Annual Mycobacterium tuberculosis infection risk and interpretation of clustering statistics

Several recent studies have used proportions of tuberculosis cases sharing identical DNA fingerprint patterns (i.e., isolate clustering) to estimate the extent of disease attributable to recent transmission. Using a model of introduction and transmission of strains with different DNA fingerprint patterns, we show that the properties and interpretation of clustering statistics may differ substantially between settings. For some unindustrialized countries, where the annual risk for infection has changed little over time, 70% to 80% of all age groups may be clustered during a 3-year period, which underestimates the proportion of disease attributable to recent transmission. In contrast, for a typical industrialized setting (the Netherlands), clustering declines with increasing age (from 75% to 15% among young and old patients, respectively) and underestimates the extent of recent transmission only for young patients. We conclude that, in some settings, clustering is an unreliable indicator of the extent of recent transmission.