Differentiating between acute febrile illnesses (AFIs) caused by arboviruses like dengue virus (DENV) and other pathogens is challenging, particularly in the case of coinfections, which often require comprehensive diagnostic testing for accurate identification. Recognizing DENV coinfections is important because they may contribute to increased disease severity, and their identification can aid in patient management decisions. Using data from the Sentinel Enhanced Dengue Surveillance System in Puerto Rico (2012-2024), we compared patients with DENV monoinfection to those coinfected with DENV and another pathogen. All pathogens were identified via nucleic acid detection by using real-time, reverse transcriptase-polymerase chain reaction or serology. We examined demographic and clinical features linked to coinfection using Mann-Whitney-Wilcoxon, χ2, or Fisher's exact tests. Among 50,189 participants tested for DENV, 1,218 (2.4%) had DENV infections, with 1,172 (96.2%) monoinfections and 46 (3.8%) coinfections. The most frequent coinfecting pathogens were adenovirus (17.4%), influenza A (15.2%), human metapneumovirus (15.2%), and respiratory syncytial virus (10.9%). Dengue virus coinfections were associated with younger age (median: 13 versus 16 years; P = 0.011) and symptoms of rhinorrhea (52.2% versus 27.3%; P <0.001) and cough (60.9% versus 36.4%; P = 0.001). Among 549 hospitalized dengue patients, 20 (3.6%) had coinfections. Five of seven participants with DENV/influenza A coinfection were hospitalized. Hospitalization, intensive care unit admission, the administration of blood products, and severe dengue indicators (plasma leakage, severe bleeding, and organ involvement) were not significantly associated with DENV coinfection. Overall, DENV coinfections were uncommon in AFI cases in Puerto Rico, and they primarily involved respiratory viruses. Overlapping symptoms may complicate clinical management, emphasizing the importance of comprehensive pathogen testing in settings where arboviruses and respiratory viruses cocirculate.

Trachoma is targeted for global elimination as a public health problem by 2030. Measurement of IgG antibodies in children is being considered for surveillance and programmatic decision-making. There are currently no programmatic guidelines based on serology, which represents a generalizable problem in seroepidemiology and disease elimination. Here, we collate Chlamydia trachomatis Pgp3 and CT694 IgG measurements from 48 serosurveys across Africa, Latin America, and the Pacific Islands (41,168 children ages 1-5 years) and propose a novel approach to estimate the probability that population C. trachomatis transmission is below or above levels requiring ongoing programmatic action. We determine that trachoma programs could halt control measures with >90% certainty when seroconversion rates (SCRs) are ≤2.2 per 100 person-years. Conversely, SCRs ≥4.5 per 100 person-years correspond with >90% certainty that further control interventions are needed. More extreme SCR thresholds correspond with higher levels of confidence of elimination (lower SCR) or ongoing action needed (higher SCR). This study demonstrates a robust approach for using trachoma serosurveys to guide elimination program decisions.

A nationwide cross-sectional study led by the Agency for Toxic Substances and Disease Registry in collaboration with research and community partners, was designed to investigate health outcomes linked to per- and polyfluoroalkyl substances (PFAS) exposure among residents of communities with contaminated drinking water. The objective was to describe the study design, methods, participant demographics, and PFAS serum concentrations. From 2019 to 2023, adult (18+) and child (ages 4-17) participants were recruited from communities with past or ongoing PFAS contamination of drinking water across eight sites in California, Colorado, Massachusetts, Michigan, New Hampshire, New York, New Jersey, and Pennsylvania. Data on demographics, lifestyle factors, and residential, occupational, and medical history were collected via questionnaires. Extensive clinical tests assessed cardiometabolic, liver, thyroid, kidney, glycemic, and immune parameters. Neurobehavioral tests were administered to children (ages 5-17). PFAS quantified in serum included MeFOSAA, PFHxS, PFOS, PFOA, PFNA, PFDA, and PFUnDA. Serum, whole blood, and urine samples were banked for future analyses. The study enrolled 5826 adults (geometric mean age: 53.6 years; 60.2 % female; 77.2 % non-Hispanic White) and 710 children (geometric mean age: 10.7 years; 48.5 % female; 69 % non-Hispanic White). Compared with NHANES data (2017-2020), adults showed elevated geometric mean concentrations of PFHxS and PFOA; only PFHxS was elevated in children. These serum concentrations reflect a wide range of PFAS exposures in communities affected by contamination from firefighting activities and industrial emissions, and other sources. This large study is a valuable resource for exploring associations between PFAS exposure and health effects in adults and children.

INTRODUCTION: Given the increasing usage of vaping during pregnancy and limited longitudinal health-related data, there is an urgent need to assess the potential risks of vaping. AIMS AND METHODS: A cross-sectional study was conducted among pregnant UK adults (n = 140). Five study groups were purposively recruited: exclusive-smokers (n = 38), exclusive-vapers (former smokers) (n = 35), dual users of smoking and vaping (n = 25), dual users of smoking and nicotine replacement therapy (n = 10), and "never-users" of nicotine or tobacco products (n = 32). Sociodemographic, smoking, and vaping characteristics were assessed. Participants' urine samples were analyzed for biomarkers of exposure to tobacco alkaloids, and toxicants, including 14 volatile organic compounds (VOCs), tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), heavy metals (cadmium, lead, chromium, nickel, copper, and tin) and a polycyclic aromatic hydrocarbon (2-naphthol). Regression analysis was used to compare biomarkers by group. RESULTS: Nicotine levels varied across product users, but not significantly. After controlling for confounders, for most VOCs, biomarker levels were similar for exclusive-vapers and never-users and significantly lower than for exclusive-smokers and any dual users. There were generally no significant differences between groups for 2-naphthol or heavy metals. For NNAL, cadmium and chromium, a high percentage of values were below the limit of detection, making analyses unreliable. CONCLUSIONS: During pregnancy, former smokers who are established exclusive vapers, but not dual users, had levels of selected VOCs that were substantially lower than those for exclusive smokers and comparable with those who have never used nicotine or tobacco products. IMPLICATIONS: Based on the biomarkers assessed in this study, during pregnancy, on average, exclusive-vapers are likely to have similar levels of exposure to selected VOCs as never-users and far lower levels than exclusive-smokers or dual-users (although dual-vaping and smoking may result in less exposure than exclusive-smoking). This provides preliminary information about exposure to vaping during pregnancy and suggests that, for some biomarkers, exclusive vaping is likely to result in lower exposures than exclusive smoking or dual-use. There may be exposure to other vaping toxicants that were not explored in this study. Studies are needed to assess pregnancy and birth outcomes as well as early life effects.

Reliance on traditional vector control methods, such as insecticides and "clean-up" source reduction efforts for reducing mosquito breeding sites, has proven increasingly ineffective and costly in the battle against dengue. The Wolbachia-based mosquito replacement strategy, which replaces wild mosquitoes with mosquitoes trans-infected with Wolbachia bacteria, preventing up to 77% dengue transmission, represents an advancement in prevention. Integrating this approach into current routine dengue control efforts could reduce dengue incidence. However, challenges such as implementation costs, the need for country ownership, alignment of released mosquitoes with local mosquito populations, increased education and sensitization for government authorities and the public on the benefits of Wolbachia, identifying international funding partners, and recognizing areas where the strategy may be less effective due to environmental or socio-political factors, must be addressed. Furthermore, Wolbachia replacement must focus in areas with high population density and high dengue incidence since it is not feasible to cover all endemic areas. Establishing robust surveillance systems to monitor efficacy against different dengue serotypes is also critical. Despite these challenges, the Wolbachia strategy is the one of the most promising developments in dengue prevention to date. By complementing this approach with effective vaccines, we have the unprecedented opportunity to significantly reduce dengue.

OBJECTIVE: The Diabetes in Children, Adolescents, and Young Adults (DiCAYA) network seeks to create a nationwide electronic health record (EHR)-based diabetes surveillance system. This study aimed to develop a DiCAYA-wide EHR-based computable phenotype (CP) to identify prevalent cases of diabetes. RESEARCH DESIGN AND METHODS: We conducted network-wide chart reviews of 2,134 youth (aged <18 years) and 2,466 young adults (aged 18 to <45 years) among people with possible diabetes. Within this population, we compared the performance of three alternative CPs, using diabetes diagnoses determined by chart review as the gold standard. CPs were evaluated based on their accuracy in identifying diabetes and its subtype. RESULTS: The final DiCAYA CP requires at least one diabetes diagnosis code from clinical encounters. Subsequently, diabetes type classification was based on the ratio of type 1 diabetes (T1D) or type 2 diabetes (T2D) diagnosis codes in the EHR. For both youth and young adults, the sensitivity, specificity, and positive and negative predictive values (PPV and NPV, respectively) in finding diabetes cases were >90%, except for the specificity and NPV in young adults, which were slightly lower at 83.8% and 80.6%, respectively. The final DiCAYA CP achieved >90% sensitivity, specificity, PPV, and NPV in classifying T1D, and demonstrated lower but robust performance in identifying T2D, consistently maintaining >80% across metrics. CONCLUSIONS: The DiCAYA CP effectively identifies overall diabetes and T1D in youth and young adults, though T2D misclassification in youth highlights areas for refinement. The simplicity of the DiCAYA CP enables broad deployment across diverse EHR systems for diabetes surveillance.

BACKGROUND: Subpatent Plasmodium falciparum infections, defined as infections with parasite density below the detection limit of routine malaria diagnostic tests, contribute to infectious reservoirs, sustain transmission, and cause the failure of elimination strategies in target areas. This study assessed the prevalence of subpatent P. falciparum infections and associated risk factors in 14 regions of Mainland Tanzania. METHODS: The study used samples randomly selected from RDT-negative dried blood spots (DBS) (n = 2685/10,101) collected in 2021 at 100 health facilities across 10 regions of Mainland Tanzania, and four communities in four additional regions. The regions were selected from four transmission strata; high (five regions), moderate (three regions), low (three regions), and very low (three regions). DNA was extracted by Tween-Chelex method, and the Pf18S rRNA gene was amplified by quantitative polymerase chain reaction (qPCR). Logistic regression analysis was used to assess the associations between age groups, sex, fever status, and transmission strata with subpatent infection status, while linear regression analysis was used to assess the association between these factors and subpatent parasite density. RESULTS: Of the selected samples, 525/2685 (19.6%) were positive by qPCR for P. falciparum, and the positivity rates varied across different regions. Under-fives (aOR: 1.4, 95% CI 1.04-1.88; p < 0.05) from health facilities had higher odds of subpatent infections compared to other groups, while those from community surveys (aOR: 0.33, 95% CI 0.15-0.72; p = 0.005) had lower odds. Participants from very low transmission stratum had significantly lower odds of subpatent infection compared to those from high transmission stratum (aOR = 0.53, 95% CI = 0.37-0.78; p < 0.01). The log-transformed median parasite density (interquartile range) was 6.9 (5.8-8.5) parasites/µL, with significantly higher parasitaemia in the low transmission stratum compared to a very low one (11.4 vs 7.0 parasites/µL, p < 0.001). CONCLUSION: Even in very low transmission settings, the prevalence of subpatent infections was 13%, and in low transmission settings it was even higher at 29.4%, suggesting a substantial reservoir that is likely to perpetuate transmission but can be missed by routine malaria case management strategies. Thus, control and elimination programmes may benefit from adoption of more sensitive detection methods to ensure that a higher proportion of subpatent infections are detected.

BACKGROUND: Understanding virus-virus interactions is important for evaluating disease transmission and severity. Positive interactions suggest concurrent circulation, while negative interactions indicate reduced transmission of one virus when another is prevalent. This study examines interactions among seven respiratory viruses using a Bayesian approach that accounts for seasonality and long-term trends. METHODS: We analyzed data from 43,385 acute febrile illness cases in the Sentinel Enhanced Dengue Surveillance System in Puerto Rico (2013-2023). Viruses studied included influenza A (IAV), influenza B (IBV), respiratory syncytial virus (RSV), human parainfluenza viruses 1 and 3 (HPIV-1, HPIV-3), human adenovirus (HAdV), and human metapneumovirus (HMPV). Wavelet coherence analysis investigated synchronous or asynchronous viral co-variation, while a Bayesian hierarchical model estimated pairwise interactions. RESULTS: Among 43,385 participants, 26.0% tested positive for at least one virus, with IAV (9.5%), HAdV (4.1%), RSV (3.6%), and IBV (3.6%) being most frequent. Coinfections occurred in 0.5% of cases, often involving HAdV. Wavelet coherence identified significant synchronization among RSV/HMPV, HPIV-1/HMPV, and other virus pairs, with minimal coherence during the COVID-19 pandemic. Bayesian modeling suggested five virus-virus associations: four positive (RSV/HPIV-3, HMPV/HPIV-1, IBV/HAdV, IBV/HMPV) and one negative (IAV/HAdV). However, when restricting the analysis to the pre-pandemic period, fewer associations remained statistically credible. CONCLUSIONS: Respiratory viruses in Puerto Rico demonstrate patterns of co-circulation that may reflect complex interactions, but these associations appear context-dependent. Findings highlight the need for continued surveillance to better understand virus-virus dynamics and their implications for public health interventions.

Dengue, a mosquitoborne viral infection, is a public health threat in Puerto Rico, where multiple dengue virus (DENV) serotypes circulate. Dengue causes an acute febrile illness that can progress to severe disease or death. The last outbreak declared by the Puerto Rico Department of Health occurred during 2013. In January 2024, the number of dengue cases in Puerto Rico surpassed the epidemic threshold and remained elevated, prompting the Puerto Rico Department of Health to declare a public health emergency in March 2024. In collaboration with CDC, a dengue outbreak response was initiated to monitor the outbreak and implement vector-control measures alongside public health campaigns to raise awareness about increasing dengue case numbers and strategies to prevent mosquito bites. During 2024, a total of 6,291 confirmed dengue cases were reported; the highest numbers of cases were reported in the municipalities of San Juan (1,200; 17.3%), Carolina (354; 5.1%), and Rincón (252; 3.6%). DENV serotype 3 predominated, accounting for 59.2% of cases with known serotype. Approximately one half of ill patients (52.3%) required hospitalization, with the highest percentages of hospitalizations (33.9%) and severe dengue cases (28.4%) occurring among persons aged 10-19 years. Overall, severe dengue was identified in 4.2% of cases, with 11 reported fatalities (0.2%). Transmission remains elevated in multiple regions, underscoring the need for tailored public health measures, including vaccination among eligible populations, vector management, community outreach, and provider education to facilitate improved outcomes. To reduce the risk for mosquito bites, residents of and visitors to Puerto Rico should consider using repellents, wearing protective clothing, and staying in places with door and window screens.

Mosquito-transmitted viruses such as dengue are a global and growing public health challenge. Without widely available vaccines, mosquito control is the primary tool for fighting the spread of these viruses. New mosquito control technologies are needed to complement existing methods, given current challenges with scalability, acceptability, and effectiveness. A field trial was conducted in collaboration with the Communities Organized to Prevent Arboviruses project in Ponce, Puerto Rico, to measure entomological and epidemiological effects of reducing Aedes aegypti populations using Wolbachia incompatible insect technique. We packed and shipped Wolbachia-males from California and released them into 19 treatment clusters from September 2020 to December 2020. Preliminary evaluation revealed sub-optimal Wolbachia-male densities and impact on the wild-type population. In 2021, we shifted to a phased release strategy starting in four clusters, reducing the mosquito population by 49% (CI 29-63%). We describe the investigation into male quality and other factors that may have limited the impact of Wolbachia-male releases. Laboratory assays showed a small but significant impact of packing and shipping on male fitness. However, mark-release-recapture assessments suggest that male daily survival rates in the field may have been significantly impacted. We compared induced-sterility levels and suppression of the wild population and found patterns consistent with mosquito population compensation in response to our intervention. Analysis of epidemiological impact was not possible due to very low viral transmission rates during the intervention period. Our entomological impact data provide evidence that Wolbachia incompatible-male releases reduced Ae. aegypti populations, although efficacy will be maximized when releases are part of an integrated control program. With improvement of shipping vessels and shipped male fitness, packing and shipping male mosquitoes could provide a key solution for expanding access to this technology. Our project underscores the challenges involved in large and complex field effectiveness assessments of novel vector control methods.

BACKGROUND: Dengue virus, a major global health threat, consists of four serotypes (DENV1-4) that cause a range of clinical manifestations from mild to severe and potentially fatal disease. METHODS: This study, based on 19 years of data from the Pediatric Dengue Cohort Study and Pediatric Dengue Hospital-based Study in Managua, Nicaragua, investigates the relationship of serotype and immune status with dengue severity. Dengue cases were confirmed by molecular, serological, and/or virological methods, and study participants 6 months to 17 years old were followed during their hospital stay or as ambulatory patients. RESULTS: We enrolled a total of 15,833 participants, of whom 3,308 (21%) were positive for DENV infection. Of 2,644 cases with serotype result by RT-PCR, 559 corresponded to DENV1, 1,002 to DENV2, 760 to DENV3 and 323 to DENV4. Severe disease was more prevalent among secondary DENV2 and DENV4 cases, while similar disease severity was observed in both primary and secondary DENV1 and DENV3 cases. According to the 1997 World Health Organization (WHO) severity classification, both DENV2 and DENV3 caused a higher proportion of severe disease compared to other serotypes, whereas DENV3 caused the greatest percentage of severity according to the WHO-2009 classification. DENV2 was associated with increased odds of pleural effusion and low platelet count, while DENV3 was associated with both hypotensive and compensated shock. CONCLUSIONS: These findings demonstrate differences in dengue severity by serotype and immune status and emphasize the critical need for a dengue vaccine with balanced effectiveness against all four serotypes, particularly as existing vaccines show variable efficacy by serotype and serostatus.

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.

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

We compared the number of Aedes aegypti females per trap and the number of detections of this mosquito species per week during 8 wk in 3 types of autocidal gravid traps, the Centers for Disease Control and Prevention (CDC) Autocidal Gravid Ovitrap (AGO), Biogents Gravid Aedes Trap (GAT), and Singapore Gravitrap (SGT), in central Puerto Rico. These traps use the same principles for attracting gravid Ae. aegypti females as traditional ovitraps, such as dark colors, standing water, and decomposing plant materials. The traps differ in size, AGO being the biggest and SGT the smallest. Average captures of female Ae. aegypti per trap per week were 11.1, 7.2, and 1.7 in AGO, GAT, and SGT traps, respectively, a pattern consistent with the sizes of the traps. These results indicated that GAT traps and SGT traps captured 35.5% and 84.7% fewer females of Ae. aegypti, respectively, than AGO traps. Although Ae. aegypti was present in all 20 sites during the 8 wk of observations, AGO, GAT, and SGT traps did not catch specimens in 1, 9, and 58 out of 160 observations per trap type (trap-wk), respectively. Trap failures were 1, 6, and 1 for the AGO, GAT, and SGT traps, respectively. Despite the absence of females of Ae. aegypti at some sites and weeks in each of the traps, all 3 traps were able to detect the presence of this mosquito at each of the 20 sites during the 8 wk of observations and could be used for Ae. aegypti surveillance.

Dengue is a mosquitoborne viral illness that can cause acute febrile illness, severe disease, or death. Worldwide, the number of dengue cases is increasing. During the last dengue outbreaks in Puerto Rico throughout 2010-2013, dengue virus (DENV) serotype 1 (DENV-1) predominated, and the largest proportion of cases occurred among adolescents and young adults aged 10-19 years. Dengue case data from January 1, 2010-November 4, 2024, were obtained from the Puerto Rico Department of Health. Bivariate analyses were conducted to evaluate the distribution of cases by patient age, DENV serotype, and hospitalization status during three periods: 2010-2019, 2020-2022, and 2023-2024. During 2023-2024, the median age of dengue cases increased to 26 years (95% CI = 25-27 years) compared with that during 2020-2022 (17 years; 95% CI = 17-18 years) and 2010-2019 (19 years; 95% CI = 19-19 years). After >10 years of DENV-1 predominance, the proportions of DENV serotypes 2 (DENV-2) and 3 (DENV-3) increased significantly during 2023-2024, with DENV-3 replacing DENV-1 as the predominant serotype. In addition, the proportion of dengue patients who were hospitalized increased from 35.7% (2010-2019) to 53.5% (2023-2024). The current dengue outbreak in Puerto Rico marks a shift in serotype predominance to DENV-3 and increasing percentages of cases in older age groups (61.7% in adults aged ≥20 years), although a high proportion of cases still occur among adolescents aged 10-19 years (29.5%). The current dengue outbreak also has a higher rate of hospitalizations than those in previous years. Understanding the changing epidemiology of dengue is crucial to guiding public health strategies for dengue control, including clinical management, surveillance and health care system resilience, and public outreach and education.

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

Beyond its physical health impact, the COVID-19 pandemic also resulted in grief from loss of loved ones, isolation due to social distancing, stress, fear, and economic distress-all of which impacted mental health. How Right Now/Qué Hacer Ahora (HRN) is an award-winning, national campaign that provides emotional support to people disproportionately affected by COVID-19. We conducted a theory-based, culturally responsive evaluation to assess the campaign's effect on coping behaviors and resiliency between summer 2020 and spring 2021. We surveyed HRN's priority audiences (older adults/caregivers and those with preexisting health conditions, experiencing violence, or economic distress) in English and Spanish using NORC's national probability panel, AmeriSpeak, over three waves. We also analyzed social media data and monitored HRN website traffic and triangulated these data to understand the campaign's full impact. Campaign exposure was associated with people who were experiencing higher levels of stress and were more likely to seek information to support their emotional well-being. Campaign exposure was also positively associated with increased feelings of resilience and confidence in using coping strategies, especially for people experiencing violence or economic distress and people from racial and ethnic groups. Findings demonstrate the campaign's success in reaching its intended audiences with the mental health support they needed. Additionally, the HRN evaluation's design illustrates how the use of multiple data sources can elucidate a deeper understanding of campaign impact. Findings underscore that culturally responsive health communication interventions-like HRN-can provide needed mental health support and resources to disproportionately affected communities. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

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.

CONTEXT: International Classification of Diseases (ICD) codes are used for billing but also for surveillance for injuries such as traumatic brain injuries (TBI). While specificity is possible in the ICD-10-CM scheme, use of the code for unspecified injury of head (SO9.9) remains high. OBJECTIVES: This process evaluation sought to understand medical ICD-10-CM coding behaviors for TBI in emergency department (ED) settings. DESIGN: Semi-structured interviews explored the processes that facilitate or hinder ED physicians from selecting specific ICD codes for TBI and potential points of intervention for increased coding specificity and reducing the use of unspecified codes. SETTING: Video interviews were conducted with a nationwide sample in the United States. PARTICIPANTS: A purposive snowball sampling strategy was used to recruit 26 ED physicians with experience diagnosing TBI. INTERVENTION: Semi-structured interviews identified factors related to the selection of specific ICD codes for head injury. MAIN OUTCOME MEASURE: Thematic analysis of transcribed data. RESULTS: Four main themes emerged from the data: the impact of training and expertise, factors related to diagnosis, unclear connections with medical coders, and actionable recommendations. Interviews underscored the context surrounding "unspecified" codes for TBI, including demands from patient care, time pressures, issues around how a diagnosis may impact patient management decisions, and considerations related to mapping within the electronic medical record (EMR) where options may default to an unspecified code. CONCLUSIONS: Findings from this analysis indicate that ED providers may benefit from more robust training on how documentation can better support ICD-10-CM coding for this type of trauma. Revised EMR structures could support efficient coding specificity and clarity.

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.

CONTEXT: In the emergency department (ED) setting, prioritizing triage and patient care may lead to challenges in capturing detailed documentation necessary for specific International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) coding in medical records. Consequently, the prevalent use of the "unspecified head injury" code poses concerns about the precision of ED-based administrative billing claims data when analyzed for public health surveillance of nonfatal traumatic brain injuries (TBIs). Understanding the perspective of medical coders can illuminate coding processes and opportunities to enhance coding accuracy for TBI and other head injuries in the ED. OBJECTIVE: This evaluation explores medical coders' perspectives and challenges when assigning ICD-10-CM codes to head injuries in the ED. DESIGN: This qualitative evaluation utilized a phenomenological approach, which employed semi-structured interviews to understand medical coders' perspectives, processes, and coding determinations for head injuries in the ED. SETTING: Interviews were conducted using a HIPAA-compliant video-based platform between July 2022 and January 2023. PARTICIPANTS: Seventeen medical coders with ED coding experience were interviewed. Their backgrounds were diverse, though most had more than 15 years of experience. MAIN OUTCOMES: Four qualitative themes emerged, which highlighted challenges with lack of detailed documentation, defaulting to unspecified codes, time, and productivity pressure, and additional insights into coders' assumptions and code determination processes. RESULTS: Medical coders expressed challenges assigning ICD-10-CM codes to the highest level of specificity, citing issues including insufficient documentation by ED providers and terminology variations. Workplace time constraints and pressure for expedited claims also led to defaulting to unspecified codes. CONCLUSIONS: This evaluation highlights the need for improved documentation consistency and detail in ED records to facilitate accurate ICD-10-CM coding. Alleviating time pressures, improving algorithms, and offering specialized training opportunities to medical coders could be helpful steps to improve coding specificity and data accuracy for head injuries in the ED.

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.

OBJECTIVE: To estimate the national and regional population attributable fraction (PAF) and potential number of preventable anemia cases for three nutritional risk factors (iron, red blood cell folate [RBCF], and vitamin B12 deficiencies) among women of childbearing age in Belize. METHODS: A national probability-based household and micronutrient survey capturing sociodemographic and health information was conducted among 937 nonpregnant Belizean women aged 15-49 years. Blood samples were collected to determine hemoglobin, ferritin, alpha-1-glycoprotein (AGP), RBCF, and vitamin B12 status. All analyses used sample weights and design variables to reflect a complex sample survey. Logistic regression was used to determine adjusted prevalence risk (aPR) ratios, which were then used to estimate national and regional PAF for anemia. RESULTS: The overall prevalence of anemia (hemoglobin <12 g/dL) was 21.2% (95% CI [18.7, 25.3]). The prevalence of anemia was significantly greater among women with iron deficiency (59.5%, 95% CI [48.7, 69.5]) compared to women without iron deficiency (15.2%, 95% CI [12.2, 18.3]; aPR 3.9, 95% CI [2.9, 5.1]). The three nutritional deficiencies examined contributed to 34.6% (95% CI [22.1, 47.1]) of the anemia cases. If all these nutritional deficiencies could be eliminated, then an estimated 5 953 (95% CI [3 807, 8 114]) anemia cases could be prevented. CONCLUSIONS: This study suggests that among women of child-bearing age in Belize, anemia cases might be reduced by a third if three modifiable nutritional risk factors (iron, RBCF, and vitamin B12 deficiencies) could be eliminated. Fortification is one potential strategy to improve nutritional status and reduce the burden of anemia in this population.

OBJECTIVES: The Centers for Disease Control and Prevention (CDC) needs leaders at all levels who can address technical and adaptive challenges in a changing public health landscape. We assessed the feasibility of implementing an enterprise-wide leadership development model. METHODS: In June 2023, we launched a pilot program, Learn and Lead, for nonsupervisory staff in early and mid-career levels. One hundred sixty-nine participants registered, and 149 completed at least 6 weeks of the 8-week program. We gathered quantitative and qualitative data through weekly electronic surveys and in-depth interviews. We calculated frequencies for closed-ended Likert-scale items and performed content analysis of open-ended items to assess most frequently mentioned themes. We based the pilot's design on CDC's leadership development framework to assess application of the framework and alignment of curriculum to the framework. RESULTS: Three themes emerged: logistics and facilitation, leadership development curriculum, and making connections with self and others. Findings for logistics and facilitation highlighted preferences for course length, small breakout groups, mixed weeks, and value of staff support. Findings for the leadership development curriculum underscored the relevance of the US Office of Personnel Management's fundamental competencies to leadership development. Findings for making connections with self and others supported the cohort model and the importance of networking. CONCLUSIONS: The pilot curriculum aligned well with the CDC leadership development framework. Feedback provided by pilot participants is being used to help shape CDC's ongoing leadership development efforts.

The first dengue "endgame" summit was held in Syracuse, NY over August 9 and 10, 2023. Organized and hosted by the Institute for Global Health and Translational Sciences at SUNY Upstate Medical University, the gathering brought together researchers, clinicians, drug and vaccine developers, government officials, and other key stakeholders in the dengue field for a highly collaborative and discussion-oriented event. The objective of the gathering was to discuss the current state of dengue around the world, what dengue "control" might look like, and what a potential roadmap might look like to achieve functional dengue control. Over the course of 7 sessions, speakers with a diverse array of expertise highlighted both current and historic challenges associated with dengue control, the state of dengue countermeasure development and deployment, as well as fundamental virologic, immunologic, and medical barriers to achieving dengue control. While sustained eradication of dengue was considered challenging, attendees were optimistic that significant reduction in the burden of dengue can be achieved by integration of vector control with effective application of therapeutics and vaccines.

PROBLEM/CONDITION: Dengue is the most prevalent mosquitoborne viral illness worldwide and is endemic in Puerto Rico. Dengue's clinical spectrum can range from mild, undifferentiated febrile illness to hemorrhagic manifestations, shock, multiorgan failure, and death in severe cases. The disease presentation is nonspecific; therefore, various other illnesses (e.g., arboviral and respiratory pathogens) can cause similar clinical symptoms. Enhanced surveillance is necessary to determine disease prevalence, to characterize the epidemiology of severe disease, and to evaluate diagnostic and treatment practices to improve patient outcomes. The Sentinel Enhanced Dengue Surveillance System (SEDSS) was established to monitor trends of dengue and dengue-like acute febrile illnesses (AFIs), characterize the clinical course of disease, and serve as an early warning system for viral infections with epidemic potential. REPORTING PERIOD: May 2012-December 2022. DESCRIPTION OF SYSTEM: SEDSS conducts enhanced surveillance for dengue and other relevant AFIs in Puerto Rico. This report includes aggregated data collected from May 2012 through December 2022. SEDSS was launched in May 2012 with patients with AFIs from five health care facilities enrolled. The facilities included two emergency departments in tertiary acute care hospitals in the San Juan-Caguas-Guaynabo metropolitan area and Ponce, two secondary acute care hospitals in Carolina and Guayama, and one outpatient acute care clinic in Ponce. Patients arriving at any SEDSS site were eligible for enrollment if they reported having fever within the past 7 days. During the Zika epidemic (June 2016-June 2018), patients were eligible for enrollment if they had either rash and conjunctivitis, rash and arthralgia, or fever. Eligibility was expanded in April 2020 to include reported cough or shortness of breath within the past 14 days. Blood, urine, nasopharyngeal, and oropharyngeal specimens were collected at enrollment from all participants who consented. Diagnostic testing for dengue virus (DENV) serotypes 1-4, chikungunya virus, Zika virus, influenza A and B viruses, SARS-CoV-2, and five other respiratory viruses was performed by the CDC laboratory in San Juan. RESULTS: During May 2012-December 2022, a total of 43,608 participants with diagnosed AFI were enrolled in SEDSS; a majority of participants (45.0%) were from Ponce. During the surveillance period, there were 1,432 confirmed or probable cases of dengue, 2,293 confirmed or probable cases of chikungunya, and 1,918 confirmed or probable cases of Zika. The epidemic curves of the three arboviruses indicate dengue is endemic; outbreaks of chikungunya and Zika were sporadic, with case counts peaking in late 2014 and 2016, respectively. The majority of commonly identified respiratory pathogens were influenza A virus (3,756), SARS-CoV-2 (1,586), human adenovirus (1,550), respiratory syncytial virus (1,489), influenza B virus (1,430), and human parainfluenza virus type 1 or 3 (1,401). A total of 5,502 participants had confirmed or probable arbovirus infection, 11,922 had confirmed respiratory virus infection, and 26,503 had AFI without any of the arboviruses or respiratory viruses examined. INTERPRETATION: Dengue is endemic in Puerto Rico; however, incidence rates varied widely during the reporting period, with the last notable outbreak occurring during 2012-2013. DENV-1 was the predominant virus during the surveillance period; sporadic cases of DENV-4 also were reported. Puerto Rico experienced large outbreaks of chikungunya that peaked in 2014 and of Zika that peaked in 2016; few cases of both viruses have been reported since. Influenza A and respiratory syncytial virus seasonality patterns are distinct, with respiratory syncytial virus incidence typically reaching its annual peak a few weeks before influenza A. The emergence of SARS-CoV-2 led to a reduction in the circulation of other acute respiratory viruses. PUBLIC HEALTH ACTION: SEDSS is the only site-based enhanced surveillance system designed to gather information on AFI cases in Puerto Rico. This report illustrates that SEDSS can be adapted to detect dengue, Zika, chikungunya, COVID-19, and influenza outbreaks, along with other seasonal acute respiratory viruses, underscoring the importance of recognizing signs and symptoms of relevant diseases and understanding transmission dynamics among these viruses. This report also describes fluctuations in disease incidence, highlighting the value of active surveillance, testing for a panel of acute respiratory viruses, and the importance of flexible and responsive surveillance systems in addressing evolving public health challenges. Various vector control strategies and vaccines are being considered or implemented in Puerto Rico, and data from ongoing trials and SEDSS might be integrated to better understand epidemiologic factors underlying transmission and risk mitigation approaches. Data from SEDSS might guide sampling strategies and implementation of future trials to prevent arbovirus transmission, particularly during the expansion of SEDSS throughout the island to improve geographic representation.

Dengue is the most prevalent mosquito-borne viral disease in humans, and cases are continuing to rise globally. In particular, islands in the Caribbean have experienced more frequent outbreaks, and all four dengue virus (DENV) serotypes have been reported in the region, leading to hyperendemicity and increased rates of severe disease. However, there is significant variability regarding virus surveillance and reporting between islands, making it difficult to obtain an accurate understanding of the epidemiological patterns in the Caribbean. To investigate this, we used travel surveillance and genomic epidemiology to reconstruct outbreak dynamics, DENV serotype turnover, and patterns of spread within the region from 2009-2022. We uncovered two recent DENV-3 introductions from Asia, one of which resulted in a large outbreak in Cuba, which was previously under-reported. We also show that while outbreaks can be synchronized between islands, they are often caused by different serotypes. Our study highlights the importance of surveillance of infected travelers to provide a snapshot of local introductions and transmission in areas with limited local surveillance and suggests that the recent DENV-3 introductions may pose a major public health threat in the region.