Site of infection: Adult female worms live in the connective tissues of the skin, where they become encapsulated forming distinctive nodules containing tangled pairs of groups of worms. Live microfilariae are released directly into adjacent host tissues (or blood for other filarial worms).

Pathogenesis: Onchocerca causes the disease onchocerciasis which has three principal manifestations; subcutaneous nodule formation; dermatitis; and blindness. Adult female worms become surrounded by fibrous nodules (onchocercomas), usually over bony prominences (especially the pelvis in Africa and the head in Mexico). The most pathogenic effects, however, are caused by the release of numerous microfilariae into host tissues. Early stage infections are often associated with pruritis, rash and lymphadenopathy in the groin or axilla. Over time (months to years), chronic inflammatory responses manifest as dermatitis, intradermal oedema, and pachydermia (thickened wrinkled skin colloquially known as crocodile or elephant skin). There is progressive loss of elastic fibres causing hernias or hanging groin (hanging lymph glands) and atrophy of the skin giving a premature aged appearance. In Africa, skin depigmentation resembling leprosy may occur, whereas hyperpigmentation (‘Sowda’) is common in Yemen. Ocular infections by microfilariae may result in blindness due to anterior (corneal) lesions causing a sclerosing keratitis and corneal opacities, or posterior (retinal) lesions resulting in marked sclerosis (hardening) of choroidal vessels and retinochoroiditis. People are afflicted more in savannah than forest regions, and the common name ‘river blindness’ actually indicates an association between the distribution of infections and suitable habitats for the insect vector. Infections in animals by other Onchocerca spp. do not result in severe diseases; infections in cattle may lead to devaluation of carcasses and blemished hides, although there is some evidence of ocular inflammatory reactions in horses.

Mode of transmission: All filarial worms have indirect life-cycles, involving vector-borne transmission. O. volvulus infections are transmitted by small black-flies (sometimes called buffalo gnats) of the genus Simulium. The flies are pool-feeders with coarse mouthparts that rasp and tear host tissues. They feed on a variety of mammals and birds, and their painful bites cause considerable annoyance. Microfilariae ingested during feeding migrate to the flight muscles of the fly and moult twice over 1 week. They then migrate to the proboscis and develop into infective third-stage larvae which are transmitted to vertebrate hosts during feeding. Larvae injected into subcutaneous tissues moult and develop into mature worms over 1-2 years before the females start producing microfilariae. Adult worms may live for as long as 12 years and produce billions of microfilariae. Many studies have demonstrated differences in the temporal and spatial distribution of microfilariae; many species exhibit a daily periodicity or tissue tropism which is attuned to the feeding habits of the vector species; e.g. microfilariae of Onchocerca in Africa normally concentrates in lower body to maximize transmission to low-biting Simulium damnosum but infections in Guatemala concentrate in the upper body where the vector is the high-biting Simulium ochraceum.

Differential diagnosis: The diagnosis of early stage infections on the basis of the appearance of a pruritic rash is not distinctive enough as other conditions may cause similar conditions. Infections are generally diagnosed after they have become patent and worms have formed characteristic palpable nodules under the skin. Portions of worms can be obtained by biopsy to confirm diagnosis. Infections can also be detected by examining skin-snip biopsies for active microfilariae after incubation in saline for 30 mins. Onchocerca microfilariae are rarely found in blood whereas those of other filarial worms are commonly found in peripheral blood samples (taken at different times of the day to account for any differences in periodicity). Microfilariae may be concentrated from blood samples using Knott’s technique to lyse erythrocytes with dilute formalin, or filtering blood through 3-5µm pore-size polycarbonate filters. The morphological characteristics of microfilariae are distinctive enough to differentiate all human filarial worms. A wide variety of immunoserological tests have been developed in attempts to differentially diagnose infections, especially early stage infections, but most tests have lacked sensitivity and specificity. Various molecular biological techniques are currently under development to detect parasite antigens or DNA in host fluids.

Treatment and control: A common therapeutic practice in endemic regions is that of nodulectomy, that is, the surgical removal of detectable nodules from superficial aspects to stop microfilariae production and curb attendant pathology. Some nodules, however, may by non-palpable or the adults may be freely migrating. Chemotherapy is therefore warranted, and a major advance was made with the development of ivermectin which is well tolerated in humans. Single doses were found to eliminate microfilariae from the skin, and to suppress their release from adults for over a year. Multple doses were also found to slowly kill adults. Other microfilaricidal drugs include diethylcarbamazine (DEC), mebendazole, flubendazole and benzimidazole derivatives, but they have little or no effect on adult worms. DEC treatment may also precipitate serious dermal, systemic or ocular complications caused by dying microfilariae, although such side-effects can be ameliorated by the use of anti-inflammatory drugs. Suramin does have an effect on adult worms, but it must be administered systemically and it is nephrotoxic. Preventive measures involve vector control and avoiding black-fly bites. Residual insecticides can be used around dwellings to reduce adult fly numbers, but better results are obtained using larvicides to treat rivers and streams where black-flies breed. Unfortunately, there are recurring problems with the development of insecticide resistance in black-fly populations.

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