Diagnosis and Prevention of Active TB Disease Restricted; Files Only

Malik, Amyn (Fall 2019)

Permanent URL: https://etd.library.emory.edu/concern/etds/tb09j686b?locale=es
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Abstract

Tuberculosis (TB) is an infectious disease that results in over 10 million cases each year. One million of these cases occur in children with 25% (250,000) dying from TB. More than 80% of the deaths occur in children younger than 5 years old and nearly all of them (96%) were not receiving treatment. One of the main reasons for children not being on treatment is under-diagnosis due to poor performance of available diagnostic tools in children. Another group at high risk of developing active TB disease is household contacts of TB patients. Unfortunately for contacts exposed to drug-resistant TB at home, there is no consensus on the use of preventive treatment.

In Aim 1, we attempted to validate the use of monocyte-lymphocyte ratio (MLR) as a tool for TB diagnosis in children and created a risk score to improve diagnosis. We pooled data from Vietnam, Cameroon, South Africa and Kenya for our analysis. Using multivariable logistic regression with ROC curve analysis, we created an internally validated risk score for diagnosis of active TB disease in children. 

In Aim 2, we estimated the effectiveness of fluroquinolone-based preventive treatment for drug-resistant TB exposure in household contacts. We used follow-up data from a cohort of household contacts in Pakistan that received preventive treatment. We estimated the counterfactual risk in these contacts based on reports from the literature to assess the effectiveness. We found a substantial reduction in risk of active TB disease in contacts who received preventive treatment.

In Aim 3, we identified risk factors for adverse events in household contacts receiving fluoroquinolone-based preventive treatment. We used survival analysis methods for recurrent events for our analysis using the data from Pakistan. We found preventive treatment to be safe with low incidence of adverse events with better tolerability in younger children.    

In conclusion, we derived a risk score for diagnosis of active TB disease in children and found preventive treatment for drug-resistant TB exposure to be safe and effective. Household contacts of drug-resistant TB patients including children, who are free of active TB disease after evaluation, should be offered preventive treatment. 

Table of Contents

CHAPTER 1: Background and Dissertation Aims…………………1

CHAPTER 2: Use of a blood-based bio-marker and risk score for the diagnosis of tuberculosis disease in children – a multi-country study…………… 26

CHAPTER 3: TB Preventive Therapy for individuals exposed to drug-resistant tuberculosis: feasibility and safety of a community-based delivery of fluoroquinolone-containing preventive regimen……55

CHAPTER 4: Effectiveness of fluoroquinolone-based preventive treatment for persons exposed at home to drug-resistant tuberculosis…81

CHAPTER 5: Risk factors for adverse events in household contacts prescribed preventive treatment for drug-resistant TB exposure………107

CHAPTER 6: Research summary, public health implications and future directions………………..129

REFERENCES………………………………………………………………………………………136

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