Identifying Hotspots of Multidrug-Resistant Tuberculosis Transmission Using Spatial and Molecular Genetic Data

Zelner, Jon; Murray, Megan; Becerra, Mercedes C.; Galea, Jerome T; Lecca, Leonid; Calderón, Róger; Yataco, Rosa; Contreras, Carmen; Zhang, Zibiao; Manjourides, Justin; Grenfell, Bryan T.; Cohen, Ted

doi:10.1093/infdis/jiv387

Cited by 66 publications

(73 citation statements)

References 18 publications

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“…They therefore highlight the potential impact that novel rapid diagnostic tests that include rifampicin sensitivity testing such as Xpert MTB/RIF® could have on the MDR-TB epidemic. Our findings concur with the outcomes of recent studies demonstrating that primary transmission contributes more substantially to the MDR/RR-TB burden than drug resistance acquisition or amplification during treatment [17, 25]. Interestingly, the model also suggests that failure of second-line regimens may make a significant contribution to the burden of MDR/RR-TB at re-treatment, especially in settings such as Eastern Europe where MDR vigilance is high and patients are able to access MDR/RR-TB treatment.…”

Section: Discussionsupporting

confidence: 92%

High rates of multidrug-resistant and rifampicin-resistant tuberculosis among re-treatment cases: where do they come from?

et al. 2017

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BackgroundGlobally 3.9% of new and 21% of re-treatment tuberculosis (TB) cases are multidrug-resistant or rifampicin-resistant (MDR/RR), which is often interpreted as evidence that drug resistance results mainly from poor treatment adherence. This study aims to assess the respective contributions of the different causal pathways leading to MDR/RR-TB at re-treatment.MethodsWe use a simple mathematical model to simulate progression between the different stages of disease and treatment for patients diagnosed with TB. The model is parameterised using region and country-specific TB disease burden data reported by the World Health Organization (WHO). The contributions of four separate causal pathways to MDR/RR-TB among re-treatment cases are estimated: I) initial drug-susceptible TB with resistance amplification during treatment; II) initial MDR/RR-TB inappropriately treated as drug-susceptible TB; III) MDR/RR-TB relapse despite appropriate treatment; and IV) re-infection with MDR/RR-TB.ResultsAt the global level, Pathways I, II, III and IV contribute 38% (28–49, 95% Simulation Interval), 44% (36–52, 95% SI), 6% (5–7, 95% SI) and 12% (7–19, 95% SI) respectively to the burden of MDR/RR-TB among re–treatment cases. Pathway II is dominant in the Western Pacific (74%; 67–80 95% SI), Eastern Mediterranean (68%; 60–74 95% SI) and European (53%; 48–59 95% SI) regions, while Pathway I makes the greatest contribution in the American (53%; 40–66 95% SI), African (43%; 28–61 95% SI) and South-East Asian (50%; 40–59 95% SI) regions.ConclusionsGlobally, failure to diagnose MDR/RR-TB at first presentation is the leading cause of the high proportion of MDR/RR-TB among re-treatment cases. These findings highlight the need for contextualised solutions to limit the impact and spread of MDR/RR-TB.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-016-2171-1) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 92%

High rates of multidrug-resistant and rifampicin-resistant tuberculosis among re-treatment cases: where do they come from?

et al. 2017

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“…Thus, these three variables could be used in multivariate analysis (p value < 0,25). The BCG immunization status of the children was related to children's pulmonary TB incidence, 23 but one variable failed the candidate test (p value = 0,333 > 0,25). This variable was excluded in the multivariate analysis because the variance of the data was not balanced or almost all study samples already received BCG immunization (97%).…”

Section: Discussionmentioning

confidence: 96%

Level of Exposure of Childhood Tuberculosis with Adult Pulmonary Tuberculosis Household Contacts

Asyary

Eryando

Purwantyastuti

et al. 2017

Kesmas: National Public Health Journal

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Pulmonary tuberculosis (TB) in children is a neglected global health problem, with an increasing proportion of TB cases in Indonesia. Children with TB are most often impacted by TB transmission in the population at large, especially adult TB that exists in the child's household. This study aimed to find protective factors that can keep children healthy despite household adult TB contacts. This study reports on 132 respondents with a case-control study conducted at nine referred hospitals and several primary health care based on medical records in Special Region of Yogyakarta Province. The study lasted from January to December 2014, while the data analysis was used by both of bivariate (chi-square) and multivariate (multiple logistic regression) analysis. The study found that healthy houses, especially those with healthy bedrooms and fewer exposures to adult TB sufferer, influenced by confounder variables, protected children from TB even though they were exposed to adult TB in their environment. Longer periods of living together is not a risk factor for children to contract TB when living with adult TB patients at home. However, this risk increases with frequent exposure among children to adult TB patients at home. Keywords: Children, exposure, household contact, tuberculosis Abstrak Tuberkulosis paru (TB) pada anak kian menjadi masalah kesehatan global yang masih terlupakan seiring dengan peningkatan proporsi TB di Indonesia. Penularan penyakit ini di populasi umum seringkali berdampak pada anak, terlebih ketika kontak TB terjadi di rumah tangga. Penelitian ini bertujuan untuk memperoleh faktor protektif sehingga anak tetap sehat meskipun memiliki kontak dengan penderita TB dewasa serumah. Penelitian ini dilakukan dengan pendekatan kasus-kontrol pada 132 responden anak yang berasal dari sembilan rumah sakit rujukan dan beberapa puskesmas di Provinsi Daerah Istimewa Yogyakarta. Penelitian dilakukan dalam periode Januari hingga Desember 2014 yang hasilnya dianalisis dengan uji bivariat (kai kuadrat) dan multivariat (regresi logistik ganda). Hasil penelitian menunjukkan bahwa rumah yang memenuhi syarat kesehatan, yakni ruang tidur yang sehat, serta paparan yang jarang diterima dari penderita TB dewasa mampu memproteksi anak agar tetap sehat meskipun tinggal serumah dengan penderita dewasa penyakit ini. Penelitian ini menyimpulkan bahwa lama tinggal bersama bukanlah faktor risiko penyakit TB pada anak. Hal ini karena meskipun lama tinggal bersama antara penderita TB dewasa dengan anak, namun apabila memiliki paparan yang jarang, hal ini pun tidak signifikan menjadikan anak untuk terkena TB.

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“…42,69,128 Indeed, some settings-from Estonia 129,130 to New York 131 -have seen steeper declines in the incidence of drug-resistant tuberculosis than in tuberculosis as a whole after adopting interventions to control the transmission of drug-resistant tuberculosis. Typically, these measures included universal DST, 132 individualised treatment, 133 access to tuberculosis care, 134 and sustained efforts to improve treatment completion, which is only achieved in two-thirds of cases, even in well functioning programmes.…”

Section: Clinical Implications Of the Findings Of Molecular Epidemiologymentioning

confidence: 99%

“…69 Targeting these hotspots might be highly effective for controlling drug-resistant tuberculosis. 128 However, as described by the routine strain typing service in the UK, the effect of molecular epidemiological data on patient care and public health response might not be useful if those data are not reported and acted upon quickly. 153 To achieve this, major technical and systems barriers must be overcome, including the strengthening of information technology systems to facilitate timely capture, export, and potentially automated analysis of complex data, such as in web-based systems; 148 linking molecular data to key epidemiological data (eg, geographical location); improving local scientific capacity; and providing decision makers with sufficient autonomy and resources to act in response to such data.…”

Section: Next-generation Molecular Epidemiologymentioning

confidence: 99%

The epidemiology, pathogenesis, transmission, diagnosis, and management of multidrug-resistant, extensively drug-resistant, and incurable tuberculosis

Dheda

Gumbo

Maartens

et al. 2017

The Lancet Respiratory Medicine

521

474

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Identifying Hotspots of Multidrug-Resistant Tuberculosis Transmission Using Spatial and Molecular Genetic Data

Abstract: These findings reveal that localized transmission is an important driver of the epidemic of MDR-tuberculosis in Lima. Efforts to interrupt transmission may be most effective if targeted to this area of the city.

Cited by 66 publications

References 18 publications

High rates of multidrug-resistant and rifampicin-resistant tuberculosis among re-treatment cases: where do they come from?

High rates of multidrug-resistant and rifampicin-resistant tuberculosis among re-treatment cases: where do they come from?

Level of Exposure of Childhood Tuberculosis with Adult Pulmonary Tuberculosis Household Contacts

The epidemiology, pathogenesis, transmission, diagnosis, and management of multidrug-resistant, extensively drug-resistant, and incurable tuberculosis

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