{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T21:11:17Z","timestamp":1792271477530,"version":"4.4.0"},"reference-count":40,"publisher":"American Society of Tropical Medicine and Hygiene","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,7,3]]},"abstract":"<jats:p>Treating <jats:italic>Mansonella perstans<\/jats:italic> is challenged by the low efficacy of registered antihelminthics. <jats:italic>Wolbachia<\/jats:italic> endobacteria provide an alternative treatment target because depletion results in amicrofilaremia in filarial infections with <jats:italic>Wuchereria bancrofti<\/jats:italic> and <jats:italic>Onchocerca volvulus<\/jats:italic> infections. This open-label, randomized study sought to confirm that i) <jats:italic>Wolbachia<\/jats:italic> are present in <jats:italic>M. perstans<\/jats:italic> in Ghana and ii) doxycycline treatment will deplete <jats:italic>Wolbachia<\/jats:italic> and cause a slow, sustained decline in microfilariae (MF). Two hundred and two Ghanaians with <jats:italic>M. perstans<\/jats:italic> infection were randomized into early (immediate) and delayed (6 months deferred) treatment groups, given doxycycline 200 mg\/day for 6 weeks, and monitored for MF and <jats:italic>Wolbachia<\/jats:italic> levels at baseline, 4, 12, and 24 months after the study onset (= time of randomization and start of treatment for the early group). Per protocol analysis revealed that the median MF\/mL in the early group declined from 138 at baseline to 64 at month 4 and further to 0 at month 12. In the delayed group, MF load did not change from a baseline median of 97 to 102 at month 4 but declined to 42 at month 12, that is, 6 months after receiving treatment, trailing the early group as expected. By month 24, both treatment groups had reached a median MF level of 0. After treatment, <jats:italic>Wolbachia<\/jats:italic> were depleted from MF by \u2265 1-log drop compared with baseline levels. We conclude that <jats:italic>M. perstans<\/jats:italic> in Ghana harbor <jats:italic>Wolbachia<\/jats:italic> that are effectively depleted by doxycycline with subsequent reduction in MF loads, most likely because of interruption of fertility of adult worms.<\/jats:p>","DOI":"10.4269\/ajtmh.18-0491","type":"journal-article","created":{"date-parts":[[2019,6,4]],"date-time":"2019-06-04T07:23:05Z","timestamp":1559632985000},"page":"84-92","source":"Crossref","is-referenced-by-count":47,"title":["The Efficacy of Doxycycline Treatment on Mansonella perstans Infection: An Open-Label, Randomized Trial in Ghana"],"prefix":"10.4269","volume":"101","author":[{"given":"Linda","family":"Batsa Debrah","sequence":"first","affiliation":[{"name":"Kumasi Centre for Collaborative Research in Tropical Medicine (KCCR), Kumasi, Ghana;"},{"name":"Department of Clinical Microbiology, Kwame Nkrumah University of Science and Technology, Kumasi, 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(KCCR), Kumasi, Ghana;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna-Lena","family":"Sander","sequence":"additional","affiliation":[{"name":"Institute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Bonn, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"L\u00e4mmer","sequence":"additional","affiliation":[{"name":"Institute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Bonn, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Ritter","sequence":"additional","affiliation":[{"name":"Institute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Bonn, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura E.","family":"Layland","sequence":"additional","affiliation":[{"name":"Institute for Medical Microbiology, Immunology and Parasitology, University Hospital 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Ghana","volume":"10","author":"Debrah","year":"2017"},{"key":"b5","series-title":"Acta Trop","first-page":"S109","article-title":"Mansonella perstans filariasis in Africa","volume":"120","author":"Simonsen","year":"2011"},{"key":"b6","series-title":"N Engl J Med","first-page":"1502","article-title":"Mansonella perstans\u2014the importance of an endosymbiont","volume":"361","author":"Hoerauf","year":"2009"},{"key":"b7","series-title":"Trends Parasitol","first-page":"163","article-title":"Filaria zoogeography in Africa: ecology, competitive exclusion, and public health relevance","volume":"30","author":"Molyneux","year":"2014"},{"key":"b8","series-title":"J Helminthol","first-page":"469","article-title":"The relationship between microfilaraemic and amicrofilaraemic loiasis involving co-infection with Mansonella perstans and clinical symptoms in an exposed population from Gabon","volume":"90","author":"Bouyou Akotet","year":"2016"},{"key":"b9","series-title":"Dermatol Ther","first-page":"475","article-title":"Filariasis: diagnosis and treatment","volume":"22","author":"Mendoza","year":"2009"},{"key":"b10","series-title":"PLoS Negl Trop Dis","first-page":"e1890","article-title":"Filariasis attenuates anemia and proinflammatory responses associated with clinical malaria: a matched prospective study in children and young adults","volume":"6","author":"Dolo","year":"2012"},{"key":"b11","series-title":"PLoS Negl Trop Dis","first-page":"e0006184","article-title":"Mansonella perstans microfilaremic individuals are characterized by enhanced type 2 helper T and regulatory T and B cell subsets and dampened systemic innate and adaptive immune responses","volume":"12","author":"Ritter","year":"2018"},{"key":"b12","series-title":"J Infect Dis","first-page":"920","article-title":"Plasmodium falciparum and helminth coinfection in a semi urban population of pregnant women in Uganda","volume":"198","author":"Hillier","year":"2008"},{"key":"b13","series-title":"Trans R Soc Trop Med Hyg","first-page":"899","article-title":"Associations between mild-to-moderate anaemia in pregnancy and helminth, malaria and HIV infection in Entebbe, Uganda","volume":"101","author":"Muhangi","year":"2007"},{"key":"b14","series-title":"PLoS Negl Trop Dis","first-page":"e0004319","article-title":"Ecological drivers of Mansonella perstans infection in Uganda and patterns of co-endemicity with lymphatic filariasis and malaria","volume":"10","author":"Stensgaard","year":"2016"},{"key":"b15","series-title":"Vaccine","first-page":"247","article-title":"Effects of maternal and infant co-infections, and of maternal immunisation, on the infant response to BCG and tetanus immunisation","volume":"29","author":"Elliott","year":"2010"},{"key":"b16","series-title":"Lancet","first-page":"1912","article-title":"Effect of Wuchereria bancrofti infection on HIV incidence in southwest Tanzania: a prospective cohort study","volume":"388","author":"Kroidl","year":"2016"},{"key":"b17","series-title":"PLoS Negl Trop Dis","first-page":"e3414","article-title":"Hyperreactive onchocerciasis is characterized by a combination of Th17-Th2 immune responses and reduced regulatory T cells","volume":"9","author":"Katawa","year":"2015"},{"key":"b18","series-title":"Eur J Immunol","first-page":"3101","article-title":"Tr1 and naturally occurring regulatory T cells induce IgG4 in B cells through GITR\/GITR-L interaction, IL-10 and TGF-beta","volume":"38","author":"Satoguina","year":"2008"},{"key":"b19","series-title":"Int Marit Health","first-page":"51","article-title":"Diagnosing and treatment of skin filariases based on own observations","volume":"51","author":"Goljan","year":"2000"},{"key":"b20","series-title":"Ann Trop Med Parasitol","first-page":"31","article-title":"Mansonella perstans: safety and efficacy of ivermectin alone, albendazole alone and the two drugs in combination","volume":"103","author":"Asio","year":"2009"},{"key":"b21","series-title":"Trans R Soc Trop Med Hyg","first-page":"274","article-title":"A randomised, double-blind field trial of ivermectin alone and in combination with albendazole for the treatment of Mansonella perstans infections in Uganda","volume":"103","author":"Asio","year":"2009"},{"key":"b22","series-title":"Mol Biochem Parasitol","first-page":"123","article-title":"Molecular identification of Wolbachia from the filarial nematode Mansonella perstans","volume":"160","author":"Keiser","year":"2008"},{"key":"b23","series-title":"N Engl J Med","first-page":"1448","article-title":"A randomized trial of doxycycline for Mansonella perstans infection","volume":"361","author":"Coulibaly","year":"2009"},{"key":"b24","series-title":"J Infect Dis","first-page":"1633","article-title":"Molecular evidence of Wolbachia endosymbiosis in Mansonella perstans in Gabon, central Africa","volume":"210","author":"Gehringer","year":"2014"},{"key":"b25","series-title":"Parasitol Res","first-page":"405","article-title":"No evidence of Wolbachia endosymbiosis with Loa loa and Mansonella perstans","volume":"90","author":"Grobusch","year":"2003"},{"key":"b26","series-title":"Med Microbiol Immunol","first-page":"211","article-title":"Doxycycline as a novel strategy against bancroftian filariasis-depletion of Wolbachia endosymbionts from Wuchereria bancrofti and stop of microfilaria production","volume":"192","author":"Hoerauf","year":"2003"},{"key":"b27","series-title":"PLoS Pathog","first-page":"e92","article-title":"Doxycycline reduces plasma VEGF-C\/sVEGFR-3 and improves pathology in lymphatic filariasis","volume":"2","author":"Debrah","year":"2006"},{"key":"b28","series-title":"Int J Infect Dis","first-page":"1","article-title":"Risk factors for epilepsy in Bas-Uele province, Democratic Republic of the Congo: a case-control study","volume":"49","author":"Colebunders","year":"2016"},{"key":"b29","series-title":"Med Microbiol Immunol","first-page":"335","article-title":"Wolbachia endobacteria depletion by doxycycline as antifilarial therapy has macrofilaricidal activity in onchocerciasis: a randomized placebo-controlled study","volume":"197","author":"Hoerauf","year":"2008"},{"key":"b30","series-title":"Lancet","first-page":"1415","article-title":"Depletion of Wolbachia endobacteria in Onchocerca volvulus by doxycycline and microfilaridermia after ivermectin treatment","volume":"357","author":"Hoerauf","year":"2001"},{"key":"b31","series-title":"Microbes Infect","first-page":"261","article-title":"Doxycycline in the treatment of human onchocerciasis: kinetics of Wolbachia endobacteria reduction and of inhibition of embryogenesis in female Onchocerca worms","volume":"5","author":"Hoerauf","year":"2003"},{"key":"b32","series-title":"Adv Parasitol","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/S0065-308X(05)60004-8","article-title":"Wolbachia bacterial endosymbionts of filarial nematodes","volume":"60","author":"Taylor","year":"2005"},{"key":"b33","series-title":"Clin Infect Dis","first-page":"1081","article-title":"A randomized, double-blind clinical trial of a 3-week course of doxycycline plus albendazole and ivermectin for the treatment of Wuchereria bancrofti infection","volume":"42","author":"Turner","year":"2006"},{"key":"b34","series-title":"Filaria J","first-page":"10","article-title":"Obligatory symbiotic Wolbachia endobacteria are absent from Loa loa","volume":"2","author":"B\u00fcttner","year":"2003"},{"key":"b35","series-title":"Parasitol Today","first-page":"437","article-title":"Wolbachia bacteria of filarial nematodes","volume":"15","author":"Taylor","year":"1999"},{"key":"b36","series-title":"Trop Med Int Health","first-page":"275","article-title":"Targeting of Wolbachia endobacteria 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