Comparison of Doxycycline, Minocycline, Doxycycline plus Albendazole and Albendazole Alone in Their Efficacy against Onchocerciasis in a Randomized, Open-Label, Pilot Trial

Klarmann-Schulz, Ute, Specht, Sabine, Debrah, Alexander Yaw, Batsa, Linda, Ayisi-Boateng, Nana Kwame, Osei-Mensah, Jubin, Mubarik, Yusif, Konadu, Peter, Ricchiuto, Arcangelo, Fimmers, Rolf, Arriens, Sandra, Dubben, Bettina, Ford, Louise, Taylor, Mark ORCID: https://orcid.org/0000-0003-3396-9275 and Hoerauf, Achim (2017) 'Comparison of Doxycycline, Minocycline, Doxycycline plus Albendazole and Albendazole Alone in Their Efficacy against Onchocerciasis in a Randomized, Open-Label, Pilot Trial'. PLoS Neglected Tropical Diseases, Vol 11, Issue 1, e0005156.

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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.

Item Type:	Article
Subjects:	QX Parasitology > QX 20 Research (General) QX Parasitology > Helminths. Annelida > QX 203 Nematoda WA Public Health > Preventive Medicine > WA 110 Prevention and control of communicable diseases. Transmission of infectious diseases WA Public Health > WA 30 Socioeconomic factors in public health (General) WC Communicable Diseases > Tropical and Parasitic Diseases > WC 885 Onchocerciasis
Faculty: Department:	Biological Sciences > Department of Tropical Disease Biology
Digital Object Identifer (DOI):	https://doi.org/10.1371/journal.pntd.0005156
SWORD Depositor:	JISC Pubrouter
Depositing User:	JISC Pubrouter
Date Deposited:	25 Jan 2017 18:04
Last Modified:	16 Sep 2019 09:01
URI:	https://archive.lstmed.ac.uk/id/eprint/6689

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