Onchocerciasis


Onchocerciasis
Onchocerciasis
Classification and external resources

Adult black fly (Simulium yahense) with parasite (Onchocerca volvulus) emerging from the insect's antenna, magnified 100x
ICD-10 B73
ICD-9 125.3
DiseasesDB 9218
eMedicine med/1667 oph/709
MeSH D009855

Onchocerciasis (play /ˈɒŋkɵsɜrˈs.əsɨs/ or /ˈɒŋkɵsɜrˈk.əsɨs/), also known as river blindness and Robles' disease, is a parasitic disease caused by infection by Onchocerca volvulus, a nematode (roundworm).[1] Onchocerciasis is the world's second-leading infectious cause of blindness.[1] It is not the nematode, but its endosymbiont, Wolbachia pipientis, that causes the severe inflammatory response that leaves many blind.[2] The parasite is transmitted to humans through the bite of a black fly of the genus Simulium. The larval nematodes spread throughout the body. When the worms die, their Wolbachia symbionts are released, triggering a host immune system response that can cause severe itching, and can destroy optical tissue in the eye.[3]

The vast majority of infections occur in sub-Saharan Africa, although cases have also been reported in Yemen and isolated areas of Central and South America.[4] An estimated 18 million people suffer from onchocerciasis, with approximately 270,000 cases of blindness related to the infection.[1]

In 1915, Dr. Rodolfo Robles Valverde's study on patients with river blindness in Guatemala led to the discovery that the disease is caused by filaria of O. volvulus, and sheds light on the life cycle and transmission of the parasite. Using case studies of coffee plantation workers in Guatemala, Robles hypothesized the vector of the disease is a day-biting insect, and more specifically, two anthropophilic species of Simulium flies found in the endemic areas. He published his findings on a “new disease” from Guatemala associated with subcutaneous nodules, anterior ocular (eye) lesions, dermatitis, and microfilariae in 1917.[5]

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 it prevents transmission for many months in the remaining population.[6] Other drugs are also available, including the tetracycline-class antibiotic doxycycline, which kills the Wolbachia and renders the female nematodes sterile. The removal of the palpable nodules is common in Guatemala, Ecuador, and Mexico.[7]

Contents

Classification

Onchocerciasis may be divided into the following phases or types:[8]:440-441[verification needed]

Erisipela de la costa
An acute phase, it is characterized by swelling of the face, with erythema and itching.[8]:440 Onchocerciasis causes different kinds of skin changes and these changes 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.[7]
Mal morando
This cutaneous condition is characterized by inflammation accompanied by hyperpigmentation.[8]:440
Sowda
A cutaneous condition, it is a localized type of onchocerciasis.[8]:440

Additionally, the various skin changes associated with onchocerciasis may be described as follows:[8]:440

Leopard skin
A term referring to the spotted depigmentation of the skin that may occur with onchocerciasis[8]:440
Elephant skin
A term used to describe the thickening of human skin that may be associated with onchocerciasis[8]:440
Lizard skin
A term used to describe the thickened, wrinkled skin changes that may result with onchocerciasis[8]:441

Life cycle of O. volvulus

The life of the parasite can be traced through the black fly and the human hosts in the following steps:[citation needed]

  1. A Simulium female black fly takes a blood meal on an infected human host, and ingests 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 move to the proboscis and into the saliva in its third larval stage (J3.). Maturation takes 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 undergo two more molts. They 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 worms remain in subcutaneous nodules, limiting access to the host's immune system.[citation needed] Microfilariae, in contrast, are able to induce intense inflammatory responses, especially upon their death. 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.[9] 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. The severity of illness is directly proportional to the number of infected microfilariae and the power of the resultant inflammatory response.[citation needed]

Skin involvement typically consists of intense itching, swelling, and inflammation.[10] A grading system has been developed to categorize the degree of skin involvement:[11][12][verification needed]

  • 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, and
  • Depigmentation - 'leopard skin' appearance, usually on anterior lower leg.

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.[10] 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.[citation needed].As the skin is itchy, it can lead to severe rashes and you can permanently kill off 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 for the treatment of onchocerciasis 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 the microfilaria of O. volvulus, localized pruritus and urticaria are seen at the application site.[13]

Prevention

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, it 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 onchocerciasis cannot reinvade the area of the OCP.[14]

In 1992, the Onchocerciasis Elimination Programme for the Americas (OEPA), which also relies on ivermectin, was launched.[15]

In 1995, the African Programme for Onchocerciasis Control (APOC) 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.[16]

Treatment

The burden of onchocerciasis: children leading blind adults in Africa

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 worm, it does prevent them from producing additional offspring. The drug therefore prevents both morbidity and transmission.

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.[17]

Antibiotics

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.[18][19] In four separate trials over ten 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.[20] However, doxycycline treatment requires daily dosing for at least four to six weeks, making it more difficult to administer in the affected areas.[17]

Ivermectin

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 (GluCls).[17] 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.[17] 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 occurring in synapses between neurons decreases and the nematodes experience flaccid paralysis followed by death.[21][22][23]

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.[17]

Since 1988, ivermectin has been provided free of charge for use in humans by Merck through the Mectizan donation program (MDP). The MDP works together with ministries of health and nongovernmental development organisations, such as the World Health Organization, to provide free ivermectin to those who need it in endemic areas.[24]

A study of 2501 people in Ghana showed the prevalence rate doubled between 2000 and 2005 despite treatment, suggesting the parasite is developing resistance to the drug.[20][25][26] A clinical trial of another antiparasitic agent, moxidectin (manufactured by Wyeth), began on July 1, 2009 (NCT00790998).[27]

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

About 99% of onchocerciasis cases occur in Africa.[4] As of 2008, about 18 million people were infected with this parasite; about 300,000 had been permanently blinded.[28] Onchocerciasis is currently endemic in 30 African countries, Yemen, and isolated regions of South America.[29] 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 habitat, 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.[citation needed] 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.


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, which results in an estimated reduction in life expectancy of 13 years.[29]

Research

Animal models for the disease are somewhat limited, as the parasite only lives in primates, but there are close parallels. Litomosoides sigmodontis , which will naturally infect cotton rats, has been found to fully develop in BALB/c mice. Onchocerca ochengi, the closest relative of O. volvulus, lives in intradermal cavities in cattle, and is also spread by black flies. Both systems are useful, but not exact, animal models.[30]

See also

References

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External links


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Look at other dictionaries:

  • onchocerciasis — n. (Med.) An infection with nematodes of the genus {Onchocerca}, especially {Onchocerca volvulus}. Untreated, such infections can cause serious dermatological problems, and in advanced cases may lead to blindness. In certain areas of tropical… …   The Collaborative International Dictionary of English

  • onchocerciasis — [äŋ΄kō sər kī′ə sis] n. a fly transmitted tropical disease in which parasitic filarial worms (genus Onchocerca) cause tumors, skin lesions, and blindness; river blindness …   English World dictionary

  • onchocerciasis — /ong koh seuhr kuy euh sis/, n. Pathol. an infestation with filarial worms of the genus Onchocerca, common in tropical America and Africa, transmitted by black flies, and characterized by nodules under the skin, an itchy rash, eye lesions, and in …   Universalium

  • Onchocerciasis — River blindness, a disease caused by a parasitic worm (Onchocerca volvulus) which is transmitted to persons by biting blackflies (buffalo gnats) that breed in fast flowing rivers. The adult worms can live for up to 15 years in nodules beneath the …   Medical dictionary

  • onchocerciasis — n. a tropical disease of the skin and underlying connective tissue caused by the parasitic worm Onchocerca volvulus. Fibrous nodular tumours grow around the adult worms in the skin; these may take several months to appear, and if secondary… …   The new mediacal dictionary

  • onchocerciasis — noun (plural onchocerciases) Etymology: New Latin, from Onchocerca, genus of worms Date: 1911 infestation with or disease caused by filarial worms (genus Onchocerca); especially a human disease marked by subcutaneous nodules, dermatitis, and… …   New Collegiate Dictionary

  • onchocerciasis — noun /ɒŋkəsɜːˈkaɪəsɪs/ A disease caused by a worm of the genus Onchocerca, especially as transmitted to humans by flies and often causing blindness; common in tropical Africa. Syn: river blindness …   Wiktionary

  • onchocerciasis — [ˌɒŋkəʊsə: sʌɪəsɪs, kʌɪəsɪs] noun technical term for river blindness. Origin early 20th cent.: from mod. L. Onchocerca (genus name of the parasite causing the disease, from Gk onkos barb + kerkos tail ) + iasis …   English new terms dictionary

  • onchocerciasis — on·cho·cer·ci·a·sis …   English syllables

  • onchocerciasis — noun infestation with slender threadlike roundworms (filaria) deposited under the skin by the bite of black fleas; when the eyes are involved it can result in blindness; common in Africa and tropical America • Syn: ↑river blindness • Hypernyms:… …   Useful english dictionary