In the present study, we compared the preclinical optimal dose and the corresponding active plasma concentration determined in mice with those being observed in cancer patients, i.e. 65-100 microg/ml. The preclinical optimal dose of 0.25 mg/inj was significantly lower than the current clinical dose. However, the active plasma concentration at 0.25 mg/inj is within the range of the active drug concentrations in cancer patients treated with Cetuximab under the current optimal dosing regimen. It appears that the active plasma drug concentration determined in preclinical model predicts better than the optimal preclinical dose for the clinical development of antibody drugs.

To determine if human bocavirus 2 (HBoV2) has a circular genome similar to the head-to-tail sequence of HBoV1 and the episomal form of HBoV3, 15 HBoV2 positive samples identified from 553 stool specimens from children with acute diarrhea were tested for a head-to-tail sequence using TaqMan-based real-time PCR. A circular genome with a head-to-tail sequence was identified in one (BJQ435) out of 15 samples tested by nested PCR. The complete circular genome of HBoV2-C1 (BJQ435) was 5307 nt in length and was flanked with a 520 nt-long terminal non-coding region (NCR). The secondary structure of HBoV2 -C1 had some differences compared to HBoV3-E1 (JN086998). Our study indicates that the HBoV genome exists in the form of a head-to-tail monomer and provides more information for understanding the HBoV replication mechanism.

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.

Adenoviruses have been recognized as important causal pathogens of community-acquired diarrhea (CAD) among children, but their role in hospital-acquired diarrhea (HAD) is not well-understood. Hospitalized children with acute diarrhea and children who visited the outpatient department due to diarrhea were investigated from 2011 to 2012. Adenovirus was detected in stool specimens by PCR and further characterized by sequencing and phylogenetic analysis. SPSS software (version 19.0) was used for statistical analyses. A total of 2233 diarrheal children were enrolled in this study; this sample was comprised of 1371 hospitalized children, including 885 with CAD (IP-CAD) and 486 with HAD, and 862 outpatients with CAD (OP-CAD). Among these 2,233 patients, adenovirus was detected in 219 cases (9.8%). The positive rates for adenovirus were significantly different between the IP-CAD (9.3%), HAD (13.8%) and OP-CAD (8.1%) cases (X2 = 11.76, p = 0.003). The positive rate of adenovirus was lower in infants under six months of age compared to the positive rates in the other age groups. Of the 219 of adenovirus positive patients, 91 (41.6%) were identified as having serotype 41. Although enteric adenovirus (group F) was the most frequently detected adenovirus among children with either CAD or HAD, the role of non-enteric adenoviruses, especially the adenovirus 31 type (19.7%), cannot be ignored in diarrheal children.

BackgroundDiarrhea caused by viruses is a global problem among young children. We investigated two of the most important agents, rotavirus and adenovirus, to provide epidemiological evidence for a better understanding of their role among children with acute diarrhea.MethodsA total of 3147 hospitalized children were enrolled in the study during 2010 ~ 2014. Antigen testing for rotavirus and DNA testing for adenovirus were performed on stool specimens collected from participants.ResultsThere were 1985 cases of community-acquired diarrhea (CAD) and 1162 cases of hospital-acquired diarrhea (HAD). A total of 692 cases (22.0 %) were positive for rotavirus. Rotavirus was detected in more children with HAD than in those with CAD (24.6 %; 286/1162 vs. 20.5 %; 406/1985). A total of 324 cases (10.3 %) were adenovirus positive. There was a significant difference between the CAD group and HAD group (9.5 %; 188/1985 vs. 11.7 %; 136/1162: χ2 = 3.957, p = 0.047). Co-infection was found in only 35 children (1.11 %), and the co-infection rate was similar between the CAD and HAD groups (χ2 = 1.174, p = 0.279). There was no association between sex and the detection rate of these viruses. The positive rate was significantly different for rotavirus among CAD cases (χ2 = 27.979, p < 0.001) and for adenovirus (χ2 = 34.362, p < 0.001) in the five age groups. Compared with the other four age groups (15.8–19.8 %), the prevalence of rotaviruses was highest among children aged 12–24 months (28.6 %). Adenovirus was detected in 3.6 % of neonates compared with 5.8 % of infants from 1 to 6 months old; this increased to 12.0–13.8 % in children over 6 months of age. In HAD cases, age differences were not found for rotavirus and adenovirus. Seasonal variation of rotavirus was observed, with peaks in November and December and with through in July and August; however, no clear seasonal pattern was found for adenovirus.ConclusionDetection rates for rotavirus and adenovirus were significantly higher in children with HAD than those with CAD, but co-infection was very low. A high prevalence of rotavirus was identified in neonates with diarrhea. Vaccination for rotavirus gastroenteritis should be considered in neonates.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-016-1829-z) contains supplementary material, which is available to authorized users.