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Nematode

Onchocerca volvulus is a filarial (arthropod borne) nematode (roundworm) that causes onchocerciasis (river blindness), and is the second leading cause of blindness due to infection worldwide after trachoma. It is one of the 20 neglected tropical diseases listed by the World Health Organization, with elimination from certain countries expected by 2025. John O'Neill, an Irish surgeon, first described Onchocerca volvulus in 1874, when he found it to be the causative agent of 'craw craw', a skin disease found in West Africa. A Guatemalan doctor, Rodolfo Robles, first linked it to visual impairment in 1917. O. volvulus is primarily found in sub Saharan Africa, and there is also disease transmission in some South American nations, as well as Yemen (see global map bottom right). It is spread from person to person via female biting blackflies of the genus Simulium, and humans are the only known definitive host.

O. volvulus parasites obtain nutrients from the human host by ingesting blood or by diffusion through their cuticle. They may be able to trigger blood vessel formation because dense vascular networks are often found surrounding the worms. They are distinguished from other human infecting filarial nematodes by the presence of deep transverse striations. It is a dioecious species, containing distinct males and females, which form nodules under the skin in humans. Mature female worms permanently reside in these fibrous nodules, while male worms are free to move around the subcutaneous tissue. The males are smaller than females, with male worms measuring 23 mm in length compared to 230–700 mm in females. The first larval stage, microfilariae, are 300 μm in length and unsheathed, meaning that when they mature into microfilariae, they exit from the envelope of the egg.

The average adult worm lifespan is 15 years, and mature females can produce between 500 and 1,500 microfilariae per day. The normal microfilarial lifespan is 1.0 to 1.5 years; however, their presence in the bloodstream causes little to no immune response until death or degradation of the microfilariae or adult worms.

The microfilariae of O. volvulus are found in the dermis layer of skin in the host. When a female Simulium blackfly takes a blood meal from an infected host, the microfilariae are also ingested. From here, the microfilariae penetrate the gut and migrate to the thoracic flight muscles, where they enter the first juvenile phase, J1. After maturing into J2, the second juvenile phase, they migrate to the proboscis, where they are found in the saliva. J2 stage juveniles then mature into infectious stage three juveniles, J3, in the saliva. The lifecycle in the blackfly takes between one and three weeks.

When the female blackfly takes a blood meal, J3 juveniles pass into the human bloodstream. From here, the juveniles migrate to the subcutaneous tissue, where they form nodules and mature into adult worms over a period of 6–12 months. After maturation, the smaller adult males migrate from nodules to subcutaneous tissue, where they mate with the larger adult females. The eggs mature internally to form stage one microfilariae, which are released from the female's body one at a time and remain in the subcutaneous tissue. The microfilariae are taken up by a female blackfly when it takes a blood meal, thus completing the lifecycle of O. volvulus. Ivermectin prevents female worms from releasing microfilariae for several months, thus relieving symptoms and temporarily preventing transmission. However, this does not kill adult worms, so it must be taken once annually as long as adult worms are present. O. volvulus has been proposed as one of the causative agents of nodding syndrome, a condition that affects children aged 5 to 15 and is currently only observed in South Sudan, Tanzania, and northern Uganda. Although the cause of the disease is unknown, O. volvulus is being increasingly studied as a possible cause due to its ubiquity in areas where the disease is found.

An estimated 187 million people are at risk of O. volvulus infection, with 17–25 million people infected and 0.8 million showing some impairment of vision. O. volvulus has not directly caused a single death, but has cost 1.1 million disability adjusted life years, which measure the number of years of healthy life lost due to a specific disease and show the burden of a disease. Simulium blackfly adults require moving water to breed and eggs remain in water until they exit from the pupa and enter the adult stage of their lifecycle. Due to this restriction, O. volvulus is only found around streams or rivers. Artificial water systems, such as hydroelectric power plants, built in Africa, provide ideal conditions all year for blackfly development and make controlling its spread difficult. About 99% of cases of onchocerciasis are found in 31 countries in sub Saharan Africa, although areas of limited transmission occur in Brazil, Venezuela, and Yemen. Onchocerciasis was eliminated from Colombia in 2013, Ecuador in 2014, Mexico in 2015, and Guatemala in 2016 O. volvulus has four chromosome pairs, which include a single pair of sex chromosomes. A large X sex chromosome and a smaller Y sex chromosome determine male worms, while two X chromosomes determine female worms. One of the three nonsex chromosomes is thought to have formed by a fusion event between two smaller chromosomes. This is also supported by genetic data that place O. ochengi (a cattle infecting strain) as the sister group to O. volvulus.

Adult worms are found in nodules and are hidden from most components of the human immune system. Microfilariae are more vulnerable to attack by immune cells because they exit nodules to complete their lifecycle. O. volvulus can be detected by the immune system through the release of soluble antigens and antigens found on the surface of microfilariae and infective J3 juveniles. These antigens allow the immune system to detect the presence of a foreign organism in the body and trigger an immune response to clear infection. The immune response involves raising antibodies (IgG, IgM and IgE type) that can react with soluble antigens released by Onchocerca volvulus. Opsonising antibodies that tag cells for destruction are also found against the infective J3 stage and microfilariae, but there is not enough evidence at the moment to say whether this is protective. The antigens of O. volvulus are highly complex and show cross reactivity with several other filarial worms. Little evidence indicates that antibodies made are specific to O. volvulus. However, after the age of 40, the number of parasites carried (the intensity of infection) decreases, suggesting that over time, some sort of protective immune response develops.

O. volvulus, along with most filarial nematodes, share an endosymbiotic relationship with strains of the bacterium Wolbachia. In the absence of Wolbachia, larval development of O. volvulus is disrupted or ceased. These bacteria have been proposed to enhance the symptoms and severity of onchocerciasis by triggering inflammatory responses in the host.