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Comparison of doxycycline, minocycline, doxycycline plus albendazole and albendazole alone in their efficacy against onchocerciasis in a randomized, open-label, pilot trial

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Klarmann-Schulz, Ute, Specht, Sabine, Debrah, Alexander Yaw, Batsa, Linda, Ayisi-Boateng, Nana Kwame, Osei-Mensah, Jubin, Mubarik, Yusif, Konadu, Peter +7 more·2017·PLOS Neglected Tropical Diseases
DOI 10.1371/journal.pntd.0005156PMC PMC5215804
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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. TRIAL REGISTRATION: ClinicalTrials.gov #06010453.

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  • A combination of doxycycline (200 mg daily for 21 days) with albendazole (800 mg daily for 3 days) produced better efficacy than either drug alone in onchocerciasis.

    “A combination of doxycycline (200 mg daily for 21 days) with albendazole (800 mg daily for 3 days) produced better efficacy than either drug alone [217]”

    From Albendazole and Mebendazole as Anti-Parasitic and Anti-Cancer Agents: an Update (2021) · cites this paper as [217]

    The Abstract gives the stated doses and durations, and reports greater Wolbachia depletion with the combination than with either drug alone. However, the Results (Immunohistology; page not provided) describe its advantage over three-week doxycycline as a trend in a non-confirmatory pilot trial, not an established efficacy difference. The Discussion likewise calls the additive finding preliminary and says it needs confirmation. (LLM, conf=0.86)

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Authors
Klarmann-Schulz, U., Specht, S., Debrah, A. Y., Batsa, L., Ayisi-Boateng, N. K., Osei-Mensah, J., Mubarik, Y., Konadu, P., Ricchiuto, A., Fimmers, R., Arriens, S., Dubben, B., Ford, L., Taylor, M., & Hoerauf, A.
Affiliations
  • University of Zurich (CH)
  • Kwame Nkrumah University of Science and Technology (GH)
  • University Hospital Bonn (DE)
  • Liverpool School of Tropical Medicine (GB)
Corresponding author
  • Specht, Sabine
  • Debrah, Alexander Yaw
  • Osei-Mensah, Jubin
  • Mubarik, Yusif
  • Konadu, Peter
  • Ricchiuto, Arcangelo
  • Fimmers, Rolf
  • Arriens, Sandra
  • Dubben, Bettina
  • Ford, Louise
  • Taylor, Mark
  • Hoerauf, Achim
ORCID
Venue
PLOS Neglected Tropical Diseases
Publisher
Public Library of Science (PLoS)
Published
2017-01-05
Volume
11
Issue
1
Pages
e0005156
ISSN
  • 1935-2727 (ISSN-L)
  • 1935-2735
DOI
10.1371/journal.pntd.0005156
PMC
PMC5215804
OpenAlex
W2569382675
Cited by
63
References
0
Citations by year
2026: 6 · 2025: 1 · 2024: 2 · 2023: 6 · 2022: 8 · 2021: 8 · 2020: 9 · 2019: 12 · 2018: 6 · 2017: 5
FWCI
6.74
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS neglected tropical diseases (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • LSTM Online Archive (Liverpool School of Tropical Medicine) (acceptedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
  • Greater South Information System
Funders
Bill and Melinda Gates Foundation (Anti-Wolbachia Consortium)
Topics
  • Health Sciences › Medicine › Infectious Diseases › Parasitic Diseases Research and Treatment
  • Life Sciences › Immunology and Microbiology › Parasitology › Parasites and Host Interactions
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Research on Leishmaniasis Studies
Keywords
onchocerciasis, doxycycline, minocycline, albendazole, Wolbachia, ophthalmic surgery, real-time PCR, pilot trial
MeSH terms
Adolescent, Adult, Animals, Anthelmintics, Doxycycline, Drug Therapy, Combination, Female, Ghana, Humans, Male, Middle Aged, Minocycline, Onchocerciasis, Pilot Projects, Albendazole, Treatment Outcome, Onchocerca volvulus, Young Adult

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