The Importance of Heterogeneity to the Epidemiology of Tuberculosis

Abstract

Although less well-recognized than for other infectious diseases, heterogeneity is a defining feature of tuberculosis (TB) epidemiology. To advance toward TB elimination, this heterogeneity must be better understood and addressed. Drivers of heterogeneity in TB epidemiology act at the level of the infectious host, organism, susceptible host, environment, and distal determinants. These effects may be amplified by social mixing patterns, while the variable latent period between infection and disease may mask heterogeneity in transmission. Reliance on notified cases may lead to misidentification of the most affected groups, as case detection is often poorest where prevalence is highest. Assuming that average rates apply across diverse groups and ignoring the effects of cohort selection may result in misunderstanding of the epidemic and the anticipated effects of control measures. Given this substantial heterogeneity, interventions targeting high-risk groups based on location, social determinants, or comorbidities could improve efficiency, but raise ethical and equity considerations.

Keywords: case detection; epidemiology; heterogeneity; interventions; tuberculosis.

Figure 1.

Conceptual framework for understanding heterogeneity in tuberculosis epidemiology. The cone indicates that the most local drivers are positioned toward the top of the figure and the broadest drivers toward the bottom, rather than reflecting the importance of these factors.

Figure 2.

Illustration of some selected concepts from the text. A, Degree of heterogeneity that might be observed among individuals with good access to the healthcare system (unblurred discs) compared to those with poor access (blurred discs). This may be substantially less than the heterogeneity that exists in the population as a whole (B). C, Series of transmission events. D, Subsequent relocation of infected and uninfected individuals. This results in a more homogeneous distribution of infection across the population at this later time point, even though transmission was highly heterogeneous. E, Series of individuals at variable risk of infection. F, Selection of higher-risk individuals through the infection process. Although infection is the selecting illustrated process here, similar principles would apply to progression from infection to disease, through stages of the disease process and to interaction with the health system. Abbreviation: TB, tuberculosis.

Figure 3.

Composition of a simple 2-stratum heterogeneous cohort over time from entry to an epidemiological state (active undiagnosed tuberculosis). Plot displays the percentage of patients with active tuberculosis remaining undiagnosed after the onset of infectiousness (time 0 on the horizontal axis), under the assumption that 50% of the initial cohort has an average duration of infectiousness of 1 month (high-rate group), and 50% of the cohort has a duration of infectiousness of 6 months (low-rate group). The true total percentage of patients remaining infectious with time since onset of infectiousness (solid line) is compared against the proportion that would be expected to remain if the whole cohort was assumed to have the average time to diagnosis (3.5 months), and the proportion that would be expected to remain if the whole cohort was assumed to have a rate of diagnosis that is the average of the rates of the 2 groups (dotted line). The amount of the total population comprised of high-rate and low-rate persons at each time point is indicated by colored shading, demonstrating that the remaining cohort is increasingly comprised of low-rate individuals over time.