Advances in Preclinical Platforms of Loa loa for Filarial Neglected Tropical Disease Drug and Diagnostics Research

Abstract

The tropical disease, loiasis, caused by the filarial parasite, Loa loa, has gained prominence in global public health as a cause of excess mortality and a barrier to the elimination of the related prioritized neglected tropical diseases (NTDs), lymphatic filariasis and onchocerciasis, within Central Africa. There are no effective drug cures or vaccines available to treat loiasis safely. Here we review recent advances in loiasis preclinical platform technologies, including novel in vitro culturing systems, animal models and innovations in experimental infections of the L. loa vector, Chrysops, that have facilitated access to all L. loa filarial life-cycle stages. We detail applications of these new model systems in anti-filarial drug screening, diagnostic development, immunology, and pathophysiology research. Finally, we provide an overview of how loiasis preclinical platforms may be further utilized in translational medicine applications to support the development of much needed new interventions against filarial NTDs.

Pyrvinium Pamoate and Structural Analogs Are Early Macrofilaricide Leads

“…To assess the potential use of PVP, THP and 06 in countries co-endemic for Loa loa, further in vitro studies are necessary to determine the IC 50 s of these compounds with mf, as well as validating the potency of these compounds on the mf in animal models [28].…”

Comparative development of human filariae Loa loa, Onchocerca volvulus and Mansonella perstans in immunocompromised mouse strains

“…Since no L3 could be recovered from M. perstans and O. volvulus inoculated mice, we were wondering if the isolated L3 were suitable for mouse infection experiments. However, previous studies showed that immunocompromised mice were susceptible to Loa loa L3 (27)(28)(29). Thus, we isolated Loa loa L3 from engorged Chrysops flies to inoculate the different immunocompromised mice with Loa loa L3.…”