The Annotated Genome of Wolbachia from the Filarial Nematode Brugia malayi: What It Means for Progress in Antifilarial Medicine

Filariasis The fi larial nematodes Wuchereria bancrofti, Brugia spp., and Onchocerca volvulus are insect-borne parasites that cause lymphatic or cutaneous fi lariasis. Lymphangitis, hydrocele, and elephantiasis are pathologies that result from W. bancrofti and Brugia spp. infections. O. volvulus infections can present with severe skin pathologies (acute and chronic dermatitis, atrophy) and blindness (onchocerciasis, or river blindness). The nematodes infect more than 140 million people in 90 mostly tropical countries. An additional one billion people are at risk of contracting the diseases caused by these nematodes [1,2]. Current control efforts, both vector control and mass antifi larial chemotherapies, have shown initial success, but sustainability is uncertain. For example, vector control, used for onchocerciasis in west African savannah areas, has become too expensive and therefore been stopped. Current and planned elimination programs will rely on mass administration of antifi larial drugs that require annual administration for 5–10 years for lymphatic fi lariasis and more than 20 years for onchocerciasis. Control programs based on drug administration require long treatment durations because the adult female worms, which produce thousands of larvae daily, survive many years (over 14 years for onchocerciasis) and are not killed by current drugs [1]. The success of such control programs, as shown by mathematical modeling, depends on a minimum of 60% of the people in an endemic area participating every year [3]. This is probably too optimistic an estimate, as a recent review of onchocerciasis therapy in regions that have had 10–12 years of ivermectin treatment still show infection levels of 2%–3%. These levels are enough to establish the infection within a few years after the end of annual drug administration [4]. Additionally, there is evidence that some geographic areas have worms with apparent resistance to ivermectin [5]. Therefore, it is essential that we fi nd new drugs that kill or sterilize adult worms. For almost 30 years, it has been known that fi larial nematodes contain endosymbiotic bacteria. These endobacteria are found in the hypodermis of male and female worms, and in the oocytes, embryos, and larval stages (Figure 1). As in many animal fi larial species, endobacteria are present in the human fi lariae W. bancrofti, Brugia spp., and O. volvulus [1,6,7], but not in Loa loa [8,9]. Recently, these endosymbionts were classifi ed at the molecular level to be of the genus Wolbachia, a genus of bacteria that are common endosymbionts of arthropods. The next nearest …