RAJIV GANDI UNIVERSITY OF HEALTH SCIENCES

KARNATAKA, BANGALORE

ANNEXURE-IIPROFORMA FOR REGISTRATION OF SUBJECT FOR DISSERTATION

1. NAME OF THE CANDIDATE

AND ADDRESS

(IN BLOCK LETTERS)

DR VEERESH HALLUR

POST-GRADUATE IN PAEDIATRICS,

DEPARTMENT OF PAEDIATRICS,

MYSORE MEDICAL COLLEGE AND

RESEARCH INSTITUTE,

MYSORE-570001

2. NAME OF THE INSTITUTION MYSORE MEDICAL COLLEGE AND

RESEARCH INSTITUTE

MYSORE

3. COURSE OF STUDY AND

SUBJECT

M.D (PAEDIATRICS)

4. DATE OF ADMISSION TO

COURSE AND DATE OF

COMMENCEMENT OF

COURSE

15-05-2012

01-06-2012

5. TITLE OF TOPIC CONTACT SCREENING IN

CHILDREN UNDER THE AGE OF SIX

YEARS WHO ARE HOUSE HOLD

CONTACTS OF ADULTS ON

TREATMENT UNDER

RNTCP(Revised National Tuberculosis

Control Programme).

6. BREIF RESUME OF THE INTENDED WORK

1

6.1 Need for the study

Tuberculosis(TB) is an infective disease caused by bacillus Mycobacterium

tuberculosis1. It typically affects the lungs (Pulmonary TB) but can affect other sites

as well (Extra pulmonary TB). The disease spreads by droplet infection. Once

inhaled it forms a primary complex in lungs leading to Pulmonary Tuberculosis which

is most common of all types of TB. Disease then spreads to other parts of body (Extra

Pulmonary TB) like bone, kidney, meninges, joints etc., Routinely TB is diagnosed by

Mantoux – test and chest – X – Ray1. Polymerase Chain Reaction(PCR) is rapid

method for diagnosis of TB by detecting the DNA of Mycobacterium tuberculosis1.

Global Burden of TB

Tuberculosis remains a major global health problem.

TB facts by WHO in 2012 (October)

TB is second only to Human Immuno defeciency Virus(HIV) /Aquired

Immuno Defeciency Syndrome(AIDS) as the greatest killer worldwide due to

a single infectious agent.

In 2011, 8.7 million people fell ill with TB and 1.4 million died from TB.

Over 95% of TB deaths occur in low- and middle-income countries, and it is

among the top three causes of death for women aged 15 to 44 years.

In 2010, there were about 10 million orphan children as a result of TB deaths

among parents.

TB is a leading killer of people living with HIV causing one quarter of all

deaths2.

2

Accordingly, half million children under age of 15 contracted TB and 64,000

died last year (2011). Overall prevalence of TB in children is 2.5%3.

TB burden in India

TB is a major public health problem in India. India accounts for 1/5th of global

TB cases. Each year nearly 2 million people in India develop TB, of which around

0.8 million are infectious cases. It is estimated that annually around 3,30,000 Indians

die due to TB4.

To curb TB, Govt. of India started Revised National Tuberculosis control

progrmme (RNTCP) in 1992. This programme uses the WHO recommended Directly

Observed Treatment Short course (DOTS) strategy and reaches over billion people in

632 districts / reporting units.

In 2010, RNTCP achieved treatment success rate of 87% of new sputum

positive patients as against 71% of estimated new sputum positive people in

community.

TB Burden in Indian children.

In 2002, of the 2,45,051 new smear positive pulmonary TB cases initiated on

treatment under RNTCP, 4.159 (1.7%) were aged 0-14 years.

From survey of RNTCP implementing districts, paediatric cases were seen to

make up 3% of total load of new cases registered under RNTCP. Lymphnode TB

cases predominated (>75%) among the children with extra pulmonary TB Cases

registered under RNTCP5.

3

In India, Overall estimates of annual risk of infection in children 1 – 9 years

of age has been computed as 1.5%.6

Importance of contact screening

TB is a global health problem. Out of 9 million annual TB cases worldwide,

about 1 million (11 %) cases occur in children less 15 years of age7. In India, annual

risk of infection in children 1–9 years of age is 1.5 %.6 8–20 % of deaths in children

are due to TB only, especially in endemic areas.8 Tubercular infection is transmitted

from patients with TB through droplets in air and the risk of transmission is greatest,

if the source case is sputum smear positive pulmonary TB.9 Those living in the same

household are at greater risk of acquiring TB than casual contacts, especially the

immune deficient and very young children.10 In high burdened countries, like India,

the goal of Tuberculosis Control Programme is to eliminate the disease by

interrupting the chain of transmission. This requires rapid identification and effective

treatment of source case. At the same time, it is essential to detect infected persons in

contact with them, so that the chain of transmission can be interrupted. Therefore,

presently contact screening is being promoted actively.11

WHO has recommended active screening of children less than 5 years of age

who are in household contact with sputum smear positive pulmonary tuberculosis

cases.12 WHO recommends chemoprophylaxis for all child contacts aged less than 5

years of age if they are clinically well and clinical follow up for contacts more than 5

years of age if they are well.12 India`s RNTCP also recommends screening of all

household contacts of smear-positive pulmonary tuberculosis cases, especially those

aged less than 6 years, for symptoms of TB.13 For asymptomatic children daily

Isoniazid preventive treatment at dosage 5 mg/kg is recommended for 6 months.

4

Unfortunately, RNTCP policies on contact screening are not being effectively

implemented and contact screening has not been prioritised by the RNTCP.14 Also,

clinically asymptomatic children are routinely put on single drug (Isoniazid

prophylaxis) without Mantoux test and chest X Ray. With advent of Multi Drug

Resistant TB(MDR-TB) era and no effective screening in children (less than6 years of

age) there is high probability of missing TB infection in these children and this

especially in young children may lead to severe life threatening forms of Tuberculosis

like Tuberculous Meningitis/Miliary Tuberculosis. Approximately 40% of children

less than 1 year of age, if left untreated develop radiologically significant

lymphadenopathy or segmental lesions compared with 24% of children between 1-10

years of age and 16% of children 11-15 years of age.15 Hence the present study was

undertaken to study the prevalence of Tuberculosis infection in, under 6 year age

contacts of adults on treatment under RNTCP.

6.2 REVIEW OF LITERATURE

1. Hippocrates (460BC) used the word Pthisis (Greek name for TB) in his

literature, where he  identified this illness as the most common cause of

illness in his time. He stated that it typically affected individuals between 18

and 35years and was nearly always fatal, leading him to forbid physicians

from visiting victims of the disease to protect their reputations.16 

.

.

2. On 24 March 1882, Robert Koch revealed that TB was caused by an infectious

agent. In his research he utilized a new staining method and applied it to the

5

sputum of tuberculosis patients, revealing for the first time the causal agent of

the disease: Mycobacterium tuberculosis, or Koch's bacillus. He received the

Nobel Prize in physiology for medicine in 1905 for this discovery.16

3. In 1906 the first genuine success in immunizing against tuberculosis was

developed from attenuated bovine-strain tuberculosis by Albert

Calmette and Camille Guérin. It was called "BCG" (Bacille Calmette-Guérin).

The BCG vaccine was first used on humans in 1921 in France, but it was not

until after World War II that BCG received widespread acceptance.16

4. In1908, Charles Mantoux used the same purified protein derivative which was

earlier used by Robert Koch, found it was an effective intradermal test for

diagnosing TB.16

5.   In 1944 Albert Schatz, Elizabeth Bugie, and Selman Waksman  isolated

Streptomyces griseus or streptomycin, the first antibiotic and first bacterial

agent effective against M. Tuberculosis.16

6. In 1952, with the development of Isoniazid, the first oral mycobactericidal

drug. The advent of Rifampicin in the 1970s hastened recovery times, and

significantly reduced the number of tuberculosis cases until the 1980s.16

7. In 1992 Govt. of India initiated RNTCP or the Revised National Tuberculosis

Control Programme - It incorporates the principles of directly observed

treatment-short course (DOTS), the global TB control strategy of the World

Health Organization. The program provides, free of cost, quality anti-

tubercular drugs across the country through the numerous Primary Health

Centres and the growing number of private-sector DOTS-providers.17

6

8.  In March 2000 the Stop TB Partnership produced the Amsterdam Declaration

to Stop TB, which called for action from ministerial delegations of 20

countries with the highest burden of TB. That same year the World Health

Assembly endorsed the establishment of a Global Partnership to Stop TB.18

9. In 2004 A tuberculin survey conducted by Chadha VK, Jaganath PS, Kumar P

among 45,988 children with BCG scar and 54,227 children without BCG scar

between 1 and 9 years of age and residing in selected rural areas of three

defined zones of India, observed that in majority of children BCG induced

tuberculin sensitivity does not interfere with interpretation of tuberculin test.19

10. In 2005 Krishna Feja, Lisa Saiman have studied tuberculosis in children and

observed that the epidemiology of paediatric tuberculosis is shaped by risk

factors such as age, race, immigration, poverty, overcrowding and HIV/AIDS.

Once infected, young children are at increased risk of TB disease and

progression to extra pulmonary disease. Difficulties in diagnosing children

stems from the low yield of Mycobacteriology cultures and the subsequent

reliance on clinical case definition. Inadequately treated TB infection and TB

disease in children today is the future source of disease in adults.20

11. In 2006, at the World Economic Forum in Davos, Switzerland the Global Plan

to Stop Tuberculosis was launched. The plan sets forth a roadmap for treating

50 million people for TB and enrolling 3 million patients who have both TB

and HIV on antiretroviral therapy by 2015. It aims to halve TB prevalence and

deaths compared with 1990 levels by 2015.21

12. In 2009 a study by Modugafama, et al. to determine the prevalence of

Mantoux positivity among apparently healthy children in Maiduguri, Nigeria

7

observe that 31 of 390 (7.9%) had a positive Mantoux reaction, 27 (87.1%)

with an induration of 10-14 mm and remaining 4 (12.9%) with an induration

of 15-20 mm. The prevalence of Mantoux test positivity was higher among

BCG vaccinated than non-vaccinated children. Although Mantoux response is

usually attributed to TB infection, the effect of previous BCG vaccination

should be taken into consideration when interpreting Mantoux test responses.22

13. A study by Kishore J on National Health Programme of India estimated

6-8% of all new tuberculosis cases are in pediatric age group and majority are

in 1-4 years of age. Childhood tuberculosis is a reflection of prevalence of

sputum positive pulmonary tuberculosis in community and extent of

transmission of infection in the community. Paediatric tuberculosis does not

accord high priority as it is less infectious, but because of serious form of

tuberculosis that occur in children is more likely to die if not treated

properly.23

14. In 2011, Sandhya Chauhan & Pratik Gahalaut & A. K. Rathi

conducted a study on” Tuberculin Skin Test, Chest

Radiography and Contact Screening in Children less than 5

years: Relevance in Revised National Tuberculosis Control

Programme (RNTCP)”at Sri Ram Murti Smarak Institute of

Medical Sciences Bareilly, Uttar Pradesh, India. In their study

they concluded that active contact screening must be

prioritized by RNTCP so that the diseased children can be

diagnosed at the earliest. Further unlike presently, Mantoux

test and Chest-X-Ray should be actively employed in RNTCP

for contact screening24.

8

15. Every year March 24 is celebrated as WORLD TB DAY, to create awareness

regarding TB and to educate the people about the hazards of TB. Each year it

is celebrated with new agenda.25

In 2012,WHO campaign was with following motto, ‘The World TB Day

Campaign 2012 will allow people all over the world to make an individual call

to stop TB in their lifetimes. In their lifetimes, today's children should expect

to see a world where no one gets sick with TB. In their lifetimes, women and

men should expect to see a world where no one dies from TB. People of

different ages and living in different countries could have these hopes for

stopping TB in their lifetimes:

Zero deaths from TB

Faster treatment

A quick, cheap, low-tech test

An effective vaccine

A world free of TB.

Today in every part of world various researches are going on for the

development of new diagnostic test for rapid diagnosis of TB, to prepare vaccines for

preventing TB, to shorten the duration of treatment of TB.

6.3 OBJECTIVES OF STUDY

1. To ascertain the status of Mantoux test and Chest X Ray in children aged less

than 6 years who are house hold contacts of adults on treatment under Revised

National Tuberculosis Control Progrmme (RNTCP)

9

2. To assess the correlation between Mantoux test and Chest X Ray in diagnosis

of Tuberculosis in these children.

6.4.HYPOTHESES

Inclusion of Mantoux test and Chest X-Ray in routine contact screening of

under six year old children is likely to detect more number of tuberculosis infected

children amongst the children who are contacts of adults on treatment for TB under

RNTCP.

7. MATERIALS AND METHODS

7.1 Source of Data

“Source case” is defined as an adult aged more than 18 years who is a

confirmed case of pulmonary tuberculosis. The adult shall be sputum smear positive

and registered at the RNTCP centre of K R hospital attached to Mysore Medical

College and Research Institute Mysore. These adult patients shall be classified as

Intimate (mother or father) or regular (grandfather, grandmother, uncle, aunt, brother,

sister or any other relative). Study subject shall be defined as any child less than 6

years of age living in the same house as the source case.

7.2 METHOD OF COLLECTION OF DATA

Sample size

A minimum sample size of 200 children less than 6 years of age who are

house hold contacts of adults on treatment under RNTCP was calculated using the

formula;sample size= z2pq/d2 where

10

Z=1.96,

P=prevalence of disease(calculated from the records of said RNTCP center

from January to October 2012 which showed 2312 sputum smear positive

cases)

q=1-p

d=95%confidence interval

Sampling Method:

Simple Random Sampling

Inclusion Criteria:

Children 0-6years of age who are house hold contacts of adults who have

been registered for treatment under Revised National Tuberculosis Control

Programme(RNTCP)

Exclusion Criteria:

Children who are already on Anti-Tubercular Treatment (ATT), or on

chemoprophylaxis or who have already completed ATT.

Children having HIV /AIDS.

Children on immunosuppressive drugs.

Children with severe malnutrition.

Method of study:

11

The proposed study is a descriptive study, which shall be conducted in the

department of paediatrics of Cheluvamba hospital attached to Mysore Medical college

and Research Institute, Mysore from June 2013 to May 2014. During this period all

“ source cases” as defined earlier, shall be identified by periodic visits to RNTCP

center. They shall be advised to bring contact children less than 6 years of age to the

department of paediatrics, Cheluvamba hospital on specified day for screening for

TB.

A detailed history and clinical examination shall be done for each contact

child according to predesigned proforma. A detailed history shall include –history of

fever, history of cough of more than 2 weeks, history of decrease in appetite, history

of failure to gain weight or loss of weight and history of BCG vaccination, etc… A

detailed clinical examination shall include-examination for BCG scar, anthropometric

measurements for growth assessment, detailed systemic examination and

examination for features of extra pulmonary Tuberculosis. Growth assessment shall

be done according to WHO guidelines26 . Children with severe malnutrition

according to WHO classification shall be excluded27. Mantoux test shall be

performed by the intradermal injection of 1 TU of PPD-RT23 with Tween 80. PPD

injection shall be given into the volar surface of the left forearm using 26 gauge

needle and disposable syringe. This shall be read 48- 72 hours later in good light

with forearm flexed. Induration shall be measured by pen method28and transverse

induration of greater than 10 mm shall be defined as positive Mantoux. Every child

shall undergo Chest X Ray. This shall be reported by an independent experienced

radiologist as consistent or not consistent with TB.

STATISTICAL METHOD USED:

12

Statistical methods like descriptive statistics, chi square/contingency

coefficient analysis, independent samples t-test, logistic regression shall be employed

through the SPSS for windows (version 20.0). Sample size calculation 200 is done

using the formula;Sample size= z2pq/d2 which is already explained. Mean and

Standard deviation shall be calculated. P value < 0.05 shall be taken as statistically

significant.

7.3 Does the study require any investigation/intervention to be conducted on

patients/ humans/animals

Yes.

7.4 Has ethical clearance been obtained from your institution in case of 7.3 ?

Yes.

8. REFERNCES:

1. Kliegman, Staton, St.geme, Schor, Behrman.Tuberculosis(Mycobacterial

tuberculosis), Nelson text book of paerdiatrics 19thed, Elsevier Health Sciences

Pvt. Ltd.2012.p-996-1008.

2. World Health Organisation. Fact sheet on Tuberclosis[updated on October

2012]. Available at: www.who.int/mediacentre/factsheets/fs104/en. Accessed

on 8 November 2012.

3. World health organization. TB rates down, but its "global burden" remains

huge [Posted: 17 October 2012 2323 hrs]. Available at;

www.channelnewsasia.com/stories/health/view/.../1/.html – Singapore\

Accessed on 8 November 2012.

4. World Health Organisation. Tuberculosis in India. Core Programme

Clusters. Communicable Diseases and Disease Surveillance. Tuberculosis.

13

[updated 17 July 2012]Available at; www.whoindia.org/ en/ section3/

section123.htm.Accessed on 7 November 2012.

5. Management   of  Pediatric TB under   the  Revised National   - TBC  India

[Updated July 2010 ]Available at www.tbcindia.nic.in/pdfs/Consensus

%20statement.pdf. Accessed on 7 November 2012.

6. Chadha VK, Kumar P, Jagannatha PS, Vaidyanathan PS, Unnikrishnan kP.

Average annual risk of tuberculous infection in India. Int J TuberLung Dis.

2005;9:116–124.

7. World Health Organisation . Guidance for National Tuberculosis Programmes

on the management of Tuberculosis in children. Geneva: World Health

Organisation; 2006(WHO/HTM/TB/2006.371).

8. Enarson DA. The international union against tuberculosis and lung disease

model national tuberculosis programmes. Tuber Lung Dis.1995;76:95–98.

9. Van Zwandenberg DF. The influence of the number of bacilli on development

of tuberculosis disease in children. Am Rev Respir Dis. 1960;82:31–44.

10. Screening for tuberculosis and tuberculosis infection in high-risk populations.

Recommendations of the Advisory Council for the Elimination of

Tuberculosis. MMWR Recomm Rep.1995;44:19–34 http://www.cdc.gov/

mmwr/ preview/mmwrhtml/00038873.htm. Accessed on 8 November2012.

11. Singh V, Patra S. A. Relook at preventive therapy for tuberculosis in children.

Indian J Pediatr. 2011;78:205–210.

12. World Health Organisation. Tuberculosis in Children. In: Treatmentof

Tuberculosis. Guidelines for National Programmes. 2003 available

athttp://whqlibdoc.who.int/hq/2003/who_cds_tb_2003.313_eng.pdf. Accessed

on 7 November 2012.

13. Central TB Division (CTD), Directorate General of Health Services, Ministry

of Health and Family Welfare, Government of India. Managementof pediatric

TB under RNTCP. In: Managing RevisedNational TB de Programme in your

area – a training course.2005.http://www.muhsnashik.com/academic/

14

Orientation_Internee/Training_Module_for_Medical_Practitioners_300309.

pdf. Accessed on 7 November 2012.

14. Banu Rekha VV, Jagarajamma K, Wares F, Chandrshekaran V,Swaminathan

S. Contact screening and chemoprophylaxis in India’s Revised Tuberculosis

Control Programme: a situational analysis. Int J Tuber Lung Dis. 2009;

13:1507–1522.

15. Working Group on Tuberculosis. Indian Academy of Pediatrics (IAP).

Consensus statement on childhood TB.Indian Paediatr;(47):2010;41-55.

16. History of tuberculosis   -  Wikipedia, the free encyclopedia [updated in 2012]

Available on en.wikipedia.org/wiki/History_of_tuberculosis. Accessed on 7

November 2012.

17. TBC INDIA, Directorate General Of Health Services ,Ministry Of Health

And Family Welfare. Available at; http://tbcindia.nic.in/home.html. Accessed

on 7 November 2012.

18. Stop TB Partners   Forum -  Stop TB Partnership [.updated on 5 dec

2003]Available at; www.stoptb.org/.../13%202nd%20Partners%20Forum%20

Outline.pdf.Accessed on 8 November 2012.

19. Chadha VK, Jaganath PS, Kumar P. Tuberculin sensitivity among children

vaccinated with BCG under universal immunization programme. Indian J

Pediatric 2004;71(12):1063-1068.

20. Feja K, Saiman L. Tuberculosis in children. Clin Chest Med 2005; 26:295-

312.

21. The  Global Plan to Stop TB 2006 -2015 -  World   Health

Organization[updated in January2006]. Available at

www.who.int/tb/features_ archive/global

_plan_to_stop_tb/.../index.ht.Accessed on 7 November 2012.

22. Mustapha M. Prevalence of Mantoux test positivity among apparently healthy

children in Maiduguri, Nigeria. SAJCH 2009 Oct;3(3):80

23. Kishore J. National Health Programme of India, Paediatric Tuberculosis. 9th

ed. Community Medicine Textbook;Century publications pvt ltd; 2011. p.

223-224.

15

24. Chauhan S & Gahalaut P & Rathi A K, Tuberculin Skin Test, Chest

Radiography and Contact Screeningin Children ≤5 Y: Relevance in Revised

National Tuberculosis Control Programme (RNTCP) Indian J Pediatr DOI

10.1007/s12098-012-0792-y

25. World health organisation,woarid btb day.updated in February 2012 Available

at http://www.stoptb.org/events/world_tb_day/2012/assets/documents/Stop_

TB_Campaign_document_EN_4.pdf accessed on nov 8,2012

26. World Health Organisation, Standard Deviation Scores for assessment of

nutritional status. Available at http;//www.who.int/

childgrowth/standards/en .Accessed on 8 November 2012

27. OP Ghai, Vinod Kk Paul, Aravind Bagga, Nutrition. Ghai essential

paediatrics,7thed,C B S publishers distributors ltd.2009.p-62-64

28. Center for disease control prevention, Mantoux Tuberculin Skin Test wall

chart, available at http://www.cdc.gov/tb/education/mantoux/wallchart.htm

Accessed on 7 nov 2012.

16

9.SIGNATUE OF THE CANDIATE: DR VEERESH HALLUR

10. REMARKS OF THE GUIDE:

Contact screening in Tuberculosis is the most important, yet often neglected

aspect in management of Tuberculosis.Hence,a relevant study.

11.NAME AND DESIGNATION OF

11.1 Guide: Dr SAVITHA M R

ASSOCIATE PROFESSOR

DEPARTMENT OF PAEDAITRICS

CHELUVAMBA HOSPITAL,

MYSORE MEDICAL COLLEGE

AND RESEARCH INSTITUTE

MYSORE

11.2 SIGNATURE:

17

11.3 CO-GUIDE(IF ANY):

11.4 SIGNATURE:

11.5 HEAD OF THE DEPARTMENT:

Dr B. KRISHNAMURTHY

PROFESSOR AND HEAD

DEPARTMENT OF PAEDAITRICS

CHELUVAMBA HOSPITAL,

MYSORE MEDICAL COLLEGE

AND RESEARCH INSTITUTE

MYSORE

11.6 SIGNATURE:

12 12.1 REMARKS OF DEAN

AND DIRECTOR:

12.2 SIGNATURE:

18

ETHICAL COMMITTE CLEARENCE

1. TITLE OF DISSERTATION: CONTACT SCREENING IN

CHILDREN UNDER THE AGE OF

SIX YEARS WHO ARE HOUSE

HOLD CONTACTS OF ADULTS ON

TREATMENT UNDER RNTCP

(Revised National Tubrculosis

programme)

2.NAME OF THE CANDIDATE: DR VEERESH HALLUR

3.SUBJECT: MD PAEDIATRICS

4.NAME OF THE GUIDE: DR SAVITHA M R

ASSOCIATE PROFESSOR

DEPT OF PAEDIATRICS

MMC&RI, MYSORE

5.NAME OF THE CO-GUIDE:

6.APPROVED/NOT APPROVED: APPROVED

(If not approved, suggestions)

19

MEDICAL SUPERINTENDENT MEDICAL SUPERINTENDENT

K R HOSPITAL CHELUVAMBA HOSPITAL

MYSORE MYSORE

PROFESSOR AND HOD PROFESSOR AND HOD

DEPT OF MEDICINE DEPT OF SURGERY

MMC&RI,MYSORE MMC&RI, MYSORE

SUPERINTENDENT LAW EXPERT

PKTB HOSPITAL

MYSORE

DIRECTOR AND DEAN,MMC&RI,MYSORE

PRINCIPAL

MMC & RI, MYSORE

20