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Estimating the future burden of multidrug-resistant and extensively drug-resistant tuberculosis in India, the Philippines, Russia, and South Africa: a mathematical modelling study.

ABSTRACT: BACKGROUND:Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis are emerging worldwide. The Green Light Committee initiative supported programmatic management of drug-resistant tuberculosis in 90 countries. We used estimates from the Preserving Effective TB Treatment Study to predict MDR and XDR tuberculosis trends in four countries with a high burden of MDR tuberculosis: India, the Philippines, Russia, and South Africa. METHODS:We calibrated a compartmental model to data from drug resistance surveys and WHO tuberculosis reports to forecast estimates of incident MDR and XDR tuberculosis and the percentage of incident MDR and XDR tuberculosis caused by acquired drug resistance, assuming no fitness cost of resistance from 2000 to 2040 in India, the Philippines, Russia, and South Africa. FINDINGS:The model forecasted the percentage of MDR tuberculosis among incident cases of tuberculosis to increase, reaching 12·4% (95% prediction interval 9·4-16·2) in India, 8·9% (4·5-11·7) in the Philippines, 32·5% (27·0-35·8) in Russia, and 5·7% (3·0-7·6) in South Africa in 2040. It also predicted the percentage of XDR tuberculosis among incident MDR tuberculosis to increase, reaching 8·9% (95% prediction interval 5·1-12·9) in India, 9·0% (4·0-14·7) in the Philippines, 9·0% (4·8-14·2) in Russia, and 8·5% (2·5-14·7) in South Africa in 2040. Acquired drug resistance would cause less than 30% of incident MDR tuberculosis during 2000-40. Acquired drug resistance caused 80% of incident XDR tuberculosis in 2000, but this estimate would decrease to less than 50% by 2040. INTERPRETATION:MDR and XDR tuberculosis were forecast to increase in all four countries despite improvements in acquired drug resistance shown by the Green Light Committee-supported programmatic management of drug-resistant tuberculosis. Additional control efforts beyond improving acquired drug resistance rates are needed to stop the spread of MDR and XDR tuberculosis in countries with a high burden of MDR tuberculosis. FUNDING:US Agency for International Development and US Centers for Disease Control and Prevention, Division of Tuberculosis Elimination.

SUBMITTER: Sharma A

PROVIDER: S-EPMC5599934 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Estimating the future burden of multidrug-resistant and extensively drug-resistant tuberculosis in India, the Philippines, Russia, and South Africa: a mathematical modelling study.

Sharma Aditya A Hill Andrew A Kurbatova Ekaterina E van der Walt Martie M Kvasnovsky Charlotte C Tupasi Thelma E TE Caoili Janice C JC Gler Maria Tarcela MT Volchenkov Grigory V GV Kazennyy Boris Y BY Demikhova Olga V OV Bayona Jaime J Contreras Carmen C Yagui Martin M Leimane Vaira V Cho Sang Nae SN Kim Hee Jin HJ Kliiman Kai K Akksilp Somsak S Jou Ruwen R Ershova Julia J Dalton Tracy T Cegielski Peter P

The Lancet. Infectious diseases 20170509 7

<h4>Background</h4>Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis are emerging worldwide. The Green Light Committee initiative supported programmatic management of drug-resistant tuberculosis in 90 countries. We used estimates from the Preserving Effective TB Treatment Study to predict MDR and XDR tuberculosis trends in four countries with a high burden of MDR tuberculosis: India, the Philippines, Russia, and South Africa.<h4>Methods</h4>We calibrated a compartmental ...[more]

PMID: 28499828

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Project description:BackgroundTo end the global tuberculosis epidemic, latent tuberculosis infection needs to be addressed. All standard treatments for latent tuberculosis contain drugs to which multidrug-resistant (MDR) Mycobacterium tuberculosis is resistant. We aimed to estimate the global burden of multidrug-resistant latent tuberculosis infection to inform tuberculosis elimination policy.MethodsBy fitting a flexible statistical model to tuberculosis drug resistance surveillance and survey data collated by WHO, we estimated national trends in the proportion of new tuberculosis cases that were caused by MDR strains. We used these data as a proxy for the proportion of new infections caused by MDR M tuberculosis and multiplied trends in annual risk of infection from previous estimates of the burden of latent tuberculosis to generate trends in the annual risk of infection with MDR M tuberculosis. These estimates were used in a cohort model to estimate changes in the global and national prevalence of latent infection with MDR M tuberculosis. We also estimated recent infection levels (ie, in 2013 and 2014) and made predictions for the future burden of MDR tuberculosis in 2035 and 2050.Findings19·1 million (95% uncertainty interval [UI] 16·4 million-21·7 million) people were latently infected with MDR tuberculosis in 2014-a global prevalence of 0·3% (95% UI 0·2-0·3). MDR strains accounted for 1·2% (95% UI 1·0-1·4) of the total latent tuberculosis burden overall, but for 2·9% (95% UI 2·6-3·1) of the burden among children younger than 15 years (risk ratio for those younger than 15 years vs those aged 15 years or older 2·65 [95% UI 2·11-3·25]). Recent latent infection with MDR M tuberculosis meant that 1·9 million (95% UI 1·7 million-2·3 million) people globally were at high risk of active MDR tuberculosis in 2015.InterpretationWe estimate that three in every 1000 people globally carry latent MDR tuberculosis infection, and prevalence is around ten times higher among those younger than 15 years. If current trends continue, the proportion of latent tuberculosis caused by MDR strains will increase, which will pose serious challenges for management of latent tuberculosis-a cornerstone of tuberculosis elimination strategies.FundingUK Medical Research Council, Bill & Melinda Gates Foundation, and European Research Council.

Project description:Urinary tract infections (UTIs) are among the most common bacterial infections in humans. Uropathogenic Escherichia coli (UPEC), which are the most frequent agents causing community as well as hospital-acquired UTIs, have become highly drug-resistant, thus making the treatment of these infections challenging. Recently, the use of bacteriophages (or 'phages') against multidrug-resistant (MDR) and extensively drug-resistant (XDR) microorganisms has garnered significant global attention. Bacterial biofilms play a vital role in the pathogenesis of UTIs caused by UPEC. Phages have the potential to disrupt bacterial biofilms using lytic enzymes such as EPS depolymerases and endolysins. We isolated a lytic phage (590B) from community sewage in Chandigarh, which was active against multiple MDR and XDR biofilm-forming UPEC strains. During whole-genome sequencing, the 44.3 kb long genome of phage 590B encoded 75 ORFs, of which 40 were functionally annotated based on homology with similar phage proteins in the database. Comparative analysis of associated phage genomes indicated that phage 590B evolved independently and had a distinct taxonomic position within the genus Kagunavirus in the subfamily Guernseyvirinae of Siphoviridae. The phage disrupted biofilm mass effectively when applied to 24 h old biofilms formed on the Foley silicon catheter and coverslip biofilm models. To study the effect of intact biofilm architecture on phage predation, the biofilms were disrupted. The phage reduced the viable cells by 0.6-1.0 order of magnitude after 24 h of incubation. Regrowth and intact bacterial cells were observed in the phage-treated planktonic culture and biofilms, respectively, which indicated the emergence of phage-resistant bacterial variants. The phage genome encoded an endolysin which might have a role in the disruption and inhibition of bacterial biofilms. Moreover, the genome lacked genes encoding toxins, virulence factors, antibiotic resistance, or lysogeny. Therefore, lytic phage 590B may be a good alternative to antibiotics and can be included in phage cocktails for the treatment of UTIs caused by biofilm-forming MDR and XDR UPEC strains.

Dataset Information

Estimating the future burden of multidrug-resistant and extensively drug-resistant tuberculosis in India, the Philippines, Russia, and South Africa: a mathematical modelling study.

Publications

Estimating the future burden of multidrug-resistant and extensively drug-resistant tuberculosis in India, the Philippines, Russia, and South Africa: a mathematical modelling study.

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