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Thuy-Huong Ta-Tang,1 Sergio LB Luz,2 James L Crainey,2 José M Rubio3 1Malaria and NTDs Laboratory, National Centre of Tropical Medicine, Instituto de Salud Carlos III, Madrid, Spain; 2Laboratório de Ecologia de Doenças Transmissíveis na Amazônia, Instituto Leônidas e Maria Deane, Fundação Oswaldo Cruz, Manaus, Amazonas State, Brazil; 3Malaria & Emerging Parasitic Diseases Laboratory, National Microbiology Center, Instituto de Salud Carlos III, Madrid, SpainCorrespondence: José M RubioMalaria & Emerging Parasitic Diseases Laboratory, National Microbiology Center, Instituto de Salud Carlos III, Cra. Majadahonda-Pozuelo Km 2,5, Majadahonda, Madrid, 28220, SpainTel +34918223420Fax +34915097034Email jmrubio@isciii.esJames L CraineyLaboratório de Ecologia de Doenças Transmissíveis na Amazônia, Instituto Leônidas e Maria Deane, Fundação Oswaldo Cruz, 476 Rua Terezina, Adrianópolis, Manaus, Amazonas State, CEP 69057-070, BrazilEmail james.lee@fiocruz.brAbstract: Mansonellosis is caused by three filarial parasite species from the genus Mansonella that commonly produce chronic human microfilaraemias: M. ozzardi, M. perstans and M. streptocerca. The disease is widespread in Africa, the Caribbean and South and Central America, and although it is typically asymptomatic it has been associated with mild pathologies including leg-chills, joint-pains, headaches, fevers, and corneal lesions. No robust mansonellosis disease burden estimates have yet been made and the impact the disease has on blood bank stocks and the monitoring of other filarial diseases is not thought to be of sufficient public health importance to justify dedicated disease management interventions. Mansonellosis´s Ceratopogonidae and Simuliidae vectors are not targeted by other control programmes and because of their small size and out-door biting habits are unlikely to be affected by interventions targeting other disease vectors like mosquitoes. The ivermectin and mebendazole-based mass drug administration (iMDA and mMDA) treatment regimens deployed by the WHO´s Elimination of Neglected Tropical Diseases (ESPEN) programme and its forerunners have, however, likely impacted significantly on the mansonellosis disease burden, principally by reducing the transmission of M. streptocerca in Africa. The increasingly popular plan of using iMDA to control malaria could also affect M. ozzardi parasite prevalence and transmission in Latin America in the future. However, a potentially far greater mansonellosis disease burden impact is likely to come from short-course curative anti-Wolbachia therapeutics, which are presently being developed for onchocerciasis and lymphatic filariasis treatment. Even if the WHO´s ESPEN programme does not choose to deploy these drugs in MDA interventions, they have the potential to dramatically increase the financial and logistical feasibility of effective mansonellosis management. There is, thus, now a fresh and urgent need to better characterise the disease burden and eco-epidemiology of mansonellosis so that effective management programmes can be designed, advocated for and implemented.Keywords: Mansonellosis, Mansonella perstans, Mansonella ozzardi, Mansonella streptocerca, Wolbachia, doxycycline

Thuy-Huong Ta-Tang,1 James L Crainey,2 Rory J Post,3,4 Sergio LB Luz,2 José M Rubio1 1Malaria and Emerging Parasitic Diseases Laboratory, National Microbiology Center, Instituto de Salud Carlos III, Majadahonda, Spain; 2Laboratory of Infectious Disease Ecology in the Amazon, Oswaldo Cruz Foundation, Instituto Leônidas e Maria Deane, Manaus, Brazil; 3School of Natural Sciences and Psychology, John Moores University, Liverpool, 4Department of Disease Control, Faculty of Infectious Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK Abstract: Mansonellosis is a filarial disease caused by three species of filarial (nematode) parasites (Mansonella perstans, Mansonella streptocerca, and Mansonella ozzardi) that use humans as their main definitive hosts. These parasites are transmitted from person to person by bloodsucking females from two families of flies (Diptera). Biting midges (Ceratopogonidae) transmit all three species of Mansonella, but blackflies (Simuliidae) are also known to play a role in the transmission of M. ozzardi in parts of Latin America. M. perstans and M. streptocerca are endemic in western, eastern, and central Africa, and M. perstans is also present in the neotropical region from equatorial Brazil to the Caribbean coast. M. ozzardi has a patchy distribution in Latin America and the Caribbean. Mansonellosis infections are thought to have little pathogenicity and to be almost always asymptomatic, but occasionally causing itching, joint pains, enlarged lymph glands, and vague abdominal symptoms. In Brazil, M. ozzardi infections are also associated with corneal lesions. Diagnosis is usually performed by detecting microfilariae in peripheral blood or skin without any periodicity. There is no standard treatment at present for mansonellosis. The combination therapy of diethylcarbamazine plus mebendazole for M. perstans microfilaremia is presently one of the most widely used, but the use of ivermectin has also been proven to be very effective against microfilariae. Recently, doxycycline has shown excellent efficacy and safety when used as an antimicrobial against endosymbiotic Wolbachia bacteria harbored by some strains of M. perstans and M. ozzardi. Diethylcarbamazine and ivermectin have been used effectively to treat M. streptocerca infection. There are at present no estimates of the disease burden caused by mansonellosis, and thus its importance to many global health professionals and policy makers is presently limited to how it can interfere with diagnostic tools used in modern filarial disease control and elimination programs aimed at other species of filariae. Keywords: mansonellosis, filariasis, M. perstans, M. ozzardi, M. streptocerca, neglected disease