Related Terms

• APOC, black fly, Buffalo gnats, doxycycline, EIA, elephant skin, ELISA, endemic, endosymbiont, filariasis, garlic, hanging groin, immunochromotagraphic test, intron, ivermectin, Ivexterm®, keratitis, larva, leopard skin, lizard skin, Mazzotti test, Mectizan®, microfilariae, mitochondrial genome, moxidectin, nematode, nodulectomy, OCP, OEPA, onchocerciasis, onchodermatitis, oncocercomas, O. volvulus, parasite, PCR, polymerase chain reaction, pool screening, propolis, prayer, punctate keratitis, repeated sequence, Rapid-Format Antibody card test, river blindness, Robles' disease, sclerosing keratitis, Simulium, skin-snip, slit-lamp test, sowda, Stromectol®, ungulates, vector, Wolbachia endobacteria.

Background

• Onchocerca volvulus is a nematode, a roundworm parasite that belongs to the Filarioidea superfamily. It is endemic (native) to sub-Saharan Africa, Yemen, Mexico, Guatemala, Colombia, Ecuador, Brazil, and Venezuela. It causes an infection known as river blindness or onchocerciasis. Nematodes are simple multicellular organisms that belong to the phylum Nematoda.

• O. volvulus is an obligate parasite of humans, meaning that it cannot live independently of its human host. It is notable that humans are the only definitive hosts for O. volvulus, meaning that it can mature and reproduce in humans only. Most of the other species of Onchocerca are parasites of ungulates, groups of mammals that use the tips of their toes to support their body weight, such as the horse, zebra, or donkey.

• The female worms measure 33-50 centimeters in length and 270-400 micrometers in diameter, while males measure 19-42 millimeters long and 130-210 micrometers around. The parasite O. volvulus contains three distinct genomes (collections of hereditary information): nuclear, mitochondrial, and intracellular (within the cell) endosymbionts of the genus Wolbachia. Endosymbionts are organisms that live in the body of other organisms without causing any harm to the host. Wolbachia is a genus of bacteria that infects arthropods, the largest collection of living organisms, including 75% of all insects.

• Onchocerca volvulus causes a parasitic infection known as onchocerciasis or river blindness. Onchocerciasis, first described in 1917, is the second leading cause of blindness from infectious disease in the world. The disease is transmitted to humans by the bite of Buffalo gnats, or black flies, that belong to the genus Simulium. The disease is known as river blindness, because the black flies breed in rivers and cause blindness in people who live near rivers. The fly breeds in fast-flowing rivers, that is, in well-oxygenated water, because the larvae have an aquatic stage in which they require high levels of oxygen to survive.

• When a black fly takes a blood meal from an infected individual, it ingests the microfilariae (infective larvae of the parasite) found in the layer of tissue just under the skin. The larvae mature in the fly and are later found in its saliva. When a black fly with the infective larvae bites another person, or host, the infected saliva passes into the blood of the host, causing infection. The larvae then enter the host's subcutaneous tissue, where they migrate and lodge in nodules (hard spherical structures, or bumps) and slowly mature into adult worms.

• River blindness is considered an epidemic in more than 25 countries across the central part of Africa. Researchers estimate that about 18 million people worldwide are infected with river blindness each year. Of those infected, an estimated 6.5 million suffer from severe itching or dermatitis, 770,000 suffer serious visual impairment, and 270,000 are blind. The disease generally affects more men than women, which may be attributed to the increased exposure of farmers and fishermen to breeding flies.

Risk Factors

• Onchocerca volvulus is a nematode, a type of parasite that belongs to the Filarioidea superfamily. It is endemic (native) to sub-Saharan Africa, Yemen, Mexico, Guatemala, Colombia, Ecuador, Brazil, and Venezuela.

• River blindness is considered an epidemic in more than 30 countries across the central part of Africa. Researchers estimate that about 18 million people are infected with river blindness each year worldwide. Of those infected, an estimated 6.5 million suffer from severe itching or dermatitis, 770,000 suffer serious visual impairment, and 270,000 are blind. The disease generally affects more men than women, which may be attributed to the increased exposure of farmers and fishermen to breeding flies.

• People at risk of developing the disease include adventure travelers, missionaries, and people living in agricultural villages located near rapidly flowing streams or rivers.

Causes

• The life cycle of the parasite spans two different hosts: black flies and humans. The life cycle is initiated when the parasitized female black fly takes a blood meal from an infected individual and ingests the microfilariae (infective larvae) of the parasite, found in the dermis (the layer of tissue just under the skin). While adult male flies feed on plant juices, only the female flies take blood meals by biting humans. Therefore, only the female flies carry the infective larvae. The microfilariae penetrate the gut and migrate to the thoracic flight muscles (the muscles in the thorax used in flying) of the black fly and enter their first larval stage (L1) within 28 hours after the fly's blood meal.

• Within 96 hours, the larvae mature into the second larval stage (L2), then they migrate to the proboscis, the protruding mouth part of insects used for piercing or sucking, and by day 7, they mature to the third larval stage (L3) in the fly's saliva. When the black fly bites another person, or host, saliva containing the L3 larvae of the parasite passes into the blood of the host and migrates to the tissue just under the skin to form nodules. Nodules are hard spherical structures, or bumps, under the skin.

• Over a period of 6-12 months, the larvae mature into adult worms. Female and male adult worms mate to produce millions of microfilariae, tiny worms that live together, tightly coiled up in nodules just under the skin. Nodules normally occur around the hips, knees, chest, and lymphatics of connective tissue. Lymphatics are small thin channels similar to blood vessels that carry lymph , or tissue fluid, from the body tissues to the circulatory system.

• New worms form new nodules or accumulate in existing nodules. The male worms may migrate into the blood vessels via the lymphatics between nodules and mate with female worms, because the females produce a pheromone, a chemical that attracts males. After mating, females release 1,000-3,000 eggs daily. The eggs then mature into microfilariae (300 millimeters in length and 0.8 millimeters in diameter), which are released from the female's body.

• The life cycle is complete once a black fly ingests these microfilariae in a blood meal from the skin of an infected person. The duration of the maturation of microfilariae to stage 3 larvae in the black fly is 1-3 weeks. The life span of the adult worm can be as long as 15 years, and that of microfilariae 1-2 years. Every female worm can reproduce millions of microfilariae during a lifetime, which wait in the subcutaneous nodules for a black fly to ingest them. If they are not ingested, they die within the same host, leading to an increase in inflammation and infection.

Signs and Symptoms

• General: The incubation period of onchocerciasis ranges from nine to 24 months following the bite of a black fly carrying the infective microfilariae. The incubation period is the time between exposure to a disease-causing organism and the first appearance of signs and symptoms.

• The adult worms are harmless compared with the microfilariae. The microfilariae cause intense inflammatory reactions in the skin, which lead to skin rashes, lesions, pruritus (intense itching), and changes in skin color. The microfilariae have the potential to invade other organs, but most commonly invade the eye directly, because it is a relatively easy target. Eye disease is caused by inflammatory responses to the microfilariae as they migrate through the eye.

• The microfilarial invasion into the eye is common in certain regions of Africa, Yemen, and Central and South America, such as Mexico, Guatemala, Colombia, Ecuador, Brazil, and Venezuela. Living worms cause little damage; however, their death triggers a localized inflammation that may lead to blindness. The mechanisms that protect worms from the host's immune response are still largely unknown.

• Skin lesions: The inflammatory lesions (called onchodermatitis) on the skin initially appear as small, round, red bumps on the skin, usually 0.5 centimeters or less in diameter, and they are accompanied by intense itching. Later, the elastic fibers and structural elements of the skin break down, causing the skin to appear thin and wrinkled like a "lizard's skin." Loss of skin color, or pigmentation, in the affected areas is also common in the later stages of infection and is known as "leopard skin." The skin may also thicken and appear as "elephant skin." Skin changes caused by the parasite vary from region to region.

• Eye: O. volvulus commonly affects the eye in infected individuals, leading to blindness. The blindness rates have reached up to 40% in the adult population of endemic areas. However, control of black fly breeding and treatment with an antiparasitic drug, ivermectin (e.g., Stromectol®), has considerably reduced the incidence of new infections. Studies are currently being conducted to evaluate the effect of ivermectin in preventing disease.

Diagnosis

• A parasitic infection such as the one caused by Onchocerca volvulus is suspected if a patient has signs and symptoms of an infection and lives in or has visited an area known to have the parasite. A diagnosis is confirmed after the parasite is identified in the body. Samples of blood, urine, and other bodily fluids may be analyzed for the presence of the parasite.

• Physical examination: A physical examination involves first considering the individual's demographic profile or travel history to an endemic area. Another part of the physical examination is palpation, in which the physician feels the affected part of the body with the hands to detect the subcutaneous nodules that harbor the parasite. Nodule palpation is a major diagnostic tool used to determine the prevalence of the O. volvulus infection. This method is used to identify communities that are at risk of developing the infection and selecting them for mass drug administration. However, this method has not been quantified in terms of sensitivity and its predictive capabilities, owing to huge differences in intra- and interindividual variability. Also, this method is useful only in highly endemic areas. Further research is required to develop new methods of diagnosing the infection, which may aid in long-term monitoring in low endemic as well as highly endemic areas.

• Skin snips: In this technique, a very small sample of skin is removed from the affected region, for example, the shoulder or hip, using a razor blade, without drawing any blood. Then the skin is placed in a salt solution or incubated (i.e., maintaining environmental conditions ideal for growth) in a cultured medium for four hours. The number of microfilariae is calculated by counting the larvae under the microscope. Although the method is specific, it is unpopular owing to its invasiveness. Also, it has low sensitivity, especially in mild or prepatent infection, a period between the infection with the parasite and the ability of the organism to be detected by a diagnostic test.

• Nodulectomy: Adult worms may be detected in nodules located just under the skin surface by surgically removing the nodules. This approach might also be used to treat onchocerciasis. However, this method is invasive and may not be useful in detecting the infection in a large population.

• Slit-lamp exam: A slit lamp is a low-power microscope with a light source that may be used to see structures in the front part of the eye. The examination using the slit lamp may reveal free floating microfilariae in the anterior chamber of the eye, making diagnosis of the infection possible. The presence of microfilariae indicates that the infection has started. However, if diagnosed and treated in the initial stages of infection, as indicated by mild changes in the eye, vision may be restored. If blindness has occurred by the time of diagnosis, however, vision cannot be restored.

• Mazzotti test: The Mazzotti test is usually performed when the skin snip test result is negative. An oral dose of five milligrams of diethylcarbamazine (DEC), a drug used to treat worm infections, is administered to individuals believed to be infected, because the drug inhibits neuromuscular transmission in nematodes. Neuromuscular transmission is the mechanism whereby motor nerve impulses start muscle contraction. With neuromuscular transmission inhibited, the worms die, leading to inflammatory reactions and intense itching, collectively known as the Mazzotti reaction, in individuals within two hours, if the person has onchocerciasis. Corticosteroids may be prescribed to alleviate the itching within a few days. However, this is not the preferred method of treatment because the drug may cause severe whole-body reactions such as fever, pain, swelling in the joints, and eye complications.

• DEC patch test: The DEC patch test was developed as an alternative to the Mazzotti test to avoid the side effects of DEC. This method involves the application of a gauze pad soaked in a 20% solution of DEC on the hip, one of the places on the body where the microfilariae accumulate. The skin on the hip is later examined for the presence of skin inflammation, which will be observed if the individual is infected. This test is noninvasive and may be used to detect the re-emergence of the infection. However, it is not as sensitive as the surgical removal of nodules.

• ELISA (enzyme-linked immunosorbent assay) or EIA: ELISA is a diagnostic technique used to detect the presence of an antibody or antigen in a blood sample. An antigen is a foreign substance capable of stimulating an immune response in the body. Antibodies are proteins that recognize and bind to specific antigens, or foreign substances in the body.

• This test is done on serum or blood to detect the presence of O. volvulus antigens and has a high sensitivity and specificity. Sensitivity measures the proportion of people who have the infection and are correctly identified, and specificity measures the proportion of people who do not have the infection and are correctly identified. However, the test is not used widely, because it requires expensive laboratory equipment and is not able to distinguish between present and past infections. This is because once the antibodies are produced in the body, they will "remember" and protect the individual in case of future infection.

• Polymerase chain reaction (PCR): PCR, a laboratory molecular biology technique, is an automated process that generates a number of copies of a specific DNA sequence within a short time (around 45 minutes) in a controlled environment using specific reagents and enzymes. It is widely used to make multiple copies of minute quantities of biologic material to provide adequate specimens for laboratory study.

• This test helps identify the O. volvulus infection with a high rate of sensitivity. In this method, the parasite DNA sequences taken from skin-snip specimens are amplified by the PCR machine. Only a small portion of the superficial layer of the epidermis, a layer of the skin, is removed, because the PCR can amplify the DNA sequences from a small sample to help detect infection. This is the preferred method for identifying the parasite, because it is less invasive than other tests and has a high sensitivity. However, the high cost and complex technology of the PCR-based assay are the major disadvantages of this method. PCR may also be used to detect the presence of O. volvulus DNA in experimentally infected flies. The test is sensitive enough to identify one infected Simulium fly in a pool of 100 uninfected flies.

• Rapid-format antibody card tests: The rapid-format antibody card test, also called an immunochromatographic test, is simple and similar to ELISA. It detects antibodies to the O. volvulus antigen by using a drop of blood from the finger of an individual suspected of being infected with onchocerciasis and testing it on a card designed to change color when the antibodies react with the O. volvulus antigen; the test is positive if the card shows a color change. This technique is faster and less expensive than ELISA. The limitations of this test are similar to those of ELISA, in that past and present infections cannot be distinguished. Several previous studies have indicated good specificity and sensitivity for this test, so it may have the potential to be used as a simple tool for identifying the parasite at the patient's bedside or for mass screenings.

Complications

• General: O. volvulus causes an infection known as river blindness, or onchocerciasis. The incubation period of onchocerciasis ranges from nine to 24 months following the bite of a black fly carrying the infective microfilariae. The incubation period is the time between exposure to a disease-causing organism and the first appearance of signs and symptoms.

• Infection affects multiple organ systems, but skin and eye complications are the most common. The parasite causes a wide range of infections in humans, which include onchodermatitis (mild itching, skin rashes, and lesions); depigmentation (loss of skin pigmentation), lymphadenitis (enlarged lymph nodes); visual impairment; and, in some cases, blindness.

• Skin: The earliest signs of the infection are raised nodules, known as onchocercomas, which may be seen under the skin around areas of bony prominence such as the tip of the shoulder and the iliac crest of the hip. This may be caused by the larvae becoming immobilized in such locations, as they are trapped by the cells of the body's defense mechanism.

• Skin involvement commonly involves intense itching, swelling, and inflammation. In the early stages, the skin lesions appear as small, round, red bumps, usually 0.5 centimeters or less in diameter, and are accompanied by intense itching.

• The lesions, also known as papules, then slightly increase in size, followed by an increase in pigmentation, or hyperpigmentation . This stage is called chronic papular dermatitis. The infection progresses to lichenified dermatitis, in which there is formation of hyperpigmented plaques with swelling, along with lymph node swelling. A plaque is an elevated area of skin about 0.5 centimeters in diameter with a broad flat surface. The itching and hyperpigmentation experienced by those infected in Yemen is known as sowda and often only occurs on one limb.

• In the next stage, the skin breaks down, slowly losing elasticity and resembling lizard's skin. The skin lesions further progress to cause a loss of skin pigmentation creating a "leopard skin" appearance and leading to the formation of redundant folds on the skin. Folds of inelastic skin and enlarged lymph nodes in the inguinal (groin) area of the body may cause a complication known as "hanging groin," especially in females.

• Eye: Eye complications occur because of the migration of microfilariae to the surface of the cornea, the transparent front part of the eye. This migration leads to punctate keratitis (snowflake opacities), the death of the cells on the surface of the cornea, which causes painful, watery eyes and blurred vision. Symptoms usually subside once the infection is treated.

• Additional eye complications may include anterior uveitis, in which the microfilariae invade other parts of the eye such as the iris and ciliary body, and they may cause a cataract, the inflammation and clouding of the lens of the eye. The iris is the round, colored part of the eye that adjusts pupil size and regulates the amount of light reaching the retina in the back of the eye. The ciliary body is a structure that releases a transparent liquid called the aqueous humor within the eye.

• If the infection persists for a long time, inflammation may develop in the cornea, causing opacity (preventing light from passing through the eye). This condition, sclerosing keratitis, causes decreased visual acuity, or clarity of vision. This may progress to cause opacity of the entire cornea and finally blindness. An average of 10% of all people with river blindness become permanently blind. One of the major complications of the infection is that the blindnesscausedby O. volvulus is irreversible.

• Associated infection with Wolbachia: Several studies have also found that microfilariae release antigens derived from Wolbachia and stimulate the innate defense mechanisms of infected individuals. This leads to inflammation in the affected region, such as the eye or certain areas of bony prominence, such as the shoulder and hip. Wolbachia is a genus of bacteria that infects arthropods such as insects and arachnids, which are endosymbionts of O. volvulus. Endosymbionts are organisms that live in the body of host organisms without causing it any harm.

Treatment

• Those infected by O. volvulus may need to consult an infectious disease specialist, ophthalmologist, and dermatologist to develop a well-rounded treatment plan.

• The primary treatment for O. volvulus infection is ivermectin, a broad-spectrum antiparasitic used against worms, mites, and some types of lice. The common brand names include Stromectol® in the United States, Mectizan® (Merck & Co., Inc.) in Canada, and Ivexterm® (Valeant Pharmaceuticals International) in Mexico.

• Ivermectin is given either by mouth or by injection at a dose of 150 micrograms per kilogram of body weight every 6-12 months for a duration of 16-18 years to suppress the microfilariae. The drug does not kill the adult worms, but it paralyzes the microfilariae (the most infective stage of the worm), thus preventing the occurrence of symptoms and temporarily suppressing reproduction of the worms. Currently there are no drugs that kill the adult worms.

• The development of drug resistance to ivermectin, a safe drug for mass treatment, by O. volvulus is a concern in effective treatment, because no other drug is as effective at controlling the disease.

• Adverse effects caused by ivermectin, although rare, may include eye irritation, fever, joint or muscle pain, rapid heartbeat, pruritus (itching), and adenopathy (enlarged lymph nodes) due to the dying microfilaria. Ivermectin may also cause edema and aggravated onchodermatitis in patients with sowda (severe dermatitis). Safety of use during pregnancy or breastfeeding is lacking.

• The antibiotic doxycycline may be added to the ivermectin treatment regimen to help kill Wolbachia bacteria. Doses studied include 100-200 milligrams daily for six weeks. Several studies have shown that microfilarial load and adult worms may be reduced using this combination treatment regimen. Nodulectomy, or the excision of nodules containing adult worms, may be curative for patients with minimal nodules so that all adult worms may be eliminated. However, the costly and invasive nature of this procedure limits its use. It may be used as an adjunct to ivermectin therapy.

Integrative Therapies

• Note: There is a lack of scientific evidence for the effect of integrative therapies on the prevention or treatment of Onchocerca volvulus. The therapies below have been studied for their effect on infections in general. They should be used only under the supervision of a qualified healthcare provider and should not be used in replacement of other proven therapies.

• Unclear or conflicting scientific evidence:

• Blessed thistle: Human research of blessed thistle as a treatment for bacterial infections is currently lacking. Laboratory studies report that blessed thistle (and chemicals contained in blessed thistle, such as cnicin and polyacetylene) may have activity against several types of bacterial infections and no effects on some types. Early studies report no activity of blessed thistle against herpes viruses, influenza, or poliovirus. Further evidence is necessary in this area before a firm conclusion can be drawn.

• Blessed thistle is generally considered to be safe when taken by mouth in recommended doses for short periods of time, with few reported side effects such as birth defects, bleeding, breathing problems, bruising, cancer of the nose or throat, increased production of stomach acid, itching, kidney disease, liver toxicity, skin rash, stomach discomfort, stomach ulcers, and vomiting. Allergic reactions to blessed thistle including rash may occur, as well as cross-sensitivity to mugwort and Echinacea. Cross-reactivity may also occur with bitter weed, blanket flower, Chrysanthemum, coltsfoot, daisy, dandelion, dwarf sunflower, goldenrod, marigold, prairie sage, ragweed, or other plants in the Asteraceae or Compositae family. Avoid if pregnant or breastfeeding.

• Cranberry: Limited laboratory research has examined the antibacterial activity of cranberry. Further research is warranted in this area.

• Avoid if allergic to cranberries, blueberries, or other plants of the Vaccinium species. Sweetened cranberry juice may affect blood sugar levels. Use cautiously with a history of kidney stones. Pregnant and breastfeeding women should avoid cranberry in higher amounts than what is typically found in foods.

• Lavender: Early laboratory studies suggest that lavender oils may have topical antibiotic activity. However, this has not been well tested in human studies.

• Avoid if allergic or hypersensitive to lavender. Avoid with a history of seizures, bleeding disorders, eating disorders (such as anorexia or bulimia), or anemia (low levels of iron). Avoid if pregnant or breastfeeding.

• Propolis: Propolis is a natural resin created by bees to make their hives. Propolis is made from the buds of conifer and poplar trees and combined with beeswax and other bee secretions. Animal and laboratory studies suggest that propolis may be a beneficial treatment for various types of bacterial infections. Additional research is needed to confirm these findings.

• Avoid if allergic or hypersensitive to propolis, black poplar (Populus nigra), poplar bud, bee stings, bee products, honey, or balsam of Peru. Severe allergic reactions have been reported. There has been one report of kidney failure with the ingestion of propolis that improved upon discontinuing therapy and deteriorated with re-exposure. Avoid if pregnant or breastfeeding because of the high alcohol content in some products.

• Seaweed, kelp, bladderwrack: Bladderwrack (Fucus vesiculosus) is a brown seaweed found along the northern coasts of the Atlantic and Pacific oceans and North and Baltic Seas. Another seaweed that grows alongside bladderwrack is Ascophyllum nodosum, and it is often combined with bladderwrack in kelp preparations. Laboratory research suggests that bladderwrack may have antibacterial activity. However, reliable human studies to support this use are currently lacking in the available literature.

• Avoid if allergic or hypersensitive to Fucus vesiculosus or iodine. Avoid with a history of thyroid disease, bleeding, acne, kidney disease, blood clots, nerve disorders, high blood pressure, stroke, or diabetes. Avoid if pregnant or breastfeeding.

• Selenium: Selenium is a mineral found in soil, water, and some foods. Preliminary research reports that selenium may be beneficial in the prevention of several types of infection, including recurrence of erysipelas (a bacterial skin infection associated with lymphedema) or Mycoplasma pneumonia. Further research is needed to confirm the effects of selenium for infection prevention.

• Avoid if allergic or hypersensitive to products containing selenium. Avoid with a history of nonmelanoma skin cancer. Selenium is generally regarded as safe for pregnant or breastfeeding women. However, animal research reports that large doses of selenium may lead to birth defects.

• Sorrel: There is currently not enough evidence on the proposed antibacterial effects of sorrel. More research is needed.

• Avoid large doses of sorrel, because there have been reports of toxicity and death. This may be because of the oxalate found in sorrel. Many sorrel tinctures contain high levels of alcohol and should be avoided when driving or operating heavy machinery. These sorrel formulations may cause nausea or vomiting when taken with the prescription drugs metronidazole (Flagyl®) or disulfiram (Antabuse®). Avoid if pregnant or breastfeeding.

Prevention

• Black flies usually bite during the day. Therefore, frequently used methods of preventing infection include using insecticides such as DEET (N,N-diethyl-meta-toluamide) and wearing long-sleeved shirts and pants, because black flies cannot bite through clothing. Individuals who plan to travel to areas where parasitic infections are common, such as Africa, Asia, the Middle East, South America, and Central America, should talk to a healthcare provider to learn how to reduce their risks of acquiring infections.

• Scientists who study insects, called entomologists, suggest that the black fly must be attacked at its vulnerable stage , that is, at the larval stage, using special insecticide compounds that kill the larvae in rivers where black flies are usually present. This technique is known as vector control, as the larvae are the vectors (carriers) of the infection.

• Mass control programs: Three internationally supported programs have been initiated in the past 30 years to eliminate onchocerciasis as a public health problem. They are the Onchocerciasis Control Programme in West Africa (OCP), the African Program for Onchocerciasis Control (APOC), and the Onchocerciasis Elimination Program in the Americas (OEPA). The life span of adult worms is about 15 years, so disease elimination programs should be conducted for at least 20 years.

• OCP: OCP was launched in 1974 and was instrumental in eliminating onchocerciasis as a public health problem in 11 countries of West Africa, covering more than 30 million people, across 1,200,000 square kilometers. This program, which successfully ended in December 2002, was a joint effort of the World Health Organization (WHO), the World Bank, the United Nations Development Programme (UNDP), and the United Nations Food and Agriculture Organization (FAO).

• For 14 years, the program involved spraying insecticides from helicopters and aircraft over black fly breeding sites to kill the larvae. In 1989, Merck & Co., Inc., donated Mectizan® (ivermectin) to be used with vector control to treat the disease. The highlights of the program include prevention of 600,000 cases of blindness, achievement of 18 million newborn children without the disease, and 25 million hectares of land safe for cultivation. These details were obtained by comparing the statistics of newly infected cases with infected cases that were cured from the 11 countries during the period from 1974 to 2002.

• APOC: APOC is a unique partnership that has brought together donors, 19 affected countries in Africa, nongovernmental development organizations (NGDOs), the private sector, and affected communities. It was initiated in 1995 following the success of OCP to eliminate onchocerciasis from 19 African nations that were not covered in OCP. The conditions are not viable for aerial spraying of larvicides, because of thick forests and great distances to cover. This approach is also not cost effective. Therefore, the program, which is still currently active, has distributed ivermectin tablets to all the affected communities.

• OEPA: Formed in 1996, the OPEA is a regional initiative to reduce illness and prevent the spread of river blindness in six endemic countries in South and Central America: Brazil, Colombia, Ecuador, Guatemala, Mexico, and Venezuela. The program, which is currently active, provides ivermectin mass treatment every six months and has eliminated eye lesions from onchocerciasis in nine of the 13 targets in the Americas.

Research

• Genetic marker: Understanding the genome of the parasite is important, because development of resistance to ivermectin, the safest drug for mass treatment of O. volvulus, could affect onchocerciasis control programs. Therefore, researchers have found that repeated treatment with ivermectin effects specific alleles (one of a set of alternative forms of a gene) of p-glycoprotein-like protein, which is associated with multidrug resistance. Hence, this protein may serve as a genetic marker for ivermectin resistance in O. volvulus.

• Drug development: Treatment with the antibiotic azithromycin against microfilariae and Wolbachia endobacteria of O. volvulus has been studied. In one study, azithromycin administered by mouth at 250 milligrams daily or 1,200 milligrams per week was not found suitable for treating onchocerciasis. However, further research is required to examine the effects of daily azithromycin in combination with such other drugs as doxycycline or rifampicin. Wolbachia is a genus of bacteria that infects arthropods such as insects and arachnids.

• Researchers have identified the mechanism by which endosymbiotic Wolbachia bacteria cause blindness in onchocerciasis. They studied the effect of toll-like receptors (TLRs) in the recruitment and activation of neutrophils, a type of white blood cell, when infected with O. volvulus. TLRs are proteins on the outside of certain cells that identify and help destroy disease-causing organisms that have entered the body. Wolbachia activates these receptors that are present on cells in the corneal stroma, which is the connective tissue that supports the cornea. This initiates neutrophil activation, which helps in the secretion of products that are harmful to cells, such as nitric oxide and oxygen radicals that disrupt the normal function of corneal cells and lead to a loss of corneal clarity and can potentially lead to blindness. These findings may help in finding a cure or treatment method to prevent blindness by blocking the receptor.

• Moxidectin is an antiparasitic agent used to prevent and treat heartworms and intestinal worms in animals. It is currently being studied by the World Health Organization (WHO) to evaluate its potential use in treating O. volvulus infection in humans in comparison to ivermectin.

• Future research: Studies have indicated that a human gene might influence the intensity of O. volvulus infection because there is a variation in the intensity of the infection in different people that cannot be attributed to differences in exposure alone. The study of a possible association may help in identifying the genetic variants responsible for the infection, thereby helping to control the infection.

• Because ivermectin does not kill the adult forms of O. volvulus, scientists are conducting studies to find a drug that can prevent the transmission of the infection. They are investigating the efficacy of UMF 078, a modified flubendazole, which is a compound used for controlling intestinal parasites such as roundworms and tapeworms, against Onchocerca ochengi in African cattle. Because some studies have reported damage to the nervous system leading to limb weakness and loss of memory, the evaluation of this drug has been suspended.

• Scientists are targeting O. volvulus GST1 (OvGST1), a unique glutathione S-transferase (GST), for the treatment of onchocerciasis. This enzyme is being studied for use as a vaccine, because it is present in all the life stages of the filarial worm and has the potential to modify immune responses by producing special mediators of inflammatory reactions that boost the defense mechanism of the host. Vaccines work by stimulating the body's immune system by introducing small amounts of disease-causing organisms into the body that allow the immune system to produce antibodies to the foreign invader. Once antibodies are developed, the immune system is able to respond quickly to infection if the disease-causing organism enters the body in the future.

Author Information

• This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

Bibliography

Natural Standard developed the above evidence-based information based on a thorough systematic review of the available scientific articles. For comprehensive information about alternative and complementary therapies on the professional level, go to www.naturalstandard.com. Selected references are listed below.

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