The effect of assortative mixing on stability of low helminth transmission levels and on the impact of mass drug administration: model explorations for onchocerciasis

Abstract

BackgroundStable low pre-control prevalences of helminth infection are not uncommon in field settings, yet it is poorly understood how such low levels can be sustained, thereby challenging efforts to model them. Disentangling possible facilitating mechanisms is important, since these may differently affect intervention impact. Here we explore the role of assortative (i.e. non-homogenous) mixing and exposure heterogeneity in helminth transmission, using onchocerciasis as an example.\n\nMethodology/Principal FindingsWe extended the established individual-based model ONCHOSIM to allow for assortative mixing, assuming that individuals who are relatively more exposed to fly bites are more connected to each other than other individuals in the population as a result of differential exposure to a sub-population of blackflies. We used the model to investigate how transmission stability, equilibrium microfilariae (mf) prevalence and intensity, and impact of mass drug administration depend on the assumed degree of assortative mixing and exposure heterogeneity, for a typical rural population of about 400 individuals. The model clearly demonstrated that with homogeneous mixing and moderate levels of exposure heterogeneity, onchocerciasis could not be sustained below 35% mf prevalence. In contrast, assortative mixing stabilised onchocerciasis prevalence at levels as low as 8% mf prevalence. Increasing levels of assortative mixing significantly reduced the probability of interrupting transmission, given the same duration and coverage of mass drug administration.\n\nConclusions/SignificanceAssortative mixing patterns are an important factor to explain stable low prevalence situations and are highly relevant for prospects of elimination. Their effect on the pre-control distribution of mf intensities in human populations is only detectable in settings with mf prevalences <30%, where high skin mf density in mf-positive people may be an indication of assortative mixing. Local spatial variation in larval infection intensity in the blackfly intermediate host may also be an indicator of assortative mixing.\n\nAuthor summaryMost mathematical models for parasitic worm infections predict that at low prevalences transmission will fade out spontaneously because of the low mating probability of male and female worms. However, sustained low prevalence situations do exist in reality. Low prevalence areas have become of particular interest now that several worm infections are being targeted for elimination and the question arises whether transmission in such areas is driven locally and should be targeted with interventions. We hypothesise that an explanation for the existence of low prevalence areas is assortative mixing, which is the preferential mixing of high-risk groups among themselves and which has been shown to play an important role in transmission of other infectious diseases. For onchocerciasis, assortative mixing would mean that transmission is sustained by a sub-group of people and a connected sub-population of the blackfly intermediate host that mix preferentially with each other. Using a mathematical model, we study how assortative mixing allows for sustained low prevalences and show that it decreases the probability of interrupting transmission by means of mass drug administration. We further identify data sources that may be used to quantify the degree of assortative mixing in field settings.