Analysis of complete capsid sequences of the emerging norovirus GII.17 Kawasaki 308 from 13 countries demonstrated that they originated from a single haplotype since the initial emergence in China in late 2014. Global spread of a sublineage SL2 was identified. A new sublineage SL3 emerged in China in 2016.
Non-bacterial acute gastroenteritis (AGE) associated with virus infection affects individuals living in developing countries, especially children. To investigate whether shedding of certain human enterovirus (EV) is more frequently detected in the stool of individuals with AGE of unknown etiology than individuals without AGE symptoms, we tested fecal samples collected from 2,692 individuals with diarrhea between January 2010 and December 2016. Samples were tested for rotavirus, norovirus, and EV by reverse-transcription polymerase chain reaction (RT-PCR) and adenovirus by PCR. EV-positive samples were subjected to sequencing and phylogenetic analysis to identify EV species and types. Findings were compared to EV found in 1,310 fecal samples from individuals without AGE who were diagnosed with hand, foot, and mouth disease (HFMD). While the majority of viruses identified in AGE consisted of human rotavirus (22.7%), norovirus (11.4%) and adenovirus (9.3%), we identified EV (6.2%) belonging mainly to species B, C, and rhinovirus. In contrast, >92% of EV found without AGE symptoms belonged to species A. Although AGE symptoms are not often attributed to EV infection, EV was associated with diarrhea of unknown etiology at least in 3.4% of AGE cases. While CV-A6 was most likely to be found in stools of HFMD patients, rhinovirus A and C were the two most common EV species associated with AGE. Elucidating group-specific EV infection in diseases with and without AGE will be useful in assisting identification, clinical management, and the surveillance of EV infection in the community.
Background: Ageing and chronic kidney disease (CKD) affect pharmacokinetic (PK) parameters. Since mechanisms are related and remain unclear, cytochrome P450 (CYP) 3A and drug transporter activities were investigated in the elderly with or without CKD and compared to healthy adults using a microdose cocktail.Methods: Healthy young participants (n = 20), healthy elderly participants (n = 16) and elderly patients with CKD (n = 17) received, in study period 1, a single dose of microdose cocktail probe containing 30 µg midazolam, 750 µg dabigatran etexilate, 100 µg atorvastatin, 10 µg pitavastatin, and 50 µg rosuvastatin. After a 14-day wash-out period, healthy young participants continued to study period 2 with the microdose cocktail plus rifampicin. PK parameters including area under the plasma concentration-time curve (AUC), maximum plasma drug concentration (Cmax), and half-life were estimated before making pairwise comparisons of geometric mean ratios (GMR) between groups.Results: AUC and Cmax GMR (95% confidence interval; CI) of midazolam, a CYP3A probe substrate, were increased 2.30 (1.70–3.09) and 2.90 (2.16–3.88) fold in healthy elderly and elderly patients with CKD, respectively, together with a prolonged half-life. AUC and Cmax GMR (95%CI) of atorvastatin, another CYP3A substrate, was increased 2.14 (1.52–3.02) fold in healthy elderly and 4.15 (2.98–5.79) fold in elderly patients with CKD, indicating decreased CYP3A activity related to ageing. Associated AUC changes in the probe drug whose activity could be modified by intestinal P-glycoprotein (P-gp) activity, dabigatran etexilate, were observed in patients with CKD. However, whether the activity of pitavastatin and rosuvastatin is modified by organic anion transporting polypeptide 1B (OATP1B) and of breast cancer resistance protein (BCRP), respectively, in elderly participants with or without CKD was inconclusive.Conclusions: CYP3A activity is reduced in ageing. Intestinal P-gp function might be affected by CKD, but further confirmation appears warranted.Clinical Trial Registration:http://www.thaiclinicaltrials.org/ (TCTR 20180312002 registered on March 07, 2018)
Global eradication of poliovirus (PV) has previously relied on the live attenuated oral poliovirus vaccine (OPV). However, in order to eliminate the risk of vaccineassociated paralytic poliomyelitis, the use of OPV will soon be discontinued. Thailand has introduced inactivated polio vaccine since December 2015 and replaced trivalent with bivalent OPV since April 2016. To provide crucial surveillance data during this polio vaccine transition period, poliovirus shedding in stool was performed. A total of 7446 stool samples between 2010 and September 2018 were tested for poliovirus using reverse-transcription polymerase chain reaction. Approximately 0.44% (33/ 7446) of the samples tested were positive for PV. All positive specimens had more than 99% homology with the Sabin vaccine strain, based on complete VP1 nucleotide sequences. Although trivalent OPV use has been discontinued in Thailand since April 2016, PV type 2 could be detected in stool samples collected in May 2016 but has not been found afterwards. The use of bivalent OPV was able to reduce PV type 2 shedding in stools and could contribute to the reduction of vaccine-associated paralytic poliomyelitis in Thai children.
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