Abstract

The tropical disease, loiasis, caused by the filarial parasite, 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.

Highlights

  • Loiasis is a tropical parasitic infection caused by the filarial nematode, Loa loa, endemic in forested areas of Central and West Africa

  • Following clinical evidence that W. bancrofti antigen-based immunodiagnostic tests cross-react with L. loa patients with high microfilaraemias [63], laboratory investigations were initiated to understand the molecular basis of cross-reactivity

  • Proteomic pulldown experiments have identified a specific ‘Av33-like’ secreted L. loa protein antigen derived from immature adult L. loa cultures and from loiasis patient serum that is recognised by the monoclonal antibody, AD12, used in lymphatic filariasis (LF) immuno-chromatographic test (ICT)/FTS rapid diagnostic tests [65]

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Summary

INTRODUCTION

Loiasis is a tropical parasitic infection caused by the filarial nematode, Loa loa, endemic in forested areas of Central and West Africa. A distinct complication of L. loa co-endemicity, disrupting the elimination of LF in Central Africa, is the occurrence of cross-reactivity to current point-of-care rapid diagnostic tests (RDTs) used in mapping of LF endemic regions and decision making to stop MDA [20, 21]. For these reasons, development of new tools to address the treatment of filarial disease in Central Africa are urgently required. We focus on these most recent advances and applications in loiasis pathophysiology, drug and diagnostic translational medicine

LOIASIS IN VITRO CULTURES
APPLICATION OF LOIASIS IN VITRO CULTURES IN DRUG SCREENING
Preclinical Platforms of Loa loa B
APPLICATION OF IN VIVO LOIASIS MODELS IN PATHOPHYSIOLOGY STUDIES
APPLICATIONS OF LOIASIS PRECLINICAL PLATFORMS IN DIAGNOSTICS RESEARCH
CONCLUSIONS
Findings
AUTHOR CONTRIBUTIONS
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