Modelling variability in lymphatic filariasis: macrofilarial dynamics in the Brugia pahangi–cat model

Abstract

A striking feature of lymphatic filariasis is the considerable heterogeneity in infection burden observed between hosts, which greatly complicates the analysis of the population dynamics of the disease. Here, we describe the first application of the moment closure equation approach to model the sources and the impact of this heterogeneity for macrofilarial population dynamics. The analysis is based on the closest laboratory equivalent of the life cycle and immunology of infection in humans--cats chronically infected with the filarial nematode Brugia pahangi. Two sets of long-term experiments are analysed: hosts given either single primary infections or given repeat infections. We begin by quantifying changes in the mean and aggregation of adult parasites (inversely measured by the negative binomial parameter, kappa in cohorts of hosts using generalized linear models. We then apply simple stochastic models to interpret observed patterns. The models and empirical data indicate that parasite aggregation tracks the decline in the mean burden with host age in primary infections. Conversely, in repeat infections, aggregation increases as the worm burden declines with experience of infection. The results show that the primary infection variability is consistent with heterogeneities in parasite survival between hosts. By contrast, the models indicate that the reduction in parasite variability with time in repeat infections is most likely due to the 'filtering' effect of a strong, acquired immune response, which gradually acts to remove the initial variability generated by heterogeneities in larval mortality. We discuss this result in terms of the homogenizing effect of host immunity-driven density-dependence on macrofilarial burden in older hosts.

Transmission dynamics of lymphatic filariasis: density‐dependence in the uptake ofWuchereria bancroftimicrofilariae by vector mosquitoes

“…This framework has allowed us to reveal for the first time evidence not only for the presence of density‐dependence in this filarial transmission process in each of the three major vector mosquito genera, but also for the existence of significant variation in the degree of such regulation between these vectors. These results represent significant new findings regarding filariasis transmission, and are thus of great value to our overall aim of gaining a better quantitative understanding of the population dynamics and control of this parasite (Chan et al ., 1998; Michael et al ., 1998; Norman et al ., 2000; Michael, 2002).…”

Pathogen Growth in Insect Hosts: Inferring the Importance of Different Mechanisms Using Stochastic Models and Response-Time Data

“…An important assumption made by deterministic models is that pathogen populations are so large that there are no effects of demographic stochasticity, the variability in population growth that results from the timing of chance events such as reproduction or death (Borsuk and Lee 2009). A growing body of theoretical literature, however, suggests that stochastic events are important (Michael et al 1998;Grant et al 2008;Vaughan et al 2012), suggesting in turn that deterministic models are insufficient for describing these dynamics.…”

Transmission intensity and the patterns of Onchocerca volvulus infection in human communities.

“…In contrast, there are strong indications in favor of the operation of exposure-dependent, and possibly immunologically mediated, constraints on infection rates. [21][22][23][24][25] These mechanisms would act mainly against incoming parasites, not upon established worms. [26][27][28] In consequence, we focus upon parasite establishment within humans, although our approach is more phenomenological than mechanistic, i.e., we do not intend to model, at this stage, the precise nature of the underlying processes by which such constraints operate.…”