Abstract
Onchocerciasis is a devastating skin and eye disease that afflicts about 21 million people, most of whom live in sub-Saharan Africa. Its control with the microfilaricidal drug ivermectin is limited, thus necessitating the development of preclinical animal models to aid in the discovery of a macrofilaricide. Previously, we found that Onchocerca ochengi (the closest relative of the human O. volvulus) worm masses survive better in hamsters than in gerbils. The aim of this study was to compare the survival of O. ochengi adult male worms and their susceptibility to flubendazole (FBZ, a macrofilaricide) in gerbils and hamsters. The animals were intraperitoneally implanted with O. ochengi male worms, treated with FBZ, and sacrificed 35 days post-implantation. Unlike gerbils which had some worms moving freely in the peritoneum and some in newly formed nodules (neo-nodules), all the worms in the hamsters were found in neo-nodules. FBZ significantly decreased worm burden, motility, and viability in gerbils whereas it had no significant effect in hamsters. These results highlight a major difference in how O. ochengi adult male worms are sustained and affected by FBZ in gerbils compared to hamsters. Understanding the difference between these two models is important in the development of effective macrofilaricides for onchocerciasis.
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Data can be made available upon request but not material as it was all used in the study.
References
Ayiseh RB, Mbah GE, Manfo FPT, Kulu TK, Njotu FN, Monya E et al (2023a) Survival of worm masses of Onchocerca ochengi in gerbils and hamsters: implications for the development of an in vivo macrofilaricide screening model. Parasitol Res 122(7):1581–1591. https://doi.org/10.1007/s00436-023-07859-7
Ayiseh RB, Mbah GE, Monya E, Ndi EM, Sakanari J, Lustigman S et al (2023b) Development and validation of small animal models for onchocerciasis and loiasis microfilaricide discovery. PLoS neglected tropical diseases 17(2):e0011135. PNTD-D-22-00617. https://doi.org/10.1371/journal.pntd.0011135
Beher WT, Filus AM, Rao B, Beher ME (1969) A comparative study of bile acid metabolism in the rat, mouse, hamster, and gerbil. Proc Soc Exp Biol Med 130(4):1067–1074. https://doi.org/10.3181/00379727-130-33722
Burchard GD, Büttner DW, Bierther M (1979) Electron microscopical studies on onchocerciasis. III. The onchocerca-nodule. Tropenmed Parasitol 30(1):103–12
Cho-Ngwa F, Abongwa M, Ngemenya MN, Nyongbela KD (2010) Selective activity of extracts of Margaritaria discoidea and Homalium africanum on Onchocerca ochengi. BMC Complement Altern Med 10(1):62
Cho-Ngwa F, Mbah GE, Ayiseh RB, Ndi EM, Monya E, Tumanjong IM et al (2019) Development and validation of an Onchocerca ochengi adult male worm gerbil model for macrofilaricidal drug screening. PLoS Negl Trop Dis 13(7):e0007556
Gebrezgabiher G, Mekonnen Z, Yewhalaw D, Hailu A (2019) Reaching the last mile: main challenges relating to and recommendations to accelerate onchocerciasis elimination in Africa. Infect Dis Poverty 8(1):60. https://doi.org/10.1186/s40249-019-0567-z
Halliday A, Guimaraes A, Tyrer H, Metuge H, Patrick C, Arnaud K-O et al (2014) A murine macrofilaricide pre-clinical screening model for onchocerciasis and lymphatic filariasis. Parasites Vectors 7(1):1–14. https://doi.org/10.1186/s13071-014-0472-z
Makepeace BL, Tanya VN (2016) 25 Years of the Onchocerca ochengi model. Trends Parasitol 32(12):966-978. S1471-4922(16)30143-X. https://doi.org/10.1016/j.pt.2016.08.013
Mbah GE, Ayiseh RB, Cho-Ngwa F (2016) Development and validation of an Onchocerca ochengi microfilarial hamster model for onchocerciasis drug screens. BMC Infect Dis 16(1):404. https://doi.org/10.1186/s12879-016-1753-2
Ngwewondo A, Scandale I, Specht S (2021) Onchocerciasis drug development: from preclinical models to humans. Parasitol Res 120(12):3939–3964. https://doi.org/10.1007/s00436-021-07307-4
Patton JB, Bennuru S, Eberhard ML, Hess JA, Torigian A, Lustigman S et al (2018) Development of Onchocerca volvulus in humanized NSG mice and detection of parasite biomarkers in urine and serum. PLoS Negl Trop Dis 12(12):e0006977
Wildenburg G, Plenge-Bonig A, Renz A, Fischer P, Buttner DW (1997) Distribution of mast cells and their correlation with inflammatory cells around Onchocerca gutturosa, O. tarsicola, O. ochengi, and O. flexuosa. Parasitol Res 83(2):109–20
Acknowledgements
We thank Mr. Gamua Stanley and the staff of the Biotechnology Unit, Faculty of Science, University of Buea, Cameroon, for their technical support.
Funding
This study was supported by grants from the Bill and Melinda Gates Foundation (www.gatesfoundation.org. Grant numbers OPP1098475 and OPP1017584) to Fidelis Cho-Ngwa, Judy Sakanari, and Sara Lustigman. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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G.E.M. performed the experiments, analyzed the results, and drafted the manuscript. R.B.A. performed the experiments, analyzed the results, and drafted the manuscript.T-K.K. and F.N.N. assisted in performing the experiments and acquiring data. E.M. and E.M.N. provided laboratory samples and contributed in developing the methodology. J.S. and S.L. were involved in conception, funding and reviewing the manuscript. F.C-N. did the conception, sourced for funding, designed and supervised the experiments, and reviewed the manuscript.
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Not applicable for humans as they were not involved in this study. The animal protocol (UB-IACUC No 002/2017) was approved by the University of Buea Animal Care and Use Committee.
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Mbah, G.E., Ayiseh, R.B., Monya, E. et al. Differential susceptibility of Onchocerca ochengi adult male worms to flubendazole in gerbils and hamsters. Parasitol Res 123, 186 (2024). https://doi.org/10.1007/s00436-024-08207-z
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DOI: https://doi.org/10.1007/s00436-024-08207-z