Progress towards onchocerciasis elimination in the participating countries of the African Programme for Onchocerciasis Control: Epidemiological evaluation results

Background: The African Programme for Onchocerciasis Control (APOC) was created in 1995 to establish community-directed treatment with ivermectin (CDTi) in order to control onchocerciasis as a public health problem in 20 African countries that had 80 % of the global disease burden. When research showed that CDTi may ultimately eliminate onchocerciasis infection, APOC was given in 2008 the additional objective to determine when and where treatment can be safely stopped. We report the results of epidemiological evaluations undertaken from 2008 to 2014 to assess progress towards elimination in CDTi areas with ≥6 years treatment. Methods: Skin snip surveys were undertaken in samples of first-line villages to determine the prevalence of O. volvulus microfilariae. There were two evaluation phases. The decline in prevalence was evaluated in phase 1A. Observed and model-predicted prevalences were compared after correcting for endemicity level and treatment coverage. Bayesian statistics and Monte Carlo simulation were used to classify the decline in prevalence as faster than predicted, on track or delayed. Where the prevalence approached elimination levels, phase 1B was launched to determine if treatment could be safely stopped. Village sampling was extended to the whole CDTi area. Survey data were analysed within a Bayesian framework to determine if stopping criteria (overall prevalence <1.4 % and maximum stratum prevalence <5 %) were met. Results: In phase 1A 127 665 people from 639 villages in 54 areas were examined. The prevalence had fallen dramatically. The decline in prevalence was faster than predicted in 23 areas, on track in another 23 and delayed in eight areas. In phase 1B 108 636 people in 392 villages were examined in 22 areas of which 13 met the epidemiological criteria for stopping treatment. Overall, 32 areas (25.4 million people) had reached or were close to elimination, 18 areas (17.4 million) were on track but required more years treatment, and in eight areas (10.4 million) progress was unsatisfactory. Conclusions: Onchocerciasis has been largely controlled as a public health problem. Great progress has been made towards elimination which already appears to have been achieved for millions of people. For most APOC countries, nationwide onchocerciasis elimination is within reach

African Program for Onchocerciasis Control 1995–2010: Impact of Annual Ivermectin Mass Treatment on Off-Target Infectious Diseases

Since its initiation in 1995, the African Program for Onchocerciasis Control (APOC) has had a substantial impact on the prevalence and burden of onchocerciasis through annual ivermectin mass treatment. Ivermectin is a broad-spectrum anti-parasitic agent that also has an impact on other co-endemic parasitic infections. In this study, we roughly assessed the additional impact of APOC activities on the burden of the most important off-target infections: soil-transmitted helminthiases (STH; ascariasis, trichuriasis, hookworm, and strongyloidiasis), lymphatic filariasis (LF), and scabies. Based on a literature review, we formulated assumptions about the impact of ivermectin treatment on the disease burden of these off-target infections. Using data on the number of ivermectin treatments in APOC regions and the latest estimates of the burden of disease, we then calculated the impact of APOC activities on off-target infections in terms of disability-adjusted life years (DALYs) averted. We conservatively estimated that between 1995 and 2010, annual ivermectin mass treatment has cumulatively averted about 500 thousand DALYs from co-endemic STH infections, LF, and scabies. This impact comprised approximately an additional 5.5% relative to the total burden averted from onchocerciasis (8.9 million DALYs) and indicates that the overall cost-effectiveness of APOC is even higher than previously reported

Projected Number of People With Onchocerciasis-Loiasis Coinfection in Africa, 1995 to 2025

BACKGROUND: Onchocerciasis elimination through mass drug administration (MDA) is hampered by coendemicity of Loa loa, as people with high L. loa microfilariae (mf) density can develop serious adverse events (SAEs) after ivermectin treatment. We assessed the geographical overlap of onchocerciasis and loiasis prevalence and estimated the number of coinfected individuals at risk of post-ivermectin SAEs in West and Central Africa from 1995 to 2025. METHODS: Focusing on regions with suspected loiasis transmission in 14 countries, we overlaid precontrol maps of loiasis and onchocerciasis prevalence to calculate precontrol prevalence of coinfection by 5 km2 × 5 km2 pixel, distinguishing different categories of L. loa mf intensity. Using statistical and mathematical models, we predicted prevalence of both infections and coinfection for 2015 and 2025, accounting for the impact of MDA with ivermectin. RESULTS: The number of people infected with onchocerciasis was predicted to decline from almost 19 million in 1995 to 4 million in 2025. Of these, 137 000 people were estimated to also have L. loa hypermicrofilaremia (≥20 000 L. loa mf/mL) in 1995, declining to 31 000 in 2025. In 2025, 92.8% of coinfecte

How can onchocerciasis elimination in Africa be accelerated? Modelling the impact of increased ivermectin treatment frequency and complementary vector control

Background: Great strides have been made toward onchocerciasis elimination by mass drug administration (MDA) of ivermectin. Focusing on MDA-eligible areas, we investigated where the elimination goal can be achieved by 2025 by continuation of current practice (annual MDA with ivermectin) and where intensification or additional vector control is required. We did not consider areas hypoendemic for onchocerciasis with loiasis coendemicity where MDA is contraindicated. Methods: We used 2 previously published mathematical models, ONCHOSIM and EPIONCHO, to simulate future trends in microfilarial prevalence for 80 different settings (defined by precontrol endemicity and past MDA frequency and coverage) under different future treatment scenarios (annual, biannual, or quarterly MDA with different treatment coverage through 2025, with or without vector control strategies), assessing for each strategy whether it eventually leads to elimination. Results: Areas with 40%–50% precontrol microfilarial prevalence and ≥10 years of annual MDA may achieve elimination with a further 7 years of annual MDA, if not achieved already, according to both models. For most areas with 70%–80% precontrol prevalence, ONCHOSIM predicts that either annual or biannual MDA is sufficient to achieve elimination by 2025, whereas EPIONCHO predicts that elimination will not be achieved even with complementary vector control. Conclusions: Whether elimination will be reached by 2025 depends on precontrol endemicity, control history, and strategies chosen from now until 2025. Biannual or quarterly MDA will accelerate progress toward elimination but cannot guarantee it by 2025 in high-endemicity areas. Long-term concomitant MDA and vector control for high-endemicity areas might be useful

Baseline mapping of neglected tropical diseases in Africa: the accelerated WHO/AFRO mapping project

Mapping is a prerequisite for effective implementation of interventions against neglected tropical diseases (NTDs). Before the accelerated World Health Organization (WHO)/Regional Office for Africa (AFRO) NTD Mapping Project was initiated in 2014, mapping efforts in many countries were frequently carried out in an ad hoc and nonstandardized fashion. In 2013, there were at least 2,200 different districts (of the 4,851 districts in the WHO African region) that still required mapping, and in many of these districts, more than one disease needed to be mapped. During its 3-year duration from January 2014 through the end of 2016, the project carried out mapping surveys for one or more NTDs in at least 2,500 districts in 37 African countries. At the end of 2016, most (90%) of the 4,851 districts had completed the WHO-required mapping surveys for the five targeted Preventive Chemotherapy (PC)-NTDs, and the impact of this accelerated WHO/AFRO NTD Mapping Project proved to be much greater than just the detailed mapping results themselves. Indeed, the AFRO Mapping Project dramatically energized and empowered national NTD programs, attracted donor support for expanding these programs, and developed both a robust NTD mapping database and data portal. By clarifying the prevalence and burden of NTDs, the project provided not only the metrics and technical framework for guiding and tracking program implementation and success but also the research opportunities for developing improved diagnostic and epidemiologic sampling tools for all 5 PC-NTDs-lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminthiasis, and trachoma

Model-based geostatistical mapping of the prevalence of onchocerca volvulus in West Africa.

Background: The initial endemicity (pre-control prevalence) of onchocerciasis has been shown to be an important determinant of the feasibility of elimination by mass ivermectin distribution. We present the first geostatistical map of microfilarial prevalence in the former Onchocerciasis Control Programme in West Africa (OCP) before commencement of antivectorial and antiparasitic interventions. Methods and Findings: Pre-control microfilarial prevalence data from 737 villages across the 11 constituent countries in the OCP epidemiological database were used as ground-truth data. These 737 data points, plus a set of statistically selected environmental covariates, were used in a Bayesian model-based geostatistical (B-MBG) approach to generate a continuous surface (at pixel resolution of 5 km x 5km) of microfilarial prevalence in West Africa prior to the commencement of the OCP. Uncertainty in model predictions was measured using a suite of validation statistics, performed on bootstrap samples of held-out validation data. The mean Pearson’s correlation between observed and estimated prevalence at validation locations was 0.693; the mean prediction error (average difference between observed and estimated values) was 0.77%, and the mean absolute prediction error (average magnitude of difference between observed and estimated values) was 12.2%. Within OCP boundaries, 17.8 million people were deemed to have been at risk, 7.55 million to have been infected, and mean microfilarial prevalence to have been 45% (range: 2–90%) in 1975. Conclusions and Significance: This is the first map of initial onchocerciasis prevalence in West Africa using B-MBG. Important environmental predictors of infection prevalence were identified and used in a model out-performing those without spatial random effects or environmental covariates. Results may be compared with recent epidemiological mapping efforts to find areas of persisting transmission. These methods may be extended to areas where data are sparse, and may be used to help inform the feasibility of elimination with current and novel tools

Sensitivity analysis for the impact of assumed parameter values on the total averted burden.

<p>For each parameter (y-axis), the figure between brackets indicates the relative amount by which it was varied in the sensitivity analysis.</p

Plots of model performance.

<p>A) Scatter-plot of observed versus estimated microfilarial prevalence in those aged ≥ 5 years (<i>P</i>_<i>mf</i>) at validation locations. The Pearson’s correlation coefficient between observed and estimated values was 0.693. The 1:1 line of perfect correlation is shown for reference. The data are coloured by the absolute difference between observed and expected values, mapped from a continuum between 0 and 1. B) Receiver Operating Characteristic (ROC) curves for each endemicity class (black line, hypoendemic; red line, mesoendemic; green line, hyperendemic; blue line, holoendemic). AUC values for each endemicity class are also displayed on the plot. C) Probability-probability plot of the proportion of true values of <i>P</i>_<i>mf</i> at validation locations that exceed their predicted probability threshold for a series of probability thresholds from 1% to 100%. Deviation from the 1:1 dashed line in this plot represents the difference between the distributions of observed and estimated microfilarial prevalence values at validation locations. D) Frequency histogram of observed and estimated <i>P</i>_<i>mf</i> at validation locations, classified according to their true class (Observed <i>P</i>_<i>mf</i> panel) and estimated endemicity class (Expected <i>P</i>_<i>mf</i> panel).</p