onchocerciasis

Onchocerciasis (pronounced /ˈɒnkɵsɜrˈsaɪ.əsɨs/ or /ˈɒnkɵsɜrˈkaɪ.əsɨs/),^[1] also known as river blindness and Robles' Disease, is the world's second^[2] leading infectious cause of blindness. It is caused by Onchocerca volvulus, a nematode that can live for up to fifteen years in the human body^[3] though it can also live in other mammals. It is transmitted to humans through the bite of a black fly. The worms spread throughout the body, and when they die, they cause intense itching and a strong immune system response that can destroy nearby tissue, such as the eye.^[4]

Treatment may involve the use of the drug ivermectin. For best effect, entire communities are treated at the same time. A single dose may kill first-stage larvae (microfilariae) in infected people and prevents transmission for many months in the remaining population.^[5] Other drugs are also available. The removal of the palpable nodules is popular in Guatemala, Ecuador, and Mexico.^[6]

Classification

Onchocerciasis may be divided into the following phases or types:^[7]:440-441

• Erisipela de la costa
• Mal morando
• Sowda

Additionally, the various skin changes associated with onchocerciasis may be described as follows:^[7]:440

• Leopard skin
• Elephant skin
• Lizard skin

Life Cycle of Onchocerca volvulus

The life of the O. Volvulus parasite can be traced through the black fly and the human hosts in the following steps:^[8]

1. A Simulium female black fly takes a blood meal on an infected human host ingesting microfilaria.

2. The microfilaria enter the gut and thoracic flight muscles of the black fly progressing into the first larval stage (J1.).

3. The larvae mature into the second larval stage (J2.) and moves to the proboscis and into the saliva in its third larval stage (J3.). Mature in about 7 days.

4. The black fly takes another blood meal passing the larvae into the next human host’s blood.

5. The larvae migrate to the subcutaneous tissue and form nodules as they mature into adult worms over six to twelve months.

6. After maturing, adult male worms mate with female worms in the subcutaneous tissue to produce between 700 and 1,500 microfilaria per day.

7. The microfilaria migrate to the skin during the day and the black flies only feed in the day, so the parasite is in a prime position for the female fly to ingest it. Black flies take blood meals to ingest these microfilaria to restart the cycle.

Signs and symptoms

Adult Black Fly (Simulium yahense) with parasite (Onchocerca volvulus) emerging from the insect's antenna. Magnified 100x.

Adult worms remain in subcutaneous nodules, limiting access to the host's immune system. Microfilariae, in contrast, are able to induce intense inflammatory responses, especially upon their death. Dying microfilariae have been recently discovered to release Wolbachia-derived antigens, triggering innate immune responses and producing the inflammation and its associated morbidity. Wolbachia species have been found to be endosymbionts of O. volvulus adults and microfilariae, and are thought to be the driving force behind most of O. volvulus morbidity. Severity of illness is directly proportional to the number of microfilariae and the power of the resultant inflammatory response.

Skin involvement typically consists of intense itching, swelling, and inflammation. A grading system has developed to categorize the degree of skin involvement:

• Acute papular onchodermatitis - scattered pruritic papules;
• Chronic papular onchodermatitis - larger papule, resulting in hyperpigmentation;
• Lichenified onchodermatitis - hyperpigmented papules and plaques, with edema, lymphadenopathy, pruritus and common secondary bacterial infections;
• Skin atrophy - loss of elasticity, skin resembles tissue paper, 'lizard skin' appearance;
• Depigmentation - 'leopard skin' appearance, usually on anterior lower leg.

Ocular involvement provides the common name associated with onchocerciasis, river blindness. The microfilariae migrate to the surface of the cornea. Punctate keratitis occurs in the infected area. This clears up as the inflammation subsides. However, if the infection is chronic, sclerosing keratitis can occur, making the affected area become opaque. Over time the entire cornea may become opaque, thus leading to blindness. There is some evidence to suggest that the effect on the cornea is caused by an immune response to bacteria present in the worms.

Prevention

There are various control programs that aim to stop onchocerciasis from being a public health problem. The first was the Onchocerciasis Control Programme (OCP), which was launched in 1974 and at its peak covered 30 million people in eleven countries. Through the use of larvicide spraying of fast flowing rivers to control black fly populations and, from 1988 onwards, the use of ivermectin to treat infected people, the OCP eliminated onchocerciasis as a public health problem. The OCP, a joint effort of the World Health Organisation, the World Bank, the United Nations Development Programme and the UN Food and Agriculture Organization, was considered to be a success and came to an end in 2002. Continued monitoring ensures that onchocerciasis cannot reinvade the area of the OCP.

In 1992 the Onchocerciasis Elimination Programme for the Americas (OEPA) was launched. The OEPA also relies on ivermectin.

In 1995 the African Programme for Onchocerciasis Control (APOC) began covering another nineteen countries and mainly relying upon the use of ivermectin. Its goal is to set up a community-directed supply of ivermectin for those who are infected. In these ways, transmission has declined.

Treatment

The burden of onchocerciasis: children leading blind adults in Africa.

The treatment for onchocerciasis is ivermectin (Mectizan); infected people can be treated with two doses of Ivermectin, six months apart, repeated every three years. The drug paralyses and kills the microfilariae, causing fever, itching, and possibly oedema, arthritis and lymphadenopathy. Intense skin itching is eventually relieved and progression towards blindness halted. In addition, while the drug does not kill the adult worm, it does prevent them from producing additional offspring. The drug therefore prevents both morbidity and transmission. Doxycycline kills a bacteria, Wolbachia, that lives in adult worms. This adjunct therapy has been shown to significantly lower microfilarial loads in the host, and may have activity against the adult worms, due to the symbiotic relationship between Wolbachia and the worm.^[9][10]

Since 1988, ivermectin has been provided free of charge by Merck & Co. through the Mectizan Donation Program (MDP). The MDP works together with ministries of health and non-governmental development organisations such as the World Health Organization to provide free Mectizan to those who need it in endemic areas.

A study of 2501 people in Ghana showed that the prevalence rate doubled between 2000 and 2005 despite treatment, suggesting that the parasite is developing resistance to the drug.^[11][12] A clinical trial of another parasitic agent, moxidectin (manufactured by Wyeth), began on July 1, 2009 (NCT00790998).^[13]

Mechanism of Ivermectin

Ivermectin kills the parasite by interfering with the nervous system and muscle function, in particular, by enhancing inhibitory neurotransmission. The drug may bind to and activate glutamate-gated chloride channels (GluCls). These channels are invertebrate-specific and present in neurons and myocytes. Ivermectin is thought to irreversibly activate these channel receptors in the worm, eventually causing an inhibitory postsynaptic potential (IPSP). The chance of a future action potential occuring in synapses between neurons decreases and the nematodes experience flaccid paralysis followed by death. ^{[14] [15]}

Ivermectin is most effective against the larval stage microfilariae Onchocerca volvulus The exact reasoning for ineffectiveness of the drug in the adult worms is not yet understood, but one possible explanation could be that GluCl expression between the adult and larval stages is different.^{[16] [17]}

Epidemiology

Disability-adjusted life year for onchocerciasis per 100,000 inhabitants.

     no data      less than 10      10-50      50-60      60-70      70-80      80-90      90-100      100-150      150-200      200-300      300-400      more than 400

99% of onchocerciasis cases occur in Africa.^[18] About 18 million people are currently infected with this parasite; approximately 300,000 have been permanently blinded.^[19] Onchocerciasis is currently endemic in 30 African countries, Yemen, and isolated regions of South America. Travelers who do not stay long in those areas have little risk of developing the disease as it requires prolonged exposure to the fly bites and parasite introduction.

Onchocerciasis is endemic in 36 countries across Africa, Latin America and Yemen.^[20] Over 85 million people live in endemic areas and half of these reside in Nigeria. Another 120 million people are at risk for contracting the disease. Due to the vector’s breeding habit, the disease is more severe along the major rivers in the northern and central areas of the continent, and severity declines in villages farther from rivers.

According to a 2002 WHO report, Onchocerciasis has not caused a single death, but its global burden is 987,000 Disability Adjusted Life Years (DALYs). The severe pruritis alone accounts for 60% of the DALYs. Infection reduces the host’s immunity and resistance to other diseases. This results in an estimated reduction in life expectancy of 13 years.^[20]

See also

• Carter Center River Blindness Program
• Neglected Diseases
• Rodolfo Robles
• List of parasites (human)
• United Front Against Riverblindness

References

External links

• Onchocerciasis Research Project at the University of Tuebingen
• Mectizan Donation Program
• River Blindness Documentary "37 Million and Counting" by Aaron Edell
• SightSavers
• What is River Blindness?, CBM International
• CDC Parasites of Public Health Concern
• American NGDO Treating River Blindness in the Democratic Republic of the Congo