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.

North-south pathways, emerging variants, and high climate suitability characterize the recent spread of dengue virus serotypes 2 and 3 in the Dominican Republic.

BACKGROUND: Dengue fever remains a significant public health challenge in tropical and subtropical regions, with its transmission dynamics being influenced by both environmental factors and human mobility. The Dominican Republic, a biodiversity hotspot in the Caribbean, has experienced recurrent dengue outbreaks, yet detailed understanding of the virus's transmission pathways and the impact of climatic factors remains limited. This study aims to elucidate the recent transmission dynamics of the dengue virus (DENV) in the Dominican Republic, utilizing a combination of genomic sequencing and epidemiological data analysis, alongside an examination of historical climate patterns. METHODS: We conducted a comprehensive study involving the genomic sequencing of DENV samples collected from patients across different regions of the Dominican Republic over a two-year period. Phylogenetic analyses were performed to identify the circulation of DENV lineages and to trace transmission pathways. Epidemiological data were integrated to analyze trends in dengue incidence and distribution. Additionally, we integrated historical climate data spanning several decades to assess trends in temperature and their potential impact on DENV transmission potential. RESULTS: Our results highlight a previously unknown north-south transmission pathway within the country, with the co-circulation of multiple virus lineages. Additionally, we examine the historical climate data, revealing long-term trends towards higher theoretical potential for dengue transmission due to rising temperatures. CONCLUSION: This multidisciplinary study reveals intricate patterns of dengue virus transmission in the Dominican Republic, characterized by the co-circulation of multiple DENV lineages and a novel transmission pathway. The observed correlation between rising temperatures and increased dengue transmission potential emphasizes the need for integrated climate-informed strategies in dengue control efforts. Our findings offer critical insights for public health authorities in the Dominican Republic and similar settings, guiding resource allocation and the development of preparedness strategies to mitigate the impacts of climate change on dengue transmission.

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.

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.

Investigating SARS-CoV-2 Incidence and Morbidity in Ponce, Puerto Rico: Protocol and Baseline Results From a Community Cohort Study.

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

North-south pathways, emerging variants, and high climate suitability characterize the recent spread of dengue virus serotypes 2 and 3 in the Dominican Republic.

We employ a multidisciplinary approach, integrating genomics and epidemiology, to uncover recent dengue virus transmission dynamics in the Dominican Republic. Our results highlight a previously unknown north-south transmission pathway within the country, with the co-circulation of multiple virus lineages. Additionally, we examine the historical climate data, revealing long-term trends towards higher theoretical potential for dengue transmission due to rising temperatures. These findings provide information for targeted interventions and resource allocation, informing as well towards preparedness strategies for public health agencies in mitigating climate and geo-related dengue risks.

Identification of risk factors and mosquito vectors associated with dengue virus infection in American Samoa, 2017.

INTRODUCTION: The first outbreak of dengue in American Samoa was reported in 1911. Sporadic outbreaks have been reported since, as were outbreaks of other pathogens transmitted by Aedes species mosquitoes including Ross River, chikungunya, and Zika viruses. During an outbreak of dengue virus-type 2 (DENV-2) in 2016-2018, we conducted household-based cluster investigations to identify population-specific risk factors associated with infection and performed entomologic surveillance to determine the relative abundance of Ae. aegypti and Ae. polynesiensis. METHODS AND FINDINGS: We contacted dengue patients who had tested positive for DENV infection and offered them as well as their household members participation in household-based cluster investigations. For those that accepted participation, we also offered participation to residents of households within a 50-meter radius of each case-patient's home. Questionnaires were administered and serum specimens collected for testing by RT-PCR and anti-DENV IgM ELISA. Adult female mosquitoes were aspirated from inside and outside participating households and tested by RT-PCR. We analyzed characteristics associated with DENV infection in bivariate analyses. A total of 226 participants was enrolled from 91 households in 20 clusters. Median age of participants was 34 years (range: <1-94), and 56.2% were female. In total, 7 (3.2%) participants had evidence of DENV infection by IgM ELISA (n = 5) or RT-PCR (n = 2). Factors significantly associated with DENV infection were reporting a febrile illness in the past three months (prevalence ratio: 7.5 [95% confidence interval: 1.9-29.8]) and having a household septic tank (Fisher's Exact Test, p = 0.004). Of 93 Ae. aegypti and 90 Ae. polynesiensis females collected, 90% of Ae. aegypti were collected inside homes whereas 83% of Ae. polynesiensis were collected outside homes. DENV nucleic acid was not detected in any mosquito pools. Sequencing of the DENV-2 from patient specimens identified the Cosmopolitan genotype of DENV-2 and was most closely related to virus detected in the Solomon Islands during 2016. CONCLUSIONS: This investigation demonstrated that dengue is a continuing risk in American Samoa. Increased frequency of infection among residents with a septic tank suggests a need to investigate whether septic tanks serve as larval habitats for mosquito vectors of DENV in American Samoa. Future efforts should also evaluate the role of Ae. polynesiensis in DENV transmission in the wild.

Previous Dengue Infection among Children in Puerto Rico and Implications for Dengue Vaccine Implementation.

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

Reemergence of Dengue Virus Serotype 3, Brazil, 2023.

We characterized 3 autochthonous dengue virus serotype 3 cases and 1 imported case from 2 states in the North and South Regions of Brazil, 15 years after Brazil's last outbreak involving this serotype. We also identified a new Asian lineage recently introduced into the Americas, raising concerns about future outbreaks.

SARS-CoV-2 Omicron Replacement of Delta as Predominant Variant, Puerto Rico.

We reconstructed the SARS-CoV-2 epidemic caused by Omicron variant in Puerto Rico by sampling genomes collected during October 2021-May 2022. Our study revealed that Omicron BA.1 emerged and replaced Delta as the predominant variant in December 2021. Increased transmission rates and a dynamic landscape of Omicron sublineage infections followed.

Clinical Features of COVID-19, Dengue, and Influenza among Adults Presenting to Emergency Departments and Urgent Care Clinics-Puerto Rico, 2012-2021.

Dengue and influenza are pathogens of global concern and cause febrile illness similar to COVID-19. We analyzed data from an enhanced surveillance system operating from three emergency departments and an urgent care clinic in Puerto Rico to identify clinical features predictive of influenza or dengue compared with COVID-19. Participants with fever or respiratory symptoms and aged ≥18 years enrolled May 2012-January 2021 with dengue, influenza, or SARS-CoV-2 confirmed by reverse transcriptase polymerase chain reaction were included. We calculated adjusted odds ratios (aORs) and 95% CIs using logistic regression to assess clinical characteristics of participants with COVID-19 compared to those with dengue or influenza, adjusting for age, subregion, and days from illness onset to presentation for clinical care. Among 13,431 participants, we identified 2,643 with dengue (N = 303), influenza (N = 2,064), or COVID-19 (N = 276). We found differences in days from onset to presentation among influenza (2 days [interquartile range: 1-3]), dengue (3 days [2-4]), and COVID-19 cases (4 days [2-7]; P < 0.001). Cough (aOR: 0.12 [95% CI: 0.07-0.19]) and shortness of breath (0.18 [0.08-0.44]) were less common in dengue compared with COVID-19. Facial flushing (20.6 [9.8-43.5]) and thrombocytopenia (24.4 [13.3-45.0]) were more common in dengue. Runny nose was more common in influenza compared with COVID-19 (8.3 [5.8-12.1]). In summary, cough, shortness of breath, facial flushing, and thrombocytopenia helped distinguish between dengue and COVID-19. Although few features distinguished influenza from COVID-19, presentation > 4 days after symptom onset suggests COVID-19. These findings may assist clinicians making time-sensitive decisions regarding triage, isolation, and management while awaiting pathogen-specific testing.

Genomic surveillance of SARS-CoV-2 in Puerto Rico enabled early detection and tracking of variants.

Background: Puerto Rico has experienced the full impact of the COVID-19 pandemic. Since SARS-CoV-2, the virus that causes COVID-19, was first detected on the island in March of 2020, it spread rapidly though the island's population and became a critical threat to public health. Methods: We conducted a genomic surveillance study through a partnership with health agencies and academic institutions to understand the emergence and molecular epidemiology of the virus on the island. We sampled COVID-19 cases monthly over 19 months and sequenced a total of 753 SARS-CoV-2 genomes between March 2020 and September 2021 to reconstruct the local epidemic in a regional context using phylogenetic inference. Results: Our analyses reveal that multiple importation events propelled the emergence and spread of the virus throughout the study period, including the introduction and spread of most SARS-CoV-2 variants detected world-wide. Lineage turnover cycles through various phases of the local epidemic were observed, where the predominant lineage was replaced by the next competing lineage or variant after ~4 months of circulation locally. We also identified the emergence of lineage B.1.588, an autochthonous lineage that predominated in Puerto Rico from September to December 2020 and subsequently spread to the United States. Conclusions: The results of this collaborative approach highlight the importance of timely collection and analysis of SARS-CoV-2 genomic surveillance data to inform public health responses.

Emergence of Dengue Virus Serotype 2 Cosmopolitan Genotype, Brazil.

We used nanopore sequencing and phylogenetic analyses to identify a cosmopolitan genotype of dengue virus serotype 2 that was isolated from a 56-year-old male patient from the state of Goiás in Brazil. The emergence of a cosmopolitan genotype in Brazil will require risk assessment and surveillance to reduce epidemic potential.

Risk factors for infection with chikungunya and Zika viruses in southern Puerto Rico: A community-based cross-sectional seroprevalence survey.

Chikungunya virus (CHIKV) caused a large outbreak in Puerto Rico in 2014, followed by a Zika virus (ZIKV) outbreak in 2016. Communities Organized for the Prevention of Arboviruses (COPA) is a cohort study in southern Puerto Rico, initiated in 2018 to measure arboviral disease risk and provide a platform to evaluate interventions. To identify risk factors for infection, we assessed prevalence of previous CHIKV infection and recent ZIKV and DENV infection in a cross-sectional study among COPA participants. Participants aged 1-50 years (y) were recruited from randomly selected households in study clusters. Each participant completed an interview and provided a blood specimen, which was tested by anti-CHIKV IgG ELISA assay and anti-ZIKV and anti-DENV IgM MAC-ELISA assays. We assessed individual, household, and community factors associated with a positive result for CHIKV or ZIKV after adjusting for confounders. During 2018-2019, 4,090 participants were enrolled; 61% were female and median age was 28y (interquartile range [IQR]: 16-41). Among 4,035 participants tested for CHIKV, 1,268 (31.4%) had evidence of previous infection. CHIKV infection prevalence was lower among children 1-10 years old compared to people 11 and older (adjusted odds ratio [aOR] 2.30; 95% CI 1.71-3.08). Lower CHIKV infection prevalence was associated with home screens (aOR 0.51; 95% CI 0.42-0.61) and air conditioning (aOR 0.64; 95% CI 0.54-0.77). CHIKV infection prevalence also varied by study cluster of residence and insurance type. Few participants (16; 0.4%) had evidence of recent DENV infection by IgM. Among 4,035 participants tested for ZIKV, 651 (16%) had evidence of recent infection. Infection prevalence increased with older age, from 7% among 1-10y olds up to 19% among 41-50y olds (aOR 3.23; 95% CI 2.16-4.84). Males had an increased risk of Zika infection prevalence compared with females (aOR 1.31; 95% CI 1.09-1.57). ZIKV infection prevalence also decreased with the presence of home screens (aOR 0.66; 95% CI 0.54-0.82) and air conditioning (aOR 0.69; 95% CI 0.57-0.84). Similar infection patterns were observed for recent ZIKV infection prevalence and previous CHIKV infection prevalence by age, and the presence of screens and air conditioners in the home decreased infection risk from both viruses by as much as 50%.

Predominance of Severe Plasma Leakage in Pediatric Patients With Severe Dengue in Puerto Rico.

BACKGROUND: We evaluated clinical and laboratory findings among patients with nonsevere or severe dengue in Puerto Rico to examine whether clinical manifestations vary by age. METHODS: During 2012-2014, we enrolled patients who arrived at the emergency department with fever or history of fever within 7 days of presentation. Serum samples were tested for dengue virus (DENV) by reverse transcriptase-polymerase chain reaction (RT-PCR) and IgM enzyme-linked immunosorbent assay (ELISA). Severe dengue was defined as severe plasma leakage or shock, severe bleeding, or organ involvement at presentation, during hospitalization, or follow-up. RESULTS: Of 1089 dengue patients identified, 281 (26%) were severe. Compared to those with nonsevere dengue, patients with severe dengue were more often aged 10-19 years (55% vs 40%, P < .001) and hospitalized (87% vs 30%, P < .001). Severe plasma leakage or shock was more common among children aged 0-9 (59%) or 10-19 years (86%) than adults (49%) (P < .01). Severe bleeding was less common among 10-19 year olds (24%) compared to 0-9 year olds (45%) and adults (52%; P < .01). CONCLUSIONS: Severe plasma leakage was the most common presentation among children, highlighting important differences from adults. Vaccination against dengue could help prevent severe dengue among children in Puerto Rico.

Evaluation of Serologic Cross-Reactivity Between Dengue Virus and SARS-CoV-2 in Patients with Acute Febrile Illness - United States and Puerto Rico, April 2020-March 2021.

The diagnosis of dengue disease, caused by the dengue virus (DENV) (a flavivirus), often requires serologic testing during acute and early convalescent phases of the disease. Some symptoms of DENV infection, such as nonspecific fever, are similar to those caused by infection with SARS-CoV-2, the virus that causes COVID-19. In studies with few COVID-19 cases, positive DENV immunoglobulin M (IgM) results were reported with various serologic tests, indicating possible cross-reactivity in these tests for DENV and SARS-CoV-2 infections (1,2). DENV antibodies can cross-react with other flaviviruses, including Zika virus. To assess the potential cross-reactivity of SARS-CoV-2, DENV, and Zika virus IgM antibodies, serum specimens from 97 patients from Puerto Rico and 12 U.S.-based patients with confirmed COVID-19 were tested using the DENV Detect IgM Capture enzyme-linked immunosorbent assay (ELISA) (InBios International).* In addition, 122 serum specimens from patients with confirmed dengue and 121 from patients with confirmed Zika virus disease (all from Puerto Rico) were tested using the SARS-CoV-2 pan-Ig Spike Protein ELISA (CDC).† Results obtained for DENV, Zika virus IgM, and SARS-CoV-2 antibodies indicated 98% test specificity and minimal levels of cross-reactivity between the two flaviviruses and SARS-CoV-2. These findings indicate that diagnoses of dengue or Zika virus diseases with the serological assays described in this report are not affected by COVID-19, nor do dengue or Zika virus diseases interfere with the diagnosis of COVID-19.

Genomic surveillance of SARS-CoV-2 in Puerto Rico reveals emergence of an autochthonous lineage and early detection of variants.

Puerto Rico has experienced the full impact of the COVID-19 pandemic. Since SARS-CoV-2, the virus that causes COVID-19, was first detected on the island in March of 2020, it spread rapidly though the island’s population and became a critical threat to public health. We conducted a genomic surveillance study through a partnership with health agencies and academic institutions to understand the emergence and molecular epidemiology of the virus on the island. We sampled COVID-19 cases monthly over 19 months and sequenced a total of 753 SARS-CoV-2 genomes between March 2020 and September 2021 to reconstruct the local epidemic in a regional context using phylogenetic inference. Our analyses revealed that multiple importation events propelled the emergence and spread of the virus throughout the study period, including the introduction and spread of most SARS-CoV-2 variants detected world-wide. Lineage turnover cycles through various phases of the local epidemic were observed, where the predominant lineage was replaced by the next competing lineage or variant after approximately 4 months of circulation locally. We also identified the emergence of lineage B.1.588, an autochthonous lineage that predominated circulation in Puerto Rico from September to December 2020 and subsequently spread to the United States. The results of this collaborative approach highlight the importance of timely collection and analysis of SARS-CoV-2 genomic surveillance data to inform public health responses.

Capacity of a Multiplex IgM Antibody Capture ELISA to Differentiate Zika and Dengue Virus Infections in Areas of Concurrent Endemic Transmission.

Serological cross-reactivity has proved to be a challenge to diagnose Zika virus (ZIKV) infections in dengue virus (DENV) endemic countries. Confirmatory testing of ZIKV IgM positive results by plaque reduction neutralization tests (PRNTs) provides clarification in only a minority of cases because most individuals infected with ZIKV were previously exposed to DENV. The goal of this study was to evaluate the performance of a ZIKV/DENV DUO IgM antibody capture ELISA (MAC-ELISA) for discriminating between DENV and ZIKV infections in endemic regions. Our performance evaluation included acute and convalescent specimens from patients with real-time reverse transcription polymerase chain reaction (RT-PCR)-confirmed DENV or ZIKV from the Sentinel Enhanced Dengue Surveillance System in Ponce, Puerto Rico. The ZIKV/DENV DUO MAC-ELISA specificity was 100% for DENV (N = 127) and 98.4% for ZIKV (N = 275) when specimens were tested during the optimal testing window (days post-onset of illness [DPO] 6-120). The ZIKV/DENV DUO MAC-ELISA sensitivity of RT-PCR confirmed specimens reached 100% for DENV by DPO 6 and for ZIKV by DPO 9. Our new ZIKV/DENV DUO MAC-ELISA was also able to distinguish ZIKV and DENV regardless of previous DENV exposure. We conclude this novel serologic diagnostic assay can accurately discriminate ZIKV and DENV infections. This can potentially be useful considering that the more labor-intensive and expensive PRNT assay may not be an option for confirmatory diagnosis in areas that lack PRNT capacity, but experience circulation of both DENV and ZIKV.

Tracing the Origin, Spread, and Molecular Evolution of Zika Virus in Puerto Rico, 2016-2017.

We reconstructed the 2016-2017 Zika virus epidemic in Puerto Rico by using complete genomes to uncover the epidemic's origin, spread, and evolutionary dynamics. Our study revealed that the epidemic was propelled by multiple introductions that spread across the island, intricate evolutionary patterns, and ≈10 months of cryptic transmission.