In the Netherlands, the 7-valent pneumococcal conjugate vaccine (PCV) was introduced to the childhood immunization programme in 2006 and replaced by the 10-valent PCV (PCV10, GSK) in 2011. To describe invasive pneumococcal disease in the era of childhood PCV vaccination on pneumococcal bacteraemia across all ages, we collected and sequenced 979 pneumococcal blood isolates from consecutive patients with pneumococcal bacteraemia in the Gelderland area, the Netherlands, between 2000 and 2020. In total, 58% of the bacteraemia cases (n=563/979) occurred in the elderly population. Compared to the pre-PCV period (2000-2005), the odds ratio for non-PCV10 bacteraemia was 17.5 (CI 9.9-31.6; P<0.001) in the late-PCV10 period, showing an overall increase in the proportion of bacteraemia cases being caused by non-vaccine serotype pneumococci (2016-2020). The increase in non-PCV10 serotypes is mainly driven by an expansion of lineage global pneumococcal sequencing cluster 3 (GPSC3) expressing serotype 8, alongside the emergence of serotype 12F that was mediated by multiple lineages (GPSC32/GPSC26/GPSC55). Both serotypes 8 and 12F were included in the latest PCV20 formulation that is licensed to be used in children and adults in Europe. Over 20 years, we observed a low prevalence of antimicrobial resistance (AMR) as predicted by genome data. There were no significant changes in AMR prevalence after vaccine introduction (P>0.05 for all comparisons). We saw a stably low prevalence of reduced penicillin susceptibility, which was observed in multiple pneumococcal lineages, with GPSC10 being the most common in the Gelderland collection, whilst GPSC1 and GPSC6 were common among the penicillin-resistant pneumococcal blood culture isolates provided by the Netherlands Reference Laboratory for Bacterial Meningitis. Comparison to global collections of GPSC10, GPSC1 and GPSC6 isolates favored the likelihood of separate introductions of penicillin-resistant isolates rather than cloncal expansion. Genomic surveillance of pneumococcal bacteraemia in this unbiased population sample in the Netherlands supports the use of higher valency PCVs, such as PCV20, especially in adults, to prevent future bacteraemia cases caused by Streptococcus pneumoniae in the Gelderland area, the Netherlands, while maintaining a low prevalence of AMR in the pneumococcal population.

BACKGROUND: Household transmission of respiratory viruses may drive community spread. Few recent studies have examined household respiratory syncytial virus (RSV) transmission in the United States. METHODS: We conducted a prospective community-based cohort study from 1 June 2022 to 31 May 2023. Participants had blood samples collected and completed nasal swabs and surveys at least weekly, irrespective of symptoms. We tested serum for RSV antibody, nasal swabs by quantitative reverse transcription polymerase chain reaction (RT-qPCR), and performed whole genome sequencing. We evaluated secondary RSV transmission and associated risk factors based on a log-linear Poisson regression model. RESULTS: RSV was detected among 310 (10%) participants within 200 (20%) households. Most (94%) index cases were symptomatic. We identified 37 cases of potential secondary transmission within 14 days of a distinct index case (10%, 95% confidence interval [CI]: 7%, 14%); median age of index and secondary cases were 6 (interquartile range [IQR]: 3-10) and 35 (7-41) years, respectively, with 89% (24/27) of index cases aged 6 months to 12 years. Factors associated with increased risk of RSV transmission included index case viral detection ≥1 week and contact age ≤12 years. Of 120 sequenced specimens, the main lineages represented were A.d.5.2 (n = 37) and A.d.1 (n = 30). Sequenced viruses from households with ≥2 RSV infections were similar when occurring within ≤14 days (mean pairwise difference 4 [range 0-13], n = 17 households), compared to those >14 days (137 [37-236], n = 2). CONCLUSIONS: Most RSV household transmission occurs from infants and young children to adults. Viral genome sequencing demonstrated that multiple household infections within a 14-day period are likely due to within-household transmission.

Highly pathogenic avian influenza (HPAI) A(H5N1) virus, clade 2.3.4.4b, genotype B3.13 infection has been documented in cats on U.S. dairy cattle farms. In May 2024, the detection of HPAI A(H5N1) virus infection in two cats that were reported to be exclusively indoor, and that had respiratory and neurologic illness in different households, prompted an investigation by the Michigan Department of Health and Human Services and Mid-Michigan District Health Department (MDHHS/MMDHD). The cats' owners and household members were interviewed and offered testing for influenza A(H5) virus. The owner of one cat worked on a dairy farm but declined A(H5) testing; three other household members received negative A(H5) test results. The owner of the other cat lived alone and worked on multiple dairy farms transporting unpasteurized milk; this worker also reported getting splashed in the face and eyes by unpasteurized milk but declined A(H5) testing. Both workers were employed in a county known by MDHHS/MMDHD to have HPAI A(H5N1) virus, clade 2.3.4.4b, genotype B3.13-positive dairy cattle. In states with confirmed HPAI A(H5N1) in livestock, veterinary care can be aided if veterinarians obtain household members' occupational information, especially when evaluating cats with signs of respiratory or neurologic illness. If occupational exposure to HPAI A(H5N1)-infected livestock is identified among cat owners, and their companion cats are suspected to have HPAI A(H5N1) virus infection, it is important that veterinarians contact state and federal public health and animal health officials to collaborate on joint One Health investigations and testing to protect human and animal health.

BACKGROUND: Respiratory syncytial virus (RSV) is the leading cause of hospitalization among infants in the United States (US). RSV immunization, in the form of a monoclonal antibody (mAb) for infants and vaccines for pregnant people, may reduce infant RSV risk. METHODS: In April and May 2023, we surveyed adults with children in Oregon and Washington about the likelihood to accept infant mAb and maternal RSV vaccine and RSV awareness. We used multivariable logistic regression to identify predictors of self-reported likelihood of accepting RSV immunization. RESULTS: Among 1082 respondents, 68% and 70% responded they would very likely accept infant mAb or maternal RSV vaccine, respectively. Respondents had lower odds of accepting infant mAb (OR: 0.10, 95% CI: 0.07-0.15) and maternal RSV vaccine (OR: 0.16, 95% CI: 0.12-0.23) if they were somewhat or very concerned about side effects. Respondents had higher odds of accepting infant mAb if they received an influenza vaccination (OR: 3.79, 95% CI: 1.88-7.63). Respondents had higher odds of accepting maternal vaccine if they had an advanced degree (OR: 1.70, 95% CI: 1.06-2.73), had received an influenza vaccination (OR: 3.62, 95% CI: 1.80-7.25), or were aware of RSV before our survey (OR: 2.03, 95% CI: 1.03-4.01). CONCLUSION: Most respondents reported that they would likely accept RSV mAb for their infant or an RSV vaccine during pregnancy. Concerns about side effects lowered the odds of accepting immunization, however, nearly one-half of those concerned about side effects still expressed a high likelihood of accepting either immunization.

COVID-19 vaccines mitigate severe disease, yet uptake remains low among people experiencing homelessness (PEH) despite the risk of transmission in congregate settings like homeless shelters. This study evaluated retrospective COVID-19 vaccination intent and decision-making between March 2020-October 2021 to identify modifiable factors to improve vaccine acceptance among PEH. We conducted 31 semi-structured interviews and eight focus group discussions across six homeless shelters in Seattle-King County, Washington. Residents and staff aged >= 18 years were recruited through purposive sampling for interviews and convenience sampling for focus groups. Thematic analysis was conducted. Participants reported that too much contradictory and changing information about COVID-19 vaccines led to confusion. Information deemed trustworthy contributed to individual's knowledge and in some cases changed their vaccination intent. While many intended to get vaccinated without external motivators, others were motivated by incentives and requirements. Despite intention to vaccinate, participants reported barriers to COVID-19 vaccine access including availability of vaccine doses, timely eligibility for vaccination, and availability of appointments. Participants presented recommendations to improve COVID-19 information content and dissemination, access, and use of incentives in shelter settings. Future research should test recommended vaccination strategies rooted in the voices and experiences of PEH to determine feasibility and effectiveness in shelter settings. (PsycInfo Database Record (c) 2025 APA, all rights reserved)

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.

BACKGROUND: In Africa, the scale-up of malaria-control interventions has reduced malaria burden, but progress towards elimination has stalled. Mass drug administration (MDA) is promising as a transmission-reducing strategy, but evidence from low-to-moderate transmission settings is needed. We aimed to assess the safety, coverage, and effect of three cycles of MDA with dihydroartemisinin-piperaquine plus single, low-dose primaquine on Plasmodium falciparum incidence and prevalence in southeast Senegal. METHODS: We conducted a two-arm, open-label, cluster-randomised controlled trial in villages in the Tambacounda health district of southeast Senegal. Eligible villages had a population size of 200-800, were within a health-post catchment area with an annual malaria incidence of 60-160 cases per 1000 people, and had an established or planned Prise en Charge à Domicile Plus model. We randomly assigned villages (1:1) using a stratified, constrained randomisation approach to receive either three cycles of MDA with oral dihydroartemisinin-piperaquine plus single, low-dose primaquine administered at 6-week intervals (intervention) or to standard of care, which included three cycles of seasonal malaria chemoprevention (SMC) with oral sulfadoxine-pyrimethamine plus amodiaquine administered at 4-week intervals (control). Participants, the field team, and all investigators, including those who assessed outcomes and analysed data, were unmasked to allocation assignment. Laboratory technicians were masked to intervention assignment. The primary outcome was village-level, P falciparum-confirmed malaria incidence in the post-intervention year (ie, July to December, 2022). Secondary outcomes included malaria incidence during the intervention year (ie, July to December, 2021), coverage and safety of MDA, and adverse events. We conducted analyses using an intention-to-treat approach. The trial is registered with ClinicalTrials.gov (NCT04864444) and is completed. FINDINGS: Between Sept 1 and Oct 25, 2020, 523 villages were geolocated and screened for eligibility; 111 met the inclusion criteria. Of these, 60 villages were randomly selected and assigned to the intervention arm or control arm. Distribution coverage of all three doses of dihydroartemisinin-piperaquine was 6057 (73·6%) of 8229 participants in the first cycle, 6836 (78·8%) of 8673 participants in the second cycle, and 7065 (81·3%) of 8690 participants in the third cycle. Distribution coverage of single, low-dose primaquine was 6286 (78·6%) of 7999 participants in the first cycle, 6949 (82·1%) of 8462 participants in the second cycle, and 7199 (84·0%) of 8575 participants in the third cycle. Distribution coverage of all three doses of SMC was 3187 (92·2%) of 3457 children aged 3-120 months in the first cycle, 3158 (91·8%) of 3442 children aged 3-120 months in the second cycle, and 3139 (91·4%) of 3434 children aged 3-120 months in the third cycle. In the intervention year (ie, July to December, 2021), the adjusted effect of MDA was 55% (95% CI 28 to 71). In the post-intervention year (ie, July to December 2022), the adjusted MDA effect was 26% (-17 to 53). Malaria incidence during the transmission season of the post-intervention year was 126 cases per 1000 population in the intervention arm and 146 cases per 1000 population in the control arm. No serious adverse events were reported. INTERPRETATION: In southeast Senegal, a low-to-moderate transmission setting where malaria-control measures have been scaled up, three cycles of MDA with dihydroartemisinin-piperaquine plus single, low-dose primaquine was safe and reduced malaria burden during the intervention year. However, its sustained effect was weak and continuation of MDA or another transmission-reducing strategy could be required. FUNDING: US President's Malaria Initiative.

BACKGROUND: Institutions of higher education (IHE) have been a focus of SARS-CoV-2 transmission studies but there is limited information on how viral diversity and transmission at IHE changed as the pandemic progressed. METHODS: Here we analyze 3606 viral genomes from unique COVID-19 episodes collected at a public university in Seattle, Washington from September 2020 to September 2022. RESULTS: Across the study period, we found evidence of frequent viral transmission among university affiliates with 60% (n = 2153) of viral genomes from campus specimens genetically identical to at least one other campus specimen. Moreover, viruses from students were observed in transmission clusters at a higher frequency than in the overall dataset while viruses from symptomatic infections were observed in transmission clusters at a lower frequency. Although only a small percentage of community viruses were identified as possible descendants of viruses isolated in university study specimens, phylodynamic modeling suggested a high rate of transmission events from campus into the local community, particularly during the 2021-2022 academic year. CONCLUSIONS: We conclude that viral transmission was common within the university population throughout the study period but that not all university affiliates were equally likely to be involved. In addition, the transmission rate from campus into the surrounding community may have increased during the second year of the study, possibly due to return to in-person instruction.

BACKGROUND: Understanding protection against SARS-CoV-2 infection by vaccine and hybrid immunity is important for informing public health strategies as new variants emerge. METHODS: We analyzed data from three cohort studies spanning September 1, 2022-July 31, 2023, to estimate COVID-19 vaccine effectiveness (VE) against SARS-CoV-2 infection and symptomatic COVID-19 among adults with and without prior infection in the United States. Participants collected weekly nasal swabs, irrespective of symptoms, annual blood draws, and completed periodic surveys, which included vaccination status and prior infection history. Swabs were tested molecularly for SARS-CoV-2. VE was estimated using Cox proportional hazards models for the hazard ratios of infections, adjusting for covariates. VE was calculated considering prior infection and recency of vaccination. RESULTS: Among 3,344 adults, adjusted VE of bivalent vaccine against infection was 37.2% (95% CI: 12.3-55.7%) within 7-59 days of vaccination and 21.1% (95% CI: -0.5-37.1%) within 60-179 days of vaccination compared to participants who were unvaccinated/received an original monovalent vaccine dose ≥180 days prior. Overall, adjusted VE of bivalent vaccine against infection, in conjunction with prior infection, was 62.2% (95% CI: 46.0-74.5%) within 7-179 days of vaccination and 39.4% (95% CI: 12.5-61.6%) ≥180 days compared to naïve participants who were unvaccinated/received a monovalent vaccine dose ≥180 days prior. CONCLUSIONS: Adults with both prior infection and recent vaccination had high protection against infection and symptomatic illness. Recent vaccination alone provided moderate protection.

SUMMARYHenipaviruses were first identified 30 years ago and have since been associated with over 30 outbreaks of disease in humans. Highly pathogenic henipaviruses include Hendra virus (HeV) and Nipah virus (NiV), classified as biosafety level 4 pathogens. In addition, NiV has been listed as a priority pathogen by the World Health Organization (WHO), the Coalition for Epidemic Preparedness Innovations (CEPI), and the UK Vaccines Research and Development Network (UKVN). Here, we re-examine epidemiological, ecological, clinical, and pathobiological studies of HeV and NiV to provide a comprehensive guide of the current knowledge and application to identify and evaluate countermeasures. We also discuss therapeutic and vaccine development efforts. Furthermore, with case identification, prevention, and treatment in mind, we highlight limitations in research and recognize gaps necessitating additional studies.

Development of broad-spectrum antiviral therapies is critical for outbreak and pandemic preparedness against emerging and reemerging viruses. Viruses inducing hemorrhagic fevers cause high morbidity and mortality in humans and are associated with several recent international outbreaks, but approved therapies for treating most of these pathogens are lacking. Here, we show that 4'-fluorouridine (4'-FlU; EIDD-2749), an orally available ribonucleoside analog, has antiviral activity against multiple hemorrhagic fever viruses in cell culture, including Nipah virus, Crimean-Congo hemorrhagic fever virus, orthohantaviruses, and arenaviruses. We performed preclinical in vivo evaluation of oral 4'-FlU against two arenaviruses, Old World Lassa virus (LASV) and New World Junín virus (JUNV), in guinea pig models of lethal disease. 4'-FlU demonstrated both advantageous pharmacokinetic characteristics and high efficacy in both of these lethal disease guinea pig models. Additional experiments supported protection of the infected animals even when 4'-FlU delivery was reduced to a low dose of 0.5 milligram per kilogram. To demonstrate clinical utility, 4'-FlU treatment was evaluated when initiated late in the course of infection (12 or 9 days after infection for LASV and JUNV, respectively). Delayed treatment resulted in rapid resolution of clinical signs, demonstrating an extended window for therapeutic intervention. These data support the use of 4'-FlU as a potent and efficacious treatment against highly pathogenic arenaviruses of public health concern with a virus inhibition profile suggesting broad-spectrum utility as an orally available antiviral drug against a wide variety of viral pathogens.

Legionnaires disease is a serious pneumonia caused by Legionella bacteria. During November 2022-June 2024, CDC was notified of 12 cases of Legionnaires disease among travelers on two cruise ships; eight on cruise ship A and four on cruise ship B. CDC, in collaboration with the cruise lines, initiated investigations to ascertain the potential sources of on-board exposure after notification of the second potentially associated case for each ship. Epidemiologic data collected from patient interviews and environmental assessment and sampling results identified private hot tubs on selected cabin balconies as the most likely exposure source. To minimize Legionella growth, both cruise lines modified the operation and maintenance of these devices by removing the heating elements, draining water between uses, and increasing the frequency of hyperchlorination and cleaning. Hot tubs offer favorable conditions for Legionella growth and transmission when maintained and operated inadequately, regardless of location. Private hot tubs on cruise ships are not subject to the same maintenance requirements as are public hot tubs in common areas. Given the range of hot tub-type devices offered as amenities across the cruise industry, to reduce risk for Legionella growth and transmission, it is important for cruise ship water management program staff members to inventory and assess private balcony hot tubs and adapt public hot tub maintenance and operations protocols for use on private outdoor hot tubs.

Invasive pneumococcal disease (IPD) due to non-vaccine serotypes after the introduction of pneumococcal conjugate vaccines (PCV) remains a global concern. This study used pathogen genomics to evaluate changes in invasive pneumococcal lineages before, during and after vaccine introduction in South Africa. We included genomes (N = 3104) of IPD isolates from individuals aged <18 years (2005-20), spanning four periods: pre-PCV, PCV7, early-PCV13, and late-PCV13. Significant incidence reductions occurred among vaccine-type lineages in the late-PCV13 period compared to the pre-PCV period. However, some vaccine-type lineages continued to cause invasive disease and showed increasing effective population size trends in the post-PCV era. A significant increase in lineage diversity was observed from the PCV7 period to the early-PCV13 period (Simpson's diversity index: 0.954, 95% confidence interval 0.948-0.961 vs 0.965, 0.962-0.969) supporting intervention-driven population structure perturbation. Increases in the prevalence of penicillin, erythromycin, and multidrug resistance were observed among non-vaccine serotypes in the late-PCV13 period compared to the pre-PCV period. In this work we highlight the importance of continued genomic surveillance to monitor disease-causing lineages post vaccination to support policy-making and future vaccine designs and considerations.

Nipah virus (NiV) causes near-annual outbreaks of fatal encephalitis and respiratory disease in South Asia with a high mortality rate (∼70%). Since there are no approved therapeutics for NiV disease in humans, the WHO has designated NiV and henipaviral diseases priority pathogens for research and development. We generated a new recombinant green fluorescent reporter NiV of the circulating Bangladesh genotype (rNiV-B-ZsG) and optimized it alongside our previously generated Malaysian genotype reporter counterpart (rNiV-M-ZsG) for antiviral screening in primary-like human respiratory cell types. Validating our platform for rNiV-B-ZsG with a synthetic compound library directed against viral RNA-dependent RNA polymerases, we identified a hit compound and confirmed its sub-micromolar activity against wild-type NiV, green fluorescent reporter, and the newly constructed bioluminescent red fluorescent double reporter (rNiV-B-BREP) NiV. We furthermore demonstrated that rNiV-B-ZsG and rNiV-B-BREP viruses showed pathogenicity comparable to wild-type NiV-B in the Syrian golden hamster model of disease, supporting additional use of these tools for both pathogenesis and advanced pre-clinical studies in vivo.

ABSTRACTNipah virus (NiV) is an emerging zoonotic RNA virus that can cause fatal respiratory and neurological disease in animals and humans. Accurate NiV diagnostics and surveillance tools are crucial for the identification of acute and resolved infections and to improve our understanding of NiV transmission and circulation. Here, we have developed and validated a split NanoLuc luciferase NiV glycoprotein (G) biosensor for detecting antibodies in clinical and animal samples. This assay is performed by simply mixing reagents and measuring luminescence, which depends on the complementation of the split NanoLuc luciferase G biosensor following its binding to antibodies. This anti-NiV-G "mix-and-read" assay was validated using the WHO's first international standard for anti-NiV antibodies and more than 700 serum samples from the NiV-endemic country of Bangladesh. Anti-NiV antibodies from survivors persisted for at least 8 years according to both ⍺NiV-G mix-and-read and NiV neutralization assays. The ⍺NiV-G mix-and-read assay sensitivity (98.6%) and specificity (100%) were comparable to anti-NiV IgG ELISA performance but failed to detect anti-NiV antibodies in samples collected less than a week following the appearance of symptoms. Overall, the anti-NiV-G biosensor represents a simple, fast, and reliable tool that could support the expansion of NiV surveillance and retrospective outbreak investigations.

Streptococcus pneumoniae is a leading cause of pneumonia and meningitis worldwide. Many different serotypes co-circulate endemically in any one location(1,2). The extent and mechanisms of spread and vaccine-driven changes in fitness and antimicrobial resistance remain largely unquantified. Here using geolocated genome sequences from South Africa (n = 6,910, collected from 2000 to 2014), we developed models to reconstruct spread, pairing detailed human mobility data and genomic data. Separately, we estimated the population-level changes in fitness of strains that are included (vaccine type (VT)) and not included (non-vaccine type (NVT)) in pneumococcal conjugate vaccines, first implemented in South Africa in 2009. Differences in strain fitness between those that are and are not resistant to penicillin were also evaluated. We found that pneumococci only become homogenously mixed across South Africa after 50 years of transmission, with the slow spread driven by the focal nature of human mobility. Furthermore, in the years following vaccine implementation, the relative fitness of NVT compared with VT strains increased (relative risk of 1.68; 95% confidence interval of 1.59-1.77), with an increasing proportion of these NVT strains becoming resistant to penicillin. Our findings point to highly entrenched, slow transmission and indicate that initial vaccine-linked decreases in antimicrobial resistance may be transient.

We present a novel small molecule antiviral chemotype that was identified by an unconventional cell-free protein synthesis and assembly-based phenotypic screen for modulation of viral capsid assembly. Activity of PAV-431, a representative compound from the series, has been validated against infectious viruses in multiple cell culture models for all six families of viruses causing most respiratory diseases in humans. In animals, this chemotype has been demonstrated efficacious for porcine epidemic diarrhoea virus (a coronavirus) and respiratory syncytial virus (a paramyxovirus). PAV-431 is shown to bind to the protein 14-3-3, a known allosteric modulator. However, it only appears to target the small subset of 14-3-3 which is present in a dynamic multi-protein complex whose components include proteins implicated in viral life cycles and in innate immunity. The composition of this target multi-protein complex appears to be modified upon viral infection and largely restored by PAV-431 treatment. An advanced analog, PAV-104, is shown to be selective for the virally modified target, thereby avoiding host toxicity. Our findings suggest a new paradigm for understanding, and drugging, the host-virus interface, which leads to a new clinical therapeutic strategy for treatment of respiratory viral disease.

BACKGROUND: In response to the 2015-2016 Zika virus (ZIKV) outbreak and the causal relationship established between maternal ZIKV infection and adverse infant outcomes, we conducted a cohort study to estimate the incidence of ZIKV infection in pregnancy and assess its impacts in women and infants. METHODOLOGY/PRINCIPAL FINDINGS: From May 2018-January 2020, we prospectively followed pregnant women recruited from 134 participating hospitals in two non-adjacent provinces in northeastern Thailand. We collected demographic, clinical, and epidemiologic data and blood and urine at routine antenatal care visits until delivery. ZIKV infections were confirmed by real-time reverse transcriptase polymerase chain reaction (rRT-PCR). Specimens with confirmed ZIKV underwent whole genome sequencing. Among 3,312 women enrolled, 12 (0.36%) had ZIKV infections, of which two (17%) were detected at enrollment. Ten (83%, 3 in 2nd and 7 in 3rd trimester) ZIKV infections were detected during study follow-up, resulting in an infection rate of 0.15 per 1,000 person-weeks (95% CI: 0.07-0.28). The majority (11/12, 91.7%) of infections occurred in one province. Persistent ZIKV viremia (42 days) was found in only one woman. Six women with confirmed ZIKV infections were asymptomatic until delivery. Sequencing of 8 ZIKV isolates revealed all were of Asian lineage. All 12 ZIKV infected women gave birth to live, full-term infants; the only observed adverse birth outcome was low birth weight in one (8%) infant. Pregnancies in 3,300 ZIKV-rRT-PCR-negative women were complicated by 101 (3%) fetal deaths, of which 67 (66%) had miscarriages and 34 (34%) had stillbirths. There were no differences between adverse fetal or birth outcomes of live infants born to ZIKV-rRT-PCR-positive mothers compared to live infants born to ZIKV-rRT-PCR-negative mothers. CONCLUSIONS/SIGNIFICANCE: Confirmed ZIKV infections occurred infrequently in this large pregnancy cohort and observed adverse maternal and birth outcomes did not differ between mothers with and without confirmed infections.

BACKGROUND: Early isolation and care for Ebola Disease patients at Ebola Treatment Units (ETU) curb outbreak spread. We evaluated time to ETU entry and associated factors during the 2022 Sudan virus disease (SVD) outbreak in Uganda. METHODS: We included persons with RT-PCR-confirmed SVD with onset September 20-November 30, 2022. We categorized days from symptom onset to ETU entry ('delays') as short (≤2), moderate (3-5), and long (≥6); the latter two were 'delayed isolation'. We categorized symptom onset timing as 'earlier' or 'later,' using October 15 as a cut-off. We assessed demographics, symptom onset timing, and awareness of contact status as predictors for delayed isolation. We explored reasons for early vs late isolation using key informant interviews. RESULTS: Among 118 case-patients, 25 (21%) had short, 43 (36%) moderate, and 50 (43%) long delays. Seventy-five (64%) had symptom onset later in the outbreak. Earlier symptom onset increased risk of delayed isolation [cRR=1∙8, 95%CI (1∙2-2∙8)]. Awareness of contact status and SVD symptoms, and belief that early treatment-seeking was lifesaving facilitated early care-seeking. Patients with long delays reported fear of ETUs and lack of transport as contributors. CONCLUSION: Delayed isolation was common early in the outbreak. Strong contact tracing and community engagement could expedite presentation to ETUs.

BACKGROUND: Widespread outbreaks of person-to-person transmitted hepatitis A virus (HAV), particularly among people who inject drugs (PWID), continue across the United States and globally. However, the herd immunity threshold and vaccination coverage required to prevent outbreaks are unknown. We used surveillance data and dynamic modeling to estimate herd immunity thresholds among PWID in 16 US states. METHODS: We used a previously published dynamic model of HAV transmission calibrated to surveillance data from outbreaks involving PWID in 16 states. Using state-level calibrated models, we estimated the basic reproduction number (R0) and herd immunity threshold for PWID in each state. We performed a meta-analysis of herd immunity thresholds to determine the critical vaccination coverage required to prevent most HAV outbreaks among PWID. RESULTS: Estimates of R0 for HAV infection ranged from 2.2 (95% confidence interval [CI], 1.9-2.5) for North Carolina to 5.0 (95% CI, 4.5-5.6) for West Virginia. Corresponding herd immunity thresholds ranged from 55% (95% CI, 47%-61%) for North Carolina to 80% (95% CI, 78%-82%) for West Virginia. Based on the meta-analysis, we estimated a pooled herd immunity threshold of 64% (95% CI, 61%-68%; 90% prediction interval, 52%-76%) among PWID. Using the prediction interval upper bound (76%) and assuming 95% vaccine efficacy, we estimated that vaccination coverage of 80% could prevent most HAV outbreaks. CONCLUSIONS: Hepatitis A vaccination programs in the United States may need to achieve vaccination coverage of at least 80% among PWID in order to prevent most HAV outbreaks among this population.

INTRODUCTION: A lateral flow rapid diagnostic test (RDT) enables detection of measles specific immunoglobulin M (IgM) antibody in serum, capillary blood, and oral fluid with accuracy consistent with enzyme immunoassay (EIA). The objectives of the study were: 1) to assess measles RDT inter-reader agreement between two clinic staff; 2) to assess the sensitivity and specificity of the measles RDT relative to standard surveillance testing in a low transmission setting; 3) to evaluate the knowledge, attitudes, and practices of staff in clinics using the RDT; and 4) to assess the impact of RDT testing on the measles public health response in Malaysia. MATERIALS AND METHODS: The clinic-based prospective evaluation included all suspected measles cases captured by routine measles surveillance at 34 purposely selected clinics in 15 health districts in Malaysia between September 2019 and June 2020, following day-long regional trainings on RDT use. Following informed consent, four specimens were collected from each suspected case, including those routinely collected for standard surveillance [serum for EIA and throat swabs for quantitative reverse transcriptase polymerase chain reaction (RT-qPCR)] together with capillary blood and oral fluid tested with RDTs during the study. RDT impact was evaluated by comparing the rapidity of measles public health response between the pre-RDT implementation (December 2018 to August 2019) and RDT implementation periods (September 2019 to June 2020). To assess knowledge, attitudes, and practices of RDT use, staff involved in the public health management of measles at the selected sites were surveyed. RESULTS: Among the 436 suspect cases, agreement of direct visual readings of measles RDT devices between two health clinic staff was 99% for capillary blood (k = 0.94) and 97% for oral fluid (k = 0.90) specimens. Of the total, 45 (10%) were positive by measles IgM EIA (n = 44, including five also positive by RT-qPCR) or RT-qPCR only (n = 1), and 38 were positive by RDT (using either capillary blood or oral fluid). Using measles IgM EIA or RT-qPCR as reference, RDT sensitivity using capillary blood was 43% (95% CI: 30%-58%) and specificity was 98% (95% CI: 96%-99%); using oral fluid, sensitivity (26%, 95% CI: 15%-40%) and specificity (97%, 95% CI: 94%-98%) were lower. Nine months after training, RDT knowledge was high among staff involved with the public health management of measles (average quiz score of 80%) and was highest among those who received formal training (88%), followed by those trained during supervisory visits (83%). During the RDT implementation period, the number of days from case confirmation until initiation of public response decreased by about 5 days. CONCLUSION: The measles IgM RDT shows >95% inter-reader agreement, high retention of RDT knowledge, and a more rapid public health response. However, despite ≥95% RDT specificity using capillary blood or oral fluid, RDT sensitivity was <45%. Higher-powered studies using highly specific IgM assays and systematic RT-qPCR for case confirmation are needed to establish the role of RDT in measles elimination settings.

Vaccine effectiveness (VE) studies utilizing the test-negative design are typically conducted in clinical settings, rather than community populations, leading to bias in VE estimates against mild disease and limited information on VE in healthy young adults. In a community-based university population, we utilized data from a large SARS-CoV-2 testing program to estimate relative VE of COVID-19 mRNA vaccine primary series and monovalent booster dose versus primary series only against symptomatic SARS-CoV-2 infection from September 2021 to July 2022. We used the test-negative design and logistic regression implemented via generalized estimating equations adjusted for age, calendar time, prior SARS-CoV-2 infection, and testing frequency (proxy for test-seeking behavior) to estimate relative VE. Analyses included 2,218 test-positive cases (59 % received monovalent booster dose) and 9,615 test-negative controls (62 %) from 9,066 individuals, with median age of 21 years, mostly students (71 %), White (56 %) or Asian (28 %), and with few comorbidities (3 %). More cases (23 %) than controls (6 %) had COVID-19-like illness. Estimated adjusted relative VE of primary series and monovalent booster dose versus primary series only against symptomatic SARS-CoV-2 infection was 40 % (95 % CI: 33-47 %) during the overall analysis period and 46 % (39-52 %) during the period of Omicron circulation. Relative VE was greater for those without versus those with prior SARS-CoV-2 infection (41 %, 34-48 % versus 33 %, 9 %-52 %, P < 0.001). Relative VE was also greater in the six months after receiving a booster dose (41 %, 33-47 %) compared to more than six months (27 %, 8-42 %), but this difference was not statistically significant (P = 0.06). In this relatively young and healthy adult population, an mRNA monovalent booster dose provided increased protection against symptomatic SARS-CoV-2 infection, overall and with the Omicron variant. University testing programs may be utilized for estimating VE in healthy young adults, a population that is not well-represented by routine VE studies.

In October 2021, 59 scientists from 14 countries and 13 U.S. states collaborated virtually in the Third Annual Baylor College of Medicine & DNANexus Structural Variation hackathon. The goal of the hackathon was to advance research on structural variants (SVs) by prototyping and iterating on open-source software. This led to nine hackathon projects focused on diverse genomics research interests, including various SV discovery and genotyping methods, SV sequence reconstruction, and clinically relevant structural variation, including SARS-CoV-2 variants. Repositories for the projects that participated in the hackathon are available at https://github.com/collaborativebioinformatics.

Nipah virus (NiV) is a highly pathogenic paramyxovirus. The Syrian hamster model recapitulates key features of human NiV disease and is a critical tool for evaluating antivirals and vaccines. Here we describe longitudinal humoral immune responses in NiV-infected Syrian hamsters. Samples were obtained 1-28 days after infection and analyzed by ELISA, neutralization, and Fc-mediated effector function assays. NiV infection elicited robust antibody responses against the nucleoprotein and attachment glycoprotein. Levels of neutralizing antibodies were modest and only detectable in surviving animals. Fc-mediated effector functions were mostly observed in nucleoprotein-targeting antibodies. Antibody levels and activities positively correlated with challenge dose.

This 2023 Clinical Policy from the American College of Emergency Physicians is an update of the 2008 “Clinical Policy: Neuroimaging and Decisionmaking in Adult Mild Traumatic Brain Injury in the Acute Setting.” A writing subcommittee conducted a systematic review of the literature to derive evidence-based recommendations to answer the following questions: 1) In the adult emergency department patient presenting with minor head injury, are there clinical decision tools to identify patients who do not require a head computed tomography? 2) In the adult emergency department patient presenting with minor head injury, a normal baseline neurologic examination, and taking an anticoagulant or antiplatelet medication, is discharge safe after a single head computed tomography? and 3) In the adult emergency department patient diagnosed with mild traumatic brain injury or concussion, are there clinical decision tools or factors to identify patients requiring follow-up care for postconcussive syndrome or to identify patients with delayed sequelae after emergency department discharge? Evidence was graded and recommendations were made based on the strength of the available data. Widespread and consistent implementation of evidence-based clinical recommendations is warranted to improve patient care.

Escherichia albertii is an emerging foodborne pathogen. To better understand the pathogenesis and health risk of this pathogen, comparative genomics and phenotypic characterization were applied to assess the pathogenicity potential of E. albertii strains isolated from wild birds in a major agricultural region in California. Shiga toxin genes stx(2f) were present in all avian strains. Pangenome analyses of 20 complete genomes revealed a total of 11,249 genes, of which nearly 80% were accessory genes. Both core gene-based phylogenetic and accessory gene-based relatedness analyses consistently grouped the three stx(2f)-positive clinical strains with the five avian strains carrying ST7971. Among the three Stx2f-converting prophage integration sites identified, ssrA was the most common one. Besides the locus of enterocyte effacement and type three secretion system, the high pathogenicity island, OI-122, and type six secretion systems were identified. Substantial strain variation in virulence gene repertoire, Shiga toxin production, and cytotoxicity were revealed. Six avian strains exhibited significantly higher cytotoxicity than that of stx(2f)-positive E. coli, and three of them exhibited a comparable level of cytotoxicity with that of enterohemorrhagic E. coli outbreak strains, suggesting that wild birds could serve as a reservoir of E. albertii strains with great potential to cause severe diseases in humans.

BACKGROUND: SARS-CoV-2 has extensively spread in cities and rural communities, and studies are needed to quantify exposure in the population. We report seroprevalence of SARS-CoV-2 in two well-characterized populations in Kenya at two time points. These data inform the design and delivery of public health mitigation measures. METHODS: Leveraging on existing population based infectious disease surveillance (PBIDS) in two demographically diverse settings, a rural site in western Kenya in Asembo, Siaya County, and an urban informal settlement in Kibera, Nairobi County, we set up a longitudinal cohort of randomly selected households with serial sampling of all consenting household members in March and June/July 2021. Both sites included 1,794 and 1,638 participants in the March and June/July 2021, respectively. Individual seroprevalence of SARS-CoV-2 antibodies was expressed as a percentage of the seropositive among the individuals tested, accounting for household clustering and weighted by the PBIDS age and sex distribution. RESULTS: Overall weighted individual seroprevalence increased from 56.2% (95%CI: 52.1, 60.2%) in March 2021 to 63.9% (95%CI: 59.5, 68.0%) in June 2021 in Kibera. For Asembo, the seroprevalence almost doubled from 26.0% (95%CI: 22.4, 30.0%) in March 2021 to 48.7% (95%CI: 44.3, 53.2%) in July 2021. Seroprevalence was highly heterogeneous by age and geography in these populations-higher seroprevalence was observed in the urban informal settlement (compared to the rural setting), and children aged <10 years had the lowest seroprevalence in both sites. Only 1.2% and 1.6% of the study participants reported receipt of at least one dose of the COVID-19 vaccine by the second round of serosurvey-none by the first round. CONCLUSIONS: In these two populations, SARS-CoV-2 seroprevalence increased in the first 16 months of the COVID-19 pandemic in Kenya. It is important to prioritize additional mitigation measures, such as vaccine distribution, in crowded and low socioeconomic settings.

In "Stepping Forward: A Scoping Review of Physical Activity in Osteoarthritis," White and colleagues(1) aimed to help patients, policymakers, investigators, and healthcare providers (HCPs) better understand how physical activity (PA) is defined and measured, the benefits of PA for knee osteoarthritis (KOA), the potential role of PA in the development and/or progression of KOA, and the PA guidelines for Americans.(2) This correspondence aims to reinforce the importance of PA for adults with arthritis; clarify definitions for "inactive" and "insufficiently active" from the PA guidelines for Americans(2) and supplement White and colleagues' scoping review by (1) highlighting arthritis-appropriate evidence-based interventions (AAEBIs) for PA and self-management education; and (2) providing resources to facilitate HCP screening, counseling, and referral to evidencebased PA interventions for adults with arthritis.

Due to the emergence of non-vaccine serotypes in vaccinated populations, Streptococcus pneumoniae remains a major global health challenge despite advances in vaccine development. Serotype 16F is among the predominant non-vaccine serotypes identified among vaccinated infants in South Africa (SA). To characterize lineages and antimicrobial resistance in 16F isolates obtained from South Africa and place the local findings in a global context, we analysed 10 923 S. pneumoniae carriage isolates obtained from infants recruited as part of a broader SA birth cohort. We inferred serotype, resistance profile for penicillin, chloramphenicol, cotrimoxazole, erythromycin and tetracycline, and global pneumococcal sequence clusters (GPSCs) from genomic data. To ensure global representation, we also included S. pneumoniae carriage and disease isolates from the Global Pneumococcal Sequencing (GPS) project database (n=19 607, collected from 49 countries across 5 continents, 1995-2018, accessed 17 March 2022). Nine per cent (934/10923) of isolates obtained from infants in the Drakenstein community in SA and 2 %(419/19607) of genomes in the GPS dataset were serotype 16F. Serotype 16F isolates were from 28 different lineages of S. pneumoniae, with GPSC33 and GPSC46 having the highest proportion of serotype 16F isolates at 26 % (346/1353) and 53 % (716/1353), respectively. Serotype 16F isolates were identified globally, but most isolates were collected from Africa. GPSC33 was associated with carriage [OR (95 % CI) 0.24 (0.09-0.66); P=0.003], while GPSC46 was associated with disease [OR (95 % CI) 19.9 (2.56-906.50); P=0.0004]. Ten per cent (37/346) and 15 % (53/346) of isolates within GPSC33 had genes associated with resistance to penicillin and co-trimoxazole, respectively, and 18 % (128/716) of isolates within GPSC46 had genes associated with resistance to co-trimoxazole. Resistant isolates formed genetic clusters, which may suggest emerging resistant lineages. Serotype 16F lineages were common in southern Africa. Some of these lineages were associated with disease and resistance to penicillin and cotrimoxazole. We recommend continuous genomic surveillance to determine the long-term impact of serotype 16F lineages on vaccine efficacy and antimicrobial therapy globally. Investing in vaccine strategies that offer protection over a wide range of serotypes/lineages remains essential. This paper contains data hosted by Microreact.

Broad spectrum oral antivirals are urgently needed for the early treatment of many RNA viruses of clinical concern. We previously described the synthesis of 1-O-octadecyl-2-O-benzyl-glycero-3-phospho-RVn (V2043), an orally bioavailable lipid prodrug of remdesivir nucleoside (RVn, GS-441524) with broad spectrum antiviral activity against viruses with pandemic potential. Here we compared the relative activity of V2043 with new RVn lipid prodrugs containing sn-1 alkyl ether or sn-2 glycerol modifications. We found that 3-F-4-MeO-Bn, 3-CN-Bn, and 4-CN-Bn sn-2 glycerol modifications improved antiviral activity compared to V2043 when tested in vitro against clinically important RNA viruses from 5 virus families. These results support the continued development of V2043 and sn-2 glycerol modified RVn lipid prodrugs for the treatment of a broad range of RNA viruses for which there are limited therapies.