice and

treatment should be given in a tertiary care facility.

Asymptomatic Parasitaemia:

There is no recommendation to use any drugs for asymptomatic parasitaemia. The parasitological or

PCR based diagnosis should be followed up for development of symptom. As soon as symptom

develops, patient should be treated as NKA.

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3.5 COMPLETE TREATMENT OF KALA-AZAR:

Efforts should be made to ensure the complete treatment of kala-azar. The following measures are

recommended to complete the treatment:

Counseling: Every patient should be counseled so that the patient and family understand the

importance of complete treatment and the consequences of the incomplete treatment.

Free Medicine: All treatment should be free of cost to eliminate the economic constrains as a reason

for discontinuation of treatment.

Treatment Box: Each patient should have a separate treatment box kept at the health facility. The

box contains full dose of drugs labeled with the name, individual identification number, and number

of days the treatment received by the patients.

Follow-up patient: It is highly advisable to follow-up the patient during treatment, immediately after

treatment, and up to 12 months year (at 1st, 5th, 9th and 12th month). The treatment should be

directly observed as per SOP.

Coordination: There should be coordination amongst the public and private sector providers, and a

follow up plan should be develop for each patient.

40 | P a g e

Is there any evidence of another disease other

than kala-azar? Yes

Additional signs of kala-azar: Weight loss Anemia Darkening of skin

rK39 RDT Positive

Diagnosis: New Kala-azar (NKA)

No

Diagnosis: Post Kala-azar Dermal Leishmaniasis

(PKDL)

Diagnosis: Retreatment Kala-azar

Residing/travelling in the KA endemic areas,

H/O treatment for KA any time in the past,

Suggestive skin lesion without loss of sensation, which may be hypo-melanotic, macular, papular, nodular or mixed,

Exclusion of skin disease like Leprosy, Vitiligo, Pityriasis, Ring worm, Arsenicosis etc.

H/o fever ≥ 2weeks

Residing/traveling in endemic areas

Splenomegaly

If H/o treatment for KA

No improvement of initial treatment within one month or reappearance of symptoms & sign of KA

Confirmation: parasitologically by splenic smear or bone marrow examination or PCR.

rk39 RDT/Splenic aspirate/Slit skin smear/PCR Bone marrow positive

DIAGNOSIS

Kala-azar

Figure-9: Diagnosis of Kala-azar

Diagnosis: Kala-azar Treatment Failure (KATF)

Diagnosis: Relapse KA

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Figure 10: Treatment Chart for NKA

Treatment Chart

New Kala-azar (NKA)

1st Line of Treatment for NKA

1. Liposomal Amphotericin B (LAmB):Drug of choice 10 mg/kg IV infusion single dose with 5% dextrose

2. Miltefosine: 1st Alterative Choice a. Age 2-11 years: 2.5 mg/kg twice daily with meal x 28 days

(Not exceeding 50 mg/day) b. Age ≥ 12 years & wt < 25 kg: 50 mg daily in the morning with

meal x 28 days (Total 50 mg/day) c. Age ≥12 years & wt 25-50 kg: 50 mg twice daily with meal x

28 days (Total 100 mg/day) d. Adult > 50 kg: 75 mg twice daily with meal x 28 days (Total

150 mg/day)

3. Combination Treatment: 2nd Alternative Choice

a. LAmB 5 mg/kg IV infusion single dose on day 1 plus Paromomycin 15mg/kg IM from day 2 to day 11 OR

b. Miltefosine oral for 10 days plus Paromomycin 15mg/kg IM for 10 days OR

c. LAmB 5 mg/kg IV fusion single dose on day 1 plus Miltefosine oral for 7 days (from day 2 to day 8)

LAmB (special situations): Dose- 3-5mg/kg/day total 15mg/kg in every alternate day

2nd Line of Treatment for NKA

1. Liposomal Amphotericin B (LAmB) 3mg/kg/day total 15gm/kg in alternate day 5 doses

2. Amphotericin B deoxycholate

0.75-1.0 mg/kg daily or alternate day for 15 doses

3. Sodium Stibogluconate (SSG)

20mg/kg daily IM injection for 30 days

Note: In several phases, 3 studies done in India, three separate combinations showed 98-99% cure rate. The 2nd line of treatment including Amphotericin B Deoxycholate and Sodium Stibogluconate (SSG) are no longer used in NKEP of Bangladesh since the 1st line of treatment is found much more superior and effective.

42 | P a g e

TREATMENT OF PKDL

1. First Line of Treatment:

a. Miltefosine Adult dose: 100 mg daily in two divided doses for 12 weeks. Children: 2.5 mg/kg/day in two divided doses, not exceeding 50mg/day for 12 weeks.

2. Second Line of Treatment

a. LAmB 5mg/kg/day total 20mg/kg in 4 divided dose once in a week.

b. Sodium Stibogluconate (SSG) 20-mg/kg/day in intramuscular route. Total 6 cycles and each cycle consists of 20 days of treatment and 10 days in between two cycles.

c. Amphotericin B deoxycholate

Dose: 4 courses of 20 injections IV over 5-6 months in every alternate day dose.

TREATMENT FOR RKA

1. Combination Therapy: 1st Alternative Choice

LAmB + Paromomycin: LAmB B 5mg/kg IV infusion on day 1 Paromomycin 15mg/kg IM from day 2 to day 11

If for any reason this combination cannot be given for intolerance, hypersensitivity or relative contraindication, subsequent choice should be decided

2. Combination Therapy: 2nd Alternative Choice a.

Miltefosine + Paromomycin Miltefosine- oral form, the dose would be same as that of NKA for 10 days Paromomycin 15mg/kg IM for 10 days

LAmB + Miltefosine LAmB 5mg/kg IV infusion on 1

st day

Miltefosine oral tablet from 2nd

day - 8th

day x 7 days

Liposomal Amphotericin B (LAmB) (When combination fails) Dose- 3-5mg/kg/day total 15mg/kg in every alternate day

Treatment Chart

RKA, PKDL & CL

Figure-11: Treatment Chart of RKA and PKDL

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3.6 CLINICAL/TREATMENT OUTCOMES IN KALA-AZAR

The NKEP of Bangladesh has approved and adopted clinical/treatment outcomes for NKA and assessed

treatment outcomes twice in the following schedules:

Initial outcome is assessed in the last day of drug treatment, i.e., at the end of treatment (EoT);

Final outcome is assessed at the six month (6M) after the last drug was taken12

.

The NKEP has conducted training for doctors, nurses, medical laboratory technologist, and others health

personnel to distinguish four main outcomes in NKA treatment. The Table-11 shows the clinical

outcomes with case definitions of NKA.

Table-9: The Clinical/Treatment Outcomes with Case Definitions of NKA:

SN Treatment Outcomes Case Definitions

1.

Cure of NKA:

A patient is considered clinically cured if s/he has completed full course of treatment and there are no signs and symptoms of new Kala-azar.

2. Kala-azar Treatment Failure (KATF):

KATF: No improvement of initial treatment within one month or reappearance of Kala-azar signs and symptoms within 6 months will be defined as Kala-azar treatment failure Kala azar (KATF).

3. Relapse Kala-azar: Relapse: Any reappearance of Kala-azar signs and symptoms after 6 months after the end of treatment will be defined as Relapse case.

4. Non-Response: The signs and symptoms of the patient persist or recur despite satisfactory treatment for more than two weeks.

5. PKDL If a patient has developed PKDL within 6 months after completion of treatment of NKA.

6. Death Any death, whether or not related to Kala-azar within 6 months after completion of treatment.

All efforts should be made to diagnose RKA parasitologically by splenic smear or bone marrow examination or PCR

Early Treatment Outcomes: Early treatment outcomes are assessed in the last day of drug treatment,

i.e., at the end of treatment (EoT). The patient may have any of the following outcomes as a result of drug

treatment: (i) Initial cure: The patient has completed full course of treatment and has clinically improved

with no fever, regression of enlarged spleen, return to appetite and body weight gain; (ii) Non-response:

Despite receiving full course of treatment, the signs and symptoms of the disease persist or recur resulting

to switching to a second line of drug because of non-response to the first-line of drug; (iii) Side-effects

related change: Side-effects or adverse reaction may necessitate a change of treatment; (iv) Default (Loss-

to-Follow-up): The patient does not complete the treatment and/or does not present for assessment after

treatment ending up to loss-to-follow up; (v) The patient may develop PKDL, and (vi) Death: The patient

may die, whether or not the death is related to kala-azar.

Final Treatment Outcomes: Final treatment outcomes are assessed at the six month (6M) after the last

drug was taken. The final outcomes can only be reported on those patients with initial cure. The patient

12

Indicators for monitoring and evaluation of the Kala-azar elimination program, August 2010, WHO and TDR. P-5-7

44 | P a g e

may have any of the following final outcomes: (i) Final cure: The initial cure patient may have symptoms

free at six months follow up after the end of treatment; (ii) Kala-azar Treatment Failure (KATF):

Persistence presence of Kala-azar sign and symptoms after treatment or reappearance of Kala-azar sign

and symptoms within 6 months; (iii) Relapse: Any reappearance of kala-azar symptoms within a period of

six months after the end of treatment. This relapse should be identified preferably by parasitological

confirmation (spleen or bone marrow aspiration); (iv) Default or Loss-to-follow up: Patient does not

present for clinical assessment/evaluation at six months, and tracing has been unsuccessful; (v) PKDL:

patient has developed PKDL within 6 months after completion of treatment and (vi) Death: The patient

may die, whether or not the death is related to kala-azar.

Table-10: Early Treatment Outcomes with Case Definitions: (at 4 weeks after treatment completion)

SN Early Treatment Outcomes Case Definitions

1. Initial Cure Full course of drugs has been completed. The patient has clinically improved. Clinical criteria for cure is assessed as:

no fever, plus

regression of enlarged spleen, plus

return to appetite and/or body weight gain.

2. Non-response Signs and symptoms persist or recur despite satisfactory treatment for more than 4 weeks.

3. Adverse Drug Reaction (ADR) Side-effects related change or adverse drug reaction may necessitate a change of treatment

4. Default (Loss-to-Follow-up) The patient does not complete treatment and/or does not present for assessment after treatment.

5. PKDL If a patient has developed PKDL.

6. Death Any death, whether or not related to Kala-azar.

Table-11: Final Treatment Outcomes with Case Definition: (Final assessment should be done at 6 month after last drug taken)

SN Final Treatment Outcomes Case Definitions

1. Final Cure An initial cure patient who is symptom-free at six months after the end of treatment.

2. Kala-azar Treatment Failure

(KATF)

KATF: Persistence presence of Kala-azar sign and symptoms after treatment or reappearance of Kala-azar sign and symptoms within 6 months will be defined as KATF.

3. Relapse Kala-azar Relapse KA: Any reappearance of Kala-azar symptoms after a period of 6 months after the end of treatment. All efforts should be made to diagnose RKA parasitologically by splenic smear or bone marrow examination or PCR

4. Default (Loss-to-follow-up): Patient does not present for clinical assessment/evaluation at 6 months, and tracing has been unsuccessful.

5. PKDL If a patient has developed PKDL within 6 months after completion of treatment.

6. Death Any death, whether or not related to Kala-azar (at 6 months).

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3.6.1 Monitoring of Clinical/Treatment Outcomes Rates:

Monitoring of clinical/treatment outcomes of kala-azar treatment is programmatically considered very

important for the fact that the clinical outcomes help the program manager to provide information on

performance of the health care facilities and guide about drug policy at the national program level. The

results of the clinical outcomes can be achieved by (i) recording information about patients in the hospital

register, (ii) providing health education to patients and their relatives about the importance of treatment

adherence and needs for follow-up visit, and (iii) taking actions to trace the patients by the health

personnel in case of default or loss to follow-up. The monitoring clinical outcomes such as initial cure,

final cure, treatment failure, loss to follow-up, and mortality can be expressed by the help of the following

rates13

. Table-14 below shows the monitoring clinical/treatment outcomes rates.

Table-12: Monitoring Clinical/treatment Outcomes Rates

SN Monitoring Clinical/Treatment Outcomes Rates

1.

Initial Cure Rate (%)

=𝑵𝒐. 𝒐𝒇 𝒑𝒂𝒕𝒊𝒆𝒏𝒕𝒔 𝒘𝒊𝒕𝒉 𝒊𝒏𝒊𝒕𝒊𝒂𝒍 𝒄𝒖𝒓𝒆

𝑻𝒐𝒕𝒂𝒍 𝒏𝒖𝒎𝒃𝒆𝒓 𝒐𝒇 𝒑𝒂𝒕𝒊𝒆𝒏𝒕𝒔 𝒘𝒉𝒐 𝒔𝒕𝒂𝒓𝒕𝒆𝒅 𝒕𝒓𝒆𝒂𝒕𝒎𝒆𝒏𝒕𝑥 100

2. Final Cure Rate (%) =𝑵𝒐. 𝒐𝒇 𝒑𝒂𝒕𝒊𝒆𝒏𝒕𝒔 𝒘𝒊𝒕𝒉 𝒇𝒊𝒏𝒂𝒍 𝒄𝒖𝒓𝒆


3. Treatment Failure Rate (%) =𝑵𝒐. 𝒐𝒇 𝑵𝒐𝒏−𝑹𝒆𝒔𝒑𝒐𝒏𝒔𝒆𝒔+𝑲𝑨𝑻𝑭 +𝑲𝑨 𝑹𝒆𝒍𝒂𝒕𝒆𝒅 𝑫𝒆𝒂𝒕𝒉


4. Relapse Rate (%) =𝑹𝒆𝒍𝒂𝒑𝒔𝒆+𝑲𝑨 𝑹𝒆𝒍𝒂𝒕𝒆𝒅 𝑫𝒆𝒂𝒕𝒉


5. Loss to Follow-up Rate (%) =𝑵𝒐. 𝒐𝒇 𝑫𝒆𝒇𝒂𝒖𝒍𝒕𝒔+𝑵𝒐. 𝒐𝒇 𝒍𝒐𝒔𝒔𝒆𝒔 𝒕𝒐 𝒇𝒐𝒍𝒍𝒐𝒘−𝒖𝒑


6. PKDL Rate (%) =𝑵𝒐. 𝒐𝒇 𝑷𝑲𝑫𝑳 𝒄𝒂𝒔𝒆𝒔


7. Mortality Rate (%) =𝑵𝒐. 𝒐𝒇 𝑫𝒆𝒂𝒕𝒉𝒔


3.6.2 Key Indicator for Treatment Completion Rate of Kala-azar:

The target for treatment completion rate in any UHC, District Hospital, Tertiary Hospital or specialized

hospital should be above 90%14

.Without adherence to treatment, the patients will not benefit from it. They

will continue to spread the disease with the risk that the parasites may become resistant to the drug. The

treatment completion rate can be calculated as the number of patients that took a full course of first line of

drugs divided by all new Kala-azar patients that started treatment in a given period. The following table-

13 shows the treatment calculation rate.

13

Indicators for monitoring and evaluation of the Kala-azar elimination program, August 2010, WHO and TDR. P-9 14

Indicators for monitoring and evaluation of the Kala-azar elimination program, August 2010.. WHO and TDR, p-8

46 | P a g e

Table-13: Treatment Completion Rates

Treatment Completion Rate (%)

Treatment Completion Rate (%):

=𝑵𝒖𝒎𝒃𝒆𝒓 𝒐𝒇 𝒑𝒂𝒕𝒊𝒆𝒏𝒕𝒔 𝒕𝒉𝒂𝒕 𝒕𝒐𝒐𝒌 𝒂 𝒇𝒖𝒍𝒍 𝒄𝒐𝒖𝒓𝒔𝒆 𝒐𝒇 𝒇𝒊𝒓𝒔𝒕 𝒍𝒊𝒏𝒆 𝒅𝒓𝒖𝒈𝒔

𝑨𝒍𝒍 𝒏𝒆𝒘 𝑲𝑨 𝒄𝒂𝒔𝒆𝒔 𝒕𝒉𝒂𝒕 𝒔𝒕𝒂𝒓𝒕𝒆𝒅 𝒕𝒓𝒆𝒂𝒕𝒎𝒆𝒏𝒕 𝒊𝒏 𝒂 𝒈𝒊𝒗𝒆𝒏 𝒑𝒆𝒓𝒊𝒐𝒅 (𝒀𝑹)𝑥 𝟏𝟎𝟎

3.6.3 Monitoring of Clinical/Treatment Outcomes Variables:

In order to be able calculate the monitoring of treatment outcomes rates such as initial cure rate, final cure

rate, treatment failure rate, loss-to-follow-up rate, mortality rate, treatment completion rate, case detection

rate, and coverage rate of vector control in Kala-azar endemic areas within a given period of time (usually

in one quarter and one year), the NKEP should plan and design the functional strategy with annual action

plan and budget well ahead of time, develop appropriate forms and register book, and train the health

personnel how to fill-up the register book and different monitoring forms with an accuracy so that the all

relevant data flow from the UHC, hospitals and specialized centre to the NKEP, CDC- Dhaka. The annex-

9 shows monitoring clinical/treatment outcomes variables with starting and evaluation treatment.

3.6.4 The Clinical/Treatment Outcomes of PKDL:

Treatment outcomes in PKDL are also clinically assessed at primary health care level. The UHC facilities

should have the clinical capacity to resolve at least 80% cases of macules and/or a decrease in erythema

and flattening of lesions. These cases should be followed up in accordance with 4 follow up visit

schedules and among them 2 visits will be done for initial cure and final cure assessment:

1st visit: Immediately after completion of treatment

2nd

visit: 3 months after completion of treatment

3rd

visit: 6 months after completion of treatment

4th visit: 12 months after completion of treatment

The Treatment Outcomes of PKDL are shown in the table-14 as follows:

Table-14: Treatment Outcomes in PKDL Patients

SN Treatment Outcomes Case Definitions of PKDL

1. Initial Cure: Clinical improvement at the end of treatment that defined as a considerable reduction in the number and size of skin lesions in PKDL cases.

2. Final Cure: Clinical cure at 12 months after the end of treatment that defined as a complete resolution of macules, papules, plaques and nodules.

3. Partial Response More than 50% reduction in skin lesions (number and/or size of lesions) at one year only (on examination and/or as per patients statement)

4. PKDL Treatment Failure Less than 50% reduction in skin lesions (number and/or size of lesions) at one year only (on examination and/or as per patients statement)

47 | P a g e

3.6.5 Monitoring Treatment Outcomes Rates Calculations:

Patients Treatment records: For documentation of monitoring Kala-azar clinical/treatment outcomes,

the patient‟s history including registration number, name, NID, age, sex, address, and contact

mobile/telephone number should be recorded in the patient registrar book. The patient‟s history, physical

examination, laboratory diagnostic test results, treatment history, and any possible adverse drug reactions

(ADR) should be well recorded in the register book as well as appropriate formats and should be

preserved into the hospital‟s record room. All the records of the patients should be checked by the

relevant health personnel and should be countersigned by the Resident Medical Officer (RMO) of UHC,

Registrar of the Tertiary Hospital and Specialized Laboratory at SK-KRC.

Treatment compliance and follow-up strategy: During discharge from hospital after providing initial

treatment, the patients and his/her attendants should be counseled on treatment adherence in case of long-

term treatments (e.g., Miltefosine for 28 days or AmBisome if provided in 3-5 days duration, etc.). The

patient‟s follow-up strategy should be well designed and ensured that the patients make follow-up visit to

hospital according the follow-up schedule. Compliance of complete treatment and total follow-up

schedule are the two most important aspects that will ensure both initial and final cure, the most important

clinical outcomes of kala-azar patients. In order to be able to make complete follow-up visit, the

incentive-based approach should be implemented in the endemic areas and should be executed throughout

the year within the community focusing on the newly detected and treated KA and PKDL cases. Failure

to make complete treatment and compliance to total follow-up may produce default and loss-to-follow-up,

and may act as a reservoir for transmitting the disease.

RKA and TFKA: Despite complete and satisfactory treatment with full course of medicine, the patient‟s

signs and symptoms may persist or may recur producing Non-Response to treatment. In some cases the

Kala-azar signs and symptoms may reappear within six months after the end of treatment resulting

Relapse Kala-azar (RKA). In some cases the anti-kala-azar drug may not cure the disease resulting Kala-

azar Treatment Failure (KATF). Sometime adverse drug reaction may occur and the side effects

necessitate a change of treatment. In some rare occasion, kala-azar patient may die.

Monitoring toolkit: With early and final clinical/treatment outcomes to be recorded, the reporting format

should be developed in such as a way that it includes the summary of the outcomes, e.g., (i) the end-of-

treatment (EoT) outcomes of the most recently completed month/quarter to assess the Early Clinical

Outcomes (Annex-11: Monthly/Quarterly Format On Early Treatment Outcomes) and (ii) the 6 months

(6M) post-treatment outcomes to assess the Final Clinical Outcomes of the patients that were closed to 7

months (Annex-12: Monthly/Quarterly Format Of Final Treatment Outcomes).

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3.7 PHARMACOVIGILANCE ACTIVITIES:

3.7.1 Operational Plan for Pharmacovigilance Activities: The NKEP of Bangladesh has developed a guideline titled: “Operational Plan for Pharmacovigilance

Activities for Visceral Leishmaniasis in Bangladesh” and implemented the plan since September 2014

(25). The objective of the operational plan is to detect, assess, understand, document and prevent adverse

drug reaction (ADR) of the various regimens used to treat kala-azar patients and to improve the clinical

and treatment outcomes. The operational plan recommends the collection of safety and ADR of the drugs

such as Liposomal Amphotericin B, Miltefosine, Paromomycin, and Amphotericin B deoxycholate used

to treat kala-azar patients. The serious adverse events due to drug reactions may result in death, life

threatening or risk of dying, require inpatient hospitalization or prolongation of hospitalization, result in

persistent or significant disability or incapacity, and cause congenital anomaly or birth defect.

The scope of the operational plan is to orient and educate all healthcare professionals engaged with

diagnosis and treatment of Primary Kala-azar (PKA) and Post Kala azar Dermal Leishmaniasis (PKDL).

The followings are broad functions of pharmacovigilance articulated in operational plan such as:

detection and study of adverse reactions; measurement of risk; measurement of effectiveness; benefit and

harm evaluation; dissemination of information; education; early warning; and rational and safe use of

medicines. The functions of pharmacovigilance is also applicable to those dispensing drugs for kala-azar

patients, providing nursing care to such patients or other personnel directly involved in the collection and

analysis of adverse drug reaction data.

Kala-azar Elimination Program (KEP) in collaboration with icddr,b Dhaka, conducted training on

“Pharmacovigilance Activities for Kala-azar in Bangladesh” in two phases (first phase: 18-19 October

2014 and second phase: 14-15 November 2014). A total of 230 health care professionals (Doctors-78,

Nurses-73 and Statisticians-79) from 80 endemic upazilas of 26 districts received training on

pharmacovigilance activities. Health care professionals are expected to monitor for signs and symptoms

indicative of adverse drug reactions, and record promptly in the treatment sheet. Senior Staff Nurse (SSN)

of each UHC and other health facilities is the focal point person responsible to fill up the ADR Form and

the Doctor/RMO will check and sign the form and send it to KEP and icddr,b Dhaka Office on a monthly

basis (Annex: ADR Form). A soft copy should also be sent to icddr,b Dhaka Office. Sending report on a

monthly basis is applicable to non-fatal cases only. However, for fatal cases, the ADR report should be

sent to icddr,b Dhaka Office within seven days.

Analysis of the reported ADR information: The ADR data collected at KEP will be shared with the

Directorate General of Drug Administration (DGDA), Government of Bangladesh. Data Quality will be

checked and medically evaluated and causality will be assessed according to the WHO-UMC causality

assessment algorithm (Annex: WHO-UMC Causality Assessment Algorithm). The data are analyzed for

signals or alerts. Based on the data processing and analysis, appropriate recommendations and risk

mitigation plans will be developed and communicated to the relevant stakeholders. An expert committee

at KEP, Dhaka will review the data and generate information on a half yearly basis and make

recommendations to kala-azar elimination program.

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3.7.2 Indicators of Pharmacovigilance Activities: Operational plan for pharmacovigilance activities for Visceral Leishmaniasis is developed, approved and

operationalized in Bangladesh. Suspected Adverse Drug Reaction (ADR) reporting format have been

developed and both hard and soft copies are sent to health facilities of kala-azar endemic upazilas. The

ADR form is divided into five parts including (a) patient and hospital information, (b) history of VL

therapy, (c) suspected adverse event information, (d) other concomitant product information and (e)

reporter information. WHO-UMC Causality Assessment Algorithm is attached as an annex in the

operational plan and defined six causality terms with assessment criteria.

The operational guidelines should include the names of drugs, side effects/adverse drug reactions

produced as results of therapy and list of laboratory tests to be done as per the following table-15.

Table 15: Names of drug with side effects and the types of laboratory tests indicated

SN Names of Drugs

Adverse Drug Reaction/Side Effects Types of Laboratory Tests Indicated

1. LAmB Fever, chills and rigors during infusion; back pain, chest tightness or pain, headache, dyspnea, bronchospasm, flushing, tachycardia, hypotension; nephrotoxicity,

Complete blood counts; Electrolyte counts, Liver function tests, Blood urea and blood creatinine

2. MLF Gastrointestinal (nausea, vomiting, diarrhea & abdominal pain), nephrotoxicity (edema & decrease urine output), hepatotoxicity (jaundice), teratogenicity, fatal nephron/hepato toxicity in about 1% cases

Complete blood counts; Electrolytes; Liver function tests; kidney function tests

3. PMIM Nephrotoxicity, Ototoxicity, Hepatotoxicity

Kidney function tests including Blood Urea Nitrogen (BUN); Liver function tests; Vestibular testing

4. AMP-B Nephrotoxicity Kidney function tests including Blood Urea Nitrogen (BUN);

5. SSG Phlebotoxic (causing harm to vein), Pancreatitis, Cardiotoxicity, Nephrotoxicity, Vomiting, Diarrhea

Electrolytes; Renal functions tests; ECG

L.AmB = Liposomal Amphotericin B (IV); MLF = Miltefosine (Oral); PMIM = Paromomycin (IM); AMP-B = Amphotericin B deoxycholate (IV); SSG = Sodium Stibogluconate (Pentavalent antimonials) (IM/IV).

Each drug used in the program has some side effects. Common signs and symptoms likely to occur from

the drug given should be looked for. Although laboratory tests like haemogram, liver and kidney

functions tests, electrolytes and ECG are recommended to monitor patients, the inclusion of these tests in

the program is difficult. It is recommended that these tests could be a part of the protocol in selected

health facilities. Laboratory tests can help to recognize the occurrence of the side effects early. The

program strategy should take advantages of the experience of the health centers where monitoring of side

effects are done. The information can be complemented by regular reporting of major and minor side

effects by the program.

Laboratory Guidelines for Monitoring Anti-leishmaniasis Drugs should be developed. The guideline

should include the protocol, list of drugs used for VL treatment, list of side effects, list of laboratory tests

to be done to identify the levels and extents side effects; monitoring and evaluation the patients; tests to

be recommended in the special health facilities and monitor the results; indications for adopting timely

50 | P a g e

measures even before the signs appear; revision of reports of major and minor side effects obtained from

UHC; regular reporting the side effects on the ADR Reporting Forms to be sent to icddr,b Dhaka Office

once in a month for review and feedback. This will help guide the program in recommending tests that

should be done to monitor the patients on treatment. The Annex-13 shows the indicators for

monitoring pharmacovigilance activities.

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CHAPTER: FOUR

KALA-AZAR SURVEILLANCE SYSTEM

52 | P a g e

4. KALA-AZAR SURVEILLANCE SYSTEM

4.1 INTRODUCTION TO SURVEILLANCE

Bangladesh, an endemic country, is committed to eliminate Kala-azar and the country has declared Kala-

azar as a reportable disease. It is therefore mandatory for every health facility including upazila health

complexes, clinic/hospitals to report kala-azar cases to Diseases Control Unit (CDC), Directorate General

of Health Services (DGHS) of the Ministry of Health and Family Welfare (MoHFW). Since the disease

surveillance is mandated by the Government of Bangladesh and since the reporting of cases of kala-azar

is required by rules and regulation, the disease surveillance system should be far more complete.

Therefore, it is important to improve and strengthen disease surveillance system and data management

skills at program level.

Kala-azar disease surveillance is an information-based activity involving the systematic collection,

analysis and interpretation of outcome-specific data originating from a variety of sources such as

community, upazila health facilities, and secondary and tertiary health facilities. The information collated

is then used in a number of ways as follows: (i) to evaluate the effectiveness of health measures for kala-

azar prevention, control and elimination program, (ii) to monitor changes in kala-azar agents including the

trends in development of anti-kala-azar drug resistance, (iii) to support national kala-azar elimination

strategic plan and the allocation of appropriate resources within the healthcare system, (iv) identify high

risk populations or areas to target interventions, and (v) provide a valuable archive of disease activity for

future reference. To be effective, the collection of kala-azar surveillance data must be standardized on a

national basis and be made available at local, regional and national level.

The main role of kala-azar disease surveillance is to predict, observe, and minimize the harm caused by

outbreak, epidemic, and pandemic situations, as well as increase knowledge about which factors

contribute to such circumstances. A key part of modern kala-azar disease surveillance is the practice of

disease case reporting.

Kala-azar Surveillance System Components: The components of a kala-azar surveillance system

include:

1. Health facilities such as upazila health complexes, clinics and/or hospitals for the collection of primary data,

for example the number of NKA and PKDL cases, based on established case definitions and structured

reporting formats (paper and/or electronic);

2. Standard methods and frequencies of reporting, collating and monitoring of kala-azar disease as whole;

3. Description and definition of activities and initiates for public health actions, for example the number of NKA

cases within an endemic area that triggers an outbreak investigation (i.e., Index case search, No Kala-azar

Transmission Activities and/or indoor residual spraying);

4. Continuous monitoring and evaluation of the system for timeliness and effectiveness; and

5. Regular analysis of collated data for trends over time and space.

The kala-azar surveillance system is unlikely to capture all the cases of kala-azar and therefore, it is

essential to evaluate differences in reporting over time and between surveillance sites for interpretation of

data. In the design of such a system, evaluation is greatly facilitated by the use of indicators of

effectiveness, which are collated and monitored as part of surveillance. Surveillance data should also be

collated from the private health sector and non-governmental organizations. A surveillance protocol or

53 | P a g e

guidelines should be designed for monitoring the burden of Kala-azar and trends in Kala-azar co-

infections and for evaluating the effectiveness of control measures.

Kala-azar Surveillance System comprises of passive case surveillance and active case detection of cases

and vector surveillance. Passive case surveillance includes reporting of all cases of New Kala-azar (NKA)

and PKDL (Web-based Patient Registration). To make the disease surveillance effective, it is necessary to

organize a method of systemic surveillance activity, regular reporting, and analysis of data, review,

feedback and dissemination of information. Regular reporting and exchange information should be

organized upwards, downwards and laterally in the system that comprises government, private sector,

NGOs and the community as partners. Feedback linked to surveillance system is a critical element of the

kala-azar elimination program. Surveillance of the disease should also be used for sharing of reports

periodically to higher authorities on a regular basis to facilitate and rationalize the planning of elimination

program. Surveillance is useful for planning indoor residual spray of the endemic areas to be sprayed and

in monitoring the trends of kala-azar.

4.2 TYPES OF KALA-AZAR SURVEILLANCE

4.2.1 Passive Case Surveillance

Passive case surveillance of kala-azar includes reporting of cases of New Kala-azar (NKA) and Post

Kala-azar Dermal Leishmaniasis (PKDL). The passive surveillance is the basic foundation of the kala-

azar elimination program. The National Kala-azar Elimination Program (NKEP) has started with

reporting of cases, who seek diagnosis and treatment of kala-azar from a level of upazila health

complexes, tertiary hospitals and specialized hospitals in the government health facilities since beginning

from its implementation. However, the passive surveillance of NKEP does not provide real time true

picture since (i) a portion of kala-azar cases visit private doctors including Homeopathic, Unani and other

unqualified practitioners as there is no reporting of cases from these health care providers; (ii)

asymptomatic cases of kala-azar remains undiagnosed and untreated, and act as continuous foci of

transmission of disease; (iii) treatment is often started without a definitive diagnosis of kala-azar specially

by the unqualified doctors; and (iii) many cases do not seek health care at all because of poverty and

socio-cultural conditions.

Despite the variety of information needs, many elements of data collected in surveillance are very similar

and the data source is often the same individual or facility. However, there may be differences in: (i) the

specific case detection method used (passive vs. active case detection); (ii) the speed at which data need

to flow through the system (routine vs. immediate); (iii) the rapidity of response required (immediate

investigation of cases or clusters of cases vs. analysis of data on a regular basis with subsequent

adjustments to a control program). For the surveillance system to function as an early warning system,

reporting, confirmation, decision-making and response must be rapid. On the other hand, for kala-azar

endemic disease, the aim may be to carefully consider data collected in order to adjust or target the

control program. The national surveillance system should therefore be able to accommodate both needs,

and will require two-speed reporting mechanisms.

The NKEP has improved over the period of times, the capacity has increased, and the passive case

detection at the health facilities in the endemic areas has improved. Passive surveillance has been done on

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a format approved by national health authority at Disease Control Unit of CDC-DGHS Dhaka Office.

Patient‟s treatment files should be the starting point for passive surveillance and the following

information in Table-16 shown should be extracted from the records at each level:

Table-16: Indicators and information for Passive Surveillance

SN.

Indicators for Surveillance

Reporting Criteria: Information for Passive Surveillance

1.

KA Positive by rK39 RDT

Number of cases of kala-azar identified on the basis of clinical case definitions and on rK39 RDT positive,

2. KA Positive by Parasite Number of cases of kala-azar diagnosed by parasitic diagnosis,

3. NKA, PKDL and CL Number of cases who are currently on treatment categorized according to the treatment provided,

4. Treatment Completion Number of cases who completed treatment,

5. Dropped out Number of cases who dropped out before completing the treatment,

6. KA Treatment Failure Number of cases who did not respond to treatment categorized according to the treatment provided,

7. Relapse KA Number of cases if the fever relapse after treatment of KA,

8. Hospitalization Number of cases who were admitted to the hospital,

9. Died in Hospital Number of cases who died in the hospital,

10. Died at Home Number of cases who died at home,

11. Adverse Drug Reaction Number of cases who developed major side effect of medicine.

12. KA with Co-infection Number of KA with TB co-infection; HIV/AID co-infection; Malaria co-infection;

13. KA in Pregnancy Number of KA in Pregnancy

Indicators for Monitoring Passive Case Surveillance: At input level, the two most important inputs

should be required to make the progress and performance at desired level, these are: (i) guideline for

diagnosis of NKL and PKDL and (ii) guideline or protocol for surveillance. The guideline or protocol for

surveillance is important input because it will reflect kala-azar elimination, control priorities, improve

efficiency, take advantages of new methods and techniques to strengthen surveillance; assist health

professionals in the process of prioritization of kala-azar as a neglected tropical disease for public health

problems both at national and local levels.

The guideline for surveillance should contain the core functions of kala-azar as follows: (i) case detection,

(ii) reporting, (iii) investigation and confirmation, (iv) analysis and interpretation, (v) action:

control/response, policy and feedback.These functions are made possible by improving core surveillance

functions such as: (i) setting of standards (e.g. case definitions), (ii) training and supervision, (iii) setting

up laboratory support, (iv) setting up communications, and (v) developing and managing resources. The

level of coordination/integration in the national surveillance system can affect performance of the system,

cost of the system, and sustainability of the system.

At process level, the KEP is being implemented at 100 endemic upazilas and provides diagnostic services

using rK39 RDT and treatment to PKA and PKDL cases. Four medical college hospitals such as Dhaka,

Suhrawardy, Rajshahi and Mymensingh Medical College Hospitals including SK-KRC as specialized

laboratory are acting as referral centers proving rK39 RDT services with facilities of PCR, parasite

identification with splenic/bone marrow aspirate, and slit-skin smear or biopsy.

55 | P a g e

Reporting of surveillance data is considered as one of the most important surveillance processes. A total

of 104 reporting health facilities have been in operations at the government sector. However, private and

NGO sector at the upazila level are yet to be involved in the surveillance process. It is therefore, the

responsibility of the local upazila health manager to coordinate among private and local NGO to make

them to becoming a part of surveillance system to report cases of NKA and PKDL.

All health facilities enter data on NKA and PKDL in the reporting format and send complete report to

District Civil Surgeon Office and CDC-Dhaka Office on a monthly basis. If there is no case, then it

should be a zero report. A zero report is as important report that enumerates the cases seen; Lack of a

report will not lead to the conclusion that there was no case. At the process level of the passive

surveillance system, the data is compiled at each level of UHC. Private and NGO facilities should be

involved to develop a common understanding of the kala-azar endemicity and encouraged to report of

kala-azar at UHC. The Table-17 below shows the number of different indicators for monitoring passive

case surveillance.

Table-17: Indicators for Monitoring Passive Case Surveillance

Passive Case Surveillance: Upazila Level Progress & Performance

Input: Describes the resources

1. Guideline for Diagnosis of KA and PKDL

2. Guideline for Surveillance or Protocol

Process: Describes the activities and performance

3. No. of HF providing diagnostic services to PKA and PKDL/ Number of all

Health Facilities (HF)

4. % of HF providing diagnostic services

5. No. of training sessions conducted /no. of sessions planned on diagnosis of KA

and PKDL

Outputs: Measures direct products/deliverables

6. Number of providers trained in PKA and PKDL,

7. Number of MT-Lab trained on diagnostic services of KA,

8. Number of PKA cases registered by passive case surveillance,

9. Number of PKDL cases registered by passive case surveillance,

Outcome: Behavioral change and health impacts

10. NKA Detection Rate: by health facilities Per 10 000 pop. in upazila level.

11. PKDL Detection Rate: by health facilities per 10 000 pop. in upazila level.

12. Percentage (%) of KA treated: No. of KA cases treated divided by the no. of

KA cases diagnosed by the health facilities.

Source of data: From data base system

13. Monthly reports generated at UHC to district level

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i. Active Case Surveillance

Active disease surveillance plays a more dynamic role in data gathering in kala-azar elimination program.

The active case detection is more resource intensive and is usually done in association with passive

surveillance. The basic principle and criteria of any disease elimination program is to have a robust active

case detection system that will contribute to early diagnosis and complete treatment of kala-azar cases.

Moreover, active case detection is recognized as one of the most important indicators for monitoring kala-

azar elimination activities at village/union level.

Four approaches of active case detection (ACD) have been validated for its utility in NKA and PKDL

case detection. These are Blanket Approach, Camp Based Approach, Index Based Approach, and

Incentive Based Approach.

4.2.2.1 Blanket Approach: In blanket approach, the trained health workers make house-to-house visit in

the entire endemic areas for the detection of NKA and PKDL cases; The blanket approach is considered

the „gold standarnd‟, but due to the additional high cost incurred with this method, it is only

recommended in outbreak situations.

4.2.2.2 Camp Based Approach: The camp approach is done by organizing health camp in defined kala-

azar endemic areas where screening of kala-azar is done by mobile health teams of medical officers,

nurses, lab technician, health inspectors, assistant health inspectors, health workers and health volunteers;

The camp based approach is a sensitive tool for the detection of new kala-azar and PKDL cases

particularly in high KA endemic areas.

4.2.2.3 Index Case-based Approach: The index case-based approach includes the search of kala-azar

cases among the households members through house-to-house search around a house (radius of 50 meters

or 100 HHs were searched) of a recently diagnosed cases of kala-azar usually in the previous six months;

For the moderate to low KA endemic areas and in those areas where households are scattered, the index

based approach is the prefered method for active case detection; and

4.2.2.4 Incentive Based Approach: In the incentive based approach, the search for new kala-azar cases

is done through health workers who receive an incentive for each newly detected case. The use of the

incentive based approch can be useful method which can be applied particulary in low KA endemic

upazilas or in combination with any of the approaces mentioned above. The incentive based approach of

case detection may initiate the snow ball technique for NKA and PDKL case finding. However, this

method needs meticulaous supervision and monitoring to prevent misuse of funds. Incentive based ACD

is currently practiced in India and by some research teams in Bangladesh15

.

4.2.2.5 No Kala-azar Transmission Activity (NKTA): The KEP in its ACD strategy have implemented

index based approach. While doing index based approach IRS has been done to about 60-100 HHs. The

objective of conduction of IRS under the index case approach is to stop further transmission of new cases

of kala-azar from the index case. This strategy is known as “No Kala-azar Transmission Activity

(NKTA)”. During the implementation of NKTA under index based approach, the epidemiological team

consisting of medical officer use to investigat the index case and conduct active searching for NKA &

15 Regional Strategic Framework for Elimination of Kala-azar from South-East Asia Region, 2016-2020 WHO/SEARO

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PKDL cases in and the around the 60-100 HH of the Index Case. At the same time, entomological team

has conducted KA vector and larval survey arround the index case. After the end survey, the IRS team

will conduct IRS of 60-100 HH and larvicidal spraying is done in the breeding sites considering the

vector and larval density.

Figure- 12: Diagrammatic view of Activities and Responsibilities of NRRT in NKTA

“No- Kala-azar Transmission” Activity

37

Team Leader & Spray man

MO (DC), MO, SACMO, MT LAB

IRS & Larvicide Spray

HI , AHI, Team leader

Entomologist & Ento-Tech

Case Search-at 60 HH Supervise IRS & Larvicide

Vector and Larval survey Supervise IRS & Larvicide

HH of Index case

Case investigation (IC)‘rk39’ test in HH Supervise Case Searching

For Implementation of “No Kala-azar Transmission Activity”, the following activities have to be ensured:

Orientation training for the members of the NKTS; development of checklist for case investigation,

necessary forms and format; conduction of case investigation and vector survey immediately after

receiving reporting of New KA & PKDL cases; conduction of focal spray to the 60-100 HH surrounding

the Index Cases; distribution of long-lasting insecticide bed nets (LLINs) to all the index or new case; and

monitoring and supervision of the concerned personnel.

The expected outcome indicators for NKTA are as follows: formation of NKTA Team; conduction

training/workshop on for the team members of NKTS; development and organization of necessary

checklist required for implementation of NKTA; implementation of NKTA activity to all endemic upazila

throughout the year; distribution of LLINs to all new or index cases (when LLINs available at endemic

upazila); and monitoring of follow-up of LLINs so that case can use LLINs correctly.

Active surveillance requires substantially more time and resources and is therefore less commonly used in

emergencies. But it is often more complete than passive surveillance. It is often used if an outbreak has

begun or is suspected to keep close track of the number of cases. Community health workers may be

asked to do active case finding in the community in order to detect those patients who may not come to

health facilities for treatment. Index case-based approach and camp-based approaches have been tried on

a random basis both at hyper and moderate endemic upazilas and documented some positive results.

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Implementation of Active Case Detection: The KEP had implemented active search during the last

operational plan and the strategy has been found to be effective in identifying case of kala-azar as

follows:

Formation of Kala-azar Active Search Team: This team is consisted of 2-3 volunteers and AHI/HI as the

first line supervisor. One team has to conduct active search to about 60-100 HH/day surrounding an index case

and refer the suspected cases of kala-azar to UHC for diagnosis with rK39 RDT;

Formation of IRS Team: The IRS team is a 6-member team with spray man and mixture man. The team is

supervised by AHI/HI. The IRS team would search suspected case of kala-azar during indoor residual spraying

(IRS) and refer the cases to UHC for proper diagnosis; and

Formation of Kala-azar Search Volunteer (KSV): During the camp based approach, the KSV have

conducted searching for new suspected cases of kala-azar in 100 HH/day in every village of a designated union

of hyper-endemic upazilas. Suspected cases of NKA detected by the KSV are referred to a central search camp

based at the community, where the MT-Lab performed test using rK39 RDT following a camp-based approach

and refer the positive cases to UHC for treatment.

4.2.2.6 Approach to Manage Asymptomatic Kala-azar Cases

The approach or strategy for the management of asymptomatic kala-azar infection poses an important

challenge because of the two critical reasons. First, the identification of asymptomatic cases and the

management of the carriers have become a great threat for kala-azar elimination program in the country.

Second, the absence of validated markers for asymptomatic infection poses another challenge. An

asymptomatic infective host may serve as silent reservoir and jeopardize the sustainability of elimination

program activities if their role in transmission is confirmed. However, the potential of asymptomatic

infections as a reservoir is not clearly understood.

The number of asymptomatic cases is much higher than the number of infected cases presenting with

clinical illness. Recent studies have revealed that the ratio of full-blown kala-azar cases to asymptomatic

kala-azar infection varies from 1: 2.4 in Sudan, 1:4 in Bangladesh, 1:4 in Kenya, 1:6 in Ethiopia, 1:9 in

Indian and Nepal, and 1:18 in Brazil16

. Many people infected with Leishmania species develop an

effective immune response and do not manifest clinical disease. It is, therefore, important from the

program point of view to know how many infected persons will develop full blown disease and how

many of they can be diagnosed before they show clinical manifestation.

Asymptomatic kala-azar infection is not well defined, but is usually ascertained by a positive serological

test, PCR or Leishmanin Skin Test in the healthy populations living in the endemic areas. The role of

asymptomatic carriers in transmission or the prognosis of asymptomatic infection at the individual level is

not fully explained. Epidemiological studies should be undertaken to identify the factors that lead to the

development of disease in asymptomatic infections.

Genetic factors, poverty, poor housing, mud-wall house, ownership of cattle and poor nutritional status

have been shown to increase the risk of progression from asymptomatic infection to clinical kala-azar;

children with moderate to severe protein energy malnutrition have been found to have nine-fold increased

risk of developing kala-azar. Malnutrition is considered to be associated with impaired immune responses

16 Om Prakash Singh,, et al, (2014). Asymptomatic leishmania infection: A new challenge for leishmania control. Oxford Journal of Clinical Infectious Diseases (CID,) February 27, 2014

59 | P a g e

against the parasite and can weaken both innate as well as T cell immunity. This, however, requires a

longitudinal prospective follow-up design study that allows for the exploration of the combination of

epidemiological, parasitological, immunological and genetic risk factors in the same population.

Sarman S, et. al, (2002) 17

in his research reported their findings on the host immune responses against

L. donovani specific antigen (recombinant K39) and its value in predicting the development of clinical

disease. A total of 240 clinical kala-azar cases and 150 asymptomatic family members and neighbors of

the index case patients were tested for anti-rK39 immunoglobulin G (IgG) and IgA. Fifty five (36.7%)

asymptomatic cases were found to be seropositive. These individuals were monitored every 3 months for

1 year. On follow-up, 24 cases (43.9%) of the asymptomatic seropositive contacts develop kala-azar

within the first 3 months, and a cumulative total of 38 cases (69%) developed kala-azar within 1 year. The

rest 17 (31%) seropositive cases remained asymptomatic and the infection got self-healed in the

subsequent period. The study concluded that the mass screening of family members and immediate

neighboring contacts by using rK39 ELISA could be a highly reliable tool for early diagnosis and to plan

prophylactic treatment of latently infected asymptomatic carriers to eradicate kala-azar.

Based on the research finding, the National Kala-azar Elimination Program will adopt the following

strategy and conduct the following activities:

1. Index Case Search: Index case search should be made mandatory under the kala-azar elimination

program activity. During the index case search, all the names of the family members of the index

cases and the immediate neighboring contact should be listed using prescribed formats.

2. Diagnosis: All the family members and the immediate neighbor should be tested with rK39 antigen.

The names of the asymptomatic seropositive cases with rK39 RDT should be listed using prescribed

format.

3. Distribution of LLIN: Long Lasting Insectiside Impregnated Bednets (LLIN) will be used

selectively to prevent the transmission of disease to the other healthy population.

4. Follow-up and Counseling: Both the index cases and asymptomatic seropositive cases should be

followed-up every 3 months for at least 1 year (Follow-up Formats). The asymptomatic cases should

be health education and counseling. Mobile follow-up may cost effective.

5. Treatment: Asymptomatic seropositive cases who develop clinical symptoms and signs should be

treated with 1st line of anti-leishmania drug and should be follow-up.

6. Sand Fly Density Survey and IRS: The Entomological team should conduct sandfly density survey

to each area arround the index case and conducte IRS to about 60-100 households arround the index

case.

The above program strategy would help correctly diagnosed all most 100% of cases who are

exposed to L. donovani. The program could also predict the disease development in the family

and neighborhood contacts of the patients by using anti-rK39 test. However, it would be difficult

17 Sarman Sing, Veena Kumari and Niti Sing (2002). Predicting Kala-azar Disease Manifestation in Asymptomatic Patients with Latent Leishmania donovani Infection by Detection of Antibody against Recombinant K39 Antigen. Clinical and Diagnostic Laboratory Immunology, May 2002.

60 | P a g e

to rule out re-infection as opposed to re-activation of latent infection in asymptomatic

individuals, who are still residing in the endemic area.

4.3 MANAGEMENT OF KALA-AZAR SURVEILLANCE

Kala-azar surveillance is a part of web-based national disease surveillance system centrally managed by

Kala-azar Elimination Program (KEP), Disease Control Unit of Communicable Disease Control (CDC) of

the Directorate General of Health Services (DGHS). Kala-azar Elimination Program having specific

indicators have been incorporated in the reporting format. In order to strengthen Kala-azar surveillance

system, KA Surveillance Unit has been set up at upazila and district level.

4.3.1 Kala-azar Surveillance Unit:

A. UHC Level: Upazila Kala-azar Surveillance Unit

Head: Upazila Health and Family Planning Officer (UH&FPO)

Focal person: Medical Officer (Disease Control)

Senior Staff Nurse (SSN) and

Statistician

B. District Level: District Kala-azar Surveillance Unit:

Head: Civil Surgeon (CS)

Focal Person: MO (CS/DC)

District Public Health Nurse (DPHN) and

Statistical Assistant

C. Government Medical College Hospitals:

Director (Hospital)

Focal Person: to be assigned by the Hospital Director

Senior Staff Nurse (SSN) and

Statistical Officer/Statistician

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4.3.2 National Rapid Response Team (NRRT):

Members at the Central Level Members at the Upazila Level

Director, CDC and Line Director, CDC-1

Deputy Director, M&PDC-1

Assistant Director, CDC-1

DPM, KEP-1

National Consultant, Kala-azar, WHO BD-1

MO, KEP-1

SMO, KEP, WHO Bangladesh-1

Entomologist- 3

Ento-technologist-3

DM, KEP, WHO Bangladesh-1

UHFPO-1

MO (DC)/ MO/ SACMO- 1

SSN-1

MT (Lab)-1

Store Keeper-1

Statistician-1

HI (In charge)-1

HIs- Corresponding Unions-1

AHIs- Corresponding Villages-1

Team Leader-

Spray man-5

4.3.3 Surveillance Reporting from UHC

UH&FPO is responsible for implementation of KA surveillance activities at the Upazila level. The

surveillance activities will include:

Community awareness building through advocacy meetings

Organizing training for the health personnel

Identification of „suspected cases‟ of Kala-azar and PKDL at the community level and their referral

(as per flow chart given thereof)

Confirmation of diagnosis by RDT „rK39‟ based ICT

Line listing of the confirmed cases at all levels using software which is compatible with web-based

disease surveillance (software to be provided by the program)

Reporting of confirmed Kala-azar and PKDL cases including the program monitoring indicators

Generation of a unique identification number for each case with confirmation of diagnosis of KA

and PKDL at all reporting levels

4.3.4 NKA and PKDL Detection from Community

The suspected cases of kala-azar cases with or without skin lessons are identified at the community at

Health and Family Center, Union Sub-center, Community Clinic, NGO Clinic, Health Workers, Private

Practitioners. The suspected cases are referred to the nearest UHC using prescribed referral form. In the

UHC, the diagnostic test using rK39 RDT is done as follows:

Identification of ‘Suspected Cases’ of New KA and PKDL by First Contact Points

Referral of the Suspected Cases of New KA and PKDL using prescribed referral form

Diagnosis of the cases at UHC

Reporting of incidence of New KA and PKDL through the web-based disease

Surveillance System at Health and Family Welfare Center, Union Sub-centre, Community Clinic, NGO Health Clinic, Field Staff of Health and Family Welfare Center, Private Practitioner, Informal Health

Care Providers and IPD and OPD of UHC

62 | P a g e

OPD of

UHC

IPD of UHC

Community

Clinics

Informal Health

Care Providers

H&FWC,

Union Sub

Centre

Private

Practitioners

NGO Health

Centre

Health worker/ FP

Worker

Level-I

Upazila KA Surveillance Unit (UHC)

Level-II

District KA Surveillance Unit

(Civil Surgeon Office)

Level-III

Central Level

National KA Surveillance Centre at

IEDCR

Director, DC

Focal point/ PM/ DPM

Kala-azar

Web-based

SK-KRC (Surya Kanta Kala-azar

Research Centre)

Sadar Hospital OPD/IPD

Medical College

Hospital

Divisional Health Office

MIS

Figure 13: Flow Chart for NKA and PKDL Detection from Community

First Point of Contact

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6.2.5 Reporting Format for Diagnosis of NKA and PKDL

All suspected cases of New KA and PKDL attending UHC should be screened using the check list given

below (Table-18 and 19). All reporting units are expected to enter the information using the reporting

format mentioned. Prototype formats including the check list for identification of cases for reporting are

summarized in the tables below.

Table-18: Screening tool for diagnosis of PKA attending UHC (Check List)

SN History, Symptoms and Signs (Indicators) Put a tick (√) mark

1. History of fever more than 2 weeks

2. History of living in the Kala-azar endemic area

3. Palpable Spleen (Splenomegaly)

If all the above indicators are found positive, then rK39 RDT is done. The result of rK39 RDT may be either positive or negative.

Results of rK39 RDT: +ve -ve Patients are labeled as:

• Suspected Kala-azar Case: if the three indicators mentioned above are positive.

• Probable Kala-azar Case: if rK39 RDT test is found positive in Suspected Kala-azar Case. All Probable Kala-azar Cases must be treated according to National Guideline for Kala-azar Case Management.

• Confirmed Kala-azar Case: if they meet the criteria for Probable Kala-azar Case and parasitologically confirmed by spleen or bone marrow aspiration.

Suspected cases and probable cases are required to be reported for the surveillance system.

Table-19: Screening tool for “Suspected Cases of PKDL” attending UHC (Check List)

SN History, Symptoms and Signs (Indicators) Put a tick (√) mark

1. History of previous Kala-azar

2. History of living in the Kala-azar endemic area

3. Skin manifestation with macule, papule or nodule without

sensation

If all the above indicators are found positive, then rK39 RDT is done. The result of rK39 RDT may be either positive or negative.

Results of rK39 RDT: +ve -ve Results of Skin Biopsy: +ve -ve Patients are labeled as:

Suspected PKDL Case: if the three indicators mentioned above are positive.

Probable PKDL Case: if rK39 RDT test is found positive in Suspected PKDL Case.

Confirmed PKDL Case: if the skin biopsy is positive for PKDL Case.

All three categories of PKDL cases should be reported for the surveillance system.

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4.2.6 Reporting of Surveillance Information

The data flow for reporting of cases of New KA and PKDL should follow the flow chart shown in Fig 7.

Upazila Kala-azar surveillance unit should send complete information on Kala-azar to the district focal

point once in a month before the first Wednesday of each month and directly to Program Manager of

Kala-azar Elimination Program through hard and soft copy. After compilation Focal Person (Kala-azar)

will send the report to Central Level. Once web-based surveillance is in place, surveillance data should be

uploaded to the server maintained at Kala-azar Elimination Program, Disease Control Unit of DGHS from

all levels.

A unique identifier should be used for each case during diagnosis to avoid duplication of reporting. If

there are no cases then it should be a zero report. The data should be compiled at each level for the

government, private and facilities, and reported mainly at Upazila and District levels in a coordinated

way. Data from tertiary level health facilities including the medical college hospitals may be reported

through District level or uploaded directly to web-based surveillance system if the facilities are available.

There should be a feedback mechanism to make the best use of surveillance data by the government,

private and NGO facilities for a common understanding of the problems that will lead to identification of

possible solutions. The reports after compilation should be submitted to MO (Kala-azar elimination) of

the UHC. The statistical Assistant will compile information from the reporting units from the

government, private and NGO facilities and add their own.

A consolidated report should be sent to the district. The data will cover information for the preceding

month. In the district, the information from each reporting facility should be entered on the computer and

will send to the central level.

Report on review and feedback: The focal points at all levels have the responsibility to provide

regular written feedback to relevant stakeholders every month. Review and feedback are important at all

levels to take appropriate action. The written feedback from upazila and district will have to be copied to

the program.

Report on treatment: Information available from the treatment cards provided to patients and registers

will be used for preparing treatment report. The basic information recorded is:

Personal information about the patient including address, age, sex, weight, marital status,

pregnancy and lactating status

Contact Number (Mobile Number)

Drugs used for treatment of Kala-azar

Number of days treatment provided

If treatment course has been completed or not

Side effects of drugs

Outcome of treatment

Treatment provider (public, private, NGO)

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Report on hospitalized cases: Separate reports are needed for the indoor patients of Kala-azar. This

should include the total number of admissions, the total number of patients admitted for Kala-azar, the

total number of deaths and the total number of deaths due to Kala-azar. The report should be categorized

according to age (under five, 5-14 and 15 and above) and sex. Information on pregnant women should be

included separately in the monthly report. The outcome should be summarized as (a) improved (b)

referred (c) died. To indicate the number of patients who worsened and were referred. The report should

indicate the number of patients who used the referral services. The monthly report should indicate the

number of patients who completed the treatment and the number of patients who are being treated but

have not completed treatment. It is also necessary to indicate the number of patients who were started

treatment but have dropped out.

4.2.7 Web-based Registration of Kala-azar Cases and Follow-up Form:

The overall goal of the Web-based Registration of Kala-azar Cases and Follow-up Form is to record

all Kala-azar cases diagnosed and treated at health care facilities (Upazila Health Complexes, District

Hospitals and Tertiary & Specialized Hospitals) and ensure required numbers of follow-up visits. The

information generated from the web-based registration will help the health program personnel to take

immediate actions to prevent the transmission of the disease in the epidemic and outbreak situation, and

help the program managers to make better decision to improve the Kala-azar elimination program

activities. Every health facilities situated at the endemic areas are equipped with computer and data are

entered using statistical package called “Health Management Information System 2 (DHIS2)”.

KEP will be able to manage its operations more effectively, monitor processes and improve

communication with help of DHIS 2. DHIS 2 is typically used as national health information systems at

DGHS-Dhaka for data management and analysis purposes, for health program monitoring and evaluation,

as facility registries and service availability mapping, for logistics management and for mobile tracking of

pregnant mothers in rural communities. With the help of DHIS 2, KEP will be able to capture data on any

type of device, including desktops, laptops, tablets, smartphones and feature phones. It works in most

solutions in work-offline, enabling improved reach in locations with poor connectivity. DHIS 2 provides

a wide range of solutions based on HTML5, SMS and Java.

The Web-based Registration of Kala-azar Case and Follow-Form has following subsections:

1. General Information (of the patients)

2. Patient‟s Information (Before Treatment)

3. Patient‟s Information (After Treatment and beofre Discharge)

4. Suspected Adverse Drug Reaction (ADR) and List of Adverse Events

5. Follow-up Information

The web-based registration form is attached in Annex-13 (Page___)

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CHAPTER: FIVE

MONITORING AND EVALUATION (M&E)

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5. MONITORING AND EVALUATION:

The availability and use of quality data is essential for evidence based decision making to improve

program activities. The lack of accurate and timely data can be an impediment to progress in

implementation. The monitoring and evaluation component of the program will provide important data on

the scope, coverage and effectiveness on the programs activities. The M&E data will be used to monitor

progress in key program outcomes as well as provide data on inputs and outputs.

Routine monitoring, periodic assessment and evaluation would be done by the program at all levels to

ensure effective implementation of different activities as per plan. A set of objectively verifiable

indicators will be used to measure progress and assess the achievement of elimination program in line

with national Kala-azar strategy. For regular monitoring checklists or formats will be used to see any gaps

of the ongoing activities. Further, impact evaluations will be obtained from external independent

organization who competent authority will do the evaluation.

In this chapter the activities mentioned in the national guideline for Kala-azar case management will be

monitored and evaluated; however “national guideline for M&E for the NKEP” will be used to monitor

and evaluate the NKEP.

5.1 The Monitoring & Evaluation Framework

The following input-output-outcome-impacts framework is used for monitoring and evaluation of the

activities mention in the national Kala-azar case management guideline.

Input: describes the resources allocated to an activity.

Process: describes the activities and performance within the services.

Output: measures the direct products (deliverables) of an activity.

Outcome: describes the effect of these activities in terms of behavioral change

Impact: describes the status of health (not covered by this chapter)

A set of objectively verifiable indicators has been developed to measure progress and assess the

achievement of the planned activities. The indicators, operation definition of the indicators, sources of

verification and the responsible person to collect these indicators are summarized in sub-chapter 5.3 to 5.5

in the nest pages. Data flow of the M&E is presented in Figure-13.

5.2 Monitoring and Evaluation Team

For monitoring and supervision there different teams will be deployed.

Central level District/Tertiary level Upazila level

Line Director (DC)

Assistant director (DC)

Deputy Program Manager-

Kala-azar

Surveillance Medical

Officer- Kala-azar

Monitoring & Evaluation

Manager

Civil Surgeon

Deputy Civil Surgeon

Director, Tertiary level

Hospital

Consultant, Tertiary level

Hospital

Upazila Health & Family

planning officer

MO (DC)

Sr. Staff Nurse (SSN)

MT (Lab)

Statistician

68 | P a g e

5.3 Indicators related to Kala-azar and PKDL diagnosis:

Indicators related to Kala-azar and PKDL diagnosis, with the means of calculation (operational indicator) and source of data for each

indicator

Level Indicators Operational indicator Verification Frequency Responsible Person

Input 1. Guideline and SOPs for diagnostic

sent to the health facility

2. Fund available for diagnostic kits

3. Staff training

1. Yes/No

2. Yes/No

3. Training coverage= # of HF trained/# of HF

treating Kala-azar

Records at

central level.

Once in a

year

DPM (Kala-azar)

Process 1. Available diagnostic kit (rK39) and

associated accessories in place

2. Molecular diagnostic test for

VL/PKDL functioning (if applicable

)

3. Diagnosis perform as per

SOP/National Guideline

4. Maintaining diagnostic record

properly

5. Diagnostic kits stock in last month

1. # of HF with enough diagnostic kits (rK39)/ # of

HF visited

2. # of HF where molecular diagnostic equipment is

functioning/ # of HF with molecular diagnostic

equipment

3. # of HF where diagnostic test perform properly/# of

HF visited

4. # of HF where diagnostic registered maintained

properly/ # of HF visited

5. # of kits had last month/ # of kits required for test in

last month

Direct

observation/H

F visit

(Annex-16)

Quarterly Representative of

central level program

managers assigned by

Director, CDC /DPM

(Kala-azar)/ District

level program

managers (CS)

Output 1. Proportion of test done for case

detection (NKA/RKA/KATF/

PKDL)

2. Positivity rate for cases

(NKA/RKA/KATF/ PKDL)

3. Proportion of cases referred for

further confirmation :

4. Diagnostic kits stock in reporting

month

1. Proportion of test done=

# of test done for cases (NKA/RKA/KATF/ PKDL)

/ # of suspected (NKA/RKA/KATF/ PKDL) cases

at the HF

2. Positivity rate=

# of test positive for cases (NKA/RKA/KATF/

PKDL) / # of test done for cases

(NKA/RKA/KATF/PKDL)

3. # of case referred for further confirmation test/ # of

suspected cases reported at the HF

4. # of kits had in reporting month/ # of kits required

for test in reporting month

Monthly

report using

(Annex-17)

Monthly UH&FPO/ MO

(DC)/Assigned by

Head of district and/or

tertiary level hospital

Outcome Improve diagnostic at HF Increase positivity rate (in %)

Reduction of miss use of kits (in %)

Analysis of

annual

surveillance

data

Yearly Director, CDC /DPM

(Kala-azar)

69 | P a g e

5.4 Indicators related to Kala-azar and PKDL treatment:

Indicators related to Kala-azar and PKDL Treatment, with the means of calculation (operational indicator) and source of data.

Level Indicator (measurement) Operational indicator Verification Frequency Responsible person

Input 1. Guideline and SOPs for treatment of VL

sent to the health facility

2. Fund available for drugs

3. Staff training

1. Yes/No

2. Yes/No

3. Training coverage= # of Health Facility (HF) trained/# of

HF treating Kala-azar

Records at

central level.

Once in a

year

DPM (Kala-azar)

Process 1. Available drugs and associated

accessories in place

2. Drug storage properly

3. Treatment provided as per

SOP/National Guideline

4. Maintaining treatment record properly

5. Drugs stock in last month

1. # of HF with adequate diagnostic kits (rK39)/ # of HF

visited

2. # of HF where molecular diagnostic equipment is

functioning/ # of HF with molecular diagnostic

equipment

3. # of HF where diagnostic test perform properly/# of HF

visited

4. # of HF where diagnostic registered maintained properly/

# of HF visited

5. Quantity of drug had in last month/ quantity of drug

required for treatment in last month

Direct

observation/H

F visit

(Annex-16)




Director, CDC /DPM


level program

managers (CS)

Output 1. Patient treatment compliance

(NKA/RKA/KATF/ PKDL/Co-infection

with Kala-azar)

2. Patient referred for treatment

((NKA/RKA/KATF/ PKDL/Co-

infection with Kala-azar))

3. Patient follow-up compliance

(NKA/RKA/KATF/ PKDL/Co-infection

with Kala-azar)

4. Drugs stock in reporting month

1. Patient treatment compliance (proportion):

# of cases (NKA/RKA/KATF/ PKDL/Co-infection with

Kala-azar) complete the treatment/ # of cases

(NKA/RKA/KATF/ PKDL/Co-infection with Kala-azar)

diagnosed

2. Proportion of patient referred for treatment of:


Kala-azar) referred for treatment/ # of cases


diagnosed

3. Patient follow-up compliance (proportion):


Kala-azar) complete follow-up/ # of case


follow-up scheduled for that month

4. Quantity of had in reporting month/ quantity of drug

required for treatment in reporting month

Monthly

report using

(Annex-17)

Monthly UH&FPO/

MO(DC)/Assigned by



Outcome 1. Treatment outcome

Initial cure rate

Final cure rate

Treatment Failure rate

Relapse rate

Loss-to-follow-up rate

Transfer rate

Death/Mortality rate

2. Improved treatment of Kala-azar at HF

1. Treatment outcome

# of cases initially cured / # of cases treated

# of cases finally cured / # of cases treated

# of treatment failure cases / # of treated cases

# of relapse cases / # of treated cases

# of cases lost to follow-up/ # of cases schedule for

follow-up

# of cases transfer/ # of cases treated

# of cases death/# of cases treated

2. Increase cure rate (in %)

Analysis of

annual

surveillance

data

Yearly

Director, CDC /DPM

(Kala-azar)

70 | P a g e

5.5: Indicators related to Kala-azar and PKDL Surveillance:

Indicators related to Kala-azar and PKDL surveillance, with the means of calculation (operational indicator) and source of data.

Level Indicator (measurement) Operational indicator Verification Frequency Responsible person

Input 1. Guideline and SOPs for how to use

surveillance form and web based

system sent to the health facility

2. Staff training

3. Fund for ACD available

1. Yes/No

2. Training coverage= # of HF trained/# of HF

treating Kala-azar

3. Yes/No

Records at

central level.

Once in a

year

DPM (Kala-azar)

Process 1. Surveillance form used from the

national guideline

2. Case recording compliance in last

month

3. Case reporting compliance in last

month

4. Web based data entry compliance in

last month

5. ACD conducted as per SOP in the

national guideline

6. Follow-up compliance in last month

1. # if HF used surveillance form from the guideline/ #

of HF visited

2. # of cases recorded in surveillance form in last

month/ # of case treated in last month

3. # of cases reported to the central level in last month/

# of case treated in last month

4. # of cases entered in web based system in last

month/ # of case treated in last month

5. # of ACD done properly/ # of ACD conducted

6. # of follow-up done in last month/ # of scheduled in

last month

Direct

observation/H

F visit

(Annex-16)




Director, CDC /DPM


level program

managers (CS)

Output 1. Case recording compliance in

reporting month

2. Case reporting compliance in

reporting month

3. Web based data entry compliance in

reporting month

4. Proportion of cases detected by

ACD in reporting month

1. # of cases recorded in surveillance form in reporting

month/ # of case treated in reporting month

2. # of cases reported to the central level in reporting


3. # of cases entered in web based system in reporting


4. # of case detected through ACD in reporting month/

total # of cases detected in reporting month

Monthly

report using

(Annex-17)

Monthly UH&FPO/

MO(DC)/Assigned by



Outcome Reduction of underreporting Increase case detection (in %)

Timely case reporting to central level

Yearly Director, CDC /DPM

(Kala-azar)

71 | P a g e

MCR, QCR, ACR

UHC level District level Tertiary level

UHFPO

Statistician

Medical Officer

Consultant

Civil Surgeon

Director

Consultant

Deputy Program

Manager

Data Manager/

M&E Manager

Line Director

MPR

MCR, QCR, ACR

MPR MPR

MPR,

QOR

MPR,

QOR MPR

Others source (NGOs)

MPR, QOR,

QCR

Figure-14: Data flow of M&E

MPR=Monthly Progress Report

MCR=Monthly Compiled Report

QCR=Quarterly Compiled Report

ACR= Annual Compiled Report

QOR= Quarterly Observation Report

72 | P a g e

ANNEXURES

73 | P a g e

ANNEX-1: HOUSE HOLD SURVEY FORM

National Kala-azar Elimination Program House Hold Survey Form

Disease Control Unit, DGHS, Mohakhali, Dhaka

Name of KA Search Volunteer:_____________________________________ Date:____________________________

Village:______________________ Union:_________________________ Upazila:__________________________

District:

S.N Name of head of Household

No. of members

No. of Present

members

No. of Suspected KA Cases

Mobile no. (Only for suspected

Kala-azar cases)

Comments

Total number of Household visited =

Signature of supervisor:________________________________________ Date:____________________________

Name of supervisor:_________________________________________________________________________________

74 | P a g e

ANNEX 2: LIST OF SUSPECTED CASES OF KALA-AZAR PATIENT


List of Suspected Kala-azar Patients

Disease Control unit, DGHS, Mohakhali, Dhaka

Name of Kala-azar Search Volunteer

Date:

District: Upazila:

S.N Name of Patients Age Father's/ husband's Name

Mobile no. HH ID Para/ Moholla

Village Union rK-39 (+/-)

Types of Disease

Remark

NKA PKDL

Name of the supervisor: Signature of Supervisor: Date:

75 | P a g e

ANNEX 3: FIELD REFERRAL FORM


Government of the People’s Republic of Bangladesh CDC, DGHS, Mohakhali, Dhaka.

SL. No:____________________ Date:____________

Patient’s Name:__________________________________ Sex(M/F)____________Age:______( Ys)

Parent/Husband’s Name: _______________________________________________________________

Village:______________________Upazila:________________________District:___________________

Type of Suspected case of Kala-azar: 1. NKA 2. PKDL

Signature of KA Search Volunteer: _______________________________________________________

Name of KA Search Volunteer: ___________________________________________________________

Referred to: ___________________________________________________ Upazila Health Complex

Name of Medical Officer: Dr. _____________________________________Mobile no.:_________________

For Any Information at Central Level

Please Contact:

Surveillance Medical Officer

Kala-azar Elimination Programme

CDC, DGHS, Mohakhali, Dhaka.

Mobile no: 01797-131317

Tel:+8802 9899203

Referral Form

Tel:+8802

76 | P a g e

ANNEX 4: REGISTRATION AND FOLLOW-UP BOOK

77 | P a g e

ANNEX 5: TREATMENT CARD

National Kala-azar Elimination Program Disease Control (CDC), DGHS, Mohakhali, Dhaka

Treatment and Follow up Card for Kala-azar Patients UHC/Sadar Hospital/Medical College Hospital

TREATMENT CARD

District:

Patient’s ID: ………………………………………………………………………………………..Date: …………………………………………….

Patient’s Name: …………………………………………………………………….................... Sex: …………………Age: …………….

Father/Husband’s name: ………………………………………………………….…………………………………………………………………

Address: Household Identification: …………….……………..Para/ Moholla: ….…………………………Village: ………..………………… Union: ……………………………………………….…………Upazila: .……………………………………………………………………………….

Patient’s Information: Date of Diagnosis: …………………………………………………………………………….………………

Pregnant: Yes/No Breast feeding: Yes/No

Diagnosis: 1. NKA 2. RKA 3. PKDL

Any other disease diagnosed: …………………………………………..…………………………………………………………………….. Date of treatment started: …………………………………………………………………………………………………………………………. Signature of MO: ………………………………………………….……………………………………………………………………………………. Name: …………………………………..……………………………………………..Date: ………………………………………..………………….

78 | P a g e

Treatment Chart

Name of drugs: 1.AmBisome 2.Miltefosine 3. Paromomycin 4. Miltefosine+ Paromomycin

5. LAmB+ Miltefosine 6. LAmB + Paromomycin

Date of administration:

Dose of the drug:

Duration of treatment:

Date of 1st treatment received:

Treatment Given at- daily/ alternative day

Dose schedule

Single drug/ 1st drug of combination (day/week) 2nd drugs weakly (applied for combination) (day/ week)

1 4 7 10 1 4 7 10

2 5 8 11 2 5 8 11

3 6 9 12 3 6 9 12

Findings before and after treatment

Date of Visit (Before Treatment) Date of Visit (after Treatment):

Temp: °F Temp: °F

Weight: kg Weight: kg

Pulse: /min Pulse: /min

BP: BP:

Spleen size: Spleen size:

Hb%: Hb%:

Others: Others:

79 | P a g e

ANNEX-6: FOLLOW-UP CHART

National Kala-azar Elimination Program Government of the People’s Republic of Bangladesh


FOLLOW-UP CHART:

Follow-up schedule

Expected date

Date of Visited

Temp (°f) Weight (kg)

Pulse (min)

Blood Pressure

Spleen size

Anemia Weakness Others Signature of Doctor

1st

Visit

2nd

Visit

3rd

Visit

4th

Visit

5th

Visit

6th

visit

7th

visit

8th

visit

9th

visit

10th

visit

11th

visit

80 | P a g e

ANNEX-7: MONTHLY KALA-AZAR REPORTING FORMAT


Monthly Reporting Format Disease Control Unit, DGHS, Mohakhali, Dhaka

District: Upazila: Date of reporting:

S.N Name of patients

Sex Age Parent's/ husband

name

Union Village Para/ identity of HH

Mobile no.

Date Type of Disease

Used Drug for treatment

Storage of drugs and diagnostics

Treatment Outcome

Name of Referred hospital

Remarks

NK

A

RK

A

PK

DL

Am

Bis

om

e

Milt

efo

sin

e

Par

om

om

ycin

Am

ph

ote

rici

n B

Am

Bis

om

e

Milt

efo

sin

e (

10m

g)

Milt

efo

sin

e (

50m

g)

Par

om

om

ycin

Am

ph

ote

rici

n B

ICT

(rk3

9)

1. Improved 2. Referred 3. Died

ANNEX-8: DESCRIPTION OF DRUGS USED FOR THE TREATMENT OF

KALA-AZAR

1. LIPOSOMAL AMPHOTERICIN B (LAMB):

Apart from treating serious systematic fungal infection and primary amoebic meningoencephalitis,

Liposomal Amphotericin B (LAmB) is first line of treatment of drug of choice for the treatment of

visceral leishmaniasis (VL). The drug has the following advantages:

LAmB has the best safety profile, well tolerated and widened the narrow therapeutic window.

LAmB can be given in a single intravenous infusion at a dose of 10 mg/kg for a period not less

than 3 hours duration. Therefore, the drug provides excellent treatment compliance.

In special situations, like Retreatment cases (relapse or failure cases), children of less than 5

years, in pregnancy, and co-infection with HIV/ AIDS could be treated with multiple dose of

LAmB (5mg/kg body weight on alternate days for 3 doses, or 3mg/kg body weight for 5 days. For

retreatment cases, this standard liposomal amphotericin B should be prescribed if the combination

treatment fails.

For standard use of LAmB please see the Annex 7: Standard operation Procedure for LAmB

(AmBisome).

For combination of first line treatment in Bangladesh, Injection Liposomal Amphotericin B would

be given as 5mg/kg body weight IV infusion for single day. It will be followed by either oral drug

(Miltefosine) or injection drug (Paromomycin) according to schedule.

LAmB (AmBisome) must be reconstituted using sterile water for injection (without a Bacteriostatic

agent) and diluted in dextrose solution (5%, 10% or 20%) for infusion only to be administered over a

period of 3-4 hours. AmBisome is not compatible with saline and must not be reconstituted or diluted

with saline or administered through an intravenous line that has previously been used for saline unless

first flushed with dextrose solution (5%, 10% or 20%) for infusion. If this is not feasible, AmBisome

should be administered through a separate line.

AmBisome should be administered by admitting the patient in a hospital during the entire period of

treatment for close supervision and monitoring of side effects. Each vial contains as active ingredient

50 mg of amphotericin B (50,000 units) encapsulated in liposomes. After reconstitution, the

concentration contains 4 mg/ml amphotericin B. AmBisome is indicated as the primary therapy of VL

in immuno-competent patients including both adult and children. AmBisome is also indicated as the

primary therapy of VL in immuno-compromised patients e.g., HIV positive.

Test Dose of AmBisome: In order to avoid anaphylaxis and anaphylactoid reactions, a test dose

should be administered initially. If a severe anaphylactic/anaphylactoid reaction occurs, the infusion

should be discarded. AmBisome has been shown to be substantially less toxic; however, adverse

reactions including renal adverse reactions may still occur.

Undesirable Side Effects of AmBisome: Fever and chills/rigors are the most frequent infusion-

related reactions expected to occur during AmBisome administration. Less frequent infusion-related

reactions such as hypotension, anorexia, nausea, vomiting, headache, dyspnea and tachypnea,

drowsiness, and generalized weakness, back pain, chest tightness or pain, bronchospasm, flushing,

and tachycardiamay occur. These resolve rapidly on stopping the infusion and may not occur on

82 | P a g e

subsequent dose. If any severe hypersensitivity reaction occurred then standard hypersensitivity

management protocol should be followed.

Precaution before using LAmB: Hb% of KA patients should be investigated before LAmB

administration. If Hb% is less than 6mg/dl, then 1 or 2 unit blood should be transfused to increase

Hemoglobin level more than 6 mg/dl and then LAmB should be infused. AmBisome should be

administered with caution in case of renal , hepatic or cardiac compromised patients

Contraindications: AmBisome is contraindicated in those patients who have demonstrated or have

known hypersensitivity to Amphotericin B deoxycholate or any other constituents of the product

unless, in the opinion of the treating physician, the benefit of therapy outweighs the risk.

Indications for alternative 1st line drugs (Oral miltefosine and Injection Paromomycin

combination)

When Liposomal Amphotericin B is not indicated due to hypersensitivity, intolerance,

contraindication

When Liposomal Amphotericin B is not available.

2. MILTEFOSINE:

Miltefosine, an oral relatively safe drug, is used as an alternative choice of 1st line of treatment of KA

in NKEP in Bangladesh. The dose of Miltefosine is depended on age and body weight, and should be

administered daily in two divided doses with meal for a period of 28 days. In case of missed doses,

treatment up to 35 days is recommended to complete the full course.

Evidence obtained from at least one properly designed randomized controlled trial shows that total

doses with 28 days treatment with Miltefosine has shown a cure rate in immuno-competent patients of

more than 94% in India and about 90% in Ethiopia18

. Disappearance of the lesions at a 12-month

follow-up visit was taken as the criterion of cure, including parasitological as well as clinical cure.

Since this drug is given for 28 days, patient compliance to treatment is a serious concern. Analysis of

data from the upazila health complexes, tertiary hospitals and SK-KRC of Bangladesh would be

useful to document the issue of compliance. Similar to the development of drug resistance in case of

any monotherapy, resistance of parasite to Miltefosine can also develop.

When to avoid the use of Miltefosine: Miltefosine is the preferred drug of choice for the treatment

of NKA and PKDL in the kala-azar elimination program. However, the drug is not recommended in

the following situations: (i) women during pregnancy, (ii) married women of child-bearing age who

are not using contraceptives regularly and are at risk of becoming pregnant, (iii) women who are

breast-feeding their babies, and (iv) children less than two years of age.

Miltefosine may not be the ideal drug for the following patients of Kala-azar: Miltefosine may

not be the ideal drug for patients of kala-azar who are severely undernourished having severe anemia

and patients with known history of kidney or liver failure. For patients with severe anemia and severe

under nutrition, before starting miltefosine treatment, patients should be built up by blood transfusion

to correct anemia and appropriate feeding to correct severe under nutrition. If dehydration is present,

it should be corrected with fluids, preferably oral rehydration solution. This would help in reducing

the side effects of the drug. Married women of childbearing age should not be given miltefosine

18

Control of the Leishmaniases: WHO Technical Report Series-949. Report of a meeting of the WHO Expert Committee on the Control of Leishmaniases, Geneva, 22-26 March 2010, WHO; p-58.

83 | P a g e

treatment if couples do not agree to use contraceptive methods to prevent pregnancy during treatment

and until three months thereafter.

Adverse reactions of Miltefosine treatment: Adverse reactions to Miltefosine are mostly mild.

Mild to moderate vomiting is seen in 40% patients and mild diarrhea in 15-20% patients. These

adverse effects are seen usually during the 1st week of treatment. There may be liver-or-kidney-

related side effects like puffiness of the eyes, jaundice or decrease urine. If any of the symptoms are

reported, the patients should be referred to a Level-2 or Level-3 health facility for advice and

treatment. Adverse reactions to Miltefosine are mostly mild. Mild to moderate vomiting is seen in

40% patients and mild diarrhea in 15-20% patients. These usually occur during first week of

treatment.

Duration of treatment of Miltefosine:

Miltefosine should not be given as mono-therapy for kala-azar cases as there is increasing resistance

of the drug used as mono-therapy. This drug should be prescribed as combination with either

Liposomal Amphotericin B or Paromomycin. If Liposomal Amphotericin B is used in combination,

Miltefosine should be prescribed as standard dose from 2nd

day to 8th day, while in combination with

Paromomycin, Miltefosine should be given from day 1 to day 10.

3. PAROMOMYCIN:

Paromomycin is an aminoglycoside antibiotic, used to treat intestinal infections such as

cryptosporidiosis and amoebiasis, and other diseases such as kala-azar. Paromomycin was

demonstrated to be effective against cutaneous leishmaniasis (CL) in clinical studies in the USSR in

the 1960s, and in trials with visceral leishmaniasis (VL) in the early 1990s. The route of

administration is intramuscular injection and in oral in capsule form. Paromomycin topical cream with

or without gentamicin is an effective treatment for ulcerative cutaneous leishmaniasis (according to

the results of a phase-3, randomized, double-blind, parallel group–controlled trial). Sundar S and Jaya

Chakravarty (2008) in their research reported that paromomycin, with its excellent efficacy, low cost,

shorter duration of administration and good safety profile has the potential to be used as a first-line

drug for the treatment of leishmaniasis19

.

Musa AM, et al (2010)conducted a research to investigate the treatment efficacy with paromomycin in

kala-azar patients and documented that at end of treatment (EoT), 85% of patients in the 20

mg/kg/day group and 90% of patients in the 15 mg/kg/day group had parasite clearance. Six months

(6M) after treatment, efficacy was 80.0% and 81.0% in the 20 mg/kg/day and 15 mg/kg/day groups,

respectively20

. There were no serious adverse events. Pharmacokinetic profiles suggested a difference

between the two doses, although numbers of patients recruited were too few to make it significant (n

= 3 in the 20 mg/kg/day and n = 6 in the 15 mg/kg/day groups respectively). Conclusion: Data suggest

that both high dose regimens were more efficacious. The dose of 15 mg/kg sulfate is equivalent to 11

mg/kg of base, and 20 mg/kg sulfate is equivalent to 15 mg/kg of base. A combination therapy of

AmBisome (single dose) and Paromomycin for 10 days with 15 mg/kg/day has been found to be

effective in treating kala-azar cases.

Mild pain at the injection site is the commonest adverse event. Reversible ototoxicity occurs in few

cases. Renal toxicity is rare. Some patients may develop hepatotoxicity, indicated by raised hepatic

19 Sunder S and Chakravarty. Paromomycin in the treatment of leishmaniasis. Banaras Hindu University, Institute of Medical Sciences, Department of Medicine, Varanasi-221005, India. May 2008, Vol. 17, No. 5 , Pages 787-794 20 Musa AM, Younis B, Fadlalla A, et al. Paromomycin for the Treatment of Visceral Leishmaniasis in Sudan: A Randomized, Open-Label, Dose-Finding Study. PloS Neglected Tropical Disease. October 2010, Volume 4, Issue 10, e855

84 | P a g e

enzyme concentration; tetany has also been reported. A topical formulation is available for cutaneous

leishmaniasis.

4. AMPHOTERICIN B DEOXYCHOLATE:

Recommended second line drug for treatment of New Kala-azar and RKA is Amphotericin B

deoxycholate. This drug is also an effective drug. But it has high toxicity profile and thus pushed to

second line. The recommended dose is 1 mg/kg daily or alternate day in the form of intravenous

infusion (in 5% Dextrose solution 500 ml) for 15 doses having a cure rate of ≥90%. A test dose

should be given before administration of Amphotericin B deoxycholate. After preparation of solution,

5 drops/minute for 30 minutes, then 10 drops/minute for another 30 minutes and if there is no reaction

occurs, then the infusion should be given slowly over a period of 4-6 hours.

5. SODIUM STIBOGLUCONATE (SSG)

SSG is an effective and widely used drug for KA and KATF. But the drug is pushed to second line

because of its cardiac toxicity and is recommended by WHO to be phased out gradually. The drug

should be given at a dosage of 20mg/kg body weight, daily IM injection for 30 days. It is essential to

weigh the patient before starting treatment. Clinical cardiac monitoring should be done throughout the

treatment period. The preferred route of administration recommended is by deep intramuscular (IM)

injection. It is better not to give the drug intravenously (IV) to avoid the risk of cardiovascular

collapse.

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ANNEX-9: MONITORING OF TREATMENT OUTCOMES VARIABLES

SN Monitoring Treatment Outcomes Variables

A. Service Delivery Area: Starting Treatment

1. No. of drugs supplied to health facilities

2. No. of pregnancy-test kits supplied

3. No. of pregnancy tests done

4. No. of women of childbearing age starting Miltefosine

5. No. of total kala-azar patients treated

6. No. of all confirmed kala-azar cases

B. Service Delivery Area: Evaluating Treatment

7. No. of new cases of kala-azar detected per year

8. No. of kala-azar patients with initial cure

9. No. of kala-azar patients with final cure

10. No. of kala-azar patients who started treatment

11. No. of non-response kala-azar patients

12. No. of relapse kala-azar

13. No. of loss to follow-up

14. No. of defaults cases of kala-azar

15. No. of kala-azar patients encountered adverse drug effects

16. No. of kala-azar-related death

ANNEX-10: INDICATORS OF KALAAZAR TREATMENT EFFECTIVENESS

PROGRAMMATIC INDICATORS OF KALA-AZAR TREATMENT EFFECTIVENESS

Name of Health Facility/UHC: ________________________ No. of New Cases: ___________

Time Period (Quarter/Year):______________________________________________________

SN Outcomes Indicators L.AmB

n:_____

MLF

n:_____

PMIM

n:_____

AMP-B

n:_____

SSG

n:_____

1 Initial Cure Rate

2 Final Cure Rate

3 Treatment Failure Rate

4 Relapse rate

5 Loss-to-Follow-up Rate

6 Transferred Rate

7 Death/Mortality Rate

L.AmB = Liposomal Amphotericin B (IV); MLF = Miltefosine (Oral); PMIM = Paromomycin (IM); AMP-B = Amphotericin B deoxycholate (IV); SSG = Sodium Stibogluconate (Pentavalent antimonial) (IM/IV).

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ANNEX-11: MONTHLY/QUARTERLY REPORT FORMAT ON

EARLY TREATMENT OUTCOMES



MONTHLY/QUARTERLY REPORT ON EARLY TREATMENT OUTCOMES21

Name of Health Facility:

_____________________________

Name of MO/RMO:

___________________________

Date of Completion:

______/______/________

District:______________________

Signature:__________________

EARLY TREATMENT OUTCOMES Patients Registered During

Quarter of Year _____

Quarter: 1st

/2nd

/3rd

/4th

____________________

1. NEW CASES (1st ttm)* Total

number

registered

Initial

Cure

Non-

Response

Defaulter

Treatment

stopped for

ADR

Others

(Transfer

out)

Death

New KA Cases

LAmB

MLF

PMIM

AMP-B

SSG

TOTAL

* Do not include transfers in and patients who were referred without being started on treatment.

2. OTHER CASES (2nd ttm) Total

number

registered

Initial

Cure

Non-

Response

Defaulter

Treatment

stopped for

ADR

Others

(Transfer

out)

Death

Re-Treatment

after Failure,

Default, ADR

or Relapse.

LAmB

MLF

PMIM

AMP-B

SSG

TOTAL

L.AmB = Liposomal Amphotericin B (IV); MLF = Miltefosine (Oral); PMIM = Paromomycin (IM); AMP-B = Amphotericin B deoxycholate (IV); SSG = Sodium Stibogluconate (Pentavalent antimonials) (IM/IV); ADR = Adverse Drug Reaction

21

Monitoring Clinical/Treatment Outcomes Forms, available at: www.leishrisk.net/kaladrug

http://www.leishrisk.net/kaladrug

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ANNEX-12: MONTHLY/QUARTERLY REPORT ON

FINAL TREATMENT OUTCOMES



MONTHLY/QUARTERLY REPORT ON FINAL TREATMENT OUTCOMES22

Name of Health Facility:

__________________________________

Name of MO/RMO:

__________________________

Date of Completion of this Form: _____/_____/____

District:____________________________

Signature:__________________

FINAL TREATMENT OUTCOMES Patients Registered During

Quarter of Year _____

Quarter:1st

/2nd

/3rd

/4th

__________________

Please put same numbers as reported on the early treatment outcomes form in the columns bellow: Total number of registered, Non-response,

Defaulter, Treatment stopped for ADR, and Others.

1. NEW CASES (1st ttm)* Total

number

registered

Final

Cure

Non-

Respo

nse

Defaul

ter

Treatment

stopped

for ADR

Others

(Transfer

out)

Death Relapse Loss-to

Follow-up

New KA

Cases

L.AmB

MLF

PMIM

AMP-B

SSG

TOTAL

* Do not include transfers in and patients who were referred without being started on treatment.

2. OTHER CASES Total

number

registered

Final

Cure

Non-

Respo

nse

Defaul

ter

Treatment

stopped

for ADR

Others

(Transfer

out)

Death Relapse Loss-to

Follow-up

Re-Treatment

after Failure,

Default, ADR

or Relapse.

L.AmB

MLF

PMIM

AMP-B

SSG

TOTAL

L.AmB = Liposomal Amphotericin B (IV); MLF = Miltefosine (Oral); PMIM = Paromomycin (IM); AMP-B = Amphotericin B deoxycholate (IV); SSG = Sodium Stibogluconate (Pentavalent antimonials) (IM/IV); ADR = Adverse Drug Reaction

22Monitoring Clinical/Treatment Outcomes Forms: www.leishrisk.net/kaladrug

http://www.leishrisk.net/kaladrug

88 | P a g e

ANNEX-13: INDICATORS SHOWING THE PHARMACOVIGILANCE

ACTIVITIES:

Pharmacovigilance (PV) Activities - at Central and Upazila

Input: Describes the resources

1. Operational plan and Suspected ADR Reporting Form

2. WHO-UMC Causality Assessment Algorithm

3. Laboratory Guidelines for Monitoring anti-kala-azar

Process: Describes the activities and performance

5. Training sessions conducted for the health professional on PV

6. Training sessions planned on pharmacovigilance

7. No. of Health Facilities sending PV Form

Outputs: Measures the direct products/deliverables

9. No. of doctors, nurses and statistician received training on PV

10. No. of participants remain untrained on pharmacovigilance

11. No. of health staff able to describe the pharmacovigilance

12 No. of New KA identified as having adverse effects

13. No. of KATF identified as having adverse effects

14. No. of RKA identified as having adverse effects

15. No. of PKDL identified as having adverse effects

Outcome: Behavioral Change and health impacts

22. No. of patients recovered

23. No. of fatal cases resulting to death

24. No. of cases requiring in-patient hospitalization

25. No. of cases resulting to disability/incapacity

26. Female having babies with cong. anomaly/birth defect

27. No. of cases with bronchospasm /convulsion/others

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ANNEX-14: WEB-BASED REGISTRATION OF KALA-AZAR CASES AND

FOLLOW-UP FORM

WEB-BASED REGISTRATION OF KALA-AZAR CASES AND FOLLOW-UP FORM

Sl. No 1. General Information

1. Name of health facility

2. Hospital indoor registration no.

3. Serial no.

4. Admission date

5. Patients ID (Dist code (UHC) + Upazila Code (UHC) + Admission

Month + Admission Year + Serial No. (00 - 00 - 00 - 0000- 000) = 13 digit)

6. Full name

7. Father's name / Husband's name

8. Guardian name

9. Date of birth

10. Age in Year

11. Gender Male Female Third gender

12. Marital Status Currently Married Separated Deserted

Divorced Widowed Never Married

13. Weight in kg

14. Height in cm

15. Contact number 1

16. Contact number 2

17. District

18. Upazila

19. Union

20. Mouza

21. Moholla/ Holding No./Para/Street No/Village

22. House Hold Head Name

23. Referred by

Self Family Member

NGO worker

Health Inspector / Health Assistant / AHI / FWA/FWF/FWV

Private Practitioner Private Qualified Doctor

Government Doctor Media Others

Others

24. Household longitude

25. Household latitude

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2. Patient's information (Before treatment)

Disease History

26. Exposure to VL endemic area /Current living in Kala-

azar endemic area Yes No

27. History of travelling in the Kala-azar endemic area Yes No

28. History of previous Kala-azar Yes No

Symptom & Sign

29. Fever for 2 weeks or more Yes No

30. Nausea Yes No

31. Vomiting Yes No

32. Pallor Yes No

33. Weakness Yes No

34. Skin lesion Yes No

35. Type of skin lesion

Papule Nodule Hypo

pigmented

Macule Mixed

36. Duration of skin lesion (In days)

37. Temperature (0c)

38. Pulse rate per minutes

39. Blood pressure _______ / _______

40. Spleen size in cm

41. Liver size in cm

Laboratory test

42. Hemoglobin in gm/dl

43. rk39 test Positive Negative

44. Other test

Fill up the blank (if applicable)

45. Pregnancy test Positive Negative

Not Applicable Not done

46. Using contraceptive method Yes No

47. Lactating Yes No

Diagnosis and treatment

48. Disease type

KA KATF

Relapse

PKDL CL

49.

Treatment

received

Mono Therapy Combo Therapy

50. Drug received

Liposomal

Amphotericin B Miltefosine Paromomycin Non-Liposomal

Amphotericin B

Sodium Stibo

Gluconate

Trade name

Drug dose Single Multi dose

Cumulative

Drug start date

Drug start time

Drug stop date

Drug stop time

51. Other disease

52. Treatment given for other disease

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3. Patient's information (After treatment/before discharge)

Symptom & Sign

53. Temperature in 0c


55. Anorexia Yes No Not Mentioned

56. Pallor Yes No Not Mentioned

57. Weakness Yes No Not Mentioned

58. Nausea Yes No Not Mentioned

59. Vomiting Yes No Not Mentioned

Laboratory test

60. Hemoglobin in gm/dl

61. Blood (RE)

Status

62. Status

Improved & Discharge

Discharge on request (DOR)

Discharge on risk bond

Absconded

Referred / Transferred

Expired/Died

63. Date of discharge

Suspected Adverse Drug Reaction(ADR) Information

64. Suspected AE Yes No [ If no then skip to Q.73 ]

65.

Type ADR

Adverse drug reaction

Product quality problem

Medication error

Other:______________

Suspected Drug

Trade name _____________________Generic

name__________________

Indication____________________________

Dose [strength, unit] _____________ Dosage

form_________________

Frequency__________________Batch/Lot

number________________

Manufacturer_____________

66.

Describe ADR including relevant tests and laboratory results:

67.

Date & Time of the ADR started Date & Time of the ADR was reported Date &

Time of the ADR stopped

________________________ ____________________________

_______________________ (DD/MM/YYYY; HH:MM AM/PM) (DD/MM/YYYY; HH:MM AM/PM ) (DD/MM/YYYY;

HH:MM AM/PM)

68.

Was the adverse event treated? Yes No

If yes, please specify

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69.

Action taken after the Adverse Drug

Reaction or Adverse Event

Dose stopped

[ Dose reduced

No action taken

Did reaction subside after stopping/reducing the dose of the

suspected Product?

Yes No Not applicable

Did reaction appear after reintroducing the suspected product?

Yes No Not applicable

70.

Seriousness of the adverse event:

Not serious

Hospitalization or prolongation of

hospitalization

Disability or permanent damage

Congenital anomaly/birth defect

Life threatening

Other serious

Death

Outcomes of the adverse event:

Recovered

Recovered/resolved with sequel

Not recovered

Unknown

Fatal (date of death: ______________________)

71. Other relevant history (including pre-existing medical conditions, allergies, pregnancy, smoking, alcohol use,

liver or kidney problems, hypersensitivity, history of ADRs, etc.):

72. Other concomitant product information

Drug 1 Drug 2 Drug 3 Drug 4

Trade name

Generic name

Indication

Dosage form

Route

Dose

Frequency

Date started

Time started

Date stopped

Time stopped

73. Reporter Information

Name_________________________________________Designation__________________________________

__

Email

address_________________________________________________________________________________

Mobile phone__________________________________ Land

phone______________________________________

Signature______________________________________Date of

submission________________________________

93 | P a g e

5. Follow-up information

74. Patient ID

75. Follow-up type ....... Follow up / Unscheduled

76. Follow-up visit done? Yes No

77. If No then reason Death Did not attend

Others

78. If Yes, Date

79. Follow-up for KA KATF RELAPSE PKDL

Symptom & Sign

80. Fever for 2 weeks or more Yes No Not Mentioned

81. Nausea Yes No Not Mentioned

82. Vomiting Yes No Not Mentioned

83. Pallor Yes No Not Mentioned

84. Weakness Yes No Not Mentioned

85. Skin lesion Yes No Not Mentioned

86. Type of skin lesion

Papule Nodule Hypo pigmented

Macule Mixed

87. Duration of skin lesion in days

88. Temperature in 0C

89. Weight in kg

90. Blood pressure _______ / _______


92. Spleen size in cm

93. Liver size in cm

Laboratory test

94. Hemoglobin (gm/dl)

95. Blood (RE)

96. Other test

Status

97. Any other complain

98. Treatment given for other complain

99. Status

Improved Referred (After 1 month and 6 month follow up considered as Initial Cure and Final Cure) Treatment failure Relapse

PKDL Death

100. Drug used for treatment given in the

follow up

Liposomal Amphotericin B Miltefosine

Paromomycin Amphotericin B Deoxycholate

Sodium stibogluconate (SSG)

Reporter Information

Name _____________________________________________

Designation___________________________________

Email address

____________________________________________________________________________________

Mobile phone_______________________________________ Land

phone____________________________________

Signature___________________________________________Date of submission____________________

94 | P a g e

SL.No Name of the Adverse

Event Yes No

1 Fever ☐ ☐

2 Chills ☐ ☐

3 Rigor ☐ ☐

4 Malaise ☐ ☐

5 Sweating ☐ ☐

6 Facial Flushing ☐ ☐

7 Rash ☐ ☐

8 Vertigo ☐ ☐

9 Dyspnoea ☐ ☐

10 Hypotension ☐ ☐

11 Hypertension ☐ ☐

12 Dyspepsia ☐ ☐

13 Anorexia ☐ ☐

14 Diarrhea ☐ ☐

15 Nausea ☐ ☐

16 Vomiting ☐ ☐

17 Abdominal pain ☐ ☐

18 Headache ☐ ☐

19 Back pain ☐ ☐

20 Chest pain ☐ ☐

21 Arthralgia ☐ ☐

22 Allergic reaction ☐ ☐

23 Nephrotoxicity ☐ ☐

24 Hepatitis ☐ ☐

25 Retinal degeneration ☐ ☐

SL. No Name of the Adverse

Event Yes No

26 Bronchospasm ☐ ☐

27 Tachycardia ☐ ☐

28 Musculoskeletal pain ☐ ☐

29 Thrombocytopenia ☐ ☐

30 Anaphylactoid reaction ☐ ☐

31 Hypokalaemia ☐ ☐

32 Hyponatraemia ☐ ☐

33 Hypocalcaemia ☐ ☐

34 Hypomagnesaemia ☐ ☐

35 Hyperglycaemia ☐ ☐

36 Vasodilatation ☐ ☐

37 Liver function test abnormal ☐ ☐

38 Hyperbilirubinaemia ☐ ☐

39 Increased creatinine ☐ ☐

40 Blood urea increased ☐ ☐

41 Pyrexia ☐ ☐

42 Phlebitis ☐ ☐

43 Others /Unexpected ☐ ☐

44 Death ☐ ☐

4

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ANNEX-15: SOP OF AMBISOME

Standard Operating Procedure (SOP) of

AmBisome DESCRIPTION

AmBisome for Injection is a sterile, non-pyrogenic lyophilized product for intravenous infusion. Each

vial contains 50 mg of amphotericin B, USP, intercalated into a liposomal membrane consisting of

approximately 213 mg hydrogenated soy phosphatidylcholine; 52 mg cholesterol, NF; 84 mg

Distearoyl phosphatidyl glycerol; 0.64 mg alpha tocopherol, USP; together with 900 mg sucrose, NF;

and 27 mg disodium succinate hexahydrate as buffer. Following reconstitution with Sterile Water for

Injection, USP and the resulting pH of the suspension is between 5-6.

Mechanism of Action:

The active ingredient of AmBisome acts by binding to the sterol component, ergosterol of the cell

membrane of susceptible fungi. By forming a trans-membrane channel it leads to alterations in cell

permeability which causes leak out of monovalent ions (Na+, K+, H+ and Cl+) from the cell and

finally causes cell death. Amphotericin B has higher affinity for the ergosterol component of the

fungal cell membrane and also binds with cholesterol component of the mammalian cell leading to the

cytotoxicity. The liposomal preparation of Amphotericin B (AmBisome) has been shown to penetrate

the cell wall of both extracellular and intracellular forms of susceptible fungi.

Adverse effects:

AmBisome is well tolerated. AmBisome has a lower incidence of chills, hypertension, hypotension,

tachycardia, hypoxia, hypokalemia, and various events related to decreased kidney function as

compared to Amphotericin B deoxycholate. There have been a few reports of flushing, back pain with

or without chest tightness, and chest pain associated with AmBisome administration; on occasion this

has been severe. Where these symptoms noted, the reaction developed within a few minutes after the

start of infusion and disappeared rapidly when the infusion is stopped. The symptoms do not occur

with every dose and usually do not recur on subsequent administrations when the infusion rate is

slowed.

Infusion Related Reactions

In Study 94-0-002, the large, double-blind study of pediatric and adult febrile neutropenic patients, no

premedication to prevent infusion related reaction was administered prior to the first dose of study

drug (Day 1). AmBisome-treated patients had a lower incidence of infusion related fever (17% versus

44%), chills/rigors (18% versus 54%) and vomiting (6% versus 8%) on Day 1 as compared to

Amphotericin B deoxycholate-treated patients.

Contraindications:

AmBisome is contraindicated in those patients who have demonstrated or have known

hypersensitivity to Amphotericin B deoxycholate or any other constituents of the product unless, in

the opinion of the treating physician, the benefit of therapy outweighs the risk.

Administration of AmBisome

Objective of SOP: To administer single dose intravenous AmBisome accurately and with proper

aseptic precaution.

Materials required:

1. A pair of disposable hand gloves.

2. Disposable IV cannula of appropriate size.

3. Ball of cotton.

4. Chlorohexidine / 70% isopropyl alcohol/ spirit.

96 | P a g e

5. Micropore 2 inches.

6. Disposable infusion set.

7. Saline stand.

8. A 10 ml syringe containing test dose of AmBisome 1 mg (0.25 of dissolved AmBisome with

distilled water) prepared according to SOP for AmBisome preparation.

9. Measured Total dose of AmBisome diluted in 5% DA prepared according to SOP guideline.

Procedure:

1. Explain the procedure to the patient and give assurance that it is a very simple procedure.

2. Patient should be lying on bed with the head on a soft pillow.

3. Wash your hands with soap and water vigorously before preparation.

4. Take proper aseptic precaution.

5. Wear a pair of gloves.

6. Bind the tourniquet in the arm of the patient to make the cubital vein prominent.

7. Take a ball of cotton soaked with chlorohexidine and gently rub the site of injection.

8. Wait until it is dried up.

9. Take the IV canula and prick the vein and ensure that it is placed in the vein.

10. Fix the canula with micropore.

11. Take the syringe loaded with the test dose of AmBisome as described above.

12. Start pushing the plunger very slowly and give the whole 10ml of test dose AmBisome in 10

minutes through i.v. canula.

13. Look for any hypersensitivity reaction.

14. If any hypersensitivity reaction occurs then give:

a. Tab. Chlorpheniramine 4mg in Adult and 0.1-0.2mg/kg body weight in children orally

(maximum 4mg per dose).

b. Tab. Paracetamol (500mg ) in Adult and 15-20mg/g body weight in Children orally.

15. If the symptoms do not disappear, then call the duty / study physician.

16. If there is any evidence of hypersensitivity reaction the patient should not be given the

AmBisome infusion.

17. After finishing the test dose wait for 30 minutes and closely observe the patient for any

adverse drug reaction.

18. If there are no symptoms or signs of hypersensitivity reaction after 30 minutes then take a

disposable infusion set and fix it with the bottle/pack containing Measured Total dose of

AmBisome diluted in 5% DA (please see SOP for preparation of AmBisome and the table for

calculation of AmBisome)

19. Label the bottle/pack with patient‟s initial and ID, time of starting and drops per minutes to be

infused.

20. Give oral premedication with paracetamol 10mg/kg and Chlorpheniramine 0.1-0.2 mg/kg

(maximum 4 mg per dose)

21. Measure vital parameter (respiratory rate, blood pressure, pulse) before the start of infusion.

22. Start the IV channel very slowly initially.

23. Then calculate the drops per minute to give the whole volume in a period of 3-4 hours.

24. Observe the patient closely for any adverse drug reaction for 30 minutes.

25. Discard all the sharp instruments in Red colored waste disposal container.

26. Discard all the soft materials in the yellow colored waste disposal container.

27. Monitor vital parameters at one hour after infusion, at the end of infusion and one hour later

after completion of infusion.

Responsible person: Trained Staff nurse of Upazila Health complex is responsible for the task but

the whole procedure should be in close observation by hospital duty physician.

Applicability to other SOP: This SOP is applicable to the SOP for preparation and calculation of

AmBisome.

97 | P a g e

Glossary/ Definition:

1. IV- Intravenous

2. 5% DA- 5% dextrose in aqua

3. Kg- Kilogram

4. Ml- Milliliter

Reference:

Leaflet provided with the AmBisome vial

Glossary/ Definition:

5. 5% DA: 5% dextrose in aqua

6. Kg: Kilogram

7. Ml: Milliliter

8. UHC: Upazila Health Complex

9. Icddr,b: International Centre For Diarrheal Disease Research, Bangladesh

Reference:

Leaflet provided with the AmBisome vial

Guideline provided by Scientist Shyam Sundar

SOP used in AmBisome preparation in trial in India

Table of volume of reconstituted AmBisome and D5W according to rounded-off body weight

Body weight

(kg)

Total dose (mg)

No. of vials is to be

reconstituted

Vials to be used

Reconstituted volume in ml (4mg per ml)

Total volume needed from the vial (ml)

Volume 5% DA (ml) to make

1mg/ml

Total volume of 5% DA after dilution

(1 mg/ml)

Rate of infusion

(drops/min)

Time required (In hour)

10 100 2 2 25 25 75 (25+75)=100 10 2.50

10.5 105 3 2+1 25+1.25 26.25 78.75 (26.25+78.75) = 105 11 2.50

11 110 3 2+1 25+ 2.50 27.5 82.5 (27.50+82.50) =110 11 2.50

11.5 115 3 2+1 25+3.75 28.75 86.25 (28.75+86.25) =115 12 2.50

12 120 3 2+1 25+5 30 90 (30+90) =120 12 2.50

12.5 125 3 2+1 25+6.25 31.25 93.75 (31.25+93.75)= 125 13 2.50

13 130 3 2+1 25+7.50 32.5 97.5 (32.50+97.50)=130 13 2.50

13.5 135 3 2+1 25+8.75 33.75 101.25 (33.75+101.25)=135 14 2.50

14 140 3 2+1 25+10 35 105 (35+105)=140 14 2.50

14.5 145 3 2+1 25+11.25 36.25 108.75 (36.25+108.75)=145 15 2.50

15 150 3 3 37.5 37.5 112.5 (37.5+112.50) =150 15 2.50

15.5 155 4 3+1 37.5+1.25 38.75 116.25 (38.75+116.25)=155 16 2.50

16 160 4 3+1 37.5+ 2.5 40 120 (40+120) = 160 16 2.50

16.5 165 4 3+1 37.5+ 3.75 41.25 123.75 (41.25+123.75)=165 17 2.50

17 170 4 3+1 37.5+5 42.5 127.5 (42.5+127.50)=170 17 2.50

17.5 175 4 3+1 37.5+6.25 43.75 131.25 (43.75+131.25)=175 18 2.50

18 180 4 3+1 37.5+ 7.50 45 135 (45+135)= 180 18 2.50

18.5 185 4 3+1 37.5+8.75 46.25 138.75 (46.25+138.75)=185 19 2.50

19 190 4 3+1 37.5+10 47.5 142.5 (47.5+142.5)=190 19 2.50

19 190 4 3+1 37.5+10 47.5 142.5 (47.5+142.5)=190 19 2.50

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19.5 195 4 3+1 37.5+11.25 48.75 146.25 (48.75+146.25)=195 20 2.50

20 200 4 4 50 50 150 (50+150)=200 20 2.50

20.5 205 5 4+1 50+1.25 51.25 153.75 (51.25+153.75)=205 21 2.50

21 210 5 4+1 50+2.50 52.5 157.5 (52.50+157.5)=210 21 2.50

21.5 215 5 4+1 50+3.75 53.75 161.25 (53.75+161.25)=215 22 2.50

22 220 5 4+1 50+5.0 55 165 (55+165)=220 22 2.50

22.5 225 5 4+1 50+6.25 56.25 168.75 (56.25+168.75)=225 23 2.50

23 230 5 4+1 50+7.50 57.5 172.5 (57.50+172.5)=230 23 2.50

23.5 235 5 4+1 50+8.75 58.75 176.25 (58.75+176.25)=235 24 2.50

24 240 5 4+1 50+10 60 180 (60+180)=240 24 2.50

24.5 245 5 4+1 50+11.25 61.25 183.75 (61.25+183.75)=245 25 2.50

25 250 5 5 62 62 188 (62+188)=250 25 2.50

25.5 255 6 5+1 62+1.25 63.25 191.75 (63.25+191.75)=255 26 2.50

26 260 6 5+1 62+2.50 64.5 195.5 (64.50+195.5)=260 26 2.50

26.5 265 6 5+1 62+3.75 65.75 199.25 (65.75+199.25)=265 27 2.50

27 270 6 5+1 62+5.0 67 203 (67+203)=270 27 2.50

27.5 275 6 5+1 62+6.25 68.25 206.75 (68.25+206.75)=275 28 2.50

28 280 6 5+1 62+7.50 69.5 210.5 (69.50+210.5)=280 28 2.50

28.5 285 6 5+1 62+8.75 70.75 214.25 (70.75+214.25)=285 29 2.50

29 290 6 5+1 62+10 72 218 (72+218)=290 29 2.50

29.5 295 6 5+1 62+11.25 73.25 221.75 (73.25+221.75)=295 30 2.50

30 300 6 6 75 75 225 (75+225)=300 30 2.50

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30.5 305 7 6+1 75+1.25 76.25 228.75 (76.25+228.75)=305 31 2.50

31 310 7 6+1 75+2.50 77.5 232.5 (77.50+232.5)=310 31 2.50

31.5 315 7 6+1 75+3.75 78.75 236.25 (78.75+236.25)=315 32 2.50

32 320 7 6+1 75+5.0 80 240 (80+240)=320 32 2.50

32.5 325 7 6+1 75+6.25 81.25 243.75 (81.25+243.75)=325 33 2.50

33 330 7 6+1 75+7.50 82.5 247.5 (82.50+247.5)=330 33 2.50

33.5 335 7 6+1 75+8.75 83.75 251.25 (83.75+251.25)=335 34 2.50

34 340 7 6+1 75+10 85 255 (85+255)=340 34 2.50

34.5 345 7 6+1 75+11.25 86.25 258.75 (86.25+258.75)=345 35 2.50

35 350 7 7 87.5 87.5 262.5 (87.5+262.5)=350 35 2.50

35.5 355 8 7+1 87.5+1.25 88.75 266.25 (88.75+266.25)=355 35 2.54

36 360 8 7+1 87.5+2.50 90 270 (90+270)=360 35 2.57

36.5 365 8 7+1 87.5+3.75 91.25 273.75 (91.25+273.75)=365 35 2.61

37 370 8 7+1 87.5+5.0 92.5 277.5 (92.50+277.5)=370 35 2.64

37.5 375 8 7+1 87.5+6.25 93.75 281.25 (93.75+281.25)=375 35 2.68

38 380 8 7+1 87.5+7.50 95 285 (95.00+285)=380 35 2.71

38.5 385 8 7+1 87.5+8.75 96.25 288.75 (96.25+288.75)=385 35 2.75

39 390 8 7+1 87.5+10 97.5 292.5 (97.5+292.5)=390 35 2.79

39.5 395 8 7+1 87.5+11.25 98.75 296.25 (98.75+296.25)=395 35 2.82

40 400 8 8 100 100 300 (100+300)=400 35 2.86

40.5 405 9 8+1 100+1.25 101.25 303.75 (101.25+303.75)=405 35 2.89

41 410 9 8+1 100+2.50 102.5 307.5 (102.50+307.50)=410 35 2.93

41.5 415 9 8+1 100+3.75 103.75 312.25 (103.75+312.25)=415 35 2.97

42 420 9 8+1 100+5.0 105 315 (105+315)=420 35 3.00

42.5 425 9 8+1 100+6.25 106.25 318.75 (106.25+318.75)=425 35 3.04

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43 430 9 8+1 100+7.50 107.5 322.5 (107.50+322.5)=430 35 3.07

43.5 435 9 8+1 100+8.75 108.75 326.25 (108.75+326.25)=435 35 3.11

44 440 9 8+1 100+10 110 330 (110+330)=440 35 3.14

44.5 445 9 8+1 100+11.25 111.25 333.75 (111.25+333.75)=445 35 3.18

45 450 9 9 112.5 112.5 337.5 (112.5+337.5)=450 35 3.21

45.5 455 10 9+1 112.5+1.25 113.75 341.25 (113.75+341.25)=455 35 3.25

46 460 10 9+1 112.5+2.50 115 345 (115+345)=460 35 3.29

46.5 465 10 9+1 112.5+3.75 116.25 348.75 (116.25+348.75)=465 35 3.32

47 470 10 9+1 112.5+5.0 117.5 352.5 (117.50+352.5)=470 35 3.36

47.5 475 10 9+1 112.5+6.25 118.75 356.25 (118.75+356.25)=475 35 3.39

48 480 10 9+1 112.5+7.50 120 360 (120+360)=480 35 3.43

48.5 485 10 9+1 112.5+8.75 121.25 363.75 (121.75+363.75)=485 35 3.46

49 490 10 9+1 112.5+10 122.5 367.5 (122.5+367.5)=490 35 3.50

49.5 495 10 9+1 112.5+11.25 123.75 371.25 (123.75+371.25)=495 35 3.54

50 500 10 10 125 125 375 (125+375)=500 35 3.57

50.5 505 11 10+1 125+1.25 126.25 378.75 (126.25+378.75)=505 35 3.61

51 510 11 10+1 125+2.50 127.5 382.5 (127.50+382.5)=510 35 3.64

51.5 515 11 10+1 125+3.75 128 387 (128+387)=515 35 3.68

52 520 11 10+1 125+5.0 130 390 (130+390)=520 35 3.71

52.5 525 11 10+1 125+6.25 131.25 393.75 (131.25+292.75)=525 35 3.75

53 530 11 10+1 125+7.50 132.5 397.5 (132.75+397.5)=530 35 3.79

53.5 535 11 10+1 125+8.75 133.75 401.25 (133.75+401.25)=535 35 3.82

54 540 11 10+1 125+10 135 405 (135+405)=540 35 3.86

54.5 545 11 10+1 125+11.25 136.25 408.75 (136.25+408.75)=545 35 3.89

55 550 11 11 137.5 137.5 412.5 (137.50+412.5)=550 35 3.93

55.5 555 12 11+1 137.5+1.25 138.75 416.25 (138.75+416.25)=555 35 3.96

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56 560 12 11+1 137.5+2.50 140 420 (140+420)=560 35 4.00

56.5 565 12 11+1 137.5+3.75 141.25 423.75 (141.25+423.75)=565 35 4.04

57 570 12 11+1 137.5+5.0 142.5 427.5 (142.50+427.5)=570 35 4.07

57.5 575 12 11+1 137.5+6.25 143.75 431.25 (143.75+431.25)=575 35 4.11

58 580 12 11+1 137.5+7.50 145 435 (145+435)=580 35 4.14

58.5 585 12 11+1 137.5+8.75 146.25 438.75 (146.25+438.75)=585 35 4.18

59 590 12 11+1 137.5+10 147.5 442.5 (147.50+442.5)=590 35 4.21

59.5 595 12 11+1 137.5+11.25 148.75 446.25 (148.75+446.25)=595 35 4.25

60 600 12 12 150 150 450 (150+450)=600 35 4.29

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ANNEX-16: M&E FORM FOR FACILITY OBSERVATION CHECKLIST

M&E Form: Facility Observation Checklist (UHC/District and Tertiary Level Hospital)

Name of hospital / health facility: ______________

Type of facility: /___/1=upazila health complex; 2=district hospital; 3=tertiary hospital, 4=others

(specify…………………………)

Sl Indicators Response a) National guideline for Kala-azar case management in place |___| 1=yes, 2=no , 3=N/A

b) SOP for diagnosis of VL and PKDL in place |___| 1=yes, 2=no , 3=N/A

c) SOP for treatment of VL and PKDL in place |___| 1=yes, 2=no , 3=N/A

1. Observation on Kala-azar Diagnosis

1.1 Guideline/SOP for Kala-azar diagnosis in place |___| 1=yes, 2=no , 3=N/A

1.2 Availability of diagnostic kits (rK39) and others associated

accessories

|___| 1=enough, 2=not enough, 3=

absent

1.3 Diagnostic Kits stored properly |___| 1=yes, 2=no, 3=No Kits

1.4 Facility of molecular diagnostics test |___| 1=present and functioning,

2= present but not functioning,

3=absent

1.5 Diagnosis (rK39) perform as per SOP/Guideline |___| 1=yes, 2=no, 3=not observed

1.6 Properly maintain register/record about diagnosis |___| 1=yes, 2=no, 3=not observed

1.7 Diagnosis kit (rK39) stock in last month (in number)

1.8 Diagnosis kit (rK39) required in last month (in number)

2. Observation on Kala-azar Treatment

2.1 Availability of drug and others associated accessories |___| 1=enough, 2=not enough, 3=

absent

2.2 Drug stored properly |___| 1=yes, 2=no, 3=no Drug

2.3 Treatment perform as per SOP/Guideline |___| 1=yes, 2=no, 3=not observed

2.4 Properly maintain record/surveillance form about treatment |___| 1=yes, 2=no, 3=not observed

2.5 Drug stock in last month (mention the name and quantity of

drug)

(in number)

2.6 Drug required in last month (mention the name and quantity

of drug)

(in number)

3. Observation on Kala-azar Surveillance

3.1 Surveillance form used from the national guideline

|___| 1=yes, 2=no, 3=not

observed 3.2 # of cases treated in last month (in number)

3.3 # of case recorded in surveillance form (in number)

3.4 # of cases reported to CDC, DGSH (in number)

3.5 # of cases entered into web based system (in number)

3.6 # of cases schedule for follow-up in last month (in number)

3.7 # of case follow-up done in last month (in number)

3.8 ACD conducted as per SOP |___| 1=yes, 2=no, 3=not observed,

4= not done

Observed by (name and designation): _________ date of observation: _________ dd/mm/yyyy

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ANNEX-17: M&E FOR MONTHLY REPORTING FORMAT

Monthly Reporting Format for M&E (UHC/District and Tertiary Level Hospital)

Name of hospital / health facility: ______________

Type of facility: /___/1=upazila health complex; 2=district hospital; 3=tertiary hospital, 4=others

(specify…………………………)

1. Monthly status of Kala-azar Diagnosis

Sl Diagnosis Response (in number)

NKA RKA KATF PKDL Co-

infection

Total

1.1 No. of suspected cases reported to HF

1.2 No. of (rK39) test done

1.3 No. of cases with (rK39) test positive

1.4 No. of cases referred for confirmation

test

1.5 No. of rK39 kits in reporting month

1.6 No. of rK39 kits was required in the

reporting month

2. Monthly Kala-azar Treatment & Follow-up Status


NKA RKA KATF PKDL Co-

infection

Total

2.1 No. of confirmed cases for treatment

at the HF

2.2 No. of cases with complete treatment

2.3 No. of cases with treatment

interruption

2.4 Reason for treatment interruption

2.5 No. of cases referred for treatment

2.6 No. of cases scheduled for follow-up

2.7 No. of cases complete the follow-up

2.8 Follow-up status (in number)

Initial cure

Final cure

Treatment Failure

Relapse

Loss-to-follow-up

Transfer

Death 2.9 Drugs available in reporting month

(quantity)

LAmB MLF PMIM AMP-B SSG Others

2.10 Drugs required in the reporting

month (quantity)

LAmB MLF PMIM AMP-B SSG Others

3. Monthly Kala-azar Surveillance Status

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3.1 No. of cases recorded in the surveillance form in the reporting month

3.2 No. of cases reported to the central level (CDC, DGHS) in the reporting

month

3.3 No. of cases entered into the web based surveillance system in the

reporting month

3.4 No. of ACD conducted in the reporting month

3.5 No. of case detected through the ACD

Reported by (name and designation): _________ date of reporting: _________ dd/mm/yyyy

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Documents

National Guideline For Kala-azar Case Management 2016kalacorebd.com/wp-content/uploads/2016/04/Kala-azar-Case-Managmen… · i | P a g e National Guideline For Kala-azar Case Management