Onchocerciasis

Published on 16/03/2015 by admin

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Last modified 16/03/2015

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Onchocerciasis

Michele E. Murdoch

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. Global estimates suggest that 37 million people carry O. volvulus, most of whom live in Africa, and a total of 90 million people are considered at risk of infection because of where they live. The disease is endemic in 23 countries in sub-Saharan Africa; small foci also exist in the Yemen and Central and Southern America (Mexico, Guatemala, Ecuador, Venezuela, and Brazil). Mass invermectin treatment has now eliminated or interrupted transmission in ten of the thirteen foci in the Americas, and in 2011 Colombia became the first country to achieve certification for elimination of onchocerciasis. The first manifestation of infection is usually intense pruritus, and subsequently a wide variety of acute and chronic skin and eye changes develop. The socioeconomic consequences of onchocerciasis are most marked in hyperendemic areas in sub-Saharan Africa. Globally, approximately 270 000 people are blind and 500 000 have significant visual loss as a direct consequence of onchocerciasis. A multi-country 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 back towards pre-treatment levels and treatment has to 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

If a strong macrofilaricidal effect is desired, the treatment of individuals living outside of areas with ongoing transmission consists of doxycycline (200 mg daily for 6 weeks), followed by a single dose of ivermectin (150 µg/kg) 4 to 6 months after completion of doxycycline. Doxycycline is given first to reduce any inflammatory reactions induced by ivermectin.

Alternative doxycycline regimens are doxycycline 200 mg daily for 4 weeks or 100 mg daily for 6 weeks followed by ivermectin single dose after 4 to 6 months if interruption of embryogenesis and cessation of microfilariae production is desired.

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 µg/kg repeated every 3 to 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 been established to coordinate 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 has distributed ivermectin to control any recrudescence. The Onchocerciasis Elimination Program in the Americas (OEPA), which started in 1991, uses 6-monthly mass ivermectin therapy and aims to eliminate onchocerciasis from the region by 2015. The largest program, the African Program for Onchocerciasis Control (APOC), commenced in 1995 and has been extended to run until 2015. It consists 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 2010 to aim for elimination. By 2015 the program intends to treat more than 90 million people.

In forested areas of central Africa and Sudan which are co-endemic with loiasis, ivermectin cannot be used because it causes serious neurological adverse reactions including encephalopathy. Whereas lengthy doxycycline regimes are deemed impractical for main large-scale treatment of onchocerciasis, in areas co-endemic with loiasis, doxycycline is a safe alternative as it is inactive against Loa loa because of the absence of Wolbachia.

Specific investigations

First-line therapies

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Ivermectin	A
Ivermectin combined with doxycycline	A

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