Hartley Ashley N, Marr Henry S, Birkenheuer Adam J
Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, USA.
Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, Tennessee, USA.
J Vet Intern Med. 2020 Nov;34(6):2432-2437. doi: 10.1111/jvim.15935. Epub 2020 Nov 4.
Atovaquone and azithromycin (A&A) with supportive care improve survival rates in cats with cytauxzoonosis. Resistance to atovaquone via parasite cytochrome b gene (cytb) mutations occurs in other Apicomplexan protozoans but is not described in Cytauxzoon felis.
To serially characterize the C. felis cytb sequences from a cat that remained persistently infected after A&A treatment.
A cat with naturally occurring C. felis infection.
Case report of the anemic cat persistently infected with C. felis before, during and after A&A treatment. Cytauxzoon felis cytb genes were amplified and sequenced before, during and after A&A treatment.
Cytauxzoon felis was detected before, during and after A&A treatment including samples collected 570 days after treatment. After A&A treatment, the cat's anemia improved slightly. Cytb sequencing revealed only wild-type cytb methionine (M128) in samples collected before treatment. In samples collected after treatment, the cytb coded for isoleucine (M128I) and valine (M128I) at 2- and 4-months after treatment. These M128I and M128V mutations persisted even after a repeat treatment course with a higher dose atovaquone combined with the standard dose of azithromycin.
This report documents C. felis atovaquone resistance associated with M128 cytb mutations. This study suggests parasites with mutations of cytb M128 can be selected and impart resistance to A&A treatment even with higher atovaquone dosing.
阿托伐醌和阿奇霉素(A&A)联合支持性治疗可提高感染嗜吞噬细胞无形体病猫的存活率。在其他顶复门原生动物中,寄生虫细胞色素b基因(cytb)突变会导致对阿托伐醌产生耐药性,但在猫嗜吞噬细胞无形体中尚未见相关报道。
对一只接受A&A治疗后仍持续感染的猫的猫嗜吞噬细胞无形体cytb序列进行连续特征分析。
一只自然感染猫嗜吞噬细胞无形体的猫。
对一只在A&A治疗前、治疗期间和治疗后持续感染猫嗜吞噬细胞无形体的贫血猫进行病例报告。在A&A治疗前、治疗期间和治疗后对猫嗜吞噬细胞无形体cytb基因进行扩增和测序。
在A&A治疗前、治疗期间和治疗后均检测到猫嗜吞噬细胞无形体,包括治疗后570天采集的样本。A&A治疗后,猫的贫血症状略有改善。cytb测序显示,治疗前采集的样本中仅存在野生型cytb甲硫氨酸(M128)。治疗后采集的样本中,治疗后2个月和4个月时cytb编码异亮氨酸(M128I)和缬氨酸(M128V)。即使在使用更高剂量的阿托伐醌与标准剂量的阿奇霉素联合进行重复治疗后,这些M128I和M128V突变仍然存在。
本报告记录了与M128 cytb突变相关的猫嗜吞噬细胞无形体对阿托伐醌的耐药性。本研究表明,即使使用更高剂量的阿托伐醌,具有cytb M128突变的寄生虫仍可被选择并对A&A治疗产生耐药性。