Onchocerca volvulus Symptoms and Causes

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.

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.

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.

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.

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.