eMedicine Specialties > Ophthalmology > Infectious Disease

Onchocerciasis

Author: Deborah R Eezzuduemhoi, MD, Assistant Professor, Department of Ophthalmology and Visual Sciences, Texas Tech University, Health Sciences Center School of Medicine
Coauthor(s): Deborah Wilson, MD, Director of Glaucoma Service, Assistant Professor, Department of Ophthalmology, Georgetown University Medical Center
Contributor Information and Disclosures

Updated: Jul 22, 2008

Introduction

Background

Onchocerciasis is an insidious nonfatal filarial disease that has caused blindness, lifelong human suffering, and grave socioeconomic problems. Onchocerciasis is a cause of clinical and epidemiological burden of skin disease in Africa. An estimated 18-40 million people are afflicted worldwide. Approximately 2 million people are blind because of this disease. About 85.5 million people in 35 countries live in endemic areas. In 1875, O'Neill first reported the presence of filaria in "craw-craw" as onchocerciasis is called in West Africa. In 1919, Robles described in the French literature an anterior uveitis and keratitis associated with acute and chronic skin changes.

Advances in prevention and treatment have decreased the prevalence of this disease in localized areas of Africa and Latin America. Most cases are found in Africa, south of the Sahara, in a wide zone that lies along the fifteenth parallel from Senegal to Ethiopia. The endemic area extends from south of the equator to Angola in the west and Tanzania in the east. Localized foci exist in Sudan and Yemen. The geographic distribution of onchocerciasis in Latin America is sporadic, with important foci in Guatemala, Ecuador, Venezuela, Mexico, Colombia, and the state of Amazonas in northern Brazil.

The parasite, Onchocerca volvulus, is a nematode that belongs to the family Filariidae. O volvulus is the only Onchocerca with a human host, although an infected spider monkey and a gorilla have been recorded. Blackflies of the genus Simulium are the only vectors of O volvulus. They are tiny ferocious biters. At least 15 different species of blackfly simuliids can transmit onchocerciasis; they vary by terrain and continent (eg, Simulium damnosum in Africa). Their eggs require fast-running rivers for breeding grounds. As a result, the numbers of flies produced fluctuate with the season. The adults emerge after 8-12 days following egg production with the ability to travel hundreds of kilometers in flight on wind currents. Their life span is about 4 weeks.

Pathophysiology

Onchocercal larvae, in the skin of infected individuals, are ingested with a blood meal. They mature to the infective stage within the fly between 6-10 days and are transmitted by the female blackflies. Development to the adult stage occurs in humans. The adult worms pair and mate in the human host, and, unlike most nematodes that produce eggs, the female Onchocerca gives birth daily to thousands of microscopic larvae known as microfilariae. These larvae mature to adult worms in about 1 year. The life span of microfilariae is 6-30 months. Those adult worms that complete their life circle may survive a decade during which time they release millions of microfilariae.

The classic lesion of onchocerciasis is the onchocercoma, a firm, painless nodule in the subcutaneous tissue. Onchocercomata are formed predominantly on the head, face, and torso, but they may be found on the pelvic girdle and lower extremities deep-seated against the bones or near the joints. The nodule usually is composed of 2-3 females and daughter microfilariae encapsulated in a fibrous coat. Dead worms may calcify within the nodules. The ocular tissues are involved via migration of the microfilariae from the neighboring tissues, through the bloodstream, or along the nerves. Intraocular organisms are evident early in the disease by direct invasion from the conjunctiva, through the sclera, or through the cornea.

Most microfilariae die as immature worms in the host. Their death causes an intense inflammatory reaction that is responsible for most of the morbidity of onchocerciasis. Antigens of the infective larvae seem to induce cell-mediated and humoral responses. Circulating immune complexes have been identified and implicated in the inflammatory response to infection. Perivascular deposits of immune complexes have been shown in various tissues. Immunoglobulin E (IgE) levels are also very high, thus implicating all of the known mechanisms of pathologic immune destruction. The lymph nodes that drain infected areas show granulomatous inflammation, fibrosis, and atrophy on histologic examination.

Frequency

United States

No current report exists of onchocerciasis due to O volvulus in the United States.

International

Onchocerciasis was considered to be one of the world's most formidable public health problems. Approximately 85.5 million people live in endemic areas. One half of the cases in the world are located in Nigeria. Ocular onchocerciasis has been found in more than 1 million individuals. Variation exists in the blindness rate in different geographical areas, possibly because of distinct strains or biological variants.

Onchocerciasis is more likely to lead to blindness in Africa than in Latin America, and it is 7 times less frequently blinding in the forested areas than in the Savannah (nonforested) areas. More than 90% of certain village populations are infected with this disease, and about 35-50% have ocular onchocerciasis.

Mortality/Morbidity

Race

• No well-described racial differences in the incidence of onchocerciasis or susceptibility to the disease exist.
• Socioeconomic differences have been clearly identified as a contributing factor.

Sex

• Although no reported differences of exposure exist between men and women, men may be afflicted more often than women because of farm and field occupations.

Age

• As many as 50% of people older than 40 years may be blind in endemic areas.

Clinical

History

• A detailed history and complete ophthalmologic examination should be performed whenever possible.

Physical

• Skin manifestations
  • The earliest skin involvement is mild pruritus and may be followed by papular rash, erosions, and lichenification. In highly endemic communities, the prevalence of itching increased until age 20 years and then plateaued.
  • The classic dermal lesion is referred to as leopard skin, which represents islands of hyperpigmented skin around hair follicles with surrounding depigmentation, most commonly located on the shins. These cutaneous manifestations affect mobility and social acceptability.
• Ocular manifestations
  • By slit lamp biomicroscopy, microfilariae can be seen within the cornea, migrating freely in the anterior chamber and vitreous humor. Although live microfilariae cause minimum reaction, dead microfilariae are associated with a severe inflammatory response.
  • Onchocerciasis-related blindness results from decades of infection and reinfection. Keratitis is one of the most devastating consequences of onchocerciasis. Various epidemiologic studies have found visible corneal or anterior chamber microfilariae (5-45%), punctate keratitis (35%), and sclerosing keratitis (10-15%).
  • Larval death induces an inflammation that results in corneal opacification and neovascularization.
    • Dead worms are surrounded by inflammatory infiltrates in the superficial stroma. Lymphocytes and eosinophils migrate to the peripheral cornea where the infection is more dense. A sclerosing keratitis follows, which may involve the visual axis over time. Corneal neovascularization and opacification with interstitial keratitis lead to corneal blindness.
    • The development of keratitis is dependent upon the previous immunization and the presence of sensitized T lymphocytes. It is associated with a predominance of T-helper type 2 (Th2) response.
    • Eosinophils are the predominant inflammatory cells in the cornea after injection of the parasite antigen. The severity of keratitis seems to be associated with the number of eosinophils in the cornea.
    • Neutrophils are prominent early in the inflammatory response and mediate keratitis in the absence of eosinophils.
  • Anterior uveitis: Early in the disease, nongranulomatous or granulomatous inflammation may result from invasion of the iris and ciliary body by the microfilariae. The frequency of iritis is about 10-20%. Posterior synechiae may distort the pupil inferiorly giving a classical pear-shaped iris. Seclusio pupillae and iris bombe with secondary angle-closure glaucoma may occur. The common sequelae include occlusio and seclusio pupillae, iris atrophy, iris bombe, inflammatory glaucoma, and cataract.
  • Chorioretinitis is seen in 10-25% of patients with ocular involvement.
  • The choroid is characterized by progressive inflammation associated with loss of pigment, pallor of the vessels from orange to yellow or white, and loss of choriocapillaris.
  • The retinal pigment epithelium is affected in the early stage of infection. Areas of hypopigmentation and hyperpigmentation, mottling, and confluent atrophy characterize it. Dark brown clumps of pigment are seen in a diffusely pale retinal pigment epithelium. Photoreceptors initially are lost, followed by loss of the inner retinal layers.
• In the early stage, chorioretinitis may mimic any other diffuse chorioretinal process, such as histoplasmosis, toxoplasmosis, or retinitis pigmentosa.
• Commonly involving the temporal retina, onchocerciasis tends to spare the macula; as a result, central visual acuity is maintained until late in the disease.
• The pathogenesis of onchocercal chorioretinopathy is not well understood. The following mechanisms have been hypothesized to cause the characteristic chorioretinopathy:
  • Inflammatory reaction to dead microfilariae
  • Deposits of immune complexes
  • Autoimmunity
  • Secretory-excretory products of microfilariae
  • Eosinophil-derived toxic effector molecules
  • Autoimmunity is supported as a mechanism for several reasons. First, the burden of microfilariae is not associated directly with the degree of chorioretinopathy. Second, the chorioretinopathy continues to progress even after effective treatment with reduction of microfilariae and vector control. Finally, retinal disease can persist throughout life unless controlled with anti-inflammatory agents.
  • Evidence favoring the autoreactivity theory for the development of onchocercal chorioretinopathy is derived from the detection of retina-specific autoantibodies in the human-infected sera.
    • Onchocercal human uveitis is associated with uveitopathogenic peptides, retinal S-antigen, and interphotoreceptor retinoid binding protein (IRBP). This evidence led Vingtain to demonstrate the presence of higher levels of S-antigen antibodies in patients with onchocerciasis who also had involvement of the posterior segment. However, these findings were not replicated.
    • Autoantibodies may have resulted from activation of T and B cells seen in parasitic infections. About 30% of B cells produce antibodies that are able to bind to autoantigens.
    • Hypergammaglobulinemia is a feature of O volvulus infection. Strong evidence exists that the chorioretinopathy is an inflammatory reaction to dead microfilariae because treatment with microfilaricidal induces characteristic retinal pathology. Similar progressive pathology also is seen after antimicrobial therapy of Toxocara uveitis in children.
    • Microfilariae load is associated with the presence of new chorioretinal lesions. Even though the incidence of new lesions is reduced after antimicrobial chemotherapy, extension and progression of existing disease is common.
    • This observation suggests that although chorioretinopathy is likely to be initiated by the presence of microfilariae, persistence is a self-perpetuating autoimmune process that does not require the presence of microfilariae.
  • Optic atrophy is seen in 10-25% of patients with ocular manifestation.
    • Loss of the ganglion cell axons leads to optic nerve head damage.
    • The optic nerve also may be involved by the infectious process or by treatment-induced inflammatory optic neuritis.
    • A heavy load of microfilariae may cause optic neuropathy.

Causes

Causes are discussed in Physical .

• Search for CME/CE on This Topic »

• Onchocerciasis (Infectious Diseases)
• Onchocerciasis (River Blindness) (Dermatology)
• Nematode Infections (Infectious Diseases)
• Orbit, Infection (Radiology)

• Drug Shows Promise Against River Blindness

• Prospects for the Control of Neglected Tropical Diseases by Mass Drug Administration
• Water Safety: Reducing the Infectious Disease Burden Due to Unsafe Water, Sanitation, and Hygiene
• Impact of Anthropogenic Environmental Alterations on Vector-Borne Diseases