河北地区腺病毒致儿童急性呼吸系统感染的分子流行病学研究

Molecular epidemiological study of adenovirus causing acute respiratory infection in children in Hebei Province

目的分析河北地区由腺病毒(adenovirus,ADV)感染致急性呼吸系统疾病的分子流行病学以及ADV与其他呼吸道病原体混合感染情况。方法收集河北省儿童医院2017年6月—2018年5月急性呼吸道感染住院儿童痰液标本,经13种呼吸道病原体多重检测试剂筛选出ADV阳性标本并用巢氏PCR方法对其六邻体基因进行扩增且测序分型。结果8839份标本中,共检出353份ADV阳性标本,阳性率为3.99%。ADV阳性检出率在不同性别组中的差异无统计学意义(χ^2=0.0003,P=0.99),在不同年龄组中的差异有统计学意义(χ^2=115.69,P<0.001)。353份ADV阳性标本包括11种血清型,259例混合感染标本。11种血清型占比分别为1型16.15%(57/353)、2型35.98%(127/353)、3型21.25%(75/353)、4型1.13%(4/353)、5型11.33%(40/353)、6型3.97%(14/353)、7型8.22%(29/353)、31型0.28%(1/353)、41型0.28%(1/353)、55型0.28%(1/353)、57型1.13%(4/353)。259份混合感染标本中常见的是ADV与人鼻病毒(human rhinovirus,HRV)占35.52%,ADV与呼吸道合胞病毒(respiratory syncytial virus,RSV)占12.74%,其中33.20%发生了三重及以上混合感染。ADV常年可检出,其中9月与4—5月检出率偏高,主要以1、2、3型检出为主。发生ADV单独感染和混合感染的两组人群年龄分别为(27.56±24.67)个月和(21.33±20.28)个月,差异有统计学意义(P=0.037)。ADV2型单独感染率(25.77%,25/97)比其他呼吸道病原体混合感染率(39.84%,102/256)低且差异有统计学意义(χ^2=6.05,P=0.014),ADV7型单独感染率(16.49%,16/97)比其与其他呼吸道病原体混合感染率(5.08%,13/256)高,差异有统计学意义(χ^2=12.16,P<0.001)。结论河北地区2017年6月—2018年5月ADV感染主要以1、2、3型为主,且常年可检出,9月与4—5月检出率偏高,年龄越小检出率越高。ADV2型易与其他呼吸道病原体发生混合感染,ADV7型不易与其他呼吸道病原体发生混合感染,且HRV与ADV的混合感染最为常见。

Objective To analyze the molecular epidemiology of adenovirus (ADV) causing acute respiratory diseases and to investigate the mixed infection of ADV and other respiratory pathogens in Hebei Province. Methods Sputum samples were collected from inpatient children with acute respiratory diseases at Children′s Hospital of Hebei Province between June 2017 and May 2018. Multiplex reverse transcription PCR assay was used to detecte 13 kinds of respiratory pathogens. Nested PCR was performed to amplify ADV hexon gene and the amplified products were then sequenced. Results A total of 353 ADV-positive specimens were detected in 8 839 specimens with a positive rate of 3.99%. Significant difference in the positive rate of ADV was not observed between male and female patients (χ^2=0.000 3, P=0.99), but found among different age groups (χ^2=115.69, P<0.001). All isolated ADV strains belonged to 11 serotypes, which were type 1 (16.15%, 57/353), type 2 (35.98%, 127/353), type 3 (21.25%, 75/353), type 4 (1.13%, 4/353), type 5 (11.33%, 40/353), type 6 (3.97%, 14/353), type 7 (8.22%, 29/353), type 31 (0.28%, 1/353), type 41 (0.28%, 1/353), type 55 (0.28%, 1/353) and type 57 (1.13%, 4/353). Among the 353 ADV-positive specimens, 259 were mixed infections mainly caused by ADV and human rhinovirus (35.52%). ADV and respiratory syncytial virus co-infections accounted for 12.74% and 33.20% of the mixed infections involved three or more pathogens. ADV could be detected throughout the year, especially in September and April to May. The predominant serotypes were types 1, 2 and 3. The average ages of the two groups of ADV infection alone and ADV mixed infection were (27.56±24.67) months and (21.33 ±20.28) months, respectively, and the difference between them was statistically significant (P=0.037). The incidence of ADV 2 infection alone was 25.77% (25/97), which was lower than that of ADV 2-involved mixed infection [39.84% (102/256), χ^2=6.05, P=0.014]. However, the rate of ADV 7 infection alone was significantly higher than that of ADV 7-involved mixed infection [16.49% 16/97) vs 5.08% (13/256), χ^2=6.05, P<0.001]. Conclusion ADV 1, ADV 2 and ADV 3 were the predominant serotypes circulating in Hebei Province from June 2017 to May 2018, especially in September and April to May. The younger the patients were, the higher the incidence would be. ADV 2 was prone to cause mixed infections with other respiratory pathogens, while ADV 7 was less common in mixed infections. Younger patients were more susceptible to mixed infections. The most common co-infection was caused by ADV and human rhinovirus.