高免血漿應用於犬瘟熱患犬治療效果之評估

Abstract

犬瘟熱(Canine distemper, CD)為一具高傳染力與高致死率的疾病，臨床上造成全身系統性感染，伴隨著免疫抑制，動物發病早期中和抗體力價之高低會影響疾病的結果，若中和抗體力價持續較低，病毒將無法被清除，進而感染中樞神經系統造成漸進性且多變的神經症狀，出現神經症狀的患犬通常會死亡，僅有少數能耐過。臨床上之治療主要為對症支持治療，但死亡率仍然很高。被動免疫被認為能有效的控制疾病的惡化，然而目前並無實際應用於犬瘟熱患犬療效的報告。本研究目的為評估高免血漿應用於自然感染犬瘟熱患犬的臨床療效。 本研究收集自2009年5月至2011年7月間，至台大動物醫院就診，以RT-nPCR方式確診為犬瘟熱感染之40隻患犬，根據治療方式之不同分為兩組(Group)，進一步分析其治療組合的效果。Group 1(n=21)為接受高免血漿與對症支持治療組，Group 2 (n=19)則為僅接受對症支持治療組。總存活率在Group 1為63.6%，Group 2則為36.8%。比較兩組中出現神經症狀患犬，group 1與group 2的存活率分別為50及7.7 %，且有統計上的差異(p<0.05)。此外，Group 1神經症狀發生率為36.4%，低於Group 2的53.8%。Group 1與Group 2於治療期間才出現神經症狀患犬存活率分別為75%和14.3%，兩組間存活率雖無顯著差異(p=0.088)，但呈現上升之趨勢。Group 1中死亡的七隻患犬有六隻於就診時已經出現神經症狀，此六隻患犬進行屍體解剖，免疫化學染色顯示各器官與腦中皆有不等程度之病毒分布，其中五隻患犬(83.3%)腦部病理結果歸類於犬瘟熱中樞神經病程之急性期。曾有報告認為過度的抗病毒體液免疫反應可能引發衛星脫髓鞘效應，此現象於這些解剖的患犬病並未被發現。Group1中出現神經症狀時，其存活組與死亡组的血液檢體陽性率分別為57%及0%，兩組間血液檢體的陽性率有統計上的差異(p<0.05)。此外，發生神經症狀同時仍有病毒血症的患犬其死亡率為100%。 本研究證實合併給予高免血漿之治療方式，能提升臨床上犬瘟熱患犬的存活率，特別是出現神經症狀的患犬。給予高免血漿能幫助病毒的清除，降低神經症狀的發生率，因此確診為犬瘟熱感染後，及早合併給予高免血漿為一極佳的治療策略。

Canine distemper virus (CDV) is a highly contagious pathogen of dogs causing high mortality. CDV infection can result in a systemic infection with severe immunosuppression. The magnitude of neutralization antibody titers correlates with the outcome of the disease. The constant lack of effective neutralization antibodies causes viral persistence in early stage, and the virus will invade central nervous system (CNS) causing diversely and progressively neurological signs. Dogs with neurological signs usually die, only a few can survive. Supportive or symptomatic therapy is most recommended, however, the mortality of neurological distemper remain very high. Passive immunity was thought to be efficacious in control of disease; nevertheless, the efficacy was never demonstrated in vivo. The aim of this study was to evaluate the clinical efficacy of canine hyperimmune plasma in dogs with canine distemper. Forty dogs confirmed with CDV infection by RT-nPCR, presented at the National Taiwan University Animal Teaching Hospital between May 2009 and July 2011, were enrolled in this study and divided into two groups for further analysis of different therapeutic combinations. Group 1 (21 dogs) was treated with combination of hyperimmune plasma and supportive therapy. 19 dogs were included in group 2 and were only treated with supportive therapy. The total survival rates were 63.6% and 36.8% in group 1 and group 2, respectively. The survival rates of dogs with neurological signs were 50% and 7.7% in group 1 and group 2, respectively. The survival rate of dogs with neurological signs was significantly higher in group1 than in group2 (p<0.05). Furthermore, the incidence of neurological signs in group 1 was 36.4% and lower than in group 2 (53.8%). The survival rate of dogs appeared neurological signs during therapy was 75% and 14.3% in group 1and group 2, respectively. No significant difference was found between the groups in survival rate (p=0.088), however, it existed an increasing trend. Six of the 7 non-survival dogs in group 1had presented neurological signs at presentation. The immunohistochemistry (IHC) examinations of the six autopsic dogs revealed different degrees of viral distributions in various organs and even in brain. According to pathological results of brain, five of them (83.3%) categorized to be acute stage of neurological distemper. A reported side effect, eg. excessive antiviral humoral immune response might trigger the bystander demyelination, was not observed in this study. In group 1, the positive detection rates of whole blood sample by RT-nPCR upon appearance of neurological signs were 57% in the non-survival group and none in the survival group. There was a significant difference between the two subgroups. In addition, the mortality of dogs presented neurological signs together with viremia was 100%. In this study, treatment combined with canine hyperimmune plasma was demonstrated to increase survival rate of CDV-infection, especially the dogs have presented with neurological signs. Administration of hyperimmune plasma benefited to eliminate the virus and to decrease the incidence of neurological signs. Therefore, administration of hyperimmune plasma as soon as possible after confirmed diagnosis represents a good therapeutic strategy in the treatment of CD dogs.