Epidemiology and clinical associations of human parechovirus respiratory infections

Abstract

Infections with human parechoviruses (HPeVs) are prevalent in young children and have been associated with mild gastroenteritis and, less frequently, with meningitis and neonatal sepsis. To investigate the involvement of these viruses in respiratory disease, a highly sensitive nested PCR was used to screen a large archive of respiratory specimens, collected between January and December 2007. Respiratory samples had previously been tested for eight respiratory viruses, including respiratory syncytial virus and adenovirus, by PCR. HPeV was detected in 34 of 3,844 specimens, representing 27 of 2,220 study subjects (1.2%). HPeV types were identified by sequencing the VP3/VP1 junction amplified by PCR directly from clinical specimens. The assay could amplify all HPeV types examined with high sensitivity (types 1 and 3 to 6) and also identified HPeV types in all but one of the screen-positive study specimens (25 HPeV1 and eight HPeV6 specimens). Infections with both HPeV1 and HPeV6 were seasonal, with highest frequencies in July and August, and restricted to children aged between 6 months and 5 years. Other respiratory viruses were frequently codetected in HPeV-positive specimens, with significant overrepresentation of adenovirus coinfections (37%). Most HPeV-positive specimens were referred from emergency departments, although no association with specific respiratory symptoms or disease was found. In summary, the low frequency of detection and lack of clear disease associations indicate that HPeV1 and -6 are not major pathogens in individuals presenting with respiratory disease. However, the screening and typing methods developed will be of value in further HPeV testing, including testing for meningitis cases and other suspected HPeV-associated disease presentations.

FIG. 1.

Identification of HPeV types by sequence comparisons of the VP3/VP1 regions. (A) Frequency histogram of pairwise distances between (gray bars) and within (black bars) HPeV types, determined using published assignments. Nucleotide p (uncorrected) distances and inferred translated amino acid sequence p distances are shown. (B) Phylogenetic analysis of the same data set, carried out using neighbor-joining trees based on maximum composite likelihood (nucleotide) distances and amino acid p distances. Bootstrap resampling was used to demonstrate the robustness of groupings; values of ≥70% are shown (percentages are shown at left). For clarity, symbols depicting sequences of HPeV2 are black, those depicting sequences of HPeV1 and HPeV4 to -6 are different shades of gray, and those depicting sequences of HPeV3 are white. GenBank accession numbers are indicated. (C) Phylogenetic analysis of sequences from clinical specimens (HPeV1, white circles; HPeV6, gray circles), determined by the same method using the single reference sequence of each HPeV type (black circles).

FIG. 2.

Epidemiology of HPeV and other respiratory viruses. Comparison of (A) age distributions and (B) referral months of HPeV infections with those of other frequently detected viruses (RSV, FLUA, PIV3, and AdV). Numbers above bars show numbers of samples (A) or study subjects (B) positive for HPeV. m, months; y, years.

FIG. 3.

Referral sources and presenting symptoms of study subjects infected with HPeV and other respiratory viruses. Relative proportions of total study group infected with each virus originating from A&E departments, general hospital wards, and critical care wards (high-dependency unit [HDU]/intensive care unit [ICU]) (other sources [e.g., general practitioners] have been excluded because of low numbers) (top) and presenting symptoms broadly categorized into LRT, URT, and those unrelated to respiratory infections (Non-resp) (bottom).