Mixture analysis of tuberculin survey data from northern Malawi and critique of the method.

SETTING: Various methods have been used to estimate the prevalence of Mycobacterium tuberculosis infection from tuberculin survey data. All are complicated by prior sensitisation to environmental mycobacteria and bacille Calmette-Guérin (BCG) vaccination. Mixture analysis has recently been proposed as a means of overcoming misclassification and improving infection prevalence estimates.
OBJECTIVE: To compare conventional and mixture model estimates of M. tuberculosis infection prevalence.
DESIGN: Mixture models with two or three univariate normal components were fitted to the results of 53 909 tuberculin tests conducted in northern Malawi during 1980-1984. Data were stratified by BCG status, sex and age and corrected for digit preference. Prevalence estimates derived from mixture models were compared with those of conventional methods.
RESULTS: The optimal model was age-dependent, with three- and one-component solutions preferred in younger and older age groups, respectively. In contrast with findings from elsewhere, a component corresponding to BCG vaccination was indistinguishable from that attributable to environmental mycobacterial exposure, and infection prevalence estimates in younger individuals with a BCG scar were inflated, irrespective of the method used.
CONCLUSION: The validity of infection prevalence and incidence estimates based on mixture modelling is probably locale-dependent, and the assumptions underlying mixture models may not realistically reflect underlying immunological processes.