Global eradication of lymphatic filariasis: the value of chronic disease control in parasite elimination programmes

Abstract

The ultimate goal of the global programme against lymphatic filariasis is eradication through irrevocable cessation of transmission using 4 to 6 years of annual single dose mass drug administration. The costs of eradication, managerial impediments to executing national control programmes, and scientific uncertainty about transmission endpoints, are challenges to the success of this effort, especially in areas of high endemicity where financial resources are limited. We used a combined analysis of empirical community data describing the association between infection and chronic disease prevalence, mathematical modelling, and economic analyses to identify and evaluate the feasibility of setting an infection target level at which the chronic pathology attributable to lymphatic filariasis--lymphoedema of the extremities and hydroceles--becomes negligible in the face of continuing transmission as a first stage option in achieving the elimination of this parasitic disease. The results show that microfilaria prevalences below a threshold of 3.55% at a blood sampling volume of 1 ml could constitute readily achievable and sustainable targets to control lymphatic filarial disease. They also show that as a result of the high marginal cost of curing the last few individuals to achieve elimination, maximal benefits can occur at this threshold. Indeed, a key finding from our coupled economic and epidemiological analysis is that when initial uncertainty regarding eradication occurs and prospects for resolving this uncertainty over time exist, it is economically beneficial to adopt a flexible, sequential, eradication strategy based on controlling chronic disease initially.

Figure 1. The association between prevalence of Wuchereria bancrofti microfilarial infection and prevalence of combined lymphoedema and hydrocele disease in filarial endemic communities from Sub-Saharan Africa (○) and India (•).

Field study references (n = 76) are given in Table S1 online. All mf prevalence values have been standardized to reflect sampling of 1 ml blood volumes (see text). The curve shows the best-fit logistic regression-based dose-response model incorporating a threshold parameter (equation 2) for the overall data with estimated values for a and τ of 1.07% (95% confidence limits (CLs): 0.54 to 1.60%) and 3.55% (95% CLs: 2.35 to 4.75%), respectively. Details of goodness of fit of the model are given in Supplemetary figure 1 online.

Figure 2

(A) Simulation results showing annual changes in overall community mf prevalence (scaled to 1 ml blood sampling volume) predicted by a deterministic model for filariasis transmission following a 5-year annual intervention programme with either the DEC/ALB (solid lines) or IVM/ALB (dashed lines) drug regimen. Initial community mf prevalence was set at 10%, and for each regimen predictions are shown for treatment coverages of 65%, 80% and 95% (portrayed by curves going from top to bottom respectively for each regimen). Upper horizontal dashed line shows the disease control mf threshold of 3.55%, while the lower line depicts the parasite elimination threshold of 0.5% mf prevalence. All figures are given at the scale of 1 ml blood sampling volume. Drug efficacy values are as given the text. (B) Numerical projections (dashed curves) of changes in LF infection prevalence (Mf % at 1 ml blood sampling scale) following different levels of reduction from initial equilibrium infection prevalence induced by annual MDA, as predicted by the EPIFIL model. Note that the greater the reduction of initial prevalence to below the mean disease threshold of 3.55% mf prevalence (solid horizontal line), the longer it will take to rebound to this threshold. For example, a reduction to a mf prevalence of 2.175% following annual MDA (second dashed curve from the bottom) will take up to 12 years to rebound to the disease incidence threshold.

Figure 3. Marginal effectiveness (numbers of individuals cured of mf) and costs of annual mass IVM/ALB chemotherapy against LF in Tanzania and the determination of the optimal level of parasite control.

Simulations of costs and effectiveness are based on the cost and demographic details given in table 2 and the impact of annual IVM/ALB mass treatment (at 80% coverage) on the prevalence of LF infection predicted by EPIFIL assuming the baseline Mf prevalence of 11.95% (at 1 ml blood sampling volume) in Tanzania. Annual costs and effectiveness are both expressed as a fraction of their total discounted figures following 10 years of intervention (table 2). The results show that the maximum number of individuals cured of mf per unit cost occurs at 85% parasite control following 3 years of annual MDA closer to achieving the long-term disease control target of 2.35% (see text) than the target of 100% parasite control or elimination.

Figure 4. The relationship between Expected Present Costs (EPCs) of implementing Strategies 3a (S3a) and 3b (S3b) (see text) and the probability of LF eradication for the Republic of Tanzania.

The lines show that as the uncertainty regarding the feasibility of eradication increases (probability of eradication becomes lower) the expected costs of these flexible strategies decline dramatically.