PART A (General Particulars)

1. Proposed Project Title: Exploring differences in the distribution of household environment, contact characteristics and food security between pulmonary and extra-pulmonary tuberculosis in rural areas 2. Principal Investigator: Detail curriculum vitae is annexed! Dr. Md. Anisur Rahman "rofessor # $ead of Department Epidemiology %&"'(M!

3.

o!investigator(s)) A copy of the curriculum vitae and list of publications in respect of each collaborating investigator is annexed! *. Dr. Md. Ri+wanul ,arim Asst. professor, Department of Epidemiology,%&"'(M Dr. .mmul ,hair Alam Medical (fficer, "opulation Dynamics, %&"'(M.

4. Place o" t#e stud$ % Institution(s): 'ixteen .p+illa D(/' centers. &. 'ponsoring % colla(orating agenc$: 0angladesh Medical Research 1ouncil ). *uration: 2 six! Months. +. *ate o" o,,ence,ent: As soon as fund will be available. -. *ate o" o,pletion) 3ithin six months from the date of starting. .. Total ost) /4. 5,66,66671/. 0t#er 'upport "or Proposed Researc#: %il *! &s this research pro8ect being supported by any other source: -! $as an application for funding of ;! &s this pro8ect been submitted to any other organi+ation s!: 9es 9es 9es %o %o %o

&f <9es< to *6 *! or *6 -! above, please indicate the organi+ation s! and amount of funds.

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11. *ate o" 'u(,ission)

-=7*67-6*;

12. 'ignature o" Principal Investigator)

>>>>>>>>>>>>>>>>>>>>>>>> Dr. Md. Anisur Rahman

13. 'ignature o" o!Investigator(s) )

*; >>>>>>>>>>>>>>>>>>>>>>>> *= Dr. Md. Ri+wanul ,arim *5 *2 *? *@ *A >>>>>>>>>>>>>>>>>>>>>>>> Dr. .mmul ,hair Alam

11. 2ndorse,ent o" t#e Institute 3ead) 'ignature) "rof. Dr. 'aro8 ,umar Ma+umder Designation) Director, %ational &nstitute of "reventive and 'ocial Medicine. %&"'(M! (fficial 'eal)

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PART!4
PRI5 IPA6 I572'TIGAT0R(') I580R9ATI05 '322T *. i! %ame) Dr. Md. Anisur Rahman ii! Designation) "rofessor # $ead, Department of Epidemiology, %&"'(M iii! (fficial Address with telephone) "rofessor # $ead, Epidemiology %ational &nstitute of "reventive and 'ocial Medicine %&"'(M! "hone) (**AA@@6-;;, Email) anisnipsomByahoo.com iv! "resent Residential Address with telephone) Clat no.0-, $ouse no. *6, Road *;7A, 'ector 2, .ttara, Dha4a. -. Academic bac4ground

%ame of the degree ''1 $'1 M00' D"$

;. Cield Experience)

9ear *A?2 *A?@ *A@5 *AA*

&nstitute Rangpur Dilla 'chool /itumir Eovt. 1ollege ''M1 %&"'(M

0oard Ra8shahi Dha4a Dha4a Dha4a

Remar4s *st *st "assed "assed

Fist is attached it is in the resume of the principal investigator! =. a! Research Experience Fist is attached it is in the resume of the principal investigator! b! (ther Experiences) Fist is attached it is in the resume of the principal investigator! 5. "ercentage of time to be devoted to this pro8ect) ;6G 2. %umber of 'cientific "ublications) Fist is attached it is in the resume of the principal investigator!

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PART ! 1. Project Title:

Exploring differences in the distribution of household environment, contact characteristics and food security between pulmonary and extra-pulmonary tuberculosis in rural areas

2. 'u,,ar$:
/uberculosis /0! has been a public health issue for many years and remains the ma8or cause of death from a single infectious agent among adults in developing countries. /0 remains one of the leading causes of adult mortality and morbidity in 0angladesh. 0angladesh ran4s sixth among higher /0 burden countries where extra-pulmonary /0 patients were *-G of all /0 cases in -66@. Age, education, income, occupation, race, sex, malnutrition Hit D deficiency!, $&H positivity, diabetes, renal disease, drin4ing unpasteuri+ed mil4, all are thought to be important predictors of extra-pulmonary tuberculosis. A case control study will be conducted in sixteen upa+illas of 0angladesh. A total of 5@@ samples -A= cases and -A= controls! will be recruited from the treatment register of the D(/' centers of the selected upa+illas. 'ocio-demographic, household characteristics, contact with index /0 cases and disease profile will be collected by a interviewer administered semi structured Iuestionnaire. 'tatistical tests -! will be performed to determine the association between exposure and outcome variables comparing cases and controls. 1rude odds ratios (R! and A5G confidence intervals 1&! will be estimated in the univariate analysis. &mportant predictors p J K6.65! of univariate analysis will be included in a bac4ward elimination logistic regression model to identify independent predictors. Risk factors for EPTB in Bangladesh may be different to those in low-burden countries, but appropriate studies to investigate this are lacking. /his study will be carried out to predict important ris4 indicators for E"/0 that are distinctive from ris4 indicators for "/0. As a result, more attention will be paid to address E"/0 cases and strategy will be formulated to combat E"/0 focusing more emphasis on those factors.

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Part * 1. Introduction
/uberculosis /0! remains a ma8or global public health problem. &t is the second greatest contributor among infectious diseases to adult mortality, causing approximately two million deaths a year worldwide. &t is estimated that about one third of the worldLs population is infected with Mycobacterium tuberculosis.*,
-

/uberculosis continues to cause a large burden of disease in the world, enhanced by poverty, poor public health, nutritional status and increasing $&H7A&D' prevalence and thus /0 continues to be a persistent challenge for global health and development.; /he 'outh East Asia Region 'EAR! with an estimated =.@@ million prevalent cases carries one third of the global burden of /0. /he control of /0 in the region is affected by variations in the Iuality and coverage of various /0 control interventions, population demographics, urbani+ation, changes in the socio-economic standards, $&H and more recently, emerging drug resistance. = Extrapulmonary involvement occurs in one fifth of all /0 casesM 26G of patients with extrapulmonary manifestations of /0 have no evidence of pulmonary infection on chest radiographs or sputum culture.5 /uberculosis is a ma8or public health problem in 0angladesh since long. /ill date /0 remains one of the leading cause of adult mortality and morbidity and preventable death in 0angladesh. 3ith a population of *56 million, 0angladesh ran4s sixth among higher /0 burden countries. Almost half of the population is infected with /0. Extra-pulmonary /0 patients were **G in -66? and *-G in -66@.2 A total of *=? among ;=- cases were diagnosed in -66?. Most of the extra-pulmonary cases were female. %ew smear negative and extra-pulmonary cases were *5.?G and *6.AG respectively. "roportions of extra-pulmonary and new smear negative cases reported from metropolitan cities and by 1hest Disease 1linics were higher compared to upa+ilas. /his is due to limited diagnostic facilities available at upa+ila level to detect smear negative or extra-pulmonary cases.?

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Researc# :uestion
Are there any differences in the distribution of household environment, contact characteristics and food security between pulmonary and extra-pulmonary tuberculosis in rural areas;

2. 0(jectives General o(jective

/o find out the differences in the distribution of household environment, contact characteristics and food security between pulmonary and extra-pulmonary tuberculosis in rural areas. .

'peci"ic o(jectives
*. /o assess the socio-demographic characteristics differences between pulmonary and extrapulmonary tuberculosis. -. /o find out the differences in household-characteristics between pulmonary and extrapulmonary tuberculosis. ;. /o identify the 4itchen environment status of pulmonary and extrapulmonary tuberculosis. =. /o find out the differences in contact related and lifestyle variables between pulmonary and extrapulmonary tuberculosis. 5. /o measure the food security status of the respondents using standard food security Iuestionnaire 2. /o predict the differences in the distribution of ris4 indicators for pulmonary and extrapulmonary tuberculosis.

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3. Rationale%<usti"ication o" t#e stud$

Differences in the li4elihood of extra-pulmonary /0 have been observed in various studies among /0 patients by demographic characteristics. Moreover, diagnosis of extra-pulmonary /0 cases was not so much successful. As a result a huge number of extra-pulmonary tuberculosis patients were undiagnosed.2 Recent studies have suggested that the sites of extra-pulmonary /0 may be according to geographic location and population. 1linical manifestations of /0 are variable and depend on a number of factors that are related to microbe, the host and the environment.@ 'tudies have examined the role of host related factors on the ris4 of development of E"/0. Ris4 factors for E"/0 in 0angladesh may be different to those in low-burden countries, but appropriate studies to investigate this is lac4ing. /his study will be carried out to identify possible ris4 indicators for E"/0 that are distinctive from ris4 indicators for "/0. As a result, more attention will be paid to address E"/0 cases and strategy will be formulated to combat E"/0 giving more emphasis on those factors.

6iterature revie=
/here are several studies regarding ris4 factors of pulmonary and extra-pulmonary tuberculosis. 'tudies in 0angladesh related to extra-pulmonary tuberculosis and related ris4 factors are very limited. 'tudies carried out in different parts of the world are viewed thoroughly to find out what others have learnt and reported relevant to extra-pulmonary tuberculosis. Extra-pulmonary tuberculosis may affect any organ or tissue, most commonly found in mediastinal lymphnodes, larynx, cervical lymphnodes, pleurae, meninges, central nervous system, spine, bones and 8oints, 4idneys, pericardium, intestines, peritoneum and s4in. Fess common extra-pulmonary involvement is eye, nasopharynx and adrenal gland.A

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linical "eatures:
A patient with pulmonary tuberculosis presents with one or more following symptoms in addition to cough) Respiratory symptoms- shortness of breath, chest pain, coughing up of blood. Eeneral symptoms- loss of weight, loss of appetite, fever, night sweats 'ign and symptoms of extra-pulmonary tuberculosis depend on the site involved. Most common examples are) /0 lymphadenitis) swelling of lymphnodes. "leural effusion) fever, chest pain, shortness of breath. Noint /0) pain and swelling of 8oints. 'pinal /0 ) radiological findings with or without loss of function. Meningitis) headache, fever, nec4 stiffness and subseIuent mental confusion. Eastro-intestinal /0) abdominal pain, chronic diarrhea, sub-acute obstruction, passage of blood in stool and right iliac fossa mass. Eenito-urinary /0 ) urinary freIuency, dysuria, hematuria and loin pain.

4urden o" tu(erculosis 4anglades# 'ituation

/uberculosis is a ma8or public health problem in 0angladesh since long. /ill date /0 remains one of the leading cause of adult mortality and morbidity and preventable death in 0angladesh. 3ith a population of *56 million, 0angladesh ran4s sixth among the highest /0 burden countries. Almost half of the population is infected with /0. &n -66@, the estimated prevalence and incidence rates of all forms of tuberculosis were respectively ;@? and --; per *, 66,666 population.

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'ituation o" e>tra! pul,onar$ tu(erculosis

EP-TB: Global Situation &n -66@, 5.? million cases of /0 new cases and relapse! were notified to %/"s, out of which -.? million were new positive cases, -.6 million new smear- negative pulmonary cases or cases for which smear status was un4nown! and 6.@ million new were extra-pulmonary /0 Elobal case notification of extra- pulmonary cases in -66@ was ?, @5,-?- Among them high burden countries contributes 5,?2,=6- cases. (ut of these, -, A5,@22 were extra-pulmonary cases *;.5G!.*6
*

&n

-66?, total case notification of tuberculosis in 'outh East Asia region was --, 6-,*=A

EP-TB: Bangladesh situation &n 0angladesh, though the pulmonary case detection rate continues to improve, the extra-pulmonary case detection had not yet been met. /he proportion of extrapulmonary tuberculosis is lower. /here is no prevalence rate of extra-pulmonary tuberculosis in 0angladesh. /he percentage of extra-pulmonary tuberculosis cases among total case notification were **G in -66? and *-G in -66@. 2 "roportions of extra-pulmonary cases reported from metropolitan cities and by 1D1s were higher compared to upa+ilas. /his is due to limited diagnostic facilities available at upa+ila level to detect extra-pulmonary cases.=

Ris? "actors "or T4

Role of background characteristics 9ounger age and female gender were found as independent ris4 factors for E"/0, relative to "/0.**,
*-

Cemales tended to be more li4ely to have any form of extra-

pulmonary tuberculosis than males, except pleural tuberculosis. /he strength of this association was strongest in the age range -5-2= yrs and less pronounced among the oldest patients. *; /his sex difference in rates of E"/0 has been previously attributed

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to various factors such as cigarette smo4ing, genetic and hormonal factors, iron status, alcohol consumption, delay in diagnosis and associated disease.*= /he other reasons for female disease preponderance may be the social exclusion of younger women who are generally homebound and have poorer nutritional status than their male counterparts, social stigma associated with /0 which discourages women from see4ing early medical care, and Hitamin D deficiency due to poor dietary inta4e as well as inadeIuate exposure to sunlight because of poor housing and the culture of wearing burIas. 'everal studies showed "a4istani women to have low levels of serum -5-hydroxyvitamin D. /here is a growing evidence of a strong association between /0 and Hitamin D deficiency.*5 A prospective study was conducted by 'hafi .llah et al to assess its freIuency in various organ systems of the body and to evaluate the role of demographic factors li4e sex and age in its causation. $igh female preponderance was noted with M) C ratio of *)-. Mean age was ;5 years and ?6G of the patients were in the age group *5=5 years. Fymph nodes were most common site of E"/0, involved in 22.=G of the cases. /hey concluded that E"/0 has high rates in females in their reproductive age. /he other li4ely socio-cultural factors could be high female illiteracy, female economic dependency and their poor access to health care. /hus, in their environments, female gender and age between *5-=5 years are two important predisposing factors for E"/0.*2 Socio-economic condition and TB Analytic epidemiological study showed women, non-$ispanic blac4s, and $&Hpositive persons to have a significantly higher ris4 for extra pulmonary tuberculosis than men, non-$ispanic whites, and $&H-negative persons.*? E"/0 is reported to be more often diagnosed in females and in young patients. Almost one-third of the tuberculosis cases in 9emen were extra-pulmonary -@G! was associated with poverty and that most of the extra pulmonary tuberculosis patients came from rural areas.

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Multivariate assessment of host factors showed that ris4 of /0 was increased with variation in occupational status. Assessment of environmental factors showed an increased ris4 with household crowding, history of household exposure to a 4nown /0 case, as well as amongst the Nola ethnic group.*@ Smoking 'mo4ers incur a - to = fold increased ris4 of invasive respiratory disease. "erhaps the greatest public health impact of smo4ing on infection is the increased ris4 of tuberculosis, a particular problem in under developed countries where smo4ing rates are increasing rapidly.
*A

A higher proportion of culture confirmed /0 cases was

found among ever smo4ers current and ex-smo4ers! than never-smo4ers. "ulmonary involvement was more prevalent among ever smo4ers than never smo4ers and the reverse was true for extra-pulmonary involvement. -6 Cemale and age were associated with E"/0, while alcohol abuse, smo4ing habit, contact with "/0 patients and 01E vaccination had a protective effect. -* Common sites of EPTB Fymph node tuberculosis comprised the greatest number of E"/0 1ases in almost all studies.----5 /he central nervous system was the next most freIuent site of E"/0 involvement, followed in descending order by s4eletal, pleural, abdominal, cutaneous, genitourinary, pericardial, miliary, and breast tuberculosis.-; Miliary tuberculosis developed in infants, lymphadenitis and meningitis in preschool children, and pleural effusion and s4eletal tuberculosis in older children. -= /he distribution of different types of E"/0 differed significantly among age groups. Meningeal and bone and or 8oint /0 were more commonly observed among the male patients, while lymphatic, genitourinary, and peritoneal /0 cases were more freIuently seen among females. -5 'tudy found that a higher number of extra pulmonary tuberculosis patients were diagnosed in private hospitals and clinics than the pulmonary tuberculosis patients which might be attributed to the fact that extra pulmonary tuberculosis presents more diagnostic and therapeutic problems than pulmonary tuberculosis which are less

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familiar to most of the 1linicians.-2 "atients with bilateral lung involvement were more li4ely to have extrapulmonary involvement, with an ad8usted odds ratio (R! of =.-* A5G confidence interval O1&P, *.@--A.?-!, while patients with cavitary lesions ad8usted (R, 6.;?M A5G 1&, 6.*2-6.@=!, and with higher levels of serum albumin ad8usted (R, 6.=5M A5G 1&, 6.-5-6.?@! had less freIuent involvement. 1linicians should be aware of the possibility of extrapulmonary involvement in /0 patients with bilateral lung involvement without cavity formation or lower levels of serum albumin.-? 'tudy suggests that in a significant number of patients with E"/0 fever is absent, E'R is normal and M/ is negative. 'o, over reliance on these clinical and laboratory data may lead to failure to diagnose E"/0.-@ Age, education, income, occupation, race, sex, malnutrition Hit D deficiency!, $&H positivity, diabetes, renal disease, drin4ing unpasteuri+ed mil4, all are thought to be important predictors of extra-pulmonary tuberculosis. Risk factors for EPTB in Bangladesh may be different to those in low-burden countries, but appropriate studies to investigate this are lacking. /he present study will also help us to gain insight into the demographic and social characteristics of E"/0 cases in 0angladesh thereby will extend the 4nowledgebase of E"/0 based on which better /0 control strategies can be developed.

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1. 9et#odolog$
1.1 'tud$ t$pe /his will be a case control study. Researcher will try to find out the differences in the distribution of household environment status, contact characteristics and food security status between extra-pulmonary case! and pulmonary control! tuberculosis patient.

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/he relationship between exposure and outcome will be interpreted by chi-sIuare test and ris4 will be interpreted by ad8usted odds ratio with A5G confidence interval applying binary logistic regression.

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'tud$ period A total period of the study will be from Nanuary to Nune -6*-. Place o" t#e stud$ D(/' centers of eighteen upa+illas of Dha4a division.

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'tud$ population 'election o" cases and controls: /he samples will be classified as either E"/0 cases! or "/0 controls!. Patients whose disease involved organs or tissues outside the thora , e cluding those patients who also had pulmonary involvement, are considered to have cases of e trapulmonary tuberculosis and will be classified as case patients. E"/0 cases will encompass lymphatic, genitourinary, bone and7or 8oint, meningeal, peritoneal, gastrointestinal, cutaneous and unclassified cases. E"/0 cases that will involve Q* E"/0 disease site will be classified according to the ma8or site. "atients in whom the sites of disease are exclusively intra-thoracic, i.e. confined to lungs, pleura, and intra-thoracic lymph nodes! are considered to have cases of pulmonary tuberculosis and will be classified as control patients.
.

/uberculous pleuritis will not be classified as E"/0 because pleura is believed to be involved by direct invasion from freIuently accompanying pulmonary parenchymal /0 or hypersensitivity reaction by M. tuberculosis rather than blood stream dissemination. 1ases of disseminated /0 and cases with concurrent E"/0-"/0 will be excluded from our principal analysis, because they are not distinctly classifiable as either E"/0 or "/0. &n order to determine the possible ramifications of this definition of E"/0, we will perform a separate analysis that will be compared, disseminated and concurrent E"/0-"/0 with E"/0 only and with "/0 only. &n addition, we will perform a separate analysis in which disseminated and concurrent E"/0 will be added to our existing E"/0 classification. /he presence of extrapulmonary involvement in patients with pulmonary /0 will be based on either of the following criteria) *! Demonstration of acid-fast bacilli or the growth of Mycobacterium tuberculosis from tissue. -! "resence of granulomas with or without caseation necrosis in tissue. ;! "ositive polymerase chain reaction
tuberculosis from tissues or

"1R! results for the D%A of M.

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=! A clinical diagnosis by duty physicians based on symptoms, laboratory, radiographic findings, and treatment response to anti-/0 medications. Addresses of the cases and controls will be noted from the D(/' center registers with a view to trace study sub8ects at home for exploration of exposure information. 1.2 'a,ple si@e 2>ecutive su,,ar$ 3ith a sample of -A= sub8ects per group the study will have power of @6G. /his means that there is @6G li4elihood that the study will yield a statistically significant effect, and allow us to conclude that the percentage of sub8ects in <Exposed< differs for 1ontrol versus 1ase. *etails /he study will compare two groups 1ontrol versus 1ase! on a collection of categories called. /he collection is composed of the following - categories) Exposed and non-exposed. (ur focus is on the category called <Exposed<. /he null hypothesis is that the proportion of sub8ects in this category is identical in 1ontrol and 1ase. (ur intent is to disprove the null, and conclude that this proportion is different in the two groups. /he computation of sample si+e is based on the following assumptions and decisions. ontrol /he expected pattern of responses for 1ontrol is as follows see plot!. <Exposed< -6G!, <%on exposed< @6G!. &n particular, the percentage in <Exposed< is -6G.

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ase /he expected pattern of responses for 1ase is as follows see plot!. RExposedL ;6G!, R%on exposedL ?6G!. &n particular, the percentage in RExposedL is ;6G.

9issing &n computing the sample si+e we assume that there will be no missing data. 'a,ple 'i@e /he study will enroll -A= people per group, for a total of 5@@ people. 3ith this sample si+e, there is an @6G li4elihood that the study will yield a statistically significant result, and allow us to conclude that the percentage of sub8ects in <Exposed< is different for 1ontrol than for 1ase.

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Anderstanding t#e assu,ptions /he decision to use a sample si+e of -A= per group is based on the assumptions outlined above. &f these assumptions are correct, then this sample si+e will result in power of @6G. $owever, if these assumptions are incorrect, then the sample si+e needed to yield power of @6G will be higher or lower than -A= per group. /herefore, it is instructive to consider what sample si+e would be reIuired if we adopted a different set of assumptions. 1omputation of the reIuired sample si+e is based on five factors, as follows. *i""erence (et=een groups (ne factor that determines the reIuired sample si+e is the mean difference between groups. A small difference is relatively hard to detect, and therefore reIuires a larger sample si+e. 1onversely, a large difference is relatively easy to detect, and therefore reIuires a smaller sample si+e. /he sample si+e of -A= is based on the assumption that groups differ by *6 percentage points. A(solute value o" t#e proportions Another factor that determines the reIuired sample si+e is the absolute value of the proportions. /he sample si+e reIuired to detect a *6 percentage points difference will be larger if the proportions fall near 56G, and will be smaller if the proportions fall near 6G or near *66G./he sample si+e of -A= is based specifically on the comparison of -6G vs. ;6G. 9issing data Another factor that determines the reIuired sample si+e is the percent of missing data. 3e compute the number of sub8ects actually needed for the analysis, and then ad8ust that number to ensure that we will have that number of responses after the missing sub8ects are excluded. &n computing the sample si+e to be -A= we assume that there will be no missing data. &f the actual rate of missing data is -G, we would need a sample si+e of ;66 per group. %ote that the ad8ustment for missing data assumes that

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the data are missing completely at random. %o attempt is made to ad8ust for the possibility that people who fail to respond differ in some ways from people who do provide a response. Alp#a Another factor that has an impact on the reIuired sample si+e is alpha, the criterion used for statistical significance. 3e used an alpha of 6.65, which is often the default value, in computing the reIuired sample si+e of -A= per group. &t is sometimes appropriate to select a more conservative criterion. Cor example, with alpha set at 6.6* the reIuired sample si+e would be =;? per group. 1onversely, it is sometimes appropriate to select a less conservative criterion. Cor example, with alpha set at 6.*6 the reIuired sample si+e would be -;* per group. Tails /he final factor we need to consider is whether the significance test is one-tailed or two-tailed. 3e assumed that the study will use a two-tailed test, which is usually appropriate, and computed the reIuired sample si+e as -A= per group. &f it were appropriate to use a one-tailed test with alpha at 6.65! the reIuired sample si+e would be -;* per group. oncluding re,ar?s /his discussion is intended to highlight the importance of the assumptions in computing sample si+e. 3here possible, it may be a good idea to ta4e account of alternate assumptions to ensure that the sample si+e is adeIuate even if for example! the mean difference is smaller than expected. 'a,pling tec#ni:ue 1onvenient sampling techniIue will be adopted due to scarcity of the cases. All available cases and one control age sex matched! for each case will be recruited within the data collection period. /he cases and controls will be selected from D(/' treatment registers who enrolled in the last 5 months and meet the selection criteria.

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1.3 *ata collecting instru,ent Data collection instruments will be a pre-tested structured Iuestionnaire and a chec4 list. 3ouse#old 8ood Insecurit$ Access 'cale /he $C&A' score is a continuous measure of the degree of food insecurity access! in the household in the past four wee4s ;6 days!. Cirst, a $C&A' score variable is calculated for each household by summing the codes for each freIuency-of-occurrence Iuestion. 0efore summing the freIuency-of-occurrence codes, the data analyst should code freIuency-ofoccurrence as 6 for all cases where the answer to the corresponding occurrence Iuestion was SnoT i.e., if U*J6 then U*aJ6, if U-J6 then U-a J6, etc.!. /he maximum score for a household is -? the household response to all nine freIuency-of-occurrence Iuestions was SoftenT, coded with response code of ;!M the minimum score is 6 the household responded SnoT to all occurrence Iuestions, freIuency-of-occurrence Iuestions were s4ipped by the interviewer, and subseIuently coded as 6 by the data analyst.! /he higher the score, the more food insecurity access! the household experienced. /he lower the score, the less food insecurity access! a household experienced. 38IA' 'core (/!2+) 'um of the freIuency-of-occurrence during the past four wee4s for the A food insecurity-related conditions 'um freIuency-of-occurrence Iuestion response code U*a V U-a V U;a V U=a V U5a V U2a V U?a V U@a V UAa! %ext, the indicator, average $ousehold Cood &nsecurity Access 'cale 'core, is calculated using the household scores calculated above. 1alculate the average of the $ousehold Cood &nsecurity Access 'cale 'cores Average 38IA' 'core B 'um of $C&A' 'cores in the sample %umber of $C&A' 'cores i.e., households! in the sample

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1.1 *ata collection procedure Cirstly an official letter will be issued from M0D1 to the .$#C( of the selected upa+illas with a copy to 1ivil 'urgeon of the corresponding district informing the study purpose. Another letter will be sent to the executives of the 0RA1 and Damien foundation reIuesting necessary assistance in the field. 'ix data collectors will be trained on several setting before collecting data. /hey will be guided and assisted by the local %E( program officer and E(H assigned /uberculosis and Feprosy 1linic Assistant /F1A!. Data will be collected through face to face interview of the household at their residence by using the Iuestionnaire. Addresses of the respondents will be ta4en from the D(/' centers treatment registers with a view to trace study sub8ects at home for exploring exposure information. 0efore the interview, the detail of the study will be explained to the eligible respondents. &nformed verbal consent will be obtained from every respondent and interviews will be held in private. /he characteristics of the head of the household will be obtained by interviewing head and in case of children necessary information will be primarily collected from the mother of the children. /o ensure Iuality control, proper attention through direct supervision will be given by the research investigators. A research officer will continuously supervise the data collection and the research investigator will also ma4e regular onsite field chec4s. &n addition, all the Iuestionnaires will be chec4ed for consistency and completeness by the investigators. A subset of Iuestionnaires will be re-chec4ed in the field for validity. 1.& *ata editing: Data will be edited both when they are collected and at stage before analysis. Data editing will involve sorting data, performing Iuality-control chec4 and data processing. 1.) *ata processing and anal$sis After data collection, each Iuestionnaire will be chec4ed for completeness and consistency. /he data will be entered into computer with the help of 'oftware S'tatistical "ac4age for 'ocial 'ciencesT '"''! for windows version *A.6.

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.nivariate comparisons between the group with pulmonary /0 and the group with extrapulmonary involvement will be performed using "earsonLs chi-sIuare test or CisherLs exact test for categorical variables and 'tudentLs t-test for continuous variables. .sing variables with p values of K6.-6 from the univariate comparisons, multiple logistic regression models will be constructed to identify predictors of the presence of extra pulmonary involvement. &n logistic regression, bac4ward elimination will be used to select variables to be maintained in the final model, using a p value of K6.65 as the criterion for statistical significance of associations. /he area under the receiver operator characteristic R(1! curve will be used to evaluate the performance of the models. Ad8usted odds ratios and A5G 1& will be reported.

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1.+ 8actors in t#e stud$ Ce$ varia(les 'ocio!de,ograp#ic varia(les Age 'ex Religion Education of the respondent (ccupation of the respondent "arentLs education "arentLs occupation Average monthly &ncome /otal family members Camily type Camily mobility Residence type Area of residence 3ouse#old c#aracteristics $ouse ownership Cloor material 3all material Roof material %o of bedrooms Area of bedrooms 1rowding %o of external windows 3indow material 3indow (pening status /ype of latrine Drin4ing water source 'ource of lighting Citc#en environ,ent ,itchen position ,itchen distance ,itchen ventilation 'tove type Cuel type 1oo4ing time

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ontact in"or,ation /ype of contact 1ontact relation 1ontact regularity CreIuency of contact 6i"est$le related varia(les 'mo4ing status %o. of smo4er in the family 'haring same room with smo4er 'haring same bed with smo4er /ime of start smo4ing /ime of Iuit smo4ing %o of stic4s smo4ed per day %onsmo4ing tobacco use Addiction type *isease related varia(les /ype of /0 /ype of symptoms 'ite of extrapulmonary /0 /ime of first appearance of symptoms Method of diagnosis /ime of Diagnosis "lace of diagnosis 'mear test result 9iscellaneous 01E vaccination Cood security status

&. Atili@ation o" results% polic$ i,plications

/he present study will be conducted to gain insight into the demographic and social characteristics of E"/0 cases in 0angladesh thereby will extend the 4nowledgebase of E"/0 based on which better /0 control strategies can be developed.

16

). 8acilities
Resources, eIuipment, chemicals, sub8ects human, animal! etc. ReIuired for the study!) ).1. 8acilities Availa(le &nfra-structure of government health service centre will be used for management of the research pro8ect. &n addition, the institutional facilities of the principal investigator and co-investigators will be used for conduction of the study.

).2. Additional 8acilities Re:uired Manpower) /wo research (fficer, 'ix data collectors

+. Approval o" t#e 3ead o" t#e *epart,ent%Institute

A roved

16

-. 8lo= c#art
'tud$ period: 1st Dee? o" <anuar$ to 1t# Dee? o" <uneE 2/13!2/11

Activities '6 no 1 2 3 1 & ) + . 1/ 9ont# Dee? "roposal Development and acceptance Fiterature Review 'election of study area "lanning and Designing "reparation of Research &nstrument "re /est Data 1ollection Data Analysis, &nterpretation Report 3riting Report 'ubmission 1 <anuar$ 2 3 1 1 8e(ruar$ 2 3 1 1 2

Period o" stud$ 9arc# 3 1 1 April 2 3 1 1 9a$ 2 3 1 1 <une 2 3 1

.. 2t#ical i,plications
"rior conducting the study, ethical clearance will be ta4en from the %&"'(M Ethical Review 1ommittee. The study will neither include any invasive procedure nor any private issue and no drug will be tested. Before initiation of the interview a brief introduction on the aims and objectives of the study will be presented to the respondents. They will be informed about their full right to participate or refuse to participate in the study. A complete assurance will be given that all information provided by them will be kept confidential and their names or anything which can identify them and only will be disseminated and published for public interest. After completion of these procedures the interview will be started with their due permission. The research will be conducted in full accord with ethical principles.

*isse,ination polic$

16

3ith the proper permission of funding agency the study findings will be disseminated through seminar and discussion meeting with policy ma4ers. Attempts will also be ta4en to publish the data in national and international 8ournals.

1/. Re"erences
*. 3orld $ealth (rgani+ation 3$(!M Elobal tuberculosis control, 3$( report -66A.

-. 'udre ", /endam E and ,ochi A. /uberculosis) a global overview of the situation today. 0ull 3orld $ealth (rgan *AA-, ?6)*=A-5A.

;. 0ehavioral barriers in tuberculosis controlW.'ilvia 3aisbord the 1$A%EE "ro8ect Academy for Education development. 'EA-/0;.

=. /uberculosis in the 'outh-East Asia Region- /he Regional Report) -66@, 3$( "ro8ect %o) 'E &1" /.0. %ew Delhi. 5. $erchline /E. /uberculosis. http)77emedicine.medscape.com7article7-;6@6--overview . last updated A DecM -6**. 2. 3orld $ealth (rgani+ation 3$(!. 'EAR() /uberculosis 1ontrol in the 'outh East Asia Region. 3$( report -66A. ?. /uberculosis 1ontrol in 0angladesh, Annual Report -66@,%/". @. American /horacic society) Diagnostic 'tandards and classification of tuberculosis in adults and children. Am N Respir 1rit 1are Med -666M *2*)*;?2A5. A. Euideline, %ational /uberculosis control "rogramme, 0angladesh, =th edition. *6. 3orld $ealth (rgani+ation 3$(!. 'EAR() /uberculosis 1ontrol in the 'outh east Aswia Region. 3$( report -66@.

16

**. 'reeramareddy 1/, "anduru ,H, Herma '1, Noshi $' and 0ates M%. 1omparison of pulmonary and extra-pulmonary tuberculosis in %epal- a hospital based retrospective study. 0M1 &nfec Dis -66@ NanM -=@)@. 12. Al-(taibi C and El $a+mi MM. Extra-pulmonary tuberculosis in 'audi Arabia. &ndian N "athol Microbiol. -6*6 Apr-NunM5; -!)--?-;*. *;. Corssbohm M, Dwahein M, Fodden4emper R and Rieder $.F. Demographic characteristics of patients with extrapulmonary tuberculosis in Eermany. Euro Respir N -66?M ;* *!) AA-*65. *=. 1ailhol 8, Decludt 0 and 1he D. 'ociodemographic factors that contribute to the development of extrapulmonary tuberculosis were identified. Nournal of 1linical Epidemiology 5@ -665! *622X*6?*. 15. 1handir ', $ussain $, 'alahuddin %, Amir M, Ali C, Fotia & and ,han AN. Extrapulmonary tuberculosis) a retrospective review of *A= cases at a tertiary care hospital in ,arachi, "a4istan. N "a4 Med Assoc. -6*6 CebM26 -!)*65-A. *2. .llah ', 'hah '$, Rehman A.. ,amal A, 0egum % and ,han E. Extrapulmonary tuberculosis in Fady Reading $ospital "eshwar, %3C", "a4istan) 'urvey of biopsy results. N Ayub Med 1oll Abbottabad. -66@ Apr-NunM -6 -!) =;2. *?. 9ang D, ,ong 9, 3ilson C, Coxman 0, Cowler 0, Cowler A$, Marrs 1C, 1ave MD and 0ates N$. &dentification of ris4 factors for extra-pulmonary tuberculosis. 1lin &nfect Dis -66=M;@)*AA--65. *@. $ill ", 'illah DN, Don4or 'A, (ut N, Adegbola RA and Fienhardt 1. Ris4 factors for pulmonary tuberculosis) a clinic based case control study in /he Eambia, 0M1 "ublic $ealth -662M2)*52. *A. Arcavi F, %eal F and infection.-66=M*2=)--62---*2. 0enowit+ MD. 1igarette smo4ing and

-6. Feung 11, Fi / and Fam /$ et al. 'mo4ing and tuberculosis among elderly in $ong ,ong. Am N Respir 1rit care Med -66=M *?6) *6-?-*6;;. 21. Earcia-Rodrigue+a NC, Alvare+-Dia+a $, Foren+o-Earciab MH, MariYno-1alle8oa A, Cernande+-Rialc A and 'esma-'anche+c ". Extrapulmonary tuberculosis)

16

epidemiology and ris4 factors Enferm &nfecc Microbiol 1lin. -6**M-A ?!)56- 56A. 22. &lga+li A, 0oyaci $, 0asyigit & and 9ildi+ C. Extrapulmonary tuberculosis) clinical and epidemiologic spectrum of 2;2 cases. Arch Med Res. -66= 'ep(ctM;5 5!)=;5-=*. -;. Cader /, "ar4s N, ,han %, Manning R, 'to4es ' and %asir %A. Extrapulmonary tuberculosis in ,abul, Afghanistan)A hospital-based retrospective review. &nternational Nournal of &nfectious Diseases. -6*6M*=, e*6-Ze**6 -=. Malte+ou $ 1, 'pyridis " and ,afet+is D A. Extra-pulmonary tuberculosis in children.Arch Dis 1hild -666M@;);=-X;=2. -5. Eunal ', 9ang D, Agarwal M, ,oroglu M, ,a+gan D and Durma+ R. Demographic and microbial characteristics of extrapulmonary tuberculosis cases diagnosed in Malatya, /ur4ey, -66*--66?. 0M1 "ublic $ealth -6**, **)*5=. -2. (thman EU, &brahim M&M and Ra8aa 9A. 1omparison of clinical and sociodemographical factors in pulmonary and extrapulmonary tuberculosis patient in 9emen.Nournal of 1linical and Diagnostic Research. -6** April, Hol-5 -!)*A**A5. -?. ,im MN, ,im $R, $wang '', ,im 93, $an ',, 'him 9', and 9im NN. "revalence and &ts "redictors of Extrapulmonary &nvolvement in "atients with "ulmonary /uberculosis.N ,orean Med 'ci. -66AM -=) -;?-=*. -@. $ussain M3, $aIue MA, 0anu 'A, E4ram 'A and Rahman MC. Extrapulmonary /uberculosis) Experience in Ra8shahi 1hest Disease 1linic and 1hest Disease $ospital. /he Nournal of /eachers Association, RM1, Ra8shahi. /AN -66=M *? *! ) *2-*A.

16

PART 2
Budget

A.Total Budget: Tk 500, 000 (Five lacs only) B. etailed !udget

Sl. No. 1 Item Personnel cost 1.1 Principal Investigator PI! 1.& 'o-Investigator 'o-I! 1.% )esearch *++icer )*!/statistician 1.( Support Sta++ M-SS! .iel/ 01penses &.1 2onorarium +or )esource Person +or Training o+ )*3 4olunteers an/ /ata collectors &.& 'ost o+ Data 'ollection &.% -ocal supervision cost &.( 'ompensation +or research Participants Supplies an/ Materials Patient 'ost Travel 'ost ".1 Non-local +iel/ cost +or PI 8 'o-I ".& Non-local +iel/ cost +or )* ".% -ocal +iel/ cost +or PI 8 'o-I -ocal +iel/ cost +or )*/ Data ".( collectors *++ice Stationeries $.1 Toner $.& *++set paper Bag/Pen/pencil/eraser/measuring $.% tape/ umbrella etc. Data processing an/ computer charges ,.1 6 Data entr93 co/ing3 cleaning Unit cost "### (### 1&### 1### ("# $### 1### 1"# Number 1 & & 1 % $ ( $## Months/ times $ ( % $ % & % 1 BDT %#### %&### ,&### $### (#"# ,&### 1&### 5#### 1,6#"# Not 7pplicable Not 7pplicable %### 1### %## 1"# $### "## -ump sum -ump sum -ump sum -ump sum -ump sum -ump sum -ump sum % 1 % 1 1 $ 1 ( &# 1## 1 1 5### (### 16### 1"### $### %### 1(### &"### &"### $3### 1&### $### 1#### &(### 1#### "#### &%### ($### Sub-total

1(####

&

% ( "

,.& Data anal9sis Printing an/ repro/uction//issemination 6.1 6.& 6.% Printing o+ :uestionnaire )eport preparation/ printing Photocop9

5 1# 11

5.1 Dissemination Miscellaneous Telephone3 internet3 postage etc.! 47T 8 Income Ta1 (;! <ran/ Total

65"# 65"# &#### &#### BDT "#####.## =Ta>a +ive lacs onl9?

16

5ational Institute o" Preventive and 'ocial 9edicine *irectorate General o" 3ealt# 'ervices Application "or 2t#ical learance 1. Principal Investigator(s): Dr. Md. Anisur Rahman "rofessor # $ead, Dept. of Epidemiology. %ational &nstitute of "reventive and 'ocial Medicine %&"'(M! 2. o!Investigator(s): Dr. Md. Ri+wanul ,arim Asst. "rofessor, Department of Epidemiology, %&"'(M Dr. .mmul ,hair Alam Medical (fficer, "opulation Dynamics, %&"'(M.

3. Place o" t#e 'tud$%Institution(s): 'ixteen .p+illa D(/' centers

Exploring differences in distribution of household environment, contact characteristics and food security between pulmonary and extra-pulmonary tuberculosis in rural areas;

1. T$pe o" 'tud$: 1ase control study &. *uration: ). Total ost: +. 8unding Agenc$)
2 six! Months /4.566,6667J 4anglades# 9edical Researc# ouncil (49R )

16

ircle t#e appropriate ans=er to eac# o" t#e "ollo=ing !"f not A licable #rite $A% 1. 'ource o" Population : 1. Are su(jects clearl$ in"or,ed a(out: a! &ll 'ub8ects b! %on[ &ll 'ub8ects c! Minors or persons under guardianship 2. *oes t#e stud$ involve : a! "hysical ris4s to the sub8ects b! 'ocial Ris4s c! "sychological ris4s to sub8ects d! Discomfort to sub8ects e! &nvasion of the body f! &nvasion of "rivacy 9es 9es 9es 9es 9es 9es %o %o %o %o %o %o %o 9es 9es 9es %o %o %o a! %ature and purposes of study b! "rocedures to be followed including alternatives used c! "hysical ris4s d! "rivate Iuestions e! &nvasion of the 0ody f! 0enefits to be derived 9es 9es %o %o

%ot applicable 9es %o

%ot applicable 9es 9es %o %o

g! Right to refuse to participate or to withdraw from study h! 1onfidential handling of data i!

9es

%o %o

g! Disclosure of 9es information damaging to sub8ect or others 3. *oes t#e stud$ involve : a! .se of records, hospital, medical, death, birth or other! b! .se of fetal tissue or abortus c! .se of organs or body fluids 9es

1ompensation 9es where there are ris4s or loss of wor4ing time or privacy is involved in any particular procedure

%o

&. Dill signed consent "or,%ver(al consent (e re:uired : a! Crom 'ub8ects 9es %o

9es 9es

%o %o

b! Crom parent or guardian if sub8ects are minors! ). Dill precautions (e ta?en to protect anon$,it$ o" su(jects

%ot applicable

9es

%o

16

T#e 2t#ical Revie= o,,ittee (2R )

/0 remains one of the leading causes of adult mortality and morbidity in 0angladesh that causing persistent crisis in health and development. 0angladesh ran4s sixth among higher /0 burden countries where extra-pulmonary /0 patients were *-G of all /0 cases in -66@. Age, education, income, occupation, race, sex, malnutrition Hit D deficiency!, $&H positivity, diabetes, renal disease, drin4ing unpasteuri+ed mil4, all are thought to be important predictors of extra-pulmonary tuberculosis. A case control study will be conducted in eighteen upa+illas of Dha4a division. A total of 5@@ samples -A= cases and -A= controls! will be recruited from the treatment register of the D(/' centers of the selected upa+illas. 'ociodemographic and disease profile will be collected by a interviewer administered semistructured Iuestionnaire. 0efore the interview, the detail of the study will be explained to the eligible respondents. &nformed verbal consent will be obtained from every respondent and interviews will be held in private. Risk factors for EPTB in Bangladesh may be different to those in low-burden countries. This study will help us identifying the risk factors that predispose to EPTB !nd will lead policymakers adopting targeted strategies to prevent it and decrease its national burden.

*ocu,ents su(,itted #ere=it# to co,,ittee: .mbrella proposal "roposal 'ummary Abstract for Ethical Review 1ommittee as per attachment &nformed consent form for sub8ects "rocedure for maintaining confidentiality &nterview schedule and chec4list

We agree to obtain approval of the Ethical Review Committee for any changes involving the rights and welfare of subjects or any changes of the Methodology before making any such changes.

"rincipal &nvestigator

(ther &nvestigator s!

Predicting ris? indicators "or Pul,onar$ and 2>tra!pul,onar$ Tu(erculosis in rural areas
/hese issues will be 4ept in concern while conducting research process)

*. Any group whose ability to give voluntary informed consent assumes Iuestionable will not be
included -. %o potential ris4s exists in designing this study

;. 0y following under mentioned steps confidentiality will be maintained) Research data will be coded
Data will be stored in a loc4ed cabinets (nly research personnel will be allowed to access data. /here is no physical, psychological, social and legal ris4. During physical examination, proper consent will be ta4en. Cor safeguarding confidentiality and protecting anonymity each of the patient will be given a special &D no. that privacy of the patient will be maintained and he7she will be compensated for loss of wor4 time if they wants

A signed informed consent will be ta4en from the patient7patientLs guardians convincing A data collection sheet should enclosed! be prepared for which a short interview of -5-;6
minutes will be reIuired

%o drug will be used for this study %o experimental new drug will be administrated %o placebo will be used here .se of hospital records outdoor! will be needed to fill up the patientLs data sheet.

=. 1onsent form will be a written statement 5. A brief interview regarding study variables will be collected from the participants. 2. /he study result will accrue the benefit to the society by providing information regarding
exploration and identification of important ris4 indicators and their distribution among pulmonary and extra-pulmonary tuberculosis cases in rural areas of 0angladesh. ?. %o experimental drug, placebo will be used.

"rincipal &nvestigator

I580R9 05'25T 80R9 80R 'A4<2 T'

Title o" researc# stud$: Exploring differences in the distribution of household

environment, contact characteristics and food security between pulmonary and extrapulmonary tuberculosis in rural areas
!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! 5a,e o" Participant: !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! 5a,e o" Investigator: !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!

*. & consent to participate in the research titled SExploring differences in the distribution of household environment, contact characteristics and food security between pulmonary and extra-pulmonary tuberculosis in rural areasT, the particulars of which-including details of interviews and Iuestionnaires have been explained to me. A written copy of the information has been given to me to 4eep. -. & authori+e the researcher to use with me the interviews and Iuestionnaires referred to under *! above. ;. & ac4nowledge that) a. /he possible effects of the interviews and Iuestionnaires have been explained to me to my satisfaction b. & have been informed that & am free to withdraw from the research at any time without explanation or pre8udice and to withdraw any unprocessed data previously suppliedM c. /he pro8ect is for the purpose of research d. & have been informed that the confidentiality of the information & provide will be safeguarded sub8ect to any legal reIuirements e. & have been informed regarding the interviews. & have also been informed that because of the number of people to be interviews is smallM it is possible that someone may still be able to identify me on the basis of any references to personal information that might allow someone to guess my identity. $owever, & will be referred by pseudonym or identified by a different name in any publications arising from the research.
'ignature Date ----------------------------------------------------------------------------------------"articipant! 'ignature Date ----------------------------------------------------------------------------------------- 3itness to consent!

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/itle of the study) Exploring differences in the distribution of household environment, contact
characteristics and food security between pulmonary and extra-pulmonary tuberculosis in rural areas.

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