AdVs were the important agent of pediatric severe pneumonia, which can induce large-scale epidemics. AdVs infection was one of the common causes of pneumonia in Beijing and Shanghai area of China from the 1950s to 1960s, with more complications and high fatality rates. In the late 1980s, the incidence declined with only some diverging cases.
RSV and AdVs are the major agents of viral pneumonia in large cities, accounting for 10%–15% respectively. AdVs accounts for 32.2% of severe pneumonia according to Liu et al. The results of virus separation in cell culture in our hospital from 1975 to 1985 showed that the years 1976, 1979, and 1980 were the highly epidemic years (data not shown). Results from ELISA and virus cultures for respiratory disease from January 2003 to December 2005 in our hospital showed the AdVs positive rate was 8.5% (70/824) (data not shown). Our results show that AdVs infection in autopsied severe pneumonia pulmonary tissues was 9.14%. Taken together, these observations indicate that AdVs is still a major agent of severe pneumonia and it plays an important role in lethal severe pneumonia in Guangzhou area. Therefore, we must strengthen the surveillance for AdVs and national recommendations for AdVs vaccine development in future.
AdVs are responsible for much of the public incidence of pneumonia. The 51 different serotypes of human AdVs are classified into six subgenera (subgenera A to F) on the basis of erythrocyte coagulation characteristics, oncogenicity and DNA sequence. The clinical pathogenicity differs among different adenovirus serotypes. The AdVs types within a subgenus are similar in their tropisms, pathogenicity, and tendencies to cause a latent infection and epidemics[17, 18]. Overall frequency of AdVs as the cause of nonbacterial pneumonia in children is less than that of RSV and parainfluenza virus type 3, but an alarming number of fatal illnesses have been noted. Severe and fatal illnesses in infants and children have been noted in association with AdVs types 1, 2, 3, 4, 5, 7a, 7h, 7i, 8, 19, 21, 35, and the intermediate strain 21/H21+35. Respiratory illness is mainly caused by AdVs serotype 3, 4, 7, 14, 21, and to a less extent by serotypes 1, 2, 5 and 6[6, 18]. Pediatric pneumonia is mainly caused by AdVs serotypes 1, 2, 3 and 7, whereas serotypes 4 and 7 are mainly responsible for adult pneumonia. According to several reports, serotypes 3, 4, 7 and 21 usually cause large scale respiratory illnesses and fulminate prevalence events, causing respiratory illness such as severe lethal pneumonia and pharyngoconjunctival fever [20, 21]. Our data identified 12 cases of AdVs serotype 4 from 175 autopsied pulmonary tissues, suggesting that AdVs serotype 4, which accounts for 75% in the positive cases, might be an important serotype responsible for pediatric fatal pneumonia in the Guangzhou area which locates in South China, and therefore it is important that we pay close attention to the detection of AdVs serotype 4 in pediatric severe pneumonia.
Our results from nested PCR and IHC are in concordance. Twelve PCR positive cases are negative in IHC, suggesting that nested PCR is a more sensitive method for the detection of AdVs and also reflecting the limitation of IHC in pathogen detecting. Results of pathological diagnosis, AdVs nested PCR and IHC were compared. The cases were all negative or positive in the three assays, or positive in pathological diagnosis, nested PCR but negative in IHC representing the coincidental cases with a concordance percentage of 84% (147/175), while others were not as concordant (Table 3). The unmatched results in the three methods indicated that PCR is a more sensitive assay than IHC. Pathological diagnosis of cell morphologic is to a large extent dependent on observation under the microscope with the naked eyes, therefore, the standards are subjective in some degree, which can result in poor specificity, high misdiagnosis or missed rate. Thus, pathological diagnosis has limitations compared with the sensitive, specific and reproducibility of nested PCR assay at the molecular level. As for the archived paraffin-embedded autopsied pulmonary tissues stored from 1988 to 2005 for PCR, the 16 positive samples distribute from 1994 to 2005 but none before 1993. The 15 cases of positive pathological diagnosis without PCR positivity (Table 3), it is possible that these cases or a number of them were older than 15 years, i.e. originating from before 1993, Perhaps the viral DNA in the older samples stored at room temperature more than 15 years degraded seriously and the materials is too old to be assayed by PCR. Concerning severe pneumonia in the clinic, we must strengthen the pathogen detection based on PCR technology, such as fluorescent quantitative PCR, nested fluorescent quantitative PCR, and nested PCR in order to provide more accurate and reliable molecular diagnostics results for pathogen identification underlying the disease and thus avoid the abuse of antibiotics.