登革熱不同時期與血液參數變化之評估

Assessment of Complete Blood Count Parameters in Dengue Fever Progression

2015年臺南市爆發嚴重登革熱 （dengue fever）疫情，以第二血清型登革病毒（dengue virus, DENV）為主，這是與過去報告所不同的。從成大醫院血液組收集確診登革熱陽性的523個案例進行統計分析，將血清學登革病毒非結構蛋白（dengue virus non-structural protein 1, DENV NS1）抗原與登革病毒特異性IgM/IgG （dengue IgM/IgG）抗體出現分成六個時期，分別與病毒量（viral load）和全套血液計數（complete blood count, CBC）參數進行接收操作特徵曲線（receiver operating characteristic, ROC）與曲線下面積 （area under curve, AUC）的統計分析。結果顯示，登革病毒量（viral load, AUC:0.833）與血小板數量 （platelet count, AUC: 0.651） 升高，在血清單一表現DENV NS1抗原時相關；血紅素（hemoglobin）在dengue IgM抗體出現後相關（AUC: 0.686），但至DENV NS1抗原消失後，血紅素即不具相關性（AUC: 0.392）；淋巴細胞（lymphocyte, AUC: 0.999）在血清開始表現dengue IgG抗體後高度相關，而非典型淋巴細胞（atypical lymphocyte, AUC: 0.914）在血清開始表現dengue IgG抗體後亦呈現高度相關，然而當DENV NS1抗原與dengue IgM抗體同時消失後，非典型淋巴細胞即不具相關性；嗜鹼性顆粒球（basophil, AUC:0.910）與單核球（monocyte, AUC: 0.809）僅在血清單一表現dengue IgG抗體時高度相關。總結，感染登革熱改變CBC顯著相關參數的表現依序為血小板、血紅素、淋巴球、嗜鹼性顆粒球與單核球。

Of the 2015 dengue outbreak in Taiwan, a significantly rising number of dengue fever cases in Tainan City, was mostly caused by an Asian strain of dengue virus type 2 (DENV-2) which differed from the previous reports. We retrospectively recruited 523 serum samples in the archives of the Hematology Laboratory in National Cheng Kung University Hospital and divided them into six groups based on the sequential detection of NS1 antigen, IgM and IgG antibodies. Meta-analyses by fitting receiver operating characteristic (ROC) and area under curve (AUC) were performed to analyze the kinetics of viral load and complete blood count (CBC) parameters in each group. The results revealed a relevance of the presence merely NS1 to viral load (AUC: 0.833) and platelet count (AUC: 0.651) and further the concomitant presence of IgM antibody to hemoglobin (AUC: 0.686) until NS1 disappeared. Next, the appearance of IgG antibody was relevant to lymphocyte (AUC: 0.999) and atypical lymphocyte (AUC: 0.914). However, IgG antibody was not relevant to atypical lymphocyte when NS1 antigen and IgM antibody were undetectable. Finally, at the merely IgG stage, the relevances to the percentages of basophil (AUC:0.910) and monocyte (AUC: 0.809) were found. In conclusion, the distinct characters of hematological changes for the dengue virus infection were sequentially identified as platelet, hemoglobin, lymphocytes, basophils and monocytes.