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.

Characteristics and clinical outcomes of patients hospitalized with laboratory-confirmed COVID-19-Puerto Rico, March-August 2020.

Hispanics are the majority ethnic population in Puerto Rico where we reviewed charts of 109 hospitalized COVID-19 patients to better understand demographic and clinical characteristics of COVID-19 and determine risk factors for poor outcomes. Eligible medical records of hospitalized patients with confirmed COVID-19 illnesses were reviewed at four participating hospitals in population centers across Puerto Rico and data were abstracted that described the clinical course, interventions, and outcomes. We found hospitalized patients had a median of 3 underlying conditions with obesity and diabetes as the most frequently reported conditions. Intensive care unit (ICU) admission occurred among 28% of patients and 18% of patients died during the hospitalization. Patients 65 or older or with immune deficiencies had a higher risk for death. Common symptoms included cough, dyspnea, and fatigue; less than half of patients in the study reported fever which was less frequent than reported elsewhere in the literature. It is important for interventions within Hispanic communities to protect high-risk groups.

Antibody-independent and dependent infection of human myeloid cells with dengue virus is inhibited by carrageenan.

This study demonstrated that the λ-carrageenan is a potent and selective inhibitor of the primary infection of human myeloid U937 and K562 cells with the four DENV serotypes, achieving a higher than 99 % reduction in virus production at the highest tested concentration of 20 µg/mL, without affecting cell viability at concentrations up to 1000 µg/mL. Since antibody-dependent enhancement (ADE) is thought to play a main role in the aggravation of severe DENV disease, we also evaluated the activity of carrageenan against ADE of DENV infection. The λ-carrageenan was also effective to block the antibody dependent infection mediated by Fcγ-RII in both cell lines, causing 96-99 % inhibition in virus production from cells infected with immune complexes of DENV-2 and DENV-3. Moreover, the inhibitory effectiveness of carrageenan was similar against prM-mediated ADE or E-mediated ADE. Mechanistic studies indicated that DENV-2 entry is the main antiviral target for carrageenan in DENV or DENV-Ab infected human myeloid cells since a strong inhibitory effect was observed when the carrageenan was present only during adsorption at 4 °C or internalization at 37 °C, whereas the infection was not altered when the compound was added after virus internalization. Thus, our findings have shown that carrageenan may be considered an interesting antiviral agent able to block DENV entry during both primary and antibody-dependent infection of human myeloid cells.

Injury-Related Emergency Department Visits After Hurricane Maria in a Southern Puerto Rico Hospital.

OBJECTIVE: The aim of this study was to describe individuals seeking care for injury at a major emergency department (ED) in southern Puerto Rico in the months after Hurricane Maria on September 20, 2017. METHODS: After informed consent, we used a modified version of the Natural Disaster Morbidity Surveillance Form to determine why patients were visiting the ED during October 16, 2017-March 28, 2018. We analyzed visits where injury was reported as the primary reason for visit and whether it was hurricane-related. RESULTS: Among 5 116 patients, 573 (11%) reported injury as the primary reason for a visit. Of these, 10% were hurricane-related visits. The most common types of injuries were abrasions, lacerations, and cuts (43% of all injury visits and 50% of hurricane-related visits). The most common mechanisms of injury were falls, slips, trips (268, 47%), and being hit by/or against an object (88, 15%). Most injury visits occurred during the first 3 months after the hurricane. CONCLUSIONS: Surveillance after Hurricane Maria identified injury as the reason for a visit for about 1 in 10 patients visiting the ED, providing evidence on the patterns of injuries in the months following a hurricane. Public health and emergency providers can use this information to anticipate health care needs after a disaster.

Evaluation of Emergency Department-Based Surveillance Systems at 2 Healthcare Facilities After Hurricane Maria: Puerto Rico, 2017-2018.

OBJECTIVES: Hurricane Maria caused catastrophic damage in Puerto Rico, increasing the risk for morbidity and mortality in the post-impact period. We aimed to establish a syndromic surveillance system to describe the number and type of visits at 2 emergency health-care settings in the same hospital system in Ponce, Puerto Rico. METHODS: We implemented a hurricane surveillance system by interviewing patients with a short questionnaire about the reason for visit at a hospital emergency department and associated urgent care clinic in the 6 mo after Hurricane Maria. We then evaluated the system by comparing findings with data from the electronic medical record (EMR) system for the same time period. RESULTS: The hurricane surveillance system captured information from 5116 participants across the 2 sites, representing 17% of all visits captured in the EMR for the same period. Most visits were associated with acute illness/symptoms (79%), followed by injury (11%). The hurricane surveillance and EMR data were similar, proportionally, by sex, age, and visit category. CONCLUSIONS: The hurricane surveillance system provided timely and representative data about the number and type of visits at 2 sites. This system, or an adapted version using available electronic data, should be considered in future disaster settings.

Role of the ERK1/2 Signaling Pathway in the Replication of Junín and Tacaribe Viruses.

We have previously shown that the infection of cell cultures with the arenaviruses Junín (JUNV), Tacaribe (TCRV), and Pichindé promotes the phosphorylation of mitogen-activated protein kinases (MAPKs) extracellular signal-regulated kinases 1 and 2 (ERK1/2) and that this activation is required for the achievement of a productive infection. Here we examined the contribution of ERK1/2 in early steps of JUNV and TCRV multiplication. JUNV adsorption, internalization, and uncoating were not affected by treatment of cultured cells with U0126, an inhibitor of the ERK1/2 signaling pathway. In contrast, U0126 caused a marked reduction in viral protein expression and RNA synthesis, while JUNV RNA synthesis was significantly augmented in the presence of an activator of the ERK1/2 pathway. Moreover, U0126 impaired the expression of a reporter gene in a TCRV-based replicon system, confirming the ability of the compound to hinder arenavirus macromolecular synthesis. By using a cell-based assay, we determined that the inhibitor did not affect the translation of a synthetic TCRV-like mRNA. No changes in the phosphorylation pattern of the translation factor eIF2α were found in U0126-treated cells. Our results indicate that U0126 impairs viral RNA synthesis, thereby leading to a subsequent reduction in viral protein expression. Thus, we conclude that ERK1/2 signaling activation is required for an efficient arenavirus RNA synthesis.

Antiviral activity of natural and synthetic ß-carbolines against dengue virus.

Dengue virus (DENV) is the most prevalent mosquito borne viral pathogen worldwide. In this work we first evaluated the antiviral activity of natural and synthetic ß-carbolines against DENV-2 multiplication in cell cultures. We determined that the natural ß-carboline harmol and a synthetic harmine derivative, 9N-methylharmine, exhibit inhibitory effect on DENV-2 production without virucidal activity. The active compounds were inhibitory of all DENV serotypes, being DENV-2 the more susceptible to their antiviral action. The mode of action of 9N-methylharmine against DENV-2 was further explored. We determined that the derivative neither affects viral adsorption-internalization events nor viral RNA synthesis. The quantification of intracellular and extracellular viral genomes and infectious virus particles indicated that 9N-methylharmine would impair the maturation and release of virus particles to the extracellular medium affecting the spreading of the infection. Furthermore, we also determined that 9N-methylharmine antiviral activity is not related to the ability of the compound to downregulate p38 MAPK phosphorylation.