中国高致病性禽流感A／H5N1病毒感染患者的临床与预后

Relationship between clinical features and prognosis of highly pathogenic avian influenza A/H5N1 infection in humans in China's Mainland

目的研究我国卫生部公布的28例高致病性禽流感A／H5N1病毒感染（简称人禽流感）病例的临床特点，评估其临床与预后的相关性。方法回顾总结我国2005年11月至2008年5月临床及实验室确诊的28例人禽流感病例的临床资料，应用EPIDATA 3．02建立数据库，并应用SPSS 13．0软件进行统计分析，计量资料采用独立样本非参数检验，计数资料应用χ^2（fisher）检验。结果我国28例人禽流感病例中，男13例，女15例，治愈10例，死亡18例。发病中位年龄为29岁（6～62岁），发热为本病最突出的临床表现（100％）。治愈患者首次血常规检测白细胞为（4．0±1．9）×10^9／L，淋巴细胞为（1．09±0．49）×10^9／L，血小板为（116±39）×10^9／L；死亡患者分别为（5．1±2．9）×10^9／L、（0．98±0．44）×10^9／L及（101±40）×10^9／L，两组比较差异均无统计学意义（P〉0．05）。治愈与死亡患者天冬氨酸转氨酶分别为（173±246）U／L和（272±263）U／L，乳酸脱氢酶（LDH）分别为（1016±568）U／L和（1512±1052）U／L，肌酸激酶分别为（1099±1590）U／L和（2534±4281）U／L，肌酸激酶同工酶分别为（28±30）U／L和（125±197）U／L。死亡患者发病初期LDH水平大于正常值上限8倍以上者6例。疾病极期均出现双侧肺部病变。22例发展为急性呼吸窘迫综合征，其中治愈患者中5例，死亡患者中17例；急性肾损伤9例，均死亡。奥司他韦抗病毒治疗的10例中，6例康复，4例死亡，康复和死亡患者开始使用奥司他韦的时间分别为（6．5±3．0）d和（11．8±3．3）d。28例患者均不同程度接受了抗生素和糖皮质激素治疗，开始应用糖皮质激素的时间和疗程治愈患者与死亡患者无差异。结论（1）发病初期LDH升高大于正常上限8倍以上者预后不良；（2）合并急性呼吸窘迫综合征及急性肾损伤者预后差；（3）发病早期应用有效抗病毒治疗可改善预后。

Objective To investigate the relationship between clinical features of patients with A/H5N1 infection and their prognosis in China's Mainland. Methods This study included 28 human cases with A/H5N1 infection in China's Mainland from October 2005 to May 2008. Data were collected and reviewed from hospital medical records and publishied papers. A database was built by EPIDATA 3. 02 and statistical analyses were performed with SPSS 13.0. Results The median age of the 28 cases was 29 years （ range 6 -62） , and 15 were females. Ten patients survived, and 18 died. The typically clinical manifestations of human influenza A/H5N1 infection included fever and lower respiratory infection. The numbers of peripheral white blood cells, lymphocytes and platelets in the survival and non-survival groups were （4. 01 ± 1.86）×10^9/L vs （5.1±2.9）×10^9/L, （1.09±0.49）×10^9/L vs （0.98 ±0.44）×10^9/L, and （116±39）×10^9/L vs （101 ± 40）×10^9/L, respectively; the differences were not statistically significant between the 2 groups （P 〉 0. 05）. There was also no statistically significant difference in the increased serum enzymes, such as aspartate aminotransferase [ （ 173 ± 246） U/L vs （ 272 ± 263 ） U/L ] , lactate dehydrogenase [ （ 1016 ± 568） U/L vs （ 1512 ± 1052） U/L], creatine kinase [ （ 1099 ± 1590） U/L vs （2534 ± 4281 ） U/L] and MB isoenzymeof creatine kinase [（28 ±30）U/L vs （125±197）U/L] （P 〉0.05） between the survival and the non-survival groups. However, there was a statistically significant difference in the number of patients with an initial LDH level more than 8 fold of the normal value between the survival and the nonsurvival groups （ none vs 6, P 〈 0. 05 ）. All of the 28 cases developed bilateral muhiple infiltrates and consolidation in chest radiographs. Acute respiratory distress syndrome occurred in 22 cases, 17 of them died. All the 9 patients with acute kidney injury died. Ten patients received antiviral treatment with oscltamivir, and 6 of them survived. There was a statistical difference in the time of initiating oseltamivir treatment between the survival and the non-survival eases [ （6. 5 ±3.0）d vs （ 11.8 ±3. 3）d, Z =3. 70, P 〈 0. 05 ]. Broad spectrum antibiotics and corticosteroids were administered in all of the 28 eases. There was no statistical difference between the survival and the non-survival groups regarding to the corticosteroid treatment （ P 〉 0. 05 ）. Conclusions Initial LDH level reaching more than 8 fold of the normal value suggests a poor prognosis for human H5N1 infection. Patients complicated with either ARDS or acute kidney injury had a higher risk of death. Early administration of effective antiviral agents might improve the prognosis and decrease case fatality.