Risk of acute gastroenteritis associated with human bocavirus infection in children: A systematic review and meta-analysis

Human bocaviruses (HBoVs), which were first identified in 2005 and are composed of genotypes 1-4, have been increasingly detected worldwide in pediatric patients with acute gastroenteritis. To investigate if HBoV infection is a risk factor of acute gastroenteritis in children younger than 5 years old, we searched PubMed, Embase (via Ovid), the Chinese Biomedical Literature Database (CBM), and the Cochrane Library for studies assessing the prevalence of HBoVs in individuals from Oct 25, 2005 to Oct 31, 2016. We included studies using PCR-based diagnostics for HBoVs from stool specimens of patients with or without acute gastroenteritis that carried out research for over 1 year on pediatric patients aged younger than 5 years old. The primary outcome was the HBoV prevalence among all cases with acute gastroenteritis. Pooled estimates of the HBoV prevalence were then generated by fitting linear mixed effect meta-regression models. Of the 36 studies included, the pooled HBoV prevalence in 20,591 patients with acute gastroenteritis was 6.90% (95% confidence interval (95% CI): 5.80-8.10%). In the ten studies with a control group, HBoVs were detected in 12.40% of the 3,620 cases with acute gastroenteritis and in 12.22% of the 2,030 control children (odds ratio (OR): 1.44; 95% CI: 0.95-2.19, p = 0.09 between case and control groups). HBoV1 and HBoV2 were detected in 3.49% and 8.59% of acute gastroenteritis cases, respectively, and in 2.22% and 5.09% of control children, respectively (OR: 1.40; 95% CI: 0.61-3.25; p = 0.43 and OR: 1.68; 95% CI: 1.21-2.32; p = 0.002, respectively). Current evidence suggests that the overall HBoV prevalence in children younger than 5 years old is not significantly different between groups with or without acute gastroenteritis. However, when HBoV1 was excluded, the HBoV2 prevalence was significantly different between these two groups, which may imply that HBoV2 is a risk factor of acute gastroenteritis in children younger than 5 years old.