犬吉貝氏焦蟲亞洲型感染之兩種不同治療策略效果之評估

犬吉貝氏焦蟲亞洲亞型的感染(Babesia gibsoni，B. gibsoni)之治療長期以來對臨床獸醫師相當具有挑戰性，自從發現對atovaquone具抗藥性的蟲體後，治療B. gibsoni除了合併給予atovaquone以及azithromycin(簡稱AA組)外，研究其他治療策略就顯得非常重要。本研究的目的在於評估合併給予clindamycin phosphate、diminazene aceturate及imidocarb diproprionate(簡稱CDI組)之療效並與AA組的治療效力做比較，進一步分析台灣焦蟲的基因突變情形。本研究將三十隻經由血液抹片檢查(blood smear examination)或聚合酶鏈鎖反應(polymerase chain reaction，PCR)確診為B. gibsoni感染的患犬，依據治療方法不同分為兩組：AA組以atovaquone (13.3mg/Kg body weight，PO，q8h) 與azithromycin (10mg/Kg body weight，PO， q24h)合併治療，CDI組則以clinidamycin phosphate (30mg/kg body weight，PO， q12h)、diminazene aceturate (3.5mg/kg body weight，IM，就診日單次注射) 與 imidocarb diproprionate(6mg/kg body weight，SC，注射完diminazene後隔天單次給予)合併治療。完整紀錄患犬就診當天(day 0)與回診第7、14、21與28天的血紅素(Hb)、血容比(PCV)、紅血球(RBC)、血小板數(platelet counts)與寄生蟲血症(parasitemia)，利用巢式多重引子PCR(multiplex-nested PCR，Nested-mPCR)區分B. gibsoni的型別，並定序B. gibsoni cytochrom b(CYTb)基因以觀察突變情形。根據本研究結果，CDI組和AA組有相同的抑制寄生蟲血症與使血液檢查異常恢復的能力，甚至在第28天時，CDI組的Hb、PCV與RBC數值都較AA組高。AA組的復發率(relapse rate)為41.2%然而在CDI組僅15.4%，並且在所有AA組未康復的犬隻中都發現CYTb基因的M121I突變。綜合上述，B. gibsoni在AA組合治療之後確實出現抗藥性，而且CYTb基因的M121I突變與抗藥性的蟲體具絕對相關。因此一旦犬隻復發，則B. gibsoni CYTb基因的定序就顯得相當重要，如果出現了M121I的突變，則需要考量AA組合以外的治療策略。和AA組合相比，CDI組合雖然需要較長的治療時間，但是降低寄生蟲血症的能力相同，且有較高的康復率及所需的花費較少且無明顯的副作用，因此，在臨床治療犬隻B. gibsoni感染上，本研究的發現提供了一個新的選擇。

關鍵字

犬；焦蟲；治療

並列摘要

The treatment of Babesia gibsoni Asian genotype (B. gibsoni Asian genotype) has long been a challenge to veterinarians as no drug can be used alone to eliminate the pathogen. Thirty client-owned dogs naturally infected with B. gibsoni as diagnosed with blood smear examination and/or polymerase chain reaction (PCR) were enrolled in this study. Dogs were divided into two groups based on the treatment strategy initially. AA group received atovaquone (13.3mg/Kg body weight, PO, q8h) and azithromycin (10mg/Kg body weight, PO, q24h) and CDI group was treated with clinidamycin phosphate (30mg/kg body weight, PO, q12h), diminazene aceturate (3.5mg/kg body weight, IM, single dose at presenting day) and imidocarb diproprionate(6mg/kg body weight, SC, single dose, the day after diminazene was administrated). PCV, Hb, RBC, platelet counts, and parasitemia were recorded at presenting day (day 0) and during treatment at day 7, 14, 21, and 28. The B. gibsoni 18S rRNA gene was amplified and B. gibsoni cytochrom b (CYTb) gene were sequenced. As compare from the efficacy of suppressing parasitemia and the recovery of hematologic abnormalities, both groups have almost equal efficacy in treating B. gibsoni infection. Values of Hb, PCV, and RBC were higher in CDI group than in AA group at day 28. There were 41.2% dogs in AA group and 15.4% dogs in CDI relapsed after treatment, AA had higher relapsed rate than CDI. M121I mutation in B. gibsoni CYTb gene was detected in all AA-relapse and AA-non-remission samples. Drug resistance do occurred after treating by AA combination and M121I mutation in B. gibsoni CYTb gene is highly correlated in atovaquone-resistant B. gibsoni. Once relapse occurred, screening of the sequence of B. gibsoni CYTb gene is important and an alternative therapeutic strategy should be considered. Compared to AA combination, CDI combination has the same efficacy to suppress parasitemia, a higher recovery rate, and is less expensive without obvious side effects, unless it took longer treatment period. The CDI combination provided a good alternative choice in treating B. gibsoni Asian genotype.

並列關鍵字

canine babesiosis ； Babesia gibsoni

參考文獻

Abdullahi S.U., Mohammed A.A., Trimnell A.R., 1990: Clinical and haematological findings in 70 naturally occurring cases of canine babesiosis. J Small Anim Pract, 31, 145-147.

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Birkenheuer A.J., Correa M.T., Levy M.G., 2005: Geographic distribution of babesiosis among dogs in the United States and association with dog bites: 150 cases (2000–2003). J Am Vet Med Assoc, 227, 942–947.

Birkenheuer A.J., Levy M.G., Breitschwerdt E.B., 2003: Development and evaluation of a seminested PCR for detection and differentiation of Babesia gibsoni (Asian genotype) and B. canis DNA in canine blood samples. J Clin Microbiol, 1, 4172-4177.

Birkenheuer A.J., Levy M.G., Savary K.C.M., 1999: Babesia gibsoni infections in dogs from North Carolina. J Am Anim Hosp Assoc 35:125-128.

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犬吉貝氏焦蟲亞洲型感染之兩種不同治療策略效果之評估

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