title: Comparison of Doxycycline, Minocycline, Doxycycline plus Albendazole and Albendazole Alone in Their Efficacy against Onchocerciasis in a Randomized, Open-Label, Pilot Trial.
abstract: The search for new macrofilaricidal drugs against onchocerciasis that can be administered in shorter regimens than required for doxycycline (DOX, 200mg/d given for 4-6 weeks), identified minocycline (MIN) with superior efficacy to DOX. Further reduction in the treatment regimen may be achieved with co-administration with standard anti-filarial drugs. Therefore a randomized, open-label, pilot trial was carried out in an area in Ghana endemic for onchocerciasis, comprising 5 different regimens: the standard regimen DOX 200mg/d for 4 weeks (DOX 4w, N = 33), the experimental regimens MIN 200mg/d for 3 weeks (MIN 3w; N = 30), DOX 200mg/d for 3 weeks plus albendazole (ALB) 800mg/d for 3 days (DOX 3w + ALB 3d, N = 32), DOX 200mg/d for 3 weeks (DOX 3w, N = 31) and ALB 800mg for 3 days (ALB 3d, N = 30). Out of 158 randomized participants, 116 (74.4%) were present for the follow-up at 6 months of whom 99 participants (63.5%) followed the treatment per protocol and underwent surgery. Histological analysis of the adult worms in the extirpated nodules revealed absence of Wolbachia in 98.8% (DOX 4w), 81.4% (DOX 3w + ALB 3d), 72.7% (MIN 3w), 64.1% (DOX 3w) and 35.2% (ALB 3d) of the female worms. All 4 treatment regimens showed superiority to ALB 3d (p < 0.001, p < 0.001, p = 0.002, p = 0.008, respectively), which was confirmed by real-time PCR. Additionally, DOX 4w showed superiority to all other treatment arms. Furthermore DOX 4w and DOX 3w + ALB 3d showed a higher amount of female worms with degenerated embryogenesis compared to ALB 3d (p = 0.028, p = 0.042, respectively). These results confirm earlier studies that DOX 4w is sufficient for Wolbachia depletion and the desired parasitological effects. The data further suggest that there is an additive effect of ALB (3 days) on top of that of DOX alone, and that MIN shows a trend for stronger potency than DOX. These latter two results are preliminary and need confirmation in a fully randomized controlled phase 2 trial.
  
  
  
  ClinicalTrials.gov #06010453.
authors.affiliation: Institute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Bonn, Germany.|Institute for Medical Biometry, Informatics and Epidemiology, University Hospital Bonn, Bonn, Germany.|German Center for Infection Research (DZIF), partner-site Bonn-Cologne, Bonn, Germany.
authors.forename: Ute
authors.initials: U
authors.lastname: Klarmann-Schulz
authors.affiliation: Institute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Bonn, Germany.|Institute of Laboratory Animal Science, University of Zurich, Zurich, Switzerland.
authors.forename: Sabine
authors.initials: S
authors.lastname: Specht
authors.affiliation: Faculty of Allied Health Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.|Kumasi Centre for Collaborative Research in Tropical Medicine (KCCR), Kumasi, Ghana.
authors.forename: Alexander Yaw
authors.initials: AY
authors.lastname: Debrah
authors.affiliation: Faculty of Allied Health Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
authors.forename: Linda
authors.initials: L
authors.lastname: Batsa
authors.affiliation: University Hospital, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
authors.forename: Nana Kwame
authors.initials: NK
authors.lastname: Ayisi-Boateng
authors.affiliation: Faculty of Allied Health Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
authors.forename: Jubin
authors.initials: J
authors.lastname: Osei-Mensah
authors.affiliation: Faculty of Allied Health Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
authors.forename: Yusif
authors.initials: Y
authors.lastname: Mubarik
authors.affiliation: School of Medical Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
authors.forename: Peter
authors.initials: P
authors.lastname: Konadu
authors.affiliation: Institute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Bonn, Germany.
authors.forename: Arcangelo
authors.initials: A
authors.lastname: Ricchiuto
authors.affiliation: Institute for Medical Biometry, Informatics and Epidemiology, University Hospital Bonn, Bonn, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Fimmers
authors.affiliation: Institute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Bonn, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Arriens
authors.affiliation: Institute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Bonn, Germany.
authors.forename: Bettina
authors.initials: B
authors.lastname: Dubben
authors.affiliation: Department of Parasitology, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
authors.forename: Louise
authors.initials: L
authors.lastname: Ford
authors.affiliation: Department of Parasitology, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
authors.forename: Mark
authors.initials: M
authors.lastname: Taylor
authors.affiliation: Institute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Bonn, Germany.|German Center for Infection Research (DZIF), partner-site Bonn-Cologne, Bonn, Germany.
authors.forename: Achim
authors.initials: A
authors.lastname: Hoerauf
mesh_terms: D000293:Adolescent; D000328:Adult; D015766:Albendazole / Q000008:administration & dosage*; D000818:Animals; D000871:Anthelmintics / Q000008:administration & dosage*; D004318:Doxycycline / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D005260:Female; D005869:Ghana; D006801:Humans; D008297:Male; D008875:Middle Aged; D008911:Minocycline / Q000008:administration & dosage*; D017181:Onchocerca volvulus / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology; D009855:Onchocerciasis / Q000188:drug therapy* / Q000469:parasitology; D010865:Pilot Projects; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000871:Anthelmintics; D015766:Albendazole; D008911:Minocycline; D004318:Doxycycline