Onchocerciasis, is a disease caused by infection with the parasitic worm Onchocerca volvulus. Symptoms include severe itching, bumps under the skin, and blindness. It is the second most common cause of blindness due to infection, after trachoma.
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. 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. Dying microfilariae have been recently discovered to release Wolbachia surface protein that activates TLR2 and TLR4, triggering innate immune responses and producing the inflammation and its associated morbidity. The severity of illness is directly proportional to the number of infected microfilariae and the power of the resultant inflammatory response.
Skin involvement typically consists of intense itching, swelling, and inflammation. A grading system has been developed to categorize the degree of skin involvement:
- Acute papular onchodermatitis – scattered pruritic papules
- Chronic papular onchodermatitis – larger papules, resulting in hyperpigmentation
- Lichenified onchodermatitis – hyperpigmented papules and plaques, with edema Lymphadenopathy, pruritus and common secondary bacterial infections
- Skin atrophy – loss of elasticity, the skin resembles tissue paper, 'lizard skin' appearance
- Depigmentation – 'leopard skin' appearance, usually on anterior lower leg
- Glaucoma effect – eyes malfunction, begin to see shadows or nothing
Ocular involvement provides the common name associated with onchocerciasis, river blindness, and may involve any part of the eye from conjunctiva and cornea to uvea and posterior segment, including the retina and optic nerve. 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. Some evidence suggests the effect on the cornea is caused by an immune response to bacteria present in the worms. The skin is itchy, with severe rashes permanently damaging patches of skin.
The Mazzotti reaction, first described in 1948, is a symptom complex seen in patients after undergoing treatment of onchocerciasis with the medication diethylcarbamazine(DEC). Mazzotti reactions can be life-threatening, and are characterized by fever, urticaria, swollen and tender lymph nodes, tachycardia, hypotension, arthralgias, oedema, and abdominal pain that occur within seven days of treatment of microfilariasis.
The phenomenon is so common when DEC is used that this drug is the basis of a skin patch test used to confirm that diagnosis. The drug patch is placed on the skin, and if the patient is infected with O. volvulus microfilaria, localized pruritus and urticaria are seen at the application site.
This is an unusual form of epidemic epilepsy associated with onchocerciasis. This syndrome was first described in Tanzania by Louise Jilek-Aall, a Norwegian psychiatric doctor in Tanzanian practice, during the 1960s. It occurs most commonly in Uganda and South Sudan. It manifests itself in previously healthy 5–15-year-old children, is often triggered by eating or low temperatures and is accompanied by cognitive impairment. Seizures occur frequently and may be difficult to control. The electroencephalogram is abnormal but cerebrospinal fluid (CSF) and magnetic resonance imagining (MRI) are normal or show non-specific changes. If there are abnormalities on the MRI they are usually present in the hippocampus. Polymerase chain reaction testing of the CSF does not show the presence of the parasite.
Onchocerciasis may be divided into the following phases or types:
Erisipela de la costa
An acute phase, it is characterized by swelling of the face, with erythema and itching. Onchocerciasis causes different kinds of skin changes, which vary in different geographic regions. This skin change, erisípela de la costa, of acute onchocerciasis is most commonly seen among victims in Central and South America.
This cutaneous condition is characterized by inflammation accompanied by hyperpigmentation.
A cutaneous condition, it is a localized type of onchocerciasis.
Additionally, the various skin changes associated with onchocerciasis may be described as follows:
The spotted depigmentation of the skin that may occur with onchocerciasis
The thickening of human skin that may be associated with onchocerciasis
The thickened, wrinkled skin changes that may result with onchocerciasis
The cause is Onchocerca volvulus.
The life of the parasite can be traced through the black fly and the human hosts in the following steps:
- A Simulium female black fly takes a blood meal on an infected human host, and ingests microfilaria.
- The microfilaria enter the gut and thoracic flight muscles of the black fly, progressing into the first larval stage (J1.).
- The larvae mature into the second larval stage (J2.), and move to the proboscis and into the saliva in its third larval stage (J3.). Maturation takes about seven days.
- The black fly takes another blood meal, passing the larvae into the next human host's blood.
- The larvae migrate to the subcutaneous tissue and undergo two more molts. They form nodules as they mature into adult worms over six to 12 months.
- After maturing, adult male worms mate with female worms in the subcutaneous tissue to produce between 700 and 1,500 microfilaria per day.
- 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.
Various control programs 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 11 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 onchocerciasis cannot reinvade the area of the OCP.
In 1992, the Onchocerciasis Elimination Programme for the Americas, which also relies on ivermectin, was launched.
In 1995, the African Programme for Onchocerciasis Control began covering another 19 countries, 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.
On July 29, 2013, the Pan American Health Organization (PAHO) announced that after 16 years of efforts, Colombia had become the first country in the world to eliminate the parasitic disease onchocerciasi.
No vaccine to prevent onchocerciasis infection in humans is available. A vaccine to prevent onchocerciasis infection for cattle is in phase three trials. Cattle injected with a modified and weakened form of O. ochengi larvae have developed very high levels of protection against infection. The findings suggest that it could be possible to develop a vaccine that protects people against river blindness using a similar approach. Unfortunately, a vaccine to protect humans is still many years off.
Usually, a sample of skin is snipped and examined for microfilariae. This method is painful. Alternatives are to test blood, but these tests are not always reliable or available. Microfilariae may also be seen in the eye using a slit lamp. Nodules can be removed and checked for adult worms, but this procedure is rarely necessary.
In mass drug administration (MDA) programmes, the treatment for onchocerciasis is ivermectin (trade name: 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 the progression towards blindness is halted. In addition, while the drug does not kill the adult worms, it does prevent them for a limited time from producing additional offspring. The drug therefore prevents both morbidity and transmission for up to several months.
Ivermectin treatment is particularly effective because it only needs to be taken once or twice a year, needs no refrigeration, and has a wide margin of safety, with the result that it has been widely given by minimally trained community health workers.
For the treatment of individuals, doxycycline is used to kill the Wolbachia bacteria that live 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. In four separate trials over 10 years with various dosing regimens of doxycycline for individualized treatment, doxycycline was found to be effective in sterilizing the female worms and reducing their numbers over a period of four to six weeks. Research on other antibiotics, such as rifampicin, has shown it to been effective in animal models at reducing Wolbachia both as an alternative and as an adjunct to doxycycline. However, doxycycline treatment requires daily dosing for at least four to six weeks, making it more difficult to administer in the affected areas.
Ivermectin kills the parasite by interfering with the nervous system and muscle function, in particular, by enhancing inhibitory neurotransmission. The drug binds to and activates glutamate-gated chloride channels. These channels, present in neurons and myocytes, are not invertebrate-specific, but are protected in vertebrates from the action of ivermectin by the blood–brain barrier. Ivermectin is thought to irreversibly activate these channel receptors in the worm, eventually causing an inhibitory postsynaptic potential. The chance of a future action potential occurring in synapses between neurons decreases and the nematodes experience flaccid paralysis followed by death.
Ivermectin is directly effective against the larval stage microfilariae of O. volvulus; they are paralyzed and can be killed by eosinophils and macrophages. It does not kill adult females (macrofilariae), but does cause them to cease releasing microfilariae, perhaps by paralyzing the reproductive tract.