A decade of human metapneumovirus in hospitalized children with acute respiratory infection: molecular epidemiology in central Vietnam, 2007-2017.

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.

A Birth Cohort Follow-Up Study on Congenital Zika Virus Infection in Vietnam.

We assessed the development, sensory status, and brain structure of children with congenital Zika virus (ZIKV) infection (CZI) at two years and preschool age. CZI was defined as either ZIKV RNA detection or positive ZIKV IgM and neutralization test in the cord or neonatal blood. Twelve children with CZI born in 2017-2018 in Vietnam, including one with Down syndrome, were assessed at 23-25.5 months of age, using Ages and Stages Questionnaire (ASQ-3), ASQ:Social-Emotional (ASQ:SE-2), Modified Checklist for Autism in Toddlers, automated auditory brainstem response (AABR), and Spot Vision Screener (SVS). They underwent brain CT and MRI. They had detailed ophthalmological examinations, ASQ-3, and ASQ:SE-2 at 51-62 months of age. None had birthweight or head circumference z-score < -3 except for the one with Down syndrome. All tests passed AABR (n = 10). No ophthalmological problems were detected by SVS (n = 10) and detailed examinations (n = 6), except for a girl's astigmatism. Communication and problem-solving domains in a boy at 24 months, gross-motor area in a boy, and gross-motor and fine-motor areas in another boy at 59-61 months were in the referral zone. Brain CT (n = 8) and MRI (n = 6) revealed no abnormalities in the cerebrum, cerebellum, or brainstem other than cerebellar hypoplasia with Down syndrome. The CZI children were almost age-appropriately developed with no brain or eye abnormalities. Careful and longer follow-up is necessary for children with CZI.

Molecular Epidemiology of Streptococcus pneumoniae Detected in Hospitalized Pediatric Acute Respiratory Infection Cases in Central Vietnam.

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.

Differences in clinical severity of respiratory viral infections in hospitalized children.

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.

Evolutionary dynamics of influenza B strains detected from paediatric acute respiratory infections in central Vietnam.

Influenza virus B belongs to the family Orthomyxoviridae with segmented negative-sense RNA genomes. Since 1970s, influenza B has diverged intoVictoria and Yamagata, which differs in antigenic and evolutionary characteristics. Yet, molecular-epidemiological information of influenza B from developing nations is limited. In central Vietnam, influenza A subtype-specific circulation pattern and clinical characteristics were previously described. However, molecular evolutionary characteristics of influenza B has not been discussed to date. We utilized the influenza B positives obtained from paediatric ARI surveillance during 2007-2013. Influenza B HA and NA genes were amplified, sequenced, and phylogenetic/molecular evolutionary analysis was performed using Maximum Likelihood and Bayesian MCMC. Phylodynamics analysis was performed with Bayesian Skyline Plot (BSP). Furthermore, we performed selection pressure analysis and estimated N-glycosylation sites. In the current study, overall positive rate for influenza B was 3.0%, and Victoria lineage immediately became predominant in post-A/H1N1pdm09 period. The noticeable shift in Victoria lineage WHO Group occurred. With respect to the evolutionary rate (substitutions/site/year), Victoria lineage HA gene was evolving faster than Yamagata lineage (2.43 × 10-3 vs 2.00 × 10-3). Furthermore, the evolutionary rate of Victoria Group 5 was greater than Group 1. BSP presented the rapid growth in Effective Population Size (EPS) of Victoria lineage occurred soon after the 1st A/H1N1pdm09 case was detected whereas the EPS of Yamagata lineage was stable for both genes. N-glycosylation pattern between lineages and among WHO Groups were slightly different, and HA gene had a total of 6 amino acid substitutions under positive section pressure (4 for Victoria and 2 for Yamagata). The current results highlight the importance of Victoria lineage in post-A/H1N1pdm09 period. Difference in evolutionary characteristics and phylodynamics may indicate lineage and WHO Group-specific evolutionary dynamics. It is necessary to further continue the molecular-epidemiological surveillance in local setting to gain a better understanding of local evolutionary characteristics of influenza B strains.

Clinical manifestations of congenital rubella syndrome: A review of our experience in Vietnam.

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.

Influenza B associated paediatric acute respiratory infection hospitalization in central vietnam.

BACKGROUND: Influenza B is one of the major etiologies for acute respiratory infections (ARI) among children worldwide; however, its clinical-epidemiological information is limited. We aimed to investigate the hospitalization incidence and clinical-epidemiological characteristics of influenza B-associated paediatric ARIs in central Vietnam. METHODS: We collected clinical-epidemiological information and nasopharyngeal swabs from ARI children hospitalized at Khanh Hoa General Hospital, Nha Trang, Vietnam from February 2007 through June 2013. Nasopharyngeal samples were screened for 13 respiratory viruses using Multiplex-PCRs. Influenza B-confirmed cases were genotyped by Haemagglutinin gene sequencing. We analyzed the clinical-epidemiological characteristics of influenza B Lineages (Victoria/Yamagata) and WHO Groups. RESULTS: In the pre-A/H1N1pdm09 period, influenza B-associated ARI hospitalization incidence among children under five was low, ranging between 14.7 and 80.7 per 100 000 population. The incidence increased to between 51.4 and 330 in the post-A/H1N1pdm09. Influenza B ARI cases were slightly older with milder symptoms. Both Victoria and Yamagata lineages were detected before the A/H1N1pdm09 outbreak; however, Victoria lineage became predominant in 2010-2013 (84% Victoria vs 16% Yamagata). Victoria and Yamagata lineages did not differ in demographic and clinical characteristics. In Victoria lineage, Group1 ARI cases were clinically more severe compared to Group5, presenting a greater proportion of wheeze, tachypnea, and lower respiratory tract infection. CONCLUSIONS: The current results highlight the increased incidence of influenza B-related ARI hospitalization among children in central Vietnam in the post-A/H1N1pdm09 era. Furthermore, the difference in clinical severity between Victoria lineage Group1 and 5 implies the importance of influenza B genetic variation on clinical presentation.

Mortality associated with pulmonary hypertension in congenital rubella syndrome.

OBJECTIVE: Outbreaks of rubella and congenital rubella syndrome (CRS) continue to arise in various countries where a rubella-containing vaccine is not included in the national immunization program. After a large-scale rubella outbreak in 2011, CRS cases emerged in Vietnam. The aim of this study was to clarify the clinical features of these cases with an emphasis on cardiovascular complications and outcomes. METHODS: From October 2011 to September 2012, we conducted a prospective surveillance study of infants <12 months of age who had manifestations suggesting CRS at the only referral hospital in Khanh Hoa Province. These infants underwent standard examinations, echocardiography, cranial ultrasonography, automated auditory brainstem responses, blood cell count measurements, and rubella-specific antibody testing. Detected cardiovascular defects were regularly followed with echocardiography. RESULTS: We enrolled 38 cases of CRS characterized by a low birth weight (71%), cardiovascular defects (72%), cataracts (13%), hearing impairment (93%), purpura (84%), hepatosplenomegaly (68%), and thrombocytopenia (76%). Patent ductus arteriosus, the most common cardiovascular complication, was often associated with progressive pulmonary hypertension (PH). As of January 2013, 13 infants (34%) had died, and PH was significantly more frequent among the fatalities (P = .004); however, therapeutic closure of the ductus reversed the PH in several cases. CONCLUSIONS: PH-associated mortality is high among infants who have CRS in Vietnam. Providing proper assessments, continuous follow-up, and timely intervention for cardiovascular defects is critical for the management of CRS patients. Echocardiography is of diagnostic and prognostic value and can support better clinical management of CRS, even in a developing country setting.