Kala-azar Control National Guideline

8/11/2019 Kala-azar Control National Guideline

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Learning Unit - 1

INTRODUCTION

Contents:

Background

Bangladesh situation

Target audience

Selection of different level of health facilities

Kala-azar elimination program-

1) Target

2) Objective

3) Regional strategies

Objectives: at the end of the session the participant will be able to:

Describe global, regional and country situation of Kala-azar.

Mention the target audience of their guideline

Identify different level of health facilities in public and private sector

for elimination of Kala-azar.

Define target, objectives and regional strategy of Kala-azar

elimination program.


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1.1 Background

Kala-azar or is one of the clinical form of leishmaniasis and is caused by the

protozoa Leishmania donovani. In the Indian sub-continent it is transmitted by the

sand fly named Phlebotomus argentipes. The disease presents as fever of long

duration with splenomegaly, anaemia, weight loss and darkening of complexion. In

endemic areas, children and young adults are its principal victims. Kala-azar is fatal

if not treated timely. Kala-azar HIV or TB co-infection has emerged as a health

problem in recent years. The disease is seen in several countries of the world with

about 500,000 cases annually. India, Sudan, Nepal, Bangladesh and Brazil account

for 90% of the total global cases. It affects largely the socially marginalized and the

poorest communities.

1.2 Kala-azar situation in Bangladesh

Kala-azar is one of the major public health problems in Bangladesh and the disease

is endemic for many

decades. During the

Malaria Eradication

Programme blanket DDT

spraying controlled kala-

azar transmission. In the late

1970s Kala-azar re-emerged

sporadically. During 1981-

85 only 8 upazilas (Sub-

district) reported Kala-azar,

which increased to 105

upazilas in 2004. During the

last few years the Kala-azar

situation has assumed

epidemic proportion with the


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number of reported cases increasing from 3978 in 1993 to 8505 in 2005. Present

surveillance is weak and the current estimated total cases are about 45,000.

Annually @ 10,000 cases are treated by the control programme but the cases

treated by the private clinics and practitioners are not reported.

Under the current surveillance system the Upazila Health Complexes (UHCs),

District Hospitals and other specialized hospitals report cases to the Malaria &

Parasitic Disease Control Unit in DGHS. This is however is a gross under

reporting because the private sector clinics and hospitals, and the cases treated by

private practitioners are not included. At present only Inj. SAG is used for

treatment, which is supplied, free of charges and passive surveillance only works

when drugs are available in the hospitals.

The bar chart below shows the number of Kala-azar cases reported during 1994-

2005. It signifies the trend of the disease @ of 8,000-10,000 cases annually. The

highest case fatality rate recorded from research on known Kala-azar patients in

Mymensingh district has been 6.4% (Desjeux P. 1991). The prevalence rate in

some selected villages in the same district has been found be as high as 6% of the

total population (unpublished report, 1993). However, definite data on morbidity

and deaths due to Kala-azar are not available from the current reporting system.

Age and sex segregated data is not available with the control programme at

present.

Yearly Kala-azar Cases and Deaths (1999-2009)

5799

7640

4283

8110

61135920

6892

9379

4932 4840

4294

23 24

6

36

27

23

16

23

17 17

14

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000

1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009

Year

Cases

0

10

20

30

40

50

Deaths

Case Death


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Cases are usually clustered in the villages having environmental and related factors

for the vectors to grow and proliferate. There is no marked seasonal variation but

the pre and post-monsoon rise in number of cases indicates two picks of

transmission. Areas in the old Brahmaputra and the Ganges basin show the highest

prevalence of the disease.

1.3 Target audience for the guidelines

These guidelines will be useful to the-

Programme managers- national/divisional/district/upazila level.

Doctors and health care providers

Supervisors at all levels

Supervisors and health workers engaged in supervising the spraying

squads

The health care providers and volunteers responsible for behaviour

change communication (BCC) can use the guidelines to (a) promote early

care seeking if Kala-azar is suspected, (b) convince the patients suffering

from Kala-azar to complete the treatment and (c) undertake advocacy

with the community for participation in ensuring complete and uniform

coverage of their households with insecticides.

This guidelines and SOPs are adopted according to the SEARO, WHO guidelines.

Whenever translation is needed for training of grass root level workers, volunteers,

NGO workers for providing training on particular areas of their involvement in

Kala-azar elimination programme, local managers are encouraged to translate it in

Bangla.


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Table 1 Level of health facilities in Bangladesh

Level 1 Level 2 Level 3

Public sector

-Upazila Health Complex

(UHC)-Community clinic

- Union Health Facilities

(Health & Family Welfare

Centre-H&FWC; Rural

Dispensary-RD; Sub-centre-

SC)

Private sector

-Qualified private

practitioners-Non qualified health care

providers including health

volunteers

-NGOs; private hospitals;

private clinics; and private

laboratories.

Public sector

-District Hospitals

Private sector

-Qualified private

practitioners;

NGOs; private

hospitals; private

clinics; and private

laboratories.

Public sector

-Medical college

Hospitals.-Specialized hospitals

Private sector

-Medical College

Hospitals

-Qualified private

practitioners;

-

NGOs; private hospitals;

private clinics; andprivate laboratories

N.B-Treatment wi l l be given in upazil a health complex in case of level I and

other pri vate and public sector of L evel I wil l r efer the patient to upazil la health

complex.

For the success of the programme it is important to develop linkages between the

three levels and establish ongoing communication with the private sector. 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.

1.4 Kala-azar elimination programme

Kala-azar can be eliminated from the Indian Subcontinent because there is no

intermediate host for transmission of the disease. The Indoor residual spray has been

very effective. As a collateral benefit of malaria Kala-azar was almost eliminated.

The disease can be easily recognized and effective treatment for Kala-azar is

available.


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1.4.1 Target

The target of Kala-azar elimination is to reduce the incidence of the disease to less

than 1 case per 10,000 populations at the upazila level in Bangladesh by the year

2015.

1.4.2 Objectives

The impact objective is to reduce the incidence of Kala-azar to less than 1 case of

Kala-azar and Post Kala-azar Dermal Leishmaniasis per 10,000 population at

district (in Nepal) or sub district/upazila level (in Bangladesh and India) by:

Reducing the incidence Kala-azar in the endemic communities including the

poor, vulnerable and un-reached populations.

Reducing case fatality rates from Kala-azar.

Treatment of Post Kala-azar Dermal Leishmaniasis (PKDL) to reduce the

parasite reservoir.

Prevention and treatment of Kala-azar-HIV-TB co-infections.

1.4.3 Elimination strategy

A regional strategy for elimination of Kala-azar has been endorsed by the Regional

Technical Advisory Group (RTAG). It comprises of the following components:

(a) Early diagnosis and complete treatment:All suspected cases of Kala-azar and

PKDL would have access to recommended diagnosis and treatment.

(b) Integrated vector management: The mainstay of vector control is indoor

residual spray (IRS) with suitable insecticides. Improvements in housing and

personal preventive methods would be promoted through community

involvement.

(c) Effective disease surveillance: A revamped surveillance system should

strengthen diagnosis treatment and reporting both in the public and the

private sector.


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(d) Social mobilization and partnerships: Behavioral Change Communication

(BCC) would aim at achieving early diagnosis and complete treatment,

participation of the community in IRS, and adoption of personal preventive

methods and micro-environmental management. Partnerships within and

outside the health sector are to be forged to promote the goals of Kala-azar

elimination.

(e) Operational research: Operational research to monitor the drug and

insecticide resistance, quality of drugs, treatment compliance, pharmaco-

vigilance, ITNs use etc.would be undertaken.


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Learning Unit - 2

DIAGNOSIS OF KALA-AZAR and PKDL

Objectives: at the end of the session the participant

will be able to-

describe lifecycle of L donovani, pathogenesisand patho-physiology of KA and PKDL

mention the clinical feature of KA and PKDL

list the complications of KA

define a case of KA and PKDL

measure the spleen

perform skin sensation test (PKDL)

perform the rK-39 test aspirate hone marrow/spleen (Optional)

prepare slides for microscopy (Optional)

Contents:

Lifecycle, Pathogenesis and Patho-physiology

Clinical Diagnosis of KA and PKDL:Clinical features of KA and PKDL

Complications of KA and PKDL

Laboratory diagnosis of KA

Direct evidence: Microscopy, PCR, Culture

Indirect evidence: Immunological

Others: Haematological, Biochemical

Laboratory diagnosis of PKDL:

Differential diagnosis

Case definition: KA, PKDL, KATF


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2.1 Lifecycle, Pathogenesis and Patho-physiology

Life cycle of Leishmania donovani

Mode of transmission :

The natural transmission of Leishmania donovani from man to man is carried out

by a certain species of sand fly of the genera Phlebotomus. The infected female

sand fly transmits LD bodies to the susceptible human through their bite.

Cycle in man:

Flagellated Promastigotes enter the body through infected sandfly bite and

subsequent events are as follows:

Parasites enter the skin

Engulfed by resident macrophages

Promastigotes develop into Amastigotes (L-D bodies) in cells of MPS

Amastigotes multiply and R.E. cells are packed with parasites, enlarged, distended

& eventually burst (50 to 200 parasites present in single cell) to release theparasites.

Free parasites pass to different organs of the body and are engulfed by new

reticuloendothelial( RE) cells where they multiply & the cycle is repeated.

In this way the entire Reticulo-Endothelial system becomes progressively infected.

A blood-sucking sandfly draws Amastigotes (L-D bodies) during its blood-meal


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Cycle in sandfly:

Amastigotes (L-D bodies) are taken with blood meal and develop into

promastigote forms in the midgut of sandfly on the third day after blood meal.

Promastigotes multiply by binary fission into enormous number

Multiplication takes place and on the 5th

day the promastigotes gather around the

proventricular end of the gut

Multiplication and forward progression continues till 7th

day

Solid mass of flagellates fill up extending up to the pharynx

A heavy pharyngeal infection of the sandfly is usually observed between 6th

and

9th

day of its infected blood meal

In certain sandflies heavy infection blocks the oesophagus. Such sandflies, at the

time of their next sucking blood cause regurgitation of promastigotes from their

buccal cavity in the puncture wound through proboscis (biting organ) and infection

results

Annex l:Life cycle of Leishmania donovani


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2.2 Pathogenesis of Kala-azar

Promastigotes are inoculated into the punctured site by the feeding sandfly.

The entry of organism attracts mononuclear phagocytes (macrophages) and

other white cells to the area. Certain macrophages can directly kill the

parasite whereas others require prior stimulation before attaining the

capability to destroy these parasites. Only resident (local) unstimulated

macrophages are suitable for the establishment of the infection. To avoid

being killed within the macrophages, the promastigotes transform

themselves to amastigotes.

Leishmania donovani is a species, which tends to visceralize in vertebrate

hosts. The infection is carried to the viscera through infected macrophages

circulating in the blood or lymph. The spleen, liver and bone marrow

become heavily infected. The skin may also get infected as a sequel of

Kala-azar.

2.3 Pathophysiology of Kala-azar

The pathology of visceral leishmaniasis is due to blockage and destruction

of the RE system with the most marked effects, being seen in the spleen,

liver, lymph glands, bone marrow and intestines.

In active visceral leishmaniasis there is lack of a cell-mediated immune

response to leishmanial antigens and therefore the parasites multiply

rapidly. Humoral response with production of large amounts of polyclonal

non-specific immunoglobulin especially IgG are found and also specific

anti-leishmanial antibody are produced. Patients who have recovered from

visceral leishmaniasis are immune from re-infection but relapses can occur.


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2.4 Pathophysiology of Post Kala-azar Dermal Leishmaniasis (PKDL)

In PKDL the epidermis shows several pathological changes in different

combinations. These include hyperkeratosis, parakeratosis, acanthosis,

follicular plugging and liquefaction degeneration of the basal layer. The

latter is associated with incontinence of pigment and the presence of many

melanin- containing macrophages in the upper dermis. Damage to the

melanocytes is the cause of hypopigmentation.

The dermis shows varying intensities of inflammation with scanty parasite,

which are best seen in slit smears of lesions. The infiltrate may be

perivascular and band-like in the upper dermis.

Electron microscopy reveals ineffective stimulation of the macrophage to

eliminate completely all the parasites. Neuritis involving the small

cutaneous nerves in the dermis has been described in PKDL. This may

suggest leprosy but lack of involvement of the superficial nerves and other

cardinal signs of leprosy help to distinguish the two conditions from one

another. Parasites can be demonstrated in only 20% of cases.

Epidemiology

Incubation period: Usually 3-6 months, which may range from 10 days to 2 years.

2.5 Clinical Presentation of Kala-azarA. Classical Presentation

Fever-usually insidious onset and intermittent& may be associated

with chills & rigor. Fever intensity decreases over time and patient

may become afebrile for weeks to months followed by relapse of

fever.

Weight loss


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Swelling of upper abdomen, specially left side.

Increased pigmentation- a feature of advanced disease.

B. Features of complication

Bleeding manifestation e.g Gum bleeding. Epistaxis and rarely GIT

bleeding. This occurs as a result of thrombocytopenia & hepatic

dysfunction.

Features of secondary infection.

C. Atypical presentation

Sub clinical- No fever.

Signs

A. General Examination

Raised temperature.

Anaemia- moderate to severe; may result from bone marrow

infiltration, hypersplenism, autoimmune haemolysis & bleeding.

Gum bleeding & epistaxis

Lymphadenopathy- more common in Africa, less in Indian

Subcontinent

B. Abdominal Examination

Splenomegaly - in 100% cases. Develops quickly in the first few

weeks and become massive as the disease progress.

Hepatomegaly

Ascites, oedema, asnasarca- in progressive disease, caused by

hypoalbuminaemia

Cardinal Clinical feature


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H/O fever more than 2 weeks

Residing/traveling in endemic area

Splenomegaly

Weight loss

Anaemia

Clinical Presentation of PKDL

PKDL usually develops months to years following an attack of untreated or

incompletely treated visceral leishmaniasis. However, 15% of PKDL cases occur

without the preceding history of Kala-azar. They have only skin lesions that are

varied. The lesions may be macular, papular, nodular or mixed. Sometimes the

lesions of PKDL are extensive.

Overlapping, of 3 stages (Macular, papular and nodular) can occur in an individual

simultaneously. In PKDL cases sensation over the lesions is preserved in

contrast to leprosy where similar lesions have no sensations or less sensation .

The skin lesions of PKDL do not ulcerate and self healing of the lesions is not

reported. Though PKDL is a rare condition (I in 50-100 cases of Kala-azar) it is

epidemiologically important because they act as the main reservoir of infection. In

PKDL cases the parasite concentrates in the skin lesion and is readily available to

the insect (Phlebotornus)vector when it bites the patient.

The clinical manifestations of these dermal lesions may be of three types:

Macular lesion: These are the earliest dermal lesions. The usual sites of

distribution of these macules are the trunk and extremities; the face is less

commonly affected. The loss of pigmentation is not complete.

Papular lesion: These are also early lesions, which appear on the nose,

cheeks and chin, often having a butterfly distribution ("butterfly erythema").


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They are very photosensitive, becoming prominent towards the middle of

the day.

Nodular lesion:These replace the earlier lesions and occasionally appear

from the very beginning. The nodules are generally found on the skin and

rarely on the mucous membrane of the tongue and eyes. They appear

mostly on the face but may appear on any part of the body. The absence of

ulceration of the nodules is a characteristic feature of PKDL.

2.6 Complications of Kala-azar:

1. Secondary infections:

Pneumonia

Pulmonary Tuberculosis

Amoebic or bacillary dysentery

Gastroenteritis

Herpes zoster

Chicken pox

Skin infection: boils, cellulitis, scabies

Cancrum oris

Septicaeemia

Otitis media

2. Bleeding manifestation- from gum, nose, GIT, retina, etc.

3. Post Kala-azar Dermal Leishmaniasis (PKDL)

4. Post Kala-azar laryngitis and colitis.

5. Post Kala-azar splenomegaly

6. Renal:

Glomerulonephritis

Nephrotic syndrome


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7. Cirrhosis of liver

2.7 Complications of PKDL:

PKDL occasionally coexist with VL; other post Kala-azar manifestations such as

post Kala-azar mucosal leishmaniasis, uveitis, conjunctivitis, and blepharitis may

be seen simultaneously in the same patient. Similarly, involvement of the mucosal

surfaces, in particular in the mouth and the larynx, as well as eye involvement such

as keratitis has also been described.

2.8 Laboratory Diagnosis of Kala-azar (annexure-2)

Diagnosis of Kala-azar may be possible by the following:

A. Indirect evidence or serological test (annexure 4)

B. Direct evidence or parasitological diagnosis

C. Others: Haernatological and Biochemical changes in blood

Laboratory Diagnosis of Kala azar


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A. Indirect evidence

1. Rapid dipstick rK-39 test (ICT for Kala-azar)

The rapid dipstick 'rK-39'test is the mainstay in the serological diagnosis of

Kala-azar. It is recommended for identifying the case of Kala-azar. (rK-39 test

may remain positive for 2 years after completion of Kala-azar treatment)

1. a. How to perform the 'rK-39'test

Remove the test strip from the pouch or the vial

With a Fresh lancet, prick the fingertip of the patient suspected to be

suffering from Kalaazar. Lancets; should not be reused because of the risk

of transmitting HIV and Hepatitis B and C.

Let the blood come out on its own. Do not use pressure or squeezing for

obtaining blood. Place one drop of blood on the absorbent pad of the strip

bottom.

Place the test strip into a test tube so that the end of the strip is facing

downwards. This would encourage the blood to migrate upwards by

capillary action..

Add 2-3 drops of buffer solution provided with the kit to the pad.

Read the results at 10 minutes. Please do not read the result after 10

minutes.

1. b How to interpret the results

Positive result

A red line appears in the control area and another red line appears in test area

where the blood has migrated through capillary action. There should be two red

lines for the test to be positive. A faint red line also is to be considered positive.


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Negative result

There is a red line in control area but there is no red line in test area where the

blood has migrated by capillary action at 10 minutes.

Invalid test

There is no red line in control area or in the test area where the blood is to migrate

by capillary action. The test is also invalid if there is a red line in the test area but

no red line in the control area where the blood was initially placed.

Table 2 If the test is invalid it should be repeated following the correct

procedure.

Control area (C) Test area (T) Interpretation

Red line Red line Positive

Red line No line Negative

No line Red line Invalid test

No line No line Invalid test

Fig: 2 rK-39 test with positive and negative results


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1. c. Storage and supply of rK-39 test strips

The test strips should be stored safely at room temperature between 20-30 degrees

Celsius. Temperature in excess of 30 degrees can reduce the quality of the test.

The buffer solution should be stored at 20-8

0c. The test strips and the buffer should

not be frozen since freezing deteriorates the quality of the reagent. The strip and

the buffer should be taken out from the vial or the pouch only at the time of

performing the rK-39 test. The strip should only be used within one hour of

taking out from the vial or the pouch.

It is not advisable to store large quantities of rK-39 in the peripheral locations

where the temperature can not be properly maintained as required in the

specifications. The districts locations (level II) should serve as the supply points

for the peripheral units from where supplies can be made once in a- month or when

the workers come for a review meeting.

1.d. Where should rK-39 test be done.

For the success of the elimination programme, it is necessary that rK-39 test is

available to the poor people in the locality/area. The programme manager should

map the various facilities in the public and private sector and identify the locations

where the test is to be provided based on the followings:

(a) The health workers can detect enlarged spleen;

(b) The facilities where treatment of Kala-azar is available;

(c) The distance of the facility from the community.

The test may be made available at the upazilla health complex (level-I) in the

Government facilities. The programme manager in the district can decide about

private and the NGO sectors where similar facilities are available. The facilities in

the private sector that should be considered are hospitals and private laboratories.Facilities where there is willingness and interest in participating in the programme


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should be selected as the sites for testing with rK-39. MOU may be signed with

the private sectors and NGOs. In the beginning of the programme, a few facilities

should be selected. After ensuring that the services provided are reliable, more

facilities may be included.

1. e. Advantages and limitations of IrK-391 test

The pros and cons of rk39 test in the diagnosis of Kala-azar are summarized intable.

Table 3 Pros and cons of rK-39 test in the diagnosis of Kala-azar

Pros Cons Test can be performed with one

drop of blood drawn from a finger

tip.

The result is obtained within 10

minutes

The test can be performed in anysetting by a trained health worker

rK-39 test is reliable andcompares well with confirmatorytests Therefore there is no need to

perform confirmatory tests in all

cases of Kala-azar

The test is also positive in cases of

PKDL

The rapid test rK-39 is positive in95-100% patients of Kala-azar.

Early cases can be detected.( the

test become positive after twoweeks)

The test strips have to be stored at

recommended temperature and

humidity to maintain its reliability.

The test will lose its quality if

stored at temperature less than 20

and more than 30 degrees Celsius

for a long time (several months)

It is not recommended in patients

who have HIV-Kala-azar co

infections

The test remains positive even after

cure of Kala-azar, so the test cannot

be used in patients who have a

relapse or a reinfection

At present rK-39 test is notrecommended to decide about the

cure from kala azar since the test

continues to be positive even after

the patient has clinically recoveredfrom the disease.


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be responsible for cross checking a proportion of positive and negative tests with

standard.

2.11 Rapid Diagnosis of Kala-azar:

The rK-39 test for kala-azar is very reliable test for diagnosis of Kala-azar in the

field situation and quick mass sero survey. Its sensitivity is -100% and specificity

(92.3% - 95%) is also comparable to ELISA. So this test is considered for

diagnosis of a Kala-azar at field situation. However, as with all diagnostic tests

result must be correlated with other clinical information available to the physician.

2.12 Diagnosis of PKDL by rK-39 test:

Suspected patients of PKDL should be screened by 'rK-39' test. In cases of PKDL

with only macular lesions, the rK-39 test may be negative. These cases should be

referred to a facility where detection of the presence of the parasite can be done.

The confirmatory diagnosis of PKDL can be made by demonstration of the

parasite (L.D.bodies) in the skin lesions by slit skin smear. The nodular, papular or

the macular lesion is slit and tissue fluid is then placed on a slide. The slide 1 then

stained (annexure 7) the same way as the bone marrow or splenic puncture

aspirate. It is then examined for LD bodies under the microscope. If smear is

negative or inconclusive, then skin puncli biopsy should be done to detect the

parasite. If the above procedures fail to detect the parasite, then the patient should

be tested by PCR for identification of parasite. It is important. to observe all safety

precautions to prevent HIV/AIDS, Hepatitis B and C and other blood borne

infections while doing the scraping of the skin for the test.)

rK-39 Slit skin smear Skin punch biopsy PCR (annexure 9)

2. The other following serological tests are in current practice.

Enzyme-Linked Immunosorbent Assay (ELISA)

Indirect Fluorescent Antibody Test (IFAT)


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Counter-Immunoelectrophoresis (CIE)

Latex Agglutition Test (LAT)

3. Hematological change:

Anaemia

Raised erythrocyte sedimentation rate (ESR)

Leucopenia: Neutropenia with relative lymphocytosis &

monocytosis.

Thrombocytopenia

4. Biochemical investigation (According to need)

Serum Bilirubin SGOT, SGPT

Serum Albumin

Serum Globulin

Urea, Creatinine

B. Direct evidence

a) Demonstration of parasites is the most conclusive evidence in the diagnosis

of Kala-azar and PKDL, Parasites are detected by microscopic examination

of smear prepared from:

Bone marrow

Splenic aspirates

Buffy coat

Liver biopsy

Lymph node biopsy

Skin lesions

b) Culture of the biopsy material in different media like N.N.N media, Eagles

media etc. for isolation of parasite.


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c) PCR for DNA detection of L.D from the peripheral blood and tissue

2.13 Bone marrow examination for amastigote of L.D bodies (annex-5)

2.14 Splenic aspiration for amastigote of L.D bodies (annex-6)

2.15 Diagnosis of Kala-azar in special situations

The diagnosis of kala-azar can be difficult in special situations. These include the

following:

Kala -azar HIV co-infection

Kala-azar in pregnancy

PKDL with macular lesions

In cases of Kala-azar HIV co-infections and in cases of PKDL with only macular

lesions the 'rK39'test may be negative. In Kala-azar HIV co- infection the

diagnosis can be confirmed by bone marrow examination or splenic aspiration in

Level III facilities. If both tests are negative or inconclusive, then patient should be

sent to specialized laboratory for PCR identification. In PKDL with macular

lesion, the diagnosis is made from the slit skin smear or a skin punch biopsy in

level III facilities. If the slit skin or biopsy is negative or inconclusive, the patient

should be tested for PCR identification. Patients with Kala-azar in special

situations should be referred to the required level of facility as appropriate.

Kala-azar HIV co-infection:rK-39 Bone marrow / Splenic aspirate PCR

Kala-azar in pregnancy:

rK-39 PCR

PKDL with macular lesions only:

Slit skin smear Skin punch biopsy PCR


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2.16 Clinical Case Definitions of Kala-azar & PKDL:

There are three case definitions: Kala-azar (KA), Kala-azar Treatment Failure

(KATF) and Post Kala-azar Dermal Leishmaniasis (PKDL)

Kala-azar (KA)

Fever or history of fever for two weeks or more: pattern of fever

1. Irregular pattern of fever

And

Splenomegaly

And

2. High index of suspicion based on residing/ traveling in endemic area

And

3. Absence of convincing evidence of any other febrile illness

And

rK-39 test positive

A Case of kala -azar:

An individual in an endemic area who has fever for more than two weeks,

splenomegaly and rK-39 test is positive should be diagnosed as a case of

Kala-azar.


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Kala-azar Treatment Failure (KATF)

1. Earlier:diagnosed as Kala-azar

And

2. Took complete treatment

And

3. Again features of Kala-azar

And

4. Any positive lab evidence: Bone Marrow (BM)/ Splenic aspiration (SP)

And

5. Period: wthin one year

Post Kala-azar Dermal Leishmaniasis (PKDL)

1. Multiple hypo pigmented areas on skin without loss of sensation

With any one or combination of the following

a) macule

b) papule

c) nodule

d) history of Kala-azar

And

2. High index of suspicion based on residing/traveling in endemic area.

And

3. rK-39 test positive

N:B: Clinically Suspected PKDL with rk39 negative cases need tissue diagnosis.


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2.17 Case Definitions for Reporting:

1. Suspected Kala-azar:Patients with fever (of more than 2 weeks) from an

endemic area who has one or more of the features -1) splenomegaly, 2)

anaemia and 3) weight loss

2. Confirmed Kala-azar:When the suspected case is confirmed by positive

rk39 test or demonstration of parasite in the tissue (BM/SP) or by PCR.

3. Kala-azar Treatment failure (KATF)

4. PKDL

When reporting the 'reporting case definition' term will be added as a prefix to the

'clinical case definition' term of Kala-azar categorized as per national guidelines.

Example:

A case is found to be KA as per clinical case definition. For

reporting purpose this will be labeled as Suspected KA. If rK-39

test is found positive or if parasite is demonstrable in any tissue

exam test e.g BM, SP then the case will be labeled as 'Confirmed

KA


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2.18 Differential diagnosis

The following common differential diagnosis should be ruled out considering their

frequency in Bangladesh. The indicators of differential diagnosis are mainly:

prolong fever, splenomegaly, hepatomegaly, progressive weight loss, emaciation,

skin changes and opportunistic infection.

1. Malaria

2. Leukemia

3.

Lymphoma

4. CLD

5.

Carcinoma of liver

6. Portal hypertension

7. CCF

8. Hemolytic anemia

9. Tuberculosis

10.Leprosy (for PKDL)

11.

Storage disease

Locations where diagnosis of Kala-azar and PKDL should be offered:

As mentioned earlier, the programme should map out the facilities in the district to

make the locations- where the diagnosis is available and it should be known to the

people through behaviour change communication.


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Table 4 Location for Kala-azar and PKDL diagnosis

A) Level 1

In endemic areas in (union subcentre,community clinic or others)1. Identify cases of fever of more than 2 weeks duration

2. Identify cases who have macular, papular or nodular skin lesions but no other signs

3. Refer the patients with above problems to Upazilla health complex for evaluation,

testing and treatment for Kala-azar or PKDL.

In endemic areas in upazilla health complex1. Check patients with fever of more than 2 weeks associated with splenomegaly

2. Check patients with macular, nodular or mixed lesions without loss of sensation.

Perform rK-39 test :(a) On all patients with fever of more than 2 weeks and have splenomegaly

(b) Patients with macular, papular or nodular or mixed lesions and no loss of sensation.

3.Treat patients of kala-azar with first line drugs4. Refer PKDL cases who need tisue biopsy and unresponsive cases of Kala azar to level

III facility.

B) Level II

1. Check patients with fever of more than 2 weeks associated with splenomegaly.

2. Check patients with macular, nodular or mixed lesions without loss of sensation.

Perform rK-39 test :(a) On all patients with fever of more than 2 weeks and have splenomegaly

(b) Patients with macular or nodular or mixed lesions and no loss of sensation.3. Treat patients of kala-azar with first line drugs

4. Refer PKDL cases to who need tisue biopsy and unresponsive cases of Kala azar to

level III facility.

C) Level III

1. Treat unresponsive Kala azar or KATF cases and refer back of PKDL cases to level

I and II for treatment after tissue diagnosis.

2. Perform the slit skin smear/biopsy in suspected cases of PKDL that are rK-39testnegative

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 assessment4. Treat any complications associated with bone marrow/splenic aspirate

D) Level IV (specialized laboratories)

1. Perform PCR test for establishing the diagnosis of PKDL in cases that are suspected

to have the disease but rK-39test is negative2. Diagnosis of HIV-Kala-azar coinfection may be done by bone marrow/splenic

aspirate


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Learning unit - 3

TREATMENT OF KALA-AZAR and PKDL

Objective: at the end of the session the participant

will be able to-

mention the Treatment of KA and PKDL

identify the AE of treatment

mention the treatment of adverse events

recognize the patient to refer

describe the management at different levels

enumerate pharmaco-vigilance

illustrate the treatment flowchart

Content:

Treatment: KA

1st line treatment

2nd line treatmentTreatment in special situations: Pregnancy, Co morbidity (Pneumonia, HIV,

Tuberculosis)

Treatment of complications:

Treatment of PKDL

Brief description on individual drug with adverse events

Management at different levels

Terms/ Criteria for referral, referral format

Management of adverse events

Pharmaco-vigilance

Treatment flowsheet/chart


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TREATMENT OF KALA-AZAR and PKDL

The objective of treatment for Kala-azar is to cure the patient, prevent the

complications of the disease and minimize side effects of medicines, contain drug

resistance and reduce the risk of spread of disease.

This can be achieved by complete treatment and monitoring. Other

symptoms/diseases in patients of Kala-azar should also be diagnosed and treated.

Appropriate drug with recommended dose and duration should be given to a

patient of Kala-azar.

3.1 Drug treatment of Kala-azar: (annexure 10 &11) 3.1.1)

1st' line of treatment for Kala-azar patients

Drug of choice-

Miltefosine

Alternate choice- (Depending on availability in our country)

1. Paromomycin

2. Liposomal Amphotericin B

2nd line of treatment for Kala-azar patients:

1. Sodium Stibogluconate (SSG)

2. Amphotericin B deoxycolate

3.2 Miltefosine:

Miltefosine is a relatively safe oral drug for the treatment of Kala-azar. It is now

recommended for use in Bangladesh. Miltefosine, a membrane-active alkyl

phospholipid developed as an antineoplastic agent and now also used topically in

breast cancer skin metastases has been shown to be active against Leishmania in

various animal and human models. It is an oral antiprotozoal agent, which has


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marked direct antiLeishmanial activity both in vitro and in vivo. Though the mode

of action of Miltefosine is not clearly known, it may act through inhibition of

phospholipid metabolism.

Miltefosine is well absorbed from the gastrointestinal tract and is widely

distributed in the human body. The plasma concentrations were roughly

proportional to the dose in the range of 50-150 mg/day. The maximum serum

concentration ranges from 24-82 g/ml with tmax of 23 days. No relevant sex

difference of the pharmacokinetic parameters have been observed. Miltefosine

does not show oxidative metabolism by the cytochrome P45o enzyme system.

3.2.1 When to avoid the use of miltefosine:

Miltefosine is the preferred first line of drug in all patients of Kala-azar in the

elimination program except in the following situations:

Pregnancy

Married women of child bearing age who are not using contraceptives

regularly and are at risk of becoming pregnant

Women who are breast feeding.

Children less than 2 yrs of age

3.2.2 Miltefosine may not be the ideal drug for patients of Kala-azar

with severe under nutrition

severe anaernia and

patients with known history of kidney or liver disease

3.2.3 Recommended dose schedule:


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Dose: 2.5mg/kg body weight, in two divided dose by mouth in the morning

and evening after meal for 28 days.

In case of missed doses, the scheduled 28 doses may be taken within a period of 35

days. The daily dose should never exceed the recommended amount.

The doses should be calculated as follows:

i) >12 years and weighing ~25kg: 100 mg. (cap 50 mg in morning and 50 mg in

evening with meals)

ii) >12 years but weighing


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separate ampoule. Any drug left over from open ampoules should be

discarded immediately.DO NOT REUSE.

Routeof administration: intramuscular (I/M)

Site: Gluteus muscle (alternative buttock cheeks). If additional sites are

required,administer in Vastus lateralis muscle in the anterolateral

thigh, alternating thighs daily.

Frequency:Once a day

Duration: 21 days

Preparation: Paromomycin I/M injection solution for intramuscular

injection, sterile, aqueous solution containing 375 mg/ml of

Paromomycin.

Prepare daily under supervision of doctors or trained health care workers.

Each dose to be taken from a separate ampoule. Any drug left over from

open ampoules should be discarded immediately. The recommended dose is

15 mg/kg/day to be given IM for 21 days.

The total estimated cost per treatment of the drug is about 10 US Dollars.

The medicine is safe with minimal ototoxicity or nephrotoxicity. In the

recommended dose, the ototoxicity is reversible.

Paromomycin should be avoided in patients with severe anaemia with

hemoglobin


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3.3.2 Liposomal amphotericin B (LAB):

To improve the tolerance and widen the narrow therapeutic window, a lipid

formulation of Amphotericin B is formulated. Amongst the three

formulations liposomal Amphotericin B has the best safety profile.

Liposomal amphotericin B is given IV in a total dose of 10-15 mg/kg

divided into 3 to 5 doses given either daily or on alternate days.

It is one of the safest drug in both immunocompetent and

immunocompromised individual and also drug of choice in special

situations( e.g. HIV and Pregnancy)

Liposomal amphotericin B should be administered by intravenous

infusion (dextrose 5% infusion 100 to 300 ml) over a 30- 60 min period

3.4 Treatment for kala azar treatment failure(KATF)

1. When a patient is diagnosed as a case of KATF after treatment with a

particular 1st line agent, another alternative 1st line agents should be

used.

2. If alternative 1st line agent is not available, then a 2nd

line agent should be

used.

3.5 Second line treatment for Kala-azar:

Indications:

1. When the first line drugs are not available

2. KATF cases when alternative 1stline drugs can not be used or not available.

3.5.1 Sodium Stibo Gluconate (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.

SSG should be given at a dosage of 20mg/kg body weight, daily IM

injection for 30 days.


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It is essential to weigh the patient before starting treatment. Clinical Cardiac

monitoring should be done throughout the treatment period.

Route of Administration of SSG:

The preferred route of administration recommended is by deep intramuscular (IM)

injection. It is better not to give the drug intravenously (I/V)to avoid the risk of

cardiovascular collapse. After each injection the patient should be kept in lying on

the bed under observation for at least half an hour because of the risk of

hypotension and syncope. Unused reconstituted drug should be discarded within

24 hours of preparation.

Adverse events of Sodium Stibogluconate Gluconate treatment:

In clinical practice of therapy with SSG, minor side effects are common, moderate

side effects are common and severe side effects very rare. The commonest

adverse events arepain at the injection site, muscle pain (myalgia), joint pain

(arthralgia), loss of appetite, nausea and increased transaminase level. These

symptoms are relatively mild and myalgia & arthralgia may be controlled byparacetamol. QT segment changes (prolong QTc> 0.5 msec, T inversion) may

occur on the ECG, and therefore in ideal circumstances ECG monitoring before

treatment and weekly during treatment should be performed. Clinically important

arrhythmias (ventricular ectopics, ventricular Tachy cardia, Torsades, de points,

ventricular fibrillation) or heart failure are very unusual, but if occur may cause

sudden death. In ideal circumstances weekly monitoring of hepatic and renal

function and estimation of amylase should be undertaken, though these rarely give

rise to symptomatic illness.

There is no absolute contra-indication to SSG treatment, and even severely ill

patients respond to treatment. SSG is not generally safe in pregnancy and only

administered in pregnancy if benefits outweigh the potential risks. If underlying

cardiac, renal or hepatic diseases are present, the patient should be carefully

monitored during treatment.


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Since alternate relatively safe drugs are now available, SSG should be phased

out from the national programme.

3.5.2 Amphotericin-B deoxycholate:

Recommended second line drug for treatment of Kala-azar and KATF is

Amphotericin Bdeoxycholate.

Amphotericin B:

Amphotericin B deoxycholate is also an effective drug. But it has high

toxicity profile and thus pushed to second line.

Amphotericin B deoxycholate 1 mg/kg daily or alternate day is

recommended in the form of 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.

After preparating solution 5 drops /min for 30 min, then 10 drops/min for

another 30 min and if there is no reaction occurs, then the infusion should

be given slowly over a period of 4-6 hours.

Adverse eventsof Amphotericin-B deoxycholate:

In some cases, there may be infusion releted side effects like fever with chills

and rigors and thrombophlebitis. Generally these can be controlled by

paracetamol and anti histaminics. Rarely hydrocortisone may be required.

Rarely there may be severe adverse events like renal or hepatic toxicity

hypokalaernia, and myocarditis and thrombocytopenia.

Amphotericin B should be administered by admitting a patient in a hospital

during the entire period of treatment for close supervision and monitoring of

side effects.


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3.6 Treatment for PKDL

Sodium Stibo Gluconate (SSG)

SSG should be given at a dosage of 20-mg/kg/day in intramuscular route. It is

essential to weight the patient every time, before starting a new cycle. Total 6

cycles of treatment should be given. Each cycle consists of 20 days of treatment

and there should be an interval of 10 days in between two cycles.

Other treatment options of PKDL cases

Other treatment options of PKDL cases are Miltefosine, AmphotericinB, liposomal

Amphotericin

Amphotericin-B

Dose: I mg/kg body wt daily or alternative IV (in 5%Dextrose solution)

for 15 doses. Sixcycles with 10 days interval in between cycles.

Route: IV

Amphotericin B (Liposomal):

Dose: 3mg/kg/day

Route: IV

Duration: Five(5) days in a cycle, sixcycles with 10 days interval in

between cycles.

Miltefosine

Longer duration of Miltefosine are being used for treatment of PKDL in

India. Dose and duration are yet to be standardized.

3.7 Complete Treatment of Kala-azar:

Patients of Kala-azar must complete treatment in the right dose without any

interruption if a cure to be achieved. All efforts should be made to ensure the

complete treatment. The followi measures are recommended to complete the

treatment:


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Counsel the patient so that the patient/family fully understands why it is

important to t complete treatment. Explain the consequences if the treatment

is not taken as advised.

It is important to tell the patient, the family and the community that the

premat discontinuation of the treatment would be the reason for continued

risk of spread of t disease to others.

All treatment is provided free of cost. So economic constraints should not

be a reason discontinuation of treatment and

Each patient should have a separate treatment box that contains the full 28

days

Miltefosine) treatment. The treatment box should have the name and

individu identification of the patient.

It is advisable to give the medicine supplies for a period of 3 days initially

so that if t patient has any problems a check up is done in the health

center/hospital and treatment provided for the side effects if required.

Use treatment card with a unique identification number. The card shows the

number of d' the treatment has been taken by the patient.

The treatment of Kala-azar should be done under observation of the health

care provider, any side effects or compliance or reinforcement can be

ensured.

There should be coordination amongst the public sector and private

providers and a foll up plan should be developed for each patient so thatthere is no interruption of treatment.

The patient usually begins to feel better after a few days of starting the

treatment but should be told that cure would occur only when full treatment

has been taken..

The patient may discontinue the treatment because of the side effects of the

medicine. The patient should be advised to contact the health worker as

soon as a problem is detected. Tile health worker should treat the side


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effects and reassure the patient so that the treatment is not discontinued. If

improvement does not occur, the patient should be referred to the hospital

(Upzilla health complex at level I or level II)

3.8 Pharmaco-vigilance:

Pharmaco vigilance is important to ensure the safety of the medicines used in the

treatment of Kalaazar. It should be the responsibility of the national programme to

ensure pharmacovogilance. The programme can provide very useful information

but unless protocols are appropriate and the supervision is strong the quality of

information may be compromised.

Each medicine used in the programme has some side effects. These may be looked

for in the form of signs and symptoms. Laboratory tests can help to recognize the

occurrence of the side effects early, Although tests like haemogram, liver and

kidney function tests, electrolytes and ECG are recommended to monitor the

patient, the inclusion of these tests in the programme is difficult. This information

can be complemented by regular reporting of major and minor adverse events. The

following measures will help to recognize early the occurrence of adverse events.

Monitor the patient regularly for signs and symptoms (indicative of adverse

events of drugs). These signs and symptoms should be classified as major

and minor.

Perform the tests if possible in treatment sites and monitor the results. This

can help to take timely measures even before the signs appear.

Periodic meetings should be organized to review the reports of major and

minor adverse events obtained from the different levels. This will help

guide the prograrnme in recommending the tests that should be done to

monitor the patients on treatment.

Regularly report the adverse events on the reporting formats to higher levels

once in a month for a review and feedback


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Figure 3

PeripheralPeripheral BloodBlood//UrineUrinerk39k39 KAtexKAtex PCRPCR

65% 8765% 87--100% 72100% 72--100%100%

POSITIVE

TREATMENT

NEGATIVE

BM/BM/SpleenSpleen AspirateAspirate

MIC CULTMIC CULT PCRPCR

6767--94% 5094% 50--100% 82100% 82--100%100%

VL NEGATIVE

NEGATIVE

DiagnosticDiagnostic atat primeattackprimeattack inin

LeishmaniaLeishmania--HIVHIV coco--infectioninfection

Table 5 Adverse events and laboratory test used

Medicine Side effects Laboratory tests

Miltefosine Vomiting, Diarrhoea, Abdominal

pain (minor)

Persistent vomiting, Dehydration

(major)

Oedema, decreased urine, jaundice

(major)

Fatal nephro/hepato toxicity in

about 1% cases

Complete blood

counts

Electrolytes

Liver and kidney

function tests

Paromomycin Ototoxicity or nephrotoxicity Kidney function tests,

Audiometry

Liposomal

Amphotericin B

Rare, Less toxic

Amphotericin B

Deoxycholate

Fever with chills and rigors (major)

Severe vomiting, dehydration

(major)

Electrolytes

Kidney function tests

ECG


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Oedema, decreased urine output

Arrhythmias (major)

SSG Arthralgia, myalgia (minor)

Arryhthmias, heart failure (major)

Oedema, decreased urine (major)

Jaundice (Major)

Electrolytes

ECG

Kidney functionstests

Liver function tests

3.9 Treatment of Kala-azar in special situations:

The treatment of Kala-azar in special situations is recommended in centers where

appropria expertise and facilities are available. The following conditions can beconsidered as special situations:

Pregnancy

Married women of reproductive age who are not using contraceptives

regularly

Women who are breast feeding their babies

Children less than 2 yrs of age

Kal-azar with severe anaemia (Haemoglobiri less than 5 g/dl)

Kala-azar with TB

Kala-azar HIV coinfection or kala azar and AIDS

Kala-azar in a patient suffering from another serious disease

3.9.1 Kala-azar in Pregnancy:

Vertical transmission of Kala-azar is possible and the instituation of treatment is

imperative in cases of pregnant women with Kala-azar. Amphotericin B is

recommended as the drug of first choice. It is reasonably safe in the mother and

foetus. US Food and Drug Administration consider liposonial Amphotericin B in

pregnancy category B. Miltefosine is contra-indicated. Antimoy containing drugs


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have reproductive toxicity and mutagenic and oncogenic potential, though the risk

is low.

Treatment of Kala-azar In Pregnancy:

1.

The best option in pregnancy with Kala-azar is Liposomal Amphotericin B

2. When Liposomal Amphotericin B is not available, then Amphotericin B

Deoxycolate or Paromomycin can be used.

3. When none of the safe drug is available,and benefit outweights risk, then inj

SSG should be used in 2nd

and 3rd

trimester of pregnancy

3.9.2. Kala-azar in women who are breast feeding their babies:

The choice is between amphotericin B and liposomal amphotericin B. Miltefosine

is contraindicated.

3.9.3. Kala-azar in married women in reproductive age not on contraceptives:

Miltfosine can be used in these patients but before initiating miltefosine, a long

acting contraceptive should be given. The contraceptive should be effective in

averting pregnancy for at least 2 months after completion of treatment.

3.9.4. Kala-azar in children less than 2 yrs of age:

1.The best option in in children less than 2 yrs of age with Kala-azar is Liposomal

Amphotericin B.

2. When Liposomal Amphotericin B is not available, then Amphotericin B

Deoxycolate or Paromomycin can be used.

3. When none of the safe drug is available,and then inj SSG should be used

3.9.5. Kala-azar with severe anaemia:

Anemia should be corrected by blood transfusion and /or supplementation of iron

and folic acid before specific treatment started. If this seems to delay the treatment

and the patient has severe Kala-azar then it is advisable to treat the patient with

amphotericin B or liposomal amphotericin B. Similarly nutritional status of the


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patient should be improved before administration of specific treatment. This

treatment is available in level 11 and level III facilities.

3.9.6. Kala-azar HIV co-infection:

Level 11 facilities cannot check the HIV status. However, level II facilities can

suspect the nfection based.on the risk profile of the patient (FSW, MSM or an

IDU). It is also possible to the opportunistic infections related to HIV and treat

Kala-azar in level 11 facilities. If HIV is suspectedbecause of the risk profile or

HIV status is known the patient should be referred to a facility where the HIV

status can be checked and facilities are available to provide ART. Since the 'rK-39'

test may not be positive in patients who have HIV it is necessary to refer such

patients with coinfection to a facility where the parasitological diagnosis can be

made.

Guidelines for treatment and care are to be provided jointly by National

programmes for Kala-azar elimination and the national AIDS control programme.

These programmes should have collaboration to effectively deal with the Kala-azar

HIV confection. The key steps in the diagnosi and treatment of HIV Kala-azar

coinfection are summarized in the diagram. The details are outsid the scope of

these guidelines. Response to SSG, Amphotericin B is far from satisfactory.

Miltefosine has been found to be promising.

Kala-azar in special situation (In HIV co-infection)

1. The best option is Liposomal Amphotericin B

2. The other agents can be given if liposomal amphotricin B is not available

3.9.7. Kala-azar TB co-infection:

The treatment of this co-infection requires treatment of TB with DOTS and of

Kala-azar as per the national guidelines. If there are any complications then the

treatment may have to be done in level III or specialized facilities.


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3.10 Treatment of Kala-azar and KATF at different levels of health facilities

The facilities referred to in the table can be in the government sector, private sector

or NGOs.

Table 6: Kala-azar and PKDL treatment in different health facilities

Level I at union level: Suspect cases of Kala-azar and PKDL and refer them for diagnosis and treatment

to upazilia Health complex

Educate and convince the patient to complete the treatment as advised

Follow up the cases of Kala-azar

Observe for vomiting, diarrhea or abdominal pain and for any other severe sign

like jaundice, oedema or decline in the volume of urine passed. If any of these are

detected, stop the treatment immediately. Refer cases e.g. severe vomiting, severe

diarrhea, jaundice, oedema or decline in the volume of urine immediately

Treat vomiting/diarrhea with ORS or home available fluids. Refer patients to level

I upazilla health complex who do not improve.

Level I at Upazilla health complex:

Treat cases with Miltefosine. Ensure availability of effective contraceptives for

three months to women at child bearing age that could get miltefosine. Refer cases

who cannot be treated with miltefosine to level II facilities.

Registrar and fill treatment cards and update them

Prepare the patient for treatment by treating anaernia and give nutiritonal guidance

for undernutrition. Treat dehydration before the patient is started on specific

medicines for Kalaazar

Provide written guidance to the health worker for follow up and observation.

Advise patients on treatment to report as soon as any side effects are observed.

Refer the PKDL cases who need tissue diagnosis to level III Treat PKDL cases who are diagnosed clinically and rk39 test positive and also

those cases who are referred back from Level III after tissue diagnosis.

Report to level II facilities on kala azar patients once in a month

Level II District and equivalent hospital: Treat cases with Miltefosine. Ensure availability of effective contraceptives for

three months to women at child bearing age that could get miltefosine. Refer cases

who cannot be treated with miltefosine or other alternate 1st line drug to level III

facilities.

Until miltefosine is available treat cases of Kala-azar with other alternate 1st line

drug.

Patients on Miltefosine who are referred from government or private facilities forside effects should be hospitalized for treatment.

Refer cases to level III if Miltefosine or other alternate 1st line drug is not

available. Non responsive Kala-aza patients and patients of KA who have an

associated disease that can not be managed at level II facilities should also be

referred..

All cases of PKDL who need tissue diagnosis and kala azar & PKDL cases

suspected to be suffering from HIV coinfection should be referred to level III

facility.

Supervise the staff working in level I facilities Report once a month all

information (include reports from all level I facilities) to the level III


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Level III

Treat cases of Kala-azar referred from level II facilities with alternative

drugs. These includ pregnant women, married women in child bearing age

who are not taking regular contraceptives, patients who do not respond to

medicines given in level II facilities patients with severe disease (severe

anaemia, severe under nutrition, kidney or liver disease) an patients with

complications and side effects of medicine.

Parasitological diagnosis is recommended before starting the treatment if

the patient require admission.

Treat Kala-azar cases who need to be treated with Amphotericin B or

Liposomal amphotericin B.

Treat uncomplicated cases of Kala-azar who are self referred withMiltefosine or other alternate 1st line drug..

Treat cases of PKDL who need tissue diagnoisis and Complicated cases.

PKDL cases may be referred back to level I/ II for treatment aftert tissue

diagnosis

Treat cases of Kala-azar HIV coinfections.

Report once a month to the National programme.

Specialized facilities

Ensure drug quality and maintain quality assurance of rK-39 by PCR.

PCR testing for diagnosis in special cases.

Study and research on developing new drugs.

Report to the national programme once in a month.


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Learning Unit - 4

KALA-AZAR SURVEILLANCE AND REPORTING SYSTEM

Contents

Introduction

Reporting system

Reporting formatReporting- data flow

Report review and feedback

Reporting of treatment, hospitalized cases

Surveillance of Kala-azar and PKDL- passive surveillance, Active

surveillance and sentinel surveillance

Objective: at the end of the session the participant will beable to

describe the background and introduction

describe the reporting system for KA/PKDL

mention the reporting format

describe the data flow

mention review and feedback of Kala-azar

describe the reporting of treatment and

hospitalized cases

to enumerate passive surveillance, sentinel

surveillance,

enumerate options of surveillance, PKDL


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4.1 Introduction

Disease surveillance is a key component of kala-azar elimination program. It

comprises passive and active surveillance of kala-azar cases and vector

surveillance. Vector surveillance is described in Chapter IV. Surveillance includes

reporting of all cases of kala-azar and PKDL. To make the disease surveillance

effective, it is necessary to organize a system of regular reporting, analysis, review

and feedback 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 elimination program.

Surveillance 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

through mapping of the areas to be sprayed and in monitoring the trends of kala

azar.

4.2 Kala-azar Surveillance

Kala-azar surveillance will be a part of web-based national disease surveillance

system centrally managed by IEDCR. Kala-azar elimination program-specific

indicators will be incorporated in the reporting format. In order to strenghten kala

azar surveillance, KA surveillance units will be set up at district and upazila level.

Kala azar Elimination Program will have access to surveillance data in real time.

The surveillance data will also be fed into the Management Information System

(MIS) of DGHS.

4.2.1 Kala-azar Surveillance Units

I. Upazila Kala-azar Surveillance Unit

Head: UHFPO

Focal Person: MO (Kala-azar Elimination)

Statistical Assistant


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II. District Kala-azar Surveillance Unit:

Head: Civil Surgeon

Focal Person: MO (CS/DC)

Statistician

III. Government Medical College Hospitals:

Hospital Director

Focal Person: to be assigned by the Hospital Director

Statistician

4.2.2 Surveillance Reporting from UZHC

UHFPO will be responsible for implementation of KA surveillance activities at the

upazila level and below. The activities will include:

1. Community awareness building through advocacy meetings

2. Organizing training for the health personnel

3.

Identification of suspected cases of kala-azar and PKDL at the community

level and their referral (as per flow chart given thereof)

4. Confirmation of diagnosis by rK39 based ICT

5. Line listing of the confirmed cases at all levels using a software which

should be compatible with the web-based disease surveillance (software to

be provided by the program)

6. Reporting of confirmed kala-azar and PKDL cases including the program

monitoring indicators

7. Generation of a unique identification number for each case with

confirmation of diagnosis of KA and PKDL at all reporting levels


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4.2.3 Flow Chart for KA and PKDL Detection from Community

Identification of suspected cases of KA and PKDL by First Contact Points*(Fig. 1)

Referral of the suspected cases of KA and PKDL using prescribed referral form

Diagnosis of the cases at UHC

Weekly reporting of incidence of KA and PKDL through the web-based disease

surveillance system

*Health and family welfare centre

Union sub-centreCommunity clinic

NGO health clinic

Field staff of health and family welfare

Private practitioner

Informal health care providers

IPD of UHC

OPD of UHC


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Fig 1:Data Flowin Kala-azar Elimination Surveillance

H&FWC,

Union Sub

Centre

NGO Health Centre Private Practition

Level I:

Upazila KA Surveillance Unit

(UHC)

OPD of UHC IPD of UHC

Level II:

District KA Surveillance Unit

(Civil Surgeon Office)

Central Level:

National KA Surveillance Centre at

IEDCR

MIS

Director, DC

Focal point/PM/DPM

Kala-azar

Division

Medical College

Hospital

Sadar Hospital

OPD/IPD

Health Worker/

FP Worker

F IRST CONTACT POINT

Informal HealthCare ProvidersCommunity

Clinics

Web-based surveillance


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4.2.4 Reporting format for diagnosis of Kala-azar and PKDL

All suspected cases of Kala-azar and PKDL attending UZHC should be screened

using the check list given below (Table 1 and 2). All reporting units are expected

to enter the information using the reporting format mentioned in Tables 3-6.

Prototype formats including the check list for identification of cases for reporting

are summarized in the Tables below.

TABLE 8 Screening tool for diagnosis of kala-azar attending UHC (Checklist)

Put a () mark onthe appropriate area.Items

1 History of fever for 2 weeks or more

2 Living in endemic area

3 Palpable spleen

If all of the above indicators are positive, then do rK39 test

Results of rK39 test: +ve -ve

PATIENTS WILL BE LABELLED AS A SUSPECTED KALA-AZARCASE IF THE THREE INDICATORS MENTIONED ABOVE AREPOSITIVE.

PATIENTS WILL BE LABELLED AS PROBABLE KALA-AZAR CASEIF rK39 TEST IS POSITIVE IN A SUSPECTED KALA-AZAR CASE. (ALL

PROBABLE KALA-AZAR CASES MUST BE TREATED ACORDING TONATIONAL GUIDELINE)

PATIENTS WILL BE LABELLED AS CONFIRMED KALA-AZARCASES IF THEY MEET THE CRITERIA FOR PROBABLE KALA AZARCASE AND ARE PARASITOLOGICALLY CONFIRMED BY SPLEEN ORBONE-MARROW ASPIRATION.

ONLY THE SUSPECTED CASES AND PROBABLE CASES AREREQUIRED TO BE REPORTED FOR THE SURVEILLANCE SYSTEM.


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TABLE 9 Screening tool for Suspected Cases of PKDL attending UHC

(Check list)

Put a () mark on the appropriate area.Items

1 Previous history of kala-azar

2 Living in endemic area

3 Skin manifestations: with macule, papule or nodule without

loss of sensation

If all of the above indicators are positive, then do rK39 test

Results of rK39 test: +ve

-ve

Results of skin biopsy: +ve

-ve

PATIENTS WILL BE LABELLED AS A SUSPECTED PKDL CASEIF THE THREE INDICATORS MENTIONED ABOVE AREPOSITIVE.

PATIENTS WILL BE LABELLED AS A PROBABLE PKDL CASEIF RK39 TEST IS POSITIVE IN A SUSPECTED PKDL CASE.

PATIENTS WILL BE LABELLED AS CONFIRMED PKDL CASEIF SKIN BIOPSY IS POSITIVE FOR PKDL. SKIN BIOPSY IS

RECOMMENDED WHEN THE FACILITY IS AVAILABLE OR IN

DOUBTFUL CASES.

ALL THREE CATEGORIES OF PKDL CASES SHOULD BE

REPORTED FOR THE SURVEILLANCE SYSTEM.


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TABLE 10 Reporting format for diagnosis of Kala-azar and PKDL

Content

Name of the Reporting Unit

Upazila: Code:

District: Code:

Number of suspected kala-azar cases

Number of probable kala-azar cases

Number of suspected PKDL cases

Number of Probable PKDL cases

Number of confirmed PKDL cases

Table 11 Reporting format for treatment of Kala-azar

Content Level I

(Upazila)

Level II

(District)

Level III

(National)

Number of patients recruited for treatment

with Miltefosine

Number of patients completing treatment

with Miltefosine

Number of patients where treatment with

miltefosine was discontinued

Number of patients recruited for treatment withParomomycin


with Paromomycin

Number of patients where treatment with

Paromomycin was discontinued

Number of patients recruited for treatment with

Amphotericin B


with Amhotericin B

Number u, patients where treatment withamphotericin B was discontinued

Number of patients recruited for treatmentwith Liposomal amphotericin B


with Liposornal amphotericin. B

Number of patients where liposornal

B was discontinued

Number of patients recruited for treatment

with SSG


with SSG

Number of patients where SSG was discontinued because

of complications

Number of patients where SSG was ontinued because of

side effects of SSG


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4.2.5 Reporting of information

The data flow for reporting of cases of kala-azar and PKDL should follow the flow

chart shown in Fig 1. 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. Once web-based surveillance is in place, surveillance

data should be uploaded to the server maintained at IEDCR 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 mapping done to identify

the hot spots of Kala-azar in the district. The information flow is summarized in

the illustration.


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Figure 2. Information flow

4.2.6 Report 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.

4.2.7 Reporting of treatment

Information available from the Treatment cards provided to patients and registers

will be used for preparing treatment report. The basic information recorded include

Personal information about the patient including address, age, sex,

weight, marital status, pregnancy and lactating status

Drugs used for treatment of kala-azar

Number of days treatment provided

If treatment course has been completed or not

Side effects of drugs


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Outcome of treatment

Treatment provider (public, private, NGO)

4.2.8 Reporting of hospitalized cases

Separate reports are needed for 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) cured(b) worsened (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.

4.2.9 Criteria for cure

The following criteria should be used to assess cure in every patient treated for

Kala-azar.

Return of normal appetite

Remission of fever

Regression of spleen size

Improvement in anaemia and a rise in hemoglobin

The full course of treatment has been taken

Increase in body weight


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4.3.4 Surveillance of PKDL

The surveillance of PKDL is as important as surveillance of kala-azar since cases

of PKDL serve as a reservoir for disease transmission during the inter epidemic

period. The program should do passive and active surveillance of PKDL.


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Learning Unit - 5

INTEGRATED VECTOR MANAGEMENT (IVM)

Contents:

Vector behaviour and bionomics

Integreted Vector Management (IVM)

Indoor Residual Spraying (IRS)

Spray Programme

Monitoring and evaluation

Informing and involving the community

Personal protection

Environmental management (EVM)

Objectives: at the end of the session the participant will be able

to

describe kala-azar vector (sand fly) behaviour and

bionomics

describe the components of integrated vector management

(IVM)

describe planning and implementation of indoor residual

spraying (IRS)

enumerate surveillance, monitoring and evaluation of

vector control measures

take measures on personal protection

learn about environmental management (EVM)-household

and surrounding conditions


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5.1. Vector behaviour and bionomics

Sand flies are small, dark grey, hairy insects measuring about 1.5- 2.5 mm in

length. Phlebotomus argentipes is probably the only species amongst about 50

phlebotomine species that transmits kala-azar to humans in the Indian subcontinent

(Bangladesh, India and Nepal). It thrives best in alluvial soil, in areas with

relatively even/warm temperature, high humidity and abundance of cattle

population. Eggs and larvae of sand fly can withstand immersion in water for a

period of 5 days and fourth instar larvae for 14 days. Thus they can survive even

flooding. Breeding places are found within a radius of about 20-50 meters from a

dwelling in dark, humid soil protected from the sunlight . In cattle sheds, the

favorite breeding places are floor periphery with moisture and organic debris.

Troughs found in and around cattle sheds are other important breeding sites.

Immature stages are also often found in loose soil, cracks and crevices in and

around dwelling houses, moist plinth and cattle sheds. Mud houses are the main

resting site but also found in old brick built houses. Adult sand fly takes rest in

cracks and crevices of both indoor and out doors of households. Only the females

suck blood and they prefer cattle to human blood. Transmission can occur after a

heavy build up of sand fly population because then the sand fly shifts from cattle

to human because of scarcity of blood.

Adult sand fly is active after dark while during the day they escape into their

resting shelters. Since the habitat of P. argentipes is mainly indoor, it has

implications on the effectiveness of control measures. The sand fly is a poor flier

and it can hop only short distances. It usually do not reach above a height of 2

meter (6 feet). P. argentipes is a wet zone species. The highest risk of disease

transmission in Bangladesh is therefore observed from the month of April to

September, the months when the humidity is high (75-85%). Susceptibility test so

far conducted by M&PDC unit of DGHS have shown that sand fly is susceptible to

insecticides like Malathion, Permethrin, Deltamethrin and Fenitrothion.

The vector behaviour and bionomics that make interruption of kala-azar

transmission achievable inBangladesh include the following factors:


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So far there is one species of sandfly,Phlebotomus argentipesthat transmit

kala-azar in Bangladesh (Ref. M&PDC unit of DGHS)

The vector is sensitive to insecticides mentioned above

The insecticide spraying can be done with economy since the spraying is

required up to a height of about 2 meters only and the operations may be

confined to only indoors of households and cattle sheds and some specific

outdoor sites. This entails a saving of about half the costs when compared to

IRS for malaria eradication programme (MEP)

There is a historical evidence of interruption of transmission as a collateral

benefit of MEP when kala-azar was virtually eliminated from the

subcontinent as a result of insecticide spraying

The operation of IRS is to be limited to geographical area affecting only the

endemic districts in Bangladesh

Cross border collaboration in IRS operations can interrupt the transmission

of the disease in the border areas.

5.2 Integrated vector management (IVM)

IVM may be defined as a decision-making process for the management of vector

population, so as to reduce or interrupt transmission of vector borne diseases.

It deals with combination of two or more approaches along with community

participation to achieve maximum benefit at a reasonable and minimal cost. IVM

is recommended as a part of public health policy since this strategy uses the

followings

decision making procedures based on the knowledge of vector biology and

disease transmission

targeting of multiple vector control methods

planning and application of targeted interventions often in combination and

synergistically

rational use of insecticides

use of cost-effective interventions


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multi-sectoral partnerships

involvement of communities including planning and decision making at the

lowest possible administrative levels

measurable impact on disease transmission risks

use of effective public health regulation and legislation.

5.2.1 Components of IVM

Prevention of kala-azar and reduction of transmission are the major strategies in

the elimination of the disease. The standards and standard operating procedures for

prevention of kala-azar require application of the right mix of interventions based

on vector behaviour and vector bionomics. IVM for elimination of kala-azar

comprises of the following options:

Indoor Residual Spraying (IRS),

Personal protection to prevent human vector contact including use of long

lasting insecticidal nets (LNs),

Environment management (EVM)

5.3 Indoor residual spraying (IRS)

At present IRS is the mainstay of vector control of kala-azar elimination

programme. To maximize the impact, IRS and case search should be synchronized.

The objective of IRS is to ensure safe and correct application (uniform and

complete) of a residual insecticide up to the height of 2 meter (6 feet) on indoor

surfaces of houses and animal shelters and also other important outdoor resting

sites, e.g. cattle troughs, outdoor base (plinth) of houses, chicken houses, pigeon

holes etc. This will help in achieving a marked reduction in the populations of

vector sand fly and consequently a sharp reduction of kala-azar transmission in the

target areas.

5.3.1 Timing of IRS

The build up in the population of the vector P. argentipes starts in Bangladeshfrom April onward. The effectiveness of insecticide deltamethrin deposits lasts for


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Documents

Kala-azar Control National Guideline