Jan H. F. Remme

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.

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.

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.

The reproductive lifespan of Onchocerca volvulus in West African savanna.

The epidemiological model ONCHOSIM--a model and computer simulation program for the transmission and control of onchocerciasis--has been used to determine the range of plausible values for the reproductive lifespan of Onchocerca volvulus. Model predictions based on different lifespan quantifications were compared with the results of longitudinal skin-snip surveys undertaken in 4 reference villages during 13 to 14 years of successful vector control in the Onchocerciasis Control Programme in West Africa. Good fits between predicted and observed trends in skin microfilarial loads could be obtained for all villages. It is concluded that the reproductive lifespan of the savanna strain of O. volvulus lies between 9 and 11 years, and that 95% of the parasites reach the end of reproduction before the age of 13 to 14 years.

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.

ONCHOSIM: A model and computer simulation program for the transmission and control of onchocerciasis

ONCHOSIM is a computer program for modelling the transmission and control of the tropical parasitic disease onchocerciasis, or river blindness. It is developed in collaboration with the Onchocerciasis Control Programme in West Africa (OCP), and is used as a tool in the evaluation and planning of control operations. The model comprises a detailed description of the life history of the parasite Onchocerca volvulus and of its transmission from person to person by Simulium flies. The effects of different control strategies, based on larvicide application and chemotherapy (ivermectin), on the transmission and on the disease symptoms can be evaluated and predicted. In the program two simulation techniques are mixed. Stochastic microsimulation is used to calculate the life events of individual persons and inhabitant parasites, while the dynamics of the Simulium population and the development of the parasite in the flies are simulated deterministically. Output of ONCHOSIM conforms to the format in which data collected by the OCP are reported. This enables detailed checking of model specifications against empirical data. Output can also consist of summarizing key indices for the intensity of onchocerciasis infection, which is especially useful for comparing the effectivity of control strategies.

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.

Impact of long-term treatment of onchocerciasis with ivermectin in Kaduna State, Nigeria: first evidence of the potential for elimination in the operational area of the African Programme for Onchocerciasis Control

BackgroundOnchocerciasis can be effectively controlled as a public health problem by annual mass drug administration of ivermectin, but it was not known if ivermectin treatment in the long term would be able to achieve elimination of onchocerciasis infection and interruption of transmission in endemic areas in Africa. A recent study in Mali and Senegal has provided the first evidence of elimination after 15-17 years of treatment. Following this finding, the African Programme for Onchocerciasis Control (APOC) has started a systematic evaluation of the long-term impact of ivermectin treatment projects and the feasibility of elimination in APOC supported countries. This paper reports the first results for two onchocerciasis foci in Kaduna, Nigeria.MethodsIn 2008, an epidemiological evaluation using skin snip parasitological diagnostic method was carried out in two onchocerciasis foci, in Birnin Gwari Local Government Area (LGA), and in the Kauru and Lere LGAs of Kaduna State, Nigeria. The survey was undertaken in 26 villages and examined 3,703 people above the age of one year. The result was compared with the baseline survey undertaken in 1987.ResultsThe communities had received 15 to 17 years of ivermectin treatment with more than 75% reported coverage. For each surveyed community, comparable baseline data were available. Before treatment, the community prevalence of O. volvulus microfilaria in the skin ranged from 23.1% to 84.9%, with a median prevalence of 52.0%. After 15 to 17 years of treatment, the prevalence had fallen to 0% in all communities and all 3,703 examined individuals were skin snip negative.ConclusionsThe results of the surveys confirm the finding in Senegal and Mali that ivermectin treatment alone can eliminate onchocerciasis infection and probably disease transmission in endemic foci in Africa. It is the first of such evidence for the APOC operational area.

Rapid epidemiological mapping of onchocerciasis (REMO): its application by the African Programme for Onchocerciasis Control (APOC)

Abstract One of the fundamental challenges that the African Programme for Onchocerciasis Control (APOC) has had to face is how to identify the endemic communities where its mass ivermectin-treatment operations are to be carried out in conformity with its stated objective of targetting the most highly endemic, aVected and at-risk populations. This it has done by adopting a technique, known as the rapid epidemiological mapping of onchocerciasis (REMO), that provides data on the distribution and prevalence of onchocerciasis. Integration of the REMO data into a geographical information system (GIS) enables delineation of zones of various levels of endemicity, and this is an important step in the planning process for onchocerciasis control. Zones are included in (or excluded from) the APOC-funded programme of community-directed treatment with ivermectin (CDTI), depending on whether or not their levels of onchocercal endemicity reach the threshold set by APOC. This review describes the application of the REMO/GIS technique by APOC in its operations, and identifies the remaining related challenges.

Rapid assessment method for prevalence and intensity of Loa loa infection

OBJECTIVE To assess the validity of observations on eye worm and Calabar swellings for the rapid assessment of the prevalence and intensity of loiasis at the community level. METHOD A total of 12895 individuals over the age of 15 years living in 102 communities in Cameroon and Nigeria took part in the study. A standardized questionnaire was administered to participants from whom finger-prick blood samples were collected and examined for Loa loa microfilariae. Rapid assessments of the prevalence and intensity of loiasis were made on the basis of a history of eye worm or Calabar swellings. FINDINGS There was a strong correlation between the indices of the rapid assessment procedures and the parasitological indices of L. loa endemicity. The rapid assessment indices were effective in diagnosing high-risk communities (sensitivity 94-100%; specificity 66-92%). The highest sensitivity (100%) and specificity (92%) were obtained with a rapid assessment procedure based on a history of eye worm lasting 1-7 days together with confirmation by the guided recognition of a photograph of adult L. loa in the eye. CONCLUSION Rapid assessment of the prevalence and intensity of loiasis at the community level can be achieved using a procedure based on the history of eye worm lasting 1-7 days together with confirmation by the guided recognition of a photograph of an adult L. loa in the eye.