Abstract

BackgroundDrug-resistant tuberculosis (TB) is a major threat to global public health. Patients with extensively drug-resistant TB (XDR-TB), particularly those with HIV-coinfection, experience high and accelerated mortality with limited available interventions. To determine modifiable factors associated with survival, we evaluated XDR-TB patients from a community-based hospital in rural South Africa where a large number of XDR-TB cases were first detected.Methodology/Principal FindingsA retrospective case control study was conducted of XDR-TB patients diagnosed from 2005–2008. Survivors, those alive at 180 days from diagnostic sputum collection date, were compared with controls who died within 180 days. Clinical, laboratory and microbiological correlates of survival were assessed in 69 survivors (median survival 565 days [IQR 384–774] and 73 non-survivors (median survival 34 days [IQR 18–90]). Among 129 HIV+ patients, multivariate analyses of modifiable factors demonstrated that negative AFB smear (AOR 8.4, CI 1.84–38.21), a lower laboratory index of routine laboratory findings (AOR 0.48, CI 0.22–1.02), CD4>200 cells/mm3 (AOR 11.53, 1.1–119.32), and receipt of antiretroviral therapy (AOR 20.9, CI 1.16–376.83) were independently associated with survival from XDR-TB.Conclusions/SignificanceSurvival from XDR-TB with HIV-coinfection is associated with less advanced stages of both diseases at time of diagnosis, absence of laboratory markers indicative of multiorgan dysfunction, and provision of antiretroviral therapy. Survival can be increased by addressing these modifiable risk factors through policy changes and improved clinical management. Health planners and clinicians should develop programmes focusing on earlier case finding and integration of HIV and drug-resistant TB diagnostic, therapeutic, and preventive activities.

Highlights

  • Drug-resistant tuberculosis (TB) has emerged as a major threat to global public health

  • Among 129 HIV+ patients, multivariate analyses of modifiable factors demonstrated that negative acid-fast bacilli (AFB) smear (AOR 8.4, Crude Odds Ratio (CI) 1.84–38.21), a lower laboratory index of routine laboratory findings (AOR 0.48, CI 0.22–1.02), CD4.200 cells/mm3 (AOR 11.53, 1.1–119.32), and receipt of antiretroviral therapy (AOR 20.9, CI 1.16–376.83) were independently associated with survival from XDR-TB

  • XDR-TB has since been reported throughout South Africa [2], in neighboring sub-Saharan African countries and in 58 countries worldwide [3] and jeopardizes both TB and antiretroviral therapy (ART) treatment programmes globally [4]

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Summary

Introduction

Drug-resistant tuberculosis (TB) has emerged as a major threat to global public health. In 2006, a large number of cases of extensively drug-resistant tuberculosis (XDR-TB), newly defined as resistance to isoniazid, rifampin, any fluoroquinolone and an injectable antimicrobial agent (kanamycin, amikacin, or capreomycin), were reported from a district hospital in Tugela Ferry, a rural site in KwaZulu Natal province, South Africa [1]. 53 XDR-TB cases were characterized by HIV-coinfection with accelerated and near-complete (98%) mortality; median survival from sputum collection was 16 days [1]. Drug-resistant tuberculosis (TB) is a major threat to global public health. Patients with extensively drugresistant TB (XDR-TB), those with HIV-coinfection, experience high and accelerated mortality with limited available interventions. To determine modifiable factors associated with survival, we evaluated XDR-TB patients from a community-based hospital in rural South Africa where a large number of XDR-TB cases were first detected

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