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.
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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.