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

Results

As shown in Figure 3, very different age patterns in the proportion of disease attributable to recent transmission were predicted for the Netherlands and for settings in which the annual risk for infection has remained unchanged over time. In the Netherlands, the proportion of disease attributed to recent infection decreased dramatically with age, e.g., from 100% in the young to approximately 50% and 10% for 45- to 54-year-old patients and persons >65 years of age, respectively. The proportion of disease attributed to recent reinfection was very low for all age groups (<3%). For constant infection risk settings, the predicted proportion of disease attributable to recent transmission (i.e., recent infection or reinfection) was very similar, falling from 100% in the young to 85%, 88%, and 90% in the oldest age groups for the 0.1%, 1%, and 3% infection risk scenarios, respectively. On the other hand, large differences between settings were predicted in the proportion of disease attributed to initial infection or to reinfection. In all instances, the proportion attributed to reinfection was zero in the youngest age groups, but this proportion increased with age to 3%, 35%, and 80% for the 0.1%, 1%, and 3% annual infection risk assumptions, respectively. The proportion attributed to recent initial infection in these settings decreased from 100% in the young to 80%, 50%, and 15%, respectively, in old patients.

Model predictions of the proportion of disease attributable to primary and exogenous disease during the period 1993-1997 in the Netherlands.

As shown in Figure 4A, for each setting, the overall clustering (i.e., that seen among all age groups) was predicted to increase with study duration, e.g., from 15% for the Netherlands for a 1-year period to approximately 25% for a 5-year period. The clustering predicted for all the constant infection risk scenarios was similar in magnitude for each study period and increased from 60% to 70% for a 1-year period to 75% to 85% for a 5-year period. Since the overall clustering was not predicted to increase much for study periods of more than 3 years, clustering is defined using a 3-year period in the remainder of these analyses (represented by 1993-1995). As shown in Figure 4B, the clustering predicted for each age group was similar for each of the settings in which the annual risk for infection remained unchanged over time, and declined only slightly with age, e.g., from 83% for the youngest age group to approximately 75% for the oldest age category. In contrast, for the Netherlands, the clustering was predicted to decrease dramatically with age, from approximately 75% among young case-patients to approximately 15% in very old patients. This prediction is consistent with observed data (Figure 4B).

Model predictions of A) the overall percentage of cases clustered during different time periods from 1993 to 1997 and B) the age-specific percentage of (male) cases.

For settings in which the annual risk for infection remained unchanged over time at 0.1%, 1%, and 3%, the predicted clustering in each age group underestimated the proportion who had been recently infected or reinfected (Figure 5). In settings with an annual risk for infection of 0.1%, at least 90% of cases in each age group were predicted to have been recently (re)infected, whereas the proportion clustered decreased from about 85% in the youngest age group to approximately 70% for the oldest persons. For the Netherlands (described elsewhere[6]), clustering underestimated the proportion of disease attributable to recent transmission in the young (by up to 43%) and overestimated that for older patients (by up to 50%).

Comparison between model predictions of the clustering in different age groups and the proportion of disease attributable to recent infection or reinfection.

The positive and negative predictive values of being in a cluster, as an indicator of recent transmission, depended both on age and the study setting (Figure 6). For settings with a high annual risk for infection that had remained unchanged over time, model predictions suggested that most patients clustered in each age group were likely to have been recently (re)infected, corresponding to a positive predictive value of clustering for recent transmission of almost 100% in each age group (Figure 6A). The positive predictive value was estimated to decrease with age in the Netherlands from 100% in the very young to about 20% for the oldest patients.

Summary of model predictions of the A) positive predictive values of clustering (proportion of cases who are in a cluster who have been infected or reinfected <5 years before onset).

When unclustered cases were considered, the proportion of clinical case-patients who were estimated to have been infected >5 years previously was low (<5%) for young patients and increased with age for all settings, approaching 100% for patients >55 years of age in the Netherlands (Figure 6B). Almost all case-patients >55 years of age who were not in a cluster in the Netherlands were therefore estimated to have been infected >5 years previously and thus owed their disease to reactivation of latent foci. Of the adult case-patients who were not in a cluster in the other settings, the proportion who had been infected >5 years previously was <45%, 35%, and 20% if the annual risk for infection was 0.1%, 1%, and 3%, respectively.

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