Geographic and ecologic heterogeneity in elimination thresholds for the major vector-borne helminthic disease, lymphatic filariasis.
BACKGROUND
Large-scale intervention programmes to control or eliminate several infectious diseases are currently underway worldwide. However, a major unresolved question remains: what are reasonable stopping points for these programmes? Recent theoretical work has highlighted how the ecological complexity and heterogeneity inherent in the transmission dynamics of macroparasites can result in elimination thresholds that vary between local communities. Here, we examine the empirical evidence for this hypothesis and its implications for the global elimination of the major macroparasitic disease, lymphatic filariasis, by applying a novel Bayesian computer simulation procedure to fit a dynamic model of the transmission of this parasitic disease to field data from nine villages with different ecological and geographical characteristics. Baseline lymphatic filariasis microfilarial age-prevalence data from three geographically distinct endemic regions, across which the major vector populations implicated in parasite transmission also differed, were used to fit and calibrate the relevant vector-specific filariasis transmission models. Ensembles of parasite elimination thresholds, generated using the Bayesian fitting procedure, were then examined in order to evaluate site-specific heterogeneity in the values of these thresholds and investigate the ecological factors that may underlie such variability


RESULTS
We show that parameters of density-dependent functions relating to immunity, parasite establishment, as well as parasite aggregation, varied significantly between the nine different settings, contributing to locally varying filarial elimination thresholds. Parasite elimination thresholds predicted for the settings in which the mosquito vector is anopheline were, however, found to be higher than those in which the mosquito is culicine, substantiating our previous theoretical findings. The results also indicate that the probability that the parasite will be eliminated following six rounds of Mass Drug Administration with diethylcarbamazine and albendazole decreases markedly but non-linearly as the annual biting rate and parasite reproduction number increases.


CONCLUSIONS
This paper shows that specific ecological conditions in a community can lead to significant local differences in population dynamics and, consequently, elimination threshold estimates for lymphatic filariasis. These findings, and the difficulty of measuring the key local parameters (infection aggregation and acquired immunity) governing differences in transmission thresholds between communities, mean that it is necessary for us to rethink the utility of the current anticipatory approaches for achieving the elimination of filariasis both locally and globally.
Department of Infectious Disease Epidemiology, Imperial College London, UK. m.gambhir@imperial.ac.uk
Manoj
M
Gambhir
Moses
M
Bockarie
Daniel
D
Tisch
James
J
Kazura
Justin
J
Remais
Robert
R
Spear
Edwin
E
Michael
D015766:Albendazole / Q000627:therapeutic use; D000818:Animals; D000871:Anthelmintics / Q000627:therapeutic use; D001499:Bayes Theorem; D003198:Computer Simulation; D004049:Diethylcarbamazine / Q000627:therapeutic use; D004605:Elephantiasis, Filarial / Q000188:drug therapy / Q000453:epidemiology / Q000517:prevention & control* / Q000635:transmission*; D006801:Humans; D007303:Insect Vectors / Q000469:parasitology
D000871:Anthelmintics; D015766:Albendazole; D004049:Diethylcarbamazine