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Onchocerciasis

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

Onchocerciasis, also known as river blindness and Robles disease, is a disease caused by infection with the neglected tropical disease.[9]

Contents

  • Signs and symptoms 1
    • Mazzotti reaction 1.1
    • Nodding disease 1.2
    • Classification 1.3
  • Cause 2
    • Life cycle 2.1
  • Prevention 3
  • Treatment 4
    • Antibiotics 4.1
    • Ivermectin 4.2
  • Epidemiology 5
  • History 6
  • Society and culture 7
  • Research 8
  • See also 9
  • References 10
  • External links 11

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]

  • 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.[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.

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

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 imaging (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

  • What is River Blindness?, CBM International
  • CDC Parasites of public health concern

External links

  1. ^ a b c d e f g h i j "Onchocerciasis Fact sheet N°374". World Health Oragnization. March 2014. Retrieved 20 March 2014. 
  2. ^ a b "Onchocerciasis (also known as River Blindness)". Parasites. CDC. May 21, 2013. Retrieved 20 March 2014. 
  3. ^ a b "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. ^ a b "Onchocerciasis (also known as River Blindness) Prevention & Control". Parasites. CDC. May 21, 2013. Retrieved 20 March 2014. 
  6. ^ a b Murray, Patrick (2013). Medical microbiology (7th ed.). Philadelphia: Elsevier Saunders. p. 792.  
  7. ^ a b c Brunette, Gary W. (2011). CDC Health Information for International Travel 2012 : The Yellow Book. Oxford University Press. p. 258.  
  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.  
  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.  
  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".  
  11. ^ a b Wani, MG (February 2008). "Onchocerciasis".  
  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".  
  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".  
  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".  
  16. ^ a b c d e f g h James, William D.; Berger, Timothy G.; Elston, Dirk M; Odom, Richard B. (2006). Andrews' Diseases of the Skin: clinical dermatology (10th ed.). Saunders Elsevier.  
  17. ^ Marty AM. "Filariasis". eMedicine. Retrieved 2009-10-22. 
  18. ^ "Onchocerciasis Control Programme (OCP)". Programmes and Projects.  
  19. ^ "African Programme for Onchocerciasis Control (APOC)". Programmes and Projects.  
  20. ^ "Onchocerciasis Elimination Program for the Americas (OEPA)". Programmes and Projects.  
  21. ^ "NEWS SCAN: Columbia ousts river blindness; Vaccine-derived polio in India; Danish Salmonella trends". CIDRAP News. July 30, 2013. 
  22. ^ "Brazil and Venezuela border is the last place in the Americas with river blindness". Outbreak News Today. Retrieved 3 October 2015. 
  23. ^ "Onchocerciasis Elimination Program for the Americas (OEPA)". World Health Organization. Retrieved 3 October 2015. 
  24. ^ "Onchocerciasis". World Health Organization. Retrieved 3 October 2015. 
  25. ^ Sauerbrey, M (September 2008). "The Onchocerciasis Elimination Program for the Americas (OEPA).". Annals of tropical medicine and parasitology. 102 Suppl 1: 25–9.  
  26. ^ a b c d e Rea PA, Zhang V, Baras YS (2010). "Ivermectin and River Blindness".  
  27. ^ Trattler, Bill; Gladwin, Mark (2007). Clinical Microbiology Made Ridiculously Simple. Miami: MedMaster.  
  28. ^ Taylor MJ, Bandi C, Hoerauf A (2005). "Wolbachia bacterial endosymbionts of filarial nematodes".  
  29. ^ a b Hoerauf A (2008). "Filariasis: new drugs and new opportunities for lymphatic filariasis and onchocerciasis".  
  30. ^ 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.  
  31. ^ Harder A (2002). "Chemotherapeutic approaches to nematodes: current knowledge and outlook". Parasitology Research 88 (3): 272–7.  
  32. ^ 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.  
  33. ^ Fenwick, A (Mar 2012). "The global burden of neglected tropical diseases.". Public health 126 (3): 233–6.  
  34. ^ "What is river blindness?". Sightsavers International. Archived from the original on 2007-12-15. Retrieved 2008-01-28. 
  35. ^ "Status of onchocerciasis in APOC countries".  
  36. ^ a b "Epidemiology". Stanford University. 2006. 
  37. ^ 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.
  38. ^ 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.
  39. ^ Zimmerman, PA; Katholi, CR; Wooten, MC; Lang-Unnasch, N; Unnasch, TR (May 1994). "Recent evolutionary history of American Onchocerca volvulus, based on analysis of a tandemly repeated DNA sequence family.". Molecular biology and evolution 11 (3): 384–92.  
  40. ^ O’Neill, John (1875). "O’Neill J. On the presence of a filaria in “ craw-craw" (PDF). The Lancet: 265. 
  41. ^ "A Short History of Onchocerciasis". Retrieved 18 October 2015. 
  42. ^ Robles, Roberto (1917). "Enfermedad nueva en Guatemala". La Juventud Médica. 
  43. ^ Strong, Richard (1942). Stitt’s Diagnosis, prevention and treatment of tropical diseases. The Blakiston. 
  44. ^ Manson-Bahr, Philip H (1943). Tropical diseases; a manual of the diseases of warm climates [Internet] (11th Edition ed.). Williams & Wilkins Co. 
  45. ^ Blacklock, DB (22 January 1927). "THE INSECT TRANSMISSION OF ONCHOCERCA VOLVULUS (LEUCKART, 1893): THE CAUSE OF WORM NODULES IN MAN IN AFRICA.". British medical journal 1 (3446): 129–33.  
  46. ^ Kluxen, G; Hoerauf, A (2008). "The significance of some observations on African ocular onchocerciasis described by Jean Hissette (1888-1965)". Bull Soc Belge Ophtalmol 307: 53-8. 
  47. ^ Hisette, Jean (1932). Mémoire sur l’Onchocerca volvulus „Leuckart“ et ses manifestations oculaires au Congo belge. p. 433-529. 
  48. ^ Ridley, Harold (1945). "OCULAR ONCHOCERCIASIS Including an Investigation in the Gold Coast". Br J Ophthalmol. 29 (Suppl): 3-58. 
  49. ^ Kluxen, G. "Harvard African Expedition [Internet]". Retrieved 18 October 2015. 
  50. ^ Thylefors B, Alleman MM, Twum-Danso NA (May 2008). "Operational lessons from 20 years of the Mectizan Donation Program for the control of onchocerciasis".  
  51. ^ Jan Andersson, Hans Forssberg, Juleen R. Zierath (5 October 2015), Avermectin and Artemisinin - Revolutionary Therapies against Parasitic Diseases (PDF), The Nobel Assembly at Karolinska Institutet, retrieved 5 October 2015 
  52. ^ 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".  
  53. ^ "River blindness resistance fears". BBC News. 2007-06-14. Retrieved 2007-06-15. 
  54. ^ 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.  
  55. ^ [No author listed] (11 July 2009). "Fighting river blindness and other ills". Lancet 374 (9684): 91.   (editorial)

References

See also

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.[29][53][54] A clinical trial of another antiparasitic agent, moxidectin (manufactured by Wyeth), began on July 1, 2009 (NCT00790998).[55]

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.[52]

Research

In 2015 William C. Campbell and Satoshi Ōmura were co-awarded half of that year's Nobel prize in Physiology or Medicine for the discovery of the avermectin family of compounds, the forerunner of ivermectin. The latter has come to decrease the occurrence of lymphatic filariasis and onchoceriasis.[51]

Since 1988, ivermectin has been provided free of charge for use in humans by endemic areas.[50]

Society and culture

[49], an American physician of tropical medicine.Richard P. Strong Ridley first postulated that the disease was brought by the slave trade. The international scientific community was initially skeptical of Hisette’s findings, but they were confirmed by the Harvard African Expedition of 1934, lead by [48], who also made extensive observations on onchocerciasis patients in north west Ghana, publishing his findings in 1945.Harold Ridley Blacklock and Strong had thought the African worm did not affect the eyes, but Hissette reported that 50% of patients with onchocerciasis near the Sankuru river in the Belgian Congo had eye disease and 20% were blind. Hisette Isolated the microfilariae from an enucleated eye and described the typical chorioretinal scarring, later called the “Hissette-Ridley fundus” after another ophthalmologist, [47] Some of the patients reported seeing tangled threads or worms in their vision, which were microfilariae moving freely in the aqueous humor of the anterior chamber of the eye.[46]. Scottish physician Donald Blacklock of the Simulium Robles hypothesized that the vector of the disease was the day-biting black fly,

Rodolfo Robles and Rafael Pacheco in Guatemala first mentioned the ocular form of the disease in the Americas about 1915. They described a tropical worm infection with adult Onchocerca that included inflammation of the skin, especially the face (‘erisipela de la costa’), and eyes.[42] The disease, commonly called the “filarial blinding disease”, and later referred to as “Robles disease”, was common among coffee plantation workers. Manifestations included subcutaneous nodules, anterior eye lesions, and dermatitis. Robles sent specimens to Émile Brumpt, a French parasitologist, who named it O. caecutiens in 1919, indicating the parasite caused blindness (Latin “caecus” meaning blind).[43] The disease was also reported as being common in Mexico.[44] By the early 1920s, it was generally agreed that the filaria in Africa and Central America were morphologically indistinguishable and the same as that described by O’Neill 50 years earlier.

[41] Onchocerca originated in Africa and was probably exported to the Americas by the slave trade, as part of the

History

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.[36]

About 37 million people are infected with this parasite;[33] about 300,000 of those had been permanently blinded.[34] As of 2008, about 99% of onchocerciasis cases occurred in Africa.[35] Onchocerciasis is currently endemic in 30 African countries, Yemen, and isolated regions of South America.[36] 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,[37] 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.[38]

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

Epidemiology

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.[26]

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.[26] 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.[26] 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.[30][31][32]

Ivermectin

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.[27][28] 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.[29] However, doxycycline treatment requires daily dosing for at least four to six weeks, making it more difficult to administer in the affected areas.[26]

Antibiotics

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.[26]

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.

The burden of onchocerciasis: children leading blind adults in Africa

Treatment

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.

In 1992, the Onchocerciasis Elimination Programme for the Americas, which also relies on ivermectin, was launched.[20] On July 29, 2013, the Colombia had become the first country in the world to eliminate the parasitic disease onchocerciasis.[21] In September 2015, the Onchocerciasis Elimination Program for the Americas announced that onchocerciasis only remained in a remote region on the border of Brazil and Venezuela.[22][23] The area is home to the Yanomami indigenous people. The first countries to receive verification of elimination were Colombia in 2013, Ecuador in 2014, and Mexico in 2015.[24] Guatemala has submitted a request for verification. The key factor in elimination is mass administration of the antiparasitic drug ivermectin. The initial projection was that the disease would be eliminated from remaining foci in the Americas by 2012.[25]

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.[19] In 2015, WHO was facilitating launch of an elimination program in Yemen.

[18]

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