High frequency of drug-resistant TB in HIV clinics in India

Alarming levels of drug-resistant tuberculosis in HIV-infected patients in metropolitan Mumbai, India.

Isaakidis P, Das M, Kumar AM, Peskett C, Khetarpal M, Bamne A, Adsul B, Manglani M, Sachdeva KS, Parmar M, Kanchar A, Rewari BB, Deshpande A, Rodrigues C, Shetty A, Rebello L, Saranchuk P. PLoS One. 2014 Oct 21;9(10):e110461. doi: 10.1371/journal.pone.0110461. eCollection 2014.

Background: Drug-resistant tuberculosis (DR-TB) is a looming threat to tuberculosis control in India. However, no countrywide prevalence data are available. The burden of DR-TB in HIV-co-infected patients is likewise unknown. Undiagnosed and untreated DR-TB among HIV-infected patients is a major cause of mortality and morbidity. We aimed to assess the prevalence of DR-TB (defined as resistance to any anti-TB drug) in patients attending public antiretroviral treatment (ART) centers in greater metropolitan Mumbai, India.

Methods: A cross-sectional survey was conducted among adults and children ART-center attendees. Smear microscopy, culture and drug-susceptibility-testing (DST) against all first and second-line TB-drugs using phenotypic liquid culture (MGIT) were conducted on all presumptive tuberculosis patients. Analyses were performed to determine DR-TB prevalence and resistance patterns separately for new and previously treated, culture-positive TB-cases.

Results: Between March 2013 and January 2014, ART-center attendees were screened during 14 135 visits, of whom 1724 had presumptive TB. Of 1724 attendees, 72 (4%) were smear-positive and 202 (12%) had a positive culture for Mycobacterium tuberculosis. Overall DR-TB was diagnosed in 68 (34%, 95% CI: 27%-40%) TB-patients. The proportions of DR-TB were 25% (29/114) and 44% (39/88) among new and previously treated cases respectively. The patterns of DR-TB were: 21% mono-resistant, 12% poly-resistant, 38% multidrug-resistant (MDR-TB), 21% pre-extensively-drug-resistant (MDR-TB plus resistance to either a fluoroquinolone or second-line injectable), 6% extensively drug-resistant (XDR-TB) and 2% extremely drug-resistant TB (XDR-TB plus resistance to any group-IV/V drug). Only previous history of TB was significantly associated with the diagnosis of DR-TB in multivariate models.

Conclusion: The burden of DR-TB among HIV-infected patients attending public ART-centers in Mumbai was alarmingly high, likely representing ongoing transmission in the community and health facilities. These data highlight the need to promptly diagnose drug-resistance among all HIV-infected patients by systematically offering access to first and second-line DST to all patients with 'presumptive TB' rather than 'presumptive DR-TB' and tailor the treatment regimen based on the resistance patterns.

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Editor’s notes: Drug-resistant tuberculosis (TB) is a major threat to public health. It is associated with substantial morbidity and mortality, particularly among people with advanced HIV disease. Standard drug regimens for multi- and extensively drug-resistant TB are unsatisfactory, requiring long courses of treatment with drugs which often have unpleasant and sometimes serious side effects. For TB programmes, treating drug-resistant TB requires substantial resources, and presents a risk to health care workers unless infection control measures are rigorously applied. 

In this study at five HIV treatment centres in Mumbai, India, adults and children attending for HIV care were systematically screened for TB by a research nurse. Individuals reporting one or more TB symptom (any of cough, weight loss, night sweats or fever, referred to in the article as people with “presumptive TB”) had sputum sent for microscopy, culture and drug susceptibility testing. Among individuals who had Mycobacterium tuberculosis on culture, some 34% had resistance to any drug. Among individuals who had never previously been treated for TB, 11% had resistance to at least rifampicin and isoniazid (multidrug-resistant tuberculosis), and several had more extensive resistance patterns. Among 15 children with culture-positive TB, seven had resistance to at least one drug, and six had at least multidrug-resistant TB. This is particularly concerning because it implies transmission of drug-resistant tuberculosis either in the community or in health care facilities or both.

As the authors illustrate, the absolute number of TB cases was relatively small, and the findings may not be generalisable to other settings in India. Nonetheless, the findings indicate transmission of drug-resistant TB among people living with HIV attending these clinics. This study underlines the need for early detection and prompt initiation of effective treatment for people with TB, including individuals with drug-resistant TB, and for infection control measures to protect individuals and staff within clinics.

Avoid TB deaths
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