eMedicine Specialties > Infectious Diseases > Parasitic Infections

Onchocerciasis

Mary Nettleman, MD, MS, Chair, Department of Medicine, Michigan State University
Apoorv Kalra, MD, Assistant Professor of Medicine, Michigan State University

Updated: Apr 16, 2009

Introduction

Background

Onchocerciasis is an infection caused by the nematode Onchocerca volvulus. Humans acquire onchocerciasis through the bite of Simulium blackflies.^1,2,3 Because the fly develops and breeds in flowing water, onchocerciasis is commonly found along rivers and is sometimes referred to as river blindness.

Simulium fly (black fly).

In the human host, the adult nematodes live in subcutaneous nodules and produce microfilariae, which are found throughout the body but preferentially reside in the skin and eye. Repeated exposures to infected flies increase the number of adult worms and microfilariae in the host. Chronic cutaneous onchocerciasis (onchodermatitis) causes pruritus, a papular rash, scarring, and lichenification. Over time, affected skin may begin to sag, leading to terms such as "hanging groin." Patchy depigmentation on the legs leads to a condition known as leopard skin. The term sowda is used to describe severe pruritus with darkening of the skin, often confined to one limb. Chronic ocular onchocerciasis may lead to sclerosing keratitis and iridocyclitis, and finally to blindness.

Onchocerciasis is endemic in Africa, Yemen, and in small foci in Central America and South America. The burden of the disease has been reduced by prevention efforts, including control of the fly vector and periodic ivermectin therapy in at-risk individuals. More recently, attention has been focused on Wolbachia organisms, which are endosymbiotic bacteria carried by adult worms and microfilariae. Treatment of Wolbachia infection has been shown to disrupt microfilariae production by the adult female nematode.

Pathophysiology

Simplified life cycle of Onchocerciasis volvulus.

Frequency

United States

Onchocerciasis is not acquired in the United States. Occasional cases are found in immigrants or travelers from endemic areas.^4,5 However, symptomatic onchocerciasis usually requires heavy infestations and repeated exposure to the vector fly. Short-term travelers are at little or no risk of the disease. Pruritus, dermatitis, and eosinophilia may occur in travelers who stay longer than 3 months in endemic areas of Africa. Symptoms may occur months to years after leaving the endemic area.

International

Currently, onchocerciasis is endemic to 30 African countries, Yemen, and in localized foci of 6 Central and South America countries. Globally, approximately 18-36 million individuals have onchocerciasis, 99% of whom reside in Africa. The World Health Organization (WHO) estimates that 750,000 people are blind or have reduced vision as a result of the disease.

Since 1975, the WHO, international foundations, nongovernmental organizations, and governments have worked cooperatively to reduce the burden of onchocerciasis.^{6,7,8,9,10,11,12,13,14} Initial efforts focused on insecticide sprays and habitat control to reduce the numbers of black fly vectors. With the introduction of effective treatment, the program became focused on periodic treatment of at-risk persons.

Since 1988, ivermectin has been provided free of charge by Merck through the Mectizan Donation Program. By 2002, most affected countries had introduced population-based programs to supply ivermectin at least annually to at-risk individuals. The drug temporarily reduces the microfilarial burden, resulting in reduced morbidity and a reduced number of flies becoming infected when they bite humans. Reports suggest that this has been highly effective in the Americas, where transmission has been interrupted entirely in several areas and ocular disease has been eliminated in 9 of the 13 foci. In Africa, morbidity and transmission have been reduced but not eliminated. This may be due, at least in part, to migration of infected people into new areas, as well as the challenges inherent in educating and motivating large numbers of people.

Despite the challenges they face, control programs have had a significant impact. In Africa alone, an estimated 600,000 cases of blindness had been prevented by 2002 and 18 million children were living in risk-free areas. In 2007, 69 million doses of ivermectin were supplied through the Mectizan Donation Program to reduce the burden of onchocerciasis.

Mortality/Morbidity

• Onchocerciasis is the second-leading infectious cause of blindness in the world.¹⁵
• Skin disease and subcutaneous nodules can be intensely pruritic.¹⁶
• Long-term onchodermatitis may cause scarring, depigmentation, loss of skin elasticity, and disfigurement.
• Although not directly fatal, blindness and skin disease caused by onchocerciasis affect the hosts’ ability to assimilate into their societies, perform daily tasks, and care for themselves.¹⁷
• Affected persons often have a low body mass.
• Blindness alone has been estimated to reduce life expectancy by 4-10 years.
• In the West African savanna, up to 10% of villagers may be blind from the disease.

Race

Onchocerciasis does not have a racial predilection. For an unclear reason, the symptoms caused by O volvulus infection appear to differ from region to region. For example, onchodermatitis is more common in forested areas, while blindness is more common in savanna areas. Some evidence has suggested that genetic variation in the host may explain part of this geographic specificity.¹⁸

Sex

Onchocerciasis does not have a sexual predilection.

Age

Onchocerciasis does not have an age predilection. Children born to mothers with onchocerciasis may be immunotolerant to O volvulus infection, potentially leading to a higher microfilarial burden. Transplacental transmission of microfilariae may occur.

Clinical

History

Symptoms of onchocerciasis reflect the developmental stage of the parasite and the degree of immune response by the host. Clinical manifestations are highly variable.

• Symptoms of onchocerciasis do not appear until after the L3 larvae mature into adult worms. On average, symptoms appear between 9 months and 2 years after the initial infecting bite. The interval between acquisition of the parasite and onset of symptoms is sometimes referred to as the prepatent phase.
• Once developed, adult worms cluster in subcutaneous nodules (onchocercomata).
• Generalized pruritus may occur early in the infection and may be severe. A papular rash known as onchodermatitis may be present. Initially, the rash may be transient, but chronic infection over several years may lead to lichenification, loss of skin elasticity, atrophy, and/or depigmentation.
• Itchy eyes, redness, or photophobia may be early symptoms of ocular onchocerciasis. Over years, the scarring progresses to cause visual loss and ultimately blindness. Acute optic neuritis is less common but may also cause blindness.
• Weight loss and generalized myalgias may occur.

Physical

• Skin examination in patients with onchocerciasis may reveal subcutaneous nodules, diffuse onchodermatitis, lymphedema, and/or atrophic changes.
  • Onchodermatitis consists of raised papules that are intensely pruritic. Vesicles and pustules may also be present. Scratching may cause secondary infection.
  • In its extreme form, skin atrophy may cause drooping of the inguinal skin, termed hanging groin.
  • In some cases, the skin is dry and resembles ichthyosis.
  • Sowda refers to severe pruritus and darkened skin, usually confined to one limb. It is most commonly described in Yemen but also occurs in Africa.
  • Leopard skin refers to bilateral, symmetric, patchy depigmentation of the shins.
  • Lymphadenopathy may occur.
  • Subcutaneous nodules are firm, nontender, and mobile and are several millimeters to centimeters in size. They develop most commonly over bony prominences on the trunk and hip (Africa) or head and shoulders (Americas).
• In the eye, the inflammatory response to dying microfilariae and Wolbachia antigens causes punctuate keratitis (snowflake opacities). Advanced cases may result in corneal fibrosis or opacification. Slit-lamp examination may reveal microfilariae in the cornea and anterior chamber. Other ocular manifestations include iridocyclitis, glaucoma, chorioiditis, and optic atrophy.¹⁹

Causes

• O volvulus is transmitted by the bite of infected Simulium flies. The fly bites during daylight hours. Simulium flies breed near fast-flowing rivers and streams.
• Ocular symptoms are caused by the inflammatory response invoked by the release of Wolbachia antigens when microfilariae die.

Differential Diagnoses

Other Problems to Be Considered

Atopic dermatitis
Contact dermatitis
Insect bites
Chronic eczema
Malnutrition
Streptocerciasis
Superficial mycoses
Glaucoma
Trachoma
Vitiligo

Workup

Laboratory Studies

• Pathological diagnosis
  • Traditionally, a diagnosis of onchocerciasis requires demonstration of microfilariae in a skin-snip biopsy sample (see Procedures). This technique yields high specificity (100%) in experienced hands but low sensitivity (20%-50%) in early stages of infection.
  • The diagnosis may also be made by direct examination of surgical specimens obtained by excision of nodules.
• Immunodiagnosis
  • Antibody detection does not distinguish between active and past infections. Various antibodies have been tested, as follows:
    • Ov16 card test: Antibodies against this antigen have been shown to yield high sensitivity (approximately 80%) and specificity (approximately 85%) and may yield positive results in early infections when skin-snip results are negative.^20,21 Capillary blood samples are collected by finger prick. The immunochromatographic card test is used to detect the presence of immunoglobulin G4 (IgG4) antibodies to recombinant Ov16 antigen.
    • Recombinant hybrid proteins (OvH2 and OvH3): This test is based on hybrid proteins of two separate Onchocerca proteins (Ov20 and Ov33). High sensitivity (>95%) and specificity (>95%) has been described in this enzyme-linked immunoassay (ELISA)–based antibody detection test.²²
    • An ELISA-based test using a cocktail of 3 antigens (Ov7, Ov11, Ov16) has also been used to detect antibodies. A comparison study showed that a mixture of these 3 proteins yielded a sensitivity of approximately 97% and a specificity 100%, superior to those of the recombinant Ov16 card test.²³
    • Testing for a low–molecular-weight antigen fraction of female O volvulus parasite yields sensitivity and specificity similar to those of skin-snip testing.²⁴
  • Antigen detection: Oncho-27 antigens have been studied in the diagnosis of Onchocerca infections. The advantage of this test is that it uses urine or tears for testing. In a study of 456 patients in a hyperendemic area of Cameroon, this technique yielded a sensitivity and specificity of 100%.²⁵
• Nucleic acid amplification tests: Polymerase chain reaction (PCR) using material from skin-snips or skin scratches provides high sensitivity and specificity, superior to older methods.^26,3 However, the limited availability of technical expertise, as well as the high cost of the test, restricts its use in resource-limited settings.

Imaging Studies

• Ultrasonography may reveal nonpalpable nodules, although this is not useful as a screening test. Ultrasonography of an adult worm in a nodule reveals a homogeneous echogenic area containing echodense particles with a lateral acoustic shadow.

Other Tests

• Diethylcarbamazine (DEC) patch test: Based on the principle of Mazzotti reaction, topical application of DEC in a cream base (DEC patch) elicits localized cutaneous reactions (pruritus, maculopapular eruptions, dermal edema) in response to dying microfilariae.²⁷ Earlier studies reported varying degree of sensitivity (30%-92%) in patients with positive skin-snip results. Severe cutaneous reactions may require steroid therapy or hospitalization. Higher concentrations of DEC and longer patch times increase the sensitivity.²⁸ However, false-positive reactions may occur in patients with other filarial diseases such as Loa loa infection.

Procedures

• Skin snip
  • In this technique, a razor blade is used to remove tiny skin samples (3-5 mg) from multiple sites (iliac crests, shoulder blades); they are then placed in saline to observe microfilariae emerging from the skin samples. Alternatively, sclerocorneal punch samples can be used to obtain skin-tissue specimens.
  • The sensitivity is low in the prepatent disease stage, areas of low prevalence, and areas of mass ivermectin use.
  • Skin-snip biopsy specimens can also be used to detect microfilariae using nucleic acid amplification.
• Nodule resection (nodulectomy, onchocercomectomy): Although this is the most invasive method, surgical removal of nodules has both diagnostic (if adult worm is observed) and therapeutic potential (elimination of the adult worms in that nodule).

Histologic Findings

Microscopic examination of excised onchocercomata reveals cross-sections of adult worms with eosinophils and lymphocytes at the periphery of the nodule.

Treatment

Medical Care

Because most of the pathogenesis of onchocerciasis is secondary to microfilariae, the goal of therapy is to eliminate the microfilarial stage of disease to improve symptoms, to prevent progression of eye lesions, and to interrupt disease transmission.

• Ivermectin is considered to be the drug of choice as a microfilaricidal agent.^29,30
  • Repeated dosing at intervals of 3–12 months is recommended for at least 10-12 years.
  • More frequent dosing is reserved for patients who experience frequent symptomatic recurrences.
  • Ivermectin is usually well-tolerated. Dying microfilaria may result in pruritus and adenopathy (Mazzotti reaction), leading to angioedema in rare cases. Ocular inflammation may also be triggered by dying microfilariae. To minimize this in individuals with microfilariae observed during slit-lamp examination, some experts recommend using a short course of prednisone (2-3 d) along with ivermectin. More frequent dosing with ivermectin (every 3 mo instead of every 12 mo) may reduce inflammatory complications because it does not permit microfilarial numbers to build, thus reducing the number of dead organisms after treatment.
  • Concomitant infection with L loa should be ruled out, as ivermectin may precipitate toxic encephalopathy in these patients.
  • Ivermectin has little effect on adult worms. It reduces the burden of microfilaria and the risk of complications but does not cure the disease.
• Targeting endosymbiotic Wolbachia species has emerged as an exciting new approach in the control of onchocerciasis. Studies of doxycycline therapy (100–200 mg/d for 6 wk) have shown great promise.^31,32,33 Doxycycline interrupts microfilarial embryogenesis, dramatically decreasing or eliminating microfilaria for at least 18 months after treatment. The drug has modest activity against adult worms, reducing numbers by approximately 50%-60%. Investigators have also studied rifampin and azithromycin, but early results appear to be inferior to those of doxycycline.^34,35

Surgical Care

Nodulectomy can result in cure only if excision eliminates all adult worms. Thus, this is not a practical choice in patients with multiple nodules or in patients in whom nodules are not clinically evident.

Consultations

• Infectious disease specialist
• Ophthalmologist
• Dermatologist

Medication

Treatment involves microfilaricidal or macrofilaricidal agents. No known nontoxic macrofilaricidal agent is available to kill adult worms.

Antiparasitics

These agents inhibit growth and proliferation of parasites.

Ivermectin (Mectizan, Stromectol)

Drug of choice for onchocerciasis. Derived from the soil actinomycete Streptomyces avermitilis. Metabolized in liver and excreted in feces over 12 d. Plasma half-life is 18 h. Its activity is the result of increased nerve and muscle cell permeability to chloride channels, leading to hyperpolarization and paralysis due to the drug's high affinity binding to glutamate-gated and gamma aminobutyric acid–gated chloride ion channels.

Dosing

Adult

150 mcg/kg PO as single dose every 3-12 mo

Pediatric

<5 years: Not established
>5 years: Administer as in adults

Interactions

Elevated INR with warfarin coadministration reported

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Some patients with hyperactive onchodermatitis may worsen after starting ivermectin, developing edema, pruritus, arthralgias, and postural hypotension; toxic encephalopathy in patients coinfected with L loa (rare); teratogenic in mice, rats, and rabbits; excreted in low levels in human milk (not recommended in breastfeeding mothers)

Diethylcarbamazine (Hetrazan)

Diethylcarbamazine (DEC) is never used in the treatment of onchocerciasis. DEC is rarely used for diagnostic purposes, when low test doses are given and patients are observed for the Mazzotti reaction, which, in mild cases, results in pruritus, dermal edema, maculopapular eruptions, lymphadenopathy, and fever and, in severe cases, results in meningismus, severe prostration, and/or death. The mechanism of action of DEC is secondary to direct effect on microfilariae by causing organelle damage and apoptosis.

Dosing

Adult

6 mg PO once (Mazzotti test)

Pediatric

Not established

Interactions

None reported

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

In heavily infected patients with onchocerciasis, severe reactions may occur following a single dose of diethylcarbamazine

Antibiotics

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.

Doxycycline (Bio-Tab, Doryx, Doxy, Periostat, Vibramycin, Vibra-Tabs)

May be used to reduce or eliminate the endosymbiotic bacteria Wolbachia. This disrupts production of microfilariae by the adult female worm.

Dosing

Adult

Several regimens under study; 100-200 mg/d for 6 wk suggested

Pediatric

Not established

Interactions

Bioavailability decreases with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate; tetracyclines can increase hypoprothrombinemic effects of anticoagulants; tetracyclines can decrease effects of oral contraceptives, causing breakthrough bleeding and increased risk of pregnancy

Contraindications

Documented hypersensitivity; severe hepatic dysfunction

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Photosensitivity may occur with prolonged exposure to sunlight or tanning equipment; reduce dose in renal impairment; consider drug serum level determinations in prolonged therapy; tetracycline use during tooth development (last one-half of pregnancy through age 8 y) can cause permanent discoloration of teeth; Fanconi-like syndrome may occur with outdated tetracyclines

Follow-up

Inpatient & Outpatient Medications

Patients with onchocerciasis should receive ivermectin 150 mcg/kg every 3-6 months.

Deterrence/Prevention

• Travelers to endemic area can avoid onchocerciasis by avoiding vector contact with protective clothing and repellants.
• Population-based prevention strategies in some of the endemic areas of Africa and South America are based on elimination of blackfly vector and regular (every 6-12 mo) mass ivermectin treatment of affected individuals.

Complications

• Ocular complications of onchocerciasis include blindness secondary to keratitis, pannus formation, and corneal fibrosis. Posterior segment complications include chorioretinitis, intraretinal deposits, open-angle glaucoma, and optic atrophy.
• Cutaneous complications of onchocerciasis include skin atrophy, depigmentation, and sowda (chronic popular dermatitis limited to one limb). A loss of skin elasticity (hanging groin) may also occur.
• Hematologic and immunologic complications of onchocerciasis include chronic lymphadenopathy.

Prognosis

• Some eye manifestations and dermatitis resolve in patients undergoing ivermectin treatment every 6-12 months for the lifetime of the adult worm (approximately 12 y).
• Blindness, skin atrophy, and depigmentation do not improve with treatment. The life expectancy in blind persons is decreased secondary to difficulty coping with activities of daily living.

Patient Education

• Travelers to areas where onchocerciasis is endemic should be counseled to use protective clothing and insect repellants.
• Patients, particularly those with high microfilarial load and ocular involvement, should be cautioned on the potential complications of ivermectin therapy that may result from dying microfilaria.

Multimedia

Media file 1: Simulium fly (black fly).

Media file 2: Histopathology of an Onchocerca volvulus nodule. Image courtesy of the CDC and Dr. Mae Melvin.

Media file 3: Simplified life cycle of Onchocerciasis volvulus.

References

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Keywords

onchocerciasis, onchocercosis, river blindness, volvulosis, craw-craw, Robles disease, Onchocerca volvulus, O volvulus, Simulium fly, blinding disease, papular dermatitis, leopard skin, sowda, sowdah, Nakalaga syndrome, ocular onchocerciasis, ocular onchocercosis, onchodermatitis, onchocercomata

Contributor Information and Disclosures

Author

Mary Nettleman, MD, MS, Chair, Department of Medicine, Michigan State University
Mary Nettleman, MD, MS is a member of the following medical societies: American College of Physicians, Association of Professors of Medicine, Central Society for Clinical Research, Infectious Diseases Society of America, and Society of General Internal Medicine
Disclosure: Nothing to disclose.

Coauthor(s)

Apoorv Kalra, MD, Assistant Professor of Medicine, Michigan State University
Disclosure: Nothing to disclose.

Medical Editor

Daniel R Lucey, MD, MPH, Chief, Fellowship Program Director, Department of Internal Medicine, Division of Infectious Diseases, Washington Hospital Center; Professor, Department of Internal Medicine, Uniformed Services University of the Health Sciences
Daniel R Lucey, MD, MPH is a member of the following medical societies: Alpha Omega Alpha and American College of Physicians
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

John W King, MD, Professor of Medicine, Section of Infectious Diseases, Louisiana State University Health Sciences Center; Director, Viral Therapeutics Clinics for Hepatitis; Consulting Staff, Department of Infectious Diseases, Overton Brook Veterans Affairs Medical Center
John W King, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Federation for Medical Research, American Society for Microbiology, Association of Subspecialty Professors, Infectious Diseases Society of America, and Sigma Xi
Disclosure: emedicine $50.00 author of chapter

CME Editor

Eleftherios Mylonakis, MD, Clinical and Research Fellow, Department of Internal Medicine, Division of Infectious Diseases, Massachusetts General Hospital
Eleftherios Mylonakis, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Society for Microbiology, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Chief Editor

Burke A Cunha, MD, Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital
Burke A Cunha, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

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