Authors

H Sjoberg¹; N Pionnier¹; H MetugeneA Njouendou F FombadP NdongmoD Tayong A Steven¹; D Cooke¹; M Taylor¹; S WanjiJ Turner¹;  ¹ Liverpool School of Tropical Medicine;  ² University of Buea, Cameroon

Discussion

Development of macrofilaricides to eliminate onchocerciasis in Africa requires assessments of toxicity to blood-stage Loa loa microfilariae (mf) which may cause severe adverse reactions. Here we describe the development of mouse models of loiasis with the goal of evaluating them as in vivo microfilaricide drug screens. Initially, susceptibility to infection was assessed using Brugia malayi mf or infectious larvae (L3). Strains evaluated were BALB/c WT, selective immune knockouts, SCID, NOD.SCID or NOD.SCID IL-2gc^-/- (NSG). Subsequently BALB/c WT or SCID (+/- splenectomy) were perfused with Loa mf. SCID strains were infected with Loa L3 and evaluated at 5 months post-inoculation. To evaluate drug responsiveness, microfilariaemic mice were treated with ivermectin. For mf perfusion, no differences in the levels of circulating mf were observed in all strains assessed, although splenectomy increased the longevity of peripheral Loa mf in WT mice. The majority of mf (~10% of initial inoculates) were sequestered in the cardiopulmonary circulation. Ivermectin induced a rapid decline (>70%) in circulating mf in WT and SCID mice. For patent Loa infections, NSG mice yielded an average recovery of adult worms of 33% of the initial inoculate. No circulating microfilariae were observed although embryograms of female worms identified occurrence of embryogenesis and inter-uterine mf. Both models show promise for use as pre-clinical counter-screens.