Macrofilaricides: An Unmet Medical Need for Filarial Diseases

Neglected parasitic helminth diseases such as onchocerciasis and lymphatic filariasis affect an estimated 145 million people worldwide, creating a serious health burden in endemic areas such as sub-Saharan Africa and India. Although these diseases are not usually lethal, these filarial nematodes, transmitted by blood-feeding insect vectors, cause severe debilitation and cause chronic disability to infected individuals. The adult worms can reproduce from 5 to up to 14 years, releasing millions of microfilariae, juvenile worms, over an infected individual's lifetime. The current treatments for controlling human filarial infections is focused on killing microfilariae, the earliest larval stage. Currently, there is an unmet medical need for treatments consisting of a macrofilaricidal regimen, one that targets the adult stage of the parasite, to increase the rate of elimination, allow for safe use in coendemic regions of Onchocerca volvulus and Loa loa, and to provide a rapid method to resolve reinfections. Herein, recent approaches for targeting human filarial diseases are discussed, including direct acting agents to target parasitic nematodes and antibacterial approaches to target the endosymbiotic bacteria, Wolbachia.