Progress Toward Poliomyelitis Eradication - Worldwide, January 2021-March 2023.

Since the World Health Assembly established the Global Polio Eradication Initiative (GPEI) in 1988, two of the three wild poliovirus (WPV) serotypes (types 2 and 3) have been eradicated, and global WPV cases have decreased by more than 99.9%. Afghanistan and Pakistan remain the only countries where indigenous WPV type 1 (WPV1) transmission has not been interrupted. This report summarizes progress toward global polio eradication during January 1, 2021-March 31, 2023, and updates previous reports (1,2). In 2022, Afghanistan and Pakistan reported 22 WPV1 cases, compared with five in 2021; as of May 5, 2023, a single WPV1 case was reported in Pakistan in 2023. A WPV1 case was reported on the African continent for the first time since 2016, when officials in Malawi confirmed a WPV1 case in a child with paralysis onset in November 2021; neighboring Mozambique subsequently reported eight genetically linked cases. Outbreaks of polio caused by circulating vaccine-derived polioviruses (cVDPVs) can occur when oral poliovirus vaccine (OPV) strains circulate for a prolonged time in underimmunized populations, allowing reversion to neurovirulence (3). A total of 859 cVDPV cases occurred during 2022, an increase of 23% from 698 cases in 2021. cVDPVs were detected in areas where poliovirus transmission had long been eliminated (including in Canada, Israel, the United Kingdom, and the United States). In addition, cocirculation of multiple poliovirus types occurred in multiple countries globally (including Democratic Republic of the Congo [DRC], Israel, Malawi, Mozambique, Republic of the Congo, and Yemen). The 2022-2026 GPEI strategic plan targeted the goal of detecting the last cases of WPV1 and cVDPV in 2023 (4). The current global epidemiology of poliovirus transmission makes the likelihood of meeting this target date unlikely. The detections of poliovirus (WPV1 and cVDPVs) in areas where it had been previously eliminated underscore the threat of continued poliovirus spread to any area where there is insufficient vaccination to poliovirus (3). Mass vaccination and surveillance should be further enhanced in areas of transmission to interrupt poliovirus transmission and to end the global threat of paralytic polio in children.

Booster vaccination protection against SARS-CoV-2 infections in young adults during an Omicron BA.1-predominant period: A retrospective cohort study.

BACKGROUND: While booster vaccinations clearly reduce the risk of severe Coronavirus Disease 2019 (COVID-19) and death, the impact of boosters on Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infections has not been fully characterized: Doing so requires understanding their impact on asymptomatic and mildly symptomatic infections that often go unreported but nevertheless play an important role in spreading SARS-CoV-2. We sought to estimate the impact of COVID-19 booster doses on SARS-CoV-2 infections in a vaccinated population of young adults during an Omicron BA.1-predominant period. METHODS AND FINDINGS: We implemented a cohort study of young adults in a college environment (Cornell University's Ithaca campus) from a period when Omicron BA.1 was the predominant SARS-CoV-2 variant on campus (December 5 to December 31, 2021). Participants included 15,800 university students who completed initial vaccination series with vaccines approved by the World Health Organization for emergency use, were enrolled in mandatory at-least-weekly surveillance polymerase chain reaction (PCR) testing, and had no positive SARS-CoV-2 PCR test within 90 days before the start of the study period. Robust multivariable Poisson regression with the main outcome of a positive SARS-CoV-2 PCR test was performed to compare those who completed their initial vaccination series and a booster dose to those without a booster dose. A total of 1,926 unique SARS-CoV-2 infections were identified in the study population. Controlling for sex, student group membership, date of completion of initial vaccination series, initial vaccine type, and temporal effect during the study period, our analysis estimates that receiving a booster dose further reduces the rate of having a PCR-detected SARS-CoV-2 infection relative to an initial vaccination series by 56% (95% confidence interval [42%, 67%], P < 0.001). While most individuals had recent booster administration before or during the study period (a limitation of our study), this result is robust to the assumed delay over which a booster dose becomes effective (varied from 1 day to 14 days). The mandatory active surveillance approach used in this study, under which 86% of the person-days in the study occurred, reduces the likelihood of outcome misclassification. Key limitations of our methodology are that we did not have an a priori protocol or statistical analysis plan because the analysis was initially done for institutional research purposes, and some analysis choices were made after observing the data. CONCLUSIONS: We observed that boosters are effective, relative to completion of initial vaccination series, in further reducing the rate of SARS-CoV-2 infections in a college student population during a period when Omicron BA.1 was predominant; booster vaccinations for this age group may play an important role in reducing incidence of COVID-19.

Fate-mapping mice: new tools and technology for immune discovery.

The fate-mapping mouse has become an essential tool in the immunologist's toolbox. Although traditionally used by developmental biologists to trace the origins of cells, immunologists are turning to fate-mapping to better understand the development and function of immune cells. Thus, an expansion in the variety of fate-mapping mouse models has occurred to answer fundamental questions about the immune system. These models are also being combined with new genetic tools to study cancer, infection, and autoimmunity. In this review, we summarize different types of fate-mapping mice and describe emerging technologies that might allow immunologists to leverage this valuable tool and expand our functional knowledge of the immune system.

Colistin resistance and plasmid-mediated mcr genes in Escherichia coli and Salmonella isolated from pigs, pig carcass and pork in Thailand, Lao PDR and Cambodia border provinces.

BACKGROUND: Colistin and carbapenem-resistant bacteria have emerged and become a serious public health concern, but their epidemiological data is still limited. OBJECTIVES: This study examined colistin and carbapenem resistance in Escherichia coli and Salmonella from pigs, pig carcasses, and pork in Thailand, Lao PDR, and Cambodia border provinces. METHODS: The phenotypic and genotypic resistance to colistin and meropenem was determined in E. coli and Salmonella obtained from pigs, pig carcasses, and pork (n = 1,619). A conjugative experiment was performed in all isolates carrying the mcr gene (s) (n = 68). The plasmid replicon type was determined in the isolates carrying a conjugative plasmid with mcr by PCR-based replicon typing (n = 7). The genetic relatedness of mcr-positive Salmonella (n = 11) was investigated by multi-locus sequence typing. RESULTS: Colistin resistance was more common in E. coli (8%) than Salmonella (1%). The highest resistance rate was found in E. coli (17.8%) and Salmonella (1.7%) from Cambodia. Colistin-resistance genes, mcr-1, mcr-3, and mcr-5, were identified, of which mcr-1 and mcr-3 were predominant in E. coli (5.8%) and Salmonella (1.7%), respectively. The mcr-5 gene was observed in E. coli from pork in Cambodia. Two colistin-susceptible pig isolates from Thailand carried both mcr-1 and mcr-3. Seven E. coli and Salmonella isolates contained mcr-1 or mcr-3 associated with the IncF and IncI plasmids. The mcr-positive Salmonella from Thailand and Cambodia were categorized into two clusters with 94%-97% similarity. None of these clusters was meropenem resistant. CONCLUSIONS: Colistin-resistant E. coli and Salmonella were distributed in pigs, pig carcasses, and pork in the border areas. Undivided-One Health collaboration is needed to address the issue.

An autoinhibitory conformation of the Bacillus subtilis spore coat protein SpoIVA prevents its premature ATP-independent aggregation.

Spores of Bacillus subtilis are dormant cell types that are formed when the bacterium encounters starvation conditions. Spores are encased in a shell, termed the coat, which is composed of approximately seventy different proteins and protects the spore's genetic material from environmental insults. The structural component of the basement layer of the coat is an exceptional cytoskeletal protein, termed SpoIVA, which binds and hydrolyzes ATP. ATP hydrolysis is utilized to drive a conformational change in SpoIVA that leads to its irreversible self-assembly into a static polymer in vitro. Here, we characterize the middle domain of SpoIVA, the predicted secondary structure of which resembles the chemotaxis protein CheX but, unlike CheX, does not harbor residues required for phosphatase activity. Disruptions in this domain did not abolish ATP hydrolysis, but resulted in mislocalization of the protein and reduction in sporulation efficiency in vivo. In vitro, disruptions in this domain prevented the ATP hydrolysis-driven conformational change in SpoIVA required for polymerization and led to the aggregation of SpoIVA into particles that did not form filaments. We propose a model in which SpoIVA initially assumes a conformation in which it inhibits its own aggregation into particles, and that ATP hydrolysis remodels the protein so that it assumes a polymerization-competent conformation.