Annual Mycobacterium tuberculosis Infection Risk and Interpretation of Clustering Statistics

Emilia Vynnycky, Martien W. Borgdorff, Dick van Soolingen, Paul E.M. Fine

Disclosures

Emerging Infectious Diseases. 2003;9(2) 

In This Article

Abstract and Introduction

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.

Studies are increasingly using levels of clustering of isolates from tuberculosis cases (proportion sharing identical DNA fingerprint patterns) to estimate the extent of disease attributable to recent transmission. To date, few studies have been conducted in unindustrialized countries, where the impact of tuberculosis and the proportion of disease attributable to recent transmission are greatest. Whether or not the properties and interpretation of clustering statistics in such settings are similar to those in industrialized populations is unclear.

Studies in industrialized countries have found relatively low overall levels of clustering (e.g., 30% to 40% during a 3-year period[1,2,3]) but much higher levels among younger versus older patients. This age differential probably reflects past trends in the annual risk for infection, which was high in the early 20th century (e.g., > 2% per year before 1940 in the Netherlands[4]) and is currently very low. Thus, a large proportion of disease in older patients is attributable to reactivation of infections acquired many years ago, and, given the short half-life of DNA fingerprint patterns,[5] only a small proportion of old patients share identical isolates with other patients. In some unindustrialized countries, on the other hand, where the annual risk for infection may not have changed much over time, the age differential in clustering might be small, given that a large proportion of disease even among older persons may be attributable to recent (re)infection. Understanding the effect of the magnitude of the annual risk for tuberculous infection on clustering frequency helps determine how molecular epidemiologic data can be best applied to estimate the extent of ongoing transmission of Mycobacterium tuberculosis, and hence to identify optimal control strategies.

We explored how the magnitude and trend in the annual risk for infection influence the age-specific proportion of clustered cases and its relationship to the extent of disease attributable to recent transmission. We use a model of the transmission dynamics of M. tuberculosis previously calibrated to data from the Netherlands,[6] where isolates from all tuberculosis cases with onset since 1993 have been routinely DNA fingerprinted.[1] We describe the general epidemiologic assumptions in the model and how it distinguishes between cases according to the DNA fingerprint pattern of the strain causing the disease episode, which is needed to calculate clustering statistics.

Comments

3090D553-9492-4563-8681-AD288FA52ACE

processing....