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It is uncertain whether clinical severity of an infection varies by pathogen or by multiple infections. Using hospital-based surveillance in children, we investigate the range of clinical severity for patients singly, multiply, and not infected with a group of commonly circulating viruses in Nha Trang, Vietnam. RT-PCR was performed to detect 13 respiratory viruses in nasopharyngeal samples from enrolled patients. We apply a novel clinical severity score and examine associations with the odds of being severe and differences in raw severity scores. We find no difference in severity between 0-, 1-, and 2-concurrent infections and little differences in severity between specific viruses. We find RSV and HMPV infections to be associated with 2- and 1.5-fold increase in odds of being severe, respectively, and that infection with ADV is consistently associated with lower risk of severity. Clinically, based on the results here, if RSV or HMPV virus is suspected, PCR testing for confirmatory diagnosis and for detection of multiple coinfecting viruses would be fruitful to assess whether a patient’s disease course is going to be severe.

Acute encephalitis is an important and severe disease in children in Vietnam. However, little is known about the etiology while such knowledge is essential for optimal prevention and treatment. To identify viral causes of encephalitis, in 2004 we conducted a one-year descriptive study at Children's Hospital Number One, a referral hospital for children in southern Vietnam including Ho Chi Minh City. Children less than 16 years of age presenting with acute encephalitis of presumed viral etiology were enrolled. Diagnostic efforts included viral culture, serology and real time (RT)-PCRs. A confirmed or probable viral causative agent was established in 41% of 194 enrolled patients. The most commonly diagnosed causative agent was Japanese encephalitis virus (n = 50, 26%), followed by enteroviruses (n = 18, 9.3%), dengue virus (n = 9, 4.6%), herpes simplex virus (n = 1), cytomegalovirus (n = 1) and influenza A virus (n = 1). Fifty-seven (29%) children died acutely. Fatal outcome was independently associated with patient age and Glasgow Coma Scale (GCS) on admission. Acute encephalitis in children in southern Vietnam is associated with high mortality. Although the etiology remains unknown in a majority of the patients, the result from the present study may be useful for future design of treatment and prevention strategies of the disease. The recognition of GCS and age as predictive factors may be helpful for clinicians in managing the patient.

Streptococcus pneumoniae is the major bacterial pathogen causing high pneumonia morbidity and mortality in children <5 years of age. This study aimed to determine the molecular epidemiology of S. pneumoniae detected among hospitalized pediatric ARI cases at Khanh Hoa General Hospital, Nha Trang, Vietnam, from October 2015 to September 2016 (pre-PCV). We performed semi-quantitative culture to isolate S. pneumoniae. Serotyping, antimicrobial susceptibility testing, resistance gene detection and multi-locus sequence typing were also performed. During the study period, 1300 cases were enrolled and 413 (31.8%) S. pneumoniae were isolated. School attendance, age <3 years old and prior antibiotic use before admission were positively associated with S. pneumoniae isolation. Major serotypes were 6A/B (35.9%), 19F (23.7%) and 23F (12.7%), which accounted for 80.3% of vaccine-type pneumococci. High resistance to Clarithromycin, Erythromycin and Clindamycin (86.7%, 85%, 78.2%) and the mutant drug-resistant genes pbp1A (98.1%), pbp2b (98.8%), pbp2x (99.6%) ermB (96.6%) and mefA (30.3%) were detected. MLST data showed high genetic diversity among the isolates with dominant ST 320 (21.2%) and ST 13223 (19.3%), which were mainly found in Vietnam. Non-typeables accounted for most of the new STs found in the study. Vaccine-type pneumococcus and macrolide resistance were commonly detected among hospitalized pediatric ARI cases.

Little is known about the kinetics of anti-H5 neutralizing antibodies in naturally H5N1-infected patients with severe clinical illness or asymptomatic infection. Using H5N1 microneutralisation (MN) and H5-pseudotype particle-based microneutralisation assays (H5pp) we analyzed sera sequentially obtained from 11 severely ill patients diagnosed by RT-PCR (follow-up range 1-139 weeks of disease onset) and 31 asymptomatically infected individuals detected in a sero-epidemiological study after exposure to H5N1 virus (follow-up range: 1-2 month-11 months after exposure). Of 44 sera from 11 patients with H5N1 disease, 70% tested positive by MN (antibody titre > or = 80) after 2 weeks and 100% were positive by 3 weeks after disease onset. The geometric mean MN titers in severely ill patients were 540 at 1-2 months and 173 at 10-12 months and thus were higher than the titers from asymptomatic individuals (149 at 1-2 months, 62.2 at 10-12 months). Fractional polynomial regression analysis demonstrated that in all severely ill patients, positive titers persisted beyond 2 years of disease onset, while 10 of 23 sera collected 10-11 months after exposure in asymptomatically infected individuals tested negative. Our results indicate that people with asymptomatic H5N1 infection have lower H5N1 antibody titres compared to those with severe illness and that in many asymptomatically infected patients the antibody titer decreased to levels below the threshold of positivity within one year. These data are essential for the design and interpretation of sero-epidemiological studies.

Influenza A (H5N1) virus with an amino acid substitution in neuraminidase that conferred high-level resistance to oseltamivir was isolated from two Vietnamese patients who died of influenza despite antiviral treatment. Resistance to oseltamivir can emerge with treatment that is initiated early and at the recommended dose. These findings may have therapeutic implications for the control of avian influenza. Influenza A (H5N1) virus with an amino acid substitution in neuraminidase that conferred high-level resistance to oseltamivir was isolated from two Vietnamese patients who died of influenza despite antiviral treatment. Influenza A (H5N1) virus causes severe disease in humans and poses an unprecedented pandemic threat. 1 – 3 The neuraminidase inhibitor oseltamivir constitutes an important treatment option, and stockpiling of this drug is part of pandemic-preparedness plans. 4 However, data on the efficacy and development of drug resistance in human influenza A (H5N1) virus are scarce. We report the isolation of oseltamivir-resistant influenza A (H5N1) variants from two patients who died of the infection, in one case despite the early initiation of treatment. Furthermore, we provide evidence suggesting that the presence of detectable virus after the completion of treatment is associated with a . . .

In southern Vietnam, a four-year-old boy presented with severe diarrhea, followed by seizures, coma, and death. His nine-year-old sister had died from a similar syndrome two weeks earlier. In both children, the clinical diagnosis was acute encephalitis. Neither had respiratory symptoms at presentation. In southern Vietnam, a four-year-old boy presented with severe diarrhea, followed by seizures, coma, and death. His sister had died from a similar syndrome two weeks earlier. These cases suggest that the spectrum of influenza H5N1 is wider than previously thought. Forty-five cases of influenza A (H5N1) were reported in humans during 2004, of which 33 were fatal. All the patients presented primarily with severe respiratory illnesses. 1 We report an additional fatal case of influenza H5N1, diagnosed by isolating the virus from cerebrospinal fluid, fecal, throat, and serum specimens, in a boy who presented with severe diarrhea but no apparent respiratory illness, followed by rapidly progressive coma, leading to a clinical diagnosis of acute encephalitis. Two weeks earlier, his sister had died of a similar illness. These cases suggest that the clinical spectrum of influenza H5N1 is wider than previously thought, . . .

Human metapneumovirus (hMPV) can cause severe acute respiratory infection (ARI). We aimed to clarify the clinical and molecular epidemiological features of hMPV. We conducted an ARI surveillance targeting hospitalized children aged 1 month to 14 years in Nha Trang, Vietnam. Nasopharyngeal swabs were tested for respiratory viruses with PCR. We described the clinical characteristics of hMPV patients in comparison with those with respiratory syncytial virus (RSV) and those with neither RSV nor hMPV, and among different hMPV genotypes. Among 8822 patients, 278 (3.2%) were hMPV positive, with a median age of 21.0 months (interquartile range: 12.7–32.5). Among single virus-positive patients, hMPV cases were older than patients with RSV ( p  < 0.001) and without RSV ( p  = 0.003). The proportions of clinical pneumonia and wheezing in hMPV patients resembled those in RSV patients but were higher than in non-RSV non-hMPV patients. Seventy percent (n = 195) were genotyped (A2b: n = 40, 20.5%; A2c: n = 99, 50.8%; B1: n = 37, 19%; and B2: n = 19, 9.7%). The wheezing frequency was higher in A2b patients (76.7%) than in those with other genotypes ( p  = 0.033). In conclusion, we found a moderate variation in clinical features among hMPV patients with various genotypes. No seasonality was observed, and the multiple genotype co-circulation was evident.

Avian influenza A (H5N1) viruses cause severe disease in humans 1 , 2 , but the basis for their virulence remains unclear. In vitro and animal studies indicate that high and disseminated viral replication is important for disease pathogenesis 3 , 4 , 5 . Laboratory experiments suggest that virus-induced cytokine dysregulation may contribute to disease severity 6 , 7 , 8 , 9 . To assess the relevance of these findings for human disease, we performed virological and immunological studies in 18 individuals with H5N1 and 8 individuals infected with human influenza virus subtypes. Influenza H5N1 infection in humans is characterized by high pharyngeal virus loads and frequent detection of viral RNA in rectum and blood. Viral RNA in blood was present only in fatal H5N1 cases and was associated with higher pharyngeal viral loads. We observed low peripheral blood T-lymphocyte counts and high chemokine and cytokine levels in H5N1-infected individuals, particularly in those who died, and these correlated with pharyngeal viral loads. Genetic characterization of H5N1 viruses revealed mutations in the viral polymerase complex associated with mammalian adaptation and virulence. Our observations indicate that high viral load, and the resulting intense inflammatory responses, are central to influenza H5N1 pathogenesis. The focus of clinical management should be on preventing this intense cytokine response, by early diagnosis and effective antiviral treatment.

Significant enhancement in students’ learning performance has been noticed in blended learning courses. Yet, the differential effect of blended learning as a function of disciplinary difference has not widely been explored. Moreover, studies on the critical factors related to students’ performance measured by objective course grades are recognized to a lesser extent compared with those using self-reported or perceived learning achievement. In the present study, the effect of blended learning in hard and soft courses is discerned. Factors related to students’ performance measured by final course grades are unraveled, controlling for the effects of gender and prior learning achievement. The participants ( N  = 571) are students following blended learning courses at a public university in Vietnam. A questionnaire is employed to collect data, which is subject to confirmatory factor analysis and hierarchical regression analyses. The results show that students in soft disciplines obtain higher grades than peers in hard disciplines. Clear goals and expectations, material quality, and collaborative learning are significant predictors of students’ performance.

•The incidence of CRS is still rising in developing countries.•Children with CRS present with a variety of disabilities.•A timely multidisciplinary approach improves the quality of life in children with CRS.•A timely multidisciplinary approach can be lifesaving in some children with CRS. Rubella vaccination programs have dramatically reduced the incidence of rubella and congenital rubella syndrome (CRS) in developed countries. However, CRS prevalence is still rising in developing countries where rubella-containing vaccines (RCV) are not included in the immunization program and even in some countries where a part of the population lacks immunity to rubella despite the presence of RCV in the regular immunization program. This review aimed to summarize the clinical features of CRS using data from our studies conducted between 2011 and 2015 in Vietnam, wherein we examined clinical manifestations in Vietnamese children with CRS who were born after the large rubella outbreak of 2011; a series of studies dealing with CRS in North America and Europe after the 1960s epidemic; and those from countries before introduction of RCVs. This review shows that children with CRS have a variety of disabilities such as hearing, visual, developmental, behavioral, cardiac, and endocrine impairments, which have variable severity and may appear in different combinations. Some of these impairments can appear or worsen later in the lives of these children. Physicians should thus complete pediatric, cardiac, auditory, ophthalmologic, and neurologic examinations along with laboratory diagnostic testing soon after birth. These assessments should be repeated during follow-up if congenital rubella infection is suspected in a neonate. Timely intervention for cardiac defects can be lifesaving. Early introduction and continuation of speech, occupational, physical, and behavior therapies and training with appropriate medical interventions by a multidisciplinary team approach are required to maximize quality of life.