Abstract
BackgroundOnchocerciasis, 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.MethodsMf 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.ResultsThe 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.ConclusionThis 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.
Highlights
Onchocerciasis, caused by the parasitic nematode, Onchocerca volvulus afflicts some 37 million people worldwide, and is the second leading infectious cause of blindness globally
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
The hamster is permissive to mf of O. ochengi, but not to those of L. loa To test if the Syrian hamster was permissive to O. ochengi mf, three preliminary exploratory experiments were done with different numbers of mf injected in each animal (Table 1)
Summary
Onchocerciasis, caused by the parasitic nematode, Onchocerca volvulus afflicts some 37 million people worldwide, and is the second leading infectious cause of blindness globally. Onchocerciasis is a neglected tropical disease caused by the filarial nematode, Onchocerca volvulus It afflicts some 37 million people globally, with 99 % of all the cases living in sub-Saharan Africa [1]. Onchocerciasis was estimated to account for 18.3 million disabilityadjusted life years (DALYs) in sub-Saharan Africa within 20 years [2] It is the second leading infectious cause of. Mbah et al BMC Infectious Diseases (2016) 16:404 the O. volvulus mf This drug is only a microfilaricide, and a major challenge with ivermectin treatment is the fact that it kills L. loa mf in blood, a situation that often leads to severe adverse events (encephalopathy and death) in individuals with high L. loa mf load [6]. There is evidence of resistance or low response rate of mf to ivermectin [7, 8], emphasizing the need for new therapeutic options
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