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Ongoing challenges to understanding multidrug- and rifampicin-resistant tuberculosis in children versus adults

C. Finn McQuaid, Ted Cohen, Anna S. Dean, Rein M.G.J. Houben, Gwenan M. Knight, Matteo Zignol, Richard G. White
European Respiratory Journal 2021 57: 2002504; DOI: 10.1183/13993003.02504-2020
C. Finn McQuaid
1TB Modelling Group, TB Centre and Centre for Mathematical Modelling of Infectious Diseases, Dept of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK
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Ted Cohen
2Yale School of Public Health, Laboratory of Epidemiology and Public Health, New Haven, CT, USA
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Anna S. Dean
3Global Tuberculosis Programme, World Health Organization, Geneva, Switzerland
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Rein M.G.J. Houben
1TB Modelling Group, TB Centre and Centre for Mathematical Modelling of Infectious Diseases, Dept of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK
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Gwenan M. Knight
1TB Modelling Group, TB Centre and Centre for Mathematical Modelling of Infectious Diseases, Dept of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK
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Matteo Zignol
3Global Tuberculosis Programme, World Health Organization, Geneva, Switzerland
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Richard G. White
1TB Modelling Group, TB Centre and Centre for Mathematical Modelling of Infectious Diseases, Dept of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK
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Abstract

Previous analyses suggest that children with tuberculosis (TB) are no more or no less likely to have multidrug (MDR)- or rifampicin-resistant (RR)-TB than adults. However, the availability of new data, particularly for high MDR/RR-TB burden countries, suggest updates of country-specific estimates are warranted.

We used data from population-representative surveys and surveillance collected between 2000 and 2018 to compare the odds ratio of MDR/RR-TB among children (aged <15 years) with TB, compared to the odds of MDR/RR-TB among adults (aged ≥15 years) with TB.

In most settings (45 out of 55 countries), and globally as a whole, there is no evidence that age is associated with odds of MDR/RR-TB. However, in some settings, such as former Soviet Union countries in general, and Georgia, Kazakhstan, Lithuania, Tajikistan and Uzbekistan in particular, as well as Peru, MDR/RR-TB is positively associated with age ≥15 years. Meanwhile, in Western Europe in general, and the United Kingdom, Poland, Finland and Luxembourg in particular, MDR/RR-TB is positively associated with age <15 years. 16 countries had sufficient data to compare over time between 2000–2011 and 2012–2018, with evidence for decreases in the odds ratio in children compared to adults in Germany, Kazakhstan and the United States of America.

Our results support findings that in most settings a child with TB is as likely as an adult with TB to have MDR/RR-TB. However, setting-specific heterogeneity requires further investigation. Furthermore, the odds ratio for MDR/RR-TB in children compared to adults is generally either stable or decreasing. There are important gaps in detection, recording and reporting of drug resistance among paediatric TB cases, limiting our understanding of transmission risks and measures needed to combat the global TB epidemic.

Abstract

Globally, the odds of drug resistance among those with TB are the same for children as for adults. However, setting-specific heterogeneity requires further investigation. Where temporal comparison is possible, the odds are stable or decreasing. https://bit.ly/2DSvzt3

Footnotes

  • This article has supplementary material available from erj.ersjournals.com

  • All data generated or analysed during this study are included in this published article and its supplementary information files.

  • Author contributions: C.F. McQuaid, T. Cohen, M. Zignol and R.G. White conceived and designed the study. C.F. McQuaid did all the data analysis and wrote a first draft of the article. C.F. McQuaid, T. Cohen, A.S. Dean, R.M.G.J. Houben, G.M. Knight, M. Zignol and R.G. White designed the methodology and critiqued the results. All authors contributed to editing the final draft.

  • Conflict of interest: C.F. McQuaid has nothing to disclose.

  • Conflict of interest: T. Cohen has nothing to disclose.

  • Conflict of interest: A.S. Dean has nothing to disclose.

  • Conflict of interest: R.M.G.J. Houben has nothing to disclose.

  • Conflict of interest: G.M. Knight has nothing to disclose.

  • Conflict of interest: M. Zignol has nothing to disclose.

  • Conflict of interest: R.G. White has nothing to disclose.

  • Support statement: The study was not funded separately. C.F. McQuaid was funded by the Bill and Melinda Gates Foundation (grant number TB MAC OPP1135288). G.M. Knight was supported by a fellowship from the UK MRC (grant number MR/P014658/1). R.M.G.J. Houben received funding from the European Research Council under the European Union's Horizon 2020 research and innovation programme (grant agreement number 757699). R.G. White is funded by the UK Medical Research Council (MRC) and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreement that is also part of the EDCTP2 programme supported by the European Union (grant number MR/P002404/1), the Bill and Melinda Gates Foundation (grant numbers TB MAC: OPP1084276/OPP1135288, CORTIS: OPP1137034/OPP1151915, Vaccines: OPP1160830), UNITAID (grant number 4214-LSHTM-Sept15; PO 8477-0-600), and ESRC (grant number ES/P008011/1).

  • Received June 25, 2020.
  • Accepted August 6, 2020.
  • Copyright ©ERS 2021
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Ongoing challenges to understanding multidrug- and rifampicin-resistant tuberculosis in children versus adults
C. Finn McQuaid, Ted Cohen, Anna S. Dean, Rein M.G.J. Houben, Gwenan M. Knight, Matteo Zignol, Richard G. White
European Respiratory Journal Feb 2021, 57 (2) 2002504; DOI: 10.1183/13993003.02504-2020

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Ongoing challenges to understanding multidrug- and rifampicin-resistant tuberculosis in children versus adults
C. Finn McQuaid, Ted Cohen, Anna S. Dean, Rein M.G.J. Houben, Gwenan M. Knight, Matteo Zignol, Richard G. White
European Respiratory Journal Feb 2021, 57 (2) 2002504; DOI: 10.1183/13993003.02504-2020
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