Onchocerciasis
Encyclopedia
Onchocerciasis also known as river blindness and Robles' disease, is a parasitic disease
caused by infection by Onchocerca volvulus
, a nematode
(roundworm). Onchocerciasis is the world's second-leading infectious cause of blindness
. It is not the nematode, but its endosymbiont, Wolbachia
pipientis, that causes the severe inflammatory response that leaves many blind. 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
.
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
. An estimated 18 million people suffer from onchocerciasis, with approximately 270,000 cases of blindness related to the infection.
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 microfilaria
e in 1917.
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 larva
e (microfilaria
e) in infected people, and it prevents transmission for many months in the remaining population. 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.
Erisipela de la costa
Mal morando
Sowda
Additionally, the various skin changes associated with onchocerciasis may be described as follows:
Leopard skin
Elephant skin
Lizard skin
s 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.
Skin involvement typically consists of intense itching, swelling, and inflammation. A grading system has been developed to categorize the degree of skin involvement:
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..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.
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.
In 1992, the Onchocerciasis Elimination Programme for the Americas (OEPA), which also relies on ivermectin, was launched.
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.
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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.
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 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. However, doxycycline treatment requires daily dosing for at least four to six weeks, making it more difficult to administer in the affected areas.
. The drug binds to and activates glutamate-gated chloride channels (GluCls). 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
(IPSP). 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.
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.
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. A clinical trial of another antiparasitic agent, moxidectin
(manufactured by Wyeth
), began on July 1, 2009 (NCT00790998).
. As of 2008, about 18 million people were infected with this parasite; about 300,000 had been permanently blinded. Onchocerciasis is currently endemic in 30 African countries, Yemen
, and isolated regions of South America. 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. 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.
s, 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.
Parasitic disease
A parasitic disease is an infectious disease caused or transmitted by a parasite. Many parasites do not cause diseases. Parasitic diseases can affect practically all living organisms, including plants and mammals...
caused by infection by Onchocerca volvulus
Onchocerca volvulus
Onchocerca volvulus is a nematode that causes onchocerciasis or "river blindness" mostly in Africa. Long-term corneal inflammation, or keratitis, leads to thickening of the corneal stroma which ultimately leads to blindness. Humans are the only definitive host for O. volvulus. The intermediate host...
, a nematode
Nematode
The nematodes or roundworms are the most diverse phylum of pseudocoelomates, and one of the most diverse of all animals. Nematode species are very difficult to distinguish; over 28,000 have been described, of which over 16,000 are parasitic. It has been estimated that the total number of nematode...
(roundworm). Onchocerciasis is the world's second-leading infectious cause of blindness
Blindness
Blindness is the condition of lacking visual perception due to physiological or neurological factors.Various scales have been developed to describe the extent of vision loss and define blindness...
. It is not the nematode, but its endosymbiont, Wolbachia
Wolbachia
Wolbachia is a genus of bacteria which infects arthropod species, including a high proportion of insects , as well as some nematodes. It is one of the world's most common parasitic microbes and is possibly the most common reproductive parasite in the biosphere...
pipientis, that causes the severe inflammatory response that leaves many blind. The parasite is transmitted to humans through the bite of a black fly
Black fly
A black fly is any member of the family Simuliidae of the Culicomorpha infraorder. They are related to the Ceratopogonidae, Chironomidae, and Thaumaleidae. There are over 1,800 known species of black flies . Most species belong to the immense genus Simulium...
of the genus Simulium
Simulium
Simulium is a genus of black flies, which may transmit diseases such as onchocerciasis . It is a large genus with several hundred species, and 41 sub-genera....
. The larval nematodes spread throughout the body. When the worms die, their Wolbachia symbionts are released, triggering a host immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
response that can cause severe itching, and can destroy optical tissue in the eye
Human eye
The human eye is an organ which reacts to light for several purposes. As a conscious sense organ, the eye allows vision. Rod and cone cells in the retina allow conscious light perception and vision including color differentiation and the perception of depth...
.
The vast majority of infections occur in sub-Saharan Africa
Sub-Saharan Africa
Sub-Saharan Africa as a geographical term refers to the area of the African continent which lies south of the Sahara. A political definition of Sub-Saharan Africa, instead, covers all African countries which are fully or partially located south of the Sahara...
, although cases have also been reported in Yemen
Yemen
The Republic of Yemen , commonly known as Yemen , is a country located in the Middle East, occupying the southwestern to southern end of the Arabian Peninsula. It is bordered by Saudi Arabia to the north, the Red Sea to the west, and Oman to the east....
and isolated areas of Central
Central America
Central America is the central geographic region of the Americas. It is the southernmost, isthmian portion of the North American continent, which connects with South America on the southeast. When considered part of the unified continental model, it is considered a subcontinent...
and South America
South America
South America is a continent situated in the Western Hemisphere, mostly in the Southern Hemisphere, with a relatively small portion in the Northern Hemisphere. The continent is also considered a subcontinent of the Americas. It is bordered on the west by the Pacific Ocean and on the north and east...
. An estimated 18 million people suffer from onchocerciasis, with approximately 270,000 cases of blindness related to the infection.
In 1915, Dr. Rodolfo Robles
Rodolfo Robles
Rodolfo Robles was a Guatemalan physician and philanthropist. He was the first to describe Robles Disease -Biography:Rodolfo Robles was born in Quetzaltenango, Guatemala...
Valverde's study on patients with river blindness in Guatemala
Guatemala
Guatemala is a country in Central America bordered by Mexico to the north and west, the Pacific Ocean to the southwest, Belize to the northeast, the Caribbean to the east, and Honduras and El Salvador to the southeast...
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
Simulium
Simulium is a genus of black flies, which may transmit diseases such as onchocerciasis . It is a large genus with several hundred species, and 41 sub-genera....
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
Dermatitis
-Etymology:Dermatitis derives from Greek derma "skin" + -itis "inflammation" and genetic disorder.-Terminology:There are several different types of dermatitis. The different kinds usually have in common an allergic reaction to specific allergens. The term may describe eczema, which is also called...
, and microfilaria
Microfilaria
The microfilaria is a stage in the life cycle of certain parasitic nematodes in the family Onchocercidae. In these species, the adults live in the circulatory system of vertebrates while the early larval stages develop in blood-feeding arthropod vectors...
e in 1917.
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 larva
Larva
A larva is a distinct juvenile form many animals undergo before metamorphosis into adults. Animals with indirect development such as insects, amphibians, or cnidarians typically have a larval phase of their life cycle...
e (microfilaria
Microfilaria
The microfilaria is a stage in the life cycle of certain parasitic nematodes in the family Onchocercidae. In these species, the adults live in the circulatory system of vertebrates while the early larval stages develop in blood-feeding arthropod vectors...
e) in infected people, and it prevents transmission for many months in the remaining population. Other drugs are also available, including the tetracycline-class antibiotic doxycycline
Doxycycline
Doxycycline INN is a member of the tetracycline antibiotics group, and is commonly used to treat a variety of infections. Doxycycline is a semisynthetic tetracycline invented and clinically developed in the early 1960s by Pfizer Inc. and marketed under the brand name Vibramycin. Vibramycin...
, which kills the Wolbachia and renders the female nematodes sterile. The removal of the palpable nodules is common in Guatemala, Ecuador, and Mexico.
Classification
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 erythemaErythemaErythema is redness of the skin, caused by hyperemia of the capillaries in the lower layers of the skin. It occurs with any skin injury, infection, or inflammation...
and itching. 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.
Mal morando
- This cutaneous condition is characterized by inflammationInflammationInflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
accompanied by hyperpigmentationHyperpigmentationIn dermatology, hyperpigmentation is the darkening of an area of skin or nails caused by increased melanin.-Causes:Hyperpigmentation may be caused by sun damage, inflammation, or other skin injuries, including those related to acne vulgaris...
.
Sowda
- A cutaneous condition, it is a localized type of onchocerciasis.
Additionally, the various skin changes associated with onchocerciasis may be described as follows:
Leopard skin
- A term referring to the spotted depigmentationDepigmentationDepigmentation is the lightening of the skin, or loss of pigment. Depigmentation of the skin can be caused by a number of local and systemic conditions. The pigment loss can be partial or complete...
of the skin that may occur with onchocerciasis
Elephant skin
- A term used to describe the thickening of human skin that may be associated with onchocerciasis
Lizard skin
- A term used to describe the thickened, wrinkled skin changes that may result with onchocerciasis
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:- 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 7 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 twelve 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.
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. 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. Wolbachia species have been found to be endosymbiontEndosymbiont
An endosymbiont is any organism that lives within the body or cells of another organism, i.e. forming an endosymbiosis...
s 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.
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 papulePapuleA papule is a circumscribed, solid elevation of skin with no visible fluid, varying in size from a pinhead to 1 cm.With regard to the quote "...varying in size from a pinhead to 1cm," depending on which text is referenced, some authors state the cutoff between a papule and a plaque as 0.5cm,...
s, - Chronic papular onchodermatitis - larger papules, resulting in hyperpigmentation,
- Lichenified onchodermatitis - hyperpigmented papules and plaques, with edemaEdemaEdema or oedema ; both words from the Greek , oídēma "swelling"), formerly known as dropsy or hydropsy, is an abnormal accumulation of fluid beneath the skin or in one or more cavities of the body that produces swelling...
, LymphadenopathyLymphadenopathyLymphadenopathy is a term meaning "disease of the lymph nodes." It is, however, almost synonymously used with "swollen/enlarged lymph nodes". It could be due to infection, auto-immune disease, or malignancy....
, 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. The microfilariae migrate to the surface of the cornea
Cornea
The cornea is the transparent front part of the eye that covers the iris, pupil, and anterior chamber. Together with the lens, the cornea refracts light, with the cornea accounting for approximately two-thirds of the eye's total optical power. In humans, the refractive power of the cornea is...
. Punctate keratitis
Keratitis
Keratitis is a condition in which the eye's cornea, the front part of the eye, becomes inflamed. The condition is often marked by moderate to intense pain and usually involves impaired eyesight.-Types:...
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
Opacity (optics)
Opacity is the measure of impenetrability to electromagnetic or other kinds of radiation, especially visible light. In radiative transfer, it describes the absorption and scattering of radiation in a medium, such as a plasma, dielectric, shielding material, glass, etc...
. 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..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
Diethylcarbamazine
Diethylcarbamazine is an anthelmintic drug that does not resemble other antiparasitic compounds. It is a synthetic organic compound which is highly specific for several parasites and does not contain any toxic metallic elements.-Uses:...
(DEC). Mazzotti reactions can be life-threatening, and are characterized by fever
Fever
Fever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...
, urticaria
Urticaria
Urticaria is a kind of skin rash notable for pale red, raised, itchy bumps. Hives is frequently caused by allergic reactions; however, there are many non-allergic causes...
, swollen and tender lymph nodes
Lymphadenopathy
Lymphadenopathy is a term meaning "disease of the lymph nodes." It is, however, almost synonymously used with "swollen/enlarged lymph nodes". It could be due to infection, auto-immune disease, or malignancy....
, tachycardia
Tachycardia
Tachycardia comes from the Greek words tachys and kardia . Tachycardia typically refers to a heart rate that exceeds the normal range for a resting heart rate...
, hypotension
Hypotension
In physiology and medicine, hypotension is abnormally low blood pressure, especially in the arteries of the systemic circulation. It is best understood as a physiologic state, rather than a disease. It is often associated with shock, though not necessarily indicative of it. Hypotension is the...
, arthralgias, oedema, and abdominal pain
Abdominal pain
Abdominal pain can be one of the symptoms associated with transient disorders or serious disease. Making a definitive diagnosis of the cause of abdominal pain can be difficult, because many diseases can result in this symptom. Abdominal pain is a common problem...
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.
Prevention
Various control programs aim to stop onchocerciasis from being a public healthPublic health
Public health is "the science and art of preventing disease, prolonging life and promoting health through the organized efforts and informed choices of society, organizations, public and private, communities and individuals" . It is concerned with threats to health based on population 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
Larvicide
A larvicide is an insecticide that is specifically targeted against the larval life stage of an insect. Their most common use is against mosquitoes...
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
World Bank
The World Bank is an international financial institution that provides loans to developing countries for capital programmes.The World Bank's official goal is the reduction of poverty...
, the United Nations Development Programme
United Nations Development Programme
The United Nations Development Programme is the United Nations' global development network. It advocates for change and connects countries to knowledge, experience and resources to help people build a better life. UNDP operates in 177 countries, working with nations on their own solutions to...
and the UN Food and Agriculture Organization
Food and Agriculture Organization
The Food and Agriculture Organization of the United Nations is a specialised agency of the United Nations that leads international efforts to defeat hunger. Serving both developed and developing countries, FAO acts as a neutral forum where all nations meet as equals to negotiate agreements and...
, 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 (OEPA), which also relies on ivermectin, was launched.
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.
Treatment
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.
Antibiotics
For the treatment of individuals, doxycyclineDoxycycline
Doxycycline INN is a member of the tetracycline antibiotics group, and is commonly used to treat a variety of infections. Doxycycline is a semisynthetic tetracycline invented and clinically developed in the early 1960s by Pfizer Inc. and marketed under the brand name Vibramycin. Vibramycin...
is used to kill the Wolbachia
Wolbachia
Wolbachia is a genus of bacteria which infects arthropod species, including a high proportion of insects , as well as some nematodes. It is one of the world's most common parasitic microbes and is possibly the most common reproductive parasite in the biosphere...
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 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
Rifampicin
Rifampicin or rifampin is a bactericidal antibiotic drug of the rifamycin group. It is a semisynthetic compound derived from Amycolatopsis rifamycinica ...
, 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
Ivermectin kills the parasite by interfering with the nervous system and muscle function, in particular, by enhancing inhibitory neurotransmissionNeurotransmission
Neurotransmission , also called synaptic transmission, is the process by which signaling molecules called neurotransmitters are released by a neuron , and bind to and activate the receptors of another neuron...
. The drug binds to and activates glutamate-gated chloride channels (GluCls). These channels, present in neurons and myocytes, are not invertebrate
Invertebrate
An invertebrate is an animal without a backbone. The group includes 97% of all animal species – all animals except those in the chordate subphylum Vertebrata .Invertebrates form a paraphyletic group...
-specific, but are protected in vertebrates from the action of ivermectin by the blood-brain barrier
Blood-brain barrier
The blood–brain barrier is a separation of circulating blood and the brain extracellular fluid in the central nervous system . It occurs along all capillaries and consists of tight junctions around the capillaries that do not exist in normal circulation. Endothelial cells restrict the diffusion...
. Ivermectin is thought to irreversibly activate these channel receptors in the worm, eventually causing an inhibitory postsynaptic potential
Inhibitory postsynaptic potential
An inhibitory postsynaptic potential is a synaptic potential that decreases the chance that a future action potential will occur in a postsynaptic neuron or α-motoneuron...
(IPSP). The chance of a future action potential
Action potential
In physiology, an action potential is a short-lasting event in which the electrical membrane potential of a cell rapidly rises and falls, following a consistent trajectory. Action potentials occur in several types of animal cells, called excitable cells, which include neurons, muscle cells, and...
occurring in synapses between neurons decreases and the nematodes experience flaccid paralysis
Flaccid paralysis
Flaccid paralysis is a clinical manifestation characterized by weakness or paralysis and reduced muscle tone without other obvious cause .-Polio:...
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.
Since 1988, ivermectin has been provided free of charge for use in humans by Merck
Merck & Co.
Merck & Co., Inc. , also known as Merck Sharp & Dohme or MSD outside the United States and Canada, is one of the largest pharmaceutical companies in the world. The Merck headquarters is located in Whitehouse Station, New Jersey, an unincorporated area in Readington Township...
through the Mectizan donation program (MDP). The MDP works together with ministries of health and nongovernmental development organisations, such as the World Health Organization
World Health Organization
The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...
, to provide free ivermectin to those who need it in endemic
Endemic (epidemiology)
In epidemiology, an infection is said to be endemic in a population when that infection is maintained in the population without the need for external inputs. For example, chickenpox is endemic in the UK, but malaria is not...
areas.
A study of 2501 people in Ghana
Ghana
Ghana , officially the Republic of Ghana, is a country located in West Africa. It is bordered by Côte d'Ivoire to the west, Burkina Faso to the north, Togo to the east, and the Gulf of Guinea to the south...
showed the prevalence rate doubled between 2000 and 2005 despite treatment, suggesting the parasite is developing resistance to the drug. A clinical trial of another antiparasitic agent, moxidectin
Moxidectin
Moxidectin is a parasiticide used for the prevention and control of heartworm and intestinal worms, and can be found in treatments prescribed for animals such as dogs, cats, horses, cattle and sheep. It is also used for the prevention of red mite in caged birds...
(manufactured by Wyeth
Wyeth
Wyeth, formerly one of the companies owned by American Home Products Corporation , was a pharmaceutical company. The company was based in Madison, New Jersey, USA...
), began on July 1, 2009 (NCT00790998).
Epidemiology
About 99% of onchocerciasis cases occur in AfricaAfrica
Africa is the world's second largest and second most populous continent, after Asia. At about 30.2 million km² including adjacent islands, it covers 6% of the Earth's total surface area and 20.4% of the total land area...
. As of 2008, about 18 million people were infected with this parasite; about 300,000 had been permanently blinded. Onchocerciasis is currently endemic in 30 African countries, Yemen
Yemen
The Republic of Yemen , commonly known as Yemen , is a country located in the Middle East, occupying the southwestern to southern end of the Arabian Peninsula. It is bordered by Saudi Arabia to the north, the Red Sea to the west, and Oman to the east....
, and isolated regions of South America. 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. 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
Who
Who may refer to:* Who , an English-language pronoun* who , a Unix command* Who?, one of the Five Ws in journalism- Art and entertainment :* Who? , a 1958 novel by Algis Budrys...
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.
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 ratCotton rat
A cotton rat is any member of the rodent genus Sigmodon. They are called cotton rats because they build their nests out of cotton, and can damage cotton crops. Cotton rats have small ears and dark coats, and are found in North and South America....
s, has been found to fully develop in BALB/c
BALB/c
BALB/c is an albino, laboratory-bred strain of the House Mouse from which a number of common substrains are derived. Now over 200 generations from their origin in New York in 1920, BALB/c mice are distributed globally, and are among the most widely used inbred strains used in animal...
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.
See also
- Carter CenterCarter CenterThe Carter Center is a nongovernmental, not-for-profit organization founded in 1982 by former U.S. President Jimmy Carter and his wife Rosalynn Carter. In partnership with Emory University, The Carter Center works to advance human rights and alleviate human suffering...
River Blindness Program - List of parasites (human)
- Neglected diseasesNeglected DiseasesThe neglected diseases are a group of tropical infections which are especially endemic in low-income populations in developing regions of Africa, Asia, and the Americas. Different organizations define the set of diseases differently...
- Rodolfo RoblesRodolfo RoblesRodolfo Robles was a Guatemalan physician and philanthropist. He was the first to describe Robles Disease -Biography:Rodolfo Robles was born in Quetzaltenango, Guatemala...
- United Front Against RiverblindnessUnited Front Against RiverblindnessUnited Front Against Riverblindness is a Non-Governmental Development Organization that provides technical, managerial and financial support for the elimination of riverblindness, or onchocerciasis, in the Kasongo region of Maniema province in the east-southern region of the Democratic Republic...
External links
- Onchocerciasis, Southern Sudan Medical Journal
- 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