Different Mechanisms for Heterogeneity in Leprosy Susceptibility Can Explain Disease Clustering within Households

Abstract

The epidemiology of leprosy is characterized by heterogeneity in susceptibility and clustering of disease within households. We aim to assess the extent to which different mechanisms for heterogeneity in leprosy susceptibility can explain household clustering as observed in a large study among contacts of leprosy patients.We used a microsimulation model, parameterizing it with data from over 20,000 contacts of leprosy patients in Bangladesh. We simulated six mechanisms producing heterogeneity in susceptibility: (1) susceptibility was allocated at random to persons (i.e. no additional mechanism), (2) a household factor, (3, 4) a genetic factor (dominant or recessive), or (5, 6) half a household factor and half genetic. We further assumed that a fraction of 5%, 10%, and 20% of the population was susceptible, leading to a total of 18 scenarios to be fitted to the data. We obtained an acceptable fit for each of the six mechanisms, thereby excluding none of the possible underlying mechanisms for heterogeneity of susceptibility to leprosy. However, the distribution of leprosy among contacts did differ between mechanisms, and predicted trends in the declining leprosy case detection were dependent on the assumed mechanism, with genetic-based susceptibility showing the slowest decline. Clustering of leprosy within households is partially caused by an increased transmission within households independent of the leprosy susceptibility mechanism. Even a large and detailed data set on contacts of leprosy patients could not unequivocally reveal the mechanism most likely responsible for heterogeneity in leprosy susceptibility.

The Long Term Effect of Current and New Interventions on the New Case Detection of Leprosy: A Modeling Study

“…We compared the results based on different hypothesized mechanisms for susceptibility, because each of these mechanisms could be valid [9]. The quantitative results were sensitive to the mechanism chosen.…”

Leprosy exposure, infection and disease: a 25-year surveillance study of leprosy patient contacts

“…The high concentration of new cases among household contacts of leprosy patients has been demonstrated in numerous international studies (Fischer et al 2010, Sales et al 2011. Brazilian studies have also highlighted the elevated risk factors associated with these close contacts (Goulart et al 2008, Sales et al 2011.…”

“…Using computer modelling techniques (SIMCOLEP) to study a cohort of contacts in Bangladesh, Fischer et al (2010) concluded that there is heterogeneity in contact susceptibility and that the household contact him/herself is a significant factor independent of other susceptibilities.…”

Proposing a Compartmental Model for Leprosy and Parameterizing Using Regional Incidence in Brazil

“…Briefly, individuals are divided into 3 categories: resistant ( R , with probability q S = 1-p s ), susceptible to paucibacillary infection (S P , with probability p s *p p ), and susceptible to multibacillary infection (S M , with probability p s *q p where q P = 1-p p ). Resistance, q s , is meant to convey both genetic resistance and socioeconomic protective factors [13,18]. Resistance to multibacillary infection, p p , is meant to convey genetic resistance [18]; this value is higher than the observed proportion of new cases that are PB (0.8 vs. 0.54), but the discrepancy is explained by the high rate of self-cure among PB cases ( α PN ).…”