Onchocerca ochengi male worms implanted in SCID mice and Gerbil: Relationship between microfilaridermia status of cows, nodular worm viability and fertility and worm survival in the rodents

Desmond N Akumtoh,Abdel J Njouendou,Haelly M Metuge,Hanna T Sjoberg,Nicolas P Pionnier,Valerine C Chunda,Narcisse Victor T Gandjui,Lontum B Ndzeshang,Fanny F Fombad,Raphael A Abong,Peter A Enyong,Jerome Fru-Cho,Mathias E Esum,Manuel Ritter,Mark J Taylor,Joseph D Turner,Samuel Wanji

doi:10.1016/j.exppara.2021.108143

Desmond N Akumtoh, Abdel J Njouendou + Show 15 more

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https://doi.org/10.1016/j.exppara.2021.108143

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Abstract

BackgroundCurrent treatment options for onchocerciasis are sub-optimal, prompting research and development of a safe cure (macrofilaricide). Onchocerca ochengi, a parasite of cattle, is used as a close surrogate for the human parasite O. volvulus in a murine model for pre-clinical screening of macrofilaricides. Skin from naturally infected cattle have been used in previous studies as a reliable source of parasite material. However, there is limited knowledge on how source-related factors such as the microfilaridermia status of the cattle, the nodule load and nodular worm viability may affect survival of male O. ochengi worms implanted in the rodent hosts. Such relationships were investigated in this study. MethodsDermal tissue and nodules were obtained from Gudali cattle, dissected and cultured to obtain migrating microfilariae (mf) and male worms. Emerged male worms were implanted into SCID mice and Gerbils (Meriones unguiculatus) and recovery rates were determined upon 42 days post implantation. Finally, nodules were processed for histology and embryogram analyses to assess the nodular worm viability and fertility, respectively. ResultsOf the 69 cattle sampled, 24 (34.8%) were mf+ and 45 (65.2%) were mf–. The mean nodule loads were 180.5 ± 117.7 (mf+) and 110.6 ± 102.7 (mf-) (p = 0.0186). The mean male worm harvest from nodules were 76.8 ± 120.3 and 47.2 ± 33.4 (p = 0.2488) for mf+ and mf– cattle, respectively. The number of male worms per 100 nodules were 57/100 and 46/100 nodules for mf+ and mf– cows, respectively. Female worms from nodules of mf– cows had higher counts of both normal and abnormal embryos with higher proportions of dead nodular worms evinced by histology compared to those from mf+ cows. A total of 651 worms were implanted into mice and gerbils, out of which 129 (19.81%) were recovered. Logistic regression analysis indicated that the microfilaridermia status of the cattle (presence of mf) (OR = 4.3319; P = 0.001) is the single most important predictor of the success of male worm recovery after implantation into rodents. ConclusionMicrofilaridermic cattle provide a promising source of adult O. ochengi. Male worms from this group of cattle have a better success rate of survival in a murine implant model. Nevertheless, in the programmatic point of view, amicrofilaridermic Gudali cattle would still constitute an important source of O. ochengi male worms with relatively good viability after implantation into rodents.

Highlights

Current treatment options for onchocerciasis are sub-optimal, prompting research and development of a safe cure
A total of 177 female worms were obtained from the 169 nodules that were digested, 72 of which, were from nodules of mf+ cattle and 105 were from mf– cattle
A total of 105 male worms were extracted from the digested nodules, 33 from nodules of mf+ cattle and 72 from mf– cattle (Table 2)

Summary

Introduction

Current treatment options for onchocerciasis are sub-optimal, prompting research and development of a safe cure (macrofilaricide). There is limited knowledge on how source-related factors such as the microfilaridermia status of the cattle, the nodule load and nodular worm viability may affect survival of male O. ochengi worms implanted in the rodent hosts. Such re lationships were investigated in this study. The mean male worm harvest from nodules were 76.8 ± 120.3 and 47.2 ± 33.4 (p = 0.2488) for mf+ and mf– cattle, respectively. Human Onchocerciasis commonly called river blindness, caused by the filarial nematode Onchocerca volvulus, is a debilitating parasitic disease, affecting human populations in Sub-Saharan Africa, Latin America and Yemen (Mahdy et al, 2018). The need for a macro filaricidal compound to overcome the present challenges and to sup plement current control strategies is of great interest and several of these drugs are currently in the pipeline for screening (Hopkins et al, 2005)

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