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.     

Population biology of human onchocerciasis.

Human onchocerciasis (river blindness) is the filarial infection caused by Onchocerca volvulus and transmitted among people through the bites of the Simulium vector. Some 86 million people around the world are at risk of acquiring the nematode, with 18 million people infected and 600,000 visually impaired, half of them partially or totally blind. 99% of cases occur in tropical Africa; scattered foci exist in Latin America. Until recently control programmes, in operation since 1975, have consisted of antivectorial measures. With the introduction of ivermectin in 1988, safe and effective chemotherapy is now available. With the original Onchocerciasis Control Programme of West Africa coming to an end, both the new African Programme for Onchocerciasis Control and the Onchocerciasis Elimination Programme for the Americas, rely heavily on ivermectin self-sustained mass delivery. In consequence, the need for understanding the processes regulating parasite abundance in human and simuliid populations is of utmost importance. We present a simple mathematical framework built around recent analyses of exposure- and density-dependent processes operating, respectively, within the human and vector hosts. An expression for the basic reproductive ratio, R0, is derived and related to the minimum vector density required for parasite persistence in localities of West Africa in general and northern Cameroon in particular. Model outputs suggest that constraints acting against parasite establishment in both humans and vectors are necessary to reproduce field observations, but those in humans may not fully protect against reinfection. Analyses of host age-profiles of infection prevalence, intensity, and aggregation for increasing levels of endemicity and intensity of transmission in the Vina valley of northern Cameroon are in agreement with these results and discussed in light of novel work on onchocerciasis immunology.     

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.     

The Mectizan® Donation Program – highlights from 2005

Through the Mectizan^® Donation Program, Merck & Co., Inc. has donated Mectizan (ivermectin, MSD) for the treatment of onchocerciasis worldwide since 1987. Mectizan has also been donated for the elimination of lymphatic filariasis (LF) since 1998 in African countries and in Yemen where onchocerciasis and LF are co-endemic; for LF elimination programs, Mectizan is co-administered with albendazole, which is donated by GlaxoSmithKline. The Mectizan Donation Program works in collaboration with the Mectizan Expert Committee/Albendazole Coordination, its scientific advisory committee. In 2005, a total of 62,201,310 treatments of Mectizan for onchocerciasis were approved for delivery via mass treatment programs in Africa, Latin America, and Yemen. Seventy-seven percent and 20% of these treatments for onchocerciasis were for countries included in the African Programme for Onchocerciasis Control (APOC) and the former-Onchocerciasis Control Programme in West Africa (OCP), respectively. The remaining 3% of treatments approved were for the six onchocerciasis endemic countries in Latin America, where mass treatment is carried out twice-yearly with the goal of completely eliminating morbidity and eventually transmission of infection, and for Yemen. All 33 onchocerciasis endemic countries where mass treatment with Mectizan is indicated have ongoing mass treatment programs. In 2005, 42,052,583 treatments of co-administered albendazole and Mectizan were approved for national Programs to Eliminate LF (PELFs) in Africa and Yemen. There are ongoing PELFs using albendazole and Mectizan in nine African countries and Yemen; these represent 35% of the total number of countries expected to require the co-administration of these two chemotherapeutic agents for LF elimination. In Africa, the expansion of existing PELFs and the initiation of new ones have been hampered by lack of resources, technical difficulties with the mapping of LF endemicity, and the co-endemicity of LF and loiasis. Included in this review are recommendations recently put forward for the co-administration of albendazole and Mectizan in areas endemic for LF, loiasis, and onchocerciasis.     

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.     

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.     

Determinants of the eradicability of filarial infections: a conceptual approach

Lymphatic filariasis and onchocerciasis are subject to major intervention programs by the WHO. The Onchocerciasis Control Programme in West Africa was launched 30 years ago and has led to considerable insights into the control of this infection. The Global Alliance to Eliminate Lymphatic Filariasis is a relatively recent control program with ambitious targets concerning its efficacy and its schedule. These expectations, however, are based on certain assumptions about the density-dependent processes of limitation and facilitation which determine eradicability: the levels of transmission thresholds and breakpoints. Here, we review these processes operating in filarial infections and show their impact on the persistence of the parasite, as well as pointing out those issues where more information is required to develop sound predictions about the eradicability of these infections.     

Elimination of the Djodji form of the blackfly Simulium sanctipauli sensu stricto as a result of larviciding by the WHO Onchocerciasis Control Programme in West Africa

Cytotaxonomic identifications of larvae of members of the Simulium damnosum Theobald (Diptera: Simuliidae) complex collected in forest zones of southeast Ghana and southwest Togo between 1977 and 1996 showed that the Djodji form of Simulium sanctipauli Vajime & Dunbar, a vector of onchocerciasis, was eliminated in 1988 by larvicide operations conducted by the World Health Organization (WHO) Onchocerciasis Control Programme (OCP) in West Africa. No members of the form were identified amongst 997 larvae collected up to 8 years after systematic control operations began in February 1988. The results are discussed in relation to estimates of the numbers of samples required to certify elimination and the possibility that other members of the S. damnosum complex were also eliminated by the OCP.     

African Programme for Onchocerciasis Control 1995–2015: Model-Estimated Health Impact and Cost

Background

Onchocerciasis causes a considerable disease burden in Africa, mainly through skin and eye disease. Since 1995, the African Programme for Onchocerciasis Control (APOC) has coordinated annual mass treatment with ivermectin in 16 countries. In this study, we estimate the health impact of APOC and the associated costs from a program perspective up to 2010 and provide expected trends up to 2015.

Methods and Findings

With data on pre-control prevalence of infection and population coverage of mass treatment, we simulated trends in infection, blindness, visual impairment, and severe itch using the micro-simulation model ONCHOSIM, and estimated disability-adjusted life years (DALYs) lost due to onchocerciasis. We assessed financial costs for APOC, beneficiary governments, and non-governmental development organizations, excluding cost of donated drugs. We estimated that between 1995 and 2010, mass treatment with ivermectin averted 8.2 million DALYs due to onchocerciasis in APOC areas, at a nominal cost of about US$257 million. We expect that APOC will avert another 9.2 million DALYs between 2011 and 2015, at a nominal cost of US$221 million.

Conclusions

Our simulations suggest that APOC has had a remarkable impact on population health in Africa between 1995 and 2010. This health impact is predicted to double during the subsequent five years of the program, through to 2015. APOC is a highly cost-effective public health program. Given the anticipated elimination of onchocerciasis from some APOC areas, we expect even more health gains and a more favorable cost-effectiveness of mass treatment with ivermectin in the near future.     

Onchocerciasis in West Africa after 2002: a challenge to take up

Initially planned for a 20 year life time, the Onchocerciasis Control Programme in West Africa (OCP) will have finally continued its activities for nearly three decades (vector control alone from 1975 to 1989, then vector control and/or therapeutic treatment until 2002). Although onchocerciasis is no longer a problem of public health importance nor an obstacle to socio-economic development in the OCP area, the control of this filariasis is not over because OCP never aimed at eradication, neither of the parasite (Onchocerca volvulus), nor of its vector (Simulium damnosum s.l.). In 2003, the eleven Participating countries of OCP will take over the responsibility of carrying out the residual activities of monitoring and the control of this disease. This mission is of great importance because any recrudescence of the transmission could lead in the long run to the reappearance of the clinical signs of onchocerciasis, if not its most serious manifestations. For epidemiological and operational reasons, and given the disparity in national health policies and infrastructures, the capacities of the countries to take over the residual activities of monitoring and control of onchocerciasis are very unequal. Indeed, the interventions to be carried out are very different from one country to another and the process of integrating the residual activities into the national health systems is not taking place at the same pace. This inequality among the countries vis-a-vis the challenges to be met does not, however, prejudge the epidemiological situation after 2002 whose evolution will also depend on the effectiveness of the provisions made before that date by OCP, then after 2002, by the Regional Office for Africa of the World Health Organization which is currently setting up a sub-regional multidisease surveillance centre.     

Progress in controlling the reinvasion of windborne vectors into the western area of the Onchocerciasis Control Programme in West Africa

Since vector control began in 1975, waves of Simulium sirbanum and S. damnosum s.str., the principal vectors of severe blinding onchocerciasis in the West African savannas, have reinvaded treated rivers inside the original boundaries of the Onchocerciasis Control Programme in West Africa. Larviciding of potential source breeding sites has shown that these 'savanna' species are capable of travelling and carrying Onchocerca infection for at least 500 km northeastwards with the monsoon winds in the early rainy season. Vector control has, therefore, been extended progressively westwards. In 1984 the Programme embarked on a major western extension into Guinea, Sierra Leone, western Mali, Senegal and Guinea-Bissau. The transmission resulting from the reinvasion of northern C?te d'Ivoire and Burkina Faso has been reduced by over 95%, but eastern Mali has proved more difficult to protect because of sources in both Guinea and Sierra Leone. Rivers in Sierra Leone were treated for the first time in 1989 and biting and transmission rates in Sierra Leone and Guinea fell by over 90%. Because of treatment problems in some complex rapids and mountainous areas, flies still reinvaded Mali, though biting rates were approximately 70% lower than those recorded before anti-reinvasion treatments started. It was concluded that transmission in eastern Mali has now been reduced to the levels required to control onchocerciasis.     

Environmental assessment of larvicide use in the onchocerciasis control programme

The objective of the Onchocerciasis Control Programme (OCP) is to eliminate onchocerciasis as a disease of public importance and as an obstacle to socio-economic development. The OCP was initially based solely on the control of the blackfly vector, Simulium damnosum sensu lato, by insecticide spraying of the breeding sites on river systems, where larval stages develop. Results of monitoring the environmental effects and the process of risk assessment for new insecticides are reviewed. The achievements of this strategy are outlined here by Davide Calamari, Laurent Yameogo, Jean-Marc Hougard and Christian Leveque.     

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.     

Density-dependent mortality of the human host in onchocerciasis: relationships between microfilarial load and excess mortality

Background

The parasite Onchocerca volvulus has, until recently, been regarded as the cause of a chronic yet non-fatal condition. Recent analyses, however, have indicated that in addition to blindness, the parasite can also be directly associated with human mortality. Such analyses also suggested that the relationship between microfilarial load and excess mortality might be non-linear. Determining the functional form of such relationship would contribute to quantify the population impact of mass microfilaricidal treatment.

Methodology/Principal Findings

Data from the Onchocerciasis Control Programme in West Africa (OCP) collected from 1974 through 2001 were used to determine functional relationships between microfilarial load and excess mortality of the human host. The goodness-of-fit of three candidate functional forms (a (log-) linear model and two saturating functions) were explored and a saturating (log-) sigmoid function was deemed to be statistically the best fit. The excess mortality associated with microfilarial load was also found to be greater in younger hosts. The attributable mortality risk due to onchocerciasis was estimated to be 5.9%.

Conclusions/Significance

Incorporation of this non-linear functional relationship between microfilarial load and excess mortality into mathematical models for the transmission and control of onchocerciasis will have important implications for our understanding of the population biology of O. volvulus, its impact on human populations, the global burden of disease due to onchocerciasis, and the projected benefits of control programmes in both human and economic terms.     

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.     

The impact of ivermectin on onchocerciasis in villages co-endemic for lymphatic filariasis in an area of onchocerciasis recrudescence in Burkina Faso

In Burkina Faso, onchocerciasis was no longer a public health problem when the WHO Onchocerciasis Control Programme in West Africa closed at the end in 2002. However, epidemiological surveillance carried out from November 2010 to February of 2011, showed a recrudescence of infection in the Cascades Region. This finding was made at a time when ivermectin, a drug recommended for the treatment of both onchocerciasis and lymphatic filariasis, had been distributed in this area since 2004 for the elimination of lymphatic filariasis. It was surprising that ivermectin distributed for treating lymphatic filariasis had not prevented the recrudescence of onchocerciasis. Faced with this situation, the aim of our study was to evaluate the effectiveness of ivermectin on the onchocerciasis parasite. The percentage reduction in microfilarial load after treatment with ivermectin was used as a proxy measure for assessing possible resistance. A cohort study was carried out with 130 individuals who had tested positive for microfilariae of Onchocerca volvulus in 2010 using microscopic examination of skin-snip biopsies from five endemic villages. Subjects were followed from July 2011 to June 2012. The microfilarial load of each individual was enumerated by skin-snip biopsy in 2010, prior to the first ivermectin treatment against onchocerciasis under community guidelines. All individuals received two ivermectin treatments six months apart. In 2012, the microfilarial loads were determined again, six months after the second round of ivermectin and the reductions in parasite loads were calculated to measure the impact of the drug. The percentage reduction of the microfilarial loads ranged from 87% to 98% in the villages. In all villages, there was a statistically significant difference between the average microfilarial loads in 2010 and 2012. The level of reduction of microfilarial loads suggests that ivermectin is effective against the recrudescent population of O. volvulus in Cascades Region of Burkina Faso. Further investigations would be necessary to determine the causes of the recrudescence of onchocerciasis. (For French language abstract, see S1 Alternative Language Abstract—Translation of the Abstract into French by the authors.)     

Displacements of Simulium damnosum and strategy of control against onchocerciasis.

Regular aerial treatment of 14 000 km of watercourses has achieved and maintained, over an area of 700 000 km2 of West African savannah, a very high degree of control of the larvae of Simulium damnosum sensu stricto and S. sirbanum, the vectors of onchocerciasis in this area. However, particular and relatively restricted parts of this area, mainly in northern Ivory Coast and neighbouring parts of Upper Volta, experience regular and prolonged reinvasions by parous female vectors, which have already taken bloodmeals (and many of them carrying the parasites) and arrive from unknown sources probably hundreds of kilometres away, from directions probably between southwest and north. This reinvasion, now experienced in three successive years, represents the outstanding scientific, epidemiological and logistic problem still facing the WHO Onchocerciasis Control Programme. An outline is presented of the multidisciplinary investigations being undertaken to find a solution.     

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.     

Epidemiological modelling for onchocerciasis control

Planning and evaluation of parasitic disease control is complicated by the many interacting factors that jointly determine the epidemiological trends under different control strategies. The Onchocerciasis Control Programme (OCP) of the World Health Organization in West Africa has recognized this problem and uses epidemiological modelling as on aid to addressing control questions. Dik Habbema, Edoh Soumbey Alley, Anton Plaisier, Gerrit van Oortmorssen and Hans Remme describe the organization of modelling in the OCP and summarize the most important achievements thus far. The experience with applied modelling in OCP is of considerable interest for other disease control programmes.     

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.