Moxidectin
Moxidectin was approved for onchocerciasis in 2018 for people over the age of 11 in the United States. The safety of multiple doses is unclear. Epidemiology
About 21 million people were infected with this parasite in 2017; about 1.2 million of those had vision loss. As of 2017, about 99% of onchocerciasis cases occurred in Africa. Onchocerciasis is currently relatively common in 31 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 vectors 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. Onchocerciasis was eliminated in the northern focus in Chiapas, Mexico, and the focus in Oaxaca, Mexico, where Onchocerca volvulus existed, was determined, after several years of treatment with ivermectin, as free of the transmission of the parasite.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 pruritus alone accounts for 60% of the DALYs. Infection reduces the hosts immunity and resistance to other diseases, which results in an estimated reduction in life expectancy of 13 years. History
Onchocerca originated in Africa and was exported to the Americas by the slave trade, as part of the Columbian exchange that introduced other old world diseases such as yellow fever into the New World.
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 be 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 neurotransmission. The drug binds to and activates glutamate-gated chloride channels. 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. 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. Ivermectin is very effective in reducing microfilarial load and reducing number of punctate opacities in individuals with onchocerciasis.