BACKGROUND: Children with hematologic malignancies (HMs) are at increased risk of invasive pneumococcal disease (IPD). Data on long-term IPD trends in U.S. children with HM after 13-valent pneumococcal conjugate vaccine (PCV13) introduction are limited. We assessed IPD trends in children with HM before and after PCV13 introduction and the proportion of IPD cases caused by serotypes contained in new pneumococcal conjugate vaccines (PCV15 and PCV20, introduced after 2019). METHODS: During 2005-2019, IPD cases among children aged <18 years were identified through the Active Bacterial Core surveillance. We characterized IPD cases by underlying conditions (HM, other IPD risk factors, no IPD risk factors) and time periods [pre-PCV13 (2005-2009), early-PCV13 (2010-2014) and late-PCV13 (2015-2019)]. We estimated incidence rate ratios (IRRs) in children aged <5 years with and without HM and during 2010-2019. RESULTS: We identified 5912 cases of IPD in children aged <18 years; 215 (3.6%) were among children with HM. The proportion of IPD cases with PCV13 serotypes decreased over time in all risk groups; however, IRRs among children with vs. without HM were 215.8 [95% confidence interval (CI): 146.1-292.4] and 240.9 (95 CI: 152.3-341.1) in early and late-PCV13 periods, respectively. In late-PCV13 period, PCV15/non-PCV13 serotypes and PCV20/non-PCV15 serotypes caused 19.4% and 4.8% of IPD cases among children with HM. CONCLUSIONS: The proportion of PCV13-type IPD decreased in all children after PCV13 introduction. However, children with HM remain at an increased risk of IPD. Continued monitoring of the impact of PCV15 and PCV20 use among children with HM is needed.

BACKGROUND: Highly pathogenic avian influenza A(H5N1) viruses have caused widespread infections in dairy cows and poultry in the United States, with sporadic human cases. We describe characteristics of human A(H5N1) cases identified from March through October 2024 in the United States. METHODS: We analyzed data from persons with laboratory-confirmed A(H5N1) virus infection using a standardized case-report form linked to laboratory results from the Centers for Disease Control and Prevention influenza A/H5 subtyping kit. RESULTS: Of 46 case patients, 20 were exposed to infected poultry, 25 were exposed to infected or presumably infected dairy cows, and 1 had no identified exposure; that patient was hospitalized with nonrespiratory symptoms, and A(H5N1) virus infection was detected through routine surveillance. Among the 45 case patients with animal exposures, the median age was 34 years, and all had mild A(H5N1) illness; none were hospitalized, and none died. A total of 42 patients (93%) had conjunctivitis, 22 (49%) had fever, and 16 (36%) had respiratory symptoms; 15 (33%) had conjunctivitis only. The median duration of illness among 16 patients with available data was 4 days (range, 1 to 8). Most patients (87%) received oseltamivir; oseltamivir was started a median of 2 days after symptom onset. No additional cases were identified among the 97 household contacts of case patients with animal exposures. The types of personal protective equipment (PPE) that were most commonly used by workers exposed to infected animals were gloves (71%), eye protection (60%), and face masks (47%). CONCLUSIONS: In the cases identified to date, A(H5N1) viruses generally caused mild illness, mostly conjunctivitis, of short duration, predominantly in U.S. adults exposed to infected animals; most patients received prompt antiviral treatment. No evidence of human-to-human A(H5N1) transmission was identified. PPE use among occupationally exposed persons was suboptimal, which suggests that additional strategies are needed to reduce exposure risk. (Funded by the Centers for Disease Control and Prevention.).

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.

Swine harbors a genetically diverse population of swine influenza A viruses (IAV-S), with demonstrated potential to transmit to the human population, causing outbreaks and pandemics. Here, we describe the development of a one-step, triplex real-time reverse transcription-polymerase chain reaction (rRT-PCR) assay that detects and distinguishes the majority of the antigenically distinct influenza A virus hemagglutinin (HA) clades currently circulating in North American swine, including the IAV-S H1 1A.1 (α), 1A.2 (β), 1A.3 (γ), 1B.2.2 (δ1) and 1B.2.1 (δ2) clades, and the IAV-S H3 2010.1 clade. We performed an in-field test at an exhibition swine show using in-field viral concentration and RNA extraction methodologies and a portable real-time PCR instrument, and rapidly identified three distinct IAV-S clades circulating within the N.A. swine population. Portable sequencing is used to further confirm the results of the in-field test of the swine triplex assay. The IAV-S triplex rRT-PCR assay can be easily transported and used in-field to characterize circulating IAV-S clades in North America, allowing for surveillance and early detection of North American IAV-S with human outbreak and pandemic potential.

BACKGROUND: Immunogenicity studies suggest that recombinant influenza vaccine (RIV) may provide better protection against influenza than standard-dose inactivated influenza vaccines (SD IIV). This randomized trial evaluated the relative vaccine effectiveness (VE) and immunogenicity of RIV versus SD IIV in frontline workers and students aged 18-64 years. METHODS: Participants were randomized to receive RIV or SD IIV and followed for reverse-transcription polymerase chain reaction (RT-PCR)-confirmed influenza during the 2022-2023 influenza season. Sera were collected from a subset of participants before and at 1 and 6 months postvaccination and tested by hemagglutination inhibition for A/H1N1, A/H3N2, B/Yamagata, and B/Victoria and against cell-grown vaccine reference viruses for A/H1N1 and A/H3N2. RESULTS: Overall, 3988 participants were enrolled and vaccinated (25% of the trial sample size goal); RT-PCR-confirmed influenza occurred in 20 of 1963 RIV recipients and 28 of 1964 SD IIV recipients. Relative VE was 29% (95% confidence interval [CI], -26% to 60%). In the immunogenicity substudy (n = 118), the geometric mean titer ratio (GMTR) comparing RIV to SD IIV at 1 month was 2.3 (95% CI, 1.4-3.7) for cell-grown A/H1N1, 2.1 (95% CI, 1.3-3.4) for cell-grown A/H3N2, 1.1 (95% CI, .7-1.6) for B/Victoria, and 1.4 (95% CI, .9-2.0) for B/Yamagata. At 6 months, GMTRs were >1 against A/H1N1, A/H3N2, and B/Yamagata. CONCLUSIONS: Relative VE of RIV compared to SD IIV did not reach statistical significance, but RIV elicited more robust humoral immune responses to 2 of 4 vaccine viruses at 1 month and 3 of 4 viruses at 6 months after vaccination, suggesting possible improved and sustained immune protection from RIV. Clinical Trials Registration. NCT05514002.

BACKGROUND: Primaquine, the only widely available treatment to prevent relapsing Plasmodium vivax malaria, is produced as 15 mg tablets, and new paediatric formulations are being developed. To inform the optimal primaquine dosing regimen for children, we aimed to determine the efficacy and safety of different primaquine dose strategies in children younger than 15 years. METHODS: We undertook a systematic review (Jan 1, 2000-July 26, 2024) for P vivax efficacy studies with at least one treatment group that was administered primaquine over multiple days, that enrolled children younger than 15 years, that followed up patients for at least 28 days, and that had data available for inclusion by June 30, 2022. Patients were excluded if they were aged 15 years or older, presented with severe malaria, received adjunctive antimalarials within 14 days of diagnosis, commenced primaquine more than 7 days after starting schizontocidal treatment, had a protocol violation in the original study, or were missing data on age, sex, or primaquine dose. Available individual patient data were collated and standardised. To evaluate efficacy, the risk of recurrent P vivax parasitaemia between days 7 and 180 was assessed by time-to-event analysis for different total mg/kg primaquine doses (low total dose of ∼3·5 mg/kg and high total dose of ∼7 mg/kg). To evaluate tolerability and safety, the following were assessed by daily mg/kg primaquine dose (low daily dose of ∼0·25 mg/kg, intermediate daily dose of ∼0·5 mg/kg, and high daily dose of ∼1 mg/kg): gastrointestinal symptoms (vomiting, anorexia, or diarrhoea) on days 5-7, haemoglobin decrease of at least 25% to less than 7g/dL (severe haemolysis), absolute change in haemoglobin from day 0 to days 2-3 or days 5-7, and any serious adverse events within 28 days. This study is registered with PROSPERO, CRD42021278085. FINDINGS: In total, 3514 children from 27 studies and 15 countries were included. The cumulative incidence of recurrence by day 180 was 51·4% (95% CI 47·0-55·9) following treatment without primaquine, 16·0% (12·4-20·3) following a low total dose of primaquine, and 10·2% (8·4-12·3) following a high total dose of primaquine. The hazard of recurrent P vivax parasitaemia in children younger than 15 years was reduced following primaquine at low total doses (adjusted hazard ratio [HR] 0·17, 95% CI 0·11-0·25) and high total doses (0·09, 0·07-0·12), compared with no primaquine. In 525 children younger than 5 years, the relative rates of recurrence were also reduced, with an adjusted HR of 0·33 (95% CI 0·18-0·59) for a low total dose and 0·13 (0·08-0·21) for a high total dose of primaquine compared with no primaquine. The rate of recurrence following a high total dose was reduced compared with a low dose in children younger than 15 years (adjusted HR 0·54, 95% CI 0·35-0·85) and children younger than 5 years (0·41, 0·21-0·78). Compared with no primaquine, children treated with any dose of primaquine had a greater risk of gastrointestinal symptoms on days 5-7 after adjustment for confounders, with adjusted risks of 3·9% (95% CI 0-8·6) in children not treated with primaquine, 9·2% (0-18·7) with a low daily dose of primaquine, 6·8% (1·7-12·0) with an intermediate daily dose of primaquine, and 9·6% (4·8-14·3) with a high daily dose of primaquine. In children with 30% or higher glucose-6-phosphate dehydrogenase (G6PD) activity, there were few episodes of severe haemolysis following no primaquine (0·4%, 95% CI 0·1-1·5), a low daily dose (0·0%, 0·0-1·6), an intermediate daily dose (0·5%, 0·1-1·4), or a high daily dose (0·7%, 0·2-1·9). Of 15 possibly drug-related serious adverse events in children, two occurred following a low, four following an intermediate, and nine following a high daily dose of primaquine. INTERPRETATION: A high total dose of primaquine was highly efficacious in reducing recurrent P vivax parasitaemia in children compared with a low dose, particularly in children younger than 5 years. In children treated with high and intermediate daily primaquine doses compared with low daily doses, there was no increase in gastrointestinal symptoms or haemolysis (in children with 30% or higher G6PD activity), but there were more serious adverse events. FUNDING: Medicines for Malaria Venture, Bill & Melinda Gates Foundation, and Australian National Health and Medical Research Council.

Following the detection of highly pathogenic avian influenza (HPAI) virus in countries bordering Kenya to the west, we conducted surveillance among domestic and wild birds along the shores of Lake Victoria. In addition, between 2018 and 2020, we conducted surveillance among poultry and poultry workers in live bird markets and among wild migratory birds in various lakes that are resting sites during migration to assess introduction and circulation of avian influenza viruses in these populations. We tested 7464 specimens (oropharyngeal (OP) and cloacal specimens) from poultry and 6531 fresh fecal specimens from wild birds for influenza A viruses by real-time RT-PCR. Influenza was detected in 3.9% (n = 292) of specimens collected from poultry and 0.2% (n = 10) of fecal specimens from wild birds. On hemagglutinin subtyping, most of the influenza A positives from poultry (274/292, 93.8%) were H9. Of 34 H9 specimens randomly selected for further subtyping, all were H9N2. On phylogenetic analysis, these viruses were genetically similar to other H9 viruses detected in East Africa. Only two of the ten influenza A-positive specimens from the wild bird fecal specimens were successfully subtyped; sequencing analysis of one specimen collected in 2018 was identified as a low-pathogenicity avian influenza H5N2 virus of the Eurasian lineage, and the second specimen, collected in 2020, was subtyped as H11. A total of 18 OP and nasal specimens from poultry workers with acute respiratory illness (12%) were collected; none were positive for influenza A virus. We observed significant circulation of H9N2 influenza viruses in poultry in live bird markets in Kenya. During the same period, low-pathogenic H5N2 virus was detected in a fecal specimen collected in a site hosting a variety of migratory and resident birds. Although HPAI H5N8 was not detected in this survey, these results highlight the potential for the introduction and establishment of highly pathogenic avian influenza viruses in poultry populations and the associated risk of spillover to human populations.

Influenza viruses continually evolve new antigenic variants, through mutations in epitopes of their major surface proteins, hemagglutinin (HA) and neuraminidase (NA). Antigenic drift potentiates the reinfection of previously infected individuals, but the contribution of this process to variability in annual epidemics is not well understood. Here, we link influenza A(H3N2) virus evolution to regional epidemic dynamics in the United States during 1997-2019. We integrate phenotypic measures of HA antigenic drift and sequence-based measures of HA and NA fitness to infer antigenic and genetic distances between viruses circulating in successive seasons. We estimate the magnitude, severity, timing, transmission rate, age-specific patterns, and subtype dominance of each regional outbreak and find that genetic distance based on broad sets of epitope sites is the strongest evolutionary predictor of A(H3N2) virus epidemiology. Increased HA and NA epitope distance between seasons correlates with larger, more intense epidemics, higher transmission, greater A(H3N2) subtype dominance, and a greater proportion of cases in adults relative to children, consistent with increased population susceptibility. Based on random forest models, A(H1N1) incidence impacts A(H3N2) epidemics to a greater extent than viral evolution, suggesting that subtype interference is a major driver of influenza A virus infection ynamics, presumably via heterosubtypic cross-immunity. | Seasonal influenza (flu) viruses cause outbreaks every winter. People infected with influenza typically develop mild respiratory symptoms. But flu infections can cause serious illness in young children, older adults and people with chronic medical conditions. Infected or vaccinated individuals develop some immunity, but the viruses evolve quickly to evade these defenses in a process called antigenic drift. As the viruses change, they can re-infect previously immune people. Scientists update the flu vaccine yearly to keep up with this antigenic drift. The immune system fights flu infections by recognizing two proteins, known as antigens, on the virus’s surface, called hemagglutinin (HA) and neuraminidase (NA). However, mutations in the genes encoding these proteins can make them unrecognizable, letting the virus slip past the immune system. Scientists would like to know how these changes affect the size, severity and timing of annual influenza outbreaks. Perofsky et al. show that tracking genetic changes in HA and NA may help improve flu season predictions. The experiments compared the severity of 22 flu seasons caused by the A(H3N2) subtype in the United States with how much HA and NA had evolved since the previous year. The A(H3N2) subtype experiences the fastest rates of antigenic drift and causes more cases and deaths than other seasonal flu viruses. Genetic changes in HA and NA were a better predictor of A(H3N2) outbreak severity than the blood tests for protective antibodies that epidemiologists traditionally use to track flu evolution. However, the prevalence of another subtype of influenza A circulating in the population, called A(H1N1), was an even better predictor of how severe A(H3N2) outbreaks would be. Perofsky et al. are the first to show that genetic changes in NA contribute to the severity of flu seasons. Previous studies suggested a link between genetic changes in HA and flu season severity, and flu vaccines include the HA protein to help the body recognize new influenza strains. The results suggest that adding the NA protein to flu vaccines may improve their effectiveness. In the future, flu forecasters may want to analyze genetic changes in both NA and HA to make their outbreak predictions. Tracking how much of the A(H1N1) subtype is circulating may also be useful for predicting the severity of A(H3N2) outbreaks. | eng

As part of the response to the highly pathogenic avian influenza A(H5N1) virus outbreak in U.S. cattle and poultry and the associated human cases, CDC and partners are monitoring influenza A virus levels and detection of the H5 subtype in wastewater. Among 48 states and the District of Columbia that performed influenza A testing of wastewater during May 12-July 13, 2024, a weekly average of 309 sites in 38 states had sufficient data for analysis, and 11 sites in four states reported high levels of influenza A virus. H5 subtype testing was conducted at 203 sites in 41 states, with H5 detections at 24 sites in nine states. For each detection or high level, CDC and state and local health departments evaluated data from other influenza surveillance systems and partnered with wastewater utilities and agriculture departments to investigate potential sources. Among the four states with high influenza A virus levels detected in wastewater, three states had corresponding evidence of human influenza activity from other influenza surveillance systems. Among the 24 sites with H5 detections, 15 identified animal sources within the sewershed or adjacent county, including eight milk-processing inputs. Data from these early investigations can help health officials optimize the use of wastewater surveillance during the upcoming respiratory illness season.

CONTEXT: Schools vary in their capacity to implement recommended strategies to prevent infectious diseases, such as COVID-19. Professional development (PD) and technical assistance (TA) are well-established tools used to strengthen school capacity and infrastructure for healthier school environments. OBJECTIVE: The authors examined the relationship between PD and TA received by districts and schools and their implementation of COVID-19 prevention strategies during the 2020-2021 school year. DESIGN AND SETTING: We conducted a descriptive analysis of survey responses collected during Spring 2021 from selected districts and schools in 9 participating states. The survey assessed the implementation of 10 COVID-19 prevention strategies recommended by the Centers for Disease Control and Prevention and whether district or school staff received PD and/or TA on topics related to COVID-19 during the same year. PARTICIPANTS: Survey responses were received from designated contacts in 310 districts and 931 schools across 9 states. MAIN OUTCOME MEASURES: The dependent variable was the number of COVID-19 prevention strategies that were reported as "in place" by each district and school ranging from 0 to 10. RESULTS: On average, districts and schools reported implementing 7 of 10 recommended COVID-19 prevention strategies during the 2020-2021 school year. Schools that received PD on at least 1 of 12 topics reported implementing 7.61 COVID-19 prevention strategies, whereas schools that did not receive PD reported implementing 6.34 strategies. Similarly, schools that received TA on at least 1 topic reported higher COVID-19 implementation scores (7.51) than schools that did not receive any TA (7.20). CONCLUSIONS: Findings reveal a positive relationship between receiving PD and/or TA and implementation of COVID-19 prevention strategies in school settings.

BACKGROUND: The 2022-23 US influenza season peaked early in fall 2022. METHODS: Late-season influenza vaccine effectiveness (VE) against outpatient, laboratory-confirmed influenza was calculated among participants of the US Influenza VE Network using a test-negative design. RESULTS: Of 2561 participants enrolled from December 12, 2022 to April 30, 2023, 91 laboratory-confirmed influenza cases primarily had A(H1N1)pdm09 (6B.1A.5a.2a.1) or A(H3N2) (3C.2a1b.2a.2b). Overall, VE was 30% (95% confidence interval -9%, 54%); low late-season activity precluded estimation for most subgroups. CONCLUSIONS: 2022-23 late-season outpatient influenza VE was not statistically significant. Genomic characterization may improve the identification of influenza viruses that circulate postinfluenza peak.

A healthcare provider unknowingly treated a patient with mpox and subsequently developed ocular mpox without rash. She breastfed during illness; her infant was not infected. This report addresses 3 challenges in mpox management and control: diagnosis in the absence of rash, exposures in healthcare settings, and management of lactating patients.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved into numerous lineages with unique spike mutations and caused multiple epidemics domestically and globally. Although COVID-19 vaccines are available, new variants with the capacity for immune evasion continue to emerge. To understand and characterize the evolution of circulating SARS-CoV-2 variants in the U.S., the Centers for Disease Control and Prevention (CDC) initiated the National SARS-CoV-2 Strain Surveillance (NS3) program and has received thousands of SARS-CoV-2 clinical specimens from across the nation as part of a genotype to phenotype characterization process. Focus reduction neutralization with various antisera was used to antigenically characterize 143 SARS-CoV-2 Delta, Mu and Omicron subvariants from selected clinical specimens received between May 2021 and February 2023, representing a total of 59 unique spike protein sequences. BA.4/5 subvariants BU.1, BQ.1.1, CR.1.1, CQ.2 and BA.4/5 + D420N + K444T; BA.2.75 subvariants BM.4.1.1, BA.2.75.2, CV.1; and recombinant Omicron variants XBF, XBB.1, XBB.1.5 showed the greatest escape from neutralizing antibodies when analyzed against post third-dose original monovalent vaccinee sera. Post fourth-dose bivalent vaccinee sera provided better protection against those subvariants, but substantial reductions in neutralization titers were still observed, especially among BA.4/5 subvariants with both an N-terminal domain (NTD) deletion and receptor binding domain (RBD) substitutions K444M + N460K and recombinant Omicron variants. This analysis demonstrated a framework for long-term systematic genotype to antigenic characterization of circulating and emerging SARS-CoV-2 variants in the U.S., which is critical to assessing their potential impact on the effectiveness of current vaccines and antigen recommendations for future updates.

Measles, a highly contagious respiratory virus with the potential to cause severe complications, hospitalization, and death, was declared eliminated from the United States in 2000; however, with ongoing global transmission, infections in the United States still occur. On March 7, 2024, the Chicago Department of Public Health (CDPH) confirmed a case of measles in a male aged 1 year residing in a temporary shelter for migrants in Chicago. Given the congregate nature of the setting, high transmissibility of measles, and low measles vaccination coverage among shelter residents, measles virus had the potential to spread rapidly among approximately 2,100 presumed exposed shelter residents. CDPH immediately instituted outbreak investigation and response activities in collaboration with state and local health departments, health care facilities, city agencies, and shelters. On March 8, CDPH implemented active case-finding and coordinated a mass vaccination campaign at the affected shelter (shelter A), including vaccinating 882 residents and verifying previous vaccination for 784 residents over 3 days. These activities resulted in 93% measles vaccination coverage (defined as receipt of ≥1 recorded measles vaccine dose) by March 11. By May 13, a total of 57 confirmed measles cases associated with residing in or having contact with persons from shelter A had been reported. Most cases (41; 72%) were among persons who did not have documentation of measles vaccination and were considered unvaccinated. In addition, 16 cases of measles occurred among persons who had received ≥1 measles vaccine dose ≥21 days before first known exposure. This outbreak underscores the need to ensure high vaccination coverage among communities residing in congregate settings.

BACKGROUND: A U.S. case-control study (2010-2014) demonstrated vaccine effectiveness (VE) for ≥ 1 dose of the thirteen-valent pneumococcal conjugate vaccine (PCV13) against vaccine-type (VT) invasive pneumococcal disease (IPD) at 86 %; however, it lacked statistical power to examine VE by number of doses and against individual serotypes. METHODS: We used the indirect cohort method to estimate PCV13 VE against VT-IPD among children aged < 5 years in the United States from May 1, 2010 through December 31, 2019 using cases from CDC's Active Bacterial Core surveillance, including cases enrolled in a matched case-control study (2010-2014). Cases and controls were defined as individuals with VT-IPD and non-PCV13-type-IPD (NVT-IPD), respectively. We estimated absolute VE using the adjusted odds ratio of prior PCV13 receipt (1-aOR x 100 %). RESULTS: Among 1,161 IPD cases, 223 (19.2 %) were VT cases and 938 (80.8 %) were NVT controls. Of those, 108 cases (48.4 %; 108/223) and 600 controls (64.0 %; 600/938) had received > 3 PCV13 doses; 23 cases (17.6 %) and 15 controls (2.4 %) had received no PCV doses. VE ≥ 3 PCV13 doses against VT-IPD was 90.2 % (95 % Confidence Interval75.4-96.1 %), respectively. Among the most commonly circulating VT-IPD serotypes, VE of ≥ 3 PCV13 doses was 86.8 % (73.7-93.3 %), 50.2 % (28.4-80.5 %), and 93.8 % (69.8-98.8 %) against serotypes 19A, 3, and 19F, respectively. CONCLUSIONS: At least three doses of PCV13 continue to be effective in preventing VT-IPD among children aged < 5 years in the US. PCV13 was protective against serotypes 19A and 19F IPD; protection against serotype 3 IPD did not reach statistical significance.

BACKGROUND: Facing a surge of COVID-19 cases in late August 2021, the U.S. state of Illinois re-enacted its COVID-19 mask mandate for the general public and issued a requirement for workers in certain professions to be vaccinated against COVID-19 or undergo weekly testing. The mask mandate required any individual, regardless of their vaccination status, to wear a well-fitting mask in an indoor setting. METHODS: We used Illinois Department of Public Health's COVID-19 confirmed case and vaccination data and investigated scenarios where masking and vaccination would have been reduced to mimic what would have happened had the mask mandate or vaccine requirement not been put in place. The study examined a range of potential reductions in masking and vaccination mimicking potential scenarios had the mask mandate or vaccine requirement not been enacted. We estimated COVID-19 cases and hospitalizations averted by changes in masking and vaccination during the period covering October 20 to December 20, 2021. RESULTS: We find that the announcement and implementation of a mask mandate are likely to correlate with a strong protective effect at reducing COVID-19 burden and the announcement of a vaccinate-or-test requirement among frontline professionals is likely to correlate with a more modest protective effect at reducing COVID-19 burden. In our most conservative scenario, we estimated that from the period of October 20 to December 20, 2021, the mask mandate likely prevented approximately 58,000 cases and 1,175 hospitalizations, while the vaccinate-or-test requirement may have prevented at most approximately 24,000 cases and 475 hospitalizations. CONCLUSION: Our results indicate that mask mandates and vaccine-or-test requirements are vital in mitigating the burden of COVID-19 during surges of the virus.

To better identify emerging or reemerging pathogens in patients with difficult-to-diagnose infections, it is important to improve access to advanced molecular testing methods. This is particularly relevant for cases where conventional microbiologic testing has been unable to detect the pathogen and the patient's specimens test negative. To assess the availability and utility of such testing for human clinical specimens, a literature review of published biomedical literature was conducted. From a corpus of more than 4,000 articles, a set of 34 reports was reviewed in detail for data on where the testing was being performed, types of clinical specimens tested, pathogen agnostic techniques and methods used, and results in terms of potential pathogens identified. This review assessed the frequency of advanced molecular testing, such as metagenomic next generation sequencing that has been applied to clinical specimens for supporting clinicians in caring for difficult-to-diagnose patients. Specimen types tested were from cerebrospinal fluid, respiratory secretions, and other body tissues and fluids. Publications included case reports and series, and there were several that involved clinical trials, surveillance studies, research programs, or outbreak situations. Testing identified both known human pathogens (sometimes in new sites) and previously unknown human pathogens. During this review, there were no apparent coordinated efforts identified to develop regional or national reports on emerging or reemerging pathogens. Therefore, development of a coordinated sentinel surveillance system that applies advanced molecular methods to clinical specimens which are negative by conventional microbiological diagnostic testing would provide a foundation for systematic characterization of emerging and underdiagnosed pathogens and contribute to national biodefense strategy goals.

Patterns of within-host influenza A virus (IAV) diversity and evolution have been described in natural human infections, but these patterns remain poorly characterized in non-human hosts. Elucidating these dynamics is important to better understand IAV biology and the evolutionary processes that govern spillover into humans. Here, we sampled an IAV outbreak in pigs during a week-long county fair to characterize viral diversity and evolution in this important reservoir host. Nasal wipes were collected on a daily basis from all pigs present at the fair, yielding up to 421 samples per day. Subtyping of PCR-positive samples revealed the co-circulation of H1N1 and H3N2 subtype swine IAVs. PCR-positive samples with robust Ct values were deep-sequenced, yielding 506 sequenced samples from a total of 253 pigs. Based on higher-depth re-sequenced data from a subset of these initially sequenced samples (260 samples from 168 pigs), we characterized patterns of within-host IAV genetic diversity and evolution. We find that IAV genetic diversity in single-subtype infected pigs is low, with the majority of intrahost Single Nucleotide Variants (iSNVs) present at frequencies of <10%. The ratio of the number of nonsynonymous to the number of synonymous iSNVs is significantly lower than under the neutral expectation, indicating that purifying selection shapes patterns of within-host viral diversity in swine. The dynamic turnover of iSNVs and their pronounced frequency changes further indicate that genetic drift also plays an important role in shaping IAV populations within pigs. Taken together, our results highlight similarities in patterns of IAV genetic diversity and evolution between humans and swine, including the role of stochastic processes in shaping within-host IAV dynamics.

The surveillance and identification of emerging, reemerging, and unknown infectious disease pathogens is essential to national public health preparedness and relies on fluidity, coordination, and interconnectivity between public and private pathogen surveillance systems and networks. Developing a national sentinel surveillance network with existing resources and infrastructure could increase efficiency, accelerate the identification of emerging public health threats, and support coordinated intervention strategies that reduce morbidity and mortality. However, implementing and sustaining programs to detect emerging and reemerging pathogens in humans using advanced molecular methods, such as metagenomic sequencing, requires making large investments in testing equipment and developing networks of clinicians, laboratory scientists, and bioinformaticians. In this study, we sought to gain an understanding of how federal government agencies currently support such pathogen agnostic testing of human specimens in the United States. We conducted a landscape analysis of federal agency websites for publicly accessible information on the availability and type of pathogen agnostic testing and details on flow of clinical specimens and data. The website analysis was supplemented by an expert review of results with representatives from the federal agencies. Operating divisions within the US Department of Health and Human Services and the US Department of Veterans Affairs have developed and sustained extensive clinical and research networks to obtain patient specimens and perform metagenomic sequencing. Metagenomic facilities supported by US agencies were not equally geographically distributed across the United States. Although many entities have work dedicated to metagenomics and/or support emerging infectious disease surveillance specimen collection, there was minimal formal collaboration across agencies.

Persons with HIV (PWH) are at increased risk for bacterial infections, and previous publications document an increased risk for invasive meningococcal disease (IMD) in particular. This analysis provides evidence that PWH face a 6-fold increase in risk for IMD based on Active Bacterial Core surveillance data collected during 2009-2019.

BACKGROUND: In 2019, the Louisiana Department of Health reported an early influenza B/Victoria (B/VIC) virus outbreak. METHOD: As it was an atypically large outbreak, we deployed to Louisiana to investigate it using genomics and a triplex real-time RT-PCR assay to detect three antigenically distinct B/VIC lineage variant viruses. RESULTS: The investigation indicated that B/VIC V1A.3 subclade, containing a three amino acid deletion in the hemagglutinin and known to be antigenically distinct to the B/Colorado/06/2017 vaccine virus, was the most prevalent circulating virus within the specimens evaluated (86/88 in real-time RT-PCR). CONCLUSION: This work underscores the value of portable platforms for rapid, onsite pathogen characterization.

Influenza viruses undergo rapid evolutionary changes, which requires continuous surveillance to monitor for genetic and potential antigenic changes in circulating viruses that can guide control and prevention decision making. We sequenced and phylogenetically analyzed A(H1N1)pdm09 virus genome sequences obtained from specimens collected from hospitalized patients of all ages with or without pneumonia between 2009 and 2018 from seven sentinel surveillance sites across Kenya. We compared these sequences with recommended vaccine strains during the study period to infer genetic and potential antigenic changes in circulating viruses and associations of clinical outcome. We generated and analyzed a total of 383 A(H1N1)pdm09 virus genome sequences. Phylogenetic analyses of HA protein revealed that multiple genetic groups (clades, subclades, and subgroups) of A(H1N1)pdm09 virus circulated in Kenya over the study period; these evolved away from their vaccine strain, forming clades 7 and 6, subclades 6C, 6B, and 6B.1, and subgroups 6B.1A and 6B.1A1 through acquisition of additional substitutions. Several amino acid substitutions among circulating viruses were associated with continued evolution of the viruses, especially in antigenic epitopes and receptor binding sites (RBS) of circulating viruses. Disease severity declined with an increase in age among children aged < 5 years. Our study highlights the necessity of timely genomic surveillance to monitor the evolutionary changes of influenza viruses. Routine influenza surveillance with broad geographic representation and whole genome sequencing capacity to inform on prioritization of antigenic analysis and the severity of circulating strains are critical to improved selection of influenza strains for inclusion in vaccines.

The COVID-19 pandemic was accompanied by an unprecedented surveillance effort. The resulting data were and will continue to be critical for surveillance and control of SARS-CoV-2. However, some genomic surveillance methods experienced challenges as the virus evolved, resulting in incomplete and poor quality data. Complete and quality coverage, especially of the S-gene, is important for supporting the selection of vaccine candidates. As such, we developed a robust method to target the S-gene for amplification and sequencing. By focusing on the S-gene and imposing strict coverage and quality metrics, we hope to increase the quality of surveillance data for this continually evolving gene. Our technique is currently being deployed globally to partner laboratories, and public health representatives from 79 countries have received hands-on training and support. Expanding access to quality surveillance methods will undoubtedly lead to earlier detection of novel variants and better inform vaccine strain selection.

Aspergillus versicolor is ubiquitous in the environment and is particularly abundant in damp indoor spaces. Exposure to Aspergillus species, as well as other environmental fungi, has been linked to respiratory health outcomes, including asthma, allergy, and even local or disseminated infection. However, the pulmonary immunological mechanisms associated with repeated exposure to A. versicolor have remained relatively uncharacterized. Here, A. versicolor was cultured and desiccated on rice then placed in an acoustical generator system to achieve aerosolization. Mice were challenged with titrated doses of aerosolized conidia to examine deposition, lymphoproliferative properties, and immunotoxicological response to repeated inhalation exposures. The necessary dose to induce lymphoproliferation was identified, but not infection-like pathology. Further, it was determined that the dose was able to initiate localized immune responses. The data presented in this study demonstrate an optimized and reproducible method for delivering A. versicolor conidia to rodents via nose-only inhalation. Additionally, the feasibility of a long-term repeated exposure study was established. This experimental protocol can be used in future studies to investigate the physiological effects of repeated pulmonary exposure to fungal conidia utilizing a practical and relevant mode of delivery. In total, these data constitute an important foundation for subsequent research in the field.

Carbapenem-resistant Enterobacterales (CRE) are an urgent public health threat. Genomic sequencing is an important tool for investigating CRE. Through the Division of Healthcare Quality Promotion Sentinel Surveillance system, we collected CRE and carbapenem-susceptible Enterobacterales (CSE) from nine clinical laboratories in the USA from 2013 to 2016 and analysed both phenotypic and genomic sequencing data for 680 isolates. We describe the molecular epidemiology and antimicrobial susceptibility testing (AST) data of this collection of isolates. We also performed a phenotype-genotype correlation for the carbapenems and evaluated the presence of virulence genes in Klebsiella pneumoniae complex isolates. These AST and genomic sequencing data can be used to compare and contrast CRE and CSE at these sites and serve as a resource for the antimicrobial resistance research community.

Persons experiencing homelessness are often at increased risk for invasive pneumococcal disease (IPD)* due to underlying health conditions or risk factors (risk conditions) (1,2). Homelessness alone is not an indication for pneumococcal vaccination according to current Advisory Committee on Immunization Practices (ACIP) recommendations (3): adults aged ≥65 years or 19–64 years with certain underlying medical conditions or risk factors† with no previous or unknown history of receipt of pneumococcal conjugate vaccine (PCV) should receive 1 dose of either 20-valent or 15-valent PCV (PCV20 or PCV15, respectively). On November 29, 2022, El Paso (Colorado) County Public Health (EPCPH) was informed by a single hospital of three cases of IPD among persons experiencing homelessness, with all illness onset dates occurring within a single week.

OBJECTIVE: To learn about the perceptions of healthcare personnel (HCP) on the barriers they encounter when performing infection prevention and control (IPC) practices in labor and delivery to help inform future IPC resources tailored to this setting. DESIGN: Qualitative focus groups. SETTING: Labor and delivery units in acute-care settings. PARTICIPANTS: A convenience sample of labor and delivery HCP attending the Infectious Diseases Society for Obstetrics and Gynecology 2022 Annual Meeting. METHODS: Two focus groups, each lasting 45 minutes, were conducted by a team from the Centers for Disease Control and Prevention. A standardized script facilitated discussion around performing IPC practices during labor and delivery. Coding was performed by 3 reviewers using an immersion-crystallization technique. RESULTS: In total, 18 conference attendees participated in the focus groups: 67% obstetrician-gynecologists, 17% infectious disease physicians, 11% medical students, and 6% an obstetric anesthesiologist. Participants described the difficulty of consistently performing IPC practices in this setting because they often respond to emergencies, are an entry point to the hospital, and frequently encounter bodily fluids. They also described that IPC training and education is not specific to labor and delivery, and personal protective equipment is difficult to locate when needed. Participants observed a lack of standardization of IPC protocols in their setting and felt that healthcare for women and pregnant people is not prioritized on a larger scale and within their hospitals. CONCLUSIONS: This study identified barriers to consistently implementing IPC practices in the labor and delivery setting. These barriers should be addressed through targeted interventions and the development of obstetric-specific IPC resources.