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Transmission of drug-resistant tuberculosis in HIV-endemic settings.

ABSTRACT: The emergence and expansion of the multidrug-resistant tuberculosis epidemic is a threat to the global control of tuberculosis. Multidrug-resistant tuberculosis is the result of the selection of resistance-conferring mutations during inadequate antituberculosis treatment. However, HIV has a profound effect on the natural history of tuberculosis, manifesting in an increased rate of disease progression, leading to increased transmission and amplification of multidrug-resistant tuberculosis. Interventions specific to HIV-endemic areas are urgently needed to block tuberculosis transmission. These interventions should include a combination of rapid molecular diagnostics and improved chemotherapy to shorten the duration of infectiousness, implementation of infection control measures, and active screening of multidrug-resistant tuberculosis contacts, with prophylactic regimens for individuals without evidence of disease. Development and improvement of the efficacy of interventions will require a greater understanding of the factors affecting the transmission of multidrug-resistant tuberculosis in HIV-endemic settings, including population-based molecular epidemiology studies. In this Series article, we review what we know about the transmission of multidrug-resistant tuberculosis in settings with high burdens of HIV and define the research priorities required to develop more effective interventions, to diminish ongoing transmission and the amplification of drug resistance.

SUBMITTER: Khan PY

PROVIDER: S-EPMC6474238 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Transmission of drug-resistant tuberculosis in HIV-endemic settings.

Khan Palwasha Y PY Yates Tom A TA Osman Muhammad M Warren Robin M RM van der Heijden Yuri Y Padayatchi Nesri N Nardell Edward A EA Moore David D Mathema Barun B Gandhi Neel N Eldholm Vegard V Dheda Keertan K Hesseling Anneke C AC Mizrahi Valerie V Rustomjee Roxana R Pym Alexander A

The Lancet. Infectious diseases 20181213 3

The emergence and expansion of the multidrug-resistant tuberculosis epidemic is a threat to the global control of tuberculosis. Multidrug-resistant tuberculosis is the result of the selection of resistance-conferring mutations during inadequate antituberculosis treatment. However, HIV has a profound effect on the natural history of tuberculosis, manifesting in an increased rate of disease progression, leading to increased transmission and amplification of multidrug-resistant tuberculosis. Interv ...[more]

PMID: 30554996

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Project description:BackgroundDrug-resistant tuberculosis threatens recent gains in the treatment of tuberculosis and human immunodeficiency virus (HIV) infection worldwide. A widespread epidemic of extensively drug-resistant (XDR) tuberculosis is occurring in South Africa, where cases have increased substantially since 2002. The factors driving this rapid increase have not been fully elucidated, but such knowledge is needed to guide public health interventions.MethodsWe conducted a prospective study involving 404 participants in KwaZulu-Natal Province, South Africa, with a diagnosis of XDR tuberculosis between 2011 and 2014. Interviews and medical-record reviews were used to elicit information on the participants' history of tuberculosis and HIV infection, hospitalizations, and social networks. Mycobacterium tuberculosis isolates underwent insertion sequence (IS)6110 restriction-fragment-length polymorphism analysis, targeted gene sequencing, and whole-genome sequencing. We used clinical and genotypic case definitions to calculate the proportion of cases of XDR tuberculosis that were due to inadequate treatment of multidrug-resistant (MDR) tuberculosis (i.e., acquired resistance) versus those that were due to transmission (i.e., transmitted resistance). We used social-network analysis to identify community and hospital locations of transmission.ResultsOf the 404 participants, 311 (77%) had HIV infection; the median CD4+ count was 340 cells per cubic millimeter (interquartile range, 117 to 431). A total of 280 participants (69%) had never received treatment for MDR tuberculosis. Genotypic analysis in 386 participants revealed that 323 (84%) belonged to 1 of 31 clusters. Clusters ranged from 2 to 14 participants, except for 1 large cluster of 212 participants (55%) with a LAM4/KZN strain. Person-to-person or hospital-based epidemiologic links were identified in 123 of 404 participants (30%).ConclusionsThe majority of cases of XDR tuberculosis in KwaZulu-Natal, South Africa, an area with a high tuberculosis burden, were probably due to transmission rather than to inadequate treatment of MDR tuberculosis. These data suggest that control of the epidemic of drug-resistant tuberculosis requires an increased focus on interrupting transmission. (Funded by the National Institute of Allergy and Infectious Diseases and others.).

Project description:ObjectiveTransmission patterns of drug-resistant Mycobacterium tuberculosis (MTB) may be influenced by differences in socio-demographics, local tuberculosis (TB) endemicity and efficaciousness of TB control programs. This study aimed to investigate the impact of DOTS on the transmission of drug-resistant TB in eastern rural China.MethodsWe conducted a cross-sectional study of all patients diagnosed with drug-resistant TB over a one-year period in two rural Chinese counties with varying lengths of DOTS implementation. Counties included Deqing, with over 11 years' DOTS implementation and Guanyun, where DOTS was introduced 1 year prior to start of this study. We combined demographic, clinical and epidemiologic information with IS6110-based restricted fragment length polymorphism (RFLP) and Spoligotyping analysis of MTB isolates. In addition, we conducted DNA sequencing of resistance determining regions to first-line anti-tuberculosis agents.ResultsOf the 223 drug-resistant isolates, 73(32.7%) isolates were identified with clustered IS6110RFLP patterns. The clustering proportion among total drug-resistant TB was higher in Guanyun than Deqing (26/101.vs.47/122; p,0.04), but not significantly different among the 53 multidrug-resistant isolates (10/18.vs.24/35; p,0.35). Patients with cavitary had increased risk of clustering in both counties. In Guanyun, patients with positive smear test or previous treatment history had a higher clustering proportion. Beijing genotype and isolates resistant to isoniazid and/or rifampicin were more likely to be clustered. Of the 73 patients with clustered drug-resistant isolates, 71.2% lived in the same or neighboring villages. Epidemiological link (household and social contact) was confirmed in 12.3% of the clustered isolates.ConclusionTransmission of drug-resistant TB in eastern rural China is characterized by small clusters and limited geographic spread. Our observations highlight the need for supplementing DOTS with additional strategies, including active case finding at the village level, effective treatment for patients with cavities and drug susceptibility testing for patients at increased risk for drug-resistance.

Dataset Information

Transmission of drug-resistant tuberculosis in HIV-endemic settings.

Publications

Transmission of drug-resistant tuberculosis in HIV-endemic settings.

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