Mother-to-Child Transmission of HBV Infection by Preventive Interventions in Southern Vietnam's Hospitals.

INTRODUCTION: The World Health Organization (WHO) recommends tenofovir disoproxil fumarate (TDF) for pregnant women with hepatitis B virus (HBV) presenting with HBV DNA levels of 106 copies/mL or more to hinder mother-to-child transmission (MTCT). Moreover, it is suggested that neonates of HBV-infected mothers receive an HBV vaccine birth dose within 24 hours of birth to mitigate transmission risk. METHODOLOGY: The study included 661 HBV-infected pregnant women and 316 infants from 3 hospitals in Southern Vietnam between October 2019 and November 2020. Infants were classified on the basis of their mothers' TDF prophylaxis into I-TDF (+) group (107 infants) whose mothers received TDF; I-TDF (-) group (56 infants) whose mothers missed TDF; and I-NTDF group (153 infants) whose mothers did not necessitate TDF. Almost all infants received an HBV vaccine birth dose with HBIG administered on the basis of parents' financial standing. RESULTS: MTCT was found in 2.2% of the cases. The respective MTCT rates for I-TDF (+), I-TDF (-), and I-NTDF groups were 2.8%, 5.4%, and 0.7%. Immune response rates to the HBV vaccination in the total cohort, I-TDF (+), I-TDF (-), and I-NTDF groups, were 88.6%, 87.9%, 85.7%, and 90.2%, respectively. Vaccinated infants exhibited a statistically lower risk of HBV infection postbirth (aRR = 0.1; 95% confidence interval, 0.0-0.6; P = .01). CONCLUSION: TDF can equate the MTCT risk in pregnant women with HBV DNA levels of 106 copies/mL or more to those with lower levels. Early administration of the HBV vaccine postbirth also effectively curtails MTCT. Thus, expanding TDF prophylaxis and vaccine coverage is pivotal to impede MTCT.

HBeAg testing is better than quantitative HBsAg assay as an alternative to HBV DNA assay among HBV-infected pregnant women.

INTRODUCTION: Using tenofovir disoproxil fumarate (TDF) is recommended in the 3rd trimester for pregnant women with HBV DNA ≥ 200,000 IU/mL to prevent mother-to-child transmission (MTCT) of hepatitis B virus (HBV). However, HBV DNA quantification is unavailable in many resource-limited areas worldwide, hence prophylaxis is often missed. The aim of this study was to determine whether HBeAg or qHBsAg is a better alternative to HBV DNA testing in HBV-infected pregnant women. METHODOLOGY: In this prospective cohort study, pregnant women with HBV infection were recruited in 3 hospitals from October 2019 to November 2020. Socio-demographic and clinical data were collected. Blood samples were taken for qHBsAg and HBV DNA testing. HBeAg results were collected from the medical records of the participants who visited a doctor during the study. RESULTS: 465 pregnant women met the study criteria. 41.9% were HBeAg positive, 33.3% had high qHBsAg levels (> 104 IU/mL), 38.3% had high HBV DNA levels (≥ 200,000 IU/mL). Pregnant women with high qHBsAg levels were 27 times more likely to have high HBV DNA levels (aOR = 27.0, 95% CI: 11.1-65.5, p < 0.001). Participants who were HBeAg positive were 57.5 times more likely to have high HBV DNA levels (aOR = 57.5, 95% CI: 23.0-140.0, p < 0.001). The sensitivity of qHBsAg and HBeAg was 80% and 94%, respectively; and specificity was 95% and 90%, respectively. CONCLUSIONS: HBeAg testing should be considered over qHBsAg assay as an alternative to HBV DNA assay because of its technical simplicity, lower cost, and fewer missed treatments.

Long-term immunogenicity and safety of tetravalent dengue vaccine (CYD-TDV) in healthy populations in Singapore and Vietnam: 4-year follow-up of randomized, controlled, phase II trials.

Dengue is prevalent in the Asia-Pacific region. Participants of two immunogenicity and safety phase II studies conducted in Singapore and Vietnam (NCT0088089 and NCT00875524, respectively) were followed for up to four years after third vaccine dose of a recombinant, live, attenuated, tetravalent dengue vaccine (CYD-TDV). Participants (2-45 years) received three doses of CYD-TDV or control at 0, 6, and 12 months. Dengue plaque reduction neutralization test (PRNT50) antibody titers were measured in both studies. Cytokine-producing antigen-specific CD4+ and CD8+ T-cells were quantified to assess cell-mediated immunity (CMI) in Singapore. Post-hoc analyses were carried out for participants aged <9 and ≥9 years old. Related and fatal serious adverse events (SAEs) were collected during long-term follow-up. Of participants who received ≥1 CYD-TDV injection in Singapore (n = 1198) and Vietnam (n = 180), 87% and 92% participants completed long-term follow-up, respectively. At four years, geometric mean titers (GMTs) in participants who received CYD-TDV ranged from 30.2 1/dil (95% CI 23.9-38.3) to 73.7 (49.3-110) 1/dil in Vietnam and 9.73 1/dil (95% CI 8.28-11.4) to 21.8 (18.9-25.1) 1/dil in Singapore. Interferon and interleukin-13 levels were lower at four years than one year post-vaccination but were still present. Tumor necrosis factor-α levels at four years were similar to those after the third vaccine dose. Seropositivity rates were higher at year four in participants who were seropositive vs. seronegative at baseline in both studies. No safety concerns were identified. CYD-TDV demonstrated long-term immunogenicity and was well-tolerated for four years after the third vaccine dose.

Identification of sympatric cryptic species of Aedes albopictus subgroup in Vietnam: new perspectives in phylosymbiosis of insect vector.

BACKGROUND: The Aedes (Stegomyia) albopictus subgroup includes 11 cryptic species of which Ae. albopictus is the most widely distributed. Its global expansion associated with a documented vector competence for several emerging arboviruses raise obvious concerns in the recently colonized regions. While several studies have provided important insights regarding medical importance of Ae. albopicus, the investigations of the other sibling species are scarce. In Asia, indigenous populations within the Ae. albopictus subgroup can be found in sympatry. In the present study, we aimed to describe and compare molecular, morphological and bacterial symbionts composition among sympatric individuals from the Ae. albopictus subgroup inhabiting a Vietnamese protected area. RESULTS: Based on morphological structure of the cibarial armarture, we identified a cryptic species in the forest park at Bù Gia Map in the south-eastern region of Vietnam. Analysis of nuclear (ITS1-5.8S-ITS2) and mitochondrial (cox1, nad5) markers confirmed the divergence between the cryptic species and Ae. albopictus. Analysis of midgut bacterial microbiota revealed a strong similarity among the two species with a notable difference; contrary to Ae. albopictus, the cryptic species did not harbour any Wolbachia infection. CONCLUSIONS: These results could reflect either a recent invasion of Wolbachia in Ae. albopictus or alternatively a loss of this symbiont in the cryptic species. We argue that neglected species of the Ae. albopictus subgroup are of main importance in order to estimate variation of host-symbionts interactions across evolution.

Symptomatic Dengue Disease in Five Southeast Asian Countries: Epidemiological Evidence from a Dengue Vaccine Trial.

Dengue incidence has increased globally, but empirical burden estimates are scarce. Prospective methods are best-able to capture all severities of disease. CYD14 was an observer-blinded dengue vaccine study conducted in children 2-14 years of age in Indonesia, Malaysia, Thailand, the Philippines, and Vietnam. The control group received no vaccine and resembled a prospective, observational study. We calculated the rates of dengue according to different laboratory or clinical criteria to make inferences about dengue burden, and compared with rates reported in the passive surveillance systems to calculate expansion factors which describe under-reporting. Over 6,933 person-years of observation in the control group there were 319 virologically confirmed dengue cases, a crude attack rate of 4.6%/year. Of these, 92 cases (28.8%) were clinically diagnosed as dengue fever or dengue hemorrhagic fever by investigators and 227 were not, indicating that most symptomatic disease fails to satisfy existing case definitions. When examining different case definitions, there was an inverse relationship between clinical severity and observed incidence rates. CYD14's active surveillance system captured a greater proportion of symptomatic dengue than national passive surveillance systems, giving rise to expansion factors ranging from 0.5 to 31.7. This analysis showed substantial, unpredictable and variable under-reporting of symptomatic dengue, even within a controlled clinical trial environment, and emphasizes that burden estimates are highly sensitive to case definitions. These data will assist in generating disease burden estimates and have important policy implications when considering the introduction and health economics of dengue prevention and control interventions.

Clinical efficacy and safety of a novel tetravalent dengue vaccine in healthy children in Asia: a phase 3, randomised, observer-masked, placebo-controlled trial.

BACKGROUND: An estimated 100 million people have symptomatic dengue infection every year. This is the first report of a phase 3 vaccine efficacy trial of a candidate dengue vaccine. We aimed to assess the efficacy of the CYD dengue vaccine against symptomatic, virologically confirmed dengue in children. METHODS: We did an observer-masked, randomised controlled, multicentre, phase 3 trial in five countries in the Asia-Pacific region. Between June 3, and Dec 1, 2011, healthy children aged 2-14 years were randomly assigned (2:1), by computer-generated permuted blocks of six with an interactive voice or web response system, to receive three injections of a recombinant, live, attenuated, tetravalent dengue vaccine (CYD-TDV), or placebo, at months 0, 6, and 12. Randomisation was stratified by age and site. Participants were followed up until month 25. Trial staff responsible for the preparation and administration of injections were unmasked to group allocation, but were not included in the follow-up of the participants; allocation was concealed from the study sponsor, investigators, and parents and guardians. Our primary objective was to assess protective efficacy against symptomatic, virologically confirmed dengue, irrespective of disease severity or serotype, that took place more than 28 days after the third injection. The primary endpoint was for the lower bound of the 95% CI of vaccine efficacy to be greater than 25%. Analysis was by intention to treat and per procotol. This trial is registered with ClinicalTrials.gov, number NCT01373281. FINDINGS: We randomly assigned 10,275 children to receive either vaccine (n=6851) or placebo (n=3424), of whom 6710 (98%) and 3350 (98%), respectively, were included in the primary analysis. 250 cases of virologically confirmed dengue took place more than 28 days after the third injection (117 [47%] in the vaccine group and 133 [53%] in the control group). The primary endpoint was achieved with 56·5% (95% CI 43·8-66·4) efficacy. We recorded 647 serious adverse events (402 [62%] in the vaccine group and 245 [38%] in the control group). 54 (1%) children in the vaccine group and 33 (1%) of those in the control group had serious adverse events that happened within 28 days of vaccination. Serious adverse events were consistent with medical disorders in this age group and were mainly infections and injuries. INTERPRETATION: Our findings show that dengue vaccine is efficacious when given as three injections at months 0, 6, and 12 to children aged 2-14 years in endemic areas in Asia, and has a good safety profile. Vaccination could reduce the incidence of symptomatic infection and hospital admission and has the potential to provide an important public health benefit. FUNDING: Sanofi Pasteur.