Onchocerciasis

"River Blindness" redirects here. For the song by The J. Geils Band, see Freeze Frame (The J. Geils Band album).
Onchocerciasis

An adult black fly with the parasite Onchocerca volvulus coming out of the insect's antenna, magnified 100x
Classification and external resources
ICD-10 B73
ICD-9 125.3
DiseasesDB 9218
eMedicine med/1667 oph/709
MeSH D009855

Onchocerciasis (/ˈɒŋkɵsɜrˈsaɪ.əsɨs/ or /ˈɒŋkɵsɜrˈkaɪ.əsɨs/), also known as river blindness and Robles disease, is a disease caused by infection with the parasitic worm Onchocerca volvulus.[1] Symptoms include severe itching, bumps under the skin, and blindness.[1] It is the second most common cause of blindness due to infection, after trachoma.[2]

The parasite worm is spread by the bites of a black fly of the Simulium type.[1] Usually many bites are required before infection occurs.[3] These flies live near rivers therefore the name of the disease.[2] Once inside a person the worms create larvae that make their way out to the skin.[1] Here they can infect the next black fly that bites the person.[1] There are a number of ways to make the diagnosis including: placing a biopsy of the skin in normal saline and watching for the larva to come out, looking in the eye for larvae, and looking within the bumps under the skin for adult worms.[4]

A vaccine against the disease does not exist.[1] Prevention is by avoiding being bitten by flies.[5] This may include the use of insect repellent and proper clothing.[5] Other efforts include those to decrease the fly population by spraying insecticides.[1] Efforts to eradicate the disease by treating entire groups of people twice a year is ongoing in a number of areas of the world.[1] Treatment of those infected is with the medication ivermectin every six to twelve months.[1][6] This treatment kills the larva but not the adult worms.[7] The medication doxycycline, which kills an associated bacterium called Wolbachia, appears to weaken the worms and is recommended by some as well.[7] Removal of the lumps under the skin by surgery may also be done.[6]

About 17 to 25 million people are infected with river blindness, with approximately 0.8 million having some amount of loss of vision.[3][7] Most infections occur in sub-Saharan Africa, although cases have also been reported in Yemen and isolated areas of Central and South America.[1] In 1915, the physician Rodolfo Robles first linked the worm to eye disease.[8] It is listed by the World Health Organization as a neglected tropical disease.[9]

Signs and symptoms

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.[10] 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.[11] A grading system has been developed to categorize the degree of skin involvement:[12][13]

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.[11] 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.

Mazzotti reaction

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.

Patch test

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.[14]

Nodding disease

Main article: Nodding disease

This is an unusual form of epidemic epilepsy associated with onchocerciasis.[15] 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.

Classification

Onchocerciasis may be divided into the following phases or types:[16]:440–441

Erisipela de la costa
An acute phase, it is characterized by swelling of the face, with erythema and itching.[16]:440 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.[17]
Mal morando
This cutaneous condition is characterized by inflammation accompanied by hyperpigmentation.[16]:440
Sowda
A cutaneous condition, it is a localized type of onchocerciasis.[16]:440

Additionally, the various skin changes associated with onchocerciasis may be described as follows:[16]:440

Leopard skin
The spotted depigmentation of the skin that may occur with onchocerciasis[16]:440
Elephant skin
The thickening of human skin that may be associated with onchocerciasis[16]:440
Lizard skin
The thickened, wrinkled skin changes that may result with onchocerciasis[16]:441

Cause

The cause is Onchocerca volvulus

Life cycle

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

  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 seven 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 12 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.

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, 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.[18]

In 1992, the Onchocerciasis Elimination Programme for the Americas, which also relies on ivermectin, was launched.[19]

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.[20]

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.[21]

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.

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 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.[22]

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.[23][24] 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.[25] However, doxycycline treatment requires daily dosing for at least four to six weeks, making it more difficult to administer in the affected areas.[22]

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.[22] 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.[22] 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.[26][27][28]

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.[22]

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 37 million people are infected with this parasite;[29] about 300,000 of those had been permanently blinded.[30] As of 2008, about 99% of onchocerciasis cases occurred in Africa.[31] Onchocerciasis is currently endemic in 30 African countries, Yemen, and isolated regions of South America.[32] 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. Onchocerciasis was eliminated in the northern focus in Chiapas, Mexico,[33] and the focus in Oaxaca, Mexico, where Onchocerca volvulus existed, was determined, after several years of treatment with ivermectin, as free of the transmission of the parasite.[34]

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 pruritus 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.[32]

According to the Panamerican Health Organization, on July 2013, Colombia became the first country to completely eliminate this disease from within its borders.[35]

History

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 to be endemic to the areas. He published his findings on a “new disease” from Guatemala associated with subcutaneous nodules, anterior ocular (eye) lesions, dermatitis, and microfilariae in 1917.[36]

Society and culture

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.[37]

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.[38]

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.[25][39][40] A clinical trial of another antiparasitic agent, moxidectin (manufactured by Wyeth), began on July 1, 2009 (NCT00790998).[41]

See also

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 1.9 "Onchocerciasis Fact sheet N°374". World Health Oragnization. March 2014. Retrieved 20 March 2014.
  2. ↑ 2.0 2.1 "Onchocerciasis (also known as River Blindness)". Parasites. CDC. May 21, 2013. Retrieved 20 March 2014.
  3. ↑ 3.0 3.1 "Parasites – Onchocerciasis (also known as River Blindness) Epidemiology & Risk Factors". CDC. May 21, 2013. Retrieved 20 March 2014.
  4. ↑ "Onchocerciasis (also known as River Blindness) Diagnosis". Parasites. CDC. May 21, 2013. Retrieved 20 March 2014.
  5. ↑ 5.0 5.1 "Onchocerciasis (also known as River Blindness) Prevention & Control". Parasites. CDC. May 21, 2013. Retrieved 20 March 2014.
  6. ↑ 6.0 6.1 Murray, Patrick (2013). Medical microbiology (7th ed.). Philadelphia: Elsevier Saunders. p. 792. ISBN 9780323086929.
  7. ↑ 7.0 7.1 7.2 Brunette, Gary W. (2011). CDC Health Information for International Travel 2012 : The Yellow Book. Oxford University Press. p. 258. ISBN 9780199830367.
  8. ↑ Lok, James B.; Walker, Edward D.; Scoles, Glen A. (2004). "9. Filariasis". In Eldridge, Bruce F.; Edman, John D.; Edman, J. Medical entomology (Revised ed.). Dordrecht: Kluwer Academic. p. 301. ISBN 9781402017940.
  9. ↑ Reddy M, Gill SS, Kalkar SR, Wu W, Anderson PJ, Rochon PA (October 2007). "Oral drug therapy for multiple neglected tropical diseases: a systematic review". JAMA 298 (16): 1911–24. doi:10.1001/jama.298.16.1911. PMID 17954542.
  10. ↑ Baldo L, Desjardins CA, Russell JA, Stahlhut JK, Werren JH (2010-02-17). "Accelerated microevolution in an outer membrane protein (OMP) of the intracellular bacteria Wolbachia". BMC Evol Biol 10: 10:48. doi:10.1186/1471-2148-10-48. PMC 2843615. PMID 20163713.
  11. ↑ 11.0 11.1 Wani, MG (February 2008). "Onchocerciasis". Southern Sudan Medical Journal.
  12. ↑ Ali MM, Baraka OZ, AbdelRahman SI, Sulaiman SM, Williams JF, Homeida MM, Mackenzie CD (15 February 2003). "Immune responses directed against microfilariae correlate with severity of clinical onchodermatitis and treatment history". Journal of Infectious Diseases 187 (4): 714–7. doi:10.1086/367709. JSTOR 30085595. PMID 12599094.
  13. ↑ Murdoch ME, Hay RJ, Mackenzie CD, Williams JF, Ghalib HW, Cousens S, Abiose A, Jones BR (September 1993). "A clinical classification and grading system of the cutaneous changes in onchocerciasis". Br J Dermatol 129 (3): 260–9. doi:10.1111/j.1365-2133.1993.tb11844.x. PMID 8286222.
  14. ↑ http://microblog.me.uk/420
  15. ↑ Dowell SF, Sejvar JJ, Riek L, Vandemaele KA, Lamunu M, Kuesel AC, Schmutzhard E, Matuja W, Bunga S, Foltz J, Nutman TB, Winkler AS, Mbonye AK (2013). "Nodding syndrome". Emerg Infect Dis 19 (9): 1374–3. doi:10.3201/eid1909.130401.
  16. ↑ 16.0 16.1 16.2 16.3 16.4 16.5 16.6 16.7 James, William D.; Berger, Timothy G.; Elston, Dirk M; Odom, Richard B. (2006). Andrews' Diseases of the Skin: clinical dermatology (10th ed.). Saunders Elsevier. ISBN 0-7216-2921-0. OCLC 62736861.
  17. ↑ Marty AM. "Filariasis". eMedicine. Retrieved 2009-10-22.
  18. ↑ "Onchocerciasis Control Programme (OCP)". Programmes and Projects. World Health Organization. Retrieved 2010-06-15.
  19. ↑ "Onchocerciasis Elimination Program for the Americas (OEPA)". Programmes and Projects. World Health Organization. Retrieved 2010-06-15.
  20. ↑ "African Programme for Onchocerciasis Control (APOC)". Programmes and Projects. World Health Organization. Retrieved 2010-06-15.
  21. ↑ "NEWS SCAN: Columbia ousts river blindness; Vaccine-derived polio in India; Danish Salmonella trends". CIDRAP News. July 30, 2013.
  22. ↑ 22.0 22.1 22.2 22.3 22.4 Rea PA, Zhang V, Baras YS (2010). "Ivermectin and River Blindness". American Scientist 98 (4): 294–303.
  23. ↑ Trattler, Bill; Gladwin, Mark (2007). Clinical Microbiology Made Ridiculously Simple. Miami: MedMaster. ISBN 0-940780-81-X. OCLC 156907378.
  24. ↑ Taylor MJ, Bandi C, Hoerauf A (2005). "Wolbachia bacterial endosymbionts of filarial nematodes". Adv. Parasitol. 60: 245–84. doi:10.1016/S0065-308X(05)60004-8. PMID 16230105.
  25. ↑ 25.0 25.1 Hoerauf A (2008). "Filariasis: new drugs and new opportunities for lymphatic filariasis and onchocerciasis". Current Opinion in Infectious Diseases 21 (6): 673–81. doi:10.1097/QCO.0b013e328315cde7. PMID 18978537.
  26. ↑ Yates DM, Wolstenholme AJ (August 2004). "An ivermectin-sensitive glutamate-gated chloride channel subunit from Dirofilaria immitis". International Journal for Parasitology 34 (9): 1075–81. doi:10.1016/j.ijpara.2004.04.010. PMID 15313134.
  27. ↑ Harder A (2002). "Chemotherapeutic approaches to nematodes: current knowledge and outlook". Parasitology Research 88 (3): 272–7. doi:10.1007/s00436-001-0535-x. PMID 11954915.
  28. ↑ Wolstenholme AJ, Rogers AT (2005). "Glutamate-gated chloride channels and the mode of action of the avermectin/milbemycin anthelmintics". Parasitology 131 (Suppl:S85–95): S85–95. doi:10.1017/S0031182005008218. PMID 16569295.
  29. ↑ Fenwick, A (Mar 2012). "The global burden of neglected tropical diseases.". Public health 126 (3): 233–6. doi:10.1016/j.puhe.2011.11.015. PMID 22325616.
  30. ↑ "What is river blindness?". Sightsavers International. Archived from the original on 2007-12-15. Retrieved 2008-01-28.
  31. ↑ "Status of onchocerciasis in APOC countries". World Health Organization. 2008. Retrieved 2010-04-26.
  32. ↑ 32.0 32.1 "Epidemiology". Stanford University. 2006.
  33. ↑ Peña Flores, G., Richards, F., et al. (2010). Lack of Onchocerca volvulus transmission in the northern focus in Chiapas. Am. J. Trop. Med. Hyg., 83(1), 15-20.
  34. ↑ Peña Flores, G., Richards, F., & Domínguez, A. (2010). Interruption of transmission of Onchocerca volvulus in the Oaxaca focus. Am. J. Trop. Med. Hyg., 83(1), 21-27.
  35. ↑ 'EFE' (29 July 2013). "Colombia, primer país libre de la 'ceguera de los ríos'". El Tiempo (Bogota). Retrieved 14 July 2014.
  36. ↑ Robles R (1917). "Enfermedad nueva en Guatemala". La Juventud Médica 17: 97–115.
  37. ↑ Thylefors B, Alleman MM, Twum-Danso NA (May 2008). "Operational lessons from 20 years of the Mectizan Donation Program for the control of onchocerciasis". Trop Med Int Health 13 (5): 689–96. doi:10.1111/j.1365-3156.2008.02049.x. PMID 18419585.
  38. ↑ Allen JE, Adjei O, Bain O, Hoerauf A, Hoffmann WH, Makepeace BL, Schulz-Key H, Tanya VN, Trees AJ, Wanji S, Taylor DW (April 2008). Lustigman, Sara, ed. "Of Mice, Cattle, and Humans: The Immunology and Treatment of River Blindness". PLoS Negl Trop Dis 2 (4): e217. doi:10.1371/journal.pntd.0000217. PMC 2323618. PMID 18446236.
  39. ↑ "River blindness resistance fears". BBC News. 2007-06-14. Retrieved 2007-06-15.
  40. ↑ Osei-Atweneboana MY, Eng JK, Boakye DA, Gyapong JO, Prichard RK (June 2007). "Prevalence and intensity of Onchocerca volvulus infection and efficacy of ivermectin in endemic communities in Ghana: a two-phase epidemiological study". Lancet 369 (9578): 2021–9. doi:10.1016/S0140-6736(07)60942-8. PMID 17574093.
  41. ↑ [No author listed] (11 July 2009). "Fighting river blindness and other ills". Lancet 374 (9684): 91. doi:10.1016/S0140-6736(09)61262-9. PMID 19595328. (editorial)

External links

Look up onchocerciasis in Wiktionary, the free dictionary.