江苏省不明原因轻型呼吸道传染病暴发的病因学研究

Etiological Research of the Unknown Mild Respiratory Tract Infectious Disease in an Outbreak in Jiangsu Province

自2004年4月18日起至6月末,江苏省东台市发生以发热、咽部充血、扁桃体肿大为临床表现的原因不明的疫情暴发,发病人群以中小学生、幼儿为主,地域以许河镇、新街镇以及临近乡镇为主.疫情涉及东台市9个镇,合计报告709例,分布在75个学校,240个班级.暴发的特点为传染性强,短期内出现大量的患者,发病有班级聚集性特点,未发现成人感染.临床表现以发烧(100%)、咽部充血(91.40%)、扁桃体肿大(60.22%)、咽痛(50.00%)为主;X线检查可发现肺纹理增强(90.3%).用Hep-2细胞从患儿20份咽拭子标本中分离到12株病毒,经PCR扩增腺病毒L3部分基因及其PCR产物的序列测定和分析,证实这12株病毒为腺病毒3型;对28份咽拭子标本直接进行DNA提取和PCR扩增,有17份标本PCR扩增L3部分基因呈阳性,经序列测定和分析,也为腺病毒3型.这29个阳性标本L3基因的1 446个核苷酸的序列与GenBank上所发表的腺病毒3型序列同源性高达99.5%.双份血IgG检测:对江苏省采集10份患儿急性期和恢复期双份血清,以从患儿咽拭子分离到的腺病毒3型作为抗原,进行病毒抗体测定,6份患儿的双份血清腺病毒总IgG滴度呈4倍以上增高.患儿急性期血IgA检测:对暴发疫情34例患儿急性期血清(发病时间为1～3天)进行腺病毒IgA抗体测定,结果有9份标本为阳性,1份标本为可疑阳性,阳性率为26.47%.IgA阳性率低可能与血清采集时间过早有关,机体还未全部产生IgA.另外,还对江苏省送检的从患儿血培养基培养的细菌毒株进行了鉴定,对其16S rRNA基因进行了基因扩增及序列分析,序列测定和分析提示为A组M3型化脓性链球菌.实验研究结果并结合此次疫情的流行病学和患儿的临床表现,证实腺病毒3型是引起此次儿童不明原因轻型呼吸道传染病暴发的病原体,部分病例伴有原发或继发化脓性链球菌感染.

An outbreak of the unknown mild respiratory tract infectious disease occurred in the children of Dongtai city of Jiangsu Province from April 18 to the late June in 2004. The clinical syndromes of the patients were fever, pharyngeal hyperemia and antiadoncus, etc. The patients were pupils, middle school students and the infants. Most of the patients distributed in Xuhe, Xinjie and the adjoining townships. 709 patients in 9 townships were reported in this outbreak, who distributed in 240 classes of 75 schools. This outbreak was characterized by high infectivity,massive patients appearing within a relatively short period, and class clustering. No adult infection was found. Clinical manifestations of the patients mainly included fever （100 % ）, pharyngeal hyperemia （91.40 % ）, antiadoncus （60.22 % ） and pharyngalgia （50.00 % ） ; X-ray examination showed intensification of pulmonary grains（90.3 % ）. 12 viral isolates from 20 throat swab specimens using Hep-2 cells were identified as adenovirus type 3 by L3 gene PCR and sequencing analysis. DNA extraction and PCR were carried out directly from 28 throat swab specimens, and 17 positives were also identified as adenovirus type 3 by sequencing analysis. Comparing 1 446 nucleotides of the amplified L3 gene of total of the 29 positive specimens using BLAST server, it showed 99.9 % homology with available adenovirus type3 strains in the GenBank so far,indicating that adenovirus type 3 strains are highly conservative. 10 paired sera of the patients were tested for IgG antibody, using adenovirus type 3 isolate from swab samples as antigen, a four-fold rise in the antibody titer of the adenovirus type 3 appeared in 6 paired sera. 34 acute phase sera （collected within 1 - 3 days after disease onset） were tested for IgA antibody. 9 samples showed positive, 1 was suspected positive, the positive rate was 26.47 %. The relatively low positive rate of IgA may be due to the early collection of sera when IgA antibody had not been totally produced yet. In addition, one bacteria strain cultured from the blood of a patient was identified belonging to A group type M3 pyogenic streptococcus using 16S rRNA gene amplification and sequencing analysis. In this paper, by comprehensive analysis of epidemiology, clinical symptoms and laboratory data, it indicated that adenovirus type 3 was the main etiologic agent of this unknown mild respiratory tract infectious disease outbreak, some patients may have original or secondary acquired pyogenic streptococcus infection.