Epidemiological, molecular, and clinical features of enterovirus respiratory infections in French children between 1999 and 2005

Abstract

Enteroviruses (EVs) can induce nonspecific respiratory tract infections in children, but their epidemiological, virological, and clinical features remain to be assessed. In the present study, we analyzed 252 EV-related infection cases (median age of subjects, 5.1 years) diagnosed among 11,509 consecutive children visiting emergency departments within a 7-year period in the north of France. EV strains were isolated from nasopharyngeal samples by viral cell culture, identified by seroneutralization assay, and genetically compared by partial amplification and sequencing of the VP1 gene. The respiratory syndromes (79 [31%] of 252 EV infections) appeared as the second most common EV-induced pediatric pathology after meningitis (111 [44%] of 252 cases) (44 versus 31%, P < 10(-3)), contributing to lower respiratory tract infection (LRTI) in 43 (54%) of 79 EV respiratory infection cases. Bronchiolitis was the most common EV-induced LRTI (34 [43%] of 79 cases, P < 10(-3)) occurring more often in infants aged 1 to 12 months (P = 0.0002), with spring-fall seasonality. Viruses ECHO 11, 6, and 13 were the more frequently identified respiratory strains (24, 13, and 11%, respectively). The VP1 gene phylogenetic analysis showed the concomitant or successive circulation of genetically distinct EV respiratory strains (species A or B) during the same month or annual epidemic period. Our findings indicated that respiratory tract infections accounted for the 30% of EV-induced pediatric pathologies, contributing to LRTIs in 54% of these cases. Moreover, the concomitant or successive circulation of genetically distinct EV strains indicated the possibility of pediatric repeated respiratory infections within the same epidemic season.

FIG. 1.

Positive respiratory viral findings in the nasopharyngeal samples of 11.509 consecutive children attending one of the five referent pediatric emergency departments of the region Champagne Ardenne (France) from 1999 through 2005. (A) Distribution (%) of the positive viral isolation of human respiratory strains by classical cell culture assays in nasopharyngeal samples of 2,444 (21%) of 11,509 children during the 7-year of the study period. (B) Distribution of the annual rates of EV-positive isolation by classical cell culture assays among the 2,444 positive nasopharyngeal samples.

FIG. 2.

Number of EV-related infections in Champagne Ardenne between 1999 and 2005. *, Years wherein the rates of EV-related respiratory infections appeared to be significantly lower than those of other EV-induced infections (chi-square test stratified according to the years of the study period; P < 0.001).

FIG. 3.

Phylogenetic tree based on partial VP1 sequences (348 pb) of 77 human EV isolates identified as the viral cause of the respiratory syndrome diagnosed in French infants between 1999 and 2005. The numbers correspond, respectively, to the month and the year of isolation (set as “month-year” in the tree) of EV strains from pediatric nasopharyngeal samples. Solid boxes indicate the cases of a cocirculation of distinct EV respiratory tropism species during the same month of the same annual epidemic season. Dotted rectangles indicate examples of cocirculation of distinct EV respiratory serotypes within the same species during the same month of the same annual epidemic season. Bootstraps in boldface indicate examples of cocirculation of phylogenetically distinct subgroups belonging to the same EV strain (bootstraps > 60%) during the same month of the same annual epidemic season.