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Onchocerciasis (river blindness), caused by the filarial nematode Onchocerca volvulus, is a neglected tropical disease mainly of sub-Saharan Africa. Worldwide, an estimated 20.9 million individuals live with infection and a further 205 million are at risk of disease. Current control methods rely on mass drug administration of ivermectin to kill microfilariae and inhibit female worm fecundity. The identification and development of efficacious vaccines as complementary preventive tools to support ongoing elimination efforts are therefore an important objective of onchocerciasis research. We evaluated the protective effects of co-administering leading O. volvulus-derived recombinant vaccine candidates (Ov-103 and Ov-RAL-2) with subsequent natural exposure to the closely related cattle parasite Onchocerca ochengi. Over a 24-month exposure period, vaccinated calves (n = 11) were shown to acquire infection and microfilaridermia at a significantly lower rate compared to unvaccinated control animals (n = 10). Furthermore, adult female worm burdens were negatively correlated with anti-Ov-103 and Ov-RAL-2 IgG1 and IgG2 responses. Peptide arrays identified several Ov-103 and Ov-RAL-2-specific epitopes homologous to those identified as human B-cell and helper T-cell epitope candidates and by naturally-infected human subjects in previous studies. Overall, this study demonstrates co-administration of Ov-103 and Ov-RAL-2 with Montanide™ ISA 206 VG is highly immunogenic in cattle, conferring partial protection against natural challenge with O. ochengi. The strong, antigen-specific IgG1 and IgG2 responses associated with vaccine-induced protection are highly suggestive of a mixed Th1/Th2 associated antibody responses. Collectively, this evidence suggests vaccine formulations for human onchocerciasis should aim to elicit similarly balanced Th1/Th2 immune responses. [ABSTRACT FROM AUTHOR]

Background: Onchocerciasis currently afflicts an estimated 15 million people and is the second leading infectious cause of blindness world-wide. The development of a macrofilaricide to cure the disease has been hindered by the lack of appropriate small laboratory animal models. This study therefore, was aimed at developing and validating the Mongolian gerbil, as an Onchocerca ochengi (the closest in phylogeny to O. volvulus) adult male worm model. Methodology/Principal findings: Mongolian gerbils (Meriones unguiculatus) were each implanted with 20 O. ochengi male worms (collected from infected cattle), in the peritoneum. Following drug or placebo treatments, the implanted worms were recovered from the animals and analyzed for burden, motility and viability. Worm recovery in control gerbils was on average 35%, with 89% of the worms being 100% motile. Treatment of the gerbils implanted with male worms with flubendazole (FBZ) resulted in a significant reduction (p = 0.0021) in worm burden (6.0% versus 27.8% in the control animals); all recovered worms from the treated group had 0% worm motility versus 91.1% motility in control animals. FBZ treatment had similar results even after four different experiments. Using this model, we tested a related drug, oxfendazole (OFZ), and found it to also significantly (p = 0.0097) affect worm motility (22.7% versus 95.0% in the control group). Conclusions/Significance: We have developed and validated a novel gerbil O. ochengi adult male worm model for testing new macrofilaricidal drugs in vivo. It was also used to determine the efficacy of oxfendazole in vivo. [ABSTRACT FROM AUTHOR]

Background: Onchocerciasis, caused by the parasitic nematode, Onchocerca volvulus afflicts some 37 million people worldwide, and is the second leading infectious cause of blindness globally. The only currently recommended drug for treatment of the disease, ivermectin, is only microfilaricidal and has serious adverse effects in individuals co-infected with high loads of Loa loa microfilariae (mf), prompting the search for new and better drugs. Onchocerciasis drug discovery studies have so far been based on in vivo models using Onchocerca species which are not the closest to O. volvulus, and which may therefore, not adequately mimic the natural infection in humans. Therefore, this study was carried out to develop a better drug screening model for onchocerciasis, based on the use of cow-derived O. ochengi, the closest known relative of O. volvulus.Methods: Mf of O. ochengi were injected subcutaneously at the nape of Syrian hamsters (Mesocricetus auratus) and BALB/c mice. The skin, and especially the earlobes of the animals were examined for mf 15-31 days after infection. For selected model validation, the hamsters were treated with ivermectin at 150 or 600 μg/kg body weight and examined 30 days after infection for mf. For L. loa studies in hamsters, isolated mf were injected intraperitoneally and animal organs were examined on day 26 for mf.Results: The Syrian hamsters were found to be the more permissive to O. ochengi mf as fully viable mf were recovered from them on day 30, compared to BALB/c mice where such mf were recovered on day 15, but not 30. However, both animals were not permissive to L. loa mf even by day 15. Interestingly, more than 50 % of the total O. ochengi mf recovered were from the earlobes. The number of mf injected was directly proportional to the number recovered. Ivermectin at both concentrations tested completely eliminated the O. ochengi mf from the hamsters.Conclusion: This study reveals the Syrian hamster as an appropriate small animal model for screening of novel compounds against O. ochengi, the closest known relative of O. volvulus. [ABSTRACT FROM AUTHOR]