Meta-analysis of epilepsy prevalence in West Africa and its relationship with onchocerciasis endemicity and control.

BACKGROUND: A high prevalence and incidence of epilepsy has been reported in onchocerciasis-endemic regions in Central and East Africa. There is compelling epidemiological evidence suggesting that this high burden is caused by onchocerciasis-associated epilepsy (OAE). We hypothesized that OAE had also occured in West African onchocerciasis foci. METHODS: We searched PubMed, the African Journals Online platform and grey literature for population-based epilepsy studies in West African countries. Epilepsy and onchocerciasis prevalence data were extracted. The pre-control onchocerciasis endemicity in the study sites was estimated from historical data of onchocerciasis control programmes. The prevalence of epilepsy in different sites was analysed, taking into account onchocerciasis endemicity and the duration of control. RESULTS: The pooled prevalence of epilepsy in the West African study sites was 13.14 per 1000 (95% confidence interval 11.28-15.00). Higher pre-control endemicity and a shorter duration of onchocerciasis control were both associated with increased epilepsy prevalence (p<0.001). Two studies in Ivory Coast that provided detailed descriptions of persons with epilepsy in onchocerciasis-endemic settings revealed that most of them had features of OAE (73.7% and 83.3%, respectively). CONCLUSIONS: Our findings suggest that before and during the early years of implementing onchocerciasis control in West Africa, high onchocerciasis endemicity resulted in a high prevalence of OAE and that subsequent control efforts significantly reduced the prevalence of OAE.

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.

Control, elimination, and eradication of river blindness: scenarios, timelines, and ivermectin treatment needs in Africa.

River blindness (onchocerciasis) causes severe itching, skin lesions, and vision impairment including blindness. More than 99% of all current cases are found in sub-Saharan Africa. Fortunately, vector control and community-directed treatment with ivermectin have significantly reduced morbidity. Studies in Mali and Senegal proved the feasibility of elimination with ivermectin administration. The treatment goal is shifting from control to elimination in endemic African regions. Given limited resources, national and global policymakers need a rigorous analysis comparing investment options. For this, we developed scenarios for alternative treatment goals and compared treatment timelines and drug needs between the scenarios. Control, elimination, and eradication scenarios were developed with reference to current standard practices, large-scale studies, and historical data. For each scenario, the timeline when treatment is expected to stop at country level was predicted using a dynamical transmission model, and ivermectin treatment needs were predicted based on population in endemic areas, treatment coverage data, and the frequency of community-directed treatment. The control scenario requires community-directed treatment with ivermectin beyond 2045 with around 2.63 billion treatments over 2013-2045; the elimination scenario, until 2028 in areas where feasible, but beyond 2045 in countries with operational challenges, around 1.48 [corrected] billion treatments; and the eradication scenario, lasting until 2040, around 1.30 billion treatments. The eradication scenario is the most favorable in terms of the timeline of the intervention phase and treatment needs. For its realization, strong health systems and political will are required to overcome epidemiological and political challenges.

The geographic distribution of onchocerciasis in the 20 participating countries of the African Programme for Onchocerciasis Control: (2) pre-control endemicity levels and estimated number infected.

BACKGROUND: The original aim of the African Programme for Onchocerciasis Control (APOC) was to control onchocerciasis as a public health problem in 20 African countries. In order to identify all high risk areas where ivermectin treatment was needed to achieve control, APOC used Rapid Epidemiological Mapping of Onchocerciasis (REMO). REMO involved spatial sampling of villages to be surveyed, and examination of 30 to 50 adults per village for palpable onchocercal nodules. REMO has now been virtually completed and we report the results in two articles. A companion article reports the delineation of high risk areas based on expert analysis. The present article reports the results of a geostatistical analysis of the REMO data to map endemicity levels and estimate the number infected. METHODS: A model-based geostatistical analysis of the REMO data was undertaken to generate high-resolution maps of the predicted prevalence of nodules and of the probability that the true nodule prevalence exceeds the high risk threshold of 20%. The number infected was estimated by converting nodule prevalence to microfilaria prevalence, and multiplying the predicted prevalence for each location with local data on population density. The geostatistical analysis included the nodule palpation data for 14,473 surveyed villages. RESULTS: The generated map of onchocerciasis endemicity levels, as reflected in the prevalence of nodules, is a significant advance with many new endemic areas identified. The prevalence of nodules was > 20% over an area of 2.5 million km2 with an estimated population of 62 million people. The results were consistent with the delineation of high risk areas of the expert analysis except for borderline areas where the prevalence fluctuated around 20%. It is estimated that 36 million people would have been infected in the APOC countries by 2011 if there had been no ivermectin treatment. CONCLUSIONS: The map of onchocerciasis endemicity levels has proven very valuable for onchocerciasis control in the APOC countries. Following the recent shift to onchocerciasis elimination, the map continues to play an important role in planning treatment, evaluating impact and predicting treatment end dates in relation to local endemicity levels.

The geographic distribution of onchocerciasis in the 20 participating countries of the African Programme for Onchocerciasis Control: (1) priority areas for ivermectin treatment.

BACKGROUND: The African Programme for Onchocerciasis Control (APOC) was created to control onchocerciasis as a public health problem in 20 African countries. Its main strategy is community directed treatment with ivermectin. In order to identify all high risk areas where ivermectin treatment was needed, APOC used Rapid Epidemiological Mapping of Onchocerciasis (REMO). REMO has now been virtually completed and we report the results in two articles. The present article reports the mapping of high risk areas where onchocerciasis was a public health problem. The companion article reports the results of a geostatistical analysis of the REMO data to map endemicity levels and estimate the number infected. METHODS: REMO consists of three stages: exclusion of areas that are unsuitable for the vector, selection of sample villages to be surveyed in each river basin, and examination of 30 to 50 adults for the presence of palpable onchocercal nodules in each selected village. The survey results and other relevant information were processed in a geographical information system. A panel of experts interpreted the data taking the river-based sampling into account and delineated high risk areas where the prevalence of nodules is greater than 20%. RESULTS: Unsuitable areas were identified in eight countries. In the remaining areas surveys were done in a total of 14,473 sample villages in which more than half a million people were examined. High-risk areas were identified in 18 APOC countries, ranging from small isolated foci to a vast contiguous endemic area of 2 million km2 running across seven countries. In five countries the high risk area covered more than 48% of the total surface area, and 31% to 48% of the population. It is estimated that 86 million people live in high risk areas in the APOC countries. CONCLUSIONS: The REMO maps have played a significant role in onchocerciasis control in the 20 APOC countries. All high-risk areas where onchocerciasis used to be a serious public health problem have been clearly delineated. This led to the creation of community-directed treatment projects that by 2012 were providing annual ivermectin treatment to over 80 million people.

Onchocerciasis: the pre-control association between prevalence of palpable nodules and skin microfilariae.

BACKGROUND: The prospect of eliminating onchocerciasis from Africa by mass treatment with ivermectin has been rejuvenated following recent successes in foci in Mali, Nigeria and Senegal. Elimination prospects depend strongly on local transmission conditions and therefore on pre-control infection levels. Pre-control infection levels in Africa have been mapped largely by means of nodule palpation of adult males, a relatively crude method for detecting infection. We investigated how informative pre-control nodule prevalence data are for estimating the pre-control prevalence of microfilariae (mf) in the skin and discuss implications for assessing elimination prospects. METHODS AND FINDINGS: We analyzed published data on pre-control nodule prevalence in males aged ≥ 20 years and mf prevalence in the population aged ≥ 5 years from 148 African villages. A meta-analysis was performed by means of Bayesian hierarchical multivariate logistic regression, accounting for measurement error in mf and nodule prevalence, bioclimatic zones, and other geographical variation. There was a strong positive correlation between nodule prevalence in adult males and mf prevalence in the general population. In the forest-savanna mosaic area, the pattern in nodule and mf prevalence differed significantly from that in the savanna or forest areas. SIGNIFICANCE: We provide a tool to convert pre-control nodule prevalence in adult males to mf prevalence in the general population, allowing historical data to be interpreted in terms of elimination prospects and disease burden of onchocerciasis. Furthermore, we identified significant geographical variation in mf prevalence and nodule prevalence patterns warranting further investigation of geographical differences in transmission patterns of onchocerciasis.

Proof-of-principle of onchocerciasis elimination with ivermectin treatment in endemic foci in Africa: final results of a study in Mali and Senegal.

BACKGROUND: Mass treatment with ivermectin controls onchocerciasis as a public health problem, but it was not known if it could also interrupt transmission and eliminate the parasite in endemic foci in Africa where vectors are highly efficient. A longitudinal study was undertaken in three hyperendemic foci in Mali and Senegal with 15 to 17 years of annual or six-monthly ivermectin treatment in order to assess residual levels of infection and transmission, and test whether treatment could be safely stopped. This article reports the results of the final evaluations up to 5 years after the last treatment. METHODOLOGY/PRINCIPAL FINDINGS: Skin snip surveys were undertaken in 131 villages where 29,753 people were examined and 492,600 blackflies were analyzed for the presence of Onchocerca volvulus larva using a specific DNA probe. There was a declining trend in infection and transmission levels after the last treatment. In two sites the prevalence of microfilaria and vector infectivity rate were zero 3 to 4 years after the last treatment. In the third site, where infection levels were comparatively high before stopping treatment, there was also a consistent decline in infection and transmission to very low levels 3 to 5 years after stopping treatment. All infection and transmission indicators were below postulated thresholds for elimination. CONCLUSION/SIGNIFICANCE: The study has established the proof of principle that onchocerciasis elimination with ivermectin treatment is feasible in at least some endemic foci in Africa. The study results have been instrumental for the current evolution from onchocerciasis control to elimination in Africa.

The geographic distribution of Loa loa in Africa: results of large-scale implementation of the Rapid Assessment Procedure for Loiasis (RAPLOA).

BACKGROUND: Loiasis is a major obstacle to ivermectin treatment for onchocerciasis control and lymphatic filariasis elimination in central Africa. In communities with a high level of loiasis endemicity, there is a significant risk of severe adverse reactions to ivermectin treatment. Information on the geographic distribution of loiasis in Africa is urgently needed but available information is limited. The African Programme for Onchocerciasis Control (APOC) undertook large scale mapping of loiasis in 11 potentially endemic countries using a rapid assessment procedure for loiasis (RAPLOA) that uses a simple questionnaire on the history of eye worm. METHODOLOGY/PRINCIPAL FINDINGS: RAPLOA surveys were done in a spatial sample of 4798 villages covering an area of 2500×3000 km centred on the heartland of loiasis in Africa. The surveys showed high risk levels of loiasis in 10 countries where an estimated 14.4 million people live in high risk areas. There was a strong spatial correlation among RAPLOA data, and kriging was used to produce spatially smoothed contour maps of the interpolated prevalence of eye worm and the predictive probability that the prevalence exceeds 40%. CONCLUSION/SIGNIFICANCE: The contour map of eye worm prevalence provides the first global map of loiasis based on actual survey data. It shows a clear distribution with two zones of hyper endemicity, large areas that are free of loiasis and several borderline or intermediate zones. The surveys detected several previously unknown hyperendemic foci, clarified the distribution of loiasis in the Central African Republic and large parts of the Republic of Congo and the Democratic Republic of Congo for which hardly any information was available, and confirmed known loiasis foci. The new maps of the prevalence of eye worm and the probability that the prevalence exceeds the risk threshold of 40% provide critical information for ivermectin treatment programs among millions of people in Africa.

Integrated rapid mapping of onchocerciasis and loiasis in the Democratic Republic of Congo: impact on control strategies.

BACKGROUND: Onchocerciasis can be effectively controlled by annual mass treatment with ivermectin in endemic communities. However, in communities that are endemic for loiasis there may be significant risk of severe adverse reactions after ivermectin treatment. Planning of control requires therefore mapping of these two infections using rapid assessment tools developed for each disease. These tools were initially implemented independently till the feasibility of combining them was demonstrated. This paper reports the results of integrated mapping in four epidemiological zones in the Democratic Republic of Congo and its implications on operational decision-making on ivermectin treatment. METHODS: Rapid assessment surveys were conducted between 2004 and 2005 using both rapid epidemiological mapping of onchocerciasis (REMO) and rapid assessment procedure for loiasis (RAPLOA). The survey results were subjected to a spatial analysis in order to generate for each of the two diseases maps of the estimated prevalence of infection throughout the four zones. RESULTS: Surveys were undertaken in 788 villages where 25,754 males were examined for palpable onchocercal nodules and 62,407 people were interviewed for history of eye worm. The results showed major differences in the geographic distribution of the two diseases. Loiasis was highly endemic in some areas, where special precautions were required, but not in others where routine ivermectin treatment could proceed. CONCLUSION: Integrated rapid mapping of onchocerciasis and loiasis reduces both time and cost of surveys and greatly facilitates operational decision-making on ivermectin treatment in areas where loiasis might be co-endemic.

Defining research to improve health systems.

Robert Terry and colleagues present working definitions of operational research, implementation research, and health systems research within the context of research to strengthen health systems.

Feasibility of onchocerciasis elimination with ivermectin treatment in endemic foci in Africa: first evidence from studies in Mali and Senegal.

BACKGROUND: Mass treatment with ivermectin is a proven strategy for controlling onchocerciasis as a public health problem, but it is not known if it can also interrupt transmission and eliminate the parasite in endemic foci in Africa where vectors are highly efficient. A longitudinal study was undertaken in three hyperendemic foci in Mali and Senegal with 15 to 17 years of annual or six-monthly ivermectin treatment in order to assess residual levels of infection and transmission and test whether ivermectin treatment could be safely stopped in the study areas. METHODOLOGY/PRINCIPAL FINDINGS: Skin snip surveys were undertaken in 126 villages, and 17,801 people were examined. The prevalence of microfilaridermia was <1% in all three foci. A total of 157,500 blackflies were collected and analyzed for the presence of Onchocerca volvulus larvae using a specific DNA probe, and vector infectivity rates were all below 0.5 infective flies per 1,000 flies. Except for a subsection of one focus, all infection and transmission indicators were below postulated thresholds for elimination. Treatment was therefore stopped in test areas of 5 to 8 villages in each focus. Evaluations 16 to 22 months after the last treatment in the test areas involved examination of 2,283 people using the skin snip method and a DEC patch test, and analysis of 123,000 black flies. No infected persons and no infected blackflies were detected in the test areas, and vector infectivity rates in other catching points were <0.2 infective flies per 1,000. CONCLUSION/SIGNIFICANCE: This study has provided the first empirical evidence that elimination of onchocerciasis with ivermectin treatment is feasible in some endemic foci in Africa. Although further studies are needed to determine to what extent these findings can be extrapolated to other endemic areas in Africa, the principle of elimination has been established. The African Programme for Onchocerciasis Control has adopted an additional objective to assess progress towards elimination endpoints in all onchocerciasis control projects and to guide countries on cessation of treatment where feasible.

Additional health and development activities for community-directed distributors of ivermectin: threat or opportunity for onchocerciasis control?

We studied the involvement of community-directed distributors (CDDs) of ivermectin for onchocerciasis control in other health and development activities in Nigeria, Togo and Cameroon. Most CDDs (82%) were involved in additional activities, especially EPI, water and sanitation and community development projects. These activities did not take up much time and were not considered an important burden. Ivermectin treatment coverage did not decline with increasing number of additional activities. Other health programmes are interested in building on the experiences and structures of community-directed treatment with ivermectin and involving CDDs in their health programmes. Some, such as EPI, provide financial incentives. Incentives by other programmes may enhance the performance of CDDs when they are selected on the basis of their CDD status. CDDs, health personnel and community members have very positive attitudes towards greater involvement of CDDs in additional health and development activities. We conclude that additional activities for CDDs do not pose a threat to but rather provide an opportunity to strengthen sustainability and effectiveness of ivermectin treatment.

Uptake of Onchocerca volvulus (Nematoda: Onchocercidae) by Simulium (Diptera: Simuliidae) is not strongly dependent on the density of skin microfilariae in the human host.

The relation between the number of microfilariae (mf) ingested by host-seeking vectors of human onchocerciasis and skin mf load is an important component of the population biology of Onchocerca volvulus, with implications for disease control and evaluation of the risk of transmission recrudescence. The microsimulation model ONCHOSIM has been used to assess such risk in the area of the Onchocerciasis Control Program (OCP) in West Africa, based on a strongly nonlinear relation between vector mf uptake and human mf skin density previously published. However, observed levels of recrudescence have exceeded predictions, warranting a recalibration of the model. To this end, we present the results of a series of fly-feeding experiments carried out in savanna and forest localities of West Africa. Flies belonging to Simulium damnosum s.s., S. sirbanum, S. soubrense, and S. leonense were fed on mf carriers and dissected to assess the number of ingested mf escaping imprisonment by the peritrophic matrix (the number of exo-peritrophic mf), a predictor of infective larval output. The method of instrumental variables was used to obtain (nearly) unbiased estimates of the parameters of interest, taking into account error in the measurement of skin mf density. This error is often neglected in these types of studies, making it difficult to ascertain the degree of density-dependence truly present in the relation between mf uptake and skin load. We conclude that this relation is weakly (yet significantly) nonlinear in savanna settings but indistinguishable from linearity in forest vectors. Exo-peritrophic mf uptake does not account for most of the density dependence in the transmission dynamics of the parasite as previously thought. The number of exo-mf in forest simuliids is at least five times higher than in the savanna vectors. Parasite abundance in human onchocerciasis is regulated by poorly known mechanisms operating mainly on other stages of the lifecycle.

Combating tropical infectious diseases: report of the Disease Control Priorities in Developing Countries Project.

Infectious diseases are responsible for >25% of the global disease toll. The new Disease Control Priorities in Developing Countries Project (DCPP) aims to decrease the burden of these diseases by producing science-based analyses from demographic, epidemiologic, disease intervention, and economic evidence for the purpose of defining disease priorities and implementing control measures. The DCPP recently reviewed selected tropical infectious diseases, examined successful control experiences, and defined unsettled patient treatment, prevention, and research issues. Disease elimination programs against American trypanosomiasis (Chagas disease), onchocerciasis, lymphatic filariasis, leprosy, trachoma, and measles are succeeding. Dengue, leishmaniasis, African trypanosomiasis, malaria, diarrheal diseases, helminthic infections, and tuberculosis have reemerged because of inadequate interventions and control strategies and the breakdown of health delivery systems. Application of technologies must be cost-effective and intensified research is essential if these and other scourges are to be controlled or eliminated in the 21st century.

Research for control: the onchocerciasis experience.

Onchocerciasis control has been very successful in Africa and research has played a critical role. An overview of the main epidemiological and implementation research activities undertaken over the last 20 years in collaboration with the African onchocerciasis control programmes and of the impact this research had on control is given. The research included the development of epidemiological modelling and its application in programme evaluation and operational planning, research on disease patterns and disease burden in different bioclimatic zones to justify and guide control operations, community trials of ivermectin to determine its safety for large-scale use and its impact on transmission, rapid assessment methods to identify target communities for treatment and community-directed treatment for sustained drug delivery. Lessons learned during this unique collaboration between research and control are discussed.

Strategic emphases for tropical diseases research: a TDR perspective.

Setting priorities for health research is a difficult task, especially for the neglected diseases of the poor. A new approach to priority setting for tropical diseases research has been adopted by the UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (known as the TDR). Priorities are defined on the basis of a comprehensive analysis of research needs and research opportunities for each of the ten major tropical diseases in the TDR portfolio. The resulting strategic emphases matrix reflects the priorities for tropical diseases research from the perspective of the TDR. Its purpose is not to impose global research priorities, but we believe the results could be useful to other organizations.

Strategic emphases for tropical diseases research: a TDR perspective.

Setting priorities for health research is a difficult task, especially for the neglected diseases of the poor. A new approach to priority setting for tropical diseases research has been adopted by the UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (known as the TDR). Priorities are defined on the basis of a comprehensive analysis of research needs and research opportunities for each of the ten major tropical diseases in the TDR portfolio. The resulting strategic emphases matrix reflects the priorities for tropical diseases research from the perspective of the TDR. Its purpose is not to impose global research priorities, but we believe the results could be useful to other organizations.