Analysis of Relationship between Participant Characteristics and Phenotypic Resistance to Second-Line Anti-Tuberculosis Drugs in KwaZulu-Natal, South Africa Restricted; Files Only

Ripper, Nicholas (Spring 2023)

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Background: Resistance to second-line drugs used to drug-resistant tuberculosis (SLDR-TB) is a public health threat in South Africa, both because of its severity and the difficulty of successful treatment. Although studies have examined risk factors of second-line drug resistance, most this work has been on older second-line regimens and little is known about newer medications and regimens. We therefore examined risk factors for resistance to second-line drugs (capreomycin, moxifloxacin or levofloxacin, linezolid, bedaquiline, and clofazimine) in the province of KwaZulu-Natal, South Africa from 2018-2022, when more current second-line regimens were being used.

Methods: Phenotypic drug-susceptibility testing (pDST) for each second-line drug was performed on M. tuberculosis isolates from individuals with SLDR-TB in KwaZulu-Natal, and participant characteristics were recorded for individuals within a subregion of the province. We calculated unadjusted odds ratios for sex and age with resistance to each drug for all study participants and unadjusted and adjusted odds ratios for sex, age, HIV status, alcohol use, and income for individuals within the subregion using binary logistic regression. We also assessed interaction between these variables and previous DR-TB treatment.

Results: Among participants in the entire study population (n=580) and within the subregion of interest (n=189), resistance varied across different second-line drugs. None of the exposures of interest were associated with resistance to any second-line drugs, and there was no significant interaction between previous treatment for DR-TB and the exposures.

Discussion: While we could not identify an association between the risk factors of interest with phenotypic resistance to second-line TB drugs, this may have been the result of the parent study population or because most resistant TB in KwaZulu-Natal is transmitted rather than acquired. Future studies could build on this work by examining the association of risk factors with resistance to other second-line drugs and focusing on differing effects between individuals with acquired and transmitted SLDR-TB.

Table of Contents

Chapter I: Background on Drug-Resistant Tuberculosis (DR-TB), Including Extensively Drug-Resistant Tuberculosis (XDR-TB), Worldwide and in South Africa 1

Part I: Tuberculosis, Its Drug-Resistant Forms, and Its Global Public Health Importance 1

Part II: Genetic Mechanisms of Second-Line Drug Resistance 4

Part III: Risk Factors for Second-Line Drug Resistance 4

Part IV: Diagnosis of Second-Line Drug Resistance 7

Part V: Treatment of DR-TB 7

Part VI: Pre-XDR-TB and XDR-TB in the Context of South Africa 8

Part VII: Gaps in the Literature and Study Aims 10

Chapter II: Analysis of Relationship between Participant Characteristics and Phenotypic Resistance to Second-Line Anti-Tuberculosis Drugs in KwaZulu-Natal, South Africa 12

Introduction 12

Methods 14

Results 19

Discussion 23

Chapter III: Public Health Implications 28

Figures and Tables 31

Appendix I: Supplementary Figures and Tables 40

Appendix II: Supplementary Methods 44

Appendix III: Example Thesis Code 60

References 72

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