OBJECTIVES: After respiratory syncytial virus (RSV), human metapneumovirus (hMPV) was the second-ranked pathogen attributed to severe pneumonia in the PERCH study. We sought to characterize hMPV-positive cases in high-burden settings, which have limited data, by comparing with RSV-positive and other cases. METHODS: Children aged 1-59 months hospitalized with suspected severe pneumonia and age/season-matched community controls in seven African and Asian countries had nasopharyngeal/oropharyngeal swabs tested by multiplex PCR for 32 respiratory pathogens, among other clinical and lab assessments at admission. Odds ratios adjusted for age and site (adjusted OR [aOR]) were calculated using logistic regression. Aetiologic probability was estimated using Bayesian nested partial latent class analysis. Latent class analysis identified syndromic constellations of clinical characteristics. RESULTS: hMPV was detected more frequently among cases (267/3887, 6.9%) than controls (115/4976, 2.3%), among cases with pneumonia chest X-ray findings (8.5%) than without (5.5%), and among controls with respiratory tract illness (3.8%) than without (1.8%; all p ≤ 0.001). HMPV-positive cases were negatively associated with the detection of other viruses (aOR, 0.18), especially RSV (aOR, 0.11; all p < 0.0001), and positively associated with the detection of bacteria (aORs, 1.77; p 0.03). No single clinical syndrome distinguished hMPV-positive from other cases. Among hMPV-positive cases, 65.2% were aged <1 year and 27.5% had pneumonia danger signs; positive predictive value for hMPV aetiology was 74.5%; mortality was 3.9%, similar to RSV-positive (2.4%) and lower than that among other cases (9.6%). DISCUSSION: HMPV-associated severe paediatric pneumonia in high-burden settings was predominantly in young infants and clinically indistinguishable from RSV. HMPV-positives had low case fatality, similar to that in RSV-positives.

BACKGROUND: We estimate annual viral influenza-associated mild-to-moderate illness, hospitalizations, and deaths in 6 South American countries (Argentina, Brazil, Chile, Ecuador, Paraguay, and Uruguay) during the 2015-2019 influenza seasons as a first step in evaluating the full value of influenza vaccination in the subregion. METHODS: We applied a multiplier method using monthly hospital discharge and vital statistics death records, influenza surveillance data, and population projections to estimate mild-to-moderate influenza-associated illness, hospitalizations, and deaths. We estimated the uncertainty bounds based on the 2.5th and 97.5th percentiles of the Monte Carlo simulated distributions for the number of cases and obtained the ranges from the minimum value of the 2.5th and the maximum value of the 97.5th percentile. RESULTS: In selected countries with a total population of 307 million people, the yearly influenza-associated burden of disease ranged between 51 and 78 million mild-to-moderate influenza illnesses, between 323 379 and 490 049 hospitalizations, and between 22 662 and 46 971 deaths during the 2015-2019 influenza seasons. CONCLUSIONS: Each year, influenza is associated with millions of illnesses, hundreds of thousands of hospitalizations, and tens of thousands of deaths in 6 South American countries, affecting a significant portion of the population. Such findings can be used to estimate the number of illnesses averted through vaccination programs and the cost-benefit of influenza vaccines.

BACKGROUND: To demonstrate the application and utility of geostatistical modelling to provide comprehensive high-resolution understanding of the population's protective immunity during a pandemic and identify pockets with sub-optimal protection. METHODS: Using data from a national cross-sectional household survey of 6620 individuals in the Dominican Republic (DR) from June to October 2021, we developed and applied geostatistical regression models to estimate and predict Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) spike (anti-S) antibodies (Ab) seroprevalence at high resolution (1 km) across heterogeneous areas. RESULTS: Spatial patterns in population immunity to SARS-CoV-2 varied across the DR. In urban areas, a one-unit increase in the number of primary healthcare units per population and 1% increase in the proportion of the population aged under 20 years were associated with higher odds ratios of being anti-S Ab positive of 1.38 (95% confidence interval [CI]: 1.35-1.39) and 1.35 (95% CI: 1.32-1.33), respectively. In rural areas, higher odds of anti-S Ab positivity, 1.45 (95% CI: 1.39-1.51), were observed with increasing temperature in the hottest month (per°C), and 1.51 (95% CI: 1.43-1.60) with increasing precipitation in the wettest month (per mm). CONCLUSIONS: A geostatistical model that integrates contextually important socioeconomic and environmental factors can be used to create robust and reliable predictive maps of immune protection during a pandemic at high spatial resolution and will assist in the identification of highly vulnerable areas.

BACKGROUND: The prevalence and risk factors for ongoing symptoms following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [SCV2]) or influenza infection are not well characterized. We conducted a prospective cohort study of households wherein ≥1 individual was infected with SCV2 or influenza to evaluate prevalence of and factors associated with ongoing symptoms at 90 days. METHODS: Index cases and their household contacts provided baseline health and sociodemographic information and collected daily respiratory specimens for 10 days following enrollment. Participants completed a follow-up survey 90 days after enrollment to characterize ongoing symptoms. RESULTS: We analyzed 1967 participants enrolled between December 2021 and May 2023. The risk of ongoing symptoms did not differ by infection status in SCV2 (SCV2-positive: 15.6%; SCV2-negative: 13.9%; odds ratio [OR]: 1.14; 95% CI: .7-1.69) or influenza (influenza-positive: 8.8%; influenza-negative: 10.0%; OR: .87; 95% CI: .45-1.72) households. However, among study participants with a documented infection, SCV2-positive participants had nearly twice the odds of ongoing symptoms as influenza-positive participants (OR: 1.92; 95% CI: 1.27-2.97). CONCLUSIONS: These results suggest that SCV2 households have a significantly higher prevalence of ongoing symptoms compared with influenza households (OR: 1.78; 95% CI: 1.28-2.47). Among participants with SCV2 infection, underlying conditions (adjusted OR [aOR]: 2.65; 95% CI: 1.80-3.90) and coronavirus disease 2019 (COVID-19)-like symptoms (aOR: 2.92; 95% CI: 1.15-7.43) during acute infection increased odds of ongoing symptoms at 90 days, whereas hybrid immunity reduced the odds of ongoing symptoms (aOR: 0.44; 95% CI: .22-.90).

Young People Living with HIV (YPLHIV, 15-24 years) are an important demographic of Persons Living with HIV (PLHIV) globally and in Southern Africa. However, YPLHIV experience poor outcomes across the HIV diagnostic and treatment cascade due to multiple factors. We estimated the prevalence and determinants of HIV viral suppression in YPLHIV on antiretroviral therapy (ART) in selected Southern African countries. We used publicly available data from Malawi, Zimbabwe, Mozambique, Lesotho, and Eswatini collected during the Population-based HIV Impact Assessments (PHIAs) of 2020 to 2021. Weighted proportions, and 95% confidence intervals (CI) were computed to estimate the prevalence of viral suppression (< 1000c/ml) and bivariate and multivariate analyses were conducted to identify determinants of viral suppression. A total of 855 records of YPLHIV on ART were included in the analysis. The prevalence of viral suppression in YPLHIV on ART was 82.4% (95% CI: 76.7, 86.9). Residing in Mozambique and duration on ART were inversely associated with viral suppression; adjusted odds ratios (AORs) of 0.37 (95% CI: 0.14, 0.95), and 0.87 (95% CI: 0.80, 0.94), respectively. A negative result in the depression screen, being married/cohabitating, and ever switching an ART regimen were positively associated with viral suppression: AORs of 5.78 (95% CI: 2.21, 15.11), 3.72 (95% CI: 1.44, 9.63), and 3.44 (95% CI: 1.69, 7), respectively. YPLHIV had suboptimal viral suppression lower than the UNAIDS 95% targets and may benefit from further research and tailored interventions addressing modifiable factors associated with viral suppression such as depression.

The coronavirus disease 2019 (COVID-19) pandemic exposed critical limitations in the availability of timely mortality data to inform situational assessments and guide evidence-based public health responses at local, national and global levels. Less than half of the Member States of the World Health Organization (WHO) (73 out of 194) generated the required mortality data. Member States able to meet the sudden demand for real-time data did so through strong public health leadership and strategies for coordinated data acquisition, analysis and dissemination. In most other countries, attempts were made to conduct mortality surveillance but yielded only partial data with limited utility. This experience highlighted the need for a series of strategic shifts to strengthen mortality surveillance programmes in all countries, towards complete recording of deaths and their causes with timely data dissemination. These shifts include modifying systems to enable streamlining of the compilation and use of death records from all sources while meeting the requirements of official registration processes; using electronic protocols for data management and release; and ensuring effective leadership, coordination and data use for public health action. Recently, the Africa Centres for Disease Control and Prevention developed a conceptual framework for strengthening national mortality surveillance and operational guidance for implementation. These activities and resources for improving national mortality surveillance can inform global initiatives to support pandemic preparedness and response programmes. Such initiatives will enable global readiness for early epidemic detection and disease control measure prioritization, while also building routine mortality statistics programmes for population health assessment, health policy and research.

A World Health Organization (WHO) Defeating Meningitis Symposium took place as part of the 3rd International Symposium on Streptococcus agalactiae disease (ISSAD) conference which was held in Rio de Janeiro, Brazil, from October 16-18, 2023. The symposium highlighted WHO's Defeating meningitis by 2030 global road map focusing on Group B Streptococcus (GBS) meningitis and provided an overview of the meningitis burden and main challenges faced to tackle the disease across the Americas, Africa, and Asia.

Candida species are the predominant cause of fungal infections in patients treated in hospital, contributing substantially to morbidity and mortality. Candidaemia and other forms of invasive candidiasis primarily affect patients who are immunocompromised or critically ill. In contrast, mucocutaneous forms of candidiasis, such as oral thrush and vulvovaginal candidiasis, can occur in otherwise healthy individuals. Although mucocutaneous candidiasis is generally not life-threatening, it can cause considerable discomfort, recurrent infections, and complications, particularly in patients with underlying conditions such as diabetes or in those taking immunosuppressive therapies. The rise of difficult-to-treat Candida infections is driven by new host factors and antifungal resistance. Pathogens, such as Candida auris (Candidozyma auris) and fluconazole-resistant Candida parapsilosis, pose serious global health risks. Recent taxonomic revisions have reclassified several Candida spp, potentially causing confusion in clinical practice. Current management guidelines are limited in scope, with poor coverage of emerging pathogens and new treatment options. In this Review, we provide updated recommendations for managing Candida infections, with detailed evidence summaries available in the appendix.

Background: Annual estimates of seasonal influenza vaccine effectiveness can guide global risk communication and vaccination strategies to mitigate influenza-associated illness. We aimed to evaluate vaccine effectiveness in countries using the 2023 southern hemisphere influenza vaccine formulation.

BACKGROUND: Pneumococcal conjugate vaccines (PCVs) introduced in childhood national immunization programs lowered vaccine-type invasive pneumococcal disease (IPD), but replacement with non-vaccine-types persisted throughout the PCV10/13 follow-up period. We assessed PCV10/13 impact on pneumococcal meningitis incidence globally. METHODS: The number of cases with serotyped pneumococci detected in cerebrospinal fluid and population denominators were obtained from surveillance sites globally. Site-specific meningitis incidence rate ratios (IRRs) comparing pre-PCV incidence to each year post-PCV10/13 were estimated by age (<5, 5-17 and ≥18 years) using Bayesian multi-level mixed effects Poisson regression, accounting for pre-PCV trends. All-site weighted average IRRs were estimated using linear mixed-effects regression stratified by age, product (PCV10 or PCV13) and prior PCV7 impact (none, moderate, or substantial). Changes in pneumococcal meningitis incidence were estimated overall and for product-specific vaccine-types and non-PCV13-types. RESULTS: Analyses included 10,168 cases <5 y from PCV13 sites and 2849 from PCV10 sites, 3711 and 1549 for 5-17 y and 29,187 and 5653 for ≥18 y from 42 surveillance sites (30 PCV13, 12 PCV10, 2 PCV10/13) in 30 countries, primarily high-income (84%). Six years after PCV10/PCV13 introduction, pneumococcal meningitis declined 48-74% across products and PCV7 impact strata for children <5 y, 35-62% for 5-17 y and 0-36% for ≥18 y. Impact against PCV10-types at PCV10 sites, and PCV13-types at PCV13 sites was high for all age groups (<5 y: 96-100%; 5-17 y: 77-85%; ≥18 y: 73-85%). After switching from PCV7 to PCV10/13, increases in non-PCV13-types were generally low to none for all age groups. CONCLUSION: Pneumococcal meningitis declined in all age groups following PCV10/PCV13 introduction. Plateaus in non-PCV13-type meningitis suggest less replacement than for all IPD. Data from meningitis belt and high-burden settings were limited.

Influenza viruses can be aerosolized when slaughtering infected chickens, which increases the risk of zoonotic transmission. We conducted pilot experiments to measure the concentrations of airborne particles <2.5 µm during slaughtering and defeathering of chickens to help identify methods that can minimize workers’ exposure to potentially hazardous aerosol particles. By using two types of airborne particle monitors stationed at different heights and angles in a controlled environment, we measured aerosolized particulate matters during exsanguination of 10 slaughtered chickens and use of a mechanical device for defeathering 10 chickens. For the slaughtering experiments, the median particle concentrations at 148 cm height were 67 µg/m3 (IQR 44–121) with a baseline count 10 µg/m3 (IQR 10–10) for the Particle and Temperature Sensor + (PATS+) monitors and 34 µg/m3 (IQR 34–64) with a baseline count 25 µg/m3 (IQR 16–44) for the SidePak™ monitor. For the defeathering experiments, the median particle concentrations recorded by the PATS+ monitors were not significantly different between 148 cm (41 µg/m3, IQR 29–49; baseline 12 µg/m3, IQR 10–19) and 107 cm height (37 µg/m3, IQR 29–44; baseline 13 µg/m3, IQR 10–22). Our protocol can be used to test the generation of airborne particles that are <2.5 µm during different slaughtering and defeathering techniques used in the live bird markets to identify procedures that produce the lowest concentrations of small aerosol particles. © 2025

Mosquito control using pyrethrins and synthetic pyrethroids (PSP) is important for preventing vector-borne diseases. Although the benefits associated with PSP use are well-documented, public concern exists regarding potential human adverse health effects. The aim of this scoping review was to describe adverse human health effects associated with PSP use for community adult mosquito control. A literature search using the databases MEDLINE, EMBASE, Agricultural and Environmental Science Collection, CAB Abstracts, and Scopus obtained 6,154 original peer-reviewed articles published during 1 January 2000 to 22 May 2024. Articles were independently reviewed for inclusion using predetermined exclusion and inclusion criteria. Data were extracted from 10 included articles. Study designs included cohort (n = 5), cross-sectional (n = 2), and risk assessment (n = 4). One article included 2 study designs. Of the cohort studies, one was prospective and the remainder were retrospective. A causal relationship between PSP application for adult mosquito control and adverse human health impacts was not identified. No increases in acute health manifestations were reported. The 4 risk assessments estimated that PSP exposures were not above the regulatory level of concern; a meta-analysis determined the likelihood of PSP exposures exceeding the regulatory level of concern was <0.0001. The limited evidence indicated that PSP applied appropriately for control of nuisance mosquitoes or mosquitoes that transmit arboviruses do not pose acute or chronic human health risks. Continued investigation into potential human health impacts of PSP would help inform guidelines for adult mosquito control and help inform public health decision making.

SUMMARYStreptococcus pneumoniae (the "pneumococcus") is a significant human pathogen. The key determinant of pneumococcal fitness and virulence is its ability to produce a protective polysaccharide (PS) capsule, and anti-capsule antibodies mediate serotype-specific opsonophagocytic killing of bacteria. Notably, immunization with pneumococcal conjugate vaccines (PCVs) has effectively reduced the burden of disease caused by serotypes included in vaccines but has also spurred a relative upsurge in the prevalence of non-vaccine serotypes. Recent advancements in serotyping and bioinformatics surveillance tools coupled with high-resolution analytical techniques have enabled the discovery of numerous new capsule types, thereby providing a fresh perspective on the dynamic pneumococcal landscape. This review offers insights into the current pneumococcal seroepidemiology highlighting important serotype shifts in different global regions in the PCV era. It also comprehensively summarizes newly discovered serotypes from 2007 to 2024, alongside updates on revised chemical structures and the de-novo determinations of structures for previously known serotypes. Furthermore, we spotlight emerging evidence on non-pneumococcal Mitis-group strains that express capsular PS that are serologically and biochemically related to the pneumococcal capsule types. We further discuss the implications of these recent findings on capsule nomenclature, pneumococcal carriage detection, and future PCV design. The review maps out the current status and also outlines the course for future research and vaccine strategies, ensuring a continued effective response to the evolving pneumococcal challenge.

Rapid and accurate diagnostics are needed to effectively detect and treat primary amoebic meningoencephalitis (PAM) caused by Naegleria fowleri (Nf). Delayed diagnosis and similarities to other causes of meningitis contribute to a case mortality rate of >97%. Thus, there is an unmet medical need for a non-invasive liquid biopsy diagnostic method. We sequenced Nf extracellular vesicles (EVs) and identified microRNAs, tRNAs and other small RNAs in Nf-EVs. From these data we selected two prevalent small RNAs as biomarker candidates. We developed an RT-qPCR assay and both small RNAs were detected in Nf-EVs and amoeba-conditioned media. In the mouse model of PAM both small RNA biomarkers were detected in 100% of mouse plasma samples at the end-stage of infection. Notably, smallRNA-1 was detected in the urine of infected mice at timepoints as early as 24h post infection (18/23 mice) and in the plasma as early as 60h post infection (8/8 mice). Additionally, smallRNA-1 was detected in 100% (n=6) of CSF samples from human PAM cases, and in whole blood samples, but not in human plasma from PAM cases. In this study, we discovered small RNAs as biomarkers of Nf infection, one which can be detected reliably in CSF, urine, and whole blood. The RT-qPCR assay is a highly sensitive diagnostic assay that can be conducted in ~3h after receipt of liquid biopsy. The data suggest detection of smallRNA-1 biomarker could provide earlier diagnosis of PAM and be used to monitor biomass of amoebae during treatment.

Background: On the basis of recent clinical trial data for the treatment of drug-susceptible and drug-resistant tuberculosis (TB), the American Thoracic Society, U.S. Centers for Disease Control and Prevention, European Respiratory Society, and Infectious Diseases Society of America have updated clinical practice guidelines for TB treatment in children and adults in settings in which mycobacterial cultures, molecular and phenotypic drug susceptibility tests, and radiographic studies, among other diagnostic tools, are available on a routine basis. Methods: A Joint Panel representing multiple interdisciplinary perspectives convened with American Thoracic Society methodologists to review evidence and make recommendations using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) and GRADE-ADOLOPMENT (adoption, adaptation, and, as needed, de novo development of recommendations) methodology. Results: New drug-susceptible TB recommendations include the use of a novel 4-month regimen for people with pulmonary TB and a shortened 4-month regimen for children with nonsevere TB. Drug-resistant TB recommendation updates include the use of novel regimens containing bedaquiline, pretomanid, and linezolid with or without moxifloxacin. Conclusions: All-oral, shorter treatment regimens for TB are now recommended for use in eligible individuals. Copyright © 2025 by the American Thoracic Society.

INTRODUCTION: Most drug-resistant tuberculosis (DR-TB) occurs due to transmission of unsuspected or ineffectively treated DR-TB. The duration of treatment to stop person-to-person spread of DR-TB is uncertain. We evaluated the impact of novel regimens, including BPaL, on DR-TB transmission using the human-to-guinea pig (H-GP) transmission model. METHODS: In Experiment 1, patients initiated an optimized DR-TB regimen including bedaquiline (BDQ) and linezolid (LZD). In Experiment 2, patients initiated the BPaL regimen (BDQ, 1200mg LZD and pretomanid). We measured baseline infectivity for each cohort by exhausting ward air to one of two GP exposure rooms (Control), each containing 90 GPs, for 8 patient-days. Then, after 72 hours of treatment, ward air was exhausted to the second GP exposure room for 8 patient-days (Intervention). The infectiousness of each cohort was compared by performing tuberculin skin tests (TST) in GPs at baseline (pre-treatment) and 6 weeks after the exposure period. RESULTS: In Experiment 1, pre-treatment, five DR-TB patients infected 24/90 (26.7%) GPs (Control). Post-treatment (72 hours after drug initiation), the same patients infected 25/90 (27.8%) GPs (Intervention) (p = 1.00). In Experiment 2, pre-treatment, nine DR-TB patients infected 40/90 (44.4%) GPs (Control). Post-treatment (beginning 72 hours after drug initiation), the same patients infected 0/90 (0%) GPs (Intervention) (p < 0.0001). CONCLUSIONS: In this study, DR-TB drug regimens including BDQ and standard-dose LZD for 72 hours did not decrease DR-TB transmission. In contrast, transmission was rapidly and completely inhibited in patients treated with BPaL for 72 hours, suggesting an early and profound impact on transmission.

Due to its natural influenza susceptibility, clinical signs, transmission, and similar sialic acid residue distribution, the ferret is the primary animal model for human influenza research. Antibodies generated following infection of ferrets with human influenza viruses are used in surveillance to detect antigenic drift and cross-reactivity with vaccine viruses and circulating strains. Inoculation of ferrets, with over 1,500 human clinical influenza isolates (1998-2019) resulted in lower antibody responses (HI <1:160) to 86% (387 out of 448) influenza B viruses (IBVs) compared to 2.7% (30 out of 1,094) influenza A viruses (IAVs). Here, we show that the immune responses in ferrets inoculated with IBV were delayed and reduced compared to IAV. Innate gene expression in the upper respiratory tract and blood indicated that IAV generated a strong inflammatory response, including an early activation of the interferon (IFN), whereas IBV elicited a delayed and reduced response. Serum levels of cytokines and IFNs were all much higher following IAV infection than IBV infection. Pro-inflammatory, IFN, TH1/TH2, and T-effector proteins were significantly higher in sera of IAV-infected than IBV-infected ferrets over 28 days following the challenge. Serum levels of Type-I/II/III IFNs were detected following IAV infection throughout this period, whereas Type-III IFN was only late for IBV. An early increase in IFN-lambda corresponded to gene expression following IAV infection. Reduced innate immune responses following IBV infection reflected the subsequent delayed and reduced serum antibodies. These findings may help in understanding the antibody responses in humans following influenza vaccination or infection and consideration of potential addition of innate immunomodulators to overcome low responses. IMPORTANCE: The ferret is the primary animal model for human influenza research. Using a ferret model, we studied the differences in both innate and adaptive immune responses following infection with influenza A and B viruses (IAV and IBV). Antibodies generated following infection of ferrets is used for surveillance assays to detect antigenic drift and cross-reactivity with vaccine viruses and circulating influenza strains. IAV infection of ferrets to generate these reagents resulted in a strong antibody response, but IBV infection generated weak antibody responses. In this study using influenza-infected ferrets, we found that IAV resulted in an early activation of the interferon (IFN) and pro-inflammatory response, whereas IBV showed a delay and reduction in these responses. Serum levels of IFNs and other cytokines or chemokines were much higher in ferrets following IAV infection. These reduced innate responses were reflected the subsequent delayed and reduced antibody responses to IBV in the sera. These findings may help in understanding low antibody responses in humans following influenza B vaccination and infection and may warrant the use of innate immunomodulators to overcome these weak responses.

BACKGROUND: Prenatally transmitted viruses can cause severe damage to the developing brain. There is unexplained variability in prenatal brain injury and postnatal neurodevelopmental outcomes, suggesting disease modifiers. Of note, prenatal Zika infection can cause a spectrum of neurodevelopmental disorders, including congenital Zika syndrome. Currently, there is no preventative treatment or cure. The Prenatal Infection and Neurodevelopmental Genetics (PING) Consortium aims to identify modulators of brain injury and adverse neurodevelopmental outcomes for Zika and other prenatal viral infections. METHODS: The Consortium pools information from eight multi-site studies conducted at 23 research centers in six countries to build a growing clinical and genomic repository, which is being mined for modifiers of virally induced brain injury. Partners include Children's National Hospital (USA), Instituto Nacional de Salud (Colombia), the Natural History of Zika Virus Infection in Gestation program (Brazil), Zika Instituto Fernandes Figueira (Brazil), the Centers for Disease Control and Prevention, and the National Institutes of Health. RESULTS: We have enrolled 4102 mothers and 3877 infants with 3063 biological samples and clinical data covering over 80 phenotypic fields and 5000 variables. Thus far, we have performed whole exome sequencing on 1226 participants. CONCLUSION: Here, we present the Consortium's formation and overarching study design. IMPACT: The PING Consortium brings together investigators and institutions to determine the causes of virally induced brain injury and neurological deficits. The clinical and genomic repository, with data from over 8000 patients, will serve as a foundation for a variety of basic and clinical studies.

Violence against nurses and other healthcare workers is a significant and escalating concern, impeding the provision of safe and effective healthcare services. A majority of nurses experience some kind of violence, including physical and nonphysical assaults during their careers. The consequences of workplace violence extend beyond individual trauma, leading to increased burnout, turnover, and significant financial costs for healthcare systems. Training programs focused on workplace violence prevention (WVP) have become ubiquitous, with elements like situational threat assessment, de-escalation techniques, and physical skills. Studies show that experiential components, such as role play, enhance the effectiveness of these trainings. Virtual Reality (VR) offers a promising solution by providing immersive, interactive training environments that enhance decision-making, physical coordination, and team dynamics. In this article we discuss how VR simulations can replicate real-world settings, allowing healthcare workers to practice and master violence prevention and management skills in a controlled, safe environment. We also describe how VR is scalable and cost-effective, enabling widespread adoption within and across organizations with minimal logistical challenges. Integrating VR into WVP training programs could significantly improve training outcomes, reduce the need for physical and chemical restraints, and ultimately enhance the overall safety and quality of healthcare services.

Background: Vaccination is one of the most effective measures to prevent influenza illness and its complications. Since the 1980s, countries and territories in the Americas have progressively implemented influenza vaccination operations in high-risk priority groups—such as older adults, pregnant persons, persons with comorbidities and health workers. Methods: In this review, we present the history and progress of the seasonal influenza program in the Americas, how the program contributed to the efficient and timely roll-out of the COVID-19 vaccines during the pandemic, and how the program can be used to promote immunization operations across the life span for existing and future vaccines. Results: The influenza A(H1N1)pdm09 pandemic in 2009 and the COVID-19 pandemic in 2020–2023 underscored the importance of having a robust seasonal influenza vaccination program for pandemic preparedness and response. Overall, countries with existing seasonal influenza vaccination programs were better prepared and rolled out the delivery of COVID-19 vaccines more quickly and effectively compared to other countries where the influenza vaccination platform was weak or non-existent. Conclusions: Traditionally, national immunization programs of developing countries have been predominately focused on newborns, children younger than five years and school-aged children while often limiting their investment in effective adult vaccination programs; these programs are typically isolated to high-income countries. Countries in Latin America have been the exception, with strong influenza vaccination programs for adults regardless of national income level. The presence of functional and effective adult influenza vaccination programs can also facilitate the acceptance and uptake of other adult vaccines targeting priority groups at higher risk for severe illness or complications. © 2024 by the authors.

BACKGROUND: Group B Streptococcus (GBS) is a leading cause of neonatal meningitis and sepsis and an important cause of disease in adults. Capsular polysaccharide and protein-based GBS vaccines are currently under development. METHODS: Through national laboratory-based surveillance, invasive GBS isolates were collected from patients of all ages between 2019 and 2020. Phenotypic serotyping and antimicrobial susceptibility testing were conducted, followed by whole-genome sequencing for analysis of population structure and surface protein and resistance genes. RESULTS: 1748 invasive GBS cases were reported. Of these, 661 isolates underwent characterization, with 658 yielding both phenotypic and genotypic results. Isolates (n=658) belonged to five clonal complexes (CC1, CC8/10, CC17, CC19, and CC23) and six serotypes were detected: III (42.8%), Ia (27.9%), V (11.9%), II (8.4%), Ib (6.7%), and IV (2.3%). Phenotypically, only one isolate exhibited reduced penicillin susceptibility (MIC 0.25ug/ml). Phenotypic resistance to erythromycin, clindamycin, and tetracycline was observed in 16.1%, 3.8%, and 91.5% of isolates, respectively. ermTR (34.9%) and mefA/E (30.1%) genes were most common among erythromycin-resistant isolates, while ermB predominated clindamycin-resistant isolates (32.0%). tetM accounted for 95.8% of tetracycline resistance. All isolates carried at least one of the three pilus gene clusters, one of the four homologous alpha/Rib family determinants, and 98% harbored one of the serine-rich repeat protein genes. hvgA was found exclusively in CC17 isolates. CONCLUSION: In our setting, β-lactam antibiotics remain appropriate for GBS treatment and polysaccharide and protein-based vaccines under development are expected to provide good coverage.

BACKGROUND: Serology for dengue viruses (DENV) and Zika virus (ZIKV) has been hindered by antibody cross-reactivity, which limits the utility of these tests for surveillance and assessment of sero-status. Our aim was to develop a multiplexed IgG-based assay with increased accuracy to assess the history of previous DENV and ZIKV infections. METHODS: We developed and assessed the analytical performance of a sample-sparing, multiplexed, microsphere-based serological assay using domain III of the envelope protein (EDIII) of DENV serotypes 1-4 and ZIKV, the most variable region between each virus. We used a reference panel of well-characterised serum samples from US-based travellers or residents of southeast Asia, central America, or Puerto Rico, who were naive or immune to either or both DENV and ZIKV, to develop an algorithm for detecting previous exposure to DENV and ZIKV and identify optimal positivity cutoffs to maximise assay performance. To independently confirm the performance of the assay and algorithm, we used a second test set of previously collected samples from healthy children (aged 9-16 years) living in Puerto Rico, whose DENV and ZIKV serostatus had been defined using the gold-standard virus neutralisation assay. We evaluated the performance of the multiplex assay compared with the gold-standard assay by estimating sensitivity and specificity for identification of past exposure to ZIKV and DENV. FINDINGS: The multiplexed EDIII assay showed reproducible results over different days and a linearity range from μg to pg levels for various EDIII antigens. Using a reference panel of serum samples from individuals who were DENV naive (n=136), DENV immune (n=38), ZIKV naive (n=67), and ZIKV immune (n=28), we optimised the assay and developed a testing algorithm that was 94·9% (95% CI 83·1-99·1) sensitive and 97·1% (92·7-98·9) specific for identifying previous exposure to DENV, and 100% (95% CI 88·0-100) sensitive and 97·0% (89·8-99·5) specific for identifying previous exposure to ZIKV. In an analysis with an independent test set of 389 samples, the assay and algorithm had 94·2% (89·9-97·1) sensitivity and 92·9% (87·3-96·5) specificity for DENV, and 94·1% (88·7-97·4) sensitivity and 95·0% (90·0-98·0) specificity for ZIKV. INTERPRETATION: The multiplexed EDIII serology assay can accurately identify the history of previous infection with either DENV or ZIKV. This high-throughput and sample-sparing assay is a promising new tool for supporting flavivirus surveillance, epidemiological and clinical studies, and serological testing for dengue vaccine eligibility. Further studies are needed to reduce the cost of the assay, eliminate high background in some samples, and to assess performance in DENV-endemic and ZIKV-endemic countries. FUNDING: US National Institutes of Health.

Blastomycosis is a fungal disease caused by inhalation of Blastomyces spores from the environment that can result in severe pulmonary illness and high hospitalization rates. In early March 2023, Public Health Delta and Menominee Counties (Michigan) reported a cluster of blastomycosis cases among paper mill workers to the Michigan Department of Health and Human Services (MDHHS). MDHHS subsequently notified CDC. On March 17, paper mill management requested a health hazard evaluation (HHE) from CDC&#8217;s National Institute for Occupational Safety and Health (NIOSH) to investigate potential workplace exposures to Blastomyces and recommend prevention and control measures at the mill. The workplace epidemiologic investigation combined a NIOSH HHE medical survey consisting of a questionnaire on work and health with Blastomyces urine antigen testing of specimens obtained from workers to assist in case finding, with additional case information from MDHHS blastomycosis surveillance data. Assessment of 645 mill workers identified 162 cases of blastomycosis with illness onset during November 1, 2022-May 15, 2023, with the weekly case count peaking at 21 cases in early March 2023. HHE environmental sampling in and around the mill did not identify the source of workers' Blastomyces exposure in the mill. This outbreak was the largest documented blastomycosis outbreak in the United States, and the first associated with a paper mill or an industrial setting. A coordinated public health response facilitated swift prevention measures with recommendations focused on reducing workers' exposure to Blastomyces, including hazard communication, respiratory protection, mill cleaning, and ventilation system improvements.

Little is known about the epidemiology of leptospirosis in the Dominican Republic, the second most populous country in the Caribbean. We report on findings from a multi-stage household survey across two regions in the country that reveals a previously under-estimated burden of human Leptospira infection. Our findings, based on the reference-standard microscopic agglutination test, indicate a complex picture of serogroup diversity, spatial heterogeneity in infection and risk, and a marked discrepancy between reported cases and serologically estimated infections. Given an overall seroprevalence of 11.3% (95% CI: 10.8-13.0%) and a lower estimated force of infection (0.30% per year [0.27%-0.35%]) the number of infections may exceed national reported case data by 145-fold or more. Icterohaemorrhagiae, associated with severe Weil's disease, was the most commonly identified serogroup with a serogroup-specific prevalence of 4.4%. Consistent with other settings, risk factors including age, male sex, and rat exposure were associated with higher seroprevalence. Our study highlights the need for targeted public health interventions informed by serogroup-specific dynamics, detailed spatial analyses, knowledge of local animal reservoirs, and strengthened laboratory surveillance to effectively control this pathogen.

BACKGROUND: Pneumococcal conjugate vaccines (PCVs) that are ten-valent (PCV10) and 13-valent (PCV13) became available in 2010. We evaluated their global impact on invasive pneumococcal disease (IPD) incidence in all ages. METHODS: Serotype-specific IPD cases and population denominators were obtained directly from surveillance sites using PCV10 or PCV13 in their national immunisation programmes and with a primary series uptake of at least 50%. Annual incidence rate ratios (IRRs) were estimated comparing the incidence before any PCV with each year post-PCV10 or post-PCV13 introduction using Bayesian multi-level, mixed-effects Poisson regressions, by site and age group. All site-weighted average IRRs were estimated using linear mixed-effects regression, stratified by product and previous seven-valent PCV (PCV7) effect (none, moderate, or substantial). FINDINGS: Analyses included 32 PCV13 sites (488 758 cases) and 15 PCV10 sites (46 386 cases) in 30 countries, primarily high income (39 sites), using booster dose schedules (41 sites). By 6 years after PCV10 or PCV13 introduction, IPD due to PCV10-type serotypes and PCV10-related serotype 6A declined substantially for both products (age <5 years: 83-99% decline; ≥65 years: 54-96% decline). PCV7-related serotype 19A increases before PCV10 or PCV13 introduction were reversed at PCV13 sites (age <5 years: 61-79% decline relative to before any PCV; age ≥65 years: 7-26% decline) but increased at PCV10 sites (age <5 years: 1·6-2·3-fold; age ≥65 years: 3·6-4·9-fold). Serotype 3 IRRs had no consistent trends for either product or age group. Non-PCV13-type IPD increased similarly for both products (age <5 years: 2·3-3·3-fold; age ≥65 years: 1·7-2·3-fold). Despite different serotype 19A trends, all-serotype IPD declined similarly between products among children younger than 5 years (58-74%); among adults aged 65 years or older, declines were greater at PCV13 (25-29%) than PCV10 (4-14%) sites, but other differences between sites precluded attribution to product. INTERPRETATION: Long-term use of PCV10 or PCV13 reduced IPD substantially in young children and more moderately in older ages. Non-vaccine-type serotypes increased approximately two-fold to three-fold by 6 years after introduction of PCV10 or PCV13. Continuing serotype 19A increases at PCV10 sites and declines at PCV13 sites suggest that PCV13 use would further reduce IPD at PCV10 sites. FUNDING: Bill & Melinda Gates Foundation as part of the WHO Pneumococcal Vaccines Technical Coordination Project.

BACKGROUND: Widespread use of pneumococcal conjugate vaccines (PCVs) has reduced vaccine-type invasive pneumococcal disease (IPD). We describe the serotype distribution of IPD after extensive use of ten-valent PCV (PCV10; Synflorix, GSK) and 13-valent PCV (PCV13; Prevenar 13, Pfizer) globally. METHODS: IPD data were obtained from surveillance sites participating in the WHO-commissioned Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project that exclusively used PCV10 or PCV13 (hereafter PCV10 and PCV13 sites, respectively) in their national immunisation programmes and had primary series uptake of at least 70%. Serotype distribution was estimated for IPD cases occurring 5 years or more after PCV10 or PCV13 introduction (ie, the mature period when the serotype distribution had stabilised) using multinomial Dirichlet regression, stratified by PCV product and age group (<5 years, 5-17 years, 18-49 years, and ≥50 years). FINDINGS: The analysis included cases occurring primarily between 2015 and 2018 from 42 PCV13 sites (63 362 cases) and 12 PCV10 sites (6806 cases) in 41 countries. Sites were mostly high income (36 [67%] of 54) and used three-dose or four-dose booster schedules (44 [81%]). At PCV10 sites, PCV10 serotypes caused 10·0% (95% CI 6·3-12·9) of IPD cases in children younger than 5 years and 15·5% (13·4-19·3) of cases in adults aged 50 years or older, while PCV13 serotypes caused 52·1% (49·2-65·4) and 45·6% (40·0-50·0), respectively. At PCV13 sites, PCV13 serotypes caused 26·4% (21·3-30·0) of IPD cases in children younger than 5 years and 29·5% (27·5-33·0) of cases in adults aged 50 years or older. The leading serotype at PCV10 sites was 19A in children younger than 5 years (30·6% [95% CI 18·2-43·1]) and adults aged 50 years or older (14·8% [11·9-17·8]). Serotype 3 was a top-ranked serotype, causing about 9% of cases in children younger than 5 years and 14% in adults aged 50 years or older at both PCV10 and PCV13 sites. Across all age and PCV10 or PCV13 strata, the proportion of IPD targeted by higher-valency PCVs beyond PCV13 was 4·1-9·7% for PCV15, 13·5-36·0% for PCV20, 29·9-53·8% for PCV21, 15·6-42·0% for PCV24, and 31·5-50·1% for PCV25. All top-ten ranked non-PCV13 serotypes are included in at least one higher-valency PCV. INTERPRETATION: The proportion of IPD due to serotypes included in PCVs in use was low in mature PCV10 and PCV13 settings. Serotype distribution differed between PCV10 and PCV13 sites and age groups. Higher-valency PCVs target most remaining IPD and are expected to extend impact. FUNDING: Bill & Melinda Gates Foundation as part of the WHO Pneumococcal Vaccines Technical Coordination Project.

BACKGROUND: Indoor residual spraying (IRS) is a malaria control strategy implemented before the rainy season. Nchelenge District, Zambia is a holoendemic setting where IRS has been conducted since 2008 with little impact on malaria incidence or parasite prevalence. Pre-rainy season IRS may not reduce the post-rainy season peak abundance of the major vector, Anopheles funestus. METHODS: A controlled, pre-post, prospective cohort study assessed the impact of late-rainy season IRS on malaria prevalence, incidence, hazard, and vector abundance. Three hundred eighty-two individuals were enrolled across four household clusters, of which two were sprayed in April 2022 toward the end of the rainy season. Monthly household and individual surveys and indoor overnight vector collections were conducted through August 2022. Multivariate regression and time-to-event analyses estimated the impact of IRS on outcomes measured by rapid diagnostic tests, microscopy, and quantitative polymerase chain reaction. RESULTS: Seventy two percent of participants tested positive by rapid diagnostic test at least once and incidence by microscopy was 3.4 infections per person-year. Residing in a household in a sprayed area was associated with a 52% reduction in infection hazard (hazards ratio: 0.48, 95% confidence interval [0.29, 0.78]) but not with changes in incidence, prevalence, or vector abundance. The study-wide entomological inoculation rate was 34 infectious bites per person per year. CONCLUSION: Monthly tracking of incidence and prevalence did not demonstrate meaningful changes in holoendemic transmission intensity. However, hazard of infection, which provides greater power for detecting changes in transmission, demonstrated that late rainy season IRS reduced malaria risk.

The global spread of the highly pathogenic avian influenza (HPAI) A(H5N1) virus poses a serious pandemic threat, necessitating the swift development of effective vaccines. The success of messenger RNA (mRNA) vaccine technology in the COVID-19 pandemic, marked by its rapid development and scalability, demonstrates its potential for addressing other infectious threats, such as HPAI A(H5N1). We therefore evaluated mRNA vaccine candidates targeting panzootic influenza A(H5) clade 2.3.4.4b viruses, which have been shown to infect a range of mammalian species, including most recently being detected in dairy cattle. Ferrets were immunized with mRNA vaccines encoding either hemagglutinin alone or hemagglutinin and neuraminidase, derived from a 2.3.4.4b prototype vaccine virus recommended by the World Health Organization. Kinetics of the immune responses, as well as protection against a lethal challenge dose of A(H5N1) virus, were assessed. Two doses of mRNA vaccination elicited robust neutralizing antibody titers against a 2022 avian isolate and a 2024 human isolate. Further, mRNA vaccination conferred protection from lethal challenge, whereas all unvaccinated ferrets succumbed to infection. It also reduced viral titers in the upper and lower respiratory tracts of infected ferrets. These results underscore the effectiveness of mRNA vaccines against HPAI A(H5N1), showcasing their potential as a vaccine platform for future influenza pandemics.