Onchocerciasis (syn. onchocercosis) is a disease resulting from infection by the nematode Onchocerca volvulus. The principal characteristics of the condition are pruritic dermatitis, subcutaneous nodules and ocular lesions. Skin lesions were described at the end of the nineteenth century in Africa by Leuckart (1993) and by the Briton, John O'Neil (1875). Robles in 1915 discovered the disease in Guatemala. He was the first to associate the subcutaneous nodules with eye lesions.

The disease nowadays occurs principally in large parts of Africa, especially West and Central Africa (including both Congos and Angola), but also in Soudan, Ethiopia, the north of Uganda and even Tanzania. There are isolated foci in Yemen, in Central America such as Mexico and Guatemala (predominantly mountainous districts where coffee is cultivated) and in the north of South America (discrete foci in Columbia, Ecuador, Brazil and Venezuela). There is no onchocerciasis in Europe, Australia, Central Asia, Southeast Asia, the Far East or the Pacific Bassin.

• In Mexico there are three foci: one in Oaxaca, and two (a northern and a southern one) in Chiapas.

• In Columbia there is an infected area in the pacific department of Cauca, at municipio López de Micay).

• In Venezuela, there are three foci, two in the north: (1) north central (Aragua, Carabobo, Cojedes, Guarico, Miranda, Yaracuy), (2) north east (Anzoátegui, Monagas, Sucre) and one in the south, in Amazonas, in the Yanomami area.

• In Ecuador, The endemic area is in the north of the country, in the province of Esmeraldas, with main foci in Río Cayapas, Río Santiago and Río Onzole. There are a number of smaller satellite foci, most of the in Esmeralda, and one in the province of Pichincha (Río Tululví, Río Canandé, Río Verde, Río Viche, Río Sucio and Santo Domingo de los Colorados).

• In Brazil, the problem is concentrated in Roraima and the northern part of Amazonia, in the extreme northern part of the country. The area where the Yanomami indians live is about 90,000 km2. This enormous area straddles the border between Venezuela and Brazil. Tucuxim, Xitel, Surucucu, Homoxi and Balawau are the worst affected areas.

The infective larvae are transmitted by Simulium mosquitoes ("blackflies"). Several Simulium "species" consist of morphologically identical insects, but which exhibit biochemical, ecological and other differences. This is why reference is made for example to the Simulium damnosum complex (Africa). In Central and South America the main vectors are Simulium ochraceum and S. metallicum. Other Latin American vectors include S. guianense, S. oyopockense, S. exiguum, S. quadrivitatum and S. incrustatum. These small insects (3.5 mm) have a typical highly curved thorax ("hump") and are therefore sometimes referred to as "buffalo gnats". They reproduce in rivers and can cover large distances. The fact that the insects are good fliers makes vector control difficult. Eggs are 0.1-0.4 mm long and are surrounded by a sticky substance. They are always laid in flowing water. S. ochraceum lays its eggs while flying over water. Other Simulium species land on partially submerged objects (stones, plants, etc.) and lay 150-800 eggs on or just under the water level (females can go under water for egg-laying). Sometimes there are only a few ecologically very suitable places, where thousands of eggs are then laid. This can lead to the sudden simultaneous appearance of massive numbers of adult insects when the environmental conditions are right. The larvae are sedentary and adhere firmly to rocks or stones. The medical important species are filter feeders and this makes them susceptible to insecticides dispersed in the water. S. neavei larvae have the unusual habit of adhering to other arthropods, such as small crabs (known as a "phoretic relationship").

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Only female insects suck blood (from humans as well as animals). This happens during the day in the open at well-defined times. The bite is painful. The short mouthparts cannot penetrate deep into the skin. The mandibles and maxillae have serrated teeth and cut through superficial tissue and capillaries, producing a pool of bloody fluid that can be sucked up [these insects are known as "poolfeeders" or telmophages (Gr. "telma" = pool, marsh), in contrast for example to Culex mosquitoes which are "capillary feeders" or solenophages (Gr. "soleno" = tube, pipe)]. This feeding method is ideal for transmission, since the microfilariae are located very superficially in the skin (not in the blood). In some areas (e.g. Canada) the enormous numbers of insects make outdoor activities almost impossible at certain times (it can be compared with the disruption caused elsewhere by Culicoides and Aedes sp.).

There is no significant animal reservoir. Onchocerca volvulus microfilariae are more tissue parasites than blood parasites. An adult Simulium female can consume numerous larvae during a blood meal, but only 2 or 3 of these will develop further to infective larvae in the insect’s thoracic muscles. After maturation of the parasites, infective larvae can be introduced into a new host through a subsequent bite site. The interval between the aspiration of microfilariae and infectiousness is 6-13 days. The lifespan (adult insect) of many simulids is 3 weeks. The more insect bites someone suffers over the course of the years, the greater the worm load. After a bite from an infected insect, the infective larvae develop in humans to adult worms (=macrofilariae) that live subcutaneously. The prepatent period (time between infection and detection of microfilariae) is 3 to 15 months. The adult female is 25 to 50 cm long and 0.3 mm wide. Males are only 2 to 4 cm long. When the female lays the microfilariae, they lose their egg membrane (Onchocerca microfilariae are "unsheathed"). A female lays on average 1600 microfilariae per day. Microfilariae are 220 to 360 m m long and 5 to 9 m m wide. The nuclei at the head end lie side by side while in the fine tapering tail there are long drawn-out nuclei that do not extend as far as the end. These features are important in distinguishing them from other microfilariae that can be found in the skin such as Mansonella streptocerca and Mansonella ozzardi. The macrofilariae lie coiled subcutaneously in nodules and can live for up to 15 years. These nodules are predominantly located on the scalp and upper body in people living in Central and South America but occur more on the pelvis and legs in Africans. This has to do with the biting habits of the vector. Simulium damnosum (Africa) tends to bite on the lower half of the body (98% of bites below the belt) and Simulium ochraceum (America) preferably bite on the upper part of the body. The microfilariae concentrate in the skin, eyes and lymph nodes. When the microfilariae die, they cause a local inflammatory reaction. Microfilariae have an average life span of 13 months.

Pruritus occurs locally or systemically. There are scratch lesions often with bacterial surinfection. The chronic itching has given rise to the terms "gale filarienne" and "craw craw". If untreated, the dermatitis assumes the form of a pruritic papular dermatitis, progressing to a chronic rough, coarse, papular dermatitis, often with postinflammatory hyperpigmentation, followed by lichenification, atrophy and finally patchy depigmentation (leopard skin). Pea- to plum-sized subcutaneous nodules are found predominantly over bony protuberances such as the hip, pelvis, ribs, shoulderblades and skull. For every palpable nodule, there are 4 non-palpable nodules (forest onchocerciasis) or 10 non-palpable nodules (savanna onchocerciasis). Though not always found (in Africa in only 30 to 60% of positive people), enlargement of the inguinal nodes is sometimes also present, resulting in what is known as "hanging groin". Onchocerciasis causes elephantiasis (lymphoedema) in a number of cases. In Yemen, a syndrome of unilateral or bilateral maculopapular pruritic onchocerca dermatitis of the legs is found with hyperpigmentation and inguinal lymph node enlargement, known as "Sowda".

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Onchocerca volvulus sequesters retinol (vitamin A) by means of specific proteins. How far this contributes to hypovitaminosis A and to what extent this is significant in the pathology is a subject of intensive study.

Ocular lesions only occur after many years of severe infection and are therefore usually not present before the age of 30. They are more frequent in savanna regions than in the rainforest.

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Ocular lesions can be exacerbated by DEC therapy, but not by ivermectin. Microfilariae can be seen in the anterior chamber with a slitlamp. When microfilariae die, opaque fine 0.5 mm wide lesions corneal occur: keratitis punctata. This is a corneal inflammation with small spots on the cornea accompanied by redness of the conjunctiva. Sclerosing keratitis occurs later (hazy cornea with pannus formation) as well as iritis and uveitis, resulting in blindness (river blindness!). More rarely, there is involvement of the posterior part of the eye: chorioretinitis and optic nerve atrophy. In chorioretinitis, an active exudative form and a chronic atrophic form are recognised. There is initially a loss of retinal pigment which assumes a greyish-yellow patchy appearance, mostly in an arch around the macula (temporally to the macula and nasally to the optic disk). Pigment clumps, atrophy and subretinal fibrosis occur subsequently.

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Various techniques may be used for detecting microfilariae in the skin. A skin snip is often used. A needle is used to raise the skin and a fine piece is shaved off with a razor blade. A standardised punch biopsy is also possible. The piece of tissue is placed in some physiological saline. The specimen is then examined 15 minutes to 3 hours later to see whether or not microfilariae have emerged.

This is done by means of scarification with a sterile razor blade. Preferably several sites are examined (often 4 sites are choosen). The fluid obtained can be collected on a glass slide and stained with Giemsa to allow identification.

Occasionally O. volvulus microfilariae are found in the blood and in the urine.

This is both diagnostic and curative if all the nodules would be resected. The macrofilariae are found in the nodule.

This is a non-invasive test, but requires considerable experience. It is best to get the patient to lay his/her head on his/her knees for at least 2 minutes before the examination to allow more microfilariae to come into the anterior eye chamber.

If the diagnosis is doubtful, the patient may be given 50 mg DEC orally. If microfilariae are present, a severe itching reaction will occur within 2 hours. This is caused by an allergic reaction to the proteins released after the rapid breakdown of microfilariae. Because this is very unpleasant, this test should be used only when strictly necessary. Topical use of a DEC-containing cream has also been described (DEC patch test), in response to which a limited local skin reaction can occur.

Serology cannot distinguish between the various species of filariae. The antigen used is usually extracted from a different worm: Litosomoides sigmodontis.

This is a fairly recent technique which is relatively complicated and needs to be assessed further. The benefit for individual patients in endemic areas is probably limited.

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Alternatives are being studied, including the derivatives doramectin and moxidectin. Moxidectin has a plasma half-life of 20 days (in contrast to 2 days for ivermectin) and is macrofilaricidal. It is obtained from cultures of Streptomyces cyanogriseus ssp. noncyanogenus. At present it is only used in veterinary medicine.

Suramin was previously used as a macrofilaricidal agent, but it is much simpler and safer to give ivermectin repeatedly. Suramin has at present been abandoned in the treatment of onchocerciasis (but is still used in West African trypanosomiasis).

There is still no good macrofilaricidal agent available. Amocarzine was shown not to be active in clinical trials.

Tetracyclines such as vibramycin can kill Wolbachia endosymbionts of macrofilariae. According to initial findings, the subsequent suppression of embryogenesis by ivermectin lasts much longer (at least 18 months). The therapeutic place of vibramycin however has not been established.

This involves the removal of superficial nodules and is popular in Central America.

In 1968, the WHO decided to instigate a large scale onchocerciasis control programme (OCP). The emphasis of the programme is on vector control in areas where the disease is often associated with blindness (savanna-type onchocerciasis). Initially it involved 7 West African countries (Benin, Burkina Faso, Ivory Coast, Ghana, Mali, Niger and Togo).

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After a few years of preparation, the vector control programme started in 1974. In 1978, and subsequently in 1986, the programme was extended to the west and south (including Guinea, Guinea-Bissau, Senegal and Sierra Leone) to a total of 11 countries. It covers an area of 1,235,000 km² with 50,000 km of river. Initially 30,000,000 people lived there. In view of the fact that an adult female worm lives on average 11 years, it was estimated that a minimum of 14 years of insect control would be necessary to eradicate the human reservoir of onchocerciasis. At present, interruption of transmission has been achieved in large areas and onchocerciasis no longer constitutes a public health problem there. In these zones, the average number of microfilariae per skin sample is now almost zero. Spraying operations ceased altogether in the year 2002. In marginal areas (re-infestation) and a few well-defined foci there is still considerable transmission. In 1980, resistance to temephos (Abate®) was observed. Shortly afterwards chlorphoxim resistance was demonstrated. The programme therefore used various larvicides (insecticides) alternately to counter resistance formation: organophosphates [temephos (1975), chlorphoxim (1980), pyraclofos (1993)], the biocide Bt H14 (1985), the pyrethroid permethrin (1986) and the carbamate carbosulphan (1989). In 1997, the pseudopyrethroid etofenprox (Vectron®) was used. Bacillus thuringiensis var. israelensis (serotype H14) is a bacterium that contains toxins with specific larvicidal activity for well-defined Diptera larvae (narrow spectrum insecticide). The bacteria can be cultured simply on a large-scale, killed and afterwards sprayed as powder on the water. The dead entomopathogenic bacteria are eaten by the larvae. There are some technical drawbacks associated with this method. The bacteria rapidly sediment to the bottom, disappear from the larval feeding zone and the toxin is sensitive to UV light.

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An independent ecological group monitors any side-effects on flora and fauna in the areas concerned. The amount of collateral damage appears in practice to be limited. The insecticides should only be sprayed at a few selected sites since afterwards they are transported with the flow downstream and thus can kill larvae over long distances (each insecticide has a so-called specific carry distance). Water flow rate and depth are used to calculate the doses. There are numerous hydrological monitoring stations which transmit their data electronically to a centre in Toulouse (France), after which the data can be sent back to the field workers. This has the added bonus that hydrobiological knowledge of the West African river systems has increased considerably. The choice of insecticide is determined by several factors: water flow rate, carry distance, cost price of the insecticide including transport costs, and resistance potential. In some areas, dispersion of insecticides from the ground is difficult (enormous areas with large networks of small streams) and in these circumstances small aeroplanes or helicopters may be used.

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At the same time scientific study of vectors is encouraged. Major findings have emerged from the research programme:

• The phenomenon of simulid migration over long distances with subsequent re-invasion of treated areas was discovered. This indicated that focal vector control was not achievable.
• Development of methods for identifying simulids by cytotaxonomy, isoenzymes, DNA analysis, cuticular hydrocarbon analysis, morphometry. New species have been discovered.
• Development of DNA/PCR methods for Onchocerca identification and their application in epidemiological monitoring. Thus, for instance, many simulids were shown to be infected with the very similar looking parasite Onchocerca ochengi. Before this parasite could be identified, it caused confusion in epidemiological monitoring. This has also led to a better knowledge of the epidemiology of O. volvulus in terms of geographical distribution, strains and pathogenic potential.
• A model based on Onchocerca ochengi has been developed for evaluation of macrofilaricides
• Development of improved insecticides, e.g. Bt H14

The onchocerciasis control programme to date is a success. Already 15 million hectares of agricultural land have been made accessible for settlement and cultivation. Approximately 25 million hectares had been rendered onchocerciasis-free around the turn of the 21^st century. Larvicidal operations were phased out in 2002. This was followed by epidemiological surveys to ensure the areas remain free of vector species. The OCP is confined to a limited number of endemic countries. It is therefore not the case that onchocerciasis will be eradicated after OCP.

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Results anno 2003:

The 30-year OCP campaign has successfully ended the blight of river blindness in West Africa. When it began, about 10% of the population in high-impact regions were completely blind and 30% had severe visual disorders. No question, OCP has been a huge success in terms of its achievements in eliminating onchocerciasis as an important public-health problem throughout much of West Africa and by contributing to development in the 11 OCP countries. Moreover, OCP has been a model of effective partnership over a long-standing period. The OCP program has prevented 600,000 cases of blindness, spared 18 million children the risk of onchocerciasis, and largely eliminated the incalculable, centuries-old burden of incessant itching and disfigurement. Disease control has opened vast tracts of the best farmland in the region. Over 25 million hectares have been made safe for cultivation and settlement. By preventing and treating onchocerciasis morbidity, OCP has added roughly 10 million person-years of labour to the economies of 11 countries in West Africa.

At the beginning of 1996, a new programme (APOC: African Programme for Onchocerciasis Control) was instigated to organise treatment with ivermectin outside the OPC countries. Angola, Burundi, Cameroon, C.A.R., Chad, Congo (Brazzaville), Democratic Republic of Congo (Kin.), Equatorial Guinea, Ethiopia, Gabon, Kenya, Liberia, Malawi, Mozambique, Nigeria, Rwanda, Sudan, Tanzania and Uganda are the 19 countries participating in this project, which will probably take 12 years to complete. Ivermectin is an important microfilaricidal agent. It was tested on a large scale in the onchocerciasis chemotherapy project. In endemic regions, however, the annual free administration (mass therapy) cannot ensure interruption of transmission. This may be achieved by giving the product more frequently. Suitable epidemiological techniques are being developed: REMO ("rapid epidemiological mapping of onchocerciasis") and REA ("rapid epidemiological assessment"). In respect of the provision of medication, there is close co-operation with the various governments and several NGOs (including the Christoffel Mission for the Blind, Helen Keller International, Carter Centre Global 2000, International Eye Foundation, Organisation pour la Prévention de la Cécité, Sightsavers).

The Onchocerciasis Elimination Programme in the Americas (OEPA) was instituted in 1993. It is based on treatment with ivermectin. Six endemic countries are at present involved in the programme, which will run until ± 2008.