Modelling Neglected Tropical Diseases diagnostics: the sensitivity of skin snips for Onchocerca volvulus in near elimination and surveillance settings.

BACKGROUND: The African Programme for Onchocerciasis Control has proposed provisional thresholds for the prevalence of microfilariae in humans and of L3 larvae in blackflies, below which mass drug administration (MDA) with ivermectin can be stopped and surveillance started. Skin snips are currently the gold standard test for detecting patent Onchocerca volvulus infection, and the World Health Organization recommends their use to monitor progress of treatment programmes (but not to verify elimination). However, if they are used (in transition and in parallel to Ov-16 serology), sampling protocols should be designed to demonstrate that programmatic goals have been reached. The sensitivity of skin snips is key to the design of such protocols. METHODS: We develop a mathematical model for the number of microfilariae in a skin snip and parameterise it using data from Guatemala, Venezuela, Ghana and Cameroon collected before the start of ivermectin treatment programmes. We use the model to estimate sensitivity as a function of time since last treatment, number of snips taken, microfilarial aggregation and female worm fertility after exposure to 10 annual rounds of ivermectin treatment. RESULTS: The sensitivity of the skin snip method increases with time after treatment, with most of the increase occurring between 0 and 5 years. One year after the last treatment, the sensitivity of two skin snips taken from an individual infected with a single fertile female worm is 31 % if there is no permanent effect of multiple ivermectin treatments on fertility; 18 % if there is a 7 % reduction per treatment, and 0.6 % if there is a 35 % reduction. At 5 years, the corresponding sensitivities are 76 %, 62 % and 4.7 %. The sensitivity improves significantly if 4 skin snips are taken: in the absence of a permanent effect of ivermectin, the sensitivity of 4 skin snips is 53 % 1 year and 94 % 5 years after the last treatment. CONCLUSIONS: Our model supports the timelines proposed by APOC for post-MDA follow-up and surveillance surveys every 3-5 years. Two skin snips from the iliac region have reasonable sensitivity to detect residual infection, but the sensitivity can be significantly improved by taking 4 snips. The costs and benefits of using four versus two snips should be evaluated

Modelling the impact of ivermectin on River Blindness and its burden of morbidity and mortality in African Savannah: EpiOncho projections

BACKGROUND: The African Programme for Onchocerciasis Control (APOC) has refocused its goals on the elimination of infection where possible, seemingly achievable by 15–17 years of annual mass distribution of ivermectin in some African foci. Previously, APOC had focused on the elimination of onchocerciasis as a public health problem. Timeframes have been set by the World Health Organization, the London Declaration on Neglected Tropical Diseases and the World Bank to achieve these goals by 2020–2025. METHODS: A novel mathematical model of the dynamics of onchocercal disease is presented which links documented associations between Onchocerca volvulus infection and the prevalence and incidence of morbidity and mortality to model outputs from our host age- and sex-structured onchocerciasis transmission framework (EpiOncho). The model is calibrated for African savannah settings, and used to assess the impact of long-term annual mass administration of ivermectin on infection and ocular and skin disease and to explore how this depends on epidemiological and programmatic variables. RESULTS: Current onchocerciasis disease projections, which do not account for excess mortality of sighted individuals with heavy microfilarial loads, underestimate disease burden. Long-term annual ivermectin treatment is highly effective at reducing both the morbidity and mortality associated with onchocerciasis, and this result is not greatly influenced by treatment coverage and compliance. By contrast, impact on microfilarial prevalence and intensity is highly dependent on baseline endemicity, treatment coverage and systematic non-compliance. CONCLUSIONS: The goals of eliminating morbidity and infection with ivermectin alone are distinctly influenced by epidemiological and programmatic factors. Whilst the former goal is most certainly achievable, reaching the latter will strongly depend on initial endemicity (the higher the endemicity, the greater the magnitude of inter-treatment transmission), advising caution when generalising the applicability of successful elimination outcomes to other areas. The proportion of systematic non-compliers will become far more influential in terms of overall success in achieving elimination goals

Final report of the Conference on the eradicability of Onchocerciasis

Sixty-four experts from a variety of disciplines attended a Conference on the Eradicability of Onchocerciasis at The Carter Center, in Atlanta GA, held January 22-24, 2002. The Conference, which was organized by The Carter Center and the World Health Organization, with funding from the Bill & Melinda Gates Foundation, addressed the question: "Is onchocerciasis (River Blindness) eradicable with current knowledge and tools?" Former US President Jimmy Carter attended part of the final plenary proceedings on January 24. The Conference consisted of a series of presentations by invited expert speakers (Appendix C) and further deliberations in four workgroups (Appendix D) followed by plenary discussion of major conclusions. The presentations underlined epidemiological and entomological differences between onchocerciasis in Africa and the Americas. Whilst onchocerciasis in Africa covers extensive areas and is associated with striking human and fly population migrations and remarkably efficient black fly vectors, in the Americas onchocerciasis is found in limited foci. Human and fly population migration are not major problems in the Americas, where most black fly species are inefficient, though some efficient black flies are also found there. Vector control has been effectively applied in the Onchocerciasis Control Program in West Africa (OCP) with remarkable results, interrupting transmission in most parts of the original Program area. The use of ivermectin has given variable results: while ivermectin treatment has been effective in all endemic areas in controlling onchocerciasis as a public health problem, its potential for interrupting transmission is more promising in hypo- and mesoendemic areas. The African Program for Onchocerciasis Control (APOC), which supports onchocerciasis control in endemic African countries outside the OCP, applies ivermectin, its principal control tool, to communities in high-risk areas as determined by rapid epidemiological mapping of onchocerciasis (REMO) and Geographic Information Systems (GIS). In the Americas, through support of the Onchocerciasis Elimination Program in the Americas (OEPA), a strategy of bi-annual ivermectin treatment of at least 85% of the eligible populations in all endemic communities is showing very good results and promises to be effective in eliminating onchocerciasis in the region.The Conference concluded that onchocerciasis is not eradicable using current tools due to the major barriers to eradication in Africa. However, the Conference also concluded that in most if not all the Americas, and possibly Yemen and some sites in Africa, transmission of onchocerciasis can be eliminated using current tools. The Conference recommended that where interruption of transmission is feasible and cost effective, programs should aim for that goal using all appropriate and available interventions so that the Onchocerca volvulus can eventually be eliminated and interventions halted. Although interruption of transmission of onchocerciasis cannot currently be achieved in most of Africa, the Conference recommended that efforts be made to preserve areas in West Africa made free of onchocerciasis transmission through the Onchocerciasis Control Program over the past 25 years. In the remaining hyper and mesoendemic foci in Africa, continued annual distribution of ivermectin will keep onchocerciasis controlled to a point where it is no longer a public health problem or constraint to economic development

The burden of disease due to onchocerciasis and lymphatic filariasis in Africa:past, present and futureNNaattaalliiee

The dissertation titled “The burden of disease due to onchocerciasis and lymphatic filariasis in Africa: past, present and future” concerns two important parasitic infectious diseases of the tropics. Both infections are caused by a specific species of filarial worms and can cause a broad spectrum of clinical morbidity in the affected population, including blindness (onchocerciasis) and elephantiasis/elephant legs (Lymphatic Filariasis, LF). The research focused on how the disease burden of onchocerciasis and LF, in terms of total cases and life years with disabilities (DALYs), has changed since the introduction of large-scale mass treatment programs in Africa and what burden will remain in 2030. DALYs are a measure that takes into account both loss of quality of life and premature death. To calculate this, the association between infection and morbidity at the community level prior to mass treatment was first quantified. Subsequently, mathematical models have been used to calculate the impact of interventions on initial levels of infection by onchocerciasis and LF across Africa. The study predicted past, current and future disease prevalence, as well as the number of cases and lost DALYs due to onchocerciasis and LF. This work concludes that interventions have a remarkable impact on the prevention of onchocerciasis and LF, although by 2030 millions of people will still suffer from morbidity in Africa from one or both infections

Cellular and humoral immune responses in onchocerciasis : correlations with clinical signs and infection intensity

Thesis (Ph. D.)--Michigan State University. Department of Microbiology and Public Health, 1989Includes bibliographical references (pages 44-56

Spatial and temporal distribution of Onchocerciasis in West Africa with particular reference to Ghana

Background. Quantifying and predicting the effect of control interventions against infectious diseases requires knowledge about prevalence prior to the implementation of such control measures as well as knowledge of key parameters which affect model outcomes. Here is presented the first geostatistical map estimating the prevalence of human onchocerciasis in the former Onchocerciasis Control Programme in West Africa (OCP) before the initiation of vector control operations in 1975. The map is used to quantify the burden of onchocercal skin disease prior to interventions. The results of a socioeconomic survey investigating coverage and compliance to community-directed treatment with ivermectin are then presented. Methods and Findings. The OCP epidemiological database was investigated for spatial autocorrelation. A total of 737 village surveys had parasitological examinations conducted prior to the start of control. Using these 737 pre-control data points plus environmental covariates, a Bayesian model-based geostatistical (B-MBG) approach was used to generate a continuous surface (at a pixel resolution of 25km2) of microfilarial prevalence in West Africa prior to the commencement of the OCP. The mean Pearson’s correlation between observed prevalence and model-estimates of prevalence at hold-out locations was 0.693; mean prediction error was 0.77% and mean absolute prediction error was 12.2%. Within OCP boundaries, 17.8 million people were deemed to be at risk and 7.6 million infected in 1975 which is greater than previous estimates. The mean microfilarial prevalence across all countries was 45% (range: 2–90%). Conclusions and Significance. This is the first map of continuous onchocerciasis prevalence in West Africa, developed using robust geostatistical methods. Important environmental predictors of infection prevalence were identified and used in a model that out-performs those without spatial-random effects or environmental covariates. Our results may be compared with recent epidemiological mapping efforts to find areas of persisting transmission, informing feasibility of elimination with current and novel tools.Open Acces

Modelling onchocerciasis transmission and control

In 1990 the World Health Organization (WHO) coordinated Onchocerciasis Control Programme in West Africa (OCP) used this slogan for evaluating fifteen years of control of the parasitic disease onchocerciasis and for expressing its optimism about the future. Based on the obvious success of OCP and on the availability of a safe and effective drug (ivermectin), the UNDP/World BanklWHO Special Programme for Research & Training in Tropical Diseases (TDR) has announced onchocerciasis to be one of the tropical diseases with good prospects for worldwide elimination, at least as a public health problem (the others being Chagas disease, Lymphatic filariasis, and Leprosy!). To judge slogans and statements like these, and in particular to determine under which circumstances and with what strategies they could become a realistic perspective, one should perform an integrated and detailed study of the dynamics of the disease and the impact of control. Such a study should preferably be embedded in a comprehensive quantitative approach. In the light of this, the objectives of the work reported in this thesis were (1) to develop, quantify, and validate a model for the transmission and control of onchocerciasis in West African savanna and (2) to use this model for aiding decision making in the OCP. Through achieving these objectives we have tried to contribute to a better understanding of the dynamics of the parasite that causes the illness and the impact of intervention measures, and to the as yet successful combat against the disease. In the general introduction an outline will be given of the epidemiology and control of onchocerciasis. Secondly, an overview of the achievements of the OCP in controlling the disease in West Africa will be provided. Finally, a short history will be presented of the role of quantitative modelling within OCP prior to the work reported in this thesis