Adverse Reactions Due to Directly Observed Treatment Strategy Therapy in Chinese Tuberculosis Patients: A Prospective Study

Xiaozhen Lv,Siyan Zhan,Ru Chen,Xiaomeng Wang,Dehua Tu,Feiying Liu,Shaowen Tang,Yuan Zhang,Yinyin Xia,Daiyu Hu,Peiyuan Deng,Zhirong Yang,Yu Ma,Shanshan Wu,Yixin Chen,Yanli Yuan

doi:10.1371/journal.pone.0065037

Abstract

BackgroundMore than 1 million tuberculosis (TB) patients are receiving directly observed treatment strategy (DOTS) therapy in China every year. As to the profile of adverse drug reactions (ADRs) due to DOTS therapy, no consensus has been reached. There is no report regarding ADRs due to DOTS therapy with a large Chinese TB population. This study aimed to determine the incidence and prognosis of ADRs due to DOTS therapy, and to evaluate their impact on anti-TB treatment in China.MethodsA prospective population-based cohort study was performed during 2007–2008. Sputum smear positive pulmonary TB patients who received DOTS therapy were included and followed up for six to nine months in 52 counties of four regions in China. The suspected ADRs were recorded and reviewed by Chinese State Food and Drug Administration.ResultsA total of 4304 TB patients were included in this study. 649 patients (15.08%) showed at least one ADR and 766 cases in total were detected. The incidence (count) of ADR based on affected organ was: liver dysfunction 6.34% (273), gastrointestinal disorders 3.74% (161), arthralgia 2.51% (108), allergic reactions 2.35% (101), neurological system disorders 2.04% (88), renal impairment 0.07% (3) and others 0.05% (2). Most cases of ADRs (95%) had a good clinical outcome, while two with hepatotoxicity and one with renal impairment died. Compared with patients without ADRs, patients with ADRs were more likely to have positive smear test results at the end of the intensive phase (adjusted OR, 2.00; 95%CI, 1.44–2.78) and unsuccessful anti-TB outcomes (adjusted OR, 2.58; 95%CI, 1.43–4.68).ConclusionsThe incidence of ADRs due to DOTS therapy was 15.08%. Those ADRs had a substantial impact on TB control in China. This highlighted the importance of developing strategies to ameliorate ADRs both to improve the quality of patient care and to control TB safely.

Highlights

Tuberculosis (TB) continues to be a major cause of morbidity and mortality worldwide, with 8.7 million new cases of TB and 1.4 million people died from TB globally in 2011 [1]
In order to control the TB epidemic, China established China National Tuberculosis Prevention and Control Scheme in 1990 and has implemented directly observed treatment strategy (DOTS) therapy since 1991, which is the cornerstone of the current strategy for TB control and covers the entire population of China [2,3]
Despite the positive therapeutic effects, studies have shown that utilization of multidrug regimens can cause undesirable adverse drug reactions (ADRs) of varying degrees of severity, such as hepatotoxicity, gastrointestinal disorders, allergic reactions, arthralgia, neurological disorders and so on [5,6,7,8,9,10,11,12,13,14,15,16]

Summary

Introduction

Tuberculosis (TB) continues to be a major cause of morbidity and mortality worldwide, with 8.7 million new cases of TB and 1.4 million people died from TB globally in 2011 [1]. ADRs are regarded as one of the major causes of non-adherence to anti-TB treatment [18]. ADRs may eventually contribute to the extension of treatment duration, final termination, drug resistance and treatment failure [19]. It may increase the number of TB cases, and more rarely the number of deaths, posing a challenge to the management of TB patients and TB control. More than 1 million tuberculosis (TB) patients are receiving directly observed treatment strategy (DOTS) therapy in China every year. This study aimed to determine the incidence and prognosis of ADRs due to DOTS therapy, and to evaluate their impact on anti-TB treatment in China

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