Multiple Introductions of MDR TB into Households | CDC EID

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Volume 17, Number 6–June 2011
Research
Multiple Introductions of Multidrug-Resistant Tuberculosis into Households, Lima, Peru
Ted Cohen, Megan Murray, Ibrahim Abubakar, Zibiao Zhang, Alexander Sloutsky, Fernando Arteaga, Katiuska Chalco, Molly F. Franke, and Mercedes C. Becerra

Author affiliations: Brigham and Women's Hospital, Boston, Massachusetts, USA (T. Cohen, M. Murray, Z. Zhang, M.C. Becerra); Harvard School of Public Health, Boston (T. Cohen, M. Murray); University of East Anglia, Norwich, UK (I. Abubakar); Health Protection Agency Centre for Infections, London, UK (I. Abubakar); University of Massachusetts Medical School, Boston (A. Sloutsky); Partners In Health, Boston and Lima, Peru (F. Arteaga, K. Chalco, M.F. Franke, M.C. Becerra); and Harvard Medical School, Boston (M.F. Franke, M.C. Becerra)

Suggested citation for this article

Abstract
Two cases of multidrug-resistant tuberculosis (MDR TB) in a household are assumed to reflect within-household transmission. However, in high-incidence areas of MDR TB, secondary cases may arise through exposure to MDR TB in the community. To estimate the frequency of multiple introductions of MDR TB into households, we used spoligotyping and 24-loci mycobacterial interspersed repetitive unit–variable number tandem repeats to classify isolates from 101 households in Lima, Peru, in which > 1 MDR TB patient received treatment during 1996–2004. We found different MDR TB strains in > 10% of households. Alternate approaches for classifying matching strains produced estimates of multiple introductions in < 38% of households. At least 4% of MDR TB patients were reinfected by a second strain of MDR Mycobacterium tuberculosis. These findings suggest that community exposure to MDR TB in Lima occurs frequently. Rapid drug sensitivity testing of strains from household contacts of known MDR TB patients is needed to identify optimal treatment regimens.


The discovery and use of discriminating genetic markers such as IS6110 restriction fragment length polymorphisms (RFLPs), spacer oligonucleotides (spoligotyping), and mycobacterial interspersed repetitive unit–variable number tandem repeats (MIRU-VNTRs) (1) have improved our understanding of the transmission dynamics of tuberculosis (TB) (2,3). Genotyping studies, in which strains with matching sets of markers are considered potential members of a single transmission chain, have demonstrated that recent transmission plays a major role, even in low-incidence settings (4,5); that persons with recurrent episodes of TB may be having reinfection rather than relapse (6–8); that persons may be infected by >1 isolate of Mycobacterium tuberculosis at the same time (9–11); and that transmission may occur in casual social settings (12).

Molecular epidemiologic studies have also demonstrated that secondary cases among close associates of known case-patients are not always members of the same chain of transmission, i.e., that infection may have been acquired from independent sources (13). Molecular investigations of households of multiple TB patients showed that cohabitating TB patients may be infected with distinct isolates of M. tuberculosis (14–16). For example, in 2 suburbs of Cape Town, South Africa, which have TB notification rates of ≈320 cases per 100,000 population, researchers found that less than half (46%) of secondary TB cases within households had a TB isolate that matched an isolate from another case within the household by RFLP (16). Overall, <1 (19%) in 5 new TB cases occurring in these communities was the result of within-household transmission. Although studies have shown that household contacts with TB are likely to have acquired infection independently in high-incidence settings, there are no published estimates of the probability that 2 household members with multidrug-resistant TB (MDR TB: resistance to at least isoniazid and rifampin) share a similar genotype and are members of the same transmission chain. Molecular epidemiologic data from households with >1 MDR TB case can help shed light on the transmissibility of highly drug-resistant disease and also help guide public health policy. For example, international guidelines for the management of known contacts of MDR TB patients recommend an empirical drug regimen based either on the drug-resistance profile of an isolate from the suspected index MDR TB case-patient or on the most common drug-resistance pattern in the community while drug sensitivity tests are pending (17–19). A better understanding of the relative importance of intrahousehold or community transmission may help to inform the choice of empirical regimen.

Despite a decreasing overall incidence of TB in Peru of ≈3.7% per year since 1996, the incidence of MDR TB has increased by ≈4.5% over the same period (20). The increasing incidence of MDR TB in densely occupied urban communities of Lima, Peru, poses obvious challenges for TB control. We report a molecular epidemiologic study within households in Lima in which >1 person received a diagnosis of MDR TB. We used spoligotyping and 24-loci MIRU-VNTR typing (21,22) to identify households that have had >1 introduction of MDR TB, and we explored the association of household factors with these multiple introduction events.

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Multiple Introductions of MDR TB into Households | CDC EID


Suggested Citation for this Article
Cohen T, Murray M, Abubakar I, Zhang Z, Sloutsky A, Arteaga F, et al. Multiple introductions of multidrug-resistant tuberculosis into households, Lima, Peru. Emerg Infect Dis [serial on the Internet]. 2011 Jun [date cited].
http://www.cdc.gov/EID/content/17/6/969.htm


DOI: 10.3201/eid1706.101471


Comments to the Authors
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Ted Cohen, Division of Global Health Equity, Brigham and Women's Hospital, 641 Huntington Ave, Boston, MA 02115, USA; email: tcohen@hsph.harvard.edu