What We Know About Tuberculosis Transmission: An Overview

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Abstract

Tuberculosis remains a global health problem with an enormous burden of disease, estimated at 10.4 million new cases in 2015. To stop the tuberculosis epidemic, it is critical that we interrupt tuberculosis transmission. Further, the interventions required to interrupt tuberculosis transmission must be targeted to high-risk groups and settings. A simple cascade for tuberculosis transmission has been proposed in which (1) a source case of tuberculosis (2) generates infectious particles (3) that survive in the air and (4) are inhaled by a susceptible individual (5) who may become infected and (6) then has the potential to develop tuberculosis. Interventions that target these events will interrupt tuberculosis transmission and accelerate the decline in tuberculosis incidence and mortality. The purpose of this article is to provide a high-level overview of what is known about tuberculosis transmission, using the tuberculosis transmission cascade as a framework, and to set the scene for the articles in this series, which address specific aspects of tuberculosis transmission.

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Most cited references 37

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Comparison of two active case-finding strategies for community-based diagnosis of symptomatic smear-positive tuberculosis and control of infectious tuberculosis in Harare, Zimbabwe (DETECTB): a cluster-randomised trial

Elizabeth L. Corbett, Tsitsi Bandason, Trinh Duong … (2010)

Summary Background Control of tuberculosis in settings with high HIV prevalence is a pressing public health priority. We tested two active case-finding strategies to target long periods of infectiousness before diagnosis, which is typical of HIV-negative tuberculosis and is a key driver of transmission. Methods Clusters of neighbourhoods in the high-density residential suburbs of Harare, Zimbabwe, were randomised to receive six rounds of active case finding at 6-monthly intervals by either mobile van or door-to-door visits. Randomisation was done by selection of discs of two colours from an opaque bag, with one disc to represent every cluster, and one colour allocated to each intervention group before selection began. In both groups, adult (≥16 years) residents volunteering chronic cough (≥2 weeks) had two sputum specimens collected for fluorescence microscopy. Community health workers and cluster residents were not masked to intervention allocation, but investigators and laboratory staff were masked to allocation until final analysis. The primary outcome was the cumulative yield of smear-positive tuberculosis per 1000 adult residents, compared between intervention groups; analysis was by intention to treat. The secondary outcome was change in prevalence of culture-positive tuberculosis from before intervention to before round six of intervention in 12% of randomly selected households from the two intervention groups combined; analysis was based on participants who provided sputum in the two prevalence surveys. This trial is registered, number ISRCTN84352452. Findings 46 study clusters were identified and randomly allocated equally between intervention groups, with 55 741 adults in the mobile van group and 54 691 in the door-to-door group at baseline. HIV prevalence was 21% (1916/9060) and in the 6 months before intervention the smear-positive case notification rate was 2·8 per 1000 adults per year. The trial was completed as planned with no adverse events. The mobile van detected 255 smear-positive patients from 5466 participants submitting sputum compared with 137 of 4711 participants identified through door-to-door visits (adjusted risk ratio 1·48, 95% CI 1·11–1·96, p=0·0087). The overall prevalence of culture-positive tuberculosis declined from 6·5 per 1000 adults (95% CI 5·1–8·3) to 3·7 per 1000 adults (2·6–5·0; adjusted risk ratio 0·59, 95% CI 0·40–0·89, p=0·0112). Interpretation Wide implementation of active case finding, particularly with a mobile van approach, could have rapid effects on tuberculosis transmission and disease. Funding Wellcome Trust.

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Epidemiological benefits of more-effective tuberculosis vaccines, drugs, and diagnostics.

M. Halloran, Christopher Dye, Jonathan Sugimoto … (2009)

The Bill and Melinda Gates Foundation supports an ambitious portfolio of novel vaccines, drug regimens, and diagnostic tools for tuberculosis (TB). We elicited the expected efficacies and improvements of the novel interventions in discussions with the foundations managing their development. Using an age-structured mathematical model of TB, we explored the potential benefits of novel interventions under development and those not yet in the portfolio, focusing on the WHO Southeast Asia region. Neonatal vaccination with the portfolio vaccine decreases TB incidence by 39% to 52% by 2050. Drug regimens that shorten treatment duration and are efficacious against drug-resistant strains reduce incidence by 10-27%. New diagnostics reduce incidence by 13-42%. A triple combination of a portfolio vaccine, drug regimen, and diagnostics reduces incidence by 71%. A short mass vaccination catch-up campaign, not yet in the portfolio, to augment the triple combination, accelerates the decrease, preventing >30% more cases by 2050 than just the triple combination. New vaccines and drug regimens targeted at the vast reservoir of latently infected people, not in the portfolio, would reduce incidence by 37% and 82%, respectively. The combination of preventive latent therapy and a 2-month drug treatment regimen reduces incidence by 94%. Novel technologies in the pipeline would achieve substantial reductions in TB incidence, but not the Stop TB Partnership target for elimination. Elimination will require new delivery strategies, such as mass vaccination campaigns, and new products targeted at latently infected people.

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Feasibility of achieving the 2025 WHO global tuberculosis targets in South Africa, China, and India: a combined analysis of 11 mathematical models

Rein Houben, Nicolas Menzies, Tom Sumner … (2016)

Summary Background The post-2015 End TB Strategy proposes targets of 50% reduction in tuberculosis incidence and 75% reduction in mortality from tuberculosis by 2025. We aimed to assess whether these targets are feasible in three high-burden countries with contrasting epidemiology and previous programmatic achievements. Methods 11 independently developed mathematical models of tuberculosis transmission projected the epidemiological impact of currently available tuberculosis interventions for prevention, diagnosis, and treatment in China, India, and South Africa. Models were calibrated with data on tuberculosis incidence and mortality in 2012. Representatives from national tuberculosis programmes and the advocacy community provided distinct country-specific intervention scenarios, which included screening for symptoms, active case finding, and preventive therapy. Findings Aggressive scale-up of any single intervention scenario could not achieve the post-2015 End TB Strategy targets in any country. However, the models projected that, in the South Africa national tuberculosis programme scenario, a combination of continuous isoniazid preventive therapy for individuals on antiretroviral therapy, expanded facility-based screening for symptoms of tuberculosis at health centres, and improved tuberculosis care could achieve a 55% reduction in incidence (range 31–62%) and a 72% reduction in mortality (range 64–82%) compared with 2015 levels. For India, and particularly for China, full scale-up of all interventions in tuberculosis-programme performance fell short of the 2025 targets, despite preventing a cumulative 3·4 million cases. The advocacy scenarios illustrated the high impact of detecting and treating latent tuberculosis. Interpretation Major reductions in tuberculosis burden seem possible with current interventions. However, additional interventions, adapted to country-specific tuberculosis epidemiology and health systems, are needed to reach the post-2015 End TB Strategy targets at country level. Funding Bill and Melinda Gates Foundation

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Author and article information

Journal

Journal ID (nlm-ta): J Infect Dis

Journal ID (iso-abbrev): J. Infect. Dis

Journal ID (publisher-id): jid

Title: The Journal of Infectious Diseases

Publisher: Oxford University Press (US )

ISSN (Print): 0022-1899

ISSN (Electronic): 1537-6613

Publication date (Print): 01 October 2017

Publication date (Electronic): 03 November 2017

Publication date PMC-release: 03 November 2017

Volume: 216

Issue: Suppl 6 , Towards Zero New TB Infections: Research Needs for Halting TB Transmission

Pages: S629-S635

Affiliations

[1 ] Aurum Institute, Johannesburg, South Africa ,

[2 ] School of Public Health, University of the Witwatersrand, Johannesburg, South Africa,

[3 ] Advancing Care & Treatment for TB/HIV, Johannesburg, South Africa , and

[4 ] South African Medical Research Council , Johannesburg, South Africa;

[5 ] Division of AIDS, National Institutes of Health, Bethesda, Maryland , and

[6 ] Johns Hopkins University , Baltimore, Maryland;

[7 ] Division of Global HIV and Tuberculosis, Centers for Disease Control and Prevention, Atlanta, Georgia , and

[8 ] Rollins School of Public Health, Emory University, Atlanta, Georgia, and

[9 ] Emory School of Medicine, Emory University , Atlanta, Georgia;

[10 ] Department of Epidemiology, Mailman School of Public Health, Columbia University , New York, New York; and

[11 ] Bill and Melinda Gates Foundation , Seattle, Washington

Author notes

Correspondence: V. Cardenas, PhD, JD. Aurum Institute, Aurum House, The Ridge, 29 Queens Road, Parktown, Johannesburg, 2193 ( vcardenas@ 123456auruminstitute.org ).

Article

Publisher ID: jix362

DOI: 10.1093/infdis/jix362

PMC ID: 5791742

PubMed ID: 29112747

SO-VID: 73b53017-8c63-47aa-90e4-7012618314ac

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution 3.0 IGO (CC BY 3.0 IGO) License ( https://creativecommons.org/licenses/by/3.0/igo/) which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

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Pages: 7

Funding

Funded by: National Institute of Allergy and Infectious Diseases 10.13039/100000060

What We Know About Tuberculosis Transmission: An Overview

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Point-Of-Care Testing for Tuberculosis

Most cited references 37

Comparison of two active case-finding strategies for community-based diagnosis of symptomatic smear-positive tuberculosis and control of infectious tuberculosis in Harare, Zimbabwe (DETECTB): a cluster-randomised trial

Epidemiological benefits of more-effective tuberculosis vaccines, drugs, and diagnostics.

Feasibility of achieving the 2025 WHO global tuberculosis targets in South Africa, China, and India: a combined analysis of 11 mathematical models

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