BACKGROUND: Influenza vaccine effectiveness can be reduced in older adults and among repeatedly vaccinated groups. Results from year 1 of "PIVOT," a randomized trial among adults aged ≥65 years in Hong Kong, showed that adjuvanted (Adj), high-dose (HD), and recombinant hemagglutinin (rHA) vaccines induced greater antibody responses against vaccine viruses than standard-dose (SD) influenza vaccine. Here, we examine the breadth of A(H3N2)-reactive antibodies induced during the first 2 study years (2017/2018, 2018/2019), and compare participants who received influenza vaccination annually, or not at all, for 5 years preceding enrollment. METHODS: 14-20 PIVOT participants per vaccine and prior vaccination group (0/5 or 5/5 prior years) who provided sera on days 0, 30, and 182 in year 1 and days 0 and 30 in year 2 were assessed. Hemagglutination inhibition (HAI) antibody titers were measured against 30 viruses spanning 1968 to 2018. RESULTS: In year 1, rHA and Adj but not HD vaccines induced titers ≥40 and titer rises ≥4-fold (seroconversion) against significantly more strains than SD vaccine among participants vaccinated 0/5 prior years. Only rHA and Adj vaccines induced titers ≥40 against post-vaccine strains. Antibody responses were poor among participants vaccinated 5/5 compared with 0/5 prior years and only rHA increased the breadth of seroconversion compared with the SD vaccine in this group. Antibody responses were weaker across groups in year 2. CONCLUSIONS: The results suggest that Adj and particularly rHA vaccines may improve the breadth of protection against A(H3N2) viruses but may not overcome attenuating effects of repeated vaccination in older adults. CLINICAL TRIALS REGISTRATION: NCT03330132.

During the 2023-2024 respiratory syncytial virus (RSV) season, vaccination was recommended for adults ≥60 years based on shared clinical decision-making with their healthcare providers. We examined RSV vaccine uptake and characteristics associated with uptake among age-eligible Kaiser Permanente Southern California (KPSC) patients. Our study cohort included all patients ≥60 years from September 23, 2023 (i.e., date RSV vaccination first became available at KPSC; N = 1,003,132) to April 9, 2024 (i.e., end of local RSV season). To identify sociodemographic and clinical characteristics associated with RSV vaccination, we used multivariable robust Poisson regression to estimate the adjusted relative risk (aRR) and 95 % CI. Overall, 7.6 % of patients were vaccinated for RSV. In multivariable regression analyses, those aged 70-79.9 years (aRR: 1.36; 95 % CI: 1.34-1.39) and aged ≥80 years (aRR: 1.35; 95 % CI: 1.32-1.38) were more likely to be vaccinated, compared with those aged 60-69.9 years. Compared with Non-Hispanic White patients, Asian (aRR: 0.95; 95 % CI: 0.93-0.97), Hispanic (aRR: 0.52; 95 % CI: 0.51-0.54), Non-Hispanic Black (aRR: 0.69; 95 % CI: 0.67-0.71), Pacific Islander (aRR: 0.91; 95 % CI: 0.84-0.98), and Native American or Alaska Native (aRR: 0.80; 95 % CI: 0.70-0.92) patients were less likely to be vaccinated. Those in higher neighborhood deprivation quartiles were less likely to be vaccinated (Q2: aRR: 0.86; 95 % CI: 0.85-0.88; Q3: aRR: 0.77; 95 % CI: 0.76-0.79; and Q4: aRR: 0.67; 95 % CI: 0.65-0.68), compared with those in the lowest deprivation quartile. We found low vaccination uptake and identified disparities in vaccination that might exacerbate existing disparities in RSV infection and severe RSV disease among certain populations. CDC's ACIP recently updated their recommendations for all adults 75+ years, and this might begin to address these disparities.

INTRODUCTION: We aim to assess HPV vaccine administration among privately insured populations before and during the COVID-19 pandemic in the United States and stratify the assessments by demographic and geographic characteristics. METHODS: Using the Merative MarketScan Commercial Claims and Encounters Database, we estimated monthly and yearly HPV vaccine administration among people aged 9-26 from 2019 to 2022, measured as the proportion of the enrolled population who received ≥ 1 dose of HPV vaccine during that month or year, and their relative percent change from 2020 to 2022, compared to the same period in 2019, overall and stratified by age group, sex, and urbanicity. RESULTS: HPV vaccine administration in 2020, 2021, and 2022 was lower than in 2019 and continued to decline for all age groups. The relative percent change in rate in 2022 relative to 2019 was -6.0% among children, -38.3% among adolescents, and -42.5% among young adults. The patterns were similar across subgroups, with certain disparities in magnitude. By subpopulations, the highest percent declines in 2022 relative to 2019 in each age group were observed among children in rural areas (-13.5%), male adolescents (-39.8%), and young adults in rural areas (-46.0%). CONCLUSION: During the COVID-19 pandemic, HPV vaccine administration dropped substantially and had not exceeded the pre-pandemic levels by the end of 2022, with larger declines seen among male adolescents and young adults in rural areas. Our results highlight the need for continuing monitoring and targeted intervention strategies to improve HPV vaccine administration.

BACKGROUND: Assessing the impact of influenza epidemics provides useful information to assess both population and healthcare system burden and can inform prevention and control measures for seasonal epidemics, such as vaccination and antivirals. Furthermore, it is an important component of pandemic preparedness. METHODS: We assessed and compared three influenza impact parameters: influenza-associated excess respiratory mortality, hospitalizations and ICU admissions, under the World Health Organization Pandemic Influenza Severity Assessment framework. We used a generalized additive model to estimate these parameters from 1998 through 2019 in Hong Kong based on historical mortality, hospitalization, ICU admission and influenza surveillance data. Intensity thresholds by influenza type were estimated using quantiles from the distribution of peak values of the parameters from 1998 through 2017 and were compared to the real-time estimates of excess parameters in 2018-2019. Influenza death and hospitalization data were used for validation. FINDINGS: There was good agreement between the different impact parameters after comparing the 2018-2019 data to the thresholds. The 2019 influenza A epidemic was characterized as having moderate impact overall and in all age groups, except 0-64 years for whom the excess ICU impact was high; whereas the 2018 influenza B epidemic was characterized as having very high impact overall and in all age groups. INTERPRETATION: The impact of influenza epidemics can vary from year to year. The PISA framework facilitates the impact assessment of seasonal influenza epidemics using different data sources and can be implemented in both real-time or at the end of seasons as policy makers and public health officials prepare for the next seasonal epidemic.

Introduction: Understanding levels of HIV testing among populations at risk for acquisition is essential to meeting the goal of the United Nations that 95% of individuals living with HIV know their status. This study assessed HIV testing prevalence among men who had sex with men (MSM), characteristics of MSM who have never tested for HIV, and missed testing opportunities in Hanoi, Vietnam.Methods: We measured the prevalence of never testing for HIV and missed opportunities for testing in the baseline data of a cohort study of MSM recruited in 2017-2019 in Hanoi. Logistic regression analysis characterized MSM who had never tested prior to cohort participation.Results: Of 1,893 MSM enrolled in the cohort, 39.4% had never previously tested for HIV. MSM with children (aOR 1.75, 95% CI 1.09-2.82) and those who did not know or remember having a male partner living with HIV (aOR 1.41, 95% CI 1.07-1.84) were more likely to have never tested. Older age, university education, higher income, and having a male partner living with HIV were associated with a lower likelihood of never having been tested. The most common missed testing opportunities to test MSM who had never been tested were when receiving free condoms from health educators (35.3%), testing for other sexually transmitted infections (STIs) (23.3%), reporting their MSM status to healthcare workers (16.4%), and receiving an STI diagnosis (13.0%). The most common barriers identified by MSM who had never tested were fear of seeking health care due to their sexual orientation (82.7%) and having been refused healthcare due to their sexual oreitnation (76.2%).Conclusions: Facilitating provider-initiated HIV testing in STI clinics and other healthcare services, community-based testing, and HIV self-test kits should enhance HIV testing options for young MSM, especially those with lower education and income.

OBJECTIVES: To examine if point-of-care urine tenofovir testing-informed counseling could be used to improve virologic suppression (VS) among participants with virologic failure (VF) after ≥1 prior round of enhanced adherence counseling (EAC). METHODS: Participants were enrolled from 42 clinics across Namibia. At each monthly medication pick-up, participants completed the point-of-care urine test and received EAC informed by this testing (EAC+). If VS was not achieved after 3 months of EAC+, up to 3 additional rounds of EAC+ were provided, with resistance testing at month (M)9. RESULTS: Of 310 potentially-eligible participants across 42 clinics in Namibia, we enrolled 211 participants with VF (median age 33 years, 61% female); 195 reached M3 defined as receiving EAC+ and follow-up viral load testing; 169 achieved VS within M3 (87%, p<0(.)001) and 97% by M9 (181/186) compared to 40% (22/55) prior to the intervention (p<0.001). Resistance testing was performed in five remaining participants with VF at M9, of whom 1/5 (20%) developed dolutegravir resistance. CONCLUSIONS: The urine tenofovir assay when incorporated into adherence counseling has potential to be a cost-effective intervention among participants failing tenofovir-based regimens, increasing VS to 97% in those failing TLD. Encouraging results of this pre-post intervention will be rigorously tested in a randomized trial.

The SARS-CoV-2 BA.2.86 lineage, and its sublineage JN.1 in particular, achieved widespread transmission in the US during winter 2023-24. However, this surge in infections was not accompanied by COVID-19 hospitalizations and mortality commensurate with prior waves. To understand shifts in COVID-19 epidemiology associated with JN.1 emergence, we compared characteristics and clinical outcomes of time-matched cases infected with BA.2.86 lineages (predominantly representing JN.1) versus co-circulating XBB-derived lineages in December, 2023 and January, 2024. Cases infected with BA.2.86 lineages received greater numbers of COVID-19 vaccine doses, including XBB.1.5-targeted boosters, in comparison to cases infected with XBB-derived lineages. Additionally, cases infected with BA.2.86 lineages experienced greater numbers of documented prior SARS-CoV-2 infections. Cases infected with BA.2.86 lineages also experienced lower risk of progression to severe clinical outcomes requiring emergency department consultations or hospital admission. Sensitivity analyses suggested under-ascertainment of prior infections could not explain this apparent attenuation of severity. Our findings implicate escape from immunity acquired from prior vaccination or infection in the emergence of the JN.1 lineage and suggest infections with this lineage are less likely to experience clinically-severe disease. Monitoring of immune escape and clinical severity in emerging SARS-CoV-2 variants remains a priority to inform responses.

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: Annual influenza vaccination is recommended for older adults but repeated vaccination with standard-dose influenza vaccine has been linked to reduced immunogenicity and effectiveness, especially against A(H3N2) viruses. METHODS: Community-dwelling Hong Kong adults aged 65-82 years were randomly allocated to receive 2017-2018 standard-dose quadrivalent, MF59-adjuvanted trivalent, high-dose trivalent, and recombinant-HA quadrivalent vaccination. Antibody response to unchanged A(H3N2) vaccine antigen was compared among participants with and without self-reported prior year (2016-2017) standard-dose vaccination. RESULTS: Mean fold rise (MFR) in antibody titers from day 0 to day 30 by hemagglutination inhibition and virus microneutralization assays were lower among 2017-2018 standard-dose and enhanced vaccine recipients with (range, 1.7-3.0) versus without (range, 4.3-14.3) prior 2016-2017 vaccination. MFR was significantly reduced by about one-half to four-fifths for previously vaccinated recipients of standard-dose and all 3 enhanced vaccines (β range, .21-.48). Among prior-year vaccinated older adults, enhanced vaccines induced higher 1.43 to 2.39-fold geometric mean titers and 1.28 to 1.74-fold MFR versus standard-dose vaccine by microneutralization assay. CONCLUSIONS: In the context of unchanged A(H3N2) vaccine strain, prior-year vaccination was associated with reduced antibody response among both standard-dose and enhanced influenza vaccine recipients. Enhanced vaccines improved antibody response among older adults with prior-year standard-dose vaccination.

INTRODUCTION: We assessed trends in HIV and syphilis prevalence, HIV incidence, related risk factors, and preventive behaviors among men who have sex with men (MSM) in Vietnam from 2015 to 2020. METHODS: Data originated from the HIV Sentinel Surveillance Plus system, which sampled MSM at venues and hotspots in seven of Vietnam's 63 provinces in 2015, 2016, 2018, and 2020 (N = 1100-1445 per year; ∼150-300 per province per year). RESULTS: HIV prevalence estimates increased from 6.6% (95% CI 4.5-9.6) in 2015 to 13.8% (95% CI 10.5-18.2, p = .001 for trend) in 2020 overall, and separately in An Giang, Can Tho, Hai Phong, and Khanh Hoa provinces but not in Ho Chi Minh City, Hanoi, or Kien Giang. Syphilis prevalence increased from 2.7% (95% CI 1.4-5.1) in 2015 to 12.6% (95% CI 8.7-18.0) in 2020 overall (p < .001 for trend), and separately in An Giang, Can Tho, and Hai Phong provinces but not in Ho Chi Minh City or Kien Giang. We calculated time-at-risk from first anal sex to first HIV-positive or last HIV-negative test to estimate HIV incidence. Estimated HIV incidence suggested increasing rates of seroconversion from 1.36 per 100 person-years experienced by participants in 2015 to 2.61 per 100 person-years among participants in 2020 (hazard ratio per year 1.13, 95% CI 1.08-1.18, p < .001). There was a statistically significant increase in HIV testing, STI testing, and receipt of free condoms over the period (p < .05 for trend), and a statistically significant decrease in amphetamine use (p = .043 for trend). CONCLUSIONS: Despite prevention efforts and improvements in some risk indicators, consecutive cross-sectional sampling results provide evidence of increasing incidence of HIV and syphilis among MSM in Vietnam, especially outside the major cities. Aggressive HIV prevention and treatment services can be expanded while conducting deeper investigations into the causes of these increases.

BACKGROUND: In 2014, UNAIDS set a goal to end the AIDS epidemic by achieving targets for the percentage of people living with HIV who were aware of their status, on antiretroviral therapy (ART), and virally suppressed. In 2020, these targets were revised to 95% for each measure (known as 95-95-95), to be reached among people living with HIV by 2025. We used data from the Fifth Botswana AIDS Impact Survey (BAIS V) to measure progress towards these testing and treatment targets in Botswana. METHODS: BAIS V used a two-stage cluster design to obtain a nationally representative sample of people aged 15-64 years in Botswana. During March-August, 2021, 14 763 consenting participants were interviewed and tested for HIV in their households by survey teams. HIV-positive specimens were tested for viral load, presence of antiretroviral drugs, and recency of infection using the HIV-1 limiting antigen avidity enzyme immunoassay. Estimates of HIV-positive status and use of ART were based on self-report and the analysis of blood specimens for antiretroviral drugs. Viral load suppression was defined as an HIV RNA concentration of less than 1000 copies per mL. HIV incidence was calculated using the recent infection testing algorithm. Data were weighted to account for the complex survey design. FINDINGS: The national HIV prevalence in Botswana among people aged 15-64 years was 20·8% and the annual incidence of HIV infection was 0·2%. 95·1% (men 93·0%, women 96·4%) of people living with HIV aged 15-64 years were aware of their status, 98·0% (men 97·2%, women 98·4%) of those aware were on ART, and 97·9% (men 96·6%, women 98·6%) of those on ART had viral load suppression. Among young people (aged 15-24 years) living with HIV, 84·5% were aware of their status, 98·5% of those aware were on ART, and 91·6% of those on ART had viral load suppression. The prevalance of viral load suppression among all people living with HIV was 91·8%, and varied by district-ranging from 85·3% in Gaborone to 100·0% in Selibe Phikwe. INTERPRETATION: BAIS V is the first population-based survey worldwide to report the achievement of the UNAIDS 95-95-95 goals, both overall and among women. Strategies to reach undiagnosed men and young people, including young women, are needed. FUNDING: US President's Emergency Plan for AIDS Relief.

The nucleoprotein (NP) is a vital target for the heterosubtypic immunity of CD8(+) cytotoxic T lymphocytes (CTLs) due to its conservation among influenza virus subtypes. To further enhance the T cell immunity of NP, autophagy-inducing peptide C5 (AIP-C5) from the CFP10 protein of Mycobacterium tuberculosis was used. Mice were immunized intranasally (i.n.) with human adenoviral vectors, HAd-C5-NP(H7N9) or HAd-NP(H7N9), expressing NP of an H7N9 influenza virus with or without the AIP-C5, respectively. Both vaccines developed similar levels of NP-specific systemic and mucosal antibody titers; however, there was a significantly higher number of NP-specific CD8 T cells secreting interferon-gamma (IFN-γ) in the HAd-C5-NP(H7N9) group than in the HAd-NP(H7N9) group. The HAd-C5-NP(H7N9) vaccine provided better protection following the challenge with A/Puerto Rico/8/1934(H1N1), A/Hong Kong/1/68(H3N2), A/chukkar/MN/14951-7/1998(H5N2), A/goose/Nebraska/17097/2011(H7N9), or A/Hong Kong/1073/1999(H9N2) influenza viruses compared to the HAd-NP(H7N9) group. The autophagy transcriptomic gene analysis of the HAd-C5-NP(H7N9) group revealed the upregulation of some genes involved in the positive regulation of the autophagy process. The results support further exploring the use of NP and AIP-C5 for developing a universal influenza vaccine for pandemic preparedness.

Cardiovascular diseases (CVDs) are a major source of morbidity and mortality worldwide. Despite a decline of ≈30% over the past decade, heart disease remains the leading killer of Americans.1 For rare and familial forms of CVD, we are increasingly recognizing single-gene mutations that impart relatively large effects on individual phenotype. Examples include inherited forms of cardiomyopathy, arrhythmias, and aortic diseases. However, the prevalence of monogenic disorders typically accounts for a small proportion of the total CVD observed in the population. CVDs in the general population are complex diseases, with several contributing genetic and environmental factors. Although recent progress in monogenic disorders has occurred, we have seen a period of intense investigation to identify the genetic architecture of more common forms of CVD and related traits. | | Genomics serves several roles in cardiovascular health and disease, including disease prediction, discovery of genetic loci influencing CVD, functional evaluation of these genetic loci to understand mechanisms, and identification of therapeutic targets. For single-gene CVDs, progress has led to several clinically useful diagnostic tests, extending our ability to inform the management of afflicted patients and their family members. However, there has been little progress in developing genetic testing for complex CVD because individual common variants have only a modest impact on risk. The study of the genomics of complex CVDs is further challenged by the influence of environmental variables, phenotypic heterogeneity, and pathogenic complexity. Characterization of the clinical phenotype requires consideration of the clinical details of the diseases and traits under study.

Definitive diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD) relies on the examination of brain tissues for the pathological prion protein (PrP(Sc)). Our previous study revealed that PrP(Sc)-seeding activity (PrP(Sc)-SA) is detectable in skin of sCJD patients by an ultrasensitive PrP(Sc) seed amplification assay (PrP(Sc)-SAA) known as real-time quaking-induced conversion (RT-QuIC). A total of 875 skin samples were collected from 2 cohorts (1 and 2) at autopsy from 2-3 body areas of 339 cases with neuropathologically confirmed prion diseases and non-sCJD controls. The skin samples were analyzed for PrP(Sc)-SA by RT-QuIC assay. The results were compared with demographic information, clinical manifestations, cerebrospinal fluid (CSF) PrP(Sc)-SA, other laboratory tests, subtypes of prion diseases defined by the methionine (M) or valine (V) polymorphism at residue 129 of PrP, PrP(Sc) types (#1 or #2), and gene mutations in deceased patients. RT-QuIC assays of the cohort #1 by two independent laboratories gave 87.3% or 91.3% sensitivity and 94.7% or 100% specificity, respectively. The cohort #2 showed sensitivity of 89.4% and specificity of 95.5%. RT-QuIC of CSF available from 212 cases gave 89.7% sensitivity and 94.1% specificity. The sensitivity of skin RT-QuIC was subtype dependent, being highest in sCJDVV1-2 subtype, followed by VV2, MV1-2, MV1, MV2, MM1, MM1-2, MM2, and VV1. The skin area next to the ear gave highest sensitivity, followed by lower back and apex of the head. Although no difference in brain PrP(Sc)-SA was detected between the cases with false negative and true positive skin RT-QuIC results, the disease duration was significantly longer with the false negatives [12.0 ± 13.3 (months, SD) vs. 6.5 ± 6.4, p < 0.001]. Our study validates skin PrP(Sc)-SA as a biomarker for the detection of prion diseases, which is influenced by the PrP(Sc) types, PRNP 129 polymorphisms, dermatome sampled, and disease duration.

BACKGROUND: Understanding the long-term impact of the COVID-19 pandemic on health care utilization is important to health care organizations and policy makers for strategic planning, as well as to researchers when designing studies that use observational electronic health record data during the pandemic period. OBJECTIVE: To evaluate changes in health care utilization across all care settings among a large diverse insured population in the United States during the COVID-19 pandemic. METHODS: We conducted a retrospective cohort study within 8 health care organizations participating in the Vaccine Safety Datalink Project using electronic health record data from members of all ages during January 1, 2017 - December 31, 2021. The visit rates per person-year were calculated monthly during the study period for four health care settings combined as well as by inpatient, emergency department (ED), outpatient, and telehealth settings, both among all members and members without COVID-19. Difference-in-difference analysis and interrupted time series analysis were performed to assess the changes in visit rates from the pre-pandemic period (January 2017 to February 2020) to the early pandemic period (April 2020 to December 2020) and the later pandemic period (July 2021 to December 2021), respectively. An exploratory analysis was also conducted to assess trends through June 2023 at one of the largest sites, Kaiser Permanente Southern California (KPSC). RESULTS: The study included more than 11 million members from 2017 to 2021. Compared with the pre-pandemic period, we found reductions in visit rates during the early pandemic period for all in-person care settings. During the later pandemic period, overall utilization reached 8.36 visits per person-year, exceeding the pre-pandemic level of 7.49 visits per person-year in 2019 (adjusted percent change = 5.1%; 95% CI 0.6% to 9.9%); inpatient and ED visits returned to pre-pandemic levels, 0.103 and 0.275 visits per person-year respectively among all members, although they remained 7.5% and 8.0% lower than pre-pandemic levels among members without a documented history of COVID-19. Telehealth visits, which were approximately 42% of the volume of outpatient visits during the later pandemic period, were increased by 97.5% (95% CI 86.0% to 109.7%) from 0.865 visits per person-year in 2019 to 2.35 visits per person-year in the later pandemic period. The trends in KPSC were like those of the entire study population. Visit rates from January 2022 to June 2023 were stable and appeared to be a continuation of the utilization levels observed at the end of 2021. CONCLUSIONS: Telehealth services became a mainstay of the health care system during the late COVID-19 pandemic period. Inpatient and ED visits returned to pre-pandemic levels, although they remained low among members without evidence of COVID-19. Our findings provide valuable information for longer-term strategic resource allocation for patient care in the post-pandemic period and for designing observational studies involving the pandemic period.

OBJECTIVES: To measure the effectiveness of chlamydia control strategies, we must estimate infection incidence over time. Available data, including survey-based infection prevalence and case reports, have limitations as proxies for infection incidence. We therefore developed a novel method for estimating chlamydial incidence. METHODS: We linked a susceptible infectious mathematical model to serodynamics data from the National Health and Nutritional Examination Survey, as well as to annual case reports. We created four iterations of this model, varying assumptions about how the method of infection clearance (via treatment seeking, routine screening or natural clearance) relates to long-term seropositivity. Using these models, we estimated annual infection incidence for women aged 18-24 and 25-37 years in 2014. To assess model plausibility, we also estimated natural clearance for the same groups. RESULTS: Of the four models we analysed, the model that best explained the empirical data was the one in which longer-lasting infections, natural clearance and symptomatic infections all increased the probability of long-term seroconversion. Using this model, we estimated 5910 (quartile (Q)1, 5330; Q3, 6500) incident infections per 100 000 women aged 18-24 years and 2790 (Q1, 2500; Q3, 3090) incident infections per 100 000 women aged 25-37 years in 2014. Furthermore, we estimated that natural clearance rates increased with age. CONCLUSIONS: Our method can be used to estimate the number of chlamydia infections each year, and thus whether infection incidence increases or decreases over time and after policy changes. Furthermore, our results suggest that clearance via medical intervention may lead to short-term or no seroconversion, and the duration of untreated chlamydial infection may vary with age, underlining the complexity of chlamydial infection dynamics.

Short-term probabilistic forecasts of the trajectory of the COVID-19 pandemic in the United States have served as a visible and important communication channel between the scientific modeling community and both the general public and decision-makers. Forecasting models provide specific, quantitative, and evaluable predictions that inform short-term decisions such as healthcare staffing needs, school closures, and allocation of medical supplies. In 2020, the COVID-19 Forecast Hub (https://covid19forecasthub.org/) collected, disseminated, and synthesized hundreds of thousands of specific predictions from more than 50 different academic, industry, and independent research groups. This manuscript systematically evaluates 23 models that regularly submitted forecasts of reported weekly incident COVID-19 mortality counts in the US at the state and national level. One of these models was a multi-model ensemble that combined all available forecasts each week. The performance of individual models showed high variability across time, geospatial units, and forecast horizons. Half of the models evaluated showed better accuracy than a naïve baseline model. In combining the forecasts from all teams, the ensemble showed the best overall probabilistic accuracy of any model. Forecast accuracy degraded as models made predictions farther into the future, with probabilistic accuracy at a 20-week horizon more than 5 times worse than when predicting at a 1-week horizon. This project underscores the role that collaboration and active coordination between governmental public health agencies, academic modeling teams, and industry partners can play in developing modern modeling capabilities to support local, state, and federal response to outbreaks.Competing Interest StatementAV, MC, and APP report grants from Metabiota Inc outside the submitted work.Funding StatementFor teams that reported receiving funding for their work, we report the sources and disclosures below. CMU-TimeSeries: CDC Center of Excellence, gifts from Google and Facebook. CU-select: NSF DMS-2027369 and a gift from the Morris-Singer Foundation. COVIDhub: This work has been supported by the US Centers for Disease Control and Prevention (1U01IP001122) and the National Institutes of General Medical Sciences (R35GM119582). The content is solely the responsibility of the authors and does not necessarily represent the official views of CDC, NIGMS or the National Institutes of Health. Johannes Bracher was supported by the Helmholtz Foundation via the SIMCARD Information&amp; Data Science Pilot Project. Tilmann Gneiting gratefully acknowledges support by the Klaus Tschira Foundation. DDS-NBDS: NSF III-1812699. EPIFORECASTS-ENSEMBLE1: Wellcome Trust (210758/Z/18/Z) GT_CHHS-COVID19: William W. George Endowment, Virginia C. and Joseph C. Mello Endowments, NSF DGE-1650044, NSF MRI 1828187, research cyberinfrastructure resources and services provided by the Partnership for an Advanced Computing Environment (PACE) at Georgia Tech, and the following benefactors at Georgia Tech: Andrea Laliberte, Joseph C. Mello, Richard Rick E. &amp; Charlene Zalesky, and Claudia &amp; Paul Raines GT-DeepCOVID: CDC MInD-Healthcare U01CK000531-Supplement. NSF (Expeditions CCF-1918770, CAREER IIS-2028586, RAPID IIS-2027862, Medium IIS-1955883, NRT DGE-1545362), CDC MInD program, ORNL and funds/computing resources from Georgia Tech and GTRI. IHME: This work was supported by the Bill &amp; Melinda Gates Foundation, as well as funding from the state of Washington and the National Science Foundation (award no. FAIN: 2031096). IowaStateLW-STEM: Iowa State University Plant Sciences Institute Scholars Program, NSF DMS-1916204, NSF CCF-1934884, Laurence H. Baker Center for Bioinformatics and Biological Statistics. JHU_IDD-CovidSP: State of California, US Dept of Health and Human Services, US Dept of Homeland Security, US Office of Foreign Disaster Assistance, Johns Hopkins Health System, Office of the Dean at Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University Modeling and Policy Hub, Centers fo Disease Control and Prevention (5U01CK000538-03), University of Utah Immunology, Inflammation, &amp; Infectious Disease Initiative (26798 Seed Grant). LANL-GrowthRate: LANL LDRD 20200700ER. MOBS-GLEAM_COVID: COVID Supplement CDC-HHS-6U01IP001137-01. NotreDame-mobility and NotreDame-FRED: NSF RAPID DEB 2027718 UA-EpiCovDA: NSF RAPID Grant # 2028401. UCSB-ACTS: NSF RAPID IIS 2029626. UCSD-NEU: Google Faculty Award, DARPA W31P4Q-21-C-0014, COVID Supplement CDC-HHS-6U01IP001137-01. UMass-MechBayes: NIGMS R35GM119582, NSF 1749854. UMich-RidgeTfReg: The University of Michigan Physics Department and the University of Michigan Office of Research.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:UMass-Amherst IRBAll necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesAll data and code referred to in the manuscript are publicly available. https://github.com/reichlab/covid19-forecast-hub/ https://github.com/reichlab/covidEnsembles https://zoltardata.com/project/44

Introduction Food insecurity has a bidirectional relationship with HIV infection, with hunger driving compensatory risk behaviors, while infection can increase poverty. We used a laboratory recency assay to estimate the timing of HIV infection vis-à-vis the timing of severe food insecurity (SFI).Methods Data from population-based surveys in Zambia, Eswatini, Lesotho, Uganda, and Tanzania and Namibia were used. We defined SFI as having no food ≥three times in the past month. Recent HIV infection was identified using the HIV-1 LAg avidity assay, with a viral load (&gt;1000 copies/ml) and no detectable antiretrovirals indicating an infection in the past 6 months. Logistic regression was conducted to assess correlates of SFI. Poisson regression was conducted on pooled data, adjusted by country to determine the association of SFI with recent HIV infection and risk behaviors, with effect heterogeneity evaluated for each country. All analyses were done using weighted data.Results Of 112,955 participants aged 15-59, 10.3% lived in households reporting SFI. SFI was most common in urban, woman-headed households. Among women and not men, SFI was associated with a two-fold increase in risk of recent HIV infection (adjusted relative risk [aRR] 2.08, 95% CI 1.09-3.97), with lower risk in high prevalence countries (Eswatini and Lesotho). SFI was associated with transactional sex (aRR 1.28, 95% CI 1.17-1.41), a history of forced sex (aRR 1.36, 95% CI 1.11-1.66), and condom-less sex with a partner of unknown or positive HIV status (aRR 1.08, 95% CI 1.02-1.14) in all women, and intergenerational sex (partner ≥10 years older) in women aged 15-24 (aRR 1.23, 95% CI 1.03-1.46), although this was heterogeneous. Recent receipt of food support was protective (aRR 0.36, 95% CI 0.14-0.88).Conclusion SFI increased risk for HIV acquisition in women by two-fold. Worsening food scarcity due to climactic extremes could imperil HIV epidemic control.What is already knownThe link between food insecurity and the adoption of high-risk sexual behaviors as a coping mechanism has been shown in several settings.HIV infection can also drive food insecurity due to debilitating illness reducing productivity, the costs of treatment diverting money from supplies, and potentially reduced labor migration.Food insecurity has been associated with chronic HIV infection, but it has not been linked with HIV acquisition.What are the new findingsThis study of 112,955 adults across six countries in sub-Saharan Africa provides unique information on the association between acute food insecurity and recent HIV infection in women, as well as the potential behavioral and biological mediators, including community viremia as a measure of infectiousness.The data enabled a comprehensive analysis of factors associated with risk of infection, and how these factors differed by country and gender. Women living in food insecure households had a two-fold higher risk of recent HIV acquisition, and reported higher rates of transactional sex, early sexual debut, forced sex, intergenerational sex and sex without a condom with someone of unknown or positive HIV status. This pattern was not seen in men.This study is also the first to demonstrate a protective association for food support, which was associated with a lower risk of recent HIV infection in women.What do the new findings implyIn light of worsening food insecurity due to climate change and the recent COVID-19 pandemic, our results support further exploration of gender-specific pathways of response to acute food insecurity, particularly how women’s changes in sexual behavior heighten their risk of HIV acquisition.These and other data support the inclusion of food insecurity in HIV risk assessments for women, as well as the exploration of provision of food support to those households at highest risk based on geographic and individual factors.Competing Interest StatementThe authors have declared no competing interest.Clinical Protocols https://phia.icap.columbia.edu/ Funding StatementThis project has been supported by the Presid nt Emergency Plan for AIDS Relief (PEPFAR) through the Centers for Disease Control and Prevention (CDC) under the terms of cooperative agreement #U2GGH001226.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:The PHIA protocol and data collection tools were approved by national ethics committees for each country, and the institutional review boards at Columbia University Irving Medical Center, the US Centers for Disease Control and Prevention (CDC) and the University of California, San Francisco in the case of Namibia. Due to the inclusion of six countries and the multiple ethical boards involved, we are providing the protocol numbers for the Columbia University Irving Medical Center, which approved all protocols (AAAQ0753, AAAQ7860, AAAQ8408, AAAQ8537, AAAR2051, AAAQ889). All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesAll data used in this manuscript are publicly available at https://phia-data.icap.columbia.edu/. https://phia-data.icap.columbia.edu/

Background The 2017-2018 US influenza season was severe with low vaccine effectiveness. Circulating A(H3N2) viruses from multiple genetic groups were antigenically similar to cell-grown vaccine strains. However, most influenza vaccines are egg-propagated.Methods Serum was collected shortly after illness onset from 15 PCR confirmed A(H3N2) infected cases and 15 uninfected (controls) hospitalized adults enrolled in an influenza vaccine effectiveness study.Geometric mean titers against egg- and cell-grown A/Hong Kong/4801/2014 A(H3N2) vaccine strains and representative circulating viruses (including A/Washington/16/2017) were determined by microneutralization (MN) assays. Independent effects of strain-specific titers on susceptibility were estimated by logistic regression.Results MN titers against egg-A/Hong Kong were significantly higher among those who were vaccinated (MN GMT: 173 vs 41; P = 0.01). However, antibody titers to cell-grown viruses were much lower in all individuals (P&gt;0.05) regardless of vaccination. In unadjusted models, a 2-fold increase in MN titers against egg-A/Hong Kong was not significantly protective against infection (29% reduction; p=0.09), but a similar increase in cell-A/Washington titer (3C.2a2) was protective (60% reduction; p=0.02). A similar increase in egg-A/Hong Kong titer was not significantly associated with odds of infection when adjusting for MN titers against A/Washington (15% reduction; P=0.61). A 54% reduction of odds of infection was observed with a 2-fold increase in A/Washington (not significant; P=0.07), adjusted for egg-A/Hong Kong titer.Conclusion Although individuals vaccinated in 2017-2018 had high antibody titers against the egg-adapted vaccine strain, antibody responses to cell-grown circulating viruses may not be sufficient to provide protection, likely due to egg-adaptation in the vaccine.We thank Maryna Eichelberger, Hongquan Wan, Jin Gao, and Laura Couzens (Food and Drug Administration) for technical support and providing reassortant influenza viruses for use in the enzyme-linked lectin assays. St Jude Children’s Research Hospital provided plasmids that were used to generate these reassortant influenza viruses. We thank Mrs F Liaini Gross, Lauren Horner and Makeda Kay from Influenza Division, Centers for Disease Control and Prevention for technical support for virus propagation and specimen management.

We present a small molecule chemotype, identified by an orthogonal drug screen, exhibiting nanomolar activity against members of all the six viral families causing most human respiratory viral disease, with a demonstrated barrier to resistance development. Antiviral activity is shown in mammalian cells, including human primary bronchial epithelial cells cultured to an air-liquid interface and infected with SARS-CoV-2. In animals, efficacy of early compounds in the lead series is shown by survival (for a coronavirus) and viral load (for a paramyxovirus). The drug target is shown to include a subset of the protein 14-3-3 within a transient host multi-protein complex containing components implicated in viral lifecycles and in innate immunity. This multi-protein complex is modified upon viral infection and largely restored by drug treatment. Our findings suggest a new clinical therapeutic strategy for early treatment upon upper respiratory viral infection to prevent progression to lower respiratory tract or systemic disease. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.

Host immune responses are a key source of selective pressure driving pathogen evolution. Emergence of many SARS-CoV-2 lineages has been associated with improvements in their ability to evade population immunity resulting from both vaccination and infection. Here we show diverging trends of escape from vaccine-derived and infection-derived immunity for the emerging XBB/XBB.1.5 Omicron lineage. Among 31,739 patients tested in ambulatory settings in Southern California from December, 2022 to February, 2023, adjusted odds of prior receipt of 2, 3, 4, and >=5 COVID-19 vaccine doses were 10% (95% confidence interval: 1-18%), 11% (3-19%), 13% (3-21%), and 25% (15-34%) lower, respectively, among cases infected with XBB/XBB.1.5 than among cases infected with other co-circulating lineages. Similarly, prior vaccination was associated with greater protection against progression to hospitalization among cases with XBB/XBB.1.5 than among non-XBB/XBB.1.5 cases (70% [30-87%] and 48% [7-71%], respectively, for recipients of >=4 doses). In contrast, cases infected with XBB/XBB.1.5 had 17% (11-24%) and 40% (19-65%) higher adjusted odds of having experienced 1 and >=2 prior documented infections, respectively, including with pre-Omicron variants. As immunity acquired from SARS-CoV-2 infection becomes increasingly widespread, fitness costs associated with enhanced vaccine sensitivity in XBB/XBB.1.5 may be offset by increased ability to evade infection-derived host responses. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.

Background: We estimated SARS-CoV-2 Delta and Omicron-specific effectiveness of 2 and 3 mRNA COVID-19 vaccine doses in adults against symptomatic illness in US outpatient settings. Method(s): Between October 1, 2021, and February 12, 2022, research staff consented and enrolled eligible participants who had fever, cough, or loss of taste or smell and sought outpatient medical care or clinical SARS-CoV-2 testing within 10 days of illness onset. Using the test-negative design, we compared the odds of receiving 2 or 3 mRNA COVID-19 vaccine doses among SARS-CoV-2 cases versus controls using logistic regression. Regression models were adjusted for study site, age, onset week, and prior SARS-CoV-2 infection. Vaccine effectiveness (VE) was calculated as (1 - adjusted odds ratio) x 100%. Result(s): Among 3847 participants included for analysis, 574 (32%) of 1775 tested positive for SARS-CoV-2 during the Delta predominant period and 1006 (56%) of 1794 participants tested positive during the Omicron predominant period. When Delta predominated, VE against symptomatic illness in outpatient settings was 63% (95% CI: 51% to 72%) among mRNA 2-dose recipients and 96% (95% CI: 93% to 98%) for 3-dose recipients. When Omicron predominated, VE was 21% (95% CI: -6% to 41%) among 2-dose recipients and 62% (95% CI: 48% to 72%) among 3-dose recipients. Conclusion(s): In this adult population, 3 mRNA COVID-19 vaccine doses provided substantial protection against symptomatic illness in outpatient settings when the Omicron variant became the predominant cause of COVID-19 in the U.S. These findings support the recommendation for a 3rd mRNA COVID-19 vaccine dose. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license.

To understand genome evolution in a group of microbes, we need to know the timing of events such as duplications, deletions and horizontal transfers. A common approach is to perform a gene-tree / species-tree reconciliation. While a number of software packages perform this type of analysis, none are geared toward a complete reconstruction for all families in an entire clade. Here we describe an update to the xenoGI software package which allows users to perform such an analysis using the newly developed DTLOR (duplication-transfer-loss-origin-rearrangement) reconciliation model starting from genome sequences as input.

Host immune responses are a key source of selective pressure driving pathogen evolution. Emergence of many SARS-CoV-2 lineages has been associated with enhancements in their ability to evade population immunity resulting from both vaccination and infection. Here we show diverging trends of escape from vaccine-derived and infection-derived immunity for the emerging XBB/XBB.1.5 Omicron lineage. Among 31,739 patients tested in ambulatory settings in Southern California from December, 2022 to February, 2023, adjusted odds of prior receipt of 2, 3, 4, and ≥5 COVID-19 vaccine doses were 10% (95% confidence interval: 1-18%), 11% (3-19%), 13% (3-21%), and 25% (15-34%) lower, respectively, among cases infected with XBB/XBB.1.5 than among cases infected with other co-circulating lineages. Similarly, prior vaccination was associated with greater point estimates of protection against progression to hospitalization among cases with XBB/XBB.1.5 than among non-XBB/XBB.1.5 cases (70% [30-87%] and 48% [7-71%], respectively, for recipients of ≥4 doses). In contrast, cases infected with XBB/XBB.1.5 had 17% (11-24%) and 40% (19-65%) higher adjusted odds of having experienced 1 and ≥2 prior documented infections, respectively, including with pre-Omicron variants. As immunity acquired from SARS-CoV-2 infection becomes increasingly widespread, fitness costs associated with enhanced vaccine sensitivity in XBB/XBB.1.5 may be offset by increased ability to evade infection-derived host responses.

More than 30,000 monkeypox (mpox) cases were reported in the United States during the 2022 multinational outbreak; cases disproportionately affected gay, bisexual, and other men who have sex with men (MSM). Substantial racial and ethnic disparities in incidence were also reported (1). The national mpox vaccination strategy* emphasizes that efforts to administer the JYNNEOS mpox vaccine should be focused among the populations at elevated risk for exposure to mpox (2). During May 2022-April 2023, a total of 748,329 first JYNNEOS vaccine doses (of the two recommended) were administered in the United States.(†) During the initial months of the outbreak, lower vaccination coverage rates among racial and ethnic minority groups were reported (1,3); however, after implementation of initiatives developed to expand access to mpox vaccination,(§) coverage among racial and ethnic minority groups increased (1,4). A shortfall analysis was conducted to examine whether the increase in mpox vaccination coverage was equitable across all racial and ethnic groups (5). Shortfall was defined as the percentage of the vaccine-eligible population that did not receive the vaccine (i.e., 100% minus the percentage of the eligible population that did receive a first dose). Monthly mpox vaccination shortfalls were calculated and were stratified by race and ethnicity; monthly percent reductions in shortfall were also calculated compared with the preceding month's shortfall (6). The mpox vaccination shortfall decreased among all racial and ethnic groups during May 2022-April 2023; however, based on analysis of vaccine administration data with race and ethnicity reported, 66.0% of vaccine-eligible persons remained unvaccinated at the end of this period. The shortfall was largest among non-Hispanic Black or African American (Black) (77.9%) and non-Hispanic American Indian or Alaska Native (AI/AN) (74.5%) persons, followed by non-Hispanic White (White) (66.6%) and Hispanic or Latino (Hispanic) (63.0%) persons, and was lowest among non-Hispanic Asian (Asian) (38.5%) and non-Hispanic Native Hawaiian and other Pacific Islander (NH/OPI) (43.7%) persons. The largest percentage decreases in the shortfall were achieved during August (17.7%) and September (8.5%). However, during these months, smaller percentage decreases were achieved among Black persons (12.2% and 4.9%, respectively), highlighting the need for a focus on equity for the entirety of a public health response. Achieving equitable progress in JYNNEOS vaccination coverage will require substantial decreases in shortfalls among Black and AI/AN persons.

During May 10-December 31, 2022, a total of 29,980 confirmed and probable(†) U.S. monkeypox (mpox) cases were reported to CDC, predominantly in cisgender adult men reporting recent same-gender sexual partners (1). Urban-rural differences in health (2) and diagnosis of HIV (3,4) and other sexually transmitted infections (5) are well documented nationally. This report describes urban-rural differences in mpox incidence (cases per 100,000 population) among persons aged 15-64 years, by gender and race and ethnicity. Urbanicity was assessed using the 2013 National Center for Health Statistics (NCHS) Urban-Rural Classification Scheme for Counties (2). Substantial differences in incidence by urbanicity, gender, and race and ethnicity were observed; most (71.0%) cases occurred in persons residing in large central urban areas. Among the cases in large central urban areas, most (95.7%) were in cisgender men. The overall incidence of mpox in the United States was 13.5 per 100,000 persons aged 15-64 years and peaked in August in both urban and rural areas. Among cisgender men, incidence in rural areas was approximately 4% that in large central urban areas (risk ratio [RR] = 0.04). Among cisgender women, incidence in rural areas was approximately 11% that in large central urban areas (RR = 0.11). In both urban and rural areas, incidence among non-Hispanic Black or African American (Black) and Hispanic or Latino (Hispanic) persons was consistently higher than that among non-Hispanic White (White) persons; RRs between Black and White persons were highest in rural areas. Support and maintenance of mpox surveillance and prevention efforts including vaccinations should focus on urban areas with the highest incidence of mpox during the 2022 outbreak; however, surveillance and prevention efforts should include all genders, persons of color, and persons residing in both urban and rural areas who are at increased risk for mpox.

Automated nontreponemal rapid plasma reagin (RPR) tests were recently introduced in the United States for syphilis testing and limited performance data are available. In collaboration with the Association of Public Health Laboratories, three public health laboratories (PHL) were chosen through a competitive selection process to evaluate the performance of three FDA-cleared automated RPR test systems: BioPlex 2200 Syphilis Total & RPR assay (Bio-Rad Laboratories), AIX 1000 (Gold Standard Diagnostics), and ASI Evolution (Arlington Scientific). Panels prepared at the CDC included: a qualitative panel comprised of 734 syphilis reactive/nonreactive sera; a quantitative panel of 50 syphilis reactive sera (RPR titer 1:64 to 1:1,024); and a reproducibility panel of 15 nonreactive and reactive sera (RPR titer 1:1 to 1:64). Panels were shipped frozen to the PHL and tested on the automated RPR systems following manufacturers' instructions. Prior test results were blinded to all laboratories. When compared to manual RPR (Arlington Scientific) performed at the CDC as a reference test, the qualitative panel results demonstrated an overall concordance of 95.9% for AIX 1000, 94.6% for ASI Evolution, and 92.6% for Bioplex RPR; quantitative panel showed within range titer of 2-fold for 94% of specimens for AIX 1000, 68% for ASI Evolution, and 64% for BioPlex RPR, and the reproducibility testing panel demonstrated point estimates ranging from 69 to 95%. Automated RPR instruments could reduce turnaround time and minimize interpretation errors. However, additional evaluations with more specimens could assist laboratories with implementing automated RPR tests and understanding their limitations.

In their Correspondence, Xue and Bloom1 identify an important discrepancy in the sequence data that we provided in our 2016 paper2 on the transmission of influenza virus in Hong Kong during the first wave of the H1N1 pandemic in 2009. The goal of the study was to provide a quantitative approach to characterizing the within-host genetic diversity of influenza virus and how this genomic information might be used in tracking transmission. We have determined that the potential source of this discrepancy was due to the technical limitations of the methods used at the time, which inadvertently led to the reporting of substantially higher levels of within-host diversity than were likely to be present.

Following its emergence in Wuhan, China, in late November or early December 2019, the SARS-CoV-2 virus has rapidly spread throughout the world. On March 11, 2020, the World Health Organization declared Coronavirus Disease 2019 (COVID-19) a pandemic. Genome sequencing of SARS-CoV-2 strains allows for the reconstruction of transmission history connecting these infections. Here, we analyze 346 SARS-CoV-2 genomes from samples collected between 20 February and 15 March 2020 from infected patients in Washington State, USA. We found that the large majority of SARS-CoV-2 infections sampled during this time frame appeared to have derived from a single introduction event into the state in late January or early February 2020 and subsequent local spread, strongly suggesting cryptic spread of COVID-19 during the months of January and February 2020, before active community surveillance was implemented. We estimate a common ancestor of this outbreak clade as occurring between 18 January and 9 February 2020. From genomic data, we estimate an exponential doubling between 2.4 and 5.1 days. These results highlight the need for large-scale community surveillance for SARS-CoV-2 introductions and spread and the power of pathogen genomics to inform epidemiological understanding.

As of December 31, 2022, a total of 29,939 monkeypox (mpox) cases* had been reported in the United States, 93.3% of which occurred in adult males. During May 10-December 31, 2022, 723,112 persons in the United States received the first dose in a 2-dose mpox (JYNNEOS)(†) vaccination series; 89.7% of these doses were administered to males (1). The current mpox outbreak has disproportionately affected gay, bisexual, and other men who have sex with men (MSM) and racial and ethnic minority groups (1,2). To examine racial and ethnic disparities in mpox incidence and vaccination rates, rate ratios (RRs) for incidence and vaccination rates and vaccination-to-case ratios were calculated, and trends in these measures were assessed among males aged ≥18 years (males) (3). Incidence in males in all racial and ethnic minority groups except non-Hispanic Asian (Asian) males was higher than that among non-Hispanic White (White) males. At the peak of the outbreak in August 2022, incidences among non-Hispanic Black or African American (Black) and Hispanic or Latino (Hispanic) males were higher than incidence among White males (RR = 6.9 and 4.1, respectively). Overall, vaccination rates were higher among males in racial and ethnic minority groups than among White males. However, the vaccination-to-case ratio was lower among Black (8.8) and Hispanic (16.2) males than among White males (42.5) during the full analytic period, indicating that vaccination rates among Black and Hispanic males were not proportionate to the elevated incidence rates (i.e., these groups had a higher unmet vaccination need). Efforts to increase vaccination among Black and Hispanic males might have resulted in the observed relative increased rates of vaccination; however, these increases were only partially successful in reducing overall incidence disparities. Continued implementation of equity-based vaccination strategies is needed to further increase vaccination rates and reduce the incidence of mpox among all racial and ethnic groups. Recent modeling data (4) showing that, based on current vaccination coverage levels, many U.S. jurisdictions are vulnerable to resurgent mpox outbreaks, underscore the need for continued vaccination efforts, particularly among racial and ethnic minority groups.