Nguyen Van Trang

Background: Since the introduction of rotavirus vaccines, acute gastroenteritis (AGE) hospitalizations due to rotavirus have decreased globally; however, vaccine effectiveness (VE) differs by country, age and disease severity. We evaluated rotavirus VE by disease severity in different age groups and under-5 childhood mortality (U5M) strata. Methods: The Vesikari score is a common measure of AGE disease severity. A modified Vesikari Score (mVS) was calculated for 18,426 children with medically attended AGE across 16 countries from the Multi-National Subpopulations Study To Evaluate Rotavirus Vaccines dataset. Using a test-negative case–control design (cases had rotavirus-positive AGE and controls had rotavirus-negative AGE), we calculated complete rotavirus series VE against different severity categories among children 6–59 months old, stratified by age and country U5M level, respectively. Results: VE increased with increasing disease severity: 38% (95% confidence interval [CI]:17–53) for mild/moderate disease versus 58% (95% CI: 50–64) for severe/very severe disease, and this pattern persisted with stratification by age and U5M. Among children with severe/very severe disease, VE was higher in infants 6–11 months (62%, 95% CI: 51–70) compared with children 24–59 months old (11%, 95% CI: −78 to 56), and lower among children in the highest U5M strata (44%, 95% CI: 26–58) compared to children in the high U5M strata (60%, 95% CI: 47–69). Conclusions: Rotavirus vaccines provide the greatest protection against very severe rotavirus disease. VE remains lower in countries with higher U5M levels, even among children with very severe rotavirus disease, highlighting the need for improved vaccine performance in countries with high disease burden.

Following rotavirus vaccine implementation in Vietnam, norovirus has gradually become equally an important as a cause of acute gastroenteritis (AGE) in children as rotavirus. This study aimed to investigate the genotype distribution and compare clinical manifestations of norovirus of children < 5 years of age hospitalized with AGE from 2016 to 2021. Of 6,718 specimens collected through active surveillance from 12/2016 to 05/2021, 2,317 (34.5%) were randomly selected for norovirus testing. Among the 477 (20.6%) norovirus‐positive specimens identified from the previous surveillance, 390 (81.8%) were successfully genotyped for both partial RdRp and VP1 genes using online typing tools and 47 were selected for whole‐genome sequencing. Overall, norovirus genogroup‐II (GII) viruses dominated (97.3%) followed by GI (2.5%) and dual GI/GII infections (0.2%), with GII.4Sydney[P16] as the predominant genotype (51.5%) followed by GII.3[P12] (23.9%). Children infected with GII.4Sydney more commonly presented with thirst (65.8% vs 53.7%, p < 0.05) and showed a trend toward higher rates of sunken eyes compared with other genotypes (48.1% vs 38.1%, p = 0.053). A shift in predominant strain from GII.4Sydney[P31] viruses (50.8%) in 2016–2017 to GII.4‐Sydney[P16] (51.9%–68.9% in 2018–2021) was observed. Two cases in 2017 were typed as GII.4Hong Kong[P31]. Compared to GII.4 Sydney[P31], GII.4Hong Kong had 12 amino acid substitutions in the P1–P2 domains. This study highlights the evolving genetic diversity of norovirus genotypes in Vietnam. The shift of the predominant strain from GII.4Sydney[P31] to GII.4Sydney[P16] in 2018 and detection of GII.4 Hong Kong[P31] in 2017 emphasizes the need for continuous molecular surveillance to inform public health prevention strategies.

Female sex workers (FSW) have multiple sexual partners and are at higher risk of human papillomavirus virus (HPV) infection. They could be a target group for HPV vaccination, but their expected immune response to the HPV vaccine is unclear due to potential exposure to the virus. We conducted a pilot study (NCT04590521) in Hai Phong, Vietnam to evaluate HPV vaccine immunogenicity among FSW aged 18–26 years. All participants received the standard 3-dose schedule (0, 2, and 6 months) of the quadrivalent Gardasil vaccine (4vHPV). Cervical swabs were collected at time of vaccination to detect high-risk HPV DNA and cervical abnormalities. Blood samples were collected at baseline and at 2, 3, 6, and 7 months after the first dose to determine neutralizing antibody (nAb) responses to HPV16 and HPV18, as well as related HPV52 and HPV58. A total of 63 FSW with a median age of 23.4 years (IQR, 21.6–25.4 years) were recruited. Prevalence of any high-risk HPV type and HPV16/18 infection at baseline was 28.6% (18/63) and 9.5% (6/63), respectively. Following the first dose, 90% and 55% of individuals were seropositive for HPV16 and HPV18, respectively. By month 7, all participants were seropositive to both HPV16 and HPV18. Higher nAb responses were observed among HPV-DNA–negative participants at baseline compared with HPV-DNA–positive participants after 2 and 3 doses (HPV16, geometric mean ratio [GMR] 2.97 and 1.63, P < .05; HPV18, GMR 2.83 and 1.49, P = .06). Three doses of 4vHPV elicited robust nAb to HPV16 and HPV18 among FSW. Further studies are needed to evaluate the effectiveness of HPV vaccination in FSW. Clinical Trials Registration.NCT04590521.

Rotavin-M1 (POLYVAC) was licensed in Vietnam in 2012. The association of Rotavin-M1 with intussusception, a rare adverse event associated with rotavirus vaccines, and with adverse events following immunization (AEFI) have not been evaluated and monitored under conditions of routine use. From February 2017 to May 2021, we conducted a pilot introduction of Rotavin-M1 into the routine vaccination program in two provinces. Surveillance for intussusception was conducted at six sentinel hospitals. AEFI reports at 30 min and 7 days after vaccination were recorded. Among 443 children ®, ComBE Five^®) compared to Rotavin-M1 without pentavalent vaccines. There was no association between intussusception and Rotavin-M1. The vaccine was generally safe when administered alone and when co-administered with other vaccines.

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 ®, 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.

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.