Magnitude and sources of bias in the detection of mixed strain M. tuberculosis infection. (7th March 2015)

• Record Type: Journal Article
• Authors: Plazzotta, Giacomo; Cohen, Ted; Colijn, Caroline
• Is Part Of: Journal of theoretical biology. Volume 368(2015)
• Page Start: 67
• Page End: 73
• Publication Date: 2015-03-07
• Subjects: Study designs aimed to detect mixed infection -- Majority and minority strain -- Prevalence of mixed infection -- Posterior distribution of the prevalence of mixed infection -- Estimates of the prevalence of mixed infection; Biology -- Periodicals; Biological Science Disciplines -- Periodicals; Biology -- Periodicals; Biologie -- Périodiques; Theoretische biologie; Biology; Periodicals; 571.05
• DOI: 10.1016/j.jtbi.2014.12.009
• Languages: English
• ISSNs: 0022-5193

Abstract

Abstract: High resolution tests for genetic variation reveal that individuals may simultaneously host more than one distinct strain of Mycobacterium tuberculosis . Previous studies find that this phenomenon, which we will refer to as "mixed infection", may affect the outcomes of treatment for infected individuals and may influence the impact of population-level interventions against tuberculosis. In areas where the incidence of TB is high, mixed infections have been found in nearly 20% of patients; these studies may underestimate the actual prevalence of mixed infection given that tests may not be sufficiently sensitive for detecting minority strains. Specific reasons for failing to detect mixed infections would include low initial numbers of minority strain cells in sputum, stochastic growth in culture and the physical division of initial samples into parts (typically only one of which is genotyped). In this paper, we develop a mathematical framework that models the study designs aimed to detect mixed infections. Using both a deterministic and a stochastic approach, we obtain posterior estimates of the prevalence of mixed infection. We find that the posterior estimate of the prevalence of mixed infection may be substantially higher than the fraction of cases in which it is detected. We characterize this bias in terms of the sensitivity of the genotyping method and the relative growth rates and initial population sizes of the different strains collected in sputum. Abstract : Author-Highlights: We develop a mathematical model for study designs aimed to detect TB mixed infection. We obtain Bayesian posterior estimates of the prevalence of mixed infection. The bias between the posterior estimate and the observed prevalence is discussed. The posterior estimate can be substantially higher than the raw percentage.