Epidemiology and characterisation of enteric DNA viruses associated with gastroenteritis in children in selected regions of South Africa

Abstract

Acute gastroenteritis (AGE) is a global public health problem causing considerable morbidity and mortality among infants and children, especially in low-income settings. Viruses including group A rotaviruses (RVA), noroviruses (NoV), adenoviruses (AdV), sapoviruses (SaV) and astroviruses (AstV) are widely acknowledged to be the most common cause of AGE in children. The importance of newly recognised viruses such as human bocavirus (HBoV) as an aetiological agent of AGE is becoming increasingly evident. The aim of this study was to investigate the molecular epidemiology of HAdV and HBoV in children aged ≤5 years hospitalised for AGE in South Africa (SA) from April 2009 to April 2015. Clinical and demographic data, along with stool specimens were collected from hospitalised children who presented with AGE. Real-time polymerase chain reaction (PCR) was used to screen for the presence of enteric DNA viruses. Genotyping was achieved by nucleotide sequence analysis or multiplex PCR. Whole genome sequencing was performed on selected strains to characterise their genetic variation and evolution. Between April 2009 and December 2014, the prevalence of HAdV in hospitalised children with AGE in SA was 18.1% (656/3623); 62.3% of the HAdV_positive children were 7–24 months of age. Human AdV was detected year round. Co-infections were found in 76.3% (222/291) cases of the HAdV_positive specimens with full enteric screening and AstV was detected most frequently as a co-infecting pathogen. Prolonged hospital stay was observed in human immunodeficiency virus (HIV)-infected children with HAdV. Human AdV-F was the most common species identified (254/603, 42.1%), with almost equally distribution of -40 and -41. Recombination breakpoints of the five HAdV41 strains varied in the number and location, indicating different evolution origins. Between April 2009 and April 2015, the prevalence of HBoV in hospitalised children with AGE in SA was 5.6% (212/3765); the majority of which were from children ≤2-year of age (92%, 195/212). Viral co-infections were found in 67% (142/212) of HBoV cases, while in fully screened specimens (virus, bacteria and parasites), 83.1% (74/89) had evidence of co-infections. In all co-infections, only HAdV was significantly associated with HBoV (adjusted Odds Ratio (aOR))=1.68; (95% CI 1.10-2.52; p=0.015) in multivariate analysis. Human BoV infections were reported throughout the year. All four HBoV genotypes were detected with HBoV1 being the most prevalent (79.6% (152/191). The variation in total number of specimens screened for HAdV and HBoV is because HAdV screening was done until December 2014; while HBoV screening was done until April 2015. The current study highlights the genetic diversity of HAdV-40 and -41 strains circulating in SA and suggests possible evolution from inter-strain recombination. Furthermore, the present study highlights the wide spectrum of HBoV genotypes in children with AGE in SA. This study presents the most comprehensive recent data on HAdV diversity in SA, and new baseline data on a HBoV-associated gastroenteritis in a country where no previous report is available.