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

Ragonnet, Romain, Trauer, James M., Denholm, Justin T., Marais, Ben J., and McBryde, Emma S. (2017) High rates of multidrug-resistant and rifampicin-resistant tuberculosis among re-treatment cases: where do they come from? BMC Infectious Diseases, 17 (36). pp. 1-10.

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Background: Globally 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.

Methods: We 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.

Results: At 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.

Conclusions: Globally, 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.

Item ID: 47374
Item Type: Article (Research - C1)
ISSN: 1471-2334
Keywords: tuberculosis; multidrug-resistant tuberculosis; re-treatment; causal pathway; misdiagnosis; inappropriate therapy; drug resistance amplification
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© The Author(s). 2017 Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Date Deposited: 07 Mar 2017 01:09
FoR Codes: 32 BIOMEDICAL AND CLINICAL SCIENCES > 3202 Clinical sciences > 320211 Infectious diseases @ 50%
44 HUMAN SOCIETY > 4407 Policy and administration > 440706 Health policy @ 50%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 50%
92 HEALTH > 9202 Health and Support Services > 920207 Health Policy Evaluation @ 50%
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