COMET-LF: A Compartmental Model of Dynamics of Infection, Disease, and Elimination Strategies for Lymphatic Filariasis

Lymphatic filariasis (LF) is a mosquito-borne neglected tropical disease (NTD) caused by filarial worms. India accounted for 55% of the global population at risk of LF in 2021. The World Health Organization (WHO) has targeted LF elimination by 2030; however, India aims to achieve LF elimination prior to the global WHO NTD target. Mathematical models are useful tools to evaluate and guide elimination strategies. We propose a new compartmental model--COmpartmental Modelling of Elimination strategies and Transmission of Lymphatic Filariasis (COMET-LF)--to assess the impact of mass drug administration (MDA) on LF elimination. Our model incorporates drug efficacy data from a clinical trial and generates estimates of disease (lymphoedema and hydrocele) prevalence. The model is calibrated to publicly available microfilaria (Mf) and disease prevalence data (2008-2013) from Bihar, India. Predictions of the number of MDA rounds needed for achieving the elimination threshold were generated for various endemic scenarios. The projected estimates were compared with established micro- (LYMFASIM) and macro- (EPIFIL) simulation models for LF transmission. Disease burden estimates and the impact of MDA on disease burden were generated using COMET-LF for different endemic scenarios. Our simulations suggest that the disease burden reduces over much longer timescales - 20 years for a reduction of 8%-11.5% following 5 rounds of MDA. We extended COMET-LF to a meta-population model to investigate the role of migration among neighbouring regions on elimination and resurgence probabilities. We found that high Mf prevalence in the spatial neighbourhood can increase the number of required MDA rounds for elimination up to 3 additional rounds for the two-drug regimen. Furthermore, we assess the impact of migration on the resurgence probability in a non-endemic region which is spatially adjacent to a high-Mf prevalence region and show that there is a significant risk of resurgence if Mf prevalence exceeds 5%. Our model can be easily tailored to specific blocks and districts to guide programmatic intervention for disease management and LF elimination. Author summaryLymphatic filariasis (LF) commonly occurs in tropical regions and is transmitted to humans by mosquitoes infected with larvae of parasitic roundworms. Some patients develop external symptoms including swollen limbs/male genitals that develop from damage to lymph nodes. Others do not develop external symptoms but may transmit the disease to non-infected humans through mosquito bites. LF causes physical disability, disfigurement and mental suffering. India has more than half of the global population at risk of developing LF. Currently, medications that kill the parasites are given yearly to the population at risk. A better understanding of the disease transmission and control measures is important to meet the 2030 elimination target set by the World Health Organization. We developed a new mathematical model (COMET-LF) that takes into account India-specific disease information for more accurate predictions. To validate our model, we compared the predictions with those from established models. COMET-LF can predict the number of years the drug has to be administered to stop LF transmission and the effect of drugs on disease prevalence. COMET-LF also shows that infected patients migrating from neighboring regions can increase transmission to regions where LF is under control. Notably, our model can help policy makers plan targeted control measures for specific regions.