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Mouse models of Loa loa.
Nicolas P Pionnier1, Hanna Sjoberg1, Valerine C Chunda2,3
1Centre for Drugs and Diagnostics Research, Department of Tropical Disease Biology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK.
Nature Communications
|March 31, 2019
Summary
New mouse models for Loa loa infections help study river blindness treatments. These models show ivermectin reduces parasites but can cause allergic reactions, aiding drug development and safety research.
Area of Science:
- Parasitology
- Immunology
- Drug Development
Background:
- River blindness elimination is hindered by ivermectin's adverse reactions in patients co-infected with loiasis.
- Preclinical research tools for filarial diseases, particularly Loa loa, are limited.
Purpose of the Study:
- To develop and validate mouse models for Loa loa infection to advance filarial translational research.
- To investigate the efficacy of treatments and the etiology of adverse reactions associated with ivermectin.
Main Methods:
- Experimental infection of lymphopenic and immune-competent mice with Loa loa.
- Infusion of purified Loa loa microfilariae (mf) into mice.
- Treatment with ivermectin and benzimidazole, followed by assessment of parasitemia and inflammatory markers.
Main Results:
- Established Loa loa infection models in mice, showing adult worms, circulating mf, and biomarkers.
- Demonstrated ivermectin effectively reduces parasitemia (>90%) in microfilaraemic mice.
- Identified up-regulation of allergic type-2 immune response markers and eosinophilia post-ivermectin treatment.
Conclusions:
- Validated murine models are crucial for identifying loiasis biomarkers.
- These models can be used to counter-screen potential river blindness treatments.
- The models aid in understanding the inflammatory causes of ivermectin-associated adverse reactions in loiasis.
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