BACKGROUND: Female sexual function is important for sexual well-being, general health, fertility, and relationship satisfaction. Distressing impairments in sexual function, clinically recognized as female sexual dysfunction (FSD), can manifest as issues with interest/desire, arousal, orgasm, and pain during vaginal penetration. Some evidence suggests that exposure to endocrine-disrupting chemicals may adversely affect female sexual function, but associations for per- and polyfluoroalkyl substances (PFAS) have not been previously evaluated. OBJECTIVE: We investigated associations between serum PFAS concentrations and female sexual function among U.S. pregnancy planners. METHODS: We used cross-sectional data from participants from Pregnancy Study Online (PRESTO), a prospective preconception cohort study. Participants reported sexual function and distress at baseline on two validated measures: a modified version of the Female Sexual Function Index-6 (FSFI-6) and the Female Sexual Distress Scale (FSDS). We quantified PFAS serum concentrations in samples collected in the preconception period (i.e., at baseline) using solid phase extraction-high performance liquid chromatography-isotope-dilution-mass spectrometry. Participants reported sociodemographic information on structured baseline questionnaires. We included 78 participants with complete PFAS and sexual function data and fit multivariable linear regression models to estimate mean differences in FSFI-6 scores (β) or percent differences (%) in FSDS scores per interquartile range (IQR) increase in PFAS concentrations, adjusting for age, annual household income, years of education, parity, and body mass index. We further investigated effect measure modification by parity (parous vs. nulliparous) in stratified models. RESULTS: An IQR increase in perfluorohexanesulfonic acid was associated with a 1.0-point decrease (95% CI = -1.8, -0.1) in reported FSFI-6 scores, reflecting poorer sexual function. PFAS were consistently associated with lower FSFI-6 scores among parous participants. PFAS were also associated, though imprecisely, with greater sexual distress. CONCLUSION: Some PFAS were associated with poorer sexual function among U.S. pregnancy planners, but future studies are needed to clarify the extent to which PFAS influences female sexual health.

Unmeasured confounding is a major concern in many epidemiologic studies that are not randomized. Negative control methods can detect and reduce confounding by leveraging the proxies of the unmeasured confounders, including negative control outcomes (NCO) and exposures (NCE). An NCO is presumably unaffected by the exposure of interest but would be associated with unmeasured confounders; an NCE presumably does not affect the outcome of interest but would be associated with unmeasured confounders. A recently proposed double negative control method leverages both NCO and NCE for unmeasured confounding bias. To demonstrate this relatively new methodology in pharmacoepidemiologic studies, we re-analyzed data from a prior safety study of Recombinant Zoster Vaccine (RZV). The prior study compared risk of safety outcomes of RZV versus unvaccinated comparators, using logistic regression with propensity score adjustment. We identified NCOs and NCEs that could be used to adjust for unmeasured confounding bias that could arise if RZV recipients are incomparable to the comparators due to unmeasured factors. The double negative control analysis yielded relative risk estimates slightly closer to 1.0 than those reported previously, providing additional evidence of RZV safety that is less vulnerable to unmeasured confounding.

CDC continues to track the evolution of SARS-CoV-2, including the Omicron variant and its descendants, using national genomic surveillance. This report summarizes U.S. trends in variant proportion estimates during May 2023-September 2024, a period when SARS-CoV-2 lineages primarily comprised descendants of Omicron variants XBB and JN.1. During summer and fall 2023, multiple descendants of XBB with immune escape substitutions emerged and reached >10% prevalence, including EG.5-like lineages by June 24, FL.1.5.1-like lineages by August 5, HV.1 lineage by September 30, and HK.3-like lineages by November 11. In winter 2023, the JN.1 variant emerged in the United States and rapidly attained predominance nationwide, representing a substantial genetic shift (>30 spike protein amino acid differences) from XBB lineages. Descendants of JN.1 subsequently circulated and reached >10% prevalence, including KQ.1-like and KP.2-like lineages by April 13, KP.3 and LB.1-like lineages by May 25, and KP.3.1.1 by July 20. Surges in COVID-19 cases occurred in winter 2024 during the shift to JN.1 predominance, as well as in summer 2023 and 2024 during circulation of multiple XBB and JN.1 descendants, respectively. The ongoing evolution of the Omicron variant highlights the importance of continued genomic surveillance to guide medical countermeasure development, including the selection of antigens for updated COVID-19 vaccines.

One Health aims to achieve optimal health outcomes for people, animals, plants, and shared environments. We describe a multisector effort to understand and mitigate SARS-CoV-2 transmission risk to humans via the spread among and between captive and wild white-tailed deer. We first framed a One Health problem with three governance sectors that manage captive deer, wild deer populations, and public health. The problem framing included identifying fundamental objectives, causal chains for transmission, and management actions. We then developed a dynamic model that linked deer herds and simulated SARS-CoV-2. Next, we evaluated management alternatives for their ability to reduce SARS-CoV-2 spread in white-tailed deer. We found that single-sector alternatives reduced transmission, but that the best-performing alternative required collaborative actions among wildlife management, agricultural management, and public health agencies. Here, we show quantitative support that One Health actions outperform single-sector responses, but may depend on coordination to track changes in this evolving system.

Many individually randomized group treatment (IRGT) trials randomly assign individuals to study arms but deliver treatments via shared agents, such as therapists, surgeons, or trainers. Post-randomization interactions induce correlations in outcome measures between participants sharing the same agent. Agents can be nested in or crossed with trial arm, and participants may interact with a single agent or with multiple agents. These complications have led to ambiguity in choice of models but there have been no systematic efforts to identify appropriate analytic models for these study designs. To address this gap, we undertook a simulation study to examine the performance of candidate analytic models in the presence of complex clustering arising from multiple membership, single membership, and single agent settings, in both nested and crossed designs and for a continuous outcome. With nested designs, substantial type I error rate inflation was observed when analytic models did not account for multiple membership and when analytic model weights characterizing the association with multiple agents did not match the data generating mechanism. Conversely, analytic models for crossed designs generally maintained nominal type I error rates unless there was notable imbalance in the number of participants that interact with each agent.

BACKGROUND: Endocrine disrupting chemicals (EDCs) are widely used compounds with the potential to affect child neurodevelopmental outcomes including autism spectrum disorders (ASD). We aimed to examine the urinary concentrations of biomarkers of EDCs, including phthalates, phenols, and parabens, and investigate whether exposure during early infancy was associated with increased risk of later ASD or other non-typical development (Non-TD) or adverse cognitive development. METHODS: This analysis included infants from the Markers of Autism Risks in Babies-Learning Early Signs (MARBLES) study, a high-risk ASD cohort (n = 148; corresponding to 188 urine samples). Thirty-two EDC biomarkers were quantified in urine among infants 3 and/or 6 months of age. Trends in EDC biomarker concentrations were calculated using least square geometric means. At 36 months of age, children were clinically classified as having ASD (n = 36), nontypical development (Non-TD; n = 18), or typical development (TD; n = 81) through a clinical evaluation. Trinomial logistic regression analysis was used to test the associations between biomarkers with ASD, or Non-TD, as compared to children with TD. In single analyte analysis, generalized estimating equations were used to investigate the association between each EDC biomarkers and longitudinal changes in cognitive development using the Mullen Scales of Early Learning (MSEL) over the four assessment time points (6, 12, 24, and 36 months of age). Additionally, quantile g-computation was used to test for a mixture effect. RESULTS: EDC biomarker concentrations generally decreased over the study period, except for mono-2-ethyl-5-carboxypentyl terephthalate. Overall, EDC biomarkers at 3 and/or 6 months of age were not associated with an increased risk of ASD or Non-TD, and a few showed significant inverse associations. However, when assessing longitudinal changes in MSEL scores over the four assessment time points, elevated monoethyl phthalate (MEP) was significantly associated with reduced scores in the composite score (β = -0.16, 95% CI: 0.31, -0.02) and subscales of fine motor skills (β = -0.09, 95%CI: 0.17, 0.00), and visual reception (β = -0.11, 95% CI: 0.23, 0.01). Additionally, the sum of metabolites of di (2-ethylhexyl) terephthalate (ƩDEHTP) was associated with poorer visual reception (β = -0.09, 95% CI: 0.16, -0.02), and decreased composite scores (β = -0.11, 95% CI: 0.21, -0.01). Mixtures analyses using quantile g-computation analysis did not show a significant association between mixtures of EDC biomarkers and MSEL subscales or composite scores. CONCLUSION: These findings highlight the potential importance of infant exposures on cognitive development. Future research can help further investigate whether early infant exposures are associated with longer-term deficits and place special attention on EDCs with increasing temporal trends and whether they may adversely affect neurodevelopment.

Antimicrobial resistance (AMR) is a world-wide public health threat that is projected to lead to 10 million annual deaths globally by 2050. The AMR public health issue has led to the development of action plans to combat AMR, including improved antimicrobial stewardship, development of new antimicrobials, and advanced monitoring. The National Antimicrobial Resistance Monitoring System (NARMS) led by the United States (U.S) Food and Drug Administration along with the U.S. Centers for Disease Control and U.S. Department of Agriculture has monitored antimicrobial resistant bacteria in retail meats, humans, and food animals since the mid 1990's. NARMS is currently exploring an integrated One Health monitoring model recognizing that human, animal, plant, and environmental systems are linked to public health. Since 2020, the U.S. Environmental Protection Agency has led an interagency NARMS environmental working group (EWG) to implement a surface water AMR monitoring program (SWAM) at watershed and national scales. The NARMS EWG divided the development of the environmental monitoring effort into five areas: (i) defining objectives and questions, (ii) designing study/sampling design, (iii) selecting AMR indicators, (iv) establishing analytical methods, and (v) developing data management/analytics/metadata plans. For each of these areas, the consensus among the scientific community and literature was reviewed and carefully considered prior to the development of this environmental monitoring program. The data produced from the SWAM effort will help develop robust surface water monitoring programs with the goal of assessing public health risks associated with AMR pathogens in surface water (e.g., recreational water exposures), provide a comprehensive picture of how resistant strains are related spatially and temporally within a watershed, and help assess how anthropogenic drivers and intervention strategies impact the transmission of AMR within human, animal, and environmental systems.

As dozens of new National Immunization Technical Advisory Groups (NITAGs) were established worldwide in the past decade, and as existing NITAGs continued to play an important role in vaccine policy, global NITAG partners recognized a need for a standardized assessment tool to evaluate and strengthen their functions. This article describes the development of the NITAG Maturity Assessment Tool (NMAT), a stepwise evaluation tool that assesses NITAGs on seven key indicators of structure and process. A draft tool was developed through an iterative, consensus-based process with an expert working group before it was piloted with an economically and geographically diverse convenience sample of NITAGs. The final NMAT is a flexible tool that can be used by in-country or external evaluators to understand NITAG maturity, identify priorities for optimization, and measure the impact of strengthening efforts.

In summer 2022, a case of mpox was confirmed in a resident at the Cook County Jail (CCJ) in Chicago, Illinois, USA. We conducted in-depth interviews with CCJ residents and staff to assess mpox knowledge, attitudes, and practices; hygiene and cleaning practices; and risk behaviors. We characterized findings by using health belief model constructs. CCJ residents and staff perceived increased mpox susceptibility but were unsure about infection severity; they were motivated to protect themselves but reported limited mpox knowledge as a barrier and desired clear communication to inform preventive actions. Residents expressed low self-efficacy to protect themselves because of contextual factors, including perceived limited access to cleaning, disinfecting, and hygiene items. Our findings suggest correctional facilities can support disease prevention by providing actionable and tailored messages; educating residents and staff about risk and vaccination options; and ensuring access to and training for hygiene, cleaning, and disinfecting supplies.

During March-April 2023, a total of 51 persons reported mild to severe gastrointestinal illness after eating at restaurant A in Bozeman, Montana. The outbreak resulted in multiple severe outcomes, including three hospitalizations and two deaths. After an inspection and temporary restaurant closure, the Montana Department of Public Health and Human Services and Montana's Gallatin City-County Health Department collaborated with CDC to conduct a matched case-control study among restaurant patrons to help identify the source of the outbreak. Consumption of morel mushrooms, which are generally considered edible, was strongly associated with gastrointestinal illness. A dose-response relationship was identified, and consumption of raw morel mushrooms was more strongly associated with illness than was consumption of those that were at least partially cooked. In response to the outbreak, educational public messaging regarding morel mushroom preparation and safety was shared through multiple media sources. The investigation highlights the importance of prompt cross-agency communication and collaboration, the utility of epidemiologic studies in foodborne disease outbreak investigations, and the need for additional research about the impact of morel mushroom consumption on human health. Although the toxins in morel mushrooms that might cause illness are not fully understood, proper preparation procedures, including thorough cooking, might help to limit adverse health effects.

To end the largest known outbreak of Ebola virus disease (EVD) in West Africa and to prevent new transmissions, rapid epidemiological tracing of cases and contacts was required. The ability to quickly identify unknown sources and chains of transmission is key to ending the EVD epidemic and of even greater importance in the context of recent reports of Ebola virus (EBOV) persistence in survivors. Phylogenetic analysis of complete EBOV genomes can provide important information on the source of any new infection. A local deep sequencing facility was established at the Mateneh Ebola Treatment Centre in central Sierra Leone. The facility included all wetlab and computational resources to rapidly process EBOV diagnostic samples into full genome sequences. We produced 554 EBOV genomes from EVD cases across Sierra Leone. These genomes provided a detailed description of EBOV evolution and facilitated phylogenetic tracking of new EVD cases. Importantly, we show that linked genomic and epidemiological data can not only support contact tracing but also identify unconventional transmission chains involving body fluids, including semen. Rapid EBOV genome sequencing, when linked to epidemiological information and a comprehensive database of virus sequences across the outbreak, provided a powerful tool for public health epidemic control efforts.

BACKGROUND: Outbreaks of rotavirus gastroenteritis in elderly adults are reported infrequently but are often caused by G2P[4] strains. In 2011, outbreaks were reported in 2 Illinois retirement facilities. OBJECTIVE: To implement control measures, determine the extent and severity of illness, and assess risk factors for disease among residents and employees. DESIGN: Cohort studies using surveys and medical chart abstraction. SETTING: Two large retirement facilities in Cook County, Illinois. PATIENTS: Residents and employees at both facilities and community residents with rotavirus disease. MEASUREMENTS: Attack rates, hospitalization rates, and rotavirus genotype. RESULTS: At facility A, 84 of 324 residents (26%) were identified with clinical or laboratory-confirmed rotavirus gastroenteritis (median age, 84 years) and 11 (13%) were hospitalized. The outbreak lasted 7 weeks. At facility B, 90 case patients among 855 residents (11%) were identified (median age, 88 years) and 19 (21%) were hospitalized. The facility B outbreak lasted 9.3 weeks. Ill employees were identified at both locations. In each facility, attack rates seemed to differ by residential setting, with the lowest rates among those in more separated settings or with high baseline level of infection control measures. The causative genotype for both outbreaks was G2P[4]. Some individuals shed virus detected by enzyme immunoassay or genotyping reverse transcription polymerase chain reaction for at least 35 days. G2P[4] was also identified in 17 of 19 (89%) samples from the older adult community but only 15 of 40 (38%) pediatric samples. LIMITATION: Medical or cognitive impairment among residents limited the success of some interviews. CONCLUSION: Rotavirus outbreaks can occur among elderly adults in residential facilities and can result in considerable morbidity. Among older adults, G2P[4] may be of unique importance. Health professionals should consider rotavirus as a cause of acute gastroenteritis in adults. PRIMARY FUNDING SOURCE: None.

Une femme enceinte à 31 semaines d’aménorrhée connaissait une grossesse jusque là sans complication lorsqu’elle a appelé au cabinet de son obstétricien pour une enflure de la jambe qui durait depuis quelques jours. On lui avait conseillé de se lever et de marcher dans la journée, de surélever ses jambes lorsqu’elle s’asseyait et d’appliquer un linge froid sur la jambe enflée. Le lendemain, elle s’est présentée à l’hôpital pour un essoufflement et est décédée peu de temps après des suites d’une embolie pulmonaire. | Après une grossesse sans complication, une femme avait été admise à l’hôpital pour un déclenchement du travail à 36 semaines d’aménorrhée. Après l’accouchement, la mère et le bébé se portaient bien et le personnel infirmier n’avait aucune inquiétude. Trois jours plus tard, la mère est retournée à l’urgence pour une fièvre et est décédée d’un sepsis causé par une infection post-partum à streptocoque du groupe A (foyer d’infection inconnu). | Une adolescente multipare avait subi un avortement spontané avant son décès. Elle avait des antécédents d’abus dans son enfance, de recours aux services de santé mentale pédiatrique et de l’adolescence, de mésusage de substances psychoactives et de violence conjugale. Un diagnostic de trouble affectif bipolaire avait été soulevé sans être confirmé. La patiente avait refusé d’être orientée vers une équipe de santé mentale périnatale avant son suicide. | Ces histoires sont celles de femmes qui sont récemment décédées pendant la grossesse ou la période post-partum au Canada, au Royaume-Uni et aux États-Unis. Ces histoires sont essentiellement la même. Trois pays. Trois systèmes de santé en difficulté. Trois approches de prévention de la mortalité maternelle. Tant de leçons à tirer les uns des autres.

Influenza is a respiratory illness that can result in serious outcomes, particularly among persons who are immunocompromised, aged <5 years or aged >65 years. Traditional influenza surveillance approaches rely upon syndromic surveillance of emergency departments and public health reporting from clinicians and laboratories. Wastewater surveillance infrastructure developed to monitor SARS-CoV-2 is being used for influenza surveillance in the Chicago area. The goal was to evaluate timeliness and correlations between influenza virus detected through wastewater surveillance and traditional influenza surveillance measures to assess utility of wastewater surveillance for influenza at the county level. Specifically, we measured correlations between influenza virus gene copies in wastewater samples and 1) the number of intensive care unit admissions associated with a diagnosis of influenza, 2) the percentage emergency department (ED) visits for influenza-like-illness, and 3) the percentage of ED visits with influenza diagnosis at discharge(2) in Cook County. Influenza concentrations in wastewater were strongly correlated with traditional influenza surveillance measures, particularly for catchment areas serving >100,000 residents. Wastewater indicators lagged traditional influenza surveillance measures by approximately one week when analyzed in cross-correlations. Although wastewater data lagged traditional influenza surveillance measures in this analysis, it can serve as a useful surveillance tool as a complement to syndromic surveillance; it is a form of influenza surveillance that does not rely on healthcare-seeking behavior or reporting by healthcare providers.

A woman’s pregnancy was uneventful until 31 weeks gestation when she called her obstetrician’s office due to a few-day history of swelling in her leg. She was advised to get up and walk around throughout the day, elevate her legs while sitting, and apply a cool cloth to the leg. The next day, she presented to hospital with shortness of breath and died shortly after from a pulmonary embolus. | After an uncomplicated pregnancy, a woman was admitted with the onset of labour at 36 weeks’ gestation. After the birth, the mother and baby were doing well, and there were no nursing concerns. Three days following the birth, the mother returned to the emergency room with a fever and died from sepsis due to postpartum Group A Streptococcus infection (site of infection unknown). | A multiparous teenager had a miscarriage before her death. She had a history of child abuse, involvement with Child and Adolescent Mental Health Services, substance misuse, and domestic violence. A diagnosis of bipolar affective disorder had been raised but not confirmed. A referral to a Perinatal Mental Health Team had been declined prior to her death by suicide.

THIS REPORT UPDATES PREVIOUS CDC GUIDELINES AND RECOMMENDATIONS ON PREFERRED PREVENTION AND TREATMENT REGIMENS REGARDING NATURALLY OCCURRING ANTHRAX. ALSO PROVIDED ARE A WIDE RANGE OF ALTERNATIVE REGIMENS TO FIRST-LINE ANTIMICROBIAL DRUGS FOR USE IF PATIENTS HAVE CONTRAINDICATIONS OR INTOLERANCES OR AFTER A WIDE-AREA AEROSOL RELEASE OF: Bacillus anthracis spores if resources become limited or a multidrug-resistant B. anthracis strain is used (Hendricks KA, Wright ME, Shadomy SV, et al.; Workgroup on Anthrax Clinical Guidelines. Centers for Disease Control and Prevention expert panel meetings on prevention and treatment of anthrax in adults. Emerg Infect Dis 2014;20:e130687; Meaney-Delman D, Rasmussen SA, Beigi RH, et al. Prophylaxis and treatment of anthrax in pregnant women. Obstet Gynecol 2013;122:885-900; Bradley JS, Peacock G, Krug SE, et al. Pediatric anthrax clinical management. Pediatrics 2014;133:e1411-36). Specifically, this report updates antimicrobial drug and antitoxin use for both postexposure prophylaxis (PEP) and treatment from these previous guidelines best practices and is based on systematic reviews of the literature regarding 1) in vitro antimicrobial drug activity against B. anthracis; 2) in vivo antimicrobial drug efficacy for PEP and treatment; 3) in vivo and human antitoxin efficacy for PEP, treatment, or both; and 4) human survival after antimicrobial drug PEP and treatment of localized anthrax, systemic anthrax, and anthrax meningitis. CHANGES FROM PREVIOUS CDC GUIDELINES AND RECOMMENDATIONS INCLUDE AN EXPANDED LIST OF ALTERNATIVE ANTIMICROBIAL DRUGS TO USE WHEN FIRST-LINE ANTIMICROBIAL DRUGS ARE CONTRAINDICATED OR NOT TOLERATED OR AFTER A BIOTERRORISM EVENT WHEN FIRST-LINE ANTIMICROBIAL DRUGS ARE DEPLETED OR INEFFECTIVE AGAINST A GENETICALLY ENGINEERED RESISTANT: B. anthracis strain. In addition, these updated guidelines include new recommendations regarding special considerations for the diagnosis and treatment of anthrax meningitis, including comorbid, social, and clinical predictors of anthrax meningitis. The previously published CDC guidelines and recommendations described potentially beneficial critical care measures and clinical assessment tools and procedures for persons with anthrax, which have not changed and are not addressed in this update. In addition, no changes were made to the Advisory Committee on Immunization Practices recommendations for use of anthrax vaccine (Bower WA, Schiffer J, Atmar RL, et al. Use of anthrax vaccine in the United States: recommendations of the Advisory Committee on Immunization Practices, 2019. MMWR Recomm Rep 2019;68[No. RR-4]:1-14). The updated guidelines in this report can be used by health care providers to prevent and treat anthrax and guide emergency preparedness officials and planners as they develop and update plans for a wide-area aerosol release of B. anthracis.

BACKGROUND: To characterize neurodevelopmental abnormalities in children up to 36 months of age with congenital Zika virus exposure. METHODS: From the U.S. Zika Pregnancy and Infant Registry, a national surveillance system to monitor pregnancies with laboratory evidence of Zika virus infection, pregnancy outcomes and presence of Zika associated birth defects (ZBD) were reported among infants with available information. Neurologic sequelae and developmental delay were reported among children with ≥1 follow-up exam after 14 days of age or with ≥1 visit with development reported, respectively. RESULTS: Among 2248 infants, 10.1% were born preterm, and 10.5% were small-for-gestational age. Overall, 122 (5.4%) had any ZBD; 91.8% of infants had brain abnormalities or microcephaly, 23.0% had eye abnormalities, and 14.8% had both. Of 1881 children ≥1 follow-up exam reported, neurologic sequelae were more common among children with ZBD (44.6%) vs. without ZBD (1.5%). Of children with ≥1 visit with development reported, 46.8% (51/109) of children with ZBD and 7.4% (129/1739) of children without ZBD had confirmed or possible developmental delay. CONCLUSION: Understanding the prevalence of developmental delays and healthcare needs of children with congenital Zika virus exposure can inform health systems and planning to ensure services are available for affected families. IMPACT: We characterize pregnancy and infant outcomes and describe neurodevelopmental abnormalities up to 36 months of age by presence of Zika associated birth defects (ZBD). Neurologic sequelae and developmental delays were common among children with ZBD. Children with ZBD had increased frequency of neurologic sequelae and developmental delay compared to children without ZBD. Longitudinal follow-up of infants with Zika virus exposure in utero is important to characterize neurodevelopmental delay not apparent in early infancy, but logistically challenging in surveillance models.

INTRODUCTION: Malaria, a devastating febrile illness caused by protozoan parasites, sickened 247,000,000 people in 2021 and killed 619,000, mostly children and pregnant women in sub-Saharan Africa. A highly effective vaccine is urgently needed, especially for Plasmodium falciparum (Pf), the deadliest human malaria parasite. AREAS COVERED: Sporozoites (SPZ), the parasite stage transmitted by Anopheles mosquitoes to humans, are the only vaccine immunogen achieving > 90% efficacy against Pf infection. This review describes > 30 clinical trials of PfSPZ vaccines in the U.S.A., Europe, Africa, and Asia, based on first-hand knowledge of the trials and PubMed searches of 'sporozoites,' 'malaria,' and 'vaccines.' EXPERT OPINION: First generation (radiation-attenuated) PfSPZ vaccines are safe, well tolerated, 80-100% efficacious against homologous controlled human malaria infection (CHMI) and provide 18-19 months protection without boosting in Africa. Second generation chemo-attenuated PfSPZ are more potent, 100% efficacious against stringent heterologous (variant strain) CHMI, but require a co-administered drug, raising safety concerns. Third generation, late liver stage-arresting, replication competent (LARC), genetically-attenuated PfSPZ are expected to be both safe and highly efficacious. Overall, PfSPZ vaccines meet safety, tolerability, and efficacy requirements for protecting pregnant women and travelers, with licensure for these populations possible within five years. Protecting children and mass vaccination programs to block transmission and eliminate malaria are long-term objectives.

Antimicrobial resistance (AR) spread is a worldwide health challenge, stemming in large part, from the ability of microbes to share their genetic material through horizontal gene transfer (HGT). Overuse and misuse of antibiotics in clinical settings and in food production have been linked to this increased prevalence and spread of AR. Consequently, public health and consumer concerns have resulted in a remarkable recent reduction in antibiotics used for food animal production. This is driven by the assumption that removing this selective pressure will favor the recovery of antibiotic susceptible taxa and will limit AR sharing through HGT, allowing the currently available antibiotic arsenal to be effective for a longer period. In this study we used broiler chicks raised antibiotic-free and Salmonella enterica serovar Heidelberg (SH), as a model food pathogen, to test this hypothesis. Our results show that neonatal broiler chicks challenged with an antibiotic susceptible SH strain and raised without antibiotics carried susceptible and multidrug resistance SH strains 14 days after challenge. SH infection perturbed the microbiota of broiler chicks and gavaged chicks acquired antibiotic resistant SH at a higher rate. We determined that the acquisition of a plasmid from commensal Escherichia coli population conferred multidrug resistance phenotype to SH recipients and carriage of this plasmid increased the fitness of SH under acidic selection pressure. These results suggest that HGT of AR shaped the evolution of SH and that antibiotic use reduction alone is insufficient to limit antibiotic resistance transfer from commensal bacteria to Salmonella.Importance The reported increase in antibiotic resistant bacteria in humans have resulted in a major shift away from antibiotics use in food animal production. This has been driven by the assumption that removing antibiotics will select for antibiotic susceptible bacterial taxa, and this in turn will allow the currently available antibiotic arsenal to be more effective. This shift in practice has highlighted new questions that need to be answered to assess the effectiveness of antibiotic removal in reducing the spread of antibiotic resistance bacteria. This research demonstrates that antibiotic susceptible Salmonella Heidelberg strains can acquire multidrug resistance from commensal bacteria present in the gut of neonatal broiler chicks, even in the absence of antibiotic selection. We demonstrate that exposure to acidic pH drove the horizontal transfer of antimicrobial resistance plasmids and suggests that simply removing antibiotics from food-animal production might not be sufficient to limit the spread of antimicrobial resistance.Competing Interest StatementThe authors have declared no competing interest.

Host microbiome homeostasis ensures that gut conditions are unfavorable to an invading pathogen such as Salmonella enterica. Consequently, fostering a “balanced” gut microbiome through the administration of microbes that can competitively exclude pathogens has gained a lot of attention and use in human and animal medicine. However, little is known on how competitive exclusion affects the transfer of antibiotic resistance. To shed more light on this question, we challenged neonatal broiler chicks raised on reused broiler chicken litter – a complex environment comprising of decomposing pine shavings, feces, uric acid, feathers, and feed, with Salmonella Heidelberg (S. Heidelberg), a model pathogen. We show that chicks raised on reused litter carried lower abundance of Salmonella and harbored a more uniform and diverse microbiome comprising of bacterial species that are known to provide colonization resistance towards Salmonella compared to chicks raised on fresh bedding composed of pine shavings. Additionally, these bacterial species were associated with a lower horizontal transfer of multidrug resistance genes to S. Heidelberg. Using in vitro competition experiments, we confirmed that conjugation between S. Heidelberg and E. coli strains from chicks raised on fresh litter resulted in the acquisition of multidrug resistant plasmids. Contrastingly, bacteriophage-mediated recombination between S. Heidelberg and E. coli strains made the acquisition of plasmid-mediated β-lactamase gene (blaCMY-2) possible. Collectively, this study demonstrates that competitive exclusion can reduce the transfer of antibiotic resistance and provides information on the bacterial species that can be explored for their benefits to reduce antibiotic resistance transfer.Importance/Significance Antimicrobial resistance spread is a worldwide health challenge, stemming in large part, from the ability of microorganisms to share their genetic material through horizontal gene transfer. To address this issue, many countries and international organization have adopted a one health approach to curtail the proliferation of antibiotic resistant bacteria. This includes the removal and reduction of antibiotics used in food animal production and the development of alternatives to antibiotics. However, there is still a significant knowledge gap in our understanding of how antimicrobial resistance spreads in the absence of antibiotic selection and the role commensal bacteria play in reducing antibiotic resistance transfer. In this study, we demonstrate that commensal bacteria play a key role in reducing the horizontal transfer of antibiotic resistance to Salmonella and provide the identity and characteristics of the bacterial species that performs this function in broiler chickens.

Background Correctional and detention facilities are disproportionately affected by COVID-19 due to shared space, contact between staff and detained persons, and movement within facilities of detained persons, many with pre-existing medical conditions. On March 18, 2020, Cook County Jail, one of the United States’ largest, identified its first suspected case of COVID-19 in a detained person.Methods This analysis includes SARS-CoV-2 cases confirmed by molecular detection among detained persons and Cook County Sheriff’s Office staff. We examined occurrence of symptomatic cases in each building and proportions of asymptomatic detained persons testing positive. We describe timing of interventions including social distancing, mask use, and expanded testing and show outbreak trajectory in the jail versus contemporaneous case counts in Chicago.Results During March 1–April 30, 907 symptomatic and asymptomatic cases of SARS-CoV-2 infection were detected among detained persons (n = 628) and staff (n = 279), with nine deaths. Symptomatic cases occurred in all housing divisions; in 9/13 buildings, staff cases occurred first. Among asymptomatic detained persons in quarantine, 23.6% tested positive. Visitation stopped March 15, programmatic activities were suspended March 23, cells were converted into single occupancy beginning March 26, and universal masking was implemented for staff (April 2) and detained persons (April 13). Cases at the jail declined while cases in Chicago increased.Conclusion Aggressive intervention strategies coupled with widespread diagnostic testing of detained and staff populations can limit introduction and mitigate transmission of SARS-CoV-2 infection in correctional and detention facilities.Competing Interest StatementThe authors have declared no competing interest.Funding StatementNo external funding was received for the execution of this study or manuscript preparation.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:This study was reviewed by Centers for Disease Control and Prevention, Chicago Department of Public Health, Cook County Health, and Cook County Sheriff's Office institutional review boards or the equivalent entity and deemed not to be research involving human subjects and public health response.All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesData were provided by the Cook County Sheriff's Office, Chicago Department of Public Health, Cermak Health Services, and Cook County Health. Access to data submitted into the Illinois' National Electronic Disease Surveillance System was provided by Chicago Department of Public Health. Data represent protected health information (PHI), and cannot be made available in raw form. Results are presented in aggregate in this manuscript. Authors had access to data.

Parasitic nematodes (roundworms) and platyhelminths (flatworms) cause debilitating chronic infections of humans and animals, decimate crop production and are a major impediment to socioeconomic development. Here we compare the genomes of 81 nematode and platyhelminth species, including those of 76 parasites. From 1.4 million genes, we identify gene family births and hundreds of large expanded gene families at key nodes in the phylogeny that are relevant to parasitism. Examples include gene families that modulate host immune responses, enable parasite migration though host tissues or allow the parasite to feed. We use a wide-ranging in silico screen to identify and prioritise new potential drug targets and compounds for testing. We also uncover lineage-specific differences in core metabolism and in protein families historically targeted for drug development. This is the broadest comparative study to date of the genomes of parasitic and non-parasitic worms. It provides a transformative new resource for the research community to understand and combat the diseases that parasitic worms cause.

BackgroundPublic health guidance recommending isolation of individuals with group A streptococcal (GAS) infection or carriage for 12-24 h from antibiotic initiation to prevent onward transmission requires a strong evidence base.AimTo estimate the pooled proportion of individuals who remain GAS culture-positive at set intervals after initiation of antibiotics through a systematic literature review (PROSPERO CRD42021290364) and meta-analysis.MethodsWe searched Ovid MEDLINE (1946-), EMBASE (1974-) and Cochrane library. We included interventional or observational studies with ≥ 10 participants reporting rates of GAS throat culture positivity during antibiotic treatment for culture-confirmed GAS pharyngitis, scarlet fever and asymptomatic pharyngeal GAS carriage. We did not apply age, language or geographical restrictions.ResultsOf 5,058 unique records, 43 were included (37 randomised controlled studies, three non-randomised controlled trials and three before-and-after studies). The proportion of individuals remaining culture-positive on day 1, day 2 and days 3-9 were 6.9% (95% CI: 2.7-16.8%), 5.4% (95% CI: 2.1-13.3%) and 2.6% (95% CI: 1.6-4.2%). For penicillins and cephalosporins, day 1 positivity was 6.5% (95% CI: 2.5-16.1%) and 1.6% (95% CI: 0.04-42.9%), respectively. Overall, for 9.1% (95% CI: 7.3-11.3), throat swabs collected after completion of therapy were GAS culture-positive. Only six studies had low risk of bias.ConclusionsOur review provides evidence that antibiotics for pharyngeal GAS achieve a high rate of culture conversion within 24 h but highlights the need for further research given methodological limitations of published studies and imprecision of pooled estimates. Further evidence is needed for non-beta-lactam antibiotics and asymptomatic individuals.

Background: Public health guidance recommending isolation of individuals with group A streptococcal (GAS) infection or carriage for 12-24 hours from antibiotic initiation to prevent onward transmission requires a strong evidence-base. Method(s): We conducted a systematic review (PROSPERO CRD42021290364) and meta-analysis to estimate the pooled proportion of individuals who remain GAS culture-positive at set intervals after initiation of antibiotics. We searched Ovid MEDLINE (1946-), EMBASE (1974-) and the Cochrane library. We included interventional or observational studies with ten or more participants reporting rates of GAS throat culture during antibiotics for culture confirmed GAS pharyngitis, scarlet fever, and asymptomatic pharyngeal GAS carriage. We did not apply age, language, or geographical restrictions. Finding(s): Of 5,058 unique records identified, 43 were included; 37 (86%) randomised controlled studies, three (7%) non-randomised controlled trials and three (7%) before-and-after studies. The proportion of individuals who remained culture-positive at day 1, day 2, and day 3-9 were 6.9% (95% CI 2.7-16.8%), 5.4% (95% CI 2.1-13.3%) and 2.6% (95% CI 1.6-4.2%). For penicillins and cephalosporins, day 1 positivity was 6.5% (95% CI 2.5-16.1%) and 1.6% (95% CI 0.04-42.9%) respectively. Overall, for 9.1% (95% CI 7.3-11.3), throat swabs collected after completion of therapy were GAS culture-positive. Interpretation(s): Our review provides evidence that antibiotics for pharyngeal GAS achieve a high rate of culture conversion within 24 hours but highlights the need for further research given the methodological limitations of published studies and imprecision of pooled estimates. Further evidence is needed for non-beta-lactam antibiotics and for asymptomatic individuals. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.

Recombination between SARS-CoV-2 virus variants can result in different viral properties (e.g., infectiousness or pathogenicity). In this report, we describe viruses with recombinant genomes containing signature mutations from Delta and Omicron variants. These genomes are the first evidence for a Delta-Omicron hybrid Spike protein in the United States. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license.

The emergence and spread of SARS-CoV-2 lineage B.1.1.7, first detected in the United Kingdom, has become a global public health concern because of its increased transmissibility. Over 2500 COVID-19 cases associated with this variant have been detected in the US since December 2020, but the extent of establishment is relatively unknown. Using travel, genomic, and diagnostic data, we highlight the primary ports of entry for B.1.1.7 in the US and locations of possible underreporting of B.1.1.7 cases. Furthermore, we found evidence for many independent B.1.1.7 establishments starting in early December 2020, followed by interstate spread by the end of the month. Finally, we project that B.1.1.7 will be the dominant lineage in many states by mid to late March. Thus, genomic surveillance for B.1.1.7 and other variants urgently needs to be enhanced to better inform the public health response.

Wearing a facemask can help to decrease the transmission of COVID-19. We investigated self-reported mask use among subjects aged 18 years and older participating in the COVID-19 Community Research Partnership (CRP), a prospective longitudinal COVID-19 surveillance study in the mid-Atlantic and southeastern United States. We included those participants who completed >=5 daily surveys each month from December 1, 2020 through August 31, 2021. Mask use was defined as self-reported use of a face mask or face covering on every interaction with others outside the household within a distance of less than 6 feet. Participants were considered vaccinated if they reported receiving >=1 COVID-19 vaccine dose. Participants (n=17,522) were 91% non-Hispanic White, 68% female, median age 57 years, 26% healthcare workers, with 95% self-reported receiving >=1 COVID-19 vaccine dose through August; mean daily survey response was 85%. Mask use was higher among vaccinated than unvaccinated participants across the study period, regardless of the month of the first dose. Mask use remained relatively stable from December 2020 through April (range 71-80% unvaccinated; 86-93% vaccinated) and declined in both groups beginning in mid-May 2021 to 34% and 42% respectively in June 2021; mask use has increased again since July 2021. Mask use by all was lower during weekends and on Christmas and Easter, regardless of vaccination status. Independent predictors of higher mask use were vaccination, age >=65 years, female sex, racial or ethnic minority group, and healthcare worker occupation, whereas a history of self-reported prior COVID-19 illness was associated with lower use. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license.

The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in the emergence of many new variant lineages that have exacerbated the COVID-19 pandemic. Some of those variants were designated as variants of concern/interest (VOC/VOI) by national or international authorities based on many factors including their potential impact on vaccines. To ascertain and rank the risk of VOCs and VOIs, we analyzed their ability to escape from vaccine-induced antibodies. The variants showed differential reductions in neutralization and replication titers by post-vaccination sera. Although the Omicron variant showed the most escape from neutralization, sera collected after a third dose of vaccine (booster sera) retained moderate neutralizing activity against that variant. Therefore, vaccination remains the most effective strategy to combat the COVID-19 pandemic.

The Costa Rican pygmy rice rat (Oligoryzomys costaricensis) is the primary reservoir of Choclo orthohantavirus (CHOV), the causal agent of hantavirus disease, pulmonary syndrome, and fever in humans in Panama. Since the emergence of CHOV in early 2000, we have systematically sampled and archived rodents from >150 sites across Panama to establish a baseline understanding of the host and virus, producing a permanent archive of holistic specimens that we are now probing in greater detail. We summarize these collections and explore preliminary habitat/virus associations to guide future wildlife surveillance and public health efforts related to CHOV and other zoonotic pathogens. Host sequences of the mitochondrial cytochrome b gene form a single monophyletic clade in Panama, despite wide distribution across Panama. Seropositive samples were concentrated in the central region of western Panama, consistent with the ecology of this agricultural commensal and the higher incidence of CHOV in humans in that region. Hantavirus seroprevalence in the pygmy rice rat was >15% overall, with the highest prevalence in agricultural areas (21%) and the lowest prevalence in shrublands (11%). Host-pathogen distribution, transmission dynamics, genomic evolution, and habitat affinities can be derived from the preserved samples, which include frozen tissues, and now provide a foundation for expanded investigations of orthohantaviruses in Panama.

CDC has used national genomic surveillance since December 2020 to monitor SARS-CoV-2 variants that have emerged throughout the COVID-19 pandemic, including the Omicron variant. This report summarizes U.S. trends in variant proportions from national genomic surveillance during January 2022-May 2023. During this period, the Omicron variant remained predominant, with various descendant lineages reaching national predominance (>50% prevalence). During the first half of 2022, BA.1.1 reached predominance by the week ending January 8, 2022, followed by BA.2 (March 26), BA.2.12.1 (May 14), and BA.5 (July 2); the predominance of each variant coincided with surges in COVID-19 cases. The latter half of 2022 was characterized by the circulation of sublineages of BA.2, BA.4, and BA.5 (e.g., BQ.1 and BQ.1.1), some of which independently acquired similar spike protein substitutions associated with immune evasion. By the end of January 2023, XBB.1.5 became predominant. As of May 13, 2023, the most common circulating lineages were XBB.1.5 (61.5%), XBB.1.9.1 (10.0%), and XBB.1.16 (9.4%); XBB.1.16 and XBB.1.16.1 (2.4%), containing the K478R substitution, and XBB.2.3 (3.2%), containing the P521S substitution, had the fastest doubling times at that point. Analytic methods for estimating variant proportions have been updated as the availability of sequencing specimens has declined. The continued evolution of Omicron lineages highlights the importance of genomic surveillance to monitor emerging variants and help guide vaccine development and use of therapeutics.