Transmission of Multidrug-Resistant and Drug-Susceptible Tuberculosis within Households

A Prospective Cohort Study

Louis Grandjean, Robert H Gilman, Laura Martin, Esther Soto, Beatriz Castro, Sonia Lopez, Jorge Coronel, Edith Castillo, Valentina Alarcon, Virginia Lopez, Angela San Miguel, Neyda Quispe, Luis Asencios, Christopher Dye, David A J Moore

Research output: Contribution to journalArticle

Abstract

The “fitness” of an infectious pathogen is defined as the ability of the pathogen to survive, reproduce, be transmitted, and cause disease. The fitness of multidrug-resistant tuberculosis (MDRTB) relative to drug-susceptible tuberculosis is cited as one of the most important determinants of MDRTB spread and epidemic size. To estimate the relative fitness of drug-resistant tuberculosis cases, we compared the incidence of tuberculosis disease among the household contacts of MDRTB index patients to that among the contacts of drug-susceptible index patients. This 3-y (2010–2013) prospective cohort household follow-up study in South Lima and Callao, Peru, measured the incidence of tuberculosis disease among 1,055 household contacts of 213 MDRTB index cases and 2,362 household contacts of 487 drug-susceptible index cases. A total of 35/1,055 (3.3%) household contacts of 213 MDRTB index cases developed tuberculosis disease, while 114/2,362 (4.8%) household contacts of 487 drug-susceptible index patients developed tuberculosis disease. The total follow-up time for drug-susceptible tuberculosis contacts was 2,620 person-years, while the total follow-up time for MDRTB contacts was 1,425 person-years. Using multivariate Cox regression to adjust for confounding variables including contact HIV status, contact age, socio-economic status, and index case sputum smear grade, the hazard ratio for tuberculosis disease among MDRTB household contacts was found to be half that for drug-susceptible contacts (hazard ratio 0.56, 95% CI 0.34–0.90, p = 0.017). The inference of transmission in this study was limited by the lack of genotyping data for household contacts. Capturing incident disease only among household contacts may also limit the extrapolation of these findings to the community setting. The low relative fitness of MDRTB estimated by this study improves the chances of controlling drug-resistant tuberculosis. However, fitter multidrug-resistant strains that emerge over time may make this increasingly difficult.

Original languageEnglish (US)
Article numbere1001843
JournalPLoS Medicine
Volume12
Issue number6
DOIs
StatePublished - Jun 1 2015

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Multidrug-Resistant Tuberculosis
Cohort Studies
Prospective Studies
Tuberculosis
Pharmaceutical Preparations
Peru
Aptitude
Confounding Factors (Epidemiology)
Incidence
Sputum
Economics
HIV

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Transmission of Multidrug-Resistant and Drug-Susceptible Tuberculosis within Households : A Prospective Cohort Study. / Grandjean, Louis; Gilman, Robert H; Martin, Laura; Soto, Esther; Castro, Beatriz; Lopez, Sonia; Coronel, Jorge; Castillo, Edith; Alarcon, Valentina; Lopez, Virginia; San Miguel, Angela; Quispe, Neyda; Asencios, Luis; Dye, Christopher; Moore, David A J.

In: PLoS Medicine, Vol. 12, No. 6, e1001843, 01.06.2015.

Research output: Contribution to journalArticle

Grandjean, L, Gilman, RH, Martin, L, Soto, E, Castro, B, Lopez, S, Coronel, J, Castillo, E, Alarcon, V, Lopez, V, San Miguel, A, Quispe, N, Asencios, L, Dye, C & Moore, DAJ 2015, 'Transmission of Multidrug-Resistant and Drug-Susceptible Tuberculosis within Households: A Prospective Cohort Study', PLoS Medicine, vol. 12, no. 6, e1001843. https://doi.org/10.1371/journal.pmed.1001843
Grandjean, Louis ; Gilman, Robert H ; Martin, Laura ; Soto, Esther ; Castro, Beatriz ; Lopez, Sonia ; Coronel, Jorge ; Castillo, Edith ; Alarcon, Valentina ; Lopez, Virginia ; San Miguel, Angela ; Quispe, Neyda ; Asencios, Luis ; Dye, Christopher ; Moore, David A J. / Transmission of Multidrug-Resistant and Drug-Susceptible Tuberculosis within Households : A Prospective Cohort Study. In: PLoS Medicine. 2015 ; Vol. 12, No. 6.
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abstract = "The “fitness” of an infectious pathogen is defined as the ability of the pathogen to survive, reproduce, be transmitted, and cause disease. The fitness of multidrug-resistant tuberculosis (MDRTB) relative to drug-susceptible tuberculosis is cited as one of the most important determinants of MDRTB spread and epidemic size. To estimate the relative fitness of drug-resistant tuberculosis cases, we compared the incidence of tuberculosis disease among the household contacts of MDRTB index patients to that among the contacts of drug-susceptible index patients. This 3-y (2010–2013) prospective cohort household follow-up study in South Lima and Callao, Peru, measured the incidence of tuberculosis disease among 1,055 household contacts of 213 MDRTB index cases and 2,362 household contacts of 487 drug-susceptible index cases. A total of 35/1,055 (3.3{\%}) household contacts of 213 MDRTB index cases developed tuberculosis disease, while 114/2,362 (4.8{\%}) household contacts of 487 drug-susceptible index patients developed tuberculosis disease. The total follow-up time for drug-susceptible tuberculosis contacts was 2,620 person-years, while the total follow-up time for MDRTB contacts was 1,425 person-years. Using multivariate Cox regression to adjust for confounding variables including contact HIV status, contact age, socio-economic status, and index case sputum smear grade, the hazard ratio for tuberculosis disease among MDRTB household contacts was found to be half that for drug-susceptible contacts (hazard ratio 0.56, 95{\%} CI 0.34–0.90, p = 0.017). The inference of transmission in this study was limited by the lack of genotyping data for household contacts. Capturing incident disease only among household contacts may also limit the extrapolation of these findings to the community setting. The low relative fitness of MDRTB estimated by this study improves the chances of controlling drug-resistant tuberculosis. However, fitter multidrug-resistant strains that emerge over time may make this increasingly difficult.",
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