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Hepatitis B virus (HBV) antiviral administration and adherence are essential to reach the World Health Organization's 2030 hepatitis elimination goals. As HBV treatment guidelines are now simplified and expanded, adherence to treatment will be critical, but challenges to adherence are poorly studied. After introducing tenofovir disoproxil fumarate (TDF) monotherapy to expectant mothers with high-risk HBV in Kinshasa, DRC, we conducted semi-structured interviews to understand medication adherence behaviors, to complement pill counts and measurement of TDF metabolite levels. Key facilitators of adherence identified included trust in healthcare workers, a better understanding of HBV, and family support. Identified barriers included fear of stigma and low health literacy. Knowledge about HBV disease remains low, underscoring the importance of ongoing education of clinic staff and patients alike. [ABSTRACT FROM AUTHOR]

The WHO recommends hepatitis B birth‐dose vaccination (HepB‐BD), but it is not routinely given in most sub‐Saharan African countries. We aimed to assess the immunogenicity of HepB‐BD in addition to the existing hepatitis B vaccine (HepB3) schedule in Kinshasa, Democratic Republic of Congo among HBV‐unexposed and HBV‐exposed infants. Using an open‐label, randomised, controlled design, HBV‐unexposed infants were randomised (1:1) to receive the standard HepB3 vaccine series (group U3), or to receive HepB‐BD in addition to HepB3 (group U4). A supplemental cohort of HBV‐exposed infants (group E4) received HepB‐BD and HepB3. We compared the proportion of infants with protective antibodies against HBV (HBV surface antibody ≥ 10 mIU/mL) between groups U3 and U4 and groups U4 and E4 at 12 months of age. Between August 20 and October 9, 2019, we enrolled 281 mother/infant dyads; 88 (31.3%) returned at 12 months. Most infants had protective antibodies against HBV at 12 months: 92.9% (75.7%–98.2%) in group U3, 85.7% (67.5%–94.5%) in group U4 and 96.9% (95% CI: 81.2%–99.6%) in group E4. Trends held in estimates adjusted for loss‐to‐follow‐up (LTFU) and baseline imbalance across groups. In this first randomised trial assessing the addition of HepB‐BD to the hepatitis B vaccine schedule in SSA, we found that HBV‐unexposed infants who received the 3‐dose and 4‐dose vaccine series had similar immunogenicity against HBV at 12 months. A high proportion of infants, and notably HBV‐exposed infants, had protective antibodies. Though extrapolation of findings may be limited by LTFU, this study adds real‐world evidence regarding HepB‐BD implementation in sub‐Saharan Africa. Trial Registration: ClinicalTrials.gov identifier: NCT03897946 [ABSTRACT FROM AUTHOR]

While progress has been made toward global elimination of hepatitis B virus, many countries lag behind. A one-size-fits-all approach is not practical to address HBV. Rather, the approach should be tailored to local prevalence, risk factors, and available resources. [ABSTRACT FROM AUTHOR]

Random mutagenesis, including when it leads to loss of gene function, is a key mechanism enabling microorganisms' long-term adaptation to new environments. However, loss-of-function mutations are often deleterious, triggering, in turn, cellular stress and complex homeostatic stress responses, called "allostasis," to promote cell survival. Here, we characterize the differential impacts of 65 nonlethal, deleterious single-gene deletions on Escherichia coli growth in three different growth environments. Further assessments of select mutants, namely, those bearing single adenosine triphosphate (ATP) synthase subunit deletions, reveal that mutants display reorganized transcriptome profiles that reflect both the environment and the specific gene deletion. We also find that ATP synthase a-subunit deleted (ΔatpA) cells exhibit elevated metabolic rates while having slower growth compared to wild-type (wt) E. coli cells. At the single-cell level, compared to wt cells, individual ΔatpA cells display near normal proliferation profiles but enter a postreplicative state earlier and exhibit a distinct senescence phenotype. These results highlight the complex interplay between genomic diversity, adaptation, and stress response and uncover an "aging cost" to individual bacterial cells for maintaining population-level resilience to environmental and genetic stress; they also suggest potential bacteriostatic antibiotic targets and -as select human genetic diseases display highly similar phenotypes, - a bacterial origin of some human diseases. [ABSTRACT FROM AUTHOR]

Background COVID-19 vaccines are available for adolescents in the United States, but many parents are hesitant to have their children vaccinated. The advice of primary care professionals strongly influences vaccine uptake. Objective We examined the willingness of primary care professionals (PCPs) to recommend COVID-19 vaccination for adolescents. Methods Participants were a national sample of 1,047 US adolescent primary care professionals. They participated in an online survey in early 2021, after a COVID-19 vaccine had been approved for adults but before approval for adolescents. Respondents included physicians (71%), advanced practice providers (17%), and nurses (12%). We identified correlates of willingness to recommend COVID-19 vaccination for adolescents using logistic regression. Results The majority (89%) of respondents were willing to recommend COVID-19 vaccination for adolescents, with advanced practice providers and nurses being less likely than paediatricians to recommend vaccination (84% vs. 94%, aOR 0.47, 95% CI 0.23–0.92). Respondents who had received at least one dose of a COVID-19 vaccine were more likely to recommend adolescent vaccination (92% vs. 69%, aOR 4.20, 95% CI 2.56–6.87) as were those with more years in practice (94% vs. 88%, aOR 2.93, 95% CI 1.79–4.99). Most respondents (96%) said they would need some measure of support in order to provide COVID-19 vaccination to adolescents, with vaccine safety and efficacy information being the most commonly cited need (80%). Conclusion Adolescent primary care professionals were generally willing to recommend COVID-19 vaccination. However, most indicated a need for additional resources to be able to administer COVID-19 vaccines at their clinic. [ABSTRACT FROM AUTHOR]

Oral rotavirus vaccine efficacy estimates from randomised controlled trials are highly variable across settings. Although the randomised study design increases the likelihood of internal validity of findings, results from trials may not always apply outside the context of the study due to differences between trial participants and the target population. Here, we used a weight-based method to transport results from a monovalent rotavirus vaccine clinical trial conducted in Malawi between 2005 and 2008 to a target population of all trial-eligible children in Malawi, represented by data from the 2015–2016 Malawi Demographic and Health Survey (DHS). We reweighted trial participants to reflect the population characteristics described by the Malawi DHS. Vaccine efficacy was estimated for 1008 trial participants after applying these weights such that they represented trial-eligible children in Malawi. We also conducted subgroup analyses to examine the heterogeneous treatment effects by stunting and tuberculosis vaccination status at enrolment. In the original trial, the estimates of one-year vaccine efficacy against severe rotavirus gastroenteritis and any-severity rotavirus gastroenteritis in Malawi were 49.2% (95% CI 15.6%–70.3%) and 32.1% (95% CI 2.5%–53.1%), respectively. After weighting trial participants to represent all trial-eligible children in Malawi, vaccine efficacy increased to 62.2% (95% CI 35.5%–79.0%) against severe rotavirus gastroenteritis and 38.9% (95% CI 11.4%–58.5%) against any-severity rotavirus gastroenteritis. Rotavirus vaccine efficacy may differ between trial participants and target populations when these two populations differ. Differences in tuberculosis vaccination status between the trial sample and DHS population contributed to varying trial and target population vaccine efficacy estimates. [ABSTRACT FROM AUTHOR]

Oral rotavirus vaccine efficacy estimates from randomised controlled trials are highly variable across settings. Although the randomised study design increases the likelihood of internal validity of findings, results from trials may not always apply outside the context of the study due to differences between trial participants and the target population. Here, we used a weight-based method to transport results from a monovalent rotavirus vaccine clinical trial conducted in Malawi between 2005 and 2008 to a target population of all trial-eligible children in Malawi, represented by data from the 2015–2016 Malawi Demographic and Health Survey (DHS). We reweighted trial participants to reflect the population characteristics described by the Malawi DHS. Vaccine efficacy was estimated for 1008 trial participants after applying these weights such that they represented trial-eligible children in Malawi. We also conducted subgroup analyses to examine the heterogeneous treatment effects by stunting and tuberculosis vaccination status at enrolment. In the original trial, the estimates of one-year vaccine efficacy against severe rotavirus gastroenteritis and any-severity rotavirus gastroenteritis in Malawi were 49.2% (95% CI 15.6%–70.3%) and 32.1% (95% CI 2.5%–53.1%), respectively. After weighting trial participants to represent all trial-eligible children in Malawi, vaccine efficacy increased to 62.2% (95% CI 35.5%–79.0%) against severe rotavirus gastroenteritis and 38.9% (95% CI 11.4%–58.5%) against any-severity rotavirus gastroenteritis. Rotavirus vaccine efficacy may differ between trial participants and target populations when these two populations differ. Differences in tuberculosis vaccination status between the trial sample and DHS population contributed to varying trial and target population vaccine efficacy estimates. [ABSTRACT FROM AUTHOR]