Understanding the dynamics of antibody responses following vaccination and SARS-CoV-2 infection is important for informing effective vaccination strategies and other public health interventions. This study investigates SARS-CoV-2 antibody dynamics in a Puerto Rican cohort, analyzing how IgG levels vary by vaccination status and previous infection. We assess waning immunity and the distribution of hybrid immunity with the aim to inform public health strategies and vaccination programs in Puerto Rico and similar settings. We conducted a prospective, longitudinal cohort study to identify SARS-CoV-2 infections and related outcomes in Ponce, Puerto Rico, from June 2020-August 2022. Participants provided self-collected nasal swabs every week and serum every six months for RT-PCR and IgG testing, respectively. IgG reactivity against nucleocapsid (N) antigens, which generally indicate previous infection, and spike (S1) and receptor-binding domain (RBD) antigens, which indicate history of either infection or vaccination, was assessed using the Luminex Corporation xMAP® SARS-CoV-2 Multi-Antigen IgG Assay. Prior infection was defined by positive RT-PCRs, categorized by the predominant circulating SARS-CoV-2 variant at the event time. Demographic information, medical history, and COVID-19 vaccination history were collected through standardized questionnaires. Of 882 participants included in our analysis, 34.0% experienced at least one SARS-CoV-2 infection, with most (78.7%) occurring during the Omicron wave (December 2021 onwards). SARS-CoV-2 antibody prevalence increased over time, reaching 98.4% by the final serum collection, 67.0% attributable to vaccination alone, 1.6% from infection alone, and 31.4% from both. Regardless of prior infection status, RBD and S1 IgG levels gradually declined following two vaccine doses. A third dose boosted these antibody levels and showed a slower decline over time. N-antibody levels peaked during the Omicron surge and waned over time. Vaccination in individuals with prior SARS-CoV-2 infection elicited the highest and most durable antibody responses. N or S1 seropositivity was associated with lower odds of a subsequent positive PCR test during the Omicron period, with N antibodies showing a stronger association. By elucidating the differential decay of RBD and S1 antibodies following vaccination and the complexities of N-antibody response following infection, this study in a Puerto Rican cohort strengthens the foundation for developing targeted interventions and public health strategies.

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

There is a pressing need for innovative strategies to control arboviruses transmitted by Aedes aegypti. The modification of indoor residual spraying to target Ae. aegypti is one such strategy. A clinical trial quantifying the epidemiologic impact of targeted indoor residual spraying for Ae. aegypti control used a product with pirimiphos-methyl as the active ingredient in the city of Mérida, Mexico. To monitor the susceptibility of local Ae. aegypti populations over the course of the trial, we calculated a diagnostic dose for pirimiphos-methyl using the Centers for Disease Control and Prevention bottle assay. Two independent laboratories tested a series of 8 concentrations of pirimiphos-methyl, eliciting a range of mortality between 0% and 100% in an insecticide-susceptible reference strain of Ae. aegypti. The results suggested a diagnostic dose of 25 μg/ml at a diagnostic time of 30 min. This diagnostic dose of pirimiphos-methyl was used to monitor pirimphos-methyl susceptibility in Ae. aegypti throughout the trial.

Of 319 children with invasive candidiasis, 67 (21%) transitioned from intravenous to enteral antifungal therapy. Eight (12%) transitioned back to intravenous antifungal therapy, one due to perceived treatment failure defined by clinical progression or worsening. Global treatment response at study completion was success in 66 participants transitioned to enteral therapy.

INTRODUCTION: An error grid compares measured versus reference glucose concentrations to assign clinical risk values to observed errors. Widely used error grids for blood glucose monitors (BGMs) have limited value because they do not also reflect clinical accuracy of continuous glucose monitors (CGMs). METHODS: Diabetes Technology Society (DTS) convened 89 international experts in glucose monitoring to (1) smooth the borders of the Surveillance Error Grid (SEG) zones and create a user-friendly tool-the DTS Error Grid; (2) define five risk zones of clinical point accuracy (A-E) to be identical for BGMs and CGMs; (3) determine a relationship between DTS Error Grid percent in Zone A and mean absolute relative difference (MARD) from analyzing 22 BGM and nine CGM accuracy studies; and (4) create trend risk categories (1-5) for CGM trend accuracy. RESULTS: The DTS Error Grid for point accuracy contains five risk zones (A-E) with straight-line borders that can be applied to both BGM and CGM accuracy data. In a data set combining point accuracy data from 18 BGMs, 2.6% of total data pairs equally moved from Zones A to B and vice versa (SEG compared with DTS Error Grid). For every 1% increase in percent data in Zone A, the MARD decreased by approximately 0.33%. We also created a DTS Trend Accuracy Matrix with five trend risk categories (1-5) for CGM-reported trend indicators compared with reference trends calculated from reference glucose. CONCLUSION: The DTS Error Grid combines contemporary clinician input regarding clinical point accuracy for BGMs and CGMs. The DTS Trend Accuracy Matrix assesses accuracy of CGM trend indicators.

Aedes mosquito-borne viruses (ABVs) place a substantial strain on public health resources in the Americas. Vector control of Aedes mosquitoes is an important public health strategy to decrease or prevent spread of ABVs. The ongoing Targeted Indoor Residual Spraying (TIRS) trial is an NIH-sponsored clinical trial to study the efficacy of a novel, proactive vector control technique to prevent dengue virus (DENV), Zika virus (ZIKV), and chikungunya virus (CHIKV) infections in the endemic city of Merida, Yucatan, Mexico. The primary outcome of the trial is laboratory-confirmed ABV infections in neighborhood clusters. Despite the difficulties caused by the COVID-19 pandemic, by early 2021 the TIRS trial completed enrollment of 4,792 children aged 2-15 years in 50 neighborhood clusters which were allocated to control or intervention arms via a covariate-constrained randomization algorithm. Here, we describe the makeup and ABV seroprevalence of participants and mosquito population characteristics in both arms before TIRS administration. Baseline surveys showed similar distribution of age, sex, and socio-economic factors between the arms. Serum samples from 1,399 children were tested by commercially available ELISAs for presence of anti-ABV antibodies. We found that 45.1% of children were seropositive for one or more flaviviruses and 24.0% were seropositive for CHIKV. Of the flavivirus-positive participants, most were positive for ZIKV-neutralizing antibodies by focus reduction neutralization testing which indicated a higher proportion of participants with previous ZIKV than DENV infections within the cohort. Both study arms had statistically similar seroprevalence for all viruses tested, similar socio-demographic compositions, similar levels of Ae. aegypti infestation, and similar observed mosquito susceptibility to insecticides. These findings describe a population with a high rate of previous exposure to ZIKV and lower titers of neutralizing antibodies against DENV serotypes, suggesting susceptibility to future outbreaks of flaviviruses is possible, but proactive vector control may mitigate these risks.

Leptospirosis, an acute bacterial zoonotic disease, is endemic in Puerto Rico. Infection in approximately 10%-15% of patients with clinical disease progresses to severe, potentially fatal illness. Increased incidence has been associated with flooding in endemic areas around the world. In 2022, Hurricane Fiona, a Category 1 hurricane, made landfall and inundated Puerto Rico with heavy rainfall and severe flooding, increasing the risk for a leptospirosis outbreak. In response, the Puerto Rico Department of Health (PRDH) changed guidelines to make leptospirosis cases reportable within 24 hours, centralized the case investigation management system, and provided training and messaging to health care providers. To evaluate changes in risk for leptospirosis after Hurricane Fiona to that before the storm, the increase in cases was quantified, and patient characteristics and geographic distribution were compared. During the 15 weeks after Hurricane Fiona, 156 patients experienced signs and symptoms of leptospirosis and had a specimen with a positive laboratory result reported to PRDH. The mean weekly number of cases during this period was 10.4, which is 3.6 as high as the weekly number of cases during the previous 37 weeks (2.9). After Hurricane Fiona, the proportion of cases indicating exposure to potentially contaminated water increased from 11% to 35%, and the number of persons receiving testing increased; these factors likely led to the resulting overall surge in reported cases. Robust surveillance combined with outreach to health care providers after flooding events can improve leptospirosis case identification, inform clinicians considering early initiation of treatment, and guide public messaging to avoid wading, swimming, or any contact with potentially contaminated floodwaters.

The Advisory Committee on Immunization Practices (ACIP) recommended that dengue pre-vaccination screening tests for Dengvaxia administration have at least 98% specificity and 75% sensitivity. This study evaluates the performance of commercial anti-DENV IgG tests to identify tests that could be used for pre-vaccination screening. First, for seven tests, we evaluated sensitivity and specificity in early convalescent dengue virus (DENV) infection, using 44 samples collected 7-30 days after symptom onset and confirmed by RT-PCR. Next, for the five best-performing tests and two additional tests (with and without an external test reader) that became available later, we evaluated performance to detect past dengue infection among a panel of 44 specimens collected in 2018-2019 from healthy 9- to 16-year-old children from Puerto Rico. Finally, a full-scale evaluation was done with the four best-performing tests using 400 specimens from the same population. We used virus focus reduction neutralization test and an in-house DENV IgG ELISA as reference standards. Of seven tests, five showed ≥75% sensitivity in detecting anti-DENV IgG in early convalescent specimens with low cross-reactivity to the Zika virus. For the detection of previous DENV infections, the tests with the highest performance were the Euroimmun NS1 IgG ELISA (sensitivity 84.5%, specificity 97.1%) and CTK Dengue IgG rapid test R0065C with the test reader (sensitivity 76.2% specificity 98.1%). There are IgG tests available that can be used to accurately classify individuals with previous DENV infection as eligible for dengue vaccination to support safe vaccine implementation. IMPORTANCE: The Advisory Committee on Immunization Practices (ACIP) has set forth recommendations that dengue pre-vaccination screening tests must exhibit at least 98% specificity and 75% sensitivity. Our research rigorously assesses the performance of various commercial tests against these benchmarks using well-characterized specimens from Puerto Rico. The findings from our study are particularly relevant given FDA approval and ACIP recommendation of Sanofi Pasteur's Dengvaxia vaccine, highlighting the need for accurate pre-vaccination screening tools.

BACKGROUND: The COVID-19 pandemic underscored the need for rapid and accurate diagnostic tools. In August 2020, the Abbott BinaxNOW COVID-19 Antigen Card test became available as a timely and affordable alternative for SARS-CoV-2 molecular testing, but its performance may vary due to factors including timing and symptomatology. This study evaluates BinaxNOW diagnostic performance in diverse epidemiological contexts. METHODS: Using RT-PCR as reference, we assessed performance of the BinaxNOW COVID-19 test for SARS-CoV-2 detection in anterior nasal swabs from participants of two studies in Puerto Rico from December 2020 to May 2023. Test performance was assessed by days post symptom onset, collection strategy, vaccination status, symptomatology, repeated testing, and RT-PCR cycle threshold (Ct) values. RESULTS: BinaxNOW demonstrated an overall sensitivity of 84.1% and specificity of 98.8%. Sensitivity peaked within 1-6 days after symptom onset (93.2%) and was higher for symptomatic (86.3%) than asymptomatic (67.3%) participants. Sensitivity declined over the course of infection, dropping from 96.3% in the initial test to 48.4% in testing performed 7-14 days later. BinaxNOW showed 99.5% sensitivity in participants with low Ct values (≤ 25) but lower sensitivity (18.2%) for participants with higher Cts (36-40). CONCLUSIONS: BinaxNOW demonstrated high sensitivity and specificity, particularly in early-stage infections and symptomatic participants. In situations where test sensitivity is crucial for clinical decision-making, nucleic acid amplification tests are preferred. These findings highlight the importance of considering clinical and epidemiological context when interpreting test results and emphasize the need for ongoing research to adapt testing strategies to emerging SARS-CoV-2 variants.

The high-consequence pathogen Bacillus anthracis causes human anthrax and often results in lethal infections without the rapid administration of effective antimicrobial treatment. Antimicrobial resistance profiling is therefore critical to inform post-exposure prophylaxis and treatment decisions, especially during emergencies such as outbreaks or where intentional release is suspected. Whole-genome sequencing using a rapid long-read sequencer can uncover antimicrobial resistance patterns if genetic markers of resistance are known. To identify genomic markers associated with antimicrobial resistance, we isolated B. anthracis derived from the avirulent Sterne strain with elevated minimal inhibitory concentrations to clarithromycin. Mutants were characterized both phenotypically through broth microdilution susceptibility testing and observations during culturing, as well as genotypically with whole-genome sequencing. We identified two different in-frame insertions in the L22 ribosomal protein-encoding gene rplV, which were subsequently confirmed to be involved in clarithromycin resistance through the reversion of the mutant gene to the parent (drug-susceptible) sequence. Detection of the rplV insertions was possible with rapid long-read sequencing, with a time-to-answer within 3 h. The mutations associated with clarithromycin resistance described here will be used in conjunction with known genetic markers of resistance for other antimicrobials to strengthen the prediction of antimicrobial resistance in B. anthracis.IMPORTANCEThe disease anthrax, caused by the pathogen Bacillus anthracis, is extremely deadly if not treated quickly and appropriately. Clarithromycin is an antibiotic recommended for the treatment and post-exposure prophylaxis of anthrax by the Centers for Disease Control and Prevention; however, little is known about the ability of B. anthracis to develop resistance to clarithromycin or the mechanism of that resistance. The characterization of clarithromycin-resistant isolates presented here provides valuable information for researchers and clinicians in the event of a release of the resistant strain. Additionally, knowledge of the genetic basis of resistance provides a foundation for susceptibility prediction through rapid genome sequencing to inform timely treatment decisions.

BACKGROUND: A better understanding of SARS-CoV-2 infection risk among Hispanic and Latino populations and in low-resource settings in the United States is needed to inform control efforts and strategies to improve health equity. Puerto Rico has a high poverty rate and other population characteristics associated with increased vulnerability to COVID-19, and there are limited data to date to determine community incidence. OBJECTIVE: This study describes the protocol and baseline seroprevalence of SARS-CoV-2 in a prospective community-based cohort study (COPA COVID-19 [COCOVID] study) to investigate SARS-CoV-2 infection incidence and morbidity in Ponce, Puerto Rico. METHODS: In June 2020, we implemented the COCOVID study within the Communities Organized to Prevent Arboviruses project platform among residents of 15 communities in Ponce, Puerto Rico, aged 1 year or older. Weekly, participants answered questionnaires on acute symptoms and preventive behaviors and provided anterior nasal swab samples for SARS-CoV-2 polymerase chain reaction testing; additional anterior nasal swabs were collected for expedited polymerase chain reaction testing from participants that reported 1 or more COVID-19-like symptoms. At enrollment and every 6 months during follow-up, participants answered more comprehensive questionnaires and provided venous blood samples for multiantigen SARS-CoV-2 immunoglobulin G antibody testing (an indicator of seroprevalence). Weekly follow-up activities concluded in April 2022 and 6-month follow-up visits concluded in August 2022. Primary study outcome measures include SARS-CoV-2 infection incidence and seroprevalence, relative risk of SARS-CoV-2 infection by participant characteristics, SARS-CoV-2 household attack rate, and COVID-19 illness characteristics and outcomes. In this study, we describe the characteristics of COCOVID participants overall and by SARS-CoV-2 seroprevalence status at baseline. RESULTS: We enrolled a total of 1030 participants from 388 households. Relative to the general populations of Ponce and Puerto Rico, our cohort overrepresented middle-income households, employed and middle-aged adults, and older children (P<.001). Almost all participants (1021/1025, 99.61%) identified as Latino/a, 17.07% (175/1025) had annual household incomes less than US $10,000, and 45.66% (463/1014) reported 1 or more chronic medical conditions. Baseline SARS-CoV-2 seroprevalence was low (16/1030, 1.55%) overall and increased significantly with later study enrollment time (P=.003). CONCLUSIONS: The COCOVID study will provide a valuable opportunity to better estimate the burden of SARS-CoV-2 and associated risk factors in a primarily Hispanic or Latino population, assess the limitations of surveillance, and inform mitigation measures in Puerto Rico and other similar populations. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/53837.

BACKGROUND: Opportunistic infections (OIs) are common causes of mortality among people living with HIV (PLHIV). We determined prevalence and 30-day mortality due to histoplasmosis, cryptococcosis, and TB in PLHIV with advanced HIV disease (AHD). METHODS: PLHIV 18 years and older, with a CD4 + T-cell count of less than 350 cells/mm3 newly diagnosed with HIV infection or re-engaged in care after being without ART for more than 90 days (Group A). The second group included symptomatic PLHIV regardless of ART status or CD4 + T-cell count (Group B); all followed for 30 days. Detection of Histoplasma Ag (HisAg) in urine was done by enzyme immunoassay (EIA), Cryptococcus antigen (CrAg) was detected in serum and cerebrospinal fluid (CSF) specimens by lateral flow assay (LFA), and lipoarabinomannan (LAM) detection in urine was by LFA (TB LAM) and in sputum by GeneXpert for diagnosis of Mycobacterium infections. RESULTS: From August 2021 to June 2022, 491 PLHIV were enrolled; 482 (98%) had a CD4 + T-cell result, and 381 patients (79%) were classified with AHD according to CD4 + T-cell count (< 200 CD4/mm(3)). Frequency of an OI was 38% (n = 145/381). Antigen test positivity rate was 16% (72/467) for TB-LAM, 9% (43/464) for HisAg, and 11% (51/484) for CrAg. Twenty-one of 34 (62%) patients receiving CSF CrAg tests were positive, confirming meningitis. Significant differences in 30-day mortality were observed in patients with an OI (16%) vs. no OI (7%) (p = 0.002). Mortality was highest in patients with histoplasmosis (25%), co-infection (22%), cryptococcosis (18% overall; 19% for cryptococcal meningitis), and TB (10%). CONCLUSIONS: TB and fungal OIs, including co-infection, were common in PLHIV in Paraguay and had high associated mortality. Laboratories and health facilities need access to CD4 + T-cell testing and rapid diagnostic assays.

Novel H1N2 and H3N2 swine influenza A viruses (IAVs) have recently been identified in Chile. The objective of this study was to evaluate their zoonotic potential. We perform phylogenetic analyses to determine the genetic origin and evolution of these viruses, and a serological analysis to determine the level of cross-protective antibodies in the human population. Eight genotypes were identified, all with pandemic H1N1 2009-like internal genes. H1N1 and H1N2 were the subtypes more commonly detected. Swine H1N2 and H3N2 IAVs had hemagglutinin and neuraminidase lineages genetically divergent from IAVs reported worldwide, including human vaccine strains. These genes originated from human seasonal viruses were introduced into the swine population since the mid-1980s. Serological data indicate that the general population is susceptible to the H3N2 virus and that elderly and young children also lack protective antibodies against the H1N2 strains, suggesting that these viruses could be potential zoonotic threats. Continuous IAV surveillance and monitoring of the swine and human populations is strongly recommended.IMPORTANCEIn the global context, where swine serve as crucial intermediate hosts for influenza A viruses (IAVs), this study addresses the pressing concern of the zoonotic potential of novel reassortant strains. Conducted on a large scale in Chile, it presents a comprehensive account of swine influenza A virus diversity, covering 93.8% of the country's industrialized swine farms. The findings reveal eight distinct swine IAV genotypes, all carrying a complete internal gene cassette of pandemic H1N1 2009 origin, emphasizing potential increased replication and transmission fitness. Genetic divergence of H1N2 and H3N2 IAVs from globally reported strains raises alarms, with evidence suggesting introductions from human seasonal viruses since the mid-1980s. A detailed serological analysis underscores the zoonotic threat, indicating susceptibility in the general population to swine H3N2 and a lack of protective antibodies in vulnerable demographics. These data highlight the importance of continuous surveillance, providing crucial insights for global health organizations.

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

During the COVID-19 vaccination rollout from March 2021- December 2022, the Centers for Disease Control and Prevention funded 110 primary and 1051 subrecipient partners at the national, state, local, and community-based level to improve COVID-19 vaccination access, confidence, demand, delivery, and equity in the United States. The partners implemented evidence-based strategies among racial and ethnic minority populations, rural populations, older adults, people with disabilities, people with chronic illness, people experiencing homelessness, and other groups disproportionately impacted by COVID-19. CDC also expanded existing partnerships with healthcare professional societies and other core public health partners, as well as developed innovative partnerships with organizations new to vaccination, including museums and libraries. Partners brought COVID-19 vaccine education into farm fields, local fairs, churches, community centers, barber and beauty shops, and, when possible, partnered with local healthcare providers to administer COVID-19 vaccines. Inclusive, hyper-localized outreach through partnerships with community-based organizations, faith-based organizations, vaccination providers, and local health departments was critical to increasing COVID-19 vaccine access and building a broad network of trusted messengers that promoted vaccine confidence. Data from monthly and quarterly REDCap reports and monthly partner calls showed that through these partnerships, more than 295,000 community-level spokespersons were trained as trusted messengers and more than 2.1 million COVID-19 vaccinations were administered at new or existing vaccination sites. More than 535,035 healthcare personnel were reached through outreach strategies. Quality improvement interventions were implemented in healthcare systems, long-term care settings, and community health centers resulting in changes to the clinical workflow to incorporate COVID-19 vaccine assessments, recommendations, and administration or referrals into routine office visits. Funded partners' activities improved COVID-19 vaccine access and addressed community concerns among racial and ethnic minority groups, as well as among people with barriers to vaccination due to chronic illness or disability, older age, lower income, or other factors.

Characterisation of influenza viruses in the southern hemisphere can guide local response and provide insights to northern hemisphere jurisdictions about their upcoming influenza season.1,2 Here, we present the information on 2023 end of influenza season in the southern hemisphere about influenza lineages, incidence of medically attended, laboratory-confirmed influenza cases, and influenza vaccine effectiveness (VE) against the antigen from surveillance clinics and a hospital in San Juan de Lurigancho and San Martin de Porres, the two most populated districts of Peru. | | From Jan 1 to Sept 30, 2023, surveillance nurses sought individuals with COVID-19-like illness (CLI) of any age seeking care at outpatient sentinel sites between Monday and Saturday. CLI was defined as presenting with at least two of the following symptoms or signs—fever, chills, rigors, myalgia, headache, or sore throat for not more than 7 days from illness onset.3 On March 7, 2023, the nurses expanded their search to CLI cases hospitalised for not more than 72 h at Cayetano Heredia National Hospital. | | Nurses obtained written consent to survey and swab CLI cases. Enrolled participants provided information on pre-existing conditions and influenza vaccination status. Individuals targeted for vaccination by Peru and vaccinated between Jan and Sept 2022, more than 14 days before enrolment, were considered vaccinated (appendix p 1).

Background: Health education materials translated for limited English proficiency audiences should be clear and easy to understand. They should be reviewed by fluent and culturally competent reviewers using a standardised and validated assessment tool. Design/Setting: A total of 139 US Centers for Disease Control and Prevention COVID-19-translated health education materials were reviewed for cultural and linguistic appropriateness. Method(s): Reviewers were trained to collect data using a standardised assessment tool, and recorded issues found in translated materials by issue, material and media type. Reviewers were selected for their fluency in the language being reviewed as well as their cultural knowledge of the intended audience. Result(s): Reviewers identified 150 issues related to words, phrases and images that were confusing, difficult to interpret or held multiple possible interpretations. Reviewers took an average completion time of 16 minutes per material across all media types. Conclusion(s): This assessment demonstrated the feasibility and efficiency of conducting reviews with culturally and linguistically competent in-house reviewers using a quality assessment protocol that includes a review for cultural and linguistic accuracy. Despite mainly using certified translators, critical issues with the text and images contained in the COVID-19-translated health education materials were identified. Similar forms of assessment could provide high-quality translated materials without undergoing major document revision. Copyright © The Author(s) 2023.

Fungal infections can cause severe disease and death and impose a substantial economic burden on healthcare systems. Public health research requires a multidisciplinary approach and is essential to help save lives and prevent disability from fungal diseases. In this manuscript, we outline the main public health research priorities for fungal diseases, including the measurement of the fungal disease burden and distribution and the need for improved diagnostics, therapeutics, and vaccines. Characterizing the public health, economic, health system, and individual burden caused by fungal diseases can provide critical insights to promote better prevention and treatment. The development and validation of fungal diagnostic tests that are rapid, accurate, and cost-effective can improve testing practices. Understanding best practices for antifungal prophylaxis can optimize prevention in at-risk populations, while research on antifungal resistance can improve patient outcomes. Investment in vaccines may eliminate certain fungal diseases or lower incidence and mortality. Public health research priorities and approaches may vary by fungal pathogen.

In this case study, we aim to understand how health departments in 5 US jurisdictions addressed health inequities and implemented strategies to reach populations disproportionately affected by COVID-19 during the initial Omicron variant period. We used qualitative methods to examine health department experiences during the initial Omicron surge, from November 2021 to April 2022, assessing successful interventions, barriers, and lessons learned from efforts to promote health equity. Our findings indicate that government leadership supported prioritizing health equity from the beginning of the pandemic, seeing it as a need and vital part of the response framework. All jurisdictions acknowledged the historical trauma and distrust of the government. Health departments found that collaborating and communicating with trusted community leaders helped mitigate public distrust. Having partnerships, resources, and infrastructure in place before the pandemic facilitated the establishment of equity-focused COVID-19 response activities. Finally, misinformation about COVID-19 was a challenge for all jurisdictions. Addressing the needs of diverse populations involves community-informed decisionmaking, diversity of thought, and delivery measures that are tailored to the community. It is imperative to expand efforts to reduce and eliminate health inequities to ensure that individuals and communities recover equitably from the effects of COVID-19.

BACKGROUND: Adjunctive diagnostic studies (aDS) are recommended to identify occult dissemination in patients with candidemia. Patterns of evaluation with aDS across pediatric settings are unknown. METHODS: Candidemia episodes were included in a secondary analysis of a multicenter comparative effectiveness study that prospectively enrolled participants age 120 days -17 years with invasive candidiasis (predominantly candidemia) from 2014-2017. Ophthalmologic examination, abdominal imaging, echocardiogram, neuroimaging, and lumbar puncture were performed per clinician discretion. aDS performance and positive results were determined per episode, within 30 days from candidemia onset. Associations of aDS performance with episode characteristics were evaluated via mixed effects logistic regression. RESULTS: In 662 pediatric candidemia episodes, 490 (74%) underwent abdominal imaging, 450 (68%) ophthalmologic examination, 426 (64%) echocardiogram, 160 (24%) neuroimaging, and 76 (11%) lumbar puncture; performance of each aDS per episode varied across sites up to 16-fold. Longer durations of candidemia were associated with undergoing ophthalmologic examination, abdominal imaging, and echocardiogram. Immunocompromised status (58% of episodes) was associated with undergoing abdominal imaging (aOR 2.38; 95% CI 1.51-3.74). Intensive care at candidemia onset (30% of episodes) was associated with undergoing echocardiogram (aOR 2.42; 95% CI 1.51-3.88). Among evaluated episodes, positive ophthalmologic examination was reported in 15 (3%), abdominal imaging in 30 (6%), echocardiogram in 14 (3%), neuroimaging in 9 (6%) and lumbar puncture in 3 (4%). CONCLUSIONS: Our findings show heterogeneity in practice, with some clinicians performing aDS selectively, potentially influenced by clinical factors. The low frequency of positive results suggests that targeted application of aDS is warranted.

Histoplasma antigen can be detected in people with advanced HIV disease (AHD), allowing for early and accurate diagnosis of histoplasmosis. The aim of this analysis was to assess the cost-effectiveness of routine histoplasmosis screening using antigen detection, among people with AHD. We developed a decision analytic model to evaluate Histoplasma antigen screening among people with AHD. The model estimated the costs, effectiveness, and cost-effectiveness of routine screening for Histoplasma antigen compared to the current practice of no routine Histoplasma antigen screening. The model includes stratification by symptoms of histoplasmosis, severity of presentation, and estimates of 30-day mortality. Data sources were taken from the Pan American Health Organization (PAHO) Strategic Fund databases on public purchases of medicines, and published literature on treatment outcomes. Outcome measures are life years saved (LYS), costs (US dollars), and incremental cost-effectiveness ratios (ICERs). Routine Histoplasma antigen screening avoids an estimated 17% of deaths in persons with advanced HIV disease, and is cost-effective compared to no histoplasmosis screening, with an ICER of $26/LYS. In sensitivity analysis assuming treatment for histoplasmosis with liposomal amphotericin, Histoplasma antigen screening remains cost-effective with an ICER of $607/LYS. Histoplasma antigen screening among people with AHD is a cost-effective strategy and could potentially avert 17% of AIDS-related deaths. Prospective evaluation of histoplasmosis screening is warranted to determine effectiveness and treatment outcomes with this strategy.

Diagnostic testing for Zika virus (ZIKV) or dengue virus (DENV) infection can be accomplished by a nucleic acid detection method; however, a negative result does not exclude infection due to the low virus titer during infection depending on the timing of sample collection. Therefore, a ZIKV- or DENV-specific serological assay is essential for the accurate diagnosis of patients and to prevent potential severe health outcomes. A retrospective study design with dual approaches of collecting human serum samples for testing was developed. All serum samples were extensively evaluated by using both non-infectious virus-like particles (VLPs) and soluble non-structural protein 1 (NS1) in the standard immunoglobulin M (IgM) antibody-capture enzyme-linked immunosorbent assay (MAC-ELISA). Both VLP- and NS1-MAC-ELISAs were found to have similar sensitivity for detecting anti-premembrane/envelope and NS1 antibodies from ZIKV-infected patient sera. Group cross reactive (GR)-antibody-ablated homologous fusion peptide-mutated (FP)-VLPs consistently showed higher P/N values than homologous wild-type VLPs. Therefore, FP-VLPs were used to develop the algorithm for differentiating ZIKV from DENV infection. Overall, the sensitivity and specificity of the FP-VLP-MAC-ELISA and the NS1-MAC-ELISA were each higher than 80% with no statistical significance. A novel approach to differentiate ZIKV from DENV infection serologically has been developed. The accuracy can reach up to 95% when combining both VLP and NS1 assays. In comparison to current guidelines using neutralization tests to measure ZIKV antibody, this approach can facilitate laboratory screening for ZIKV infection, especially in regions where DENV infection is endemic and capacity for neutralization testing does not exist.

The aim of this study was to independently evaluate the diagnostic accuracy of three artificial intelligence (AI)-based computer aided detection (CAD) systems for detecting pulmonary tuberculosis (TB) on global migrants screening chest x-ray (CXR) cases when compared against both microbiological and radiological reference standards (MRS and RadRS, respectively). Retrospective clinical data and CXR images were collected from the International Organization for Migration (IOM) pre-migration health assessment TB screening global database for US-bound migrants. A total of 2,812 participants were included in the dataset used for analysis against RadRS, of which 1,769 (62.9%) had accompanying microbiological test results and were included against MRS. All CXRs were interpreted by three CAD systems (CAD4TB v6, Lunit INSIGHT v4.9.0, and qXR v2) in offline setting, and re-interpreted by two expert radiologists in a blinded fashion. The performance was evaluated using receiver operating characteristics curve (ROC), estimates of sensitivity and specificity at different CAD thresholds against both microbiological and radiological reference standards (MRS and RadRS, respectively), and was compared with that of the expert radiologists. The area under the curve against MRS was highest for Lunit (0.85; 95% CI 0.83-0.87), followed by qXR (0.75; 95% CI 0.72-0.77) and then CAD4TB (0.71; 95% CI 0.68-0.73). At a set specificity of 70%, Lunit had the highest sensitivity (81.4%; 95% CI 77.9-84.6); at a set sensitivity of 90%, specificity was also highest for Lunit (54.5%; 95% CI 51.7-57.3). The CAD systems performed comparable to the sensitivity (98.3%), and except CAD4TB, to specificity (13.7%) of the expert radiologists. Similar trends were observed when using RadRS. Area under the curve against RadRS was highest for CAD4TB (0.87; 95% CI 0.86-0.89) and Lunit (0.87; 95% CI 0.85-0.88) followed by qXR (0.81; 95% CI 0.80-0.83). At a set specificity of 70%, CAD4TB had highest sensitivity (84.1%; 95% CI 82.3-85.8) followed by Lunit (80.9%; 95% CI 78.9-82.7); and at a set sensitivity of 90%, specificity was also highest for CAD4TB (54.6%; 95% CI 51.3-57.8). In conclusion, the study demonstrated that the three CAD systems had broadly similar diagnostic accuracy with regard to TB screening and comparable accuracy to an expert radiologist against MRS. Compared with different reference standards, Lunit performed better than both qXR and CAD4TB against MRS, and CAD4TB and Lunit better than qXR against RadRS. Moreover, the performance of the CADs can be impacted by characteristics of subgroup of population. The main limitation was that our study relied on retrospective data and MRS was not routinely done in individuals with a low suspicion of TB and a normal CXR. Our findings suggest that CAD systems could be a useful tool for TB screening programs in remote, high TB prevalent places where access to expert radiologists may be limited. However, further large-scale prospective studies are needed to address outstanding questions around the operational performance and technical requirements of the CAD systems.

Nipah virus (NiV), an emerging zoonotic pathogen in Southeast Asia, is transmitted from Pteropus species of fruit bats to a wide range of species, including humans, pigs, horses, dogs, and cats. NiV has killed millions of animals and caused highly fatal human outbreaks since no vaccine is commercially available. This study characterized the immunogenicity and safety of poxvirus-based Nipah vaccines that can be used in humans and species responsible for NiV transmission. Mice were vaccinated with modified vaccinia Ankara (MVA) and raccoon pox (RCN) viral vectors expressing the NiV fusion (F) and glycoprotein (G) proteins subcutaneously (SC) and intranasally (IN). Importantly, both vaccines did not induce significant weight loss or clinical signs of disease while generating high circulating neutralizing antibodies and lung-specific IgG and IgA responses. The MVA vaccine saw high phenotypic expression of effector and tissue resident memory CD8ɑ(+) T cells in lungs and splenocytes along with the expression of central memory CD8ɑ(+) T cells in lungs. The RCN vaccine generated effector memory (SC) and tissue resident (IN) CD8ɑ(+) T cells in splenocytes and tissue resident (IN) CD8ɑ(+) T cells in lung cells. These findings support MVA-FG and RCN-FG viral vectors as promising vaccine candidates to protect humans, domestic animals, and wildlife from fatal disease outcomes and to reduce the global threat of NiV.

BACKGROUND: The massive use of insecticides in public health has exerted selective pressure resulting in the development of resistance in Aedes aegypti to different insecticides in Venezuela. Between 2010 and 2020, the only insecticides available for vector control were the organophosphates (Ops) fenitrothion and temephos which were focally applied. OBJECTIVES: To determine the state of insecticide resistance and to identify the possible biochemical and molecular mechanisms involved in three populations of Ae. aegypti from Venezuela. METHODS: CDC bottle bioassays were conducted on Ae. aegypti collected between October 2019 and February 2020 in two hyperendemic localities for dengue in Aragua State and in a malaria endemic area in Bolívar State. Insecticide resistance mechanisms were studied using biochemical assays and polymerase chain reaction (PCR) to detect kdr mutations. FINDINGS: Bioassays showed contrasting results among populations; Las Brisas was resistant to malathion, permethrin and deltamethrin, Urbanización 19 de Abril was resistant to permethrin and Nacupay to malathion. All populations showed significantly higher activity of mixed function oxidases and glutathione-S-transferases (GSTs) in comparison with the susceptible strain. The kdr mutations V410L, F1534C, and V1016I were detected in all populations, with F1534C at higher frequencies. MAIN CONCLUSION: Insecticide resistance persists in three Ae. aegypti populations from Venezuela even in the relative absence of insecticide application.

Limited dengue virus (DENV) seroprevalence estimates are available for Puerto Rico, which are needed to inform the potential use and cost-effectiveness of DENV vaccines. The Communities Organized to Prevent Arboviruses (COPA) is a cohort study initiated in 2018 in Ponce, Puerto Rico, to assess arboviral disease risk and provide a platform to evaluate interventions. We recruited participants from households in 38 study clusters, who were interviewed and provided a serum specimen. Specimens from 713 children aged 1 to 16 years during the first year of COPA were tested for the four DENV serotypes and ZIKV using a focus reduction neutralization assay. We assessed the seroprevalence of DENV and ZIKV by age and developed a catalytic model from seroprevalence and dengue surveillance data to estimate the force of infection for DENV during 2003-2018. Overall, 37% (n = 267) were seropositive for DENV; seroprevalence was 9% (11/128) among children aged 1 to 8 years and 44% (256/585) among children aged 9 to 16 years, exceeding the threshold over which DENV vaccination is deemed cost-effective. A total of 33% were seropositive for ZIKV, including 15% among children aged 0 to 8 years and 37% among children aged 9 to 16 years. The highest force of infection occurred in 2007, 2010, and 2012-2013, with low levels of transmission from 2016 to 2018. A higher proportion of children had evidence of multitypic DENV infection than expected, suggesting high heterogeneity in DENV risk in this setting.

PROBLEM/CONDITION: Dengue is one of the most common vectorborne flaviviral infections globally, with frequent outbreaks in tropical regions. In 2019 and 2020, the Pan American Health Organization reported approximately 5.5 million dengue cases from the Americas, the highest number on record. In the United States, local dengue virus (DENV) transmission has been reported from all U.S. territories, which are characterized by tropical climates that are highly suitable for Aedes species of mosquitoes, the vector that transmits dengue. Dengue is endemic in the U.S. territories of American Samoa, Puerto Rico, and the U.S. Virgin Islands (USVI). Dengue risk in Guam and the Commonwealth of the Northern Mariana Islands is considered sporadic or uncertain. Despite all U.S. territories reporting local dengue transmission, epidemiologic trends over time have not been well described. REPORTING PERIOD: 2010-2020. DESCRIPTION OF SYSTEM: State and territorial health departments report dengue cases to CDC through ArboNET, the national arboviral surveillance system, which was developed in 2000 to monitor West Nile virus infections. Dengue became nationally notifiable in ArboNET in 2010. Dengue cases reported to ArboNET are categorized using the 2015 Council of State and Territorial Epidemiologists case definition. In addition, DENV serotyping is performed at CDC's Dengue Branch Laboratory in a subset of specimens to support identification of circulating DENV serotypes. RESULTS: During 2010-2020, a total of 30,903 dengue cases were reported from four U.S. territories to ArboNET. Puerto Rico reported the highest number of dengue cases (29,862 [96.6%]), followed by American Samoa (660 [2.1%]), USVI (353 [1.1%]), and Guam (28 [0.1%]). However, annual incidence rates were highest in American Samoa with 10.2 cases per 1,000 population in 2017, followed by Puerto Rico with 2.9 in 2010 and USVI with 1.6 in 2013. Approximately one half (50.6%) of cases occurred among persons aged <20 years. The proportion of persons with dengue who were hospitalized was high in three of the four territories: 45.5% in American Samoa, 32.6% in Puerto Rico, and 32.1% in Guam. In Puerto Rico and USVI, approximately 2% of reported cases were categorized as severe dengue. Of all dengue-associated deaths, 68 (0.2%) were reported from Puerto Rico; no deaths were reported from the other territories. During 2010-2020, DENV-1 and DENV-4 were the predominant serotypes in Puerto Rico and USVI. INTERPRETATION: U.S. territories experienced a high prevalence of dengue during 2010-2020, with approximately 30,000 cases reported, and a high incidence during outbreak years. Children and adolescents aged <20 years were disproportionately affected, highlighting the need for interventions tailored for this population. Ongoing education about dengue clinical management for health care providers in U.S. territories is important because of the high hospitalization rates reported. Dengue case surveillance and serotyping can be used to guide future control and prevention measures in these areas. PUBLIC HEALTH ACTION: The Advisory Committee on Immunization Practices recommends vaccination with Dengvaxia for children aged 9-16 years with evidence of previous dengue infection and living in areas where dengue is endemic. The recommendation for the dengue vaccine offers public health professionals and health care providers a new intervention for preventing illness and hospitalization in the age group with the highest burden of disease in the four territories (Paz Bailey G, Adams L, Wong JM, et al. Dengue Vaccine: Recommendations of the Advisory Committee on Immunization Practices, United States, 2021. MMWR Recomm Rep 2021;70[No. RR-6]). American Samoa, Puerto Rico, and USVI are all considered endemic areas and persons residing in these areas are eligible for the new dengue vaccine. Persons aged 9-16 years in those jurisdictions with laboratory evidence of previous dengue infection can receive the dengue vaccine and benefit from a reduced risk for symptomatic disease, hospitalization, or severe dengue. Health care providers in these areas should be familiar with the eligibility criteria and recommendations for vaccination to reduce the burden of dengue among the group at highest risk for symptomatic illness. Educating health care providers about identification and management of dengue cases can improve patient outcomes and improve surveillance and reporting of dengue cases.

In May 2019, the Food and Drug Administration issued approval for Dengvaxia (Sanofi Pasteur), a live-attenuated, chimeric tetravalent dengue vaccine (1). In June 2021, the Advisory Committee on Immunization Practices (ACIP) recommended vaccination with Dengvaxia for children and adolescents aged 9–16 years with laboratory confirmation of previous dengue virus infection and who live in areas with endemic dengue transmission, such as the U.S. Virgin Islands (USVI)† (2). Confirming previous dengue virus infection before vaccine administration (prevaccination screening) is important because 1) although Dengvaxia decreases hospitalization and severe disease from dengue among persons with a previous infection, it increases the risk for these outcomes among persons without a previous infection; 2) many dengue virus infections are asymptomatic; and 3) many patients with symptomatic infections do not seek medical attention or receive appropriate testing (3). Sufficient laboratory evidence of previous dengue virus infection includes a history of laboratory-confirmed dengue§ or a positive serologic test result that meets ACIP-recommended performance standards for prevaccination screening, defined as high specificity (≥98%) and sensitivity (≥75%). A seroprevalence of 20% in the vaccine-eligible population (corresponding to a positive predictive value of ≥90% for a test with minimum sensitivity of 75% and minimum specificity of 98%) is recommended to maximize vaccine safety and minimize the risk for vaccinating persons without a previous dengue virus infection (2).

In late August 2021, a boy aged 7 years was bitten by a bat while he was playing outside his apartment home in Medina County, Texas. He informed his parents; however, no rabies postexposure prophylaxis (PEP) was sought because there were no visible bite marks, and the family was unaware that contact with a bat, including in the absence of visible bite marks, might cause rabies. Approximately 2 months later, the child was hospitalized for altered mental status, seizures, and hypersalivation and ultimately received a diagnosis of rabies. Experimental therapies were attempted; however, the child died 22 days after symptom onset. Fifty-seven persons who met criteria for suspected or known exposure to infectious secretions in this case were advised to consult with a medical provider about the need for rabies PEP in accordance with Advisory Committee on Immunization Practices (ACIP) guidelines (1). Rabies, an acute, progressive neuroencephalitis, is nearly always fatal. Although dogs are the most common source of human rabies deaths worldwide and account for an estimated 59,000 annual cases of human rabies globally (2), bats are the most common source of domestically acquired rabies in the United States and have been implicated in 31 (81.6%) of 38 human infections since 2000 (3). Attempts to prevent death or poor neurologic outcomes once rabies symptoms develop have been largely unsuccessful (4). Administration of rabies PEP, comprising rabies immunoglobulin and a series of doses of rabies vaccine, is critical to preventing rabies after an exposure; enhanced public education about the risk posed by bats, and the availability of PEP to prevent rabies, is needed.