Chow Nancy A, Lindsley Mark D, McCotter Orion Z, Kangiser Dave, Wohrle Ron D, Clifford Wayne R, Yaglom Hayley D, Adams Laura E, Komatsu Kenneth, Durkin Michelle M, Baker Rocky J, Shubitz Lisa F, Derado Gordana, Chiller Tom M, Litvintseva Anastasia P
Mycotic Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
Zoonotic Disease Program, Office of Environmental Public Health Sciences, Washington State Department of Health, Olympia, Washington, United States of America.
PLoS One. 2017 Apr 5;12(4):e0175081. doi: 10.1371/journal.pone.0175081. eCollection 2017.
Coccidioides is a soil-dwelling fungus that causes coccidioidomycosis, a disease also known as Valley fever, which affects humans and a variety of animal species. Recent findings of Coccidioides in new, unexpected areas of the United States have demonstrated the need for a better understanding of its geographic distribution. Large serological studies on animals could provide important information on the geographic distribution of this pathogen. To facilitate such studies, we used protein A/G, a recombinant protein that binds IgG antibodies from a variety of mammalian species, to develop an enzyme immunoassay (EIA) that detects IgG antibodies against Coccidioides in a highly sensitive and high-throughput manner. We showed the potential of this assay to be adapted to multiple animal species by testing a collection of serum and/or plasma samples from dogs, mice, and humans with or without confirmed coccidioidomycosis. We then evaluated the performance of the assay in dogs, using sera from dogs residing in a highly endemic area, and found seropositivity rates significantly higher than those in dogs of non-endemic areas. We further evaluated the specificity of the assay in dogs infected with other fungal pathogens known to cross-react with Coccidioides. Finally, we used the assay to perform a cross-sectional serosurvey investigating dogs from Washington, a state in which infection with Coccidioides has recently been documented. In summary, we have developed a Coccidioides EIA for the detection of antibodies in canines that is more sensitive and has higher throughput than currently available methods, and by testing this assay in mice and humans, we have shown a proof of principle of its adaptability for other animal species.
球孢子菌是一种生长在土壤中的真菌,可引起球孢子菌病,这是一种也被称为山谷热的疾病,会影响人类和多种动物物种。最近在美国新的、意想不到的地区发现了球孢子菌,这表明有必要更好地了解其地理分布。对动物进行大规模血清学研究可以提供有关这种病原体地理分布的重要信息。为了促进此类研究,我们使用蛋白A/G(一种能结合多种哺乳动物物种IgG抗体的重组蛋白)开发了一种酶免疫测定法(EIA),该方法能以高灵敏度和高通量的方式检测针对球孢子菌的IgG抗体。我们通过检测来自患有或未患有确诊球孢子菌病的狗、小鼠和人类的血清和/或血浆样本集,展示了该测定法适用于多种动物物种的潜力。然后,我们使用来自高度流行地区的狗的血清评估了该测定法在狗身上的性能,发现血清阳性率显著高于非流行地区的狗。我们进一步评估了该测定法在感染了已知会与球孢子菌发生交叉反应的其他真菌病原体的狗身上的特异性。最后,我们使用该测定法对来自华盛顿州的狗进行了横断面血清学调查,该州最近有球孢子菌感染的记录。总之,我们开发了一种用于检测犬类抗体的球孢子菌EIA,它比现有方法更灵敏且通量更高,并且通过在小鼠和人类中测试该测定法,我们证明了其适用于其他动物物种的原理。