A Case-Control Study to Identify Community Venues Associated with Genetically-clustered, Multidrug-resistant Tuberculosis Disease in Lima, Peru

Abstract

Background: The majority of tuberculosis transmission occurs in community settings. Our primary aim in this study was to assess the association between exposure to community venues and multidrug-resistant (MDR) tuberculosis. Our secondary aim was to describe the social networks of MDR tuberculosis cases and controls.

Methods: We recruited laboratory-confirmed MDR tuberculosis cases and community controls that were matched on age and sex. Whole-genome sequencing was used to identify genetically clustered cases. Venue tracing interviews (nonblinded) were conducted to enumerate community venues frequented by participants. Logistic regression was used to assess the association between MDR tuberculosis and person-time spent in community venues. A location-based social network was constructed, with respondents connected if they reported frequenting the same venue, and an exponential random graph model (ERGM) was fitted to model the network.

Results: We enrolled 59 cases and 65 controls. Participants reported 729 unique venues. The mean number of venues reported was similar in both groups (P = .92). Person-time in healthcare venues (adjusted odds ratio [aOR] = 1.67, P = .01), schools (aOR = 1.53, P < .01), and transportation venues (aOR = 1.25, P = .03) was associated with MDR tuberculosis. Healthcare venues, markets, cinemas, and transportation venues were commonly shared among clustered cases. The ERGM indicated significant community segregation between cases and controls. Case networks were more densely connected.

Conclusions: Exposure to healthcare venues, schools, and transportation venues was associated with MDR tuberculosis. Intervention across the segregated network of case venues may be necessary to effectively stem transmission.

Keywords: community transmission; genotyping; multidrug-resistant; social network; tuberculosis.

Figure 1.

Total venues and person-hours reported by case and control, stratified by venue type. (A) Bars indicate the total number of venues reported by cases and controls, stratified by venue type; grey bars are cases and white bars are controls. (B) Bars indicate the total number of person-hours reported by cases and controls, stratified by venue type; grey bars are cases and white bars are controls.

Figure 2.

The 2-mode location-based social network of cases and controls across both regions. The 2-mode network represent the participants connected to venues they reported frequenting. Cases are represented as dark gray circles and controls are represented as light gray circles. Venues are represented as white boxes, with a numeric code corresponding to the venue type. For clarity, only venues reported by at least 2 participants are visualized. The venue codes are: 1 = healthcare, 3 = market, 4 = store, 5 = church, 7 = restaurant, 9 = cinema, 11 = school, and 12 = transportation.

Figure 3.

The 2-mode and 1-mode location-based social networks of cases and controls, stratified by region. The 2-mode networks represent the participants connected to venues they reported frequenting. Cases are represented as dark gray circles and controls are represented as light gray circles. Venues are represented as white boxes, with a numeric code corresponding to the venue type. In the 1-mode network, participants are connected if they report frequenting the same venue. For clarity, only venues reported by at least 2 participants are visualized. The venue codes are: 1 = healthcare, 3 = market, 4 = store, 5 = church, 7 = restaurant, 9 = cinema, 11 = school, and 12 = transportation.