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Onchocerciasis
Evidence Levels: A Double-blind study B Clinical trial ≥ 20 subjects C Clinical trial < 20 subjects D Series ≥ 5 subjects E Anecdotal case reports
Onchocerciasis is a major tropical parasitic infection caused by the filarial worm Onchocerca volvulus and is transmitted by blood-sucking Simulium spp. blackflies, which breed near fast-flowing rivers. The Global Burden of Disease Study 2017 estimated that 20.9 million people carry O. volvulus, most of whom live in Africa, and a total of 205 million people are considered at risk of infection because of where they live. The disease is endemic in 31 countries in sub-Saharan Africa, and in smaller foci in Latin America and Yemen. Mass ivermectin treatment has now eliminated or interrupted transmission in 11 of the previous 13 foci in the Americas and the two remaining foci in Brazil and Venezuela together form a single transmission unit along the border of these countries. The World Health Organization has verified elimination of transmission of infection in Colombia, Ecuador, Mexico, and Guatemala. The first manifestation of infection is usually intense pruritus, and subsequently a wide variety of acute and chronic skin and eye changes develop, including blindness. The socioeconomic consequences of onchocerciasis are most marked in hyperendemic areas in sub-Saharan Africa. A multicountry study in Africa revealed that 42% of the adult population in endemic villages suffered from pruritus, and 28% of the population had onchocercal skin lesions.
Management Strategy
The mainstay of treatment is ivermectin. Ivermectin is a safe, effective microfilaricide (i.e., it kills the immature larval stages of filarial worms), but it does not kill the adult worms. After a few months of dosing, the numbers of microfilariae in the skin gradually increase again toward pretreatment levels, and treatment must be repeated throughout the lifespan of the adult worm (10–14 years).
Wolbachia spp. symbiotic endobacteria have been identified as essential for the filarial worms’ fertility and offer novel targets for treatment. Additional treatment with doxycycline to sterilize the worms significantly enhances ivermectin-induced suppression of microfilaridermia.
The approach to treatment of onchocerciasis varies for (1) treatment of individuals outside of endemic areas; (2) treatment of individuals within endemic areas; and (3) mass treatment programs.
Treatment of Individuals Outside of Endemic Areas
Treatment of individuals living outside of areas with ongoing transmission consists of a single dose of ivermectin (150 mcg/kg), followed 1 week later by doxycycline (200 mg daily for 6 weeks). Alternative doxycycline regimens are doxycycline 200 mg daily for 4 weeks or 100 mg daily for 6 weeks. If the patient is pregnant or less than 9 years of age, doxycycline is contraindicated.
Treatment of Individuals Within Endemic Areas
Treatment of individuals within areas of ongoing transmission consists of a single dose of ivermectin 150 mcg/kg repeated every 3–6 months until the patient is asymptomatic. Treatment should be repeated if there is recurrence of pruritus, itchy papular rash, or eosinophilia. Treatment with ivermectin may be required for 10 years or more.
Mass Treatment Programs
Three regional programs have coordinated global control. The Onchocerciasis Control Program (OCP, 1974–2002) successfully used aerial larviciding of rivers in West Africa to control the vector blackfly, and more recently it distributed ivermectin to control any recrudescence.
The Onchocerciasis Elimination Program in the Americas (OEPA, 1991–present) uses 6-monthly mass ivermectin therapy and from its outset aimed to eliminate onchocerciasis from the region.
The largest program, the African Program for Onchocerciasis Control (APOC, 1995–2016) consisted of large-scale, annual, community-directed treatment of ivermectin in 15 non-OCP countries and four ex-OCP countries. Its original aim was to reduce onchocerciasis until it was no longer a public health problem, but this was revised in 2009 to aim for elimination in Africa where feasible by 2025. The current Expanded Special Project for Elimination of Neglected Tropical Diseases (ESPEN) is a public-private partnership among WHO (AFRO), member states, and Neglected Tropical Diseases (NTD) partners, which aims to mobilize resources to accelerate elimination of onchocerciasis alongside other neglected tropical diseases.
In forested areas of central Africa and Sudan, which are coendemic with loiasis, ivermectin can cause serious neurologic adverse reactions, including fatal encephalopathy, associated with the death of large numbers of Loa loa microfilariae. Whereas lengthy doxycycline regimens are deemed impractical for main large-scale treatment of onchocerciasis, in areas coendemic with loiasis, doxycycline is a safe alternative as, due to the absence of Wolbachia, doxycycline is inactive against L. loa. Alternatively, in these high risk coendemic areas, individuals may be prescreened for L. loa and those with high L. loa microfilarial loads can be excluded from ivermectin treatment.
Specific Investigations
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The effects of ivermectin on onchocercal skin disease and severe itching: results of a multicentre trial
Brieger WR, Awedoba AK, Eneanya CI, et al. Trop Med Int Health 1998; 3: 951–61.
The effects of ivermectin were assessed in 3-monthly, 6-monthly, and annual doses in 4072 villagers in forest zones of Ghana, Nigeria, and Uganda who underwent interviews and clinical examinations at baseline and at five follow-up visits. Reactive skin lesions were categorized as acute papular onchodermatitis, chronic papular onchodermatitis, and lichenified onchodermatitis. From 6 months onwards there was a 40%–50% reduction in the prevalence of severe itching after ivermectin treatment compared with the placebo group. Also, a greater reduction in prevalence and severity of reactive skin lesions over time was seen in those receiving ivermectin. The differences between the various ivermectin treatment regimens were not significant.
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