Comparison of the sensitivity and specificity of commercial anti-dengue virus IgG tests to identify persons eligible for dengue vaccination.

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.

Hepatic Vitamin A Concentrations and Association with Infectious Causes of Child Death.

OBJECTIVES: To assess postmortem vitamin A (VA) concentrations in children under 5 years of age and evaluate the association between VA deficiency (VAD) and infectious causes of death (CoD). STUDY DESIGN: In this cross-sectional study from the Child Health and Mortality Prevention Surveillance (CHAMPS) Network, liver biopsies collected within 72 hours of death were analyzed from 405 stillbirths and children under 5 years in Kenya and South Africa. Total liver VA (TLVA) concentrations were quantified using ultra-performance liquid chromatography, and cutoffs of ≤0.1 µmol/g, >0.1 to <0.7 µmol/g, ≥0.7 to <1.0 µmol/g, and ≥1.0 µmol/g were used to define VAD, adequate VA status, high VA, and hypervitaminosis A, respectively. CoD were determined by expert panel review. RESULTS: Among 366 liver samples with viable extraction, pooled prevalences of VAD, adequacy, high VA, and hypervitaminosis were 34.2%, 51.1%, 6.0%, and 8.7%, respectively. VAD was more common among neonates compared with stillbirths, infants, or children, and among those with low birthweight (LBW), underweight, or stunting (P < .05). When adjusting for site, age, and sex, there was no significant association of VAD with increased infectious CoD (OR 1.9, 95% confidence interval [CI] 0.9, 3.8, P = .073). In stratified analyses, VA deficient boys, but not girls, had an increased risk of infectious CoD (OR 3.4, 95% CI 1.3, 10.3, P = .013). CONCLUSIONS: Definitive postmortem assessment of VA status identified both VAD and VA excess among children under 5 years of age in Kenya and South Africa. VAD in boys was associated with increased risk of infectious mortality. Our findings may inform a transition from universal VA supplementation (VAS) to targeted strategies in certain countries.

Modeling the impacts of antiviral prophylaxis strategies in mitigating seasonal influenza outbreaks in nursing homes.

BACKGROUND: Antiviral chemoprophylaxis is recommended for use during influenza outbreaks in nursing homes to prevent transmission and severe disease among non-ill residents. Centers for Disease Control and Prevention (CDC) guidance recommends prophylaxis be initiated for all non-ill residents once an influenza outbreak is detected and be continued for at least 14 days and until seven days after the last laboratory-confirmed influenza case is identified. However, not all facilities strictly adhere to this guidance and the impact of such partial adherence is not fully understood. METHODS: We developed a stochastic compartmental framework to model influenza transmission within an average-sized U.S. nursing home. We compared the number of symptomatic illnesses and hospitalizations under varying prophylaxis implementation strategies, in addition to different levels of prophylaxis uptake and adherence by residents and healthcare personnel (HCP). RESULTS: Prophylaxis implemented according to current guidance reduced total symptomatic illnesses and hospitalizations among residents by an average of 12% and 36%, respectively, compared with no prophylaxis. We did not find evidence that alternative implementations of prophylaxis were more effective: compared to full adoption of current guidance, partial adoption resulted in increased symptomatic illnesses and/or hospitalizations, and longer or earlier adoption offered no additional improvements. In addition, increasing uptake and adherence among nursing home residents was effective in reducing resident illnesses and hospitalizations, but increasing HCP uptake had minimal indirect impacts for residents. CONCLUSIONS: The greatest benefits of influenza prophylaxis during nursing home outbreaks will likely be achieved through increasing uptake and adherence among residents and following current CDC guidance.

Serial Interval and Incubation Period Estimates of Monkeypox Virus Infection in 12 Jurisdictions, United States, May-August 2022.

Using data from 12 US health departments, we estimated mean serial interval for monkeypox virus infection to be 8.5 (95% credible interval 7.3-9.9) days for symptom onset, based on 57 case pairs. Mean estimated incubation period was 5.6 (95% credible interval 4.3-7.8) days for symptom onset, based on 35 case pairs.

Rapid review and meta-analysis of serial intervals for SARS-CoV-2 Delta and Omicron variants.

BACKGROUND: The serial interval is the period of time between symptom onset in the primary case and symptom onset in the secondary case. Understanding the serial interval is important for determining transmission dynamics of infectious diseases like COVID-19, including the reproduction number and secondary attack rates, which could influence control measures. Early meta-analyses of COVID-19 reported serial intervals of 5.2 days (95% CI: 4.9-5.5) for the original wild-type variant and 5.2 days (95% CI: 4.87-5.47) for Alpha variant. The serial interval has been shown to decrease over the course of an epidemic for other respiratory diseases, which may be due to accumulating viral mutations and implementation of more effective nonpharmaceutical interventions. We therefore aggregated the literature to estimate serial intervals for Delta and Omicron variants. METHODS: This study followed Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. A systematic literature search was conducted of PubMed, Scopus, Cochrane Library, ScienceDirect, and preprint server medRxiv for articles published from April 4, 2021, through May 23, 2023. Search terms were: ("serial interval" or "generation time"), ("Omicron" or "Delta"), and ("SARS-CoV-2" or "COVID-19"). Meta-analyses were done for Delta and Omicron variants using a restricted maximum-likelihood estimator model with a random effect for each study. Pooled average estimates and 95% confidence intervals (95% CI) are reported. RESULTS: There were 46,648 primary/secondary case pairs included for the meta-analysis of Delta and 18,324 for Omicron. Mean serial interval for included studies ranged from 2.3-5.8 days for Delta and 2.1-4.8 days for Omicron. The pooled mean serial interval for Delta was 3.9 days (95% CI: 3.4-4.3) (20 studies) and Omicron was 3.2 days (95% CI: 2.9-3.5) (20 studies). Mean estimated serial interval for BA.1 was 3.3 days (95% CI: 2.8-3.7) (11 studies), BA.2 was 2.9 days (95% CI: 2.7-3.1) (six studies), and BA.5 was 2.3 days (95% CI: 1.6-3.1) (three studies). CONCLUSIONS: Serial interval estimates for Delta and Omicron were shorter than ancestral SARS-CoV-2 variants. More recent Omicron subvariants had even shorter serial intervals suggesting serial intervals may be shortening over time. This suggests more rapid transmission from one generation of cases to the next, consistent with the observed faster growth dynamic of these variants compared to their ancestors. Additional changes to the serial interval may occur as SARS-CoV-2 continues to circulate and evolve. Changes to population immunity (due to infection and/or vaccination) may further modify it.

Household hardships and responses to COVID-19 pandemic-related shocks in Eastern Ethiopia.

BACKGROUND: COVID-19 resulted in enormous disruption to life around the world. To quell disease spread, governments implemented lockdowns that likely created hardships for households. To improve knowledge of consequences, we examine how the pandemic period was associated with household hardships and assess factors associated with these hardships. METHODS: We conducted a cross-sectional study using quasi-Poisson regression to examine factors associated with household hardships. Data were collected between August and September of 2021 from a random sample of 880 households living within a Health and Demographic Surveillance System (HDSS) located in the Harari Region and the District of Kersa, both in Eastern Ethiopia. RESULTS: Having a head of household with no education, residing in a rural area, larger household size, lower income and/or wealth, and community responses to COVID-19, including lockdowns and travel restrictions, were independently associated with experiencing household hardships. CONCLUSIONS: Our results identify characteristics of groups at-risk for household hardships during the pandemic; these findings may inform efforts to mitigate the consequences of COVID-19 and future disease outbreaks.

Using simulated infectious disease outbreaks to inform site selection and sample size for individually randomized vaccine trials during an ongoing epidemic.

BACKGROUND: Novel strategies are needed to make vaccine efficacy trials more robust given uncertain epidemiology of infectious disease outbreaks, such as arboviruses like Zika. Spatially resolved mathematical and statistical models can help investigators identify sites at highest risk of future transmission and prioritize these for inclusion in trials. Models can also characterize uncertainty in whether transmission will occur at a site, and how nearby or connected sites may have correlated outcomes. A structure is needed for how trials can use models to address key design questions, including how to prioritize sites, the optimal number of sites, and how to allocate participants across sites. METHODS: We illustrate the added value of models using the motivating example of Zika vaccine trial planning during the 2015-2017 Zika epidemic. We used a stochastic, spatially resolved, transmission model (the Global Epidemic and Mobility model) to simulate epidemics and site-level incidence at 100 high-risk sites in the Americas. We considered several strategies for prioritizing sites (average site-level incidence of infection across epidemics, median incidence, probability of exceeding 1% incidence), selecting the number of sites, and allocating sample size across sites (equal enrollment, proportional to average incidence, proportional to rank). To evaluate each design, we stochastically simulated trials in each hypothetical epidemic by drawing observed cases from site-level incidence data. RESULTS: When constraining overall trial size, the optimal number of sites represents a balance between prioritizing highest-risk sites and having enough sites to reduce the chance of observing too few endpoints. The optimal number of sites remained roughly constant regardless of the targeted number of events, although it is necessary to increase the sample size to achieve the desired power. Though different ranking strategies returned different site orders, they performed similarly with respect to trial power. Instead of enrolling participants equally from each site, investigators can allocate participants proportional to projected incidence, though this did not provide an advantage in our example because the top sites had similar risk profiles. Sites from the same geographic region may have similar outcomes, so optimal combinations of sites may be geographically dispersed, even when these are not the highest ranked sites. CONCLUSION: Mathematical and statistical models may assist in designing successful vaccination trials by capturing uncertainty and correlation in future transmission. Although many factors affect site selection, such as logistical feasibility, models can help investigators optimize site selection and the number and size of participating sites. Although our study focused on trial design for an emerging arbovirus, a similar approach can be made for any infectious disease with the appropriate model for the particular disease.

Changes in socio-economic status and lipoproteins in Chilean adolescents: a 16-year longitudinal study.

OBJECTIVE: The present longitudinal study assessed whether changes in socio-economic status (SES) from infancy to adolescence were associated with plasma lipoprotein concentrations in adolescence, of which low HDL-cholesterol (HDL-C) and high LDL-cholesterol (LDL-C), TAG and total cholesterol (TC) concentrations are associated with higher cardiovascular risk. DESIGN: SES, assessed using the modified Graffar Index, was calculated at 1, 5, 10 and 16 years. Principal components factor analysis with varimax rotation extracted two orthogonal SES factors, termed 'environmental capital' and 'social capital'. Generalized linear models were used to analyse associations between environmental and social capital at 1 and 16 years and outcomes (HDL-C, LDL-C, TAG, TC) at 16 years, as well as changes in environmental and social capital from 1-5, 5-10, 10-16 and 1-16 years, and outcomes at 16 years. SETTING: Santiago, Chile.ParticipantsWe evaluated 665 participants from the Santiago Longitudinal Study enrolled at infancy in Fe-deficiency anaemia studies and examined every 5 years to age 16 years. RESULTS: Social capital in infancy was associated with higher HDL-C in adolescence. Environmental capital in adolescence was associated with higher LDL-C and TC during adolescence. Changing environmental capital from 1-16 years was associated with higher LDL-C. Changing environmental capital from 1-5 and 1-16 years was associated with higher TC. CONCLUSIONS: Improvements in environmental capital throughout childhood were associated with less healthy LDL-C and TC concentrations in adolescence. We found no evidence of associations between changing environmental capital and HDL-C or TAG, or changing social capital and HDL-C, LDL-C, TAG or TC.

Associations between household environmental factors and immature mosquito abundance in Quetzaltenango, Guatemala.

BACKGROUND: Aedes aegypti-borne diseases are becoming major public health problems in tropical and sub-tropical regions. While socioeconomic status has been associated with larval mosquito abundance, the drivers or possible factors mediating this association, such as environmental factors, are yet to be identified. We examined possible associations between proximity to houses and roads and immature mosquito abundance, and assessed whether these factors and mosquito prevention measures mediated any association between household environmental factors and immature mosquito abundance. METHODS: We conducted two cross-sectional household container surveys in February-March and November-December, 2017, in urban and rural areas of Quetzaltenango, Guatemala. We used principal components analysis to identify factors from 12 variables to represent the household environment. One factor which included number of rooms in house, electricity, running water, garbage service, cable, television, telephone, latrine, well, and sewer system, was termed "environmental capital." Environmental capital scores ranged from 0 to 5.5. Risk factors analyzed included environmental capital, and distance from nearest house/structure, paved road, and highway. We used Poisson regression to determine associations between distance to nearest house/structure, roads, and highways, and measures of immature mosquito abundance (total larvae, total pupae, and positive containers). Using cubic spline generalized additive models, we assessed non-linear associations between environmental capital and immature mosquito abundance. We then examined whether fumigation, cleaning containers, and distance from the nearest house, road, and highway mediated the relationship between environmental capital and larvae and pupae abundance. RESULTS: We completed 508 household surveys in February-March, and we revisited 469 households in November-December. Proximity to paved roads and other houses/structures was positively associated with larvae and pupae abundance and mediated the associations between environmental capital and total numbers of larvae/pupae (p ≤ 0.01). Distance to highways was not associated with larval/pupal abundance (p ≥ 0.48). Households with the lowest and highest environmental capital had fewer larvae/pupae than households in the middle range (p < 0.01). CONCLUSIONS: We found evidence that proximity to other houses and paved roads was associated with greater abundance of larvae and pupae. Understanding risk factors such as these can allow for improved targeting of surveillance and vector control measures in areas considered at higher risk for arbovirus transmission.

Nowcasting and forecasting the 2022 U.S. mpox outbreak: Support for public health decision making and lessons learned.

In June of 2022, the U.S. Centers for Disease Control and Prevention (CDC) Mpox Response wanted timely answers to important epidemiological questions which can now be answered more effectively through infectious disease modeling. Infectious disease models have shown to be valuable tools for decision making during outbreaks; however, model complexity often makes communicating the results and limitations of models to decision makers difficult. We performed nowcasting and forecasting for the 2022 mpox outbreak in the United States using the R package EpiNow2. We generated nowcasts/forecasts at the national level, by Census region, and for jurisdictions reporting the greatest number of mpox cases. Modeling results were shared for situational awareness within the CDC Mpox Response and publicly on the CDC website. We retrospectively evaluated forecast predictions at four key phases (early, exponential growth, peak, and decline) during the outbreak using three metrics, the weighted interval score, mean absolute error, and prediction interval coverage. We compared the performance of EpiNow2 with a naïve Bayesian generalized linear model (GLM). The EpiNow2 model had less probabilistic error than the GLM during every outbreak phase except for the early phase. We share our experiences with an existing tool for nowcasting/forecasting and highlight areas of improvement for the development of future tools. We also reflect on lessons learned regarding data quality issues and adapting modeling results for different audiences.

Prevalence of food insecurity amid COVID-19 lockdowns and sociodemographic indicators of household vulnerability in Harar and Kersa, Ethiopia.

BACKGROUND: The COVID-19 pandemic was associated with widespread social disruptions, as governments implemented lockdowns to quell disease spread. To advance knowledge of consequences for households in resource-limited countries, we examine food insecurity during the pandemic period. METHODS: We conducted a cross-sectional study and used logistic regression to examine factors associated with food insecurity. Data were collected between August and September of 2021 through a Health and Demographic Surveillance System (HDSS) using a survey instrument focused on knowledge regarding the spread of COVID-19; food availability; COVID-19 related shocks/coping; under-five child healthcare services; and healthcare services for pregnant women. The study is set in two communities in Eastern Ethiopia, one rural (Kersa) and one urban (Harar), and included a random sample of 880 households. RESULTS: Roughly 16% of households reported not having enough food to eat during the pandemic, an increase of 6% since before the pandemic. After adjusting for other variables, households were more likely to report food insecurity if they were living in an urban area, were a larger household, had a family member lose employment, reported an increase in food prices, or were food insecure before the pandemic. Households were less likely to report food insecurity if they were wealthier or had higher household income. CONCLUSIONS: After taking individual and household level sociodemographic characteristics into consideration, households in urban areas were at higher risk for food insecurity. These findings suggest a need for expanding food assistance programs to more urban areas to help mitigate the impact of lockdowns on more vulnerable households.

A systematic review and meta-analysis on the effectiveness of bivalent mRNA booster vaccines against Omicron variants.

BACKGROUND: A global shift to bivalent mRNA vaccines is ongoing to counterbalance the diminishing effectiveness of the original monovalent vaccines due to the evolution of SARS-CoV-2 variants, yet substantial variation in the bivalent vaccine effectiveness (VE) exists across studies and a complete picture is lacking. METHODS: We searched papers evaluating absolute or relative effectiveness of SARS-CoV-2 BA.1 type or BA.4/5 type bivalent mRNA vaccines on eight publication databases published from September 1st, 2022, to November 8th, 2023. Pooled VE against Omicron-associated infection and severe events (hospitalization and/or death) was estimated in reference to unvaccinated, ≥2 original monovalent doses, and ≥ 3 original monovalent doses. RESULTS: From 630 citations identified, 28 studies were included, involving 55,393,303 individuals. Bivalent boosters demonstrated higher effectiveness against symptomatic or any infection for all ages combined, with an absolute VE of 53.5 % (95 % CI: -22.2-82.3 %) when compared to unvaccinated and relative VE of 30.8 % (95 % CI: 22.5-38.2 %) and 28.4 % (95 % CI: 10.2-42.9 %) when compared to ≥ 2 and ≥ 3 original monovalent doses, respectively. The corresponding VE estimates for adults ≥ 60 years old were 22.5 % (95 % CI: 16.8-39.8 %), 31.4 % (95 % CI: 27.7-35.0 %), and 30.6 % (95 % CI: -13.2-57.5 %). Pooled bivalent VE estimates against severe events were higher, 72.9 % (95 % CI: 60.5-82.4 %), 57.6 % (95 % CI: 42.4-68.8 %), and 62.1 % (95 % CI: 54.6-68.3 %) for all ages, and 72.0 % (95 % CI: 51.4-83.9 %), 63.4 % (95 % CI: 41.0-77.3 %), and 60.7 % (95 % CI: 52.4-67.6 %) for adults ≥ 60 years old, compared to unvaccinated, ≥2 original monovalent doses, and ≥ 3 original monovalent doses, respectively. CONCLUSIONS: The bivalent boosters demonstrated superior protection against severe outcomes than the original monovalent boosters across age groups, highlighting the critical need for improving vaccine coverage, especially among the vulnerable older subpopulation.

Coronavirus awareness, prevention, and household hardship survey data for the CHAMPS HDSS network: Data collected between August and September of 2022 from the Bamako HDSS, Mali.

Data were gathered through a collaborative initiative to investigate impacts of the COVID-19 pandemic and related lockdowns on child and maternal health, economic hardships, and access to care for children and pregnant women by the Child Health and Mortality Prevention Surveillance (CHAMPS) Network. The data were gathered in Bamako, the capital city of Mali (population ∼2.9 million) between August and September of 2022 through a Health and Demographic Surveillance System (HDSS). Data collectors used a survey instrument specifically designed to measure household awareness, knowledge, and prevalence of COVID-19, as well as hardships that households experienced since the onset of the pandemic in March of 2020. The data are from two neighborhoods of Bamako, Banconi and Djicoroni; the Health and Demographic Surveillance System (HDSS) operating in these neighborhoods tracks the health of approximately 235,000 inhabitants. The data were collected using a stratified random sample of 454 households.

Coronavirus awareness and household hardship survey data for the CHAMPS HDSS network: Data collected between April 2021 and February 2022 in the Manhiça HDSS, Mozambique.

Data collection was implemented through an initiative by the Child Health and Mortality Prevention Surveillance (CHAMPS) Network to assess whether lockdowns and other social distancing policies during COVID-19 had implications for household economic status, maternal and child health, and healthcare accessibility for pregnant women and children. The data were collected from April 2021 until February 2022 from a population living in a rural community of Mozambique. This rural community is located within a Health and Demographic Surveillance System (HDSS) that operates in the Manhiça district of Maputo province. The survey instrument used for data collection was specifically designed to examine household awareness, knowledge, and prevalence of COVID-19; it was also designed to document hardships experienced by households during the pandemic period such as food insecurity, job losses and/or business closures of household members, and access to healthcare. The data are generalizable to a contiguous community in Manhiça, Mozambique of approximately 200,000 inhabitants.

Sentinel Enhanced Dengue Surveillance System - Puerto Rico, 2012-2022.

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.

Comparison of the Sensitivity and Specificity of Commercial Anti-Dengue Virus IgG Tests to Identify Persons Eligible for Dengue Vaccination.

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 7 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 5 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 9-16-year-old children from Puerto Rico. Finally, a full-scale evaluation was done with the 4 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 detecting anti-DENV IgG in early convalescent specimens with low cross-reactivity to 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.

Diagnostic Accuracy of the Abbott BinaxNOW COVID-19 Antigen Card Test, Puerto Rico.

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.

Neurological Symptoms and Cause of Death Among Young Children in Low- and Middle-Income Countries.

Importance: The emergence of acute neurological symptoms in children necessitates immediate intervention. Although low- and middle-income countries (LMICs) bear the highest burden of neurological diseases, there is a scarcity of diagnostic and therapeutic resources. Therefore, current understanding of the etiology of neurological emergencies in LMICs relies mainly on clinical diagnoses and verbal autopsies. Objective: To characterize the association of premortem neurological symptoms and their management with postmortem-confirmed cause of death among children aged younger than 5 years in LMICs and to identify current gaps and improve strategies to enhance child survival. Design, Setting, and Participants: This cross-sectional study was conducted between December 3, 2016, and July 22, 2022, at the 7 participating sites in the Child Health and Mortality Prevention Surveillance (CHAMPS) network (Bangladesh, Ethiopia, Kenya, Mali, Mozambique, Sierra Leone, and South Africa). Minimally invasive tissue sampling was performed at the CHAMPS sites with specimens from deceased children aged younger than 5 years. This study included deceased children who underwent a premortem neurological evaluation and had a postmortem-confirmed cause of death. Data analysis was performed between July 22, 2022, and January 15, 2023. Main Outcomes and Measures: Descriptive analysis was performed using neurological evaluations from premortem clinical records and from postmortem determination of cause of death (based on histopathology, microbiological testing, clinical records, and verbal autopsies). Results: Of the 2127 deaths of children codified during the study period, 1330 (62.5%) had neurological evaluations recorded and were included in this analysis. The 1330 children had a median age of 11 (IQR, 2-324) days; 745 (56.0%) were male and 727 (54.7%) presented with neurological symptoms during illness before death. The most common postmortem-confirmed neurological diagnoses related to death were hypoxic events (308 [23.2%]), meningoencephalitis (135 [10.2%]), and cerebral malaria (68 [5.1%]). There were 12 neonates with overlapping hypoxic events and meningoencephalitis, but there were no patients with overlapping meningoencephalitis and cerebral malaria. Neurological symptoms were similar among diagnoses, and no combination of symptoms was accurate in differentiating them without complementary tools. However, only 25 children (18.5%) with meningitis had a lumbar puncture performed before death. Nearly 90% of deaths (442 of 511 [86.5%]) with neurological diagnoses in the chain of events leading to death were considered preventable. Conclusions and Relevance: In this cross-sectional study of children aged younger than 5 years, neurological symptoms were frequent before death. However, clinical phenotypes were insufficient to differentiate the most common underlying neurological diagnoses. The low rate of lumbar punctures performed was especially worrying, suggesting a challenge in quality of care of children presenting with neurological symptoms. Improved diagnostic management of neurological emergencies is necessary to ultimately reduce mortality in this vulnerable population.