onchocerciasis A progressive inflammatory eye and skin disease River blindness 18 million people infected of which 770,000 already have impaired vision with 250,000 blind (estimates for annually rain) Caused by infection with the filarial nematode Onchocerca volvulus

Epidemiology The disease was most prevalent in West Africa, but now has been dramatically reduced there Significant transmission still occurs in several central African countries Transmission on the American continent is now reduced to a few very small foci.

onchocerciasis Infection occurs in proximity to fast moving water (river blindness) in some communities up to 90% of inhabitants tested positive for filaria

Morphology and biology Adult females are up to 500mm long & males up to 40mm long Adults live up to 14 years Restricted to humans (no known animal reservoirs) Transmitted by black flies (Simuliidae) Larvae live in fast-flowing water

para-lab by l. wafa menawi

Onchocercosis life cycle Adult worms (macrofilaria) live in nodules under the skin of the human host The female is ovovivipar and releases L1 (microfilaria) Microfilaria migrate through the dermis Black flies take up microfilaria through the blood meal, the worms settle in the fly thorax muscle and develop into infectious L3

onchocerciasis L1 and L2 develop in the flight muscle in the thorax These stages are intracellular similar to the Trichinella larvae in mammalian muscle that we discussed earlier

Onchocerciasis pathology The adult worms form nodules in the cutis which are enclosed by the host with a fibrotic granuloma (onchocercoma). Inflammatory reaction against macrofilaria is very mild. Onchocercomas are easily spotted especially when over bone or strong muscle

Onchocerciasis pathology Microfilaria migrate through the connective tissue especially the dermis of the skin and cause most of the pathology Living migrating microfilaria seem to cause little or no inflammation Dead microfilaria however stimulate potent inflammatory reactions (treatment can have therefore severe side effects, (mild with Ivermectin but can be pronounced with DEC)

Onchocerciasis pathology The inflammatory reaction causes progressive pathological changes of the skin These are in part due to the reaction to microfilaria and in part to secondary bacterial infection

Onchocerciasis pathology Inflammation in the skin causes an unbearable itch provoking scratching which is the main source of additional secondary infection of the skin Chronic scratching also mechanically stresses the skin

Clinical oncho. Inflammation and constant scratching often leads to depigmentation of skin (leopard skin) which is especially visible on dark skin, and progressive loss of elasticity resulting in skin hardening

onchocerciasis Late stages can present a hardened and cracked skin surface (lichenification) Hanging groin and elephantiasis of the genitals are additional severe manifestations

onchocerciasis Microfilaria also migrate through the eye Again inflammatory reactions around dead microfilaria seem to do the most damage Progressive chronic scaring of the cornea and to a lesser extend of the retina and optical nerve lead to vision impairment

onchocerciasis Chronic microfilaremia in the eye leads to sclerotizing ceratitis (a hardening inflammation of the clear front part of the eye) The cornea becomes opaque resulting in gradual loss of sight Nodules directly on the head seem to result in higher mf burden for the eyes and fast progression to blindness even in children

Are endosymbionts involved in filarial pathogenesis? Wolbachia bacteria are found as intracellular endosymbionts in the hypodermal lateral chord and the uterus of many parasitic nematodes (here Brugia malayi) The bacteria seem important for nematode development as antibiotic treatment results in sterility (and maybe even death) of the adults

Onchocerciasis diagnosis Diagnosis: skin snip, demonstration of microfilaria in the cutis. A small piece of skin is cut and placed into saline. Microfilaria emerging from the sample can be observed microscopically Antibody tests suitable for large scale epidemiology are also available now

Onchocerciasis treatment Nodulectomy: adult worms can be removed surgically to reduce microfilarial load to alleviate symptoms

Onchocerciasis treatment Diethylcarbamazine DEC (kills microfilaria and in some species macrofilaria slowly with unknown mechanism) Sudden death of many MF can lead to severe inflammatory reaction of skin and eye Ivermectin does not kill macrofiliaria but dramatically reduce MF number and has milder side effects than DEC Pretreatment with steroids can reduce side effects