Prevalence and Characterization of Gastroenteritis Viruses among Hospitalized Children during a Pilot Rotavirus Vaccine Introduction in Vietnam.

Rotavirus (RV), norovirus (NoV), sapovirus (SaV), and human astrovirus (HAstV) are the most common viral causes of gastroenteritis in children worldwide. From 2016 to 2021, we conducted a cross-sectional descriptive study to determine the prevalence of these viruses in hospitalized children under five years old in Nam Dinh and Thua Thien Hue provinces in Vietnam during the pilot introduction of the RV vaccine, Rotavin-M1 (POLYVAC, Hanoi, Vietnam). We randomly selected 2317/6718 (34%) acute diarrheal samples from children <5 years of age enrolled at seven sentinel hospitals from December 2016 to May 2021; this period included one year surveillance pre-vaccination from December 2016 to November 2017. An ELISA kit (Premier Rotaclone®, Meridian Bioscience, Inc., Cincinnati, OH, USA) was used to detect RV, and two multiplex real-time RT-PCR assays were used for the detection of NoV, SaV and HAstV. The prevalence of RV (single infection) was reduced from 41.6% to 22.7% (p < 0.0001) between pre- and post-vaccination periods, while the single NoV infection prevalence more than doubled from 8.8% to 21.8% (p < 0.0001). The SaV and HAstV prevalences slightly increased from 1.9% to 3.4% (p = 0.03) and 2.1% to 3.3% (p = 0.09), respectively, during the same period. Viral co-infections decreased from 7.2% to 6.0% (p = 0.24), mainly due to a reduction in RV infection. Among the genotypeable samples, NoV GII.4, SaV GI.1, and HAstV-1 were the dominant types, representing 57.3%, 32.1%, and 55.0% among the individual viral groups, respectively. As the prevalence of RV decreases following the national RV vaccine introduction in Vietnam, other viral pathogens account for a larger proportion of the remaining diarrhea burden and require continuing close monitoring.

Impact and effectiveness of Rotavin-M1 under conditions of routine use in two provinces in Vietnam, 2016-2021, an observational and case-control study.

Background: Half of diarrhea hospitalizations in children aged <5 years in Vietnam are due to rotavirus. Following introduction of a locally developed and licensed oral rotavirus vaccine, Rotavin-M1, into the routine immunization program in two Vietnamese provinces, Nam Dinh and TT Hue, we describe changes in rotavirus positivity among children hospitalized for diarrhea and calculate vaccine effectiveness against moderate-to-severe rotavirus hospitalizations. Methods: Active rotavirus surveillance among children <5 years began in December 2016 at sentinel hospitals in districts where rotavirus vaccine was introduced in December 2017. To estimate reductions in rotavirus detection, we calculated risk ratios comparing rotavirus positivity pre- and post-vaccine introduction. We used a test-negative case-control design to calculate vaccine effectiveness. Findings: From December 2016 to May 2021, 7228 children <5 years hospitalized for diarrhea were enrolled. Following introduction, Rotavin-M1 coverage was 77% (1066/1377) in Nam Dinh and 42% (203/489) in TT Hue. In Nam Dinh, rotavirus positivity among children <5 years significantly declined by 40.6% (95% CI: 34.8%-45.8%) during the three-year post-vaccine introduction period. In TT Hue, no change in rotavirus positivity was observed. Among children aged 6-23 months, a 2-dose series of Rotavin-M1 was 57% (95% CI: 39%-70%) effective against moderate-to-severe rotavirus hospitalizations. Interpretation: Higher vaccination coverage in Nam Dinh than TT Hue likely contributed to substantial declines in rotavirus positivity observed in Nam Dinh following rotavirus vaccine introduction. Robust vaccine effectiveness was observed through the second year of life. National rotavirus vaccine introduction with high coverage may have substantial impact on reducing rotavirus disease burden in Vietnam. Funding: Bill and Melinda Gates Foundation.

Spatiotemporal variation in risk of Shigella infection in childhood: a global risk mapping and prediction model using individual participant data.

BACKGROUND: Diarrhoeal disease is a leading cause of childhood illness and death globally, and Shigella is a major aetiological contributor for which a vaccine might soon be available. The primary objective of this study was to model the spatiotemporal variation in paediatric Shigella infection and map its predicted prevalence across low-income and middle-income countries (LMICs). METHODS: Individual participant data for Shigella positivity in stool samples were sourced from multiple LMIC-based studies of children aged 59 months or younger. Covariates included household-level and participant-level factors ascertained by study investigators and environmental and hydrometeorological variables extracted from various data products at georeferenced child locations. Multivariate models were fitted and prevalence predictions obtained by syndrome and age stratum. FINDINGS: 20 studies from 23 countries (including locations in Central America and South America, sub-Saharan Africa, and south and southeast Asia) contributed 66 563 sample results. Age, symptom status, and study design contributed most to model performance followed by temperature, wind speed, relative humidity, and soil moisture. Probability of Shigella infection exceeded 20% when both precipitation and soil moisture were above average and had a 43% peak in uncomplicated diarrhoea cases at 33°C temperatures, above which it decreased. Compared with unimproved sanitation, improved sanitation decreased the odds of Shigella infection by 19% (odds ratio [OR]=0·81 [95% CI 0·76-0·86]) and open defecation decreased them by 18% (OR=0·82 [0·76-0·88]). INTERPRETATION: The distribution of Shigella is more sensitive to climatological factors, such as temperature, than previously recognised. Conditions in much of sub-Saharan Africa are particularly propitious for Shigella transmission, although hotspots also occur in South America and Central America, the Ganges-Brahmaputra Delta, and the island of New Guinea. These findings can inform prioritisation of populations for future vaccine trials and campaigns. FUNDING: NASA, National Institutes of Health-The National Institute of Allergy and Infectious Diseases, and Bill & Melinda Gates Foundation.

Prevalence and Determinants of Vaginal Infection With Human Papillomavirus Among Female University Students in Vietnam.

BACKGROUND/AIM: Cervical cancer is the second most common malignancy among women in Vietnam, but the country is yet to introduce a national human papillomavirus (HPV) vaccine programme targeted at adolescents. We determined HPV prevalence and HPV vaccine knowledge among female university students in Vietnam. PATIENTS AND METHODS: We surveyed and screened 1,491 female university students in Hanoi, Hue, and Ho Chi Minh City for their sexual behaviours, HPV knowledge and low- and high-risk HPV infection. RESULTS: The prevalence of any HPV infection and any high-risk HPV infection were 4.2% (95%CI=3.3%-5.4%) and 3.4% (95%CI=2.5%-4.4%), respectively. Being sexually active [adjusted prevalence ratio (aPR): 6.22; 95%CI=3.4-11.37] and having ever been pregnant (aPR: 4.82; 95%CI=1.93-12.04) were positively associated with high-risk HPV infection. Whilst 60% of participants had heard of HPV vaccine, only 4.6% had received the vaccine. CONCLUSION: The low HPV prevalence found in university students in Vietnam indicates that they can benefit from HPV vaccination, along with a well-designed HPV health promotion programme.

Prevalence and risk factors for human papillomavirus infection among female sex workers in Hanoi and Ho Chi Minh City, Viet Nam: a cross-sectional study.

Objective: Female sex workers (FSWs) are at high risk of human papillomavirus (HPV) infections and cervical cancer due to their high number of sexual partners. The objectives of this study were to determine the prevalence of HPV and identify risk factors for high-risk HPV infection among FSWs in Hanoi and Ho Chi Minh City (HCMC), Viet Nam. Methods: A cross-sectional study was conducted in Hanoi and HCMC between December 2017 and May 2018. We surveyed and screened 699 FSWs aged 318 years for HPV infection and abnormal cytology. A multivariable modified Cox regression model was used to determine risk factors for high-risk HPV infection. Results: The overall prevalence of any HPV, high-risk HPV and HPV-16/18 infection in the 699 FSWs was 26.3%, 17.6% and 4.0%, respectively, and were similar in both cities. Multiple infections were identified in 127 participants (69.0%). HPV-52 was the most prevalent (7%), followed by HPV-58 (6%). Abnormal cytology was detected in 91 participants (13.0%). FSWs who are divorced (adjusted prevalence ratio [aPR]: 1.96, 95% confidence interval [CI]: 1.01-3.81), widowed (aPR: 3.26, 95% CI: 1.49-7.12) or living alone (aPR: 1.85, 95% CI: 1.01-3.39) were associated with a higher prevalence of high-risk HPV infection. Discussion: Almost one in five FSWs in Viet Nam are infected with high-risk HPV. This highlights the importance of prevention strategies such as HPV vaccination and screening in this high-risk group.

Factors associated with antenatal depression among pregnant women in Vietnam: A multisite cross-sectional survey.

This study aimed to describe the status of antenatal depression and its associated factors among pregnant women in Vietnam. A cross-sectional study was conducted in four obstetric hospitals in Vietnam from January to September 2019. A total of 1260 pregnant women were interviewed using a structured questionnaire. A Tobit regression model was used to determine factors associated with antenatal depression. Results showed that pregnant women were at high risk of antenatal depression (24.5%). Women with fetus abnormalities and higher education were at higher risk of antenatal depression. We highlighted the need for implementing formal screening programs to early detect antenatal depression.

Antioxidation of 2-phenylbenzofuran derivatives: structural-electronic effects and mechanisms.

Stilbenoid-type 2-phenylbenzofuran derivatives, which are widely distributed in nature, are now promising antioxidant agents. In the present study, a quantum computational approach principally based on the DFT/B3LYP method with the 6-311++G(d,p) basis set was used to shed light on free radical scavenging for the isolated compounds stemofurans A-K and S-W. On the basis of the findings and from a thermodynamic perspective, the antioxidant activity of all studied compounds in the gaseous phase was mostly controlled by the O-H bond dissociation enthalpy (BDE), consistent with the hydrogen atom transfer (HAT) mechanism. The solvent effect was investigated, and the hydroxyl radicals of these studied compounds possessed the lowest proton affinity (PA) enthalpy and the sequential proton loss electron transfer (SPLET) pathway occurred in water, methanol and acetone. The studied compounds interacted with DPPH radicals, which is kinetic evidence of the involvement of two intermediates and one transition state. From both thermodynamics and kinetics perspectives, it can be proposed that stemofuran U is likely to be a leader compound in antioxidant drug development due to the presence of a 4'-OH moiety. Regarding the structure-bioactivity relationship, methylation can lead to a decrease in BDE.

Infectious Etiologies of Intussusception Among Children <2 Years Old in 4 Asian Countries.

BACKGROUND: The etiology of intussusception, the leading cause of bowel obstruction in infants, is unknown in most cases. Adenovirus has been associated with intussusception and slightly increased risk of intussusception with rotavirus vaccination has been found. We conducted a case-control study among children <2 years old in Bangladesh, Nepal, Pakistan, and Vietnam to evaluate infectious etiologies of intussusception before rotavirus vaccine introduction. METHODS: From 2015 to 2017, we enrolled 1-to-1 matched intussusception cases and hospital controls; 249 pairs were included. Stool specimens were tested for 37 infectious agents using TaqMan Array technology. We used conditional logistic regression to estimate odds ratio (OR) and 95% confidence interval (CI) of each pathogen associated with intussusception in a pooled analysis and quantitative subanalyses. RESULTS: Adenovirus (OR, 2.67; 95% CI, 1.75-4.36) and human herpes virus 6 (OR, 3.50; 95% CI, 1.15-10.63) were detected more frequently in cases than controls. Adenovirus C detection <20 quantification cycles was associated with intussusception (OR, 18.59; 95% CI, 2.45-140.89). Wild-type rotavirus was not associated with intussusception (OR, 1.07; 95% CI, 0.52-2.22). CONCLUSIONS: In this comprehensive evaluation, adenovirus and HHV-6 were associated with intussusception. Future research is needed to better understand mechanisms leading to intussusception, particularly after rotavirus vaccination.

Preparing for safety monitoring after rotavirus vaccine introduction - Assessment of baseline epidemiology of intussusception among children <2 years of age in four Asian countries.

Intussusception is the invagination of one segment of the bowel into a distal segment, characterized by symptoms of bloody stool, vomiting, and abdominal pain. Previous studies have found regional differences in incidence but the etiology of most intussusception cases is unknown. Rotavirus vaccines were associated with a slightly of increased risk of intussusception in post-licensure evaluations in high- and middle-income countries, but not in low income African countries. To describe the baseline epidemiology of intussusception in young children prior to rotavirus vaccine implementation, active sentinel hospital surveillance for intussusception in children < 2 years of age was conducted in 4 low income Asian countries (Bangladesh, Nepal, Pakistan and Vietnam). Over a 24-month period, 15 sites enrolled 1,415 intussusception cases, of which 70% were enrolled in Vietnam. Overall, 61% of cases were male and 1% (n = 16) died, ranging from 8% in Pakistan to 0% in Vietnam. The median age of cases enrolled ranged from 6 months in Bangladesh and Pakistan to 12 months in Vietnam. The proportion of cases receiving surgical management was 100% in Bangladesh, 88% in Pakistan, 61% in Nepal, and 1% in Vietnam. The high proportion of males and median age of cases around 6 months of age found in this regional surveillance network are consistent with previous descriptions of the epidemiology of intussusception in these countries and elsewhere. Differences in management and the fatality rate of cases between the countries likely reflect differences in access to healthcare and availability of diagnostic modalities. These baseline data will be useful for post-rotavirus vaccine introduction safety monitoring.

Association between norovirus and rotavirus infection and histo-blood group antigen types in Vietnamese children.

Norovirus and rotavirus are the two most important causes of acute gastroenteritis in children worldwide. Both norovirus and rotavirus recognize human histo-blood group antigens (HBGAs), and multiple binding patterns for HBGAs have been reported. To explore the role of HBGAs in host susceptibility to norovirus and rotavirus, we conducted a cross-sectional study in children hospitalized with diarrhea in northern Vietnam from September 2010 through September 2012. Of 260 children with paired stool and saliva samples, 158 (61%) were classified as HBGA secretors (Lea-b+), 31 (12%) were nonsecretors (Lea+b-), and 71 (27%) were partial secretors (Lea+b+). Norovirus was detected in 50 patients (19%), with viral genotypes GII.3 (n=28) and GII.4 (n=22) being the most common. All children infected with norovirus strains of genotype GII.4 were either HBGA secretors or partial secretors. Of the 28 GII.3 cases, 12 involved HBGA secretors, 11 partial secretors, and 5 nonsecretors. A total of 85 children tested positive for rotavirus, 74 of whom were infected with genotype P[8], 5 with P[4], and 6 with P[6]; all were HBGA secretors or partial secretors. This is the first epidemiological study demonstrating in a population that HBGA phenotype is a key susceptibility factor for both norovirus and rotavirus infections in children.

Incidence and Epidemiology of Intussusception among Infants in Ho Chi Minh City, Vietnam.

OBJECTIVE: To evaluate rates of intussusception hospitalization among infants in Vietnam before the introduction of rotavirus vaccine. STUDY DESIGN: Between 2009 and 2011, we identified intussusception hospitalizations among infants using the International Statistical Classification of Diseases and Related Health Problems, 10th Revision, Clinical Modification code K56.1 at 2 large pediatric hospitals in Ho Chi Minh City, Vietnam that treat most of the intussusception cases in the city. We reviewed all medical records to confirm a Brighton level 1 case definition for intussusception. RESULTS: We identified a total of 869 intussusception cases in Ho Chi Minh City during the 3-year study period, for an annual rate of 296 per 100,000 infants. The mean age of intussusception was ∼ 37 weeks (8.6 months), with <2% of the cases occurring before age 15 weeks. Cases of intussusception were observed year-round in these hospitals with no evident seasonal pattern. Ultrasonography was used to diagnose most cases (97%), and reduction was performed by air enema in >95% of the cases, with only 1% of cases at 1 hospital and 5% at the other hospital requiring surgical intervention. Ultrasound diagnosis was confirmed by an independent radiologist in 94% of a randomly selected group of intussusception cases at 1 of the 2 hospitals. No mortality was reported. CONCLUSION: Vietnam has a substantially higher rate of intussusception in children aged >15 weeks compared with most other regions of the world. Most of our cases were diagnosed by ultrasound, and only a small proportion required surgical intervention with no fatalities, suggesting that the higher rates may be related in part to better and earlier detection of intussusception.