Focus: Onchocerciasis

Background

Causative agent. Onchocerciasis (river blindness) is a parasitic disease caused by the filarial worm Onchocerca volvulus. It is transmitted through the bite of infected black flies of the genus Simulium, which carry the immature larval form of O. volvulus (known as microfilaria). The disease manifests as a reaction to the presence of microfilaria in the skin (itching, acute and chronic papular onchodermititis, fibrosis, atrophy and depigmentation), and the eye (acute and chronic lesions in the anterior and posterior segment). The most devastating effect is blindness.

Distribution. Onchocerciasis is found in 28 countries in Africa — in the savannah as well as in the forest zone — from Senegal to Malawi, 6 countries in Latin America and in the Yemen. At present, the World Health Organization estimates that there are more than 17.7 million people infected with onchocerciasis — approximately 500,000 with visual impairments, 270,000 of whom are blind^1,2. 99% of the cases are, however, found in Africa.

Current global status and impact. Owing to a fear of blindness, there has been a depopulation of the fertile river valleys of the west African savannah — making onchocerciasis an obstacle to socio-economic development. A combination of vector control in West Africa, the use of ivermectin, large-scale Community Directed Treatment (ComDT) and the use of ONCHOSIM² (a microsimulation model for onchocerciasis transmission) has allowed the continuous annual treatment of more than 30 million people. Interruption of transmission of O. volvulus and reduction of the burden of visual impairment and blindness has been achieved in most of the West African region and in the six Latin American countries affected by this parasite, and in these areas onchocerciasis is no longer a disease of public health importance. However, the skin disease, with its adverse psycho-social and socio-economic effects, continues to be a problem in the rest of Africa³.

Recent developments

New basic knowledge. Gene discovery in O. volvulus has been based on the generation of expressed sequence tags (ESTs); 12,269 ESTs from O. volvulus (six stage-specific libraries) have been clustered to form 4,208 groups⁴. The pathogenesis of onchocerciasis is poorly understood. Recent studies have indicated that the endosymbiotic bacterium Wolbachia might play a role in the ocular and skin disease⁵. Post-treatment reactions might also be related to Wolbachia products that mediate inflammatory responses⁶.

Global distribution of onchocerciasis.

New tools and intervention methods. A review of the impact of 10–12 years of ivermectin treatment reported that ivermectin was very effective in controlling the public health aspect of the disease. However, elimination of transmission proved more difficult⁷. It is unlikely that ivermectin treatment alone can provide a complete solution to onchocerciasis and a recent conference concluded that eradication is not feasible with the present tools⁸. So there is an urgent need for the development of new tools. First, modelling revealed that the use of drugs that would kill or sterilize the adult worm would be effective in eradication⁹. The endosymbiont Wolbachia has emerged as a potential drug target because the treatment of O. volvulus-infected individuals with doxycycline resulted in irreversible elimination of skin microfilaria, presumably through direct effects on the endosymbiont¹⁰. Although effective for individuals, the duration of the treatment is considered too long for mass treatment. Attention has been drawn to the milbemycin compound moxidectin, which has been shown to severely impair embryogenesis in most onchocerciasis animal models¹¹. Second, diagnostic methods for surveillance that do not rely on taking skin samples to detect microfilaria are urgently needed. The use of specific antibodies, such as those directed to the Ov16 antigen, have been proposed as an alternative. Third, repeated treatments with ivermectin increase the risk of ivermectin resistance. Several cases of 'poor responsiveness' to ivermectin, as well as the detection of residual microfiladermia after treatment with ivermectin, have been reported^12,13. Whilst the relevance of these observations has not been established, development of a test to detect ivermectin resistance is required. Attention has been drawn to neurological reactions in individuals with a Loa loa infection after treatment with ivermectin. This could pose problems for ivermectin treatment programmes in areas that are co-endemic for L. loa (Central Africa). Rapid mapping methods based on remote-sensing data and simple questionnaires have been developed to allow identification of high L. loa prevalence areas¹⁴.

New strategies, policies and partnerships. In most of Africa, the principal control strategy is annual ComDT with ivermectin in high-risk areas to control onchocerciasis. The potential of ComDT for providing additional health services to the poor¹⁵ and the impact on programme sustainability¹⁶ has been assessed. Ongoing implementation research should determine the feasibility of using the ComDT approach for integrated delivery of community-based interventions, for example, mass treatment of other helminthic infections or home management of malaria. In the Americas, the control strategy involves 6-monthly treatments in all endemic areas with the aim to eliminate onchocercal morbidity and, where feasible, to interrupt transmission.

Conclusions and future work

In West Africa, where there has been almost complete interruption of onchocerciasis transmission, the primary objective should be effective epidemiological surveillance to detect and control disease recurrence. A sustained annual treatment is needed in the rest of Africa if transmission is to be kept at the lowest levels possible and morbidity controlled. In African disease settings with more than 14 years of ivermectin treatment, field studies and modelling will determine the conditions under which ivermectin treatment can be stopped without risking recurrence. Therapeutic approaches to reduce the load of L. loa infections are also needed to achieve ivermectin coverage. As both the O. volvulus and Wolbachia genome sequencing projects near completion, new opportunities for the identification of new drugs, vaccines and diagnostic targets will emerge. This might transform the control programmes and make eradication a reality.