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.     

An appraisal of the epidemiologic situation of onchocerciasis in Ethiopia

The existence of onchocerciasis in Ethiopia has been known since 1939 as a result of investigation by Italians in south-western Ethiopia. In the last fifty years onchocerciasis has been spreading to previously non-endemic regions of Ethiopia. Although comprehensive epidemiological surveys are lacking, it is estimated that 7.3 million people or 17.4% of the population of Ethiopia is at risk from this disease. The principal vectors are S. damnosum complex and S. woodi ethiopiense. The clinical picture is mainly dermal and ocular manifestations are rare. In view of agricultural development projects and resettlement of millions of people from the highlands into endemic areas in southern and north-western parts of Ethiopia, further spread of onchocerciasis is expected. Experience gained in the control of the disease in west Africa by WHO and the introduction of effective mass chemotherapeutic agents as well as primary health care programmes and activities currently underway in Ethiopia indicate the feasibility of starting control programmes. A plea is therefore made to consider the control of onchocerciasis in Ethiopia urgently.     

Human Onchocerciasis: Modelling the Potential Long-term Consequences of a Vaccination Programme

Background

Currently, the predominant onchocerciasis control strategy in Africa is annual mass drug administration (MDA) with ivermectin. However, there is a consensus among the global health community, supported by mathematical modelling, that onchocerciasis in Africa will not be eliminated within proposed time frameworks in all endemic foci with only annual MDA, and novel and alternative strategies are urgently needed. Furthermore, use of MDA with ivermectin is already compromised in large areas of central Africa co-endemic with Loa loa, and there are areas where suboptimal or atypical responses to ivermectin have been documented. An onchocerciasis vaccine would be highly advantageous in these areas.

Methodology/Principal Findings

We used a previously developed onchocerciasis transmission model (EPIONCHO) to investigate the impact of vaccination in areas where loiasis and onchocerciasis are co-endemic and ivermectin is contraindicated. We also explore the potential influence of a vaccination programme on infection resurgence in areas where local elimination has been successfully achieved. Based on the age range included in the Expanded Programme on Immunization (EPI), the vaccine was assumed to target 1 to 5 year olds. Our modelling results indicate that the deployment of an onchocerciasis vaccine would have a beneficial impact in onchocerciasis–loiasis co-endemic areas, markedly reducing microfilarial load in the young (under 20 yr) age groups.

Conclusions/Significance

An onchocerciasis prophylactic vaccine would reduce the onchocerciasis disease burden in populations where ivermectin cannot be administered safely. Moreover, a vaccine could substantially decrease the chance of re-emergence of Onchocerca volvulus infection in areas where it is deemed that MDA with ivermectin can be stopped. Therefore, a vaccine would protect the substantial investments made by present and past onchocerciasis control programmes, decreasing the chance of disease recrudescence and offering an important additional tool to mitigate the potentially devastating impact of emerging ivermectin resistance.     

Onchocerciasis control and elimination: coming of age in resource-constrained health systems

During the past three decades, onchocerciasis control has been successful in reducing blindness and skin disease in Africa and the Americas. In this article, I review the control and elimination of Onchocerca volvulus as a public health problem. The success of onchocerciasis control has been the result of secure financing, generous drug donation, effective partnership between stakeholders, and focused operational and implementation research. The future challenges are to ensure sustainability of existing programmes and to increase the level of integration with other health interventions in resource-deficient health systems.     

Epidemiology and control of onchocerciasis: The threshold biting rate of savannah onchocerciasis in Africa

Control of onchocerciasis currently focuses on community-directed treatment with the microfilaricide ivermectin which effectively kills Onchocerca volvulus microfilariae in the human host. The feasibility of elimination by this control strategy has recently been reported for some foci in Africa which has rekindled discussions on evaluating the threshold conditions of elimination of onchocerciasis. We developed a stochastic model based on a master equation which predicts, based on data from West and Central Africa, that elimination of savannah onchocerciasis can be expected around a threshold biting rate of 730 bites per person per year, ranging region-specifically roughly from 230 to 2300 bites per person and year. The threshold values give rise to optimism that elimination of onchocerciasis is feasible, but the associated measures of parasite prevalence and density suggest that onchocerciasis can remain endemic at very low infection intensities. Endemicity at a low level is a risk factor for elimination strategies, and we point to the necessity of investigating these issues on the basis of breakpoints which refer to threshold conditions based on parasite prevalence and density.     

Onchocerciasis control: biological research is still needed

Achievements obtained by the onchocerciasis control programmes should not lead to a relaxation in the biological research on Onchocerco volvulus. Issues such as the Loa loa-related post-ivermectin serious adverse events, the uncertainties as to whether onchocerciasis can be eliminated by ivermectin treatments, and the possible emergence of ivermectin-resistant O. volvulus populations should be addressed proactively. Doxycycline, moxidectin and emodepside appear to be promising as alternative drugs against onchocerciasis but support to researches in immunology and genomics should also be increased to develop new control tools, including both vaccines and macrofilaricidal drugs.     

Control of onchocerciasis in Africa: threshold shifts, breakpoints and rules for elimination

Control of onchocerciasis in Africa is currently based on annual community-directed treatment with ivermectin (CDTI) which has been assumed to be not efficient enough to bring about elimination. However, elimination has recently been reported to have been achieved by CDTI alone in villages of Senegal and Mali, reviving debate on the eradicability of onchocerciasis in Africa. We investigate the eradicability of onchocerciasis by examining threshold shifts and breakpoints predicted by a stochastic transmission model that has been fitted extensively to data. We show that elimination based on CDTI relies on shifting the threshold biting rate to a level that is higher than the annual biting rate. Breakpoints become relevant in the context of when to stop CDTI. In order for the model to predict a good chance for CDTI to eliminate onchocerciasis, facilitating factors such as the macrofilaricidal effect of ivermectin must be assumed. A chart predicting the minimum efficacy of CDTI required for elimination, dependent on the annual biting rate, is provided. Generalisable recommendations into strategies for the elimination of onchocerciasis are derived, particularly referring to the roles of vectors, the residual infection rate under control, and a low-spreader problem originating from patients with low parasite burdens.     

Mass drug treatment for lymphatic filariasis and onchocerciasis

This review summarizes the progress towards control of lymphatic filariasis (LF) and onchocerciasis, focussing on the impact of mass drug administration (MDA) programmes, in particular those that have developed following the donation of ivermectin and albendazole. The contrasting strategies and objectives of the different programmes are compared, and the impact on transmission, clinical disease and public health assessed. The constraints on programme success are: (i) the absence of a macrofilaricide, which can be used in a public health context; (ii) the sustainability of high coverage of ivermectin over many years in onchocerciasis control; and (iii) the problem of treatment in areas where Loa loa (tropical eye worm) is co-endemic with onchocerciasis because of the rare severe adverse events. LF programmes are expanding rapidly in over 30 countries, where circa 60 million people received treatments in 2002. No serious adverse events have been associated with MDAs for LF elimination. Research on new approaches to treatment using antibiotics are showing promising results in pilot settings because doxycyline has been shown to have long-term embryostatic effects and sustained reductions of microfilaria loads in onchocerciasis and bancroftian filariasis.     

Programmatic and Communication Issues in Relation to Serious Adverse Events Following Ivermectin Treatment in areas Co-endemic for Onchocerciasis and Loiasis

In areas co-endemic for loiasis and onchocerciasis, the classic Community-Directed Treatment using ivermectin (Mectizan(R)) must be adapted as additional program activities, better communication and tighter control of ivermectin stocks are required to minimize risk and manage serious adverse events following ivermectin treatment in patients co-infected with Loa loa. The importance of these serious adverse events on community participation in onchocerciasis control efforts has not been adequately studied. Program implementers do not as of yet fully understand the psychological impact of serious adverse events on communities and therefore have not designed communication strategies that adequately address the real concerns of community members. It is clear, however, that along with an effective case detection and management strategy, a reinforced communication strategy will be required to motivate at least 65% of the total population in onchocerciasis and loiasis co-endemic areas to participate in the treatment program and to take ivermectin over an extended period. This strategy must be based on research undertaken at the community level in order to address the concerns, fears and issues associated with adverse events due to ivermectin - to ensure that communities believe that the benefits of taking ivermectin outweigh the risks. In addition to an overall increase in the time required to sustain onchocerciasis control programs in co-endemic areas, each aspect of the reinforced program and communication strategy - rapid epidemiological assessments, materials development, training, advocacy, community sensitization and mobilization, case management and counselling, supervision, monitoring and evaluation will require additional resources and support from all stakeholders concerned.     

Onchocerciasis control: Moving towards the millennium

The recognition of onchocerciasis as a major public health problem in the savanna belts of West Africa resulted in the establishment of the Onchocerciasis Control Programme (OCP) in 1974. Control was initially based on vector control by weekly larviciding. The OCP is now in transition towards its final phase in which repeated treatment with ivermectin, a safe and effective microfilaricide, is incorporated with vector control, or in certain circumstances is used alone. Ivermectin distribution hingeing on sustainable community systems is the basis of a new programme in endemic African countries outside the OCP and in the Americas. David Molyneux and John Davies describe the latest trends and developments related to onchocerciasis control.     

Ten years of NGDO action against river blindness

For a decade, a dozen non-governmental development organizations (NGDOs) have organized themselves into a Geneva-based coordination group with the goal of global control of onchocerciasis through mass distribution of ivermectin (Mectizan(R)). Members of this group have worked with Ministries of Health and other partners to empower communities affected by the disease to take responsibility for their own treatment. The NGDO Group has played a key role in the governance of international onchocerciasis control effort, particularly as a partner within the African Programme for Onchocerciasis Control. Ten years on, it is now time to take stock of activities, review the lessons learned and confront future challenges.     

Predicting the environmental suitability for onchocerciasis in Africa as an aid to elimination planning

Recent evidence suggests that, in some foci, elimination of onchocerciasis from Africa may be feasible with mass drug administration (MDA) of ivermectin. To achieve continental elimination of transmission, mapping surveys will need to be conducted across all implementation units (IUs) for which endemicity status is currently unknown. Using boosted regression tree models with optimised hyperparameter selection, we estimated environmental suitability for onchocerciasis at the 5 × 5-km resolution across Africa. In order to classify IUs that include locations that are environmentally suitable, we used receiver operating characteristic (ROC) analysis to identify an optimal threshold for suitability concordant with locations where onchocerciasis has been previously detected. This threshold value was then used to classify IUs (more suitable or less suitable) based on the location within the IU with the largest mean prediction. Mean estimates of environmental suitability suggest large areas across West and Central Africa, as well as focal areas of East Africa, are suitable for onchocerciasis transmission, consistent with the presence of current control and elimination of transmission efforts. The ROC analysis identified a mean environmental suitability index of 0·71 as a threshold to classify based on the location with the largest mean prediction within the IU. Of the IUs considered for mapping surveys, 50·2% exceed this threshold for suitability in at least one 5 × 5-km location. The formidable scale of data collection required to map onchocerciasis endemicity across the African continent presents an opportunity to use spatial data to identify areas likely to be suitable for onchocerciasis transmission. National onchocerciasis elimination programmes may wish to consider prioritising these IUs for mapping surveys as human resources, laboratory capacity, and programmatic schedules may constrain survey implementation, and possibly delaying MDA initiation in areas that would ultimately qualify.     

Elimination of onchocerciasis from Africa: possible?

Human onchocerciasis, a parasitic disease found in 28 African countries, six Latin American countries and Yemen, causes blindness and severe dermatological problems. In 1987, efforts to control this infection shifted from vector approaches to include the mass distribution of ivermectin - a drug donated by Merck & Co. for disease control in Africa and for disease elimination in the Americas. Currently, almost 25 years later, with the Americas being highly successful and now approaching elimination, new evidence points towards the possibility of successful elimination in Africa. We suggest several major changes in the programmatic approach that through focused goal-directed effort could achieve global elimination of onchocerciasis by 2025.     

Detection of Onchocerca volvulus (Nematoda: Onchocercidae) infection in vectors from Amazonian Brazil following mass Mectizan distribution

Detection of Onchocerca volvulus in Simulium populations is of primary importance in the assessment of the effectiveness of onchocerciasis control programs. In Brazil, the main focus of onchocerciasis is in the Amazon region, in a Yanomami reserve. The main onchocerciasis control strategy in Brazil is the semi-annually mass distribution of the microfilaricide ivermectin. In accordance with the control strategy for the disease, polymerase chain reaction (PCR) was applied in pools of simuliids from the area to detect the helminth infection in the vectors, as recommended by the Onchocerciasis Elimination Program for the Americas and the World Health Organization. Systematic sampling was performed monthly from September 1998 to October 1999, and a total of 4942 blackflies were collected from two sites (2576 from Balawaú and 2366 from Toototobi). The molecular methodology was found to be highly sensitive and specific for the detection of infected and/or infective blackflies in pools of 50 blackflies. The results from the material collected under field conditions showed that after the sixth cycle of distribution of ivermectin, the prevalence of infected blackflies with O. volvulus had decreased from 8.6 to 0.3% in Balawaú and from 4 to 0.1% in Toototobi.     

Major sperm protein as a diagnostic antigen for onchocerciasis

Onchocerciasis, also known as river blindness, is the second leading infectious cause of blindness worldwide. In order to successfully control this disease, the development of efficient diagnostic tools as well as effective treatments is imperative. A number of proteins have been proposed as vaccine and diagnostic candidates, yet none have been successfully advanced to the point of general clinical use. We have prepared major sperm protein 2 (MSP2) from Onchocerca volvulus as a possible diagnostic antigen for onchocerciasis. Importantly, recombinant MSP2 is dimeric in solution, identical to alpha-MSP from the roundworm, Ascaris suum. A panel of sera obtained from Cameroonian individuals afflicted with onchocerciasis positively responded to the recombinant MSP2. Our data suggest that MSP2, like the previously described antigen Ov16, can be utilized as a diagnostic onchocerciasis antigen for monitoring the interruption of transmission.     

Demographic patterns of human antibody levels to Simulium damnosum s.l. saliva in onchocerciasis-endemic areas: An indicator of exposure to vector bites

BackgroundIn onchocerciasis endemic areas in Africa, heterogenous biting rates by blackfly vectors on humans are assumed to partially explain age- and sex-dependent infection patterns with Onchocerca volvulus. To underpin these assumptions and further improve predictions made by onchocerciasis transmission models, demographic patterns in antibody responses to salivary antigens of Simulium damnosum s.l. are evaluated as a measure of blackfly exposure.Methodology/Principal findingsRecently developed IgG and IgM anti-saliva immunoassays for S. damnosum s.l. were applied to blood samples collected from residents in four onchocerciasis endemic villages in Ghana. Demographic patterns in antibody levels according to village, sex and age were explored by fitting generalized linear models. Antibody levels varied between villages but showed consistent patterns with age and sex. Both IgG and IgM responses declined with increasing age. IgG responses were generally lower in males than in females and exhibited a steeper decline in adult males than in adult females. No sex-specific difference was observed in IgM responses.Conclusions/SignificanceThe decline in age-specific antibody patterns suggested development of immunotolerance or desensitization to blackfly saliva antigen in response to persistent exposure. The variation between sexes, and between adults and youngsters may reflect differences in behaviour influencing cumulative exposure. These measures of antibody acquisition and decay could be incorporated into onchocerciasis transmission models towards informing onchocerciasis control, elimination, and surveillance.     

Combined Utilisation of Rapid Assessment Procedures for Loiasis (RAPLOA) and Onchocerciasis (REA) in Rain forest Villages of Cameroon

BACKGROUND: Individuals with high microfilarial loads of Loa loa are at increased risk of neurologic serious adverse (SAE) events following ivermectin treatment against onchocerciasis. RAPLOA (Rapid Assessment Procedure for loiasis), a newly developed rapid assessment procedure for loiasis that relates the prevalence of key clinical manifestation of loiasis (history of eye worm) to the level of endemicity of the infection (prevalence of high intensity), is a very useful tool to identify areas at potential risk of L. loa post ivermectin treatment encephalopathy. In a perspective of treatment decision making in areas of co-endemicity of loiasis/onchocerciasis, it would be advantageous (both in time and cost savings) for national onchocerciasis control programmes to use RAPLOA and the Rapid epidemiologic assessment for onchocerciasis (REA), in combination in given surveys. Since each of the two rapid assessment tools have their own specificities, the workability of combining the two methods needed to be tested. METHODS: We worked in 10 communities of a forest area presumed co-endemic for loiasis and onchocerciasis in the North-West Province of Cameroon where the mass-treatment with ivermectin had not been carried out. A four-step approach was used and comprised: (i) generating data on the prevalence and intensity of loiasis and onchocerciasis in an area where such information is scarce; (ii) testing the relationship between the L. loa microfilaraemia prevalence and the RAPLOA prevalence, (iii) testing the relationship between the O. volvulus microfiladermia prevalence and the REA prevalence, (iv) testing the workability of combining RAPLOA/REA by study teams in which a single individual can perform the interview for RAPLOA and the nodule palpation for REA. RESULTS: The microfilaraemia prevalence of loiasis in communities ranged from 3.6% to 14.3%. 6 (0.61%) individuals had L. loa microfilarial loads above 8000 mf/ml but none of them attained 30,000 mf/ml, the threshold value above which the risk of developing neurologic SAE after ivermectin treatment is very high. None of the communities surveyed had RAPLOA prevalence above 40%. All the communities had microfiladermia prevalence above 60%. The microfiladermia results could be confirmed by the rapid epidemiologic method (nodule palpation), with all the 10 communities having REA prevalence above 20%. For the first time, this study has demonstrated that the two rapid assessment procedures for loiasis and onchocerciasis can be carried out simultaneously by a survey team, in which a single individual can administer the questionnaire for RAPLOA and perform the nodule palpation for REA. CONCLUSION: This study has: (i) Revealed that the Momo valley of the North West province of Cameroon is hyperendemic for onchocerciasis, but is of lower level of endemicity for L. loa. (ii) Confirmed the previous relationships established between RAPLOA and the L. loa microfilaraemia prevalence in one hand and between the REA and the O. volvulus microfiladermia prevalence in another hand (iii) Shown that RAPLOA and REA could be used simultaneously for the evaluation of loiasis and onchocerciasis endemicity in areas targeted by the African Programme for onchocerciasis Control for community-directed treatment with ivermectin (CDTI).     

The WHO Onchocerciasis Control Programme: retrospect and prospects

The history of onchocerciasis control in Africa and the genesis of the WHO Onchocerciasis Control Programme in West Africa (OCP) are briefly reviewed. The importance of experience gained in anti-locust campaigns in helping to plan the OCP is stressed. Members of the Simulium damnosum species complex are the vectors of onchocerciasis, which OCP is controlling with insecticide treatments on the stretches of rivers where the Simulium breed. Migrations of flies have been responsible for reinfestations of controlled areas and the spread of insecticide resistance. The management of these problems and related research are described, but it is emphasized that despite setbacks OCP is achieving its aims. A strategy for the future is outlined: vector control supplemented by chemotherapy is expected to continue until the year 2004.     

Eliminating onchocerciasis within the Meme River Basin of Cameroon: A social-ecological approach to understanding everyday realities and health systems

BackgroundOnchocerciasis affects some of the world’s most marginalized people, perpetuating poverty and inequalities. Mass Drug Administration (MDA) with Ivermectin has taken place within the Meme River basin region in Cameroon for over 15 years. Despite this, onchocerciasis is still prevalent in the region due to existing and emerging contextual challenges. Using a social-ecological approach we explore the everyday realities of communities, highlighting the challenges and potential solutions that could support Neglected Tropical Disease (NTD) programmes when transitioning from control to elimination of onchocerciasis in this highly endemic area and other similar communities.Methodology/Principal findingIn-depth interviews (71) with community members and Community Drug Distributors (CDDs) were conducted to understand current knowledge, attitudes, and behaviours in relation to transmission, prevention and treatment of onchocerciasis. Through application of the social-ecological model, four key themes were identified: 1. Contextual factors on health promotion interventions (Onchocerciasis history and understanding of the disease, prevention and mitigation strategies and MDA experience); 2. Social determinants (poverty and livelihoods, economic and social impacts on CDD volunteers and stigma); 3. Environmental determinants (exposure, housing, occupation and poverty); and 4. health seeking pathways and decision making for treatment (access, cost and preferable treatment routes).We discuss these core and cross cutting themes (gender differences and community participation/ownership) in relation to intersectoral collaboration, gender equity and health systems support, making recommendations for NTD programmes within the context of integrated and interdisciplinary approaches. These include the need for; intersectional and gender analysis at the local level, addressing environmental dimensions of onchocerciasis through integrated and regular health promotion, vector control strategies and access to safe water sources; reflection and action that embeds responses to social and economic barriers to MDA; integrated case detection and management that is responsive to onchocerciasis symptoms and related stigma and a fair and just support network for CDDs.Conclusion/SignificanceNTD programmes need to respond to diverse community circumstances and behaviours. Communities are not a homogeneous risk group and treating them in this way will delay elimination. A deeper understanding of individual needs and their capacity to seek prevention and treatment must be considered if onchocerciasis is to be eliminated and the remaining impacts managed.     

Geographical patterns of onchocerciasis in southern Venezuela: relationships between environment and infection prevalence

Onchocerciasis is a chronic filarial infection transmitted by Simulium flies that has a focal geographical distribution in Latin America. The southern Venezuelan focus has a gradient of endemicity that includes the largest number of hyperendemic communities in the continent, many of them in remote forest and mountainous areas, where it is an important public health problem among the Yanomami indigenous population. The recent introduction of Geographical Information Systems (GIS) tools and a landscape epidemiology approach for study of vector borne diseases is helping to understand relationships between environment and transmission dynamics of onchocerciasis. Striking differences in the transmission dynamics of onchocerciasis between different river courses were detected. A significant relationship between onchocerciasis and temperature was also demonstrated. The geologic substrate, kind of landscape and vegetation seemed also to influence the transmission of onchocerciasis. In the Venezuelan Amazon, different kinds of landscapes associated with distinctive vector species, show different intensities of transmission of onchocerciasis. In this sense, landscape analysis aided by GIS, may prove to be a useful tool for better identification of the spatial distribution of onchocerciasis risk in the Orinoco basin.