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Published on: April 21, 2012
Development and validation of small animal models for onchocerciasis and loiasis microfilaricide discovery
Rene Bilingwe Ayiseh1, Glory Enjong Mbah1, Elvis Monya1
1ANDI Centre of Excellence for Onchocerciasis Drug Research, Biotechnology Unit, Faculty of Science, University of Buea, Buea, Cameroon.
Background:
Onchocerciasis (river blindness) caused by the filarial worm Onchocerca volvulus is a neglected tropical disease that affects the skin and eyes of humans. Mass drug administration with ivermectin (IVM) to control the disease often suffers from severe adverse events in individuals co-injected with high loads of Loa loa microfilariae (mf). Thus loiasis animal models for counter-screening of compounds effective against onchocerciasis are needed, as are the corresponding onchocerciasis screening models. The repertoire of such models is highly limiting. Therefore, this study was aimed at developing and validating mf immunocompetent small animal models to increase tools for onchocerciasis drug discovery.
Methodology/Principal Findings:
O. ochengi mf from cattle skin and L. loa mf from human blood were used to infect BALB/c mice and Mongolian gerbils, and IVM was used for model validation. O. ochengi mf were given subcutaneously to both rodents while L. loa mf were administered intravenously to mice and intraperitoneally to gerbils. IVM was given orally. In an 8-day model of O. ochengi mf in BALB/c mice, treatment with IVM depleted all mf in the mice, unlike the controls. Also, in a 2.5-day model of L. loa mf in BALB/c, IVM significantly reduced mf in treated mice compared to the untreated. Furthermore, the gerbils were very susceptible to O. ochengi mf and IVM eradicated all mf in the treated animals. In the peritoneal L. loa mf gerbil model, IVM reduced mf motility in treated animals compared to the controls. In a 30-day gerbil co-injection model, IVM treatment cleared all O. ochengi mf and reduced motility of L. loa mf. Both mf survived for up to 50 days in a gerbil co-injection model.
Conclusions/Significance:
We have developed two immunocompetent small animal models for onchocerciasis and loiasis that can be used for microfilaricide discovery and to counter-screen onchocerciasis macrofilarides.
Insights
New immunocompetent small animal models were developed for onchocerciasis and loiasis drug discovery. These models help screen for drugs effective against river blindness and loiasis, addressing limitations in current research tools.
Area of Science:
- Parasitology
- Tropical Medicine
- Drug Discovery
Background:
- Onchocerciasis (river blindness) is a neglected tropical disease impacting skin and eyes.
- Mass drug administration with ivermectin (IVM) faces challenges due to severe adverse events in individuals with high Loa loa microfilariae (mf) loads.
- Existing animal models for onchocerciasis and loiasis are limited, hindering drug development.
Purpose of the Study:
- To develop and validate immunocompetent small animal models for onchocerciasis and loiasis.
- To provide essential tools for microfilaricide discovery and counter-screening of onchocerciasis macrofilaricides.
- To overcome limitations in current screening models for these neglected tropical diseases.
Main Methods:
- Infection of BALB/c mice and Mongolian gerbils with Onchocerca ochengi mf (cattle) and Loa loa mf (human).
- Subcutaneous, intravenous, and intraperitoneal administration routes for mf, with oral IVM administration for validation.
- Validation of models using IVM efficacy in reducing mf loads and motility.
Main Results:
- IVM treatment eradicated O. ochengi mf in BALB/c mice and gerbils.
- IVM significantly reduced L. loa mf in mice and their motility in gerbils.
- Both mf species survived up to 50 days in gerbil co-infection models, demonstrating model utility.
Conclusions:
- Successfully developed immunocompetent small animal models for onchocerciasis and loiasis.
- These models are valuable for microfilaricide discovery and counter-screening of onchocerciasis macrofilaricides.
- The new models expand the toolkit for advancing drug discovery against these parasitic diseases.
