Rotavirus causes severe gastroenteritis in infants and young children worldwide. The UK introduced the monovalent rotavirus vaccine (Rotarix®) in July 2013. Vaccination is free of charge to parents, with two doses delivered at 8 and 12 weeks of age. We evaluated vaccine impact across a health system in relation to socioeconomic deprivation. We used interrupted time-series analyses to assess changes in monthly health-care attendances in Merseyside, UK, for all ages, from July 2013 to June 2016, compared to predicted counterfactual attendances without vaccination spanning 3–11 years pre-vaccine. Outcome measures included laboratory-confirmed rotavirus gastroenteritis (RVGE) hospitalisations, acute gastroenteritis (AGE) hospitalisations, emergency department (ED) attendances for gastrointestinal conditions and consultations for infectious gastroenteritis at community walk-in centres (WIC) and general practices (GP). All analyses were stratified by age. Hospitalisations were additionally stratified by vaccine uptake and small-area-level socioeconomic deprivation. The uptake of the first and second doses of rotavirus vaccine was 91.4% (29,108/31,836) and 86.7% (27,594/31,836), respectively. Among children aged < 5 years, the incidence of gastrointestinal disease decreased across all outcomes post-vaccine introduction: 80% (95% confidence interval [CI] 70–87%; p < 0.001) for RVGE hospitalisation, 44% (95% CI 35–53%; p < 0.001) for AGE hospitalisations, 23% (95% CI 11–33%; p < 0.001) for ED, 32% (95% CI 7–50%; p = 0.02) for WIC and 13% (95% CI -3–26%; p = 0.10) for GP. The impact was greatest during the rotavirus season and for vaccine-eligible age groups. In adults aged 65+ years, AGE hospitalisations fell by 25% (95% CI 19–30%; p < 0.001). The pre-vaccine risk of AGE hospitalisation was highest in the most socioeconomically deprived communities (adjusted incident rate ratio 1.57; 95% CI 1.51–1.64; p < 0.001), as was the risk for non-vaccination (adjusted risk ratio 1.54; 95% CI 1.34–1.75; p < 0.001). The rate of AGE hospitalisations averted per 1,000 first doses of vaccine was higher among infants in the most deprived communities compared to the least deprived in 2014/15 (28; 95% CI 25–31 vs. 15; 95% CI 12–17) and in 2015/16 (26; 95% CI 23–30 vs. 13; 95% CI 11–16). Following the introduction of rotavirus vaccination, incidence of gastrointestinal disease reduced across the health-care system. Vaccine impact was greatest among the most deprived populations, despite lower vaccine uptake. Prioritising vaccine uptake in socioeconomically deprived communities should give the greatest health benefit in terms of population disease burden.

Summary: Background: COVID-19 pandemic has developed rapidly and the ability to stratify the most vulnerable patients is vital. However, routinely used severity scoring systems are often low on diagnosis, even in non-survivors. Therefore, clinical prediction models for mortality are urgently required. Methods: We developed and internally validated a multivariable logistic regression model to predict inpatient mortality in COVID-19 positive patients using data collected retrospectively from Tongji Hospital, Wuhan (299 patients). External validation was conducted using a retrospective cohort from Jinyintan Hospital, Wuhan (145 patients). Nine variables commonly measured in these acute settings were considered for model development, including age, biomarkers and comorbidities. Backwards stepwise selection and bootstrap resampling were used for model development and internal validation. We assessed discrimination via the C statistic, and calibration using calibration-in-the-large, calibration slopes and plots. Findings: The final model included age, lymphocyte count, lactate dehydrogenase and SpO ₂ as independent predictors of mortality. Discrimination of the model was excellent in both internal (c=0·89) and external (c=0·98) validation. Internal calibration was excellent (calibration slope=1). External validation showed some over-prediction of risk in low-risk individuals and under-prediction of risk in high-risk individuals prior to recalibration. Recalibration of the intercept and slope led to excellent performance of the model in independent data. Interpretation: COVID-19 is a new disease and behaves differently from common critical illnesses. This study provides a new prediction model to identify patients with lethal COVID-19. Its practical reliance on commonly available parameters should improve usage of limited healthcare resources and patient survival rate. Funding: This study was supported by following funding: Key Research and Development Plan of Jiangsu Province (BE2018743 and BE2019749), National Institute for Health Research (NIHR) (PDF-2018-11-ST2-006), British Heart Foundation (BHF) (PG/16/65/32313) and Liverpool University Hospitals NHS Foundation Trust in UK. Research in context: Evidence before this study: Since the outbreak of COVID-19, there has been a pressing need for development of a prognostic tool that is easy for clinicians to use. Recently, a Lancet publication showed that in a cohort of 191 patients with COVID-19, age, SOFA score and D-dimer measurements were associated with mortality. No other publication involving prognostic factors or models has been identified to date. Added value of this study: In our cohorts of 444 patients from two hospitals, SOFA scores were low in the majority of patients on admission. The relevance of D-dimer could not be verified, as it is not included in routine laboratory tests. In this study, we have established a multivariable clinical prediction model using a development cohort of 299 patients from one hospital. After backwards selection, four variables, including age, lymphocyte count, lactate dehydrogenase and SpO ₂ remained in the model to predict mortality. This has been validated internally and externally with a cohort of 145 patients from a different hospital. Discrimination of the model was excellent in both internal (c=0·89) and external (c=0·98) validation. Calibration plots showed excellent agreement between predicted and observed probabilities of mortality after recalibration of the model to account for underlying differences in the risk profile of the datasets. This demonstrated that the model is able to make reliable predictions in patients from different hospitals. In addition, these variables agree with pathological mechanisms and the model is easy to use in all types of clinical settings. Implication of all the available evidence: After further external validation in different countries the model will enable better risk stratification and more targeted management of patients with COVID-19. With the nomogram, this model that is based on readily available parameters can help clinicians to stratify COVID-19 patients on diagnosis to use limited healthcare resources effectively and improve patient outcome.

Despite rotavirus vaccination, diarrhea remains a leading cause of child mortality. We collected stool specimens from 684 children <5 years of age hospitalized with diarrhea (cases) and 527 asymptomatic community controls for 4 years after rotavirus vaccine introduction in Malawi. Specimens were tested for 29 pathogens, using polymerase chain reaction analysis. Three or more pathogens were detected in 71% of cases and 48% of controls. Pathogens significantly associated with diarrhea included rotavirus (in 34.7% of cases and 1.5% of controls), enteric adenovirus (in 29.1% and 2.7%, respectively), Cryptosporidium (in 27.8% and 8.2%, respectively), heat-stable enterotoxin-producing Escherichia coli (in 21.2% and 8.5%, respectively), typical enteropathogenic E. coli (in 18.0% and 8.3%, respectively), and Shigella/enteroinvasive E. coli (in 15.8% and 5.7%, respectively). Additional interventions are required to prevent diarrhea due to rotavirus and other common causal pathogens.

SUMMARY: Suboptimal uptake of the measles, mumps and rubella (MMR) vaccine by certain socioeconomic groups may have contributed to recent large measles outbreaks in the UK. We investigated whether socioeconomic deprivation was associated with MMR vaccine uptake over 16 years. Using immunization data for 72 351 children born between 1995 and 2012 in Liverpool, UK, we examined trends in vaccination uptake. Generalized linear models were constructed to examine the relative effect of socioeconomic deprivation and year of birth on MMR uptake. Uptake of MMR1 by age 24 months ranged between 82·5% in 2003 [95% confidence interval (CI) 81·2–83·7] and 93·4% in 2012 (95% CI 92·7–94·2). Uptake of MMR2 by age 60 months ranged between 65·3% (95% CI 64·4–67·4) in 2006 and 90·3% (95% CI 89·4–91·2) in 2012. In analysis adjusted for year of birth and sex, children in the most deprived communities were at significantly greater risk of not receiving MMR1 [risk ratio (RR) 1·70, 95% CI 1·45–1·99] and MMR2 (RR 1·36, 95% CI 1·22–1·52). Higher unemployment and lower household income were significantly associated with low uptake. Contrary to concerns about lower MMR uptake in affluent families, over 16 years, children from the most socioeconomically deprived communities have consistently had the lowest MMR uptake. Targeted catch-up campaigns and strategies to improve routine immunization uptake in deprived areas are needed to minimize the risk of future measles outbreaks.

Malawi experienced its deadliest Vibrio cholerae (Vc) outbreak following devastating cyclones, with >58,000 cases and >1700 deaths reported between March 2022 and May 2023. Here, we use population genomics to investigate the attributes and origin of the Malawi 2022–2023 Vc outbreak isolates. Our results demonstrate the predominance of ST69 clone, also known as the seventh cholera pandemic El Tor (7PET) lineage, expressing O1 Ogawa (~ 80%) serotype followed by Inaba (~ 16%) and sporadic non-O1/non-7PET serogroups (~ 4%). Phylogenetic reconstruction revealed that the Malawi outbreak strains correspond to a recent importation from Asia into Africa (sublineage AFR15). These isolates harboured known antimicrobial resistance and virulence elements, notably the ICE^GEN/ICEVchHai1/ICEVchind5 SXT/R391-like integrative conjugative elements and a CTXφ prophage with the ctxB7 genotype compared to historical Malawian Vc isolates. These data suggest that the devastating cyclones coupled with the recent importation of 7PET serogroup O1 strains, may explain the magnitude of the 2022–2023 cholera outbreak in Malawi.

Introduction: Rotavirus vaccination with the live-attenuated monovalent (a G1P[8] human rotavirus strain) two-dose Rotarix vaccine was introduced in England in July 2013. Since then, there have been significant reductions in rotavirus gastroenteritis incidence. Aim: We assessed the vaccine’s impact on rotavirus genotype distribution and diversity 3 years post-vaccine introduction. Methods: Epidemiological and microbiological data on genotyped rotavirus-positive samples between September 2006 and August 2016 were supplied by EuroRotaNet and Public Health England. Multinomial multivariable logistic regression adjusting for year, season and age was used to quantify changes in genotype prevalence in the vaccine period. Genotype diversity was measured using the Shannon’s index (H′) and Simpson’s index of diversity (D). Results: We analysed genotypes from 8,044 faecal samples. In the pre-vaccine era, G1P[8] was most prevalent, ranging from 39% (411/1,057) to 74% (527/709) per year. In the vaccine era, G1P[8] prevalence declined each season (35%, 231/654; 12%, 154/1,257; 5%, 34/726) and genotype diversity increased significantly in 6–59 months old children (H’ p < 0.001: D p < 0.001). In multinomial analysis, G2P[4] (adjusted multinomial odds ratio (aMOR): 9.51; 95% confidence interval (CI): 7.02–12.90), G3P[8] (aMOR: 2.83; 95% CI: 2.17–3.81), G12P[8] (aMOR: 2.46; 95% CI: 1.62–3.73) and G4P[8] (aMOR: 1.42; 95% CI: 1.02–1.96) significantly increased relative to G1P[8]. Conclusions: In the context of reduced rotavirus disease incidence, genotype diversity has increased, with a relative change in the dominant genotype from G1P[8] to G2P[4] after vaccine introduction. These changes will need continued surveillance as the number and age of vaccinated birth cohorts increase in the future.