bmrc eptb proposal 18-10-13 2
TRANSCRIPT
PART – A (General Particulars)
1. Proposed Project Title: Predicting risk indicators for Pulmonary and Extra-pulmonary Tuberculosis in rural areas
2. Principal Investigator: Dr. Md. Anisur Rahman(Detail curriculum vitae is annexed) Professor & Head, Department of
Epidemiology NIPSOM
3. Co-investigator(s): (A copy of the curriculum vitae and list of publications in respect of each collaborating investigator is annexed)
1. Dr. Md. Rizwanul KarimAsst. professor, Department of Epidemiology,NIPSOM
2 Dr. Ummul Khair AlamMedical Officer, Population Dynamics,NIPSOM.
4. Place of the study / Institution(s) : Sixteen Upzilla DOTS centers.
5. Sponsoring / collaborating agency: Bangladesh Medical Research Council
6. Duration: 6 (six) Months.
7. Date of Commencement: As soon as fund will be available.
8. Date of Completion: Within six months from the date of starting.
9. Total Cost: Tk.- 5,00,000/-
10. Other Support for Proposed Research: Nil (Font different)
(1) Is this research project being Yes No supported by any other source?
(2) Has an application for funding of Yes No
(3) Is this project been submitted to any Yes Noother organization(s)?
If 'Yes' to 10(1) or 10(2) above, please indicate the organization(s) and amount of funds.
11. Date of Submission: /10/2013
12. Signature of Principal Investigator: ________________________Dr. Md. Anisur Rahman
13. Signature of Co-Investigator(s) : ________________________Dr. Md. Rizwanul Karim
________________________Dr. Ummul Khair Alam
14. Endorsement of the Institute Head:
Signature:
Prof. Dr. Saroj Kumar MazumderDesignation: Director, National Institute of Preventive and Social Medicine. (NIPSOM)
Official Seal:
PART-B
PRINCIPAL INVESTIGATOR(S) INFORMATION SHEET
1. (i) Name: Dr. Md. Anisur Rahman
(ii) Designation: Professor & Head, Department of Epidemiology, NIPSOM
(iii) Official Address with telephone: Professor & Head, EpidemiologyNational Institute of Preventive and Social MedicinePhone. O1199880233 ,Email: [email protected]
(iv) Present Residential Address with telephone: Flat no.B2, House no. 10, Road 13/A, Sector 6, Uttara, Dhaka.
2. Academic background
Name of the degree
Year Institute Board Remarks
SSC 1976 Rangpur Zilla School Rajshahi 1stHSC 1978 Titumir Govt. College Dhaka 1stMBBS 1985 SSMC Dhaka PassedMPH Epidemiology
1991 NIPSOM Dhaka Passed
3. Field Experience:
List is attached (it is in the resume of the principal investigator)
4. (a) Research ExperienceList is attached (it is in the resume of the principal investigator)(b) Other Experiences: List is attached (it is in the resume of the principal investigator)
5. Percentage of time to be devoted to this project: 30%
6. Number of Scientific Publications: List is attached (it is in the resume of the principal investigator)
PART - C
1. Proposed Project Title:
Predicting risk indicators for Pulmonary and Extra-pulmonary Tuberculosis in rural areas
2. Executive summary:
Tuberculosis (TB) has been a public health issue for many years and remains the major
cause of death from a single infectious agent among adults in developing countries. TB
remains one of the leading causes of adult mortality and morbidity in Bangladesh.
Bangladesh ranks sixth among higher TB burden countries where extra-pulmonary TB
patients were 12% of all TB cases in 2008. Age, education, income, occupation, race,
sex, malnutrition (Vit D deficiency), HIV positivity, diabetes, renal disease, drinking
unpasteurized milk, all are thought to be important predictors of extra-pulmonary
tuberculosis. A case control study will be conducted in sixteen upazillas of Bangladesh.
A total of 588 samples ( 294 cases and 294 controls) will be recruited from the treatment
register of the DOTS centers of the selected upazillas. Sociodemographic, household
characteristics, contact with index TB cases and disease profile will be collected by a
interviewer administered semistructured questionnaire. Statistical tests (2) will be
performed to determine the association between exposure and outcome variables
comparing cases and controls. Crude odds ratios (OR) and 95% confidence intervals (CI)
will be estimated in the univariate analysis. Important predictors (p = <0.05) of univariate
analysis will be included in a backward 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. This study will be carried out to predict important risk
indicators for EPTB that are distinctive from risk indicators for PTB. As a result, more
attention will be paid to address EPTB cases and strategy will be formulated to combat
EPTB focusing more emphasis on those factors.
Part – D
Introduction
Background
Tuberculosis (TB) remains a major global public health problem. It is the second
greatest contributor among infectious diseases to adult mortality, causing
approximately two million deaths a year worldwide. It is estimated that about one
third of the world’s population is infected with Mycobacterium tuberculosis.1, 2
Tuberculosis continues to cause a large burden of disease in the world, enhanced by
poverty, poor public health, nutritional status and increasing HIV/AIDS prevalence
and thus TB continues to be a persistent challenge for global health and
development.3 The South East Asia Region (SEAR) with an estimated 4.88 million
prevalent cases carries one third of the global burden of TB. The control of TB in the
Region is affected by variations in the quality and coverage of various TB control
interventions, population demographics, urbanization, changes in the socio-economic
standards, HIV and more recently, emerging drug resistance.4 Extrapulmonary
involvement occurs in one fifth of all TB cases; 60% of patients with extrapulmonary
manifestations of TB have no evidence of pulmonary infection on chest radiographs
or sputum culture.5
Tuberculosis is a major public health problem in Bangladesh since long. Till date TB
remains one of the leading cause of adult mortality and morbidity and preventable
death in Bangladesh. With a population of 150 million, Bangladesh ranks sixth
among higher TB burden countries. Almost half of the population is infected with
TB. Extra-pulmonary TB patients were 11% in 2007 and 12% in 2008.6 A total of 147
342 cases were diagnosed in 2007. Most of the extra-pulmonary cases were female.
New smear negative and extra-pulmonary cases were 15.7% and 10.9% respectively.
Proportions of extra-pulmonary and new smear negative cases reported from
metropolitan cities and by Chest Disease Clinics were higher compared to upazilas.
This is due to limited diagnostic facilities available at upazila level to detect smear
negative or extra-pulmonary cases.7
Research questionWhat are the differences in the distribution of risk indicators between pulmonary and
extrapulmonary tuberculosis?
General objectiveTo find out the differences in the distribution of risk indicators between pulmonary
and extrapulmonary tuberculosis
Specific objectives
1. To assess the sociodemographic characteristics differences between
pulmonary and extrapulmonary tuberculosis.
2. To find out the differences in household-characteristics between pulmonary
and extrapulmonary tuberculosis.
3. To identify the kitchen environment status of pulmonary and extrapulmonary
tuberculosis.
4. To find out the differences in contact related and lifestyle variables between
pulmonary and extrapulmonary tuberculosis.
5. To predict the differencs in the distribution of risk indicators for pulmonary
and extrapulmonary tuberculosis.
Justification of the studyDifferences in the likelihood of extra-pulmonary TB have been observed in various
studies among TB patients by demographic characteristics. Moreover, diagnosis of
extra-pulmonary TB cases was not so much successful. As a result a huge number of
extra-pulmonary tuberculosis patients were undiagnosed.6
Recent studies have suggested that the sites of extra-pulmonary TB may be
according to geographic location and population. Clinical manifestations of TB are
variable and depend on a number of factors that are related to microbe, the host and
the environment.8 Studies have examined the role of host related factors on the risk of
development of EPTB. Risk factors for EPTB in Bangladesh may be different to
those in low-burden countries, but appropriate studies to investigate this is lacking.
This study will be carried out to identify possible risk indicators for EPTB that are
distinctive from risk indicators for PTB. As a result, more attention will be paid to
address EPTB cases and strategy will be formulated to combat EPTB giving more
emphasis on those factors.
Literature review
There are several studies regarding risk factors of pulmonary and extra-pulmonary
tuberculosis. Studies in Bangladesh related to extra-pulmonary tuberculosis and
related risk factors are very limited. Studies 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 joints, kidneys, pericardium, intestines, peritoneum
and skin. Less common extra-pulmonary involvement is eye, nasopharynx and
adrenal gland.9
Clinical features:
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
General symptoms- loss of weight, loss of appetite, fever, night sweats
Sign and symptoms of extra-pulmonary tuberculosis depend on the site involved.
Most common examples are:
TB lymphadenitis: swelling of lymphnodes
Pleural effusion: fever, chest pain, shortness of breath
Joint TB: pain and swelling of joints
Spinal TB : radiological findings with or without loss of function
Meningitis: headache, fever, neck stiffness and subsequent mental confusion
Gastro-intestinal TB: abdominal pain, chronic diarrhea, sub-acute obstruction,
passage of blood in stool and right iliac fossa mass.
Genito-urinary TB : urinary frequency, dysurea, hematuria and loin pain
Burden of tuberculosis
Bangladesh Situation
Tuberculosis is a major public health problem in Bangladesh since long. Till date TB
remains one of the leading cause of adult mortality and morbidity and preventable
death in Bangladesh. With a population of 150 million, Bangladesh ranks sixth
among the highest TB burden countries. Almost half of the population is infected
with TB. In 2008, the estimated prevalence and incidence rates of all forms of
tuberculosis were respectively 387 and 223 per 100 000 population.
Situation of extra- pulmonary tuberculosis
EP-TB: Global Situation
In 2008, 5.7 million eases of TB (new cases and relapse) were notified to NTPs, out
of which 2.7 million were new positive cases, 2.0 million new smear- negative
pulmonary cases (or cases for which smear status was unknown) and 0.8 million new
were extra-pulmonary TB Global case notification of extra- pulmonary cases in 2008
was 7, 85,272 Among them high burden countries contributes 5,76,402 cases. 1 In
2007, total case notification of tuberculosis in South East Asia region was 22,02,149
Out of these, 2,95,866 were extra-pulmonary cases (13.5%).10
EP-TB: Bangladesh situation
In Bangladesh, though the pulmonary case detection rate continues to improve, the
extra-pulmonary case detection had not yet been met. The proportion of extra-
pulmonary tuberculosis is lower, There is no prevalence rate of extra-pulmonary
tuberculosis in Bangladesh. The percentage of extra-pulmonary tuberculosis cases
among total case notification were 11% in 2007 and 12% in 2008.6 Proportions of
extra-pulmonary cases reported from metropolitan cities and by CDCs were higher
compared to upazilas. This is due to limited diagnostic facilities available at upazila
level to detect extra-pulmonary cases.4
Risk factors for TB
Role of background characteristics
Younger age and female gender were found as independent risk factors for EPTB,
relative to PTB.11, 12 Females tended to be more likely to have any form of extra-
pulmonary tuberculosis than males, except pleural tuberculosis. The strength of this
association was strongest in the age range 25-64 yrs and less pronounced amongst the
oldest patients. 13 This sex difference in rates of EPTB has been previously attributed
to various factors such as cigarette smoking, genetic and hormonal factors, iron
status, alcohol consumption, delay in diagnosis and associated disease.14
The 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 TB which discourages women
from seeking early medical care, and Vitamin D deficiency due to poor dietary intake
as well as inadequate exposure to sunlight because of poor housing and the culture of
wearing burqas. Several studies showed Pakistani women to have low levels of serum
25-hydroxyvitamin D. There is a growing evidence of a strong association between
TB and Vitamin D deficiency.15
A prospective study was conducted by Shafi Ullah et al to assess its frequency in
various organ systems of the body and to evaluate the role of demographic factors
like sex and age in its causation. High female preponderance was noted with M: F
ratio of 1:2. Mean age was 35 years and 70% of the patients were in the age group 15-
45 years. Lymph modes were most common site of EPTB, involved in 66.4% of the
cases. They concluded that EPTB has high rates in females in their reproductive age.
The other likely socio-cultural factors could be high female illiteracy, female
economic dependency and their poor access to health care. Thus, in their
environments, female gender and age between 15-45 years are two important
predisposing factors for EPTB.16
Socio-economic condition and TB
Analytic epidemiological study showed women, non-Hispanic blacks, and HIV-
positive persons to have a significantly higher risk for extra pulmonary tuberculosis
than men, non-Hispanic whites, and HIV-negative persons.17 EPTB is reported to be
more often diagnosed in females and in young patients. Almost one-third of the
tuberculosis cases in Yemen were extra-pulmonary (28%) was associated with
poverty and that most of the extra pulmonary tuberculosis patients came from rural
areas.
Multivariate assessment of host factors showed that risk o TB was increased with
variation in occupational status. Assessment of environmental factors showed an
increased risk with household crowding, history of household exposure to a known
TB case, as well as amongst the Jola ethnic group.18
Smoking
Smokers incur a 2 to 4 fold increased risk of invasive respiratory disease. Perhaps the
greatest public health impact of smoking on infection is the increased risk of
tuberculosis, a particular problem in under developed countries where smoking rates
are increasing rapidly. 19 A higher proportion of culture confirmed TB cases was
found among ever smokers (current and ex-smokers) than never-smokers. Pulmonary
involvement was more prevalent among ever smokers than never smokers and the
reverse was true for extra-pulmonary involvement.20 Female and age were associated
with EPTB, while alcohol abuse, smoking habit, contact with PTB patients and BCG
vaccination had a protective effect. 21
Common sites of EPTB
Lymph node tuberculosis comprised the greatest number of EPTB Cases in almost all
studies.22-25 The central nervous system was the next most frequent site of EPTB
involvement, followed in descending order by skeletal, pleural, abdominal, cutaneous,
genitourinary, pericardial, miliary, and breast tuberculosis.23 Miliary tuberculosis
developed in infants, lymphadenitis and meningitis in preschool children, and pleural
effusion and skeletal tuberculosis in older children.24 The distribution of different
types of EPTB differed significantly among age groups. Meningeal and bone and or
joint TB were more commonly observed among the male patients, while lymphatic,
genitourinary, and peritoneal TB cases were more frequently seen among females. 25
Study 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
familiar to most of the Clinicians.26 Patients with bilateral lung involvement were
more likely to have extrapulmonary involvement, with an adjusted odds ratio (OR) of
4.21 (95% confidence interval [CI], 1.82-9.72), while patients with cavitary lesions
(adjusted OR, 0.37; 95% CI, 0.16-0.84), and with higher levels of serum albumin
(adjusted OR, 0.45; 95% CI, 0.25-0.78) had less frequent involvement. Clinicians
should be aware of the possibility of extrapulmonary involvement in TB patients with
bilateral lung involvement without cavity formation or lower levels of serum
albumin.27 Study suggests that in a significant number of patients with EPTB fever is
absent, ESR is normal and MT is negative. So, over reliance on these clinical and
laboratory data may lead to failure to diagnose EPTB.28
Age, education, income, occupation, race, sex, malnutrition (Vit D deficiency), HIV
positivity, diabetes, renal disease, drinking unpasteurized milk, 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. The present study
will also help us to gain insight into the demographic and social characteristics of
EPTB cases in Bangladesh thereby will extend the knowledgebase of EPTB based on
which better TB control strategies can be developed.
4. Materials and Methods
4.1 Study design
This will be a case control study
4.2 Study period
A total period of the study will be from January to June 2012.
4.3 Place of the study
DOTS centers of eighteen upazillas of Dhaka division.
4.4 Study population
Selection of cases and controls:
The samples will be classified as either EPTB (cases) or PTB(controls). Patients whose disease involved organs or tissues outside the thorax, excluding those patients who also had pulmonary involvement, are considered to have cases of extrapulmonary tuberculosis and will be classified as case patients. EPTB cases will encompass lymphatic,
genitourinary, bone and/or joint, meningeal, peritoneal, gastrointestinal, cutaneous
and unclassified cases. EPTB cases that will involve >1 EPTB disease site will be
classified according to the major site. Patients in whom the sites of disease is
exclusively intrathoracic, (i.e., confined to lungs, pleura, and intrathoracic lymph
nodes) are considered to have cases of pulmonary tuberculosis and will be classified
as control patients.
.Tuberculous pleuritis will not be classified as EPTB because pleura is believed to be
involved by direct invasion from frequently accompanying pulmonary parenchymal
TB or hypersensitivity reaction by M. tuberculosis rather than blood stream
dissemination.
Cases of disseminated TB and cases with concurrent EPTB-PTB will be excluded
from our principal analysis, because they are not distinctly classifiable as either EPTB
or PTB. In order to determine the possible ramifications of this definition of EPTB,
we will perform a separate analysis that will be compared disseminated and
concurrent EPTB-PTB with EPTB only and with PTB only. In addition, we will
perform a separate analysis in which disseminated and concurrent EPTB will be
added to our existing EPTB classification. The presence of extra-pulmonary
involvement in patients with pulmonary TB will be based on either of the following
criteria:
1) Demonstration of acid-fast bacilli or the growth of Mycobac-terium tuberculosis
from tissue;
2) Presence of granulomas with or without caseation necrosis in tissue;
3) Positive polymerase chain reaction (PCR) results for the DNA of M.
tuberculosis from tissues; or
4) A clinical diagnosis by duty physicians based on symptoms, laboratory,
radiographic findings, and treatment response to anti-TB medications.
Addresses of the cases and controls will be noted from the DOTS center registers
with a view to trace study subjects at home for exploration of exposure information.
4.5 Sample size
The study will enroll 294 people per group, for a total of 588 people. ( using SPSS
Sample power software; IBM). With this sample size, there is an 80% likelihood that
the study will yield a statistically significant result, and allow us to conclude that the
percentage of subjects in 'selected exposure' is different for PTB than for EPTB. The
sample size of 294 is based on the assumption that groups differ by 10 percentage
points. The test will be 2-tailed, which means that an effect in either direction will be
interpreted. Based on these same parameters and assumptions the study will enable us
to report the difference in proportions with a precision (95.0% confidence level) of
approximately plus/minus 0.07 points. Specifically, an observed difference of 0.10
would be reported with a 95.0% confidence interval of 0.03 to 0.17. In computing the
sample size to be 294 we assume that there will be no missing data. If the actual rate
of missing data is 2%, we would need a sample size of 300 per group. We used an
alpha of 0.05, which is often the default value, in computing the required sample size
of 294 per group.
4.6 Sampling technique
Convenient sampling technique 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. The cases and controls will be selected from DOTS
treatment registers who enrolled in the last 5 months and meet the selection criteria.
4.7 Data collection instrument
Data collection instruments will be a pre-tested structured questionnaire and a check
list.
4.8 Data collection technique
Firstly an official letter will be issued from MBDC to the UH&FO of the selected
upazillas with a copy to Civil Surgeon of the corresponding district informing the
study purpose. Another letter will be sent to the executives of the BRAC and Damien
foundation requesting necessary assistance in the field. Six data collectors will be
trained on several setting before collecting data. They will be guided and assisted by
the local NGO program officer and GOV assigned Tuberculosis and Leprosy Clinic
Assistant (TLCA). Data will be collected through face to face interview of the
household at their residence by using the questionnaire. Addresses of the respondents
will be taken from the DOTS centers treatment registers with a view to trace study
subjects at home for exploring exposure information. Before the interview, the detail
of the study will be explained to the eligible respondents. Informed verbal consent
will be obtained from every respondent and interviews will be held in private. The
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. To ensure quality 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 make regular on-
site field checks. In addition, all the questionnaires will be checked for consistency
and completeness by the investigators. A subset of questionnaires will be re-checked
in the field for validity.
4.9 Data processing and analysis
After data collection, each questionnaire will be checked for completeness and
consistency. The data will be entered into computer with the help of Software
“Statistical Package for Social Sciences” (SPSS) for windows version 19.0.
Univariate comparisons between the group with pulmonary TB and the group with
extrapulmonary involvement will be performed using Pearson’s chi-square test or
Fisher’s exact test for categorical variables and Student’s t-test for continuous
variables. Using variables with p values of <0.20 from the univariate comparisons,
multiple logistic regression models will be constructed to identify predictors of the
presence of extra pulmonary involvement. In logistic regression, backward
elimination will be used to select variables to be maintained in the final model, using
a p value of <0.05 as the criterion for statistical significance of associations. The area
under the receiver operator characteristic (ROC) curve will be used to evaluate the
performance of the models. Adjusted odds ratios and 95% CI will be reported.
Study factors
Key variables
Sociodemographic variable
AgeSexReligionEducation of the respondentOccupation of the respondentParent’s educationParent’s occupationAverage monthly IncomeTotal family membersFamily typeFamily mobilityResidence typeArea of residence
Household characteristics
House ownershipFloor materialWall materialRoof materialNo of bedroomsArea of bedroomsCrowdingNo of external windowsWindow materialWindow Opening statusType of latrineDrinking water sourceSource of lighting
Kitchen environment
Kitchen positionKitchen distanceKitchen ventilationStove typeFuel typeCooking time
Contact information
Type of contactContact relationContact regularityFrequency of contact
Lifestyle related variables
Smoking statusNo. of smoker in the familySharing same room with smokerSharing same bed with smokerTime of start smokingTime of quit smokingNo of sticks smoked per dayNonsmoking tobacco useAddiction type
Disease related variables
Type of TBType of symptomsSite of extrapulmonary TBTime of first appearance of symptomsMethod of diagnosisTime of DiagnosisPlace of diagnosisSmear test result
Miscellaneous
BCG vaccinationFood security status
5. Utilization of results/ policy implications
The present study will be conducted to gain insight into the demographic and social
characteristics of EPTB cases in Bangladesh thereby will extend the knowledgebase
of EPTB based on which better TB control strategies can be developed.
6. Facilities
(Resources, equipment, chemicals, subjects (human, animal) etc. Required for the
study):
6.1. Facilities Available
Infra-structure of government health service centre will be used for management of
the research project. In addition, the institutional facilities of the principal investigator
and co-investigators will be used for conduction of the study.
6.2. Additional Facilities Required
Manpower: - Two research Officer,
- Six data collectors
7. Approval of the Head of the Department/Institute
Approved
8. Flow chart
Study period: 1st Week of January to 4th Week of June; 2013-2014
SL no
Activities Period of studyMonth January February March April May JuneWeek 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4
1 Proposal Development and acceptance
2 Literature Review
3 Selection of study area
4 Planning and Designing
5 Preparation of Research Instrument
6 Pre Test
7 Data Collection
8 Data Analysis, Interpretation
9 Report Writing
10 Report Submission
9. Ethical considerations
Prior conducting the study, ethical clearance will be taken from the NIPSOM Ethical
Review Committee. 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.
10. Dissemination policy
With the proper permission of funding agency the study findings will be disseminated
through seminar and discussion meeting with policy makers. Attempts will also be
taken to publish the data in international journals.
References
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4. Tuberculosis in the South-East Asia Region- The Regional Report: 2008, WHO Project No : SE ICP TUB. New Delhi.
5. Herchline TE. Tuberculosis. http://emedicine.medscape.com/article/230802-overview.
last updated 9 Dec; 2011.
6. World Health Organization (WHO). SEARO: Tuberculosis Control in the South East Asia Region. WHO report 2009.
7. Tuberculosis Control in Bangladesh, Annual Report 2008,NTP.
8. American Thoracic society: Diagnostic Standards and classification of tuberculosis in adults and children. Am J Respir Crit Care Med 2000; 161:1376-95.
9. Guideline, National Tuberculosis control Programme, Bangladesh, 4th edition.
10. World Health Organization (WHO). SEARO: Tuberculosis Control in the South east Aswia Region. WHO report 2008.
11. Sreeramareddy CT, Panduru KV, Verma SC, Joshi HS and Bates MN. Comparison of pulmonary and extra-pulmonary tuberculosis in Nepal- a hospital based retrospective study. BMC Infec Dis 2008 Jan; 248:8.
12. Al-Otaibi F and El Hazmi MM. Extra-pulmonary tuberculosis in Saudi Arabia. Indian J Pathol Microbiol. 2010 Apr-Jun;53(2):227-31.
13. Forssbohm M, Zwahein M, Loddenkemper R and Rieder H.L. Demographic characteristics of patients with extrapulmonary tuberculosis in Germany. Euro Respir J 2007; 31(1): 99-105.
14. Cailhol j, Decludt B and Che D. Sociodemographic factors that contribute to the development of extrapulmonary tuberculosis were identified. Journal of Clinical Epidemiology 58 (2005) 1066–1071.
15. Chandir S , Hussain H, Salahuddin N, Amir M, Ali F, Lotia I and Khan AJ. Extrapulmonary tuberculosis: a retrospective review of 194 cases at a tertiary care hospital in Karachi, Pakistan. J Pak Med Assoc. 2010 Feb;60(2):105-9.
16. Ullah S, Shah SH, Rehman AU. Kamal A, Begum N and Khan G. Extra-pulmonary tuberculosis in Lady Reading Hospital Peshwar, NWFP, Pakistan: Survey of biopsy results. J Ayub Med Coll Abbottabad. 2008 Apr-Jun; 20(2): 43-6.
17. Yang Z, Kong Y, Wilson F, Foxman B, Fowler B, Fowler AH, Marrs CF, Cave MD and Bates JH. Identification of risk factors for extra-pulmonary tuberculosis. Clin Infect Dis 2004;38:199-205.
18. Hill P, Sillah DJ, Donkor SA, Out J, Adegbola RA and Lienhardt C. Risk factors for pulmonary tuberculosis: a clinic based case control study in The Gambia, BMC Public Health 2006;6:156.
19. Arcavi L, Neal L and Benowitz MD. Cigarette smoking and infection.2004;164:2206-2216.
20. Leung CC, Li T and Lam TH et al. Smoking and tuberculosis among elderly in Hong Kong. Am J Respir Crit care Med 2004; 170: 1027-1033.
21. Garcia-Rodrigueza JF, Alvarez-Diaza H, Lorenzo-Garciab MV, Mari˜no-Callejoa A, Fernandez-Rialc A and Sesma-Sanchezc P. Extrapulmonary tuberculosis: epidemiology and risk factors Enferm Infecc Microbiol Clin. 2011;29(7):502–509.
22. Ilgazli A , Boyaci H, Basyigit I and Yildiz F. Extrapulmonary tuberculosis: clinical and epidemiologic spectrum of 636 cases. Arch Med Res. 2004 Sep-Oct;35(5):435-41.
23. Fader T, Parks J, Khan N, Manning R, Stokes S and Nasir NA. Extrapulmonary tuberculosis in Kabul, Afghanistan:A hospital-based retrospective review. International Journal of Infectious Diseases. 2010;14, e102—e110
24. Maltezou H C, Spyridis P and Kafetzis D A. Extra-pulmonary tuberculosis in children.Arch Dis Child 2000;83:342–346.
25. Gunal S, Yang Z, Agarwal M, Koroglu M, Kazgan Z and Durmaz R. Demographic and microbial characteristics of extrapulmonary tuberculosis cases diagnosed in Malatya, Turkey, 2001-2007. BMC Public Health 2011, 11:154.
26. Othman GQ, Ibrahim MIM and Rajaa YA. Comparison of clinical and sociodemographical factors in pulmonary and extrapulmonary tuberculosis patient in Yemen.Journal of Clinical and Diagnostic Research. 2011 April, Vol-5(2):191-195.
27. Kim MJ, Kim HR, Hwang SS, Kim YW, Han SK, Shim YS, and Yim JJ. Prevalence and Its Predictors of Extrapulmonary Involvement in Patients with Pulmonary Tuberculosis. J Korean Med Sci. 2009; 24: 237-41.
28. Hussain MW, Haque MA, Banu SA, Ekram SA and Rahman MF. Extrapulmonary Tuberculosis: Experience in Rajshahi Chest Disease Clinic and Chest Disease Hospital. The Journal of Teachers Association, RMC, Rajshahi. TAJ 2004; 17(1) : 16-19.
PART – DBudget
I. Total Budget: Tk 500, 000 (Five lacs only)Sl. No. Item
Unit cost Number
Months/ times BDT Sub-total
1 Personnel cost 1.1 Principal Investigator (PI) 5000 1 6 30000 1.2 Co-Investigator (Co-I) 4000 2 4 32000 1.3 Research Officer (RO) 12000 2 3 72000 1.4 Support Staff (MLSS) 1000 1 6 6000 140000
2 Field Expenses 2.1
Honorarium for Resource Person for Training of RO, Volunteers
450
3
3
4050
and data collectors 2.2 Cost of Data Collection 6000 6 2 72000 2.3 Local supervision cost 1000 4 3 12000 2.4 Compensation for research 150 600 1 90000 Participants 178050
3 Supplies and Materials Not Applicable 4 Patient Cost Not Applicable
5Travel Cost
5.1 Non-local field cost for PI & Co-I 3000 3 1 9000 5.2 Non-local field cost for RO 1000 1 4 4000 5.3 Local field cost for PI & Co-I 300 3 20 18000
5.4Local field cost for RO/ Data collectors 150 1 100 15000 46000
6 Office Stationeries 6.1 Toner 6000 1 1 6000 6.2 Offset paper 500 6 1 3000
6.3Bag/Pen/pencil/eraser/measuring tape/ umbrella etc.
Lump sum 14000 23000
7 Data processing and computer charges
7.1 Data entry, coding, cleaningLump sum 25000
7.2 Data analysisLump sum 25000 50000
8 Printing and reproduction/dissemination
8.1 Printing of questionnaireLump sum 6,000
8.2 Report preparation/ printingLump sum 12000
8.3 PhotocopyLump sum 6000 24000
9 9.1 DisseminationLump sum 10000 10000
10Miscellaneous (Telephone, internet, postage etc.) 8950 8950
11 VAT & Income Tax (4%) 20000 20000Grand Total BDT 500000.00
[Taka five lacs only]
National Institute of Preventive and Social Medicine Directorate General of Health Services
Application for Ethical Clearance
1. Principal Investigator(s): Dr. Md. Anisur Rahman
Professor & Head, Dept. of Epidemiology.National Institute of Preventive and Social Medicine (NIPSOM)
2. Co-Investigator(s): Dr. Md. Rizwanul KarimAsst. Professor, Department of Epidemiology, NIPSOM
Dr. Ummul Khair AlamMedical Officer, Population Dynamics,NIPSOM.
3. Place of the Study/Institution(s): Sixteen Upzilla DOTS centers
4. Title of Study: Predicting risk indicators for Pulmonary and Extra-pulmonary Tuberculosis in rural areas
5. Type of Study: Case control study
6. Duration: 6 (six) Months
7. Total Cost: Tk.500,000/=
8. Funding Agency: Bangladesh Medical Research Council (BMRC)
Circle the appropriate answer to each of the following (If not Applicable write NA)
1. Source of Population :
(a) Ill Subjects Yes No
(b) Non* Ill Subjects Yes No
(c) Minors or persons Yes No under guardianship
2. Does the study involve :
(a) Physical risks Yes No to the subjects
(b) Social Risks Yes No
(c) Psychological Yes No risks to subjects
(d) Discomfort to Yes No subjects
(e) Invasion of the Yes No body
(f) Invasion of Yes No Privacy
(g) Disclosure of Yes No information damaging to
subject or others
3. Does the study involve :
(a) Use of records, Yes No (hospital, medical, death, birth or other)
(b) Use of fetal tissue Yes No or abortus
(c) Use of organs or Yes No body fluids
4. Are subjects clearly informed about:
(a) Nature and Yes No purposes of study
(b) Procedures to be Yes No followed including
alternatives used
(c) Physical risks Not applicable
(d) Private questions Yes No (e) Invasion of the Not applicable Body
(f) Benefits to be Yes No derived
(g) Right to refuse Yes No to participate or to withdraw from study
(h) Confidential Yes No handling of data
(i) Compensation Yes No where there are risks or
loss of working time or privacy is involved in any particular procedure
5. Will signed consent form/verbal consent be required :
(a) From Subjects Yes No
(b) From parent or Not applicable guardian (if subjects
are minors)
6. Will precautions be Yes No taken to protect
anonymity of subjects
The Ethical Review Committee (ERC)
TB remains one of the leading causes of adult mortality and morbidity in Bangladesh that
causing persistent crisis in health and development. Bangladesh ranks sixth among higher
TB burden countries where extra-pulmonary TB patients were 12% of all TB cases in
2008. Age, education, income, occupation, race, sex, malnutrition (Vit D deficiency),
HIV positivity, diabetes, renal disease, drinking unpasteurized milk, all are thought to be
important predictors of extra-pulmonary tuberculosis. A case control study will be
conducted in eighteen upazillas of Dhaka division. A total of 588 samples (294 cases and
294 controls) will be recruited from the treatment register of the DOTS centers of the
selected upazillas. Sociodemographic and disease profile will be collected by a
interviewer administered semistructured questionnaire. Before the interview, the detail of
the study will be explained to the eligible respondents. Informed 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 And will lead policymakers adopting targeted strategies to prevent it and decrease its national burden.
Documents submitted herewith to committee:
Umbrella proposal
Proposal Summary
Abstract for Ethical Review Committee as per attachment
Informed consent form for subjects
Procedure for maintaining confidentiality
Interview schedule and checklist
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.
Principal Investigator Other Investigator (s)
Predicting risk indicators for Pulmonary and Extra-pulmonary
Tuberculosis in rural areasThese issues will be kept in concern while conducting research process:
1. Any group whose ability to give voluntary informed consent assumes questionable will not be included
2. No potential risks exists in designing this study3. By following under mentioned steps confidentiality will be maintained:
Research data will be coded Data will be stored in a locked cabinets Only research personnel will be allowed to access data. There is no physical, psychological, social and legal risk. During physical examination, proper consent will be taken. For safeguarding confidentiality and protecting anonymity each of the patient will be given
a special ID no. A signed informed consent will be taken from the patient/patient’s guardians convincing
that privacy of the patient will be maintained and he/she will be compensated for loss of work time if they wants
A data collection sheet should (enclosed) be prepared for which a short interview of 25-30 minutes will be required
No drug will be used for this study No experimental new drug will be administrated No placebo will be used here Use of hospital records (outdoor) will be needed to fill up the patient’s data sheet.
4. Consent form will be a written statement5. A brief interview regarding study variables will be collected from the participants.6. The study result will accrue the benefit to the society by providing information regarding
exploration and identification of important risk factors and their distribution among pulmonary and extra-pulmonary tuberculosis cases in rural areas of Bangladesh.
7. No experimental drug, placebo will be used.
Principal Investigator
INFORM CONSENT FORM FOR SUBJECTS
Title of research study: Predicting risk indicators for Pulmonary and Extra-pulmonary Tuberculosis in rural areas-----------------------------------------------------------------------------------------------Name of Participant:-----------------------------------------------------------------------------------------------Name of Investigator:
-----------------------------------------------------------------------------------------------
1. I consent to participate in the research titled “Predicting risk indicators for Pulmonary and Extra-pulmonary Tuberculosis in rural areas”, the particulars of which-including details of interviews and questionnaires have been explained to me. A written copy of the information has been given to me to keep.
2. I authorize the researcher to use with me the interviews and questionnaires referred to under (1) above.
3. I acknowledge that:a. The possible effects of the interviews and questionnaires have been explained to
me to my satisfactionb. I have been informed that I am free to withdraw from the research at any time
without explanation or prejudice and to withdraw any unprocessed data previously supplied;
c. The project is for the purpose of research d. I have been informed that the confidentiality of the information I provide will be
safeguarded subject to any legal requirementse. I have been informed regarding the interviews. I have also been informed that
because of the number of people to be interviews is small; 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. However, I will be referred by pseudonym or identified by a different name in any publications arising from the research.
Signature Date-----------------------------------------------------------------------------------------
(Participant)
Signature Date-----------------------------------------------------------------------------------------
(Witness to consent)
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