Background: Introduction: Large-scale epidemics of enterovirus A71 (EV-A71) genotype occurred with different genotypes in 2005 (genotype C5) and 2011 (genotype C4a) in southern Vietnam. B5 had replaced C4 as the predominant genotype since 2013; however, some evidence suggested the reemergence of C4 since 2018. This study aims to investigate genetic and antigenic evolution of EV-A71 in south Vietnam. Methods and materials: Methods: National Health Research Institutes (NHRI), Taiwan has collaborated with Children's Hospital 1 (CH1), Ho Chi Minh City (HCMC), Vietnam to establish a hospital-based surveillance system of EV-A71 infections since 2012. Residual sera and throat swabs were collected from hand-foot-mouth disease (HFMD) inpatients for virological tests including virus isolation tested in CH1 using RD cells, and semi-nested RT-PCR (CODEHOP) and serum neutralization test performed in NHRI. Results: Based on virus isolation, EV71 positive rates were 6.8%, 16.0%, 2.7%, 9.6%, 5.2%, 1.6%, and 3.5% from 2012 to 2018, respectively, which are significantly lower than the positive rates tested using CODEHOP in the corresponding years (14.7%, 20.1%, 6.7%, 11.0%, 22.8%, 19.6%, and 6.0%). The results of genetic analysis indicated EV-A71 was the predominant serotypes in 2013, 2016 and 2017 and EV-A71 genotypes shifted from C4 in 2012 to B5 in 2013–2017. We found C4a and B5 had comparable number of virus isolates in 2018. Based on phylogenetic analysis, the genotype C4a viruses were likely imported from China and the genotype B5 viruses could be from southern Asia. Interestingly, the genotype B5 and C4a viruses circulating in HCMC have similar antigenicity based on neutralization tests using sera collected from children infected with EV-A71. Conclusion: In conclusion, international spreading of EV-A71 is common in southern Vietnam and EV-A71 epidemics cyclically occurred in 2–3 years since 2011. Enterovirus surveillance and vaccine development is urgently needed in Vietnam.

Background: Human enteroviruses are classified into four species (A, B, C and D) and include over 100 serotypes. Since 1997, Enterovirus 71(EV71) usually causes self-limited infections with non-specific symptoms and manifests hand-food-month disease (HFMD) or herpangina in children. EV71 have caused severe life-threatening outbreaks in young children in Asian. EV71 circulation among Vietnamese children was first documented in 2005. Methods & Materials: In 2011, there is a big outbreak of EV71 in Vietnam with more than 5,000 inpatients in Children Hospital No.1 (CH1), and 32 fetal cases. National Health Research Institutes cooperates with CH1 to establish hospital-based surveillance of enterovirus in HCM City in 2011. Children <10 years of age who develop HFMD and were admitted to HCM CH1 were collected throat swabs and sera. Throat swabs were used for virus isolation and Sera were used to measure neutralizing antibody against EV71 in Taiwan NHRI. Results: Enterovirus isolate rate with HFMD-related inpatients including 38.9% (21/54) in 2011, 19.3% (79/409) in 2012, 42.0% (173/412) in 2013 and 12% (12/100) on June, 2014. Among them, EV71 positive rate from 2011 to June, 2014 were 29.6%, 6.8%, 16.0% and 5%, respectively. The age-specific seropositive rates increase from 15.2% at <0.5 years of age to 17.2, 24.0, 29.4, 58.6, 62.3, 66.1, 77.6% at 0.5-0.9, 1-1.9, 2-2.9, 3-3.9, 4-4.9, 5-5.9 and 6-6.9 years of age, respectively. Conclusion: The predominant genotype shifted from C4 in 2011 to B5 in 2013. Risk of EV71 infections in Vietnam increased after 6 months of age. Vietnamese children in HCM City acquired EV71 infections at early age and vaccine development in Vietnam should target young children.

Volume replacement was studied prospectively in 208 infants with dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). The mean volume of intravenous fluid used was 110.4 mL/kg administered over a mean period of 25.8 hours. The mean volumes of intravenous fluid replacement in infants with DSS was significantly higher than in those with non-shock DHF (129.8 mL/kg versus 102.1 mL/kg; P = 0.001). Patients with DSS had significantly higher proportional requirements for dextran and blood transfusions than non-shock infants. Recurrent shock, prolonged shock, and acute respiratory failure were recorded in 8, 6, and 13 patients, respectively. Four patients with DSS died of severe complications. Intravenous fluid replacement with special care to avoid fluid overload requires careful attention to established indications for use of colloidal solutions and blood transfusions. To improve case fatality rates, special efforts need to be directed to infants with DHF/DSS accompanied by severe complications.

The association between sex, nutritional status, and the severity of dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS), and immune status was investigated in 245 Vietnamese infants with predominantly primary infections with dengue virus. Male and female infants were at equal risk of developing DHF/DSS. However, infants of low height and weight for age were under-represented among DHF/DSS cases compared with 533 healthy baby clinic infant controls. Acute illness phase blood levels of selected cytokines (interferon-gamma and tumor necrosis factor-alpha) and serum levels of antibodies to dengue virus were elevated in the same range in male and female infants with DHF/DSS, as well as in infants with and without malnutrition.

A prospective study of clinical and cytokine profiles of 107 infants with dengue hemorrhagic fever (DHF)/dengue shock syndrome (DSS) was conducted. Fever, petechiae on the skin, and hepatomegaly were the most common clinical findings associated with DHF/DSS in infants. DSS occurred in 20.5% of the patients. Hemoconcentration and thrombocytopenia were observed in 91.5% and 92.5% of the patients, respectively. Serologic testing revealed that almost all of the patients (95.3%) had primary dengue virus infections. These data demonstrate that clinical and laboratory findings of DHF/DSS in infants are compatible with the World Health Organization's clinical diagnostic criteria for pediatric DHF. The present study is the first to report evidence of production of cytokines in infants with DHF/DSS and to describe the difference between the cytokine profile of infants with primary dengue virus infections and children with secondary infections. Overproduction of both proinflammatory cytokines (interferon-gamma and tumor necrosis factor-alpha) and anti-inflammatory cytokines (interleukin-10 and -6) may play a role in the pathogenesis of DHF/DSS in infants.