Tuberculosis Research of INA-RESPOND On Drug Resistance

Study Overview
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Brief Summary
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This study is a prospective observational cohort study of TB patients who are treated or evaluated at 10 study sites. Patients presenting with cough for 2 weeks or longer with at least one additional TB symptom and a chest X-ray suggestive of TB, will be invited to be enrolled in the study. The signed informed consent will designate their willingness to participate on this study.

Detailed Description
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This study is a prospective observational cohort study of TB patients who are treated or evaluated at 10 study sites. Patients presenting with cough for 2 weeks or longer with at least one additional TB symptom and a chest X-ray suggestive of TB, will be invited to be enrolled in the study. The signed informed consent will designate their willingness to participate on this study. Enrolled subjects will produce the sputum for bacteriological examination of M. tuberculosis by AFB, culture and Xpert. The sputum will also be tested by Xpert for drug resistance test. If the culture is positive, conventional DST will be performed, and M. tuberculosis isolates will be stored for spoligotyping and for future research on TB. All bacteriologicaly confirmed subjects will be followed for outcome assessment. For all enrolled subjects chest X-ray results, demographic data, TB co-morbidities, symptoms, nutritional status, treatment regimens, compliance and outcome will be collected. In addition, sputum, blood and urine will also be collected for storage. To estimate the proportion of MDR-TB amongst new and previously treated TB cases. To evaluate accuracy of clinical diagnosis by comparing clinically defined TB to laboratory confirmed TB. To compare AFB and Xpert MTB/RIF as TB diagnostic tests against culture result. To estimate the sensitivity and specificity of Xpert MTB/RIF in detecting Rif susceptibility against DST. To estimate the proportion of cured, completed, failed, died and lost to follow up as treatment outcomes on DS-TB and DR-TB cases To evaluate the association of treatment success (cured or completed) with the following data: Demographics (age, sex) TB contact history Smoking habit Treatment seeking behavior Co-morbidities (HIV, DM) Primary and secondary drug resistance Symptoms Cavitary disease Nutritional status Treatment regimens Patient reported compliance Numbers of bacteria by AFB test TB strains (e.g Beijing)

Official Title
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Tuberculosis Research of INA-RESPOND On Drug Resistance

Conditions
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Lung Tuberculosis, MDR TB

Intervention / Treatment
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* Other: No Intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients suspected of having pulmonary TB Cough ≥ 2 weeks At least one other TB clinical symptom Fever Unexplained weight loss Loss of appetite Hemoptysis Shortness of breath Chest pain Night sweats Fatigue Suggestive TB on chest x-ray based on pulmonologist or internist consultant of pulmonology opinion Age ≥ 18 years' old Willing to be treated or evaluated at study site Willing to have specimens stored for use in future studies Patient denies having TB treatment for more than 7 days in the last 1 month (30 days). Exclusion Criteria: Pregnancy or any serious condition includes, but not limited to, liver disease, chronic kidney disease, and psychiatric illness that might interfere with study compliance (based on the clinician judgment).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Other: No Intervention|No Intervention|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reporting the rate of MDR-TB amongst new and retreated TB cases. | Proportions of MDR will be estimated, along with exact 95% confidence intervals based on a binomial distribution | 4.5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reporting the treatment outcomes (cured, failed, died, treatment completion, and lost to follow up) | Proportions of subjects within each category as mentioned below: cured: number of subjects who have smear or culture negative in the last month of treatment and on at least one previous occasion. failed: number of subjects who have sputum smear or culture is positive at month 5 or later during treatment died: number of subjects who died from any cause during treatment treatment completion: number of subjects who have completed treatment without evidence of failure but with no records to show that sputum smear or culture negative in the last month of treatment and on at least one previous occasion were negative, either because tests were not done or results are unavailable lost to follow up: number of subjects who have did not start treatment or treatment was interrupted for two consecutive months or more. | 4.5 years | 
| Reporting the protective factors for treatment success. | Reporting the protective factors for treatment success (cured or completed treatment vs failed or died or loss to follow up) with logistic regression models will be estimated to describe associations of treatment success with these protective factors. Protective factors below will be collected by interview with the subject and this information will be captured in the medical record: a. Record the subject's data demographics (age, sex), TB contact history, smoking habit, treatment seeking behavior, co-morbidities (HIV, DM), primary drug resistance, symptoms, no cavity in the lung, nutritional status, treatment regimens, bacteria and TB strains (e.g., Beijing). Logistic regression models will be estimated to describe associations of treatment success with these protective factors. | 4.5 years | 
| Reporting the risk factors of treatment interruption (loss to follow up vs other treatment outcome). | Reporting risk factors of treatment interruption (loss to follow up vs other treatment outcome). Reporting the risk factors of treatment interruption (loss to follow up vs other treatment outcome). Risk factors below will be collected by interview with the subject and this information will be captured in the medical record: the subject's demographics (age, sex), the number of subjects with TB contact history, smoking habit, treatment seeking behavior, co-morbidities (HIV, DM), primary drug resistance, symptoms, cavity in the lung, nutritional status, treatment regimens, compliance, numbers of bacteria and TB strains (e.g., Beijing). Logistic regression models will be estimated to evaluate associations of treatment interruption with these risk factors. | 4.5 years | 
| Reporting how many percent clinically defined TB subjects compare to bacteriologically confirmed TB (AFB, X-pert, sputum culture). | Record the number of subject has clinically diagnosed TB. The physician categorized subjects as clinically TB when they have cough >= 2 weeks, have at least 1 other TB symptoms (fever, unexplained weight loss, loss of appetite, hemoptysis, shortness of breath, chest pain, night sweats, fatigue) and suggestive TB on chest x-ray based on pulmonologist or internist consultant of pulmonologist opinion. The number of subject laboratory confirmed TB with positive Mtb result on AFB, and/or X-pert, and/or sputum culture. The number of subject laboratory confirmed TB with positive AFB, Xpert and sputum culture result with Mtb bacteria. | 4.5 years | 
| Measuring the sensitivity and specificity of AFB and Xpert MTB/RIF relative to culture results. | Measuring the sensitivity AFB or Xpert MTB/RIF relative to sputum culture result: Number of subjects who have positive AFB and/or Xpert MTB/Rif result whose culture positive divide with subjects who have positive AFB and/or Xpert MTB/Rif result whose culture positive plus subjects who have negative AFB and/or Xpert MTB/Rif result whose culture positive. Measuring the specificity of AFB or Xpert MTB/RIF relative to sputum culture result: The number subjects with negative AFB and/or Xpert MTB/RIF that are also negative Mtb sputum culture divide with number subjects with negative AFB and/or Xpert MTB/RIF that are also negative Mtb sputum culture plus number subjects with negative AFB and/or Xpert MTB/RIF positive Mtb sputum. Sensitivity and specificity will be estimated along with 97.5% confidence intervals. McNemar's statistic will test whether the sensitivity and specificity differ between AFB and Xpert MTB/RIF. | 4.5 years | 
| Measuring sensitivity and specificity of Rif susceptibility results in Xpert MTB/RIF against result in DST as gold standard along with 97.5% confidence intervals. | Measuring the sensitivity Rif susceptibility results in Xpert MTB/RIF relative to sputum culture result: Number of subjects who have resistant to Rif in Xpert MTB/RIF that are also show resistancy on DST divide subjects who have resistant to Rif in Xpert MTB/RIF that also show resistancy on DST plus subjects with sensitive on Rif in Xpert MTB/RIF whose DST show resistancy 100% relative to sputum culture result: The number of subjects with sensitive of Rif in Xpert MTB/RIF that are also show no resistancy on DST divide subjects who sensitive to Rif in Xpert MTB/RIF that show no resistancy on DST plus subjects with sensitive to Rif in Xpert MTB/RIF whose DST show resistancy. | 4.5 years |