Bill & Melinda Gates Foundation.

Due to the COVID-19 pandemic, many key neglected tropical disease (NTD) activities have been postponed. This hindrance comes at a time when the NTDs are progressing towards their ambitious goals for 2030. Mathematical modelling on several NTDs, namely gambiense sleeping sickness, lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminthiases (STH), trachoma, and visceral leishmaniasis, shows that the impact of this disruption will vary across the diseases. Programs face a risk of resurgence, which will be fastest in high-transmission areas. Furthermore, of the mass drug administration diseases, schistosomiasis, STH, and trachoma are likely to encounter faster resurgence. The case-finding diseases (gambiense sleeping sickness and visceral leishmaniasis) are likely to have fewer cases being detected but may face an increasing underlying rate of new infections. However, once programs are able to resume, there are ways to mitigate the impact and accelerate progress towards the 2030 goals.

BackgroundWith the 2020 target year for elimination of lymphatic filariasis (LF) approaching, there is an urgent need to assess how long mass drug administration (MDA) programs with annual ivermectin + albendazole (IA) or diethylcarbamazine + albendazole (DA) would still have to be continued, and how elimination can be accelerated. We addressed this using mathematical modeling.MethodsWe used 3 structurally different mathematical models for LF transmission (EPIFIL, LYMFASIM, TRANSFIL) to simulate trends in microfilariae (mf) prevalence for a range of endemic settings, both for the current annual MDA strategy and alternative strategies, assessing the required duration to bring mf prevalence below the critical threshold of 1%.ResultsThree annual MDA rounds with IA or DA and good coverage (≥65%) are sufficient to reach the threshold in settings that are currently at mf prevalence <4%, but the required duration increases with increasing mf prevalence. Switching to biannual MDA or employing triple-drug therapy (ivermectin, diethylcarbamazine, and albendazole [IDA]) could reduce program duration by about one-third. Optimization of coverage reduces the time to elimination and is particularly important for settings with a history of poorly implemented MDA (low coverage, high systematic noncompliance).ConclusionsModeling suggests that, in several settings, current annual MDA strategies will be insufficient to achieve the 2020 LF elimination targets, and programs could consider policy adjustment to accelerate, guided by recent monitoring and evaluation data. Biannual treatment and IDA hold promise in reducing program duration, provided that coverage is good, but their efficacy remains to be confirmed by more extensive field studies.

BackgroundThere are growing demands for predicting the prospects of achieving the global elimination of neglected tropical diseases as a result of the institution of large-scale nation-wide intervention programs by the WHO-set target year of 2020. Such predictions will be uncertain due to the impacts that spatial heterogeneity and scaling effects will have on parasite transmission processes, which will introduce significant aggregation errors into any attempt aiming to predict the outcomes of interventions at the broader spatial levels relevant to policy making. We describe a modeling platform that addresses this problem of upscaling from local settings to facilitate predictions at regional levels by the discovery and use of locality-specific transmission models, and we illustrate the utility of using this approach to evaluate the prospects for eliminating the vector-borne disease, lymphatic filariasis (LF), in sub-Saharan Africa by the WHO target year of 2020 using currently applied or newly proposed intervention strategies.Methods and ResultsWe show how a computational platform that couples site-specific data discovery with model fitting and calibration can allow both learning of local LF transmission models and simulations of the impact of interventions that take a fuller account of the fine-scale heterogeneous transmission of this parasitic disease within endemic countries. We highlight how such a spatially hierarchical modeling tool that incorporates actual data regarding the roll-out of national drug treatment programs and spatial variability in infection patterns into the modeling process can produce more realistic predictions of timelines to LF elimination at coarse spatial scales, ranging from district to country to continental levels. Our results show that when locally applicable extinction thresholds are used, only three countries are likely to meet the goal of LF elimination by 2020 using currently applied mass drug treatments, and that switching to more intensive drug regimens, increasing the frequency of treatments, or switching to new triple drug regimens will be required if LF elimination is to be accelerated in Africa. The proportion of countries that would meet the goal of eliminating LF by 2020 may, however, reach up to 24/36 if the WHO 1% microfilaremia prevalence threshold is used and sequential mass drug deliveries are applied in countries.ConclusionsWe have developed and applied a data-driven spatially hierarchical computational platform that uses the discovery of locally applicable transmission models in order to predict the prospects for eliminating the macroparasitic disease, LF, at the coarser country level in sub-Saharan Africa. We show that fine-scale spatial heterogeneity in local parasite transmission and extinction dynamics, as well as the exact nature of intervention roll-outs in countries, will impact the timelines to achieving national LF elimination on this continent.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-017-0933-2) contains sup...

HighlightsNo single mathematical model captures all features of parasite transmission dynamics.Multi-model ensemble modelling can overcome biases of single models.A multi-model ensemble of three lymphatic filariasis models is proposed and evaluated.The multi-model ensemble outperformed the single models in predicting infection.The ensemble approach may improve use of models to inform disease control policy.

The low prevalence levels associated with lymphatic filariasis elimination pose a challenge for effective disease surveillance. As more countries achieve the World Health Organization criteria for halting mass treatment and move on to surveillance, there is increasing reliance on the utility of transmission assessment surveys (TAS) to measure success. However, the long-term disease outcomes after passing TAS are largely untested. Using 3 well-established mathematical models, we show that low-level prevalence can be maintained for a long period after halting mass treatment and that true elimination (0% prevalence) is usually slow to achieve. The risk of resurgence after achieving current targets is low and is hard to predict using just current prevalence. Although resurgence is often quick (&lt;5 years), it can still occur outside of the currently recommended postintervention surveillance period of 4–6 years. Our results highlight the need for ongoing and enhanced postintervention monitoring, beyond the scope of TAS, to ensure sustained success.

Stopping interventions is a critical decision for parasite elimination programmes. Quantifying the probability that elimination has occurred due to interventions can be facilitated by combining infection status information from parasitological surveys with extinction thresholds predicted by parasite transmission models. Here we demonstrate how the integrated use of these two pieces of information derived from infection monitoring data can be used to develop an analytic framework for guiding the making of defensible decisions to stop interventions. We present a computational tool to perform these probability calculations and demonstrate its practical utility for supporting intervention cessation decisions by applying the framework to infection data from programmes aiming to eliminate onchocerciasis and lymphatic filariasis in Uganda and Nigeria, respectively. We highlight a possible method for validating the results in the field, and discuss further refinements and extensions required to deploy this predictive tool for guiding decision making by programme managers.

Concern is growing regarding the prospects of achieving the global elimination of lymphatic filariasis (LF) by 2020. Apart from operational difficulties, evidence is emerging which points to unique challenges that could confound achieving LF elimination as extinction targets draw near. Diethylcarbamazine (DEC)-medicated salt may overcome these complex challenges posed by the endgame phase of parasite elimination. We calibrated LF transmission models using Bayesian data-model assimilation techniques to baseline and follow-up infection data from 11 communities that underwent DEC salt medication. The fitted models were used to assess the utility of DEC salt treatment for achieving LF elimination, in comparison with other current and proposed drug regimens, during the endgame phase. DEC-medicated salt consistently reduced microfilaria (mf) prevalence from 1% mf to site-specific elimination thresholds more quickly than the other investigated treatments. The application of DEC salt generally required less than one year to achieve site-specific LF elimination, while annual and biannual MDA options required significantly longer durations to achieve the same task. The use of DEC-medicated salt also lowered between-site variance in extinction timelines, especially when combined with vector control. These results indicate that the implementation of DEC-medicated salt, where feasible, can overcome endgame challenges facing LF elimination programs.