Where is tuberculosis transmission happening? Insights from the literature, new tools to study transmission and implications for the elimination of tuberculosis

Abstract

More than 10 million new cases of tuberculosis (TB) are diagnosed worldwide each year. The majority of these cases occur in low- and middle-income countries where the TB epidemic is predominantly driven by transmission. Efforts to 'end TB' will depend upon our ability to halt ongoing transmission. However, recent studies of new approaches to interrupt transmission have demonstrated inconsistent effects on reducing population-level TB incidence. TB transmission occurs across a wide range of settings, that include households and hospitals, but also community-based settings. While home-based contact investigations and infection control programmes in hospitals and clinics have a successful track record as TB control activities, there is a gap in our knowledge of where, and between whom, community-based transmission of TB occurs. Novel tools, including molecular epidemiology, geospatial analyses and ventilation studies, provide hope for improving our understanding of transmission in countries where the burden of TB is greatest. By integrating these diverse and innovative tools, we can enhance our ability to identify transmission events by documenting the opportunity for transmission-through either an epidemiologic or geospatial connection-alongside genomic evidence for transmission, based upon genetically similar TB strains. A greater understanding of locations and patterns of transmission will translate into meaningful improvements in our current TB control activities by informing targeted, evidence-based public health interventions.

Keywords: epidemiology; molecular epidemiology; public health; tuberculosis.

Figure 1

Putative transmission networks constructed from genotyping data versus whole-genome data for 32 patients. Genotyping data from analyses of mycobacterial interspersed repetitive unit–variable number tandem repeats (MIRU-VNTRs) were used in panel (A), and whole-genome data were used in panel (B). Each panel shows patients (identified by case number) represented by circles coloured according to smear status and clinical presentation as an index of infectivity: Black circles indicate smear-positive pulmonary disease, grey circles smear-positive miliary disease or smear-negative pulmonary disease and white circles indicate smear-negative extrapulmonary disease. The cases are connected by arrows on the basis of reported social relationships representing plausible transmission attributable to a single case (purple arrows) or multiple potential sources of transmission (light blue lines), with dashed arrows indicating moderately infective patients and solid lines highly infective patients. The network in panel (B), with cases shown according to tuberculosis lineage (A in blude and B in pink), provides a more accurate picture of transmission, with transmission restricted to each lineage, facilitating epidemiologic interpretation of the underlying social-network data and revealing the role of the second and third source cases (MT0010 and MT0011) (Adapted from Gardy et al., with permission).

Figure 2

Health centre-level risks of tuberculosis (TB). Annual per-100 K rates of drug-sensitive and drug-resistant TB (A) and multidrug-resistant (MDR) TB (B) by health centre catchment area. (C) Ratio of the per-capita rate of MDR to non-MDR cases by health centre. Health centre catchment areas are represented by polygons, with polygon fill colour indicating the TB or MDR TB rate in cases/100 K population. The boundaries of administrative districts of Lima are overlaid in black and labelled in white (Adapted from Zelner et al., with permission).

Figure 3

(A) Ambient parts per million of CO₂ recorded at minute intervals by the logging device carried by a subject during a 24-h period. (B) Litres per minute of rebreathed air with additional allocation to specific locations. Litres per minute of rebreathed air were calculated for a 24-h period (transformation from ambient CO₂ levels in Fig. 2A) and additionally allocated to specific locations using diary and global positioning system (GPS) information. The volume of rebreathed shared air is represented by the area under the curve for each location visited and the daily rebreathed volume is the sum of all volumes at all locations visited (Adapted from Wood et al., with permission).