Impact of ivermectin on onchocerciasis transmission: assessing the empirical evidence that repeated ivermectin mass treatments may lead to elimination/eradication in West-Africa

BACKGROUND: The Onchocerciasis Control Program (OCP) in West Africa has been closed down at the end of 2002. All subsequent control will be transferred to the participating countries and will almost entirely be based on periodic mass treatment with ivermectin. This makes the question whether elimination of infection or eradication of onchocerciasis can be achieved using this strategy of critical importance. This study was undertaken to explore this issue. METHODS: An empirical approach was adopted in which a comprehensive analysis was undertaken of available data on the impact of more than a decade of ivermectin treatment on onchocerciasis infection and transmission. Relevant entomological and epidemiological data from 14 river basins in the OCP and one basin in Cameroon were reviewed. Areas were distinguished by frequency of treatment (6-monthly or annually), endemicity level and additional control measures such as vector control. Assessment of results were in terms of epidemiological and entomological parameters, and as a measure of inputs, therapeutic and geographical coverage rates were used. RESULTS: In all of the river basins studied, ivermectin treatment sharply reduced prevalence and intensity of infection. Significant transmission, however, is still ongoing in some basins after 10-12 years of ivermectin treatment. In other basins, transmission may have been interrupted, but this needs to be confirmed by in-depth evaluations. In one mesoendemic basin, where 20 rounds of four-monthly treatment reduced prevalence of infection to levels as low as 2-3%, there was significant recrudescence of infection within a few years after interruption of treatment. CONCLUSIONS: Ivermectin treatment has been very successful in eliminating onchocerciasis as a public health problem. However, the results presented in this paper make it almost certain that repeated ivermectin mass treatment will not lead to the elimination of transmission of onchocerciasis from West Africa. Data on 6-monthly treatments are not sufficient to draw definitive conclusions.     

Pharmacology of ivermectin

Ivermectin is a semi-synthetic macrocyclic lactone (Fig. I) active in single low doses against many parasites - particularly nematodes and arthropods. It has been registered for animal health use since early 1985, and was earlier this year approved for human use by the French Directorate o f Pharmacy and Drugs. Of particular interest is ivermectin's potential as a micro filaricide for treatment o f onchocerciasis. Clinical trials leave little doubt about the potential o f ivermectin as a therapeutic tool for symptomatic relief from the effects o f infection with Onchocerca volvulus, and the drug is also recognized to have potential in reducing transmission o f the parasite. The manufacturers (Merck, Sharp and Dohme) recently arranged to provide the drug free o f charge to the WHO for mass trials against onchocerciasis in 12 African and Central American countries. In this article we focus on the pharmacological properties o f ivermectin, with a brief consideration of its absorption, fate, excretion and side-effects, and a discussion o f its micro filaricidal action.     

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.     

African Program for Onchocerciasis Control 1995–2010: Impact of Annual Ivermectin Mass Treatment on Off-Target Infectious Diseases

Since its initiation in 1995, the African Program for Onchocerciasis Control (APOC) has had a substantial impact on the prevalence and burden of onchocerciasis through annual ivermectin mass treatment. Ivermectin is a broad-spectrum anti-parasitic agent that also has an impact on other co-endemic parasitic infections. In this study, we roughly assessed the additional impact of APOC activities on the burden of the most important off-target infections: soil-transmitted helminthiases (STH; ascariasis, trichuriasis, hookworm, and strongyloidiasis), lymphatic filariasis (LF), and scabies. Based on a literature review, we formulated assumptions about the impact of ivermectin treatment on the disease burden of these off-target infections. Using data on the number of ivermectin treatments in APOC regions and the latest estimates of the burden of disease, we then calculated the impact of APOC activities on off-target infections in terms of disability-adjusted life years (DALYs) averted. We conservatively estimated that between 1995 and 2010, annual ivermectin mass treatment has cumulatively averted about 500 thousand DALYs from co-endemic STH infections, LF, and scabies. This impact comprised approximately an additional 5.5% relative to the total burden averted from onchocerciasis (8.9 million DALYs) and indicates that the overall cost-effectiveness of APOC is even higher than previously reported.     

Onchocerciasis in Ecuador: the situation in 1989.

Details are given of the prevalence rates of onchocerciasis from the most recent surveys (1989) conducted in northern Ecuador. The disease has intensified and dispersed considerably due to migration of infected individuals and the presence of a highly efficient vector. Comparison of these data with those from two previous surveys carried out in 1982/83 and 1986 and correlated with entomological findings highlight the danger of the formation of new foci of onchocerciasis in areas currently free of the disease. Recommendations are made for further entomological studies in areas either recently or likely to be affected by the disease where potential vectors are unknown or different to those registered in the Santiago focus. Ivermectin treatment with local vector control in specific areas is advocated to reduce the disease to a low level of public health importance.     

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.     

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.     

The Effects of Ivermectin on Brugia malayi Females In Vitro: A Transcriptomic Approach

BackgroundLymphatic filariasis and onchocerciasis are disabling and disfiguring neglected tropical diseases of major importance in developing countries. Ivermectin is the drug of choice for mass drug administration programs for the control of onchocerciasis and lymphatic filariasis in areas where the diseases are co-endemic. Although ivermectin paralyzes somatic and pharyngeal muscles in many nematodes, these actions are poorly characterized in adult filariae. We hypothesize that paralysis of pharyngeal pumping by ivermectin in filariae could result in deprivation of essential nutrients, especially iron, inducing a wide range of responses evidenced by altered gene expression, changes in metabolic pathways, and altered developmental states in embryos. Previous studies have shown that ivermectin treatment significantly reduces microfilariae release from females within four days of exposure in vivo, while not markedly affecting adult worms. However, the mechanisms responsible for reduced production of microfilariae are poorly understood.Conclusion/SignificanceThese changes provide insight into the mechanisms involved in ivermectin-induced reduction in microfilaria output and impaired fertility, embryogenesis, and larval development.     

Clinical picture and outcome of Serious Adverse Events in the treatment of Onchocerciasis

Ivermectin (Mectizan(R)) is the only drug currently recommended for the treatment and control of onchocerciasis. Serious adverse events rarely occur during treatment, except in subjects heavily infected with Loa Loa. This review of drug-related serious adverse events in the treatment of onchocerciasis therefore revisited the pre-Mectizan(R) reference drugs, DEC and suramin, and other candidate drugs studied extensively for the treatment of human onchocerciasis. The benzimidazole carbamate derivatives and the antibiotic doxycycline were excluded, since no serious adverse events have been reported regarding their use. Using recommended definitions, serious adverse events reported or observed after the use of each drug were summarised, the level of attribution determined, and the results tabulated. Prominence was given to treatment-related deaths. The clinical picture of severe symptomatic postural hypotension is described and used to illustrate the difference between the severity and the seriousness of an adverse event. The epidemiology, management and outcome of serious adverse events are presented. The role of future research is discussed.     

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.     

Onchocerciasis-associated epilepsy: an update and future perspectives

Onchocerciasis-associated epilepsy (OAE) is an important neglected public health problem in areas with high ongoing onchocerciasis transmission. The risk that children in such areas develop epilepsy is related to their Onchocerca volvulus microfilarial (mf) load. Before the implementation of mass treatment with ivermectin, microfilariae were detected in cerebrospinal fluid (CSF). More recently, neither O. volvulus microfilariae nor DNA were detected in CSF or brain tissue; however, these samples were obtained years after seizure onset. It is possible that during fever-induced increased blood–brain barrier permeability, microfilariae enter the brain and, upon dying, cause an inflammatory reaction inducing seizures. Including OAE in the onchocerciasis disease burden estimation may mobilise extra resources for onchocerciasis disease elimination and treatment/care of OAE-affected persons/families.     

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.     

Cattle protected from onchocerciasis by ivermectin are highly susceptible to infection after drug withdrawal

Ivermectin administration is now the major tool in the control of human onchocerciasis (caused by Onchocerca volvulus) based on its suppression of microfilariae and hence the prevention of disease. However, in Africa, transmission is not eliminated and treated populations continue to be exposed to infective larval (L(3)) challenge, albeit at reduced levels. We have investigated whether protective immunity might develop under such conditions using the analogous host-parasite system Onchocerca ochengi in cattle, based on our previous findings in cattle exposed to challenge, that in vivo ivermectin attenuates the development of adult infections and that irradiation-attenuated L(3) induce significant protection. In a two-phase prospective study over 4 years, groups of cattle were exposed to severe natural challenge. In the first phase, 38/40 animals treated either with ivermectin or with moxidectin at either monthly or 3-monthly intervals had not developed detectable infections after 22 months of exposure whereas, in a non-treated control group (n = 14) nodule prevalence was 78.6% and the geometric mean (range) nodule load was 4.8 (0-33). In the second phase, all drug treatments were withdrawn, a new control group (n = 8) introduced, and exposure continued at the same site. After 24 months, all groups had developed patent infections, with geometric mean (range) nodule loads of 17.4 (4-99), 38.4 (10-111), 50.7 (26-86), 14.3 (0-69) and 14.7 (0-55) for the control, monthly-ivermectin, 3-monthly ivermectin, monthly moxidectin and 3-monthly moxidectin groups, respectively. There was no evidence of protection-indeed the 3-monthly ivermectin group was significantly (P < 0.05) hyper-susceptible. In addition, microfilarial densities and the rate of increase in microfilarial load were significantly higher (P < 0.05) in the ivermectin-treated groups than in control animals. These results have important implications for ivermectin-based control of human onchocerciasis and suggest that humans exposed to ongoing transmission in endemic areas whilst receiving ivermectin are unlikely to develop immunity and will be highly susceptible should drug distribution cease.     

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.     

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.     

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.     

The onchocerciasis chronicle: from the beginning to the end?

The year 2012 marks the 25th anniversary of the donation of ivermectin to fight onchocerciasis and the projected date for elimination of transmission of the disease in the Americas. This review looks at the history of onchocerciasis, from its discovery through to 2025, by which time it is projected that the disease will have been eliminated as a public health problem, except in a handful of sub-Saharan countries, where it should be well on the way towards elimination.     

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.     

Doxycycline in the treatment of human onchocerciasis: Kinetics of Wolbachia endobacteria reduction and of inhibition of embryogenesis in female Onchocerca worms

Recently, experts have warned that mass treatment with ivermectin alone may not interrupt the transmission of Onchocerca. Hence, additional drugs are needed, such as antibiotics acting on symbiotic endobacteria of the filariae, the causative agents of onchocerciasis. Based on animal experiments, human onchocerciasis was treated with doxycycline, and preliminary observations published in 2001 in The Lancet showed sterility in female worms by depletion and marked reduction in symbiotic Wolbachia endobacteria from the filariae. Here, a detailed kinetic analysis of the features of the worms, following administration or not of doxycycline to the patients is reported. Sixty-three onchocerciasis patients in Ghana were treated with 100 mg doxycycline daily for 6 weeks and 2 or 6 months later with ivermectin. Onchocercomas were extirpated 2, 6, 11 and 18 months after the onset of treatment and the filariae were examined by immunohistology and PCR. The analysis showed: (i) progressive depletion of Wolbachia from adult worms and microfilariae by doxycycline over a period of 6 months; (ii) inhibition of embryogenesis by doxycycline after 6 months with respect to all embryo stages followed by decline in microfilariae after 11 months; (iii) reduction in spermatozoa in the female genital tract by doxycycline, whereas spermiogenesis was only partly reduced after 11 and 18 months; (iv) no relevant macro- or microfilaricidal activity; (v) depletion/marked reduction in endobacteria and inhibition of embryogenesis were sustained until 18 months after doxycycline and 12 months after co-administration of ivermectin; (vi) no severe adverse side effects were seen. Due to its long-lasting inhibition of embryogenesis, doxycycline presents an additional strategy for the treatment of onchocerciasis and control of Onchocerca microfilariae transmission. Extension of the existing registration will not require much time or high cost. Treatment of individual patients can be considered immediately.     

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.