Intussusception and Other Adverse Event Surveillance after Pilot Introduction of Rotavirus Vaccine in Nam Dinh and Thua Thien Hue Provinces-Vietnam, 2017-2021.

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 <12 months of age admitted for intussusception, most (92.3%) were children ≥ 6 months. Of the 388 children who were age-eligible to receive Rotavin-M1, 116 (29.9%) had received ≥1 dose. No intussusception cases occurred in the 1-21 days after dose 1 and one case occurred on day 21 after dose 2. Among the 45,367 children who received ≥1 dose of Rotavin-M1, 9.5% of children reported at least one AEFI after dose 1 and 7.3% after dose 2. Significantly higher AEFI rates occurred among children given Rotavin-M1 with pentavalent vaccines (Quinvaxem®, 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.

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.

Conformational flexibility of coenzyme A and its impact on the post-translational modification of acyl carrier proteins by 4'-phosphopantetheinyl transferases.

One central question surrounding the biosynthesis of fatty acids and polyketide-derived natural products is how the 4'-phosphopantetheinyl transferase (PPTase) interrogates the essential acyl carrier protein (ACP) domain to fulfill the initial activation step. The triggering factor of this study was the lack of structural information on PPTases at physiological pH, which could bias our comprehension of the mechanism of action of these important enzymes. Structural and functional studies on the family II PPTase PptAb of Mycobacterium abscessus show that pH has a profound effect on the coordination of metal ions and on the conformation of endogenously bound coenzyme A (CoA). The observed conformational flexibility of CoA at physiological pH is accompanied by a disordered 4'-phosphopantetheine (Ppant) moiety. Finally, structural and dynamical information on an isolated mycobacterial ACP domain, in its apo form and in complex with the activator PptAb, suggests an alternate mechanism for the post-translational modification of modular megasynthases.