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.