USAID's NTD Program

Onchocerciasis or River Blindness

• Overview
• Epidemiology
• Distribution of Onchocerciasis
• Life Cycle
• Symptoms
• Diagnosis
• Treatment
• Control and Elimination Programs

Overview

	In Nigeria, Margaret Christoba is led through her village by her great granddaughter. Margaret went blind after contracting onchocerciasis early in life. CREDIT: KATE HOLT/SIGHTSAVERS

Onchocerciasis is an eye and skin infection caused by the parasitic worm Onchocerca volvulus, which is transmitted by the bite of an infected blackfly (genus Simulium). Because the insect that spreads the disease breeds and lives near fast-flowing rivers and streams, onchocerciasis is also known as river blindness. Severely infected people usually develop severe itching and skin and/or eye lesions. While the disease is not a direct cause of mortality, the socioeconomic consequences of onchocerciasis are profound and extend beyond the individual, affecting families, communities, and countries as a whole. According to the World Health Organization (WHO), onchocerciasis is the second leading infectious cause of blindness, after trachoma.

Epidemiology

More than 99 percent of all cases of onchocerciasis and onchocerciasis-related blindness are found in the WHO African Region. Isolated areas of the disease also exist in Yemen and in six countries in Central and South America. In areas where the African Programme for Onchocerciasis Control (APOC) has been present since 1995, WHO estimated that in 2008 about 26 million people were infected with onchocerciasis, of whom 265,000 were blind and 746,000 were visually impaired. People who live in rural areas near fast-flowing rivers and streams where there are Simulium blackflies are most at risk of acquiring onchocerciasis.

Distribution of Onchocerciasis

Life Cycle

During a blood meal, an infected blackfly introduces third-stage filarial larvae onto the skin of the human host, where they penetrate into the wound and subcutaneous tissues (1). They develop into (2) adult worms called filariae. Filariae commonly reside in nodules in subcutaneous connective tissues (3), where they can live for approximately 15 years. In nodules that contain numerous male and female worms, the female worms are capable of producing larvae, called microfilariae, for approximately nine years, producing an average of 1,600 microfilariae per day. The microfilariae have a life span that may reach two years. They are occasionally found in blood, urine, and sputum but are typically found in the skin and in connective tissues (4). To repeat the transmission cycle, a blackfly ingests the microfilariae during a blood meal (5). After ingestion, the microfilariae migrate from the blackfly’s midgut to the thoracic muscles (6), where the microfilariae develop into (7) third-stage infective larvae (8). The third-stage infective larvae migrate to the blackfly’s proboscis (9) and can infect another human when the fly takes a blood meal (1).

While most nodules have three to five worms, up to 50 worms can live in one nodule, where they can live for up to 15 years. Females in subcutaneous nodules (3-4) can reproduce for about nine years, producing an average of 1,600 microfilariae per day. Microfilariae, which have an average life span of 13 months but may live for up to two years, leave the nodules and migrate throughout the body; most eventually die. Depending on their location, dying and dead microfilariae produce symptoms typical of the disease: itching and lesions of the skin and the eye.

Symptoms

	Symptoms of onchocerciasis are caused by dead and dying microfilariae, which can cause skin reactions that range from mild to intense itching and can eventually lead to severe dermatitis. CREDIT: APOC

Humans become infected when blackflies deposit Onchocerca infective larvae into the skin when biting to extract blood. Once inside the human body, the larvae mature into adults in around 3 months to 1 year. Adult worms live in nodules, usually in subcutaneous tissues, where they are safe from the immune system and can mate and reproduce. Nodules are found predominantly over bony areas such as the hip, pelvis, ribs, shoulder blades, and skull. Some people do not experience symptoms while infected with O. volvulus, as the larvae can migrate through the human body without provoking a response from the immune system. But many people do have symptoms, which include itchy skin rashes, nodules under the skin, and vision changes. Symptoms of onchocerciasis are mainly caused by the inflammatory response to dead or dying microfilariae. Skin reactions range from mild and local to generalized and intense itching. Severe itching leads to scratching that can cause skin lesions and bacterial infection. If untreated, the skin disease can progress to a chronic rough, coarse dermatitis and often has hyper-pigmentation (dark skin.) In later stages, the skin thins (cigarette-paper appearance) and finally patchy depigmentation (leopard skin) appears. Itching from onchocerciasis can be very severe, intractable, and non-responsive to medication.

Eye lesions only occur after many years of severe infection and therefore are usually not present in people under the age of 30. The inflammation caused by larvae that die in the eye results initially in reversible small opaque spots on the cornea. These spots are often accompanied by redness of the conjunctiva. At a later stage, the cornea becomes permanently cloudy, which results in vision loss. In infections that produce blindness, not only the cornea gets damaged but all anatomical parts of the eye are also affected, including the posterior part of the eye and the optic nerve.

Diagnosis

The time between infection and detection of microfilariae is three to 15 months. A physical examination of the patient can detect localized dermatitis or subcutaneous nodules. The most common method of laboratory diagnosis used to identify microfilariae is a biopsy of the skin called a skin snip. Microfilariae emerge when the skin snip is placed in a saline solution. Nodules can also be surgically removed to identify adult worms. Polymerase chain reaction, which uses a costly but highly sensitive machine, can be used to diagnosis patients with low levels of infection. A slit-lamp, a microscope with a light, can be used to examine the eye for larvae or lesions.

Antibody tests have been developed to test for infection. These tests cannot distinguish between past and current infections, so they are not as useful in people who lived in areas where the parasite exists; however, they are useful in visitors to these areas. Some of the tests are general tests for infection with any filarial parasite and some are more specific to onchocerciasis.

Treatment

Currently, the only treatment options that exist to eradicate adult worms within infected individuals are toxic to people. The recommended treatment for onchocerciasis is ivermectin (Mectizan®), which targets microfilariae and is fast-acting, safe, and effective. Ivermectin kills circulating microfilariae as well as those that are still in adult female worms; this reduces the numbers of microfilariae in the skin and the production of new microfilariae by adult worms so the disease does not progress. Standard treatment is once a year, but infected people can be treated up to three times in one year. Since adult worms are not killed and will continue to reproduce, treatment must continue for 10 to 15 years.

Before any treatment for onchocerciasis is begun, it is imperative to ascertain which individuals or communities are heavily infected with Loa loa, another filarial disease. Ivermectin can cause severe and adverse reactions in patients with Loa loa.

In Sierra Leone, community drug distributors stand with poles they use to measure the height of participants during a mass drug administration. Height is used to determine the proper treatment dosage for participants. For example, an individual who reaches the white area of the pole, which has one dot, would receive one dose of ivermectin. CREDIT: WHO SIERRA LEONE

Control and Elimination Programs

On a global level, sustainable mass drug administration of ivermectin is currently the primary control strategy for onchocerciasis. Merck & Co., Inc. has established a generous program, called the Mectizan Donation Program, to provide free drugs to any governmental or nongovernmental organization that demonstrates the need and the capability to distribute ivermectin.

WHO programs include the OCP, the APOC, and the OEPA. OCP was officially closed in December 2002 after virtually stopping the transmission of the disease in all the participating countries except Sierra Leone, where operations were interrupted by a decade-long civil war. APOC has been working with neglected tropical diseases since 1995 and is currently assisting countries in Africa outside the original OCP area in West Africa, establishing sustainable national programs for ivermectin distribution.

In most APOC countries, vector control, usually ground larviciding using environmentally safe insecticides, is not feasible or cost-effective. OEPA aims to eliminate clinical onchocerciasis and interrupt transmission using biannual ivermectin treatment to cover 85 percent of affected communities.

References

1. CDC, Laboratory Identification of Parasites of Public Health Concern: Filariasis. http://www.dpd.cdc.gov/dpdx/HTML/Filariasis.htm.
2. Dadzie KY, Remme J, Rolland A, et al: “Ocular Onchocerciasis and Intensity of the Infection in the Community. II. West African Rainforest Foci of the Vector Simulium Yahense.” Trop Med Parasitol 40:348, 1989.
3. Dadzie KY, Remme J, Backer RH, et al: “Ocular Onchocerciasis and Intensity of the Infection in the Community. III. West African Rainforest Foci of the Vector Simulium Sanctipauli.” Trop Med Parasitol 41:376, 1990.
4. Hoerauf A, Buttner DW, Adjei O, et al: “Onchocerciasis.” BMJ 326:207, 2003.
5. Kirkwood B, Smith P, Marshall T, et al: “Relationships between Mortality, Visual Acuity and Microfilarial Load in the Area of the Onchocerciasis Control Programme.” Trans R Soc Trop Med Hyg 77:862, 1983.
6. Little MP, Breitling LP, Basanez MG, et al: “Association between Microfilarial Load and Excess Mortality in Onchocerciasis: An Epidemiological Study.” The Lancet 363:1514, 2004.
7. McCarthy JS, Ottesen EA, Nutman TB: “Onchocerciasis in Endemic and Non-endemic Populations: Differences in Clinical Presentation and Immunologic Findings.” J Infect Dis 170:736, 1994.
8. Peters DH, Phillips T: “Mectizan Donation Program: Evaluation of a Public–Private Partnership.” Trop Med Int Health 9:A4, 2004.
9. Vincent JA, Lustigman S, Zhang S, et al: “A Comparison of Newer Tests for the Diagnosis of Onchocerciasis.” Ann Trop Med Parasitol 94:253, 2000.
10. WHO, First WHO Report on Neglected Tropical Diseases 2010: Working to Overcome the Global Impact of Neglected Tropical Diseases. http://www.who.int/neglected_diseases/2010report/en/index.html.
11. WHO, Prevention of Blindness and Visual Impairment: Onchocerciasis (River Blindness). http://www.who.int/blindness/partnerships/onchocerciasis_home/en/index.html.