ONCHOCERCIASIS

Synonyms - River blindness - Erysipelas de la costa - Craw-craw - Sowda

Introduction

•Chronic parasitic multi systemic disease caused by the filarial nematode O.volvulus

•characteristically includes dermatologic, lymphatic, ophthalmologic, and systemic manifestations

•Humans acquire- through the bite of black fly (genus Simulium)-fast flowing river.

•Man is the only definitive host of this parasite.

•second-leading infectious cause of blindness in the world.

•leading cause of blindness in the developing world.

Epidemiology

• Endemic -30 African countries(equatorial region) -endemic foci -Yemen (Middle East) - 6 Central and South America countries ( Brazil, Venezuela, Colombia, Ecuador, Guatemala& Mexico) • Globally, approximately 18-36 million individuals have onchocerciasis

• 80- 90 % of whom reside – Africa

•. Nigeria, Ethiopia, Cameroon, Uganda, and the Democratic Republic of the Congo have the largest number of infected people.

•. One half of the cases in the world are located in Nigeria..

Epidemiology(cont’d)

•Ocular onchocerciasis has been found in more than 1 million individual

• more likely lead to blindness in Africa(particularly west) than in Latin America.

• Variation-blindness rate in different geographical areas b/c distinct strains or biological variants.

Epidemiology(cont’d)

Epidemiology(cont’d)

•Race – no racial predilection

• Sex -M >F. - More pronounced high transmission area (savana) -partially attributed to increased occupational exposures in men

•Age -lowest in individuals aged 0-10 years -sharply increases, with a peak in individuals aged 20-30 years

Epidemiology(In Ethiopia)

•scarcity of comprehensive data on onchocerciasis in Ethiopia.

•first reported in southwestern Ethiopia in 1939 by Italian investigators

•endemic areas extend from the NW, West & SW part of the country

•highest prevalence (85.3%) - Teppi, SW Ethiopia and the lowest (6.9%) from the Kuwara province of NW Ethiopia.

• mainly dermal-the disabling itching ,thickening of the skin & -hanging groin etc -Blindness, a common m/f of this ds in West Africa, is a rare in Ethiopia

Vector and transmission of the disease

•Black flies (female) of the genus Simulium are the only vectors of O volvulus.•fly bites during daylight hours.

Vector and trans (cont’d)

•eggs require fast-running rivers for breeding grounds.

•Well-oxygenated water plays a significant role in this ds. B/c larvae of O. volvulus have an obligatory aquatic stage during which they require a high oxygen tension.

•adults emerge after 8-12 days following egg production•ability to travel hundreds of kilometers in flight on wind currents.

•Their life span is about 4 weeks.

Etiology

•Onchocerca volvulus, is a nematode that belongs to the family Filariidae

•O volvulus - only Onchocerca with a human host

• Black fly takes a blood meal from an infected human-also ingest onchocercal Mf

•Mf invade the midgut, and advance to the thoracic muscles

• differentiation of these mf into L1 larva begins in muscle within 28 hours after the blood meal

•first molt produces L2 larva within 96 hours•followed by the second molt, which produces L3 larva by day 7.

•Infective L3 larva migrates to the proboscis, for future deposition into human skin during the next blood meal.

Etiology (cont’d)

•Fly bite another person- Infective L3 larvae are transmitted to human skin

•larvae move under the skin and form nodules where they develop into adult worms in 12 to 18 months.

•male: 2-3 cm long •female: 60 cm-longer than any other insect-borne filarial.

•Adult worms have a longevity of 10-15 years

Etiology(cont’d)

•adult worms pair and mate in the human host.

•female Onchocerca gives birth daily to thousands of microscopic larvae (microfilaria)

•The maximal production of offspring occurs during the first 5 years of the worm's reproductive life

•Mf released from the nodules -easily traverse the skin and connective tissue

•subepidermal lymphatics and the anterior chamber of the eye are the most common migration sites

•Mf can also be found in the blood, cerebrospinal fluid, urine, and internal organs.

Pathogenesis

•Adult worms isolated in nodules are not directly harmful to the patient

•Their progeny(Mf) are responsible for most of the damage related to onchocerciasis

•Most microfilariae die as immature worms in the host.

•Inflammatory r/s to dead or dying mf are almost entirely responsible for the clinical manifestation of ds

•severely infected person, 100,000 or more microfilariae die each day.

•Circulating immune complexes have been identified and implicated in the inflammatory response to infection

•Immunoglobulin E (IgE) levels are also very high

Pathogenesis(cont’d)

•A symbiotic relationship has been demonstrated b/n Wolbachia bacteria&o.volvulus.

•Wolbachia species are essential for nematode fertility.

•Embryogenesis in the female worm is disrupted when Wolbachia numbers are depleted.

•murine experiments suggest that corneal inflammation secondary to onchocerciasis may be caused by endotoxins produced by Wolbachia.

•clearance of Wolbachia with antibiotic therapy affects transmission and can reduce and prevent onchocerciasis-related blindness

Clinical feature

•Patients are asymptomatic in about 10% of cases.

•The skin and the eye are the two most commonly involved organ systems

•skin lesions are characterized by pruritus, dermatitis,and onchocercoma.

•Dermatitis is variable in its appearance and probably relates to chronicity of infection,age of the patients, geographic and climatic region in which it was acquired.

Clinical feature(cont’d)

•Six different patterns of skin changes have been described Acute papular onchodermatitis (APOD) Chronic papular onchodermatitis (CPOD) Lichenified onchodermatitis (LOD) Atrophy (ATR) Depigmentation Onchocercomas (palpable onchocercal nodules)

•More than one pattern of skin involvement may be present simultaneously

•one pattern of skin involvement may evolve into another pattern

•Pruritus is often the first symptom of infection

Acute papular onchodermatitis (APOD)

•children and in the earliest cases of endemic areas•small pruritic papules, vesicles and pustule•diameter of the papules is at least 1 mm.•most often involves the face, extremities,and trunk•sometimes with associated erythema and edema•skin has an infiltrated appearance, with obliteration of surface markings.

Clinical feature(cont’d)

Acute phase(cont’d)

•In Central America, another manifestation of the acute phase - acute swelling of the face with erythema and itching erisipela de la costa.

•In Zaire and Central America, an acute urticarial eruption is seen.

•Patients may continue to present with acute phase pattern over months and years in the early phases of the disease.

Chronic papular onchodermatitis (CPOD)

• scattered, pruritic, hyperpigmented, and flat-topped papulomacular rash•The diameter of the papules is at least 3 mm, with or without excoriations. •buttocks, shoulders, and waist-mostly affected•may coexist with the acute papular eruption

Lichenified onchodermatitis (LOD)

•lichenified itchy rash confined to one limb - commonly the leg. s/s >1• composed of itchy papules and nodules, which become confluent•chxlly hyperpigmented, and it is known in Arabic-speaking areas as Sowda•regional lymph nodes are soft, nontender, and enlarged-impt feature•Skin-snips do not usually contain microfilariae. •associated with an active delayed hypersensitivity response.•mainly seen in teenagers and young adults.•first described in Yemen -also found in Ethiopia, Sudan

Atrophy (ATR)

•probably a consequence of longstanding onchocerciasis.

•develop after any of the patterns or arise from apparently normal but infected skin site

•commonest sites to detect early atrophic changes are over the buttocks,shoulders or lower limbs.

•dry and shiny, with fine wrinkles resembling tissue paper

•extreme form of this secondary ichthyosis is known as lizard skin

Clinical feature(cont’d)

apron-like fold of skin in the inguinal region containing lymph nodes

Hanging groin

Depigmentation

• common feature of late-stage onchodermatitis

• commonly seen bilaterally over the pretibial region•may affect inguinal regions, bony prominences and the shoulders

•Initially seen as discrete depigmented macules, with sparing of the hair follicles- leopard skin

•large coalescent sheets of depigmentation are present in -late stage disease

•Leopard skin is a characteristic finding in older patients. •Indicator of the prevalence of onchocerciasis in the population.

Clinical feature(cont’d)

Onchocercoma

• fibrous, subcutaneous nodules containing adult worms

• many patients with chronic onchocerciasis

•Asymptomatic-generally located over bony prominences

•No of nodules is not correlated with the microfilarial load or the severity of ds.

•In Africa, often observed along the iliac crests, ribs, ischial tuberosities.& Juxta-articular areas.

•In American forms, nodules are fewer and have a greater tendency to be located on the scalp.

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Onchocercoma (cont’d)

•In pts scalp nodules, the risk of ocular complications is generally higher than that of patients without scalp nodule.

•Identifying every nodule is important for proper management.

Diagnosis

•skin snip - identification of microfilariae •buttocks and legs are often most heavily infected, & are most likely to yield mf•heavily infected individuals, mf can even be found in the blood, sputum and urine.

•skin snips are negative, the 'Mazzotti test' may be helpful in supporting dx.•50 mg of DEC - a mild and transient pruritic rash develops within 15 minutes -reaction may be related to Wolbachia organisms within the worms.•Excision nodule- adult worm

Diagnosis(cont’d)

•Peripheral eosinophilia and elevated IgE levels are common findings.

•Antibody testing lacks specificity

•Filarial immunofluorescence test or enzyme-linked immunosorbent assay (ELISA) ispositive in 60-90% of cases.

Diagnosis(cont’d)

Histology•mixed inflammatory infiltrate with a large number of eosinophils

•Microfilariae are present within slits between collagen bundles in the upper dermis

•epidermis may show hyperplasia- as a consequence of rubbing

•Older lesions, areas of fibrosis and calcification may predominate.

DDx

depends on the skin findings at the time of presentation

•Scabies- Pruritus •APOD - CPOD-chronic eczema -Insect bites -Atopic dermatitis -eczema•Atrophy-aging Onchocercal depigmentation -post Inf hypo/depigmentation•Onchocercal nodules - epidermal inclusion cysts -leprosy -leishmaniasis

Treatment

•Ivermectin -(single dose, 150 microglkg)-drug of choise

• Kills microfilaria rapidly

• Reduces production of mf from adult worm- for several month

• After Rx mf usually disappear from the skin within1 wk & from eye within 3 month

•Skin - mf counts remain very low for 6 months•Rise slowly but do not reach pretreatment levels within 1 year.

•Repeated every 6 -12 months to suppress the dermal and ocular mf counts.

Treatment(cont’d)

DEC - alternative drug regimen, now rarely used•cause severe exacerbation of skin and eye disease, even blindness 1. first 3 days 1 mg/kg body weight once; 2. second 4 days 2 mg/kg body weight once; 3. second week 4 mg/kg body weight three times a day; 4. third week 4 mg/kg body weight three times a day.

•Prednisone should be given at 40 mg/d starting the day before DEC for heavily infected patients, or in those with severe dermatitis or with eye involvement.

•Ocular reactions - corticosteroid eye drops and mydriatics.

•Suramin-kills adult worms -severe adverse reactions and is now seldom used

Prevention

Primary means of preventing onchocerciasis

1.Vector control -applications of environmentally-safe insecticides to the black fly's breeding areas (fast-flowing rivers) during the rainy season.

2.mass treatment with Ivermectin

Ocular manifestations

•Late & serious reactions that occur in about 5-10% pts.

•live mf cause minimum reaction

•Inflammatory response to dying mf and Wolbachia antigens are a;d with severe inflammatory response.

•Infection of the cornea produces punctate keratitis -eventually clears when the inflammation settles.

•Severe & prolonged infection- sclerosing keratitis, iridocyclitis,uveitis retinal pigmentation, optic atrophy,scarring and blindness

•By slit lamp biomicroscopy •mf -within the cornea, migrating freely in the anterior chamber and vitreous humor

Treatment(cont’d)

•Single annual or semi annual dose ivermectin has no effect on adult female worm w/c can survive14 years or longer.

•Optimal benefit- throughout the life span of parasite or be combined doxycycline or -increase the frequency of ivermectin dosing to every 3 months

•Doxycycline (6 weeks) kills the endosymbiotic Wolbachia in adult worms and interrupts production of mf for 18 months or longer.

Nodulectomy

•popular method of treatment where nodules on the head are common

•removal reduces the chance of ocular disease