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

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.

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.

Dengvaxia is the first dengue vaccine recommended in the United States (U.S.). It is recommended for children aged 9-16 y with laboratory-confirmed previous dengue infection and living in areas where dengue is endemic. We conducted focus groups with parents and in-depth interviews with key informants (i.e. practicing pediatricians, physicians from immunization clinics, university researchers, and school officials) in Puerto Rico (P.R.) to examine acceptability, barriers, and motivators to vaccinate with Dengvaxia. We also carried out informal meetings and semi-structured interviews to evaluate key messages and educational materials with pediatricians and parents. Barriers to vaccination included lack of information, distrust toward new vaccines, vaccine side effects and risks, and high cost of/lack of insurance coverage for laboratory tests and vaccines. Motivators included clear information about the vaccine, a desire to prevent future dengue infections, the experience of a previous dengue infection or awareness of dengue fatality, vaccine and laboratory tests covered by health insurance, availability of rapid test results and vaccine appointments. School officials and parents agreed parents would pay a deductible of $5-20 for Dengvaxia. For vaccine information dissemination, parents preferred an educational campaign through traditional media and social media, and one-on-one counseling of parents by healthcare providers. Education about this vaccine to healthcare providers will help them answer parents' questions. Dengvaxia acceptability in P.R. will increase by addressing motivators and barriers to vaccination and by disseminating vaccine information in plain language through spokespersons from health institutions in P.R.

Pregnant women traveling abroad can be exposed to a variety of arboviruses, primarily spread by mosquitoes or ticks. Some arboviral infections can be of particular concern for pregnant women or their fetuses. Vaccination is one preventive measure that can reduce the risk for infection. Several arboviral vaccines have been licensed for many years and can be used to prevent infection in travelers, namely Japanese encephalitis, yellow fever, and tick-borne encephalitis vaccines. Recommendations on use of these vaccines in pregnancy vary. Other arboviral vaccines have been licensed but are not indicated for use in pregnant travelers (e.g., dengue vaccines) or are in development (e.g., chikungunya, Zika vaccines). This review describes arboviral vaccines for travelers, focusing on women who are pregnant and those planning travel during pregnancy.

Dengue, the leading cause of arboviral disease worldwide, can be fatal without appropriate treatment. Among 7,528 confirmed or probable travel-associated U.S. dengue cases reported during 2010-2021, one in five (1,474, 20%) was reported in 2019. This is 168% higher than the annual average number of cases reported during 2010-2018 and 2020-2021 (approximately 550 per year) and 61% higher than the 913 cases reported in 2016, the second highest year on record. The number of cases as a fraction of air traffic volume to international destinations outside North America or Europe was also highest in 2019, with 41.9 cases per million trips, compared with 21.0 per million in other years during 2010-2021. This report compares the number and characteristics of travel-associated dengue cases reported to national surveillance in the United States in 2019 with cases reported during 2010-2018 and 2020-2021. Areas with conditions suitable for dengue transmission as well as the population at risk for dengue are expected to increase, placing U.S. travelers at higher risk for infection. Health care providers should be aware that dengue is a common cause of fever in the returning traveler and be familiar with its signs and symptoms, testing, and management. Dengue vaccines are not currently recommended for U.S. travelers; therefore, persons should review areas of dengue risk and follow guidance for preventing mosquito bites.

Background: Multisystem inflammatory syndrome in children (MIS-C) is a hyperinflammatory condition associated with antecedent SARS-CoV-2 infection. In the United States, reporting of MIS-C after vaccination is required under COVID-19 vaccine emergency use authorizations. This case series describes persons aged 12-20 years with MIS-C following COVID-19 vaccination reported to passive surveillance systems or through clinician outreach to CDC. Method(s): We investigated potential cases of MIS-C after COVID-19 vaccination reported to CDC's health department-based national MIS-C surveillance, the Vaccine Adverse Event Reporting System (VAERS, co-administered by CDC and the U.S. FDA), and CDC's Clinical Immunization Safety Assessment Project (CISA) from December 14, 2020, to August 31, 2021. We describe cases meeting the CDC MIS-C case definition. Any positive SARS-CoV-2 serology test satisfied the case criteria although anti-nucleocapsid antibody indicates SARS-CoV-2 infection, while anti-spike protein antibody indicates either infection or COVID-19 vaccination. Finding(s): We identified 21 persons with MIS-C after COVID-19 vaccination. Of these 21 persons, median age was 16 years (range, 12-20 years); 13 (62%) were male. All were hospitalized; 12 (57%) had intensive care unit admission, and all were discharged home. Fifteen (71%) of the 21 had laboratory evidence of past or recent SARS-CoV-2 infection, and six (29%) did not. Through August 2021, 21,335,331 persons aged 12-20 years had received >=1 dose of COVID-19 vaccine, making the overall reporting rate for MIS-C following vaccination 1.0 case per million persons receiving >=1 vaccine dose in this age group. The reporting rate for those without evidence of SARS-CoV-2 infection was 0.3 cases per million vaccinated persons. Interpretation(s): In our case series, we describe a small number of persons with MIS-C who had received >=1 COVID-19 vaccine dose before illness onset. Continued reporting of potential cases and surveillance for MIS-C illnesses after COVID-19 vaccination is warranted. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.

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

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

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.

As of October 21, 2022, a total of 27,884 monkeypox cases (confirmed and probable) have been reported in the United States.(§) Gay, bisexual, and other men who have sex with men have constituted a majority of cases, and persons with HIV infection and those from racial and ethnic minority groups have been disproportionately affected (1,2). During previous monkeypox outbreaks, severe manifestations of disease and poor outcomes have been reported among persons with HIV infection, particularly those with AIDS (3-5). This report summarizes findings from CDC clinical consultations provided for 57 patients aged ≥18 years who were hospitalized with severe manifestations of monkeypox(¶) during August 10-October 10, 2022, and highlights three clinically representative cases. Overall, 47 (82%) patients had HIV infection, four (9%) of whom were receiving antiretroviral therapy (ART) before monkeypox diagnosis. Most patients were male (95%) and 68% were non-Hispanic Black (Black). Overall, 17 (30%) patients received intensive care unit (ICU)-level care, and 12 (21%) have died. As of this report, monkeypox was a cause of death or contributing factor in five of these deaths; six deaths remain under investigation to determine whether monkeypox was a causal or contributing factor; and in one death, monkeypox was not a cause or contributing factor.** Health care providers and public health professionals should be aware that severe morbidity and mortality associated with monkeypox have been observed during the current outbreak in the United States (6,7), particularly among highly immunocompromised persons. Providers should test all sexually active patients with suspected monkeypox for HIV at the time of monkeypox testing unless a patient is already known to have HIV infection. Providers should consider early commencement and extended duration of monkeypox-directed therapy(††) in highly immunocompromised patients with suspected or laboratory-diagnosed monkeypox.(§§) Engaging all persons with HIV in sustained care remains a critical public health priority.

As of October 11, 2022, a total of 26,577 monkeypox cases had been reported in the United States.* Although most cases of monkeypox are self-limited, lesions that involve anatomically vulnerable sites can cause complications. Ocular monkeypox can occur when Monkeypox virus (MPXV) is introduced into the eye (e.g., from autoinoculation), potentially causing conjunctivitis, blepharitis, keratitis, and loss of vision (1). This report describes five patients who acquired ocular monkeypox during July-September 2022. All patients received treatment with tecovirimat (Tpoxx)(†); four also received topical trifluridine (Viroptic).(§) Two patients had HIV-associated immunocompromise and experienced delays between clinical presentation with monkeypox and initiation of monkeypox-directed treatment. Four patients were hospitalized, and one experienced marked vision impairment. To decrease the risk for autoinoculation, persons with monkeypox should be advised to practice hand hygiene and to avoid touching their eyes, which includes refraining from using contact lenses (2). Health care providers and public health practitioners should be aware that ocular monkeypox, although rare, is a sight-threatening condition. Patients with signs and symptoms compatible with ocular monkeypox should be considered for urgent ophthalmologic evaluation and initiation of monkeypox-directed treatment. Public health officials should be promptly notified of cases of ocular monkeypox. Increased clinician awareness of ocular monkeypox and of approaches to prevention, diagnosis, and treatment might reduce associated morbidity.

Since May 2022, approximately 20,000 cases of monkeypox have been identified in the United States, part of a global outbreak occurring in approximately 90 countries and currently affecting primarily gay, bisexual, and other men who have sex with men (MSM) (1). Monkeypox virus (MPXV) spreads from person to person through close, prolonged contact; a small number of cases have occurred in populations who are not MSM (e.g., women and children), and testing is recommended for persons who meet the suspected case definition* (1). CDC previously developed five real-time polymerase chain reaction (PCR) assays for detection of orthopoxviruses from lesion specimens (2,3). CDC was granted 510(k) clearance for the nonvariola-orthopoxvirus (NVO)-specific PCR assay by the Food and Drug Administration. This assay was implemented within the Laboratory Response Network (LRN) in the early 2000s and became critical for early detection of MPXV and implementation of public health action in previous travel-associated cases as well as during the current outbreak (4-7). PCR assays (NVO and other Orthopoxvirus laboratory developed tests [LDT]) represent the primary tool for monkeypox diagnosis. These tests are highly sensitive, and cross-contamination from other MPXV specimens being processed, tested, or both alongside negative specimens can occasionally lead to false-positive results. This report describes three patients who had atypical rashes and no epidemiologic link to a monkeypox case or known risk factors; these persons received diagnoses of monkeypox based on late cycle threshold (Ct) values ≥34, which were false-positive test results. The initial diagnoses were followed by administration of antiviral treatment (i.e., tecovirimat) and JYNNEOS vaccine postexposure prophylaxis (PEP) to patients' close contacts. After receiving subsequent testing, none of the three patients was confirmed to have monkeypox. Knowledge gained from these and other cases resulted in changes to CDC guidance. When testing for monkeypox in specimens from patients without an epidemiologic link or risk factors or who do not meet clinical criteria (or where these are unknown), laboratory scientists should reextract and retest specimens with late Ct values (based on this report, Ct ≥34 is recommended) (8). CDC can be consulted for complex cases including those that appear atypical or questionable cases and can perform additional viral species- and clade-specific PCR testing and antiorthopoxvirus serologic testing.

Dengue is the disease caused by 1 of 3 distinct, but closely related dengue viruses (DENV-1-4) that are transmitted by Aedes spp. mosquito vectors. It is the most common arboviral disease worldwide, with the greatest burden in tropical and sub-tropical regions. In the absence of effective prevention and control measures, dengue is projected to increase in both disease burden and geographic range. Given its increasing importance as an etiology of fever in the returning traveler or the possibility of local transmission in regions in the United States with competent vectors, as well as the risk for large outbreaks in endemic US territories and associated states, clinicians should understand its clinical presentation and be familiar with appropriate testing, triage, and management of patients with dengue. Control and prevention efforts reached a milestone in June 2021 when the Advisory Committee on Immunization Practices (ACIP) recommended Dengvaxia for routine use in children aged 9 to 16 years living in endemic areas with laboratory confirmation of previous dengue virus infection. Dengvaxia is the first vaccine against dengue to be recommended for use in the United States and one of the first to require laboratory testing of potential recipients to be eligible for vaccination. In this review, we outline dengue pathogenesis, epidemiology, and key clinical features for front-line clinicians evaluating patients presenting with dengue. We also provide a summary of Dengvaxia efficacy, safety, and considerations for use as well as an overview of other potential new tools to control and prevent the growing threat of dengue .

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a hyperinflammatory condition associated with antecedent SARS-CoV-2 infection. In the USA, reporting of MIS-C after vaccination is required under COVID-19 vaccine emergency use authorisations. We aimed to investigate reports of individuals aged 12-20 years with MIS-C after COVID-19 vaccination reported to passive surveillance systems or through clinician outreach to the US Centers for Disease Control and Prevention (CDC). METHODS: In this surveillance activity, we investigated potential cases of MIS-C after COVID-19 vaccination reported to CDC's MIS-C national surveillance system, the Vaccine Adverse Event Reporting System (co-administered by CDC and the US Food and Drug Administration), and CDC's Clinical Immunization Safety Assessment Project. A multidisciplinary team adjudicated cases by use of the CDC MIS-C definition. Any positive SARS-CoV-2 serology test satisfied case criteria; although anti-nucleocapsid antibodies indicate previous SARS-CoV-2 infection, anti-spike protein antibodies indicate either past or recent infection or COVID-19 vaccination. We describe the demographic and clinical features of cases, stratified by laboratory evidence of SARS-CoV-2 infection. To calculate the reporting rate of MIS-C, we divided the count of all individuals meeting the MIS-C case definition, and of those without evidence of SARS-CoV-2 infection, by the number of individuals aged 12-20 years in the USA who received one or more COVID-19 vaccine doses up to Aug 31, 2021, obtained from CDC national vaccine surveillance data. FINDINGS: Using surveillance results from Dec 14, 2020, to Aug 31, 2021, we identified 21 individuals with MIS-C after COVID-19 vaccination. Of these 21 individuals, median age was 16 years (range 12-20); 13 (62%) were male and eight (38%) were female. All 21 were hospitalised: 12 (57%) were admitted to an intensive care unit and all were discharged home. 15 (71%) of 21 individuals had laboratory evidence of past or recent SARS-CoV-2 infection, and six (29%) did not. As of Aug 31, 2021, 21 335 331 individuals aged 12-20 years had received one or more doses of a COVID-19 vaccine, making the overall reporting rate for MIS-C after vaccination 1·0 case per million individuals receiving one or more doses in this age group. The reporting rate in only those without evidence of SARS-CoV-2 infection was 0·3 cases per million vaccinated individuals. INTERPRETATION: Here, we describe a small number of individuals with MIS-C who had received one or more doses of a COVID-19 vaccine before illness onset; the contribution of vaccination to these illnesses is unknown. Our findings suggest that MIS-C after COVID-19 vaccination is rare. Continued reporting of potential cases and surveillance for MIS-C illnesses after COVID-19 vaccination is warranted. FUNDING: US Centers for Disease Control and Prevention.

OBJECTIVE: To assess COVID-19 vaccine providers' adherence to best practices and identify knowledge and practice gaps to guide corrective actions and retraining activities in Puerto Rico. METHODS: A CDC supportive evaluation tool was modified to collect information on vaccine storage, handling, preparation, administration, and post-vaccination care. Assessment visits to COVID-19 vaccine providers in Puerto Rico were conducted a month after the availability of COVID-19 vaccines in the island. RESULTS: A total 16 vaccine providers were visited, 12 (75%) administering Pfizer-BioNTech vaccine and 4 (25%) administering Moderna vaccine. All providers adhered to correct handling practices after vaccine thawing. Required resources for managing anaphylaxis on site were available in all sites. Few instances of incorrect use of retractable-needle syringes, unapproved temperature monitoring devices, and lack of recorded temperature data were observed. Corrective actions were taken during the evaluation visit. CONCLUSION: No major deficiencies that could jeopardize vaccine viability or patient safety were found. The use of a supportive evaluation tool during assessment visits is helpful to determine needs for vaccine providers retraining and to continue the safe administration of COVID-19 vaccines in Puerto Rico.

Dengue is a vectorborne infectious disease caused by dengue viruses (DENVs), which are predominantly transmitted by Aedes aegypti and Aedes albopictus mosquitos. Dengue is caused by four closely related viruses (DENV-1-4), and a person can be infected with each serotype for a total of four infections during their lifetime. Areas where dengue is endemic in the United States and its territories and freely associated states include Puerto Rico, American Samoa, the U.S. Virgin Islands, the Federated States of Micronesia, the Republic of Marshall Islands, and the Republic of Palau. This report summarizes the recommendations of the Advisory Committee on Immunization Practices (ACIP) for use of the Dengvaxia vaccine in the United States. The vaccine is a live-attenuated, chimeric tetravalent dengue vaccine built on a yellow fever 17D backbone. Dengvaxia is safe and effective in reducing dengue-related hospitalizations and severe dengue among persons who have had dengue infection in the past. Previous natural infection is important because Dengvaxia is associated with an increased risk for severe dengue in those who experience their first natural infection (i.e., primary infection) after vaccination. Dengvaxia was licensed by the Food and Drug Administration for use among children and adolescents aged 9-16 years (referred to in this report as children). ACIP recommends vaccination with Dengvaxia for children aged 9-16 having evidence of a previous dengue infection and living in areas where dengue is endemic. Evidence of previous dengue infection, such as detection of anti-DENV immunoglobulin G with a highly specific serodiagnostic test, will be required for eligible children before vaccination.

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.

BACKGROUND: Little is known about how HIV infection affects influenza transmission within homes in sub-Saharan Africa. METHODS: We used respiratory illness surveillance and HIV testing data gathered in Kibera, an urban slum in Nairobi, Kenya to examine the impact of HIV status on (i) introducing influenza to the home and (ii) transmission to household contacts. RESULTS: While HIV status did not affect the likelihood of being an influenza index case, household contacts of HIV-infected influenza index cases had twice the risk of developing secondary ILI than contacts of HIV-negative index cases. CONCLUSIONS: HIV-infected influenza index cases may facilitate transmission of influenza within the home.

BACKGROUND: Prolonged pathogen shedding and increased duration of illness associated with infections in immunosuppressed individuals put close HIV-negative contacts of HIV-infected people at increased risk of exposure to infectious pathogens. METHODS: We calculated incidence and longitudinal prevalence (number of days per year) of influenza-like illness (ILI), diarrhea, and non-specific febrile illness during 2008 from a population-based surveillance program in the urban slum of Kibera (Kenya) consisting of 1830 HIV-negative household contacts of HIV-infected individuals and 13 677 individuals living in exclusively HIV-negative households. RESULTS: For individuals ≥5 years old, incidence was significantly increased for ILI (IRR, 1.47; P < .05) and diarrhea (IRR, 1.41; P < .05) in HIV-negative household contacts of HIV-infected individuals compared to exclusively HIV-negative households. The risk of illness among HIV-negative people was directly proportional to the number of HIV-infected people living in the home for ILI (IRR, 1.39; P < .05) and diarrhea (IRR, 1.36; P < .01). We found no increased rates of illness in children <5 years old who lived with HIV-infected individuals. CONCLUSIONS: Living with HIV-infected individuals is associated with modestly increased rates of respiratory and diarrheal infections in HIV-negative individuals >5 years old. Targeted interventions are needed, including ensuring that HIV-infected people are receiving appropriate care and treatment.

INTRODUCTION: Ninety-five percent of burn deaths occur in low- and middle-income countries (LMICs); however, longitudinal household-level studies have not been done in urban slum settings, where overcrowding and unsafe cook stoves may increase likelihood of injury. METHODS: Using a prospective, population-based disease surveillance system in the urban slum of Kibera in Kenya, we examined the incidence of household-level burns of all severities from 2006-2011. RESULTS: Of approximately 28,500 enrolled individuals (6000 households), we identified 3072 burns. The overall incidence was 27.9/1000 person-years-of-observation. Children <5 years old sustained burns at 3.8-fold greater rate compared to (p<0.001) those ≥5 years old. Females ≥5 years old sustained burns at a rate that was 1.35-fold (p<0.001) greater than males within the same age distribution. Hospitalizations were uncommon (0.65% of all burns). CONCLUSIONS: The incidence of burns, 10-fold greater than in most published reports from Africa and Asia, suggests that such injuries may contribute more significantly than previously thought to morbidity in LMICs, and may be increased by urbanization. As migration from rural areas into urban slums rapidly increases in many African countries, characterizing and addressing the rising burden of burns is likely to become a public health priority.

BACKGROUND: Influenza vaccine is rarely used in Kenya, and little is known about attitudes towards the vaccine. From June-September 2010, free seasonal influenza vaccine was offered to children between 6 months and 10 years old in two Population-Based Infectious Disease Surveillance (PBIDS) sites. This survey assessed attitudes about influenza, uptake of the vaccine and experiences with childhood influenza vaccination. METHODS: We administered a questionnaire and held focus group discussions with parents of children of enrollment age in the two sites before and after first year of the vaccine campaign. For pre-vaccination focus group discussions, we randomly selected mothers and fathers who had an eligible child from the PBIDS database to participate. For the post-vaccination focus group discussions we stratified parents whose children were eligible for vaccination into fully vaccinated, partially vaccinated and non-vaccinated groups. RESULTS: Overall, 5284 and 5755 people completed pre and post-vaccination questionnaires, respectively, in Kibera and Lwak. From pre-vaccination questionnaire results, among parents who were planning on vaccinating their children, 2219 (77.6%) in Kibera and 1780 (89.6%) in Lwak said the main reason was to protect the children from seasonal influenza. In the pre-vaccination discussions, no parent had heard of the seasonal influenza vaccine. At the end of the vaccine campaign, of 18,652 eligible children, 5,817 (31.2%) were fully vaccinated, 2,073 (11.1%) were partially vaccinated and, 10,762 (57.7%) were not vaccinated. In focus group discussions, parents who declined vaccine were concerned about vaccine safety or believed seasonal influenza illness was not severe enough to warrant vaccination. Parents who declined the vaccine were mainly too busy [251(25%) in Kibera and 95 (10.5%) in Lwak], or their child was away during the vaccination period [199(19.8%) in Kibera; 94(10.4%) in Lwak]. CONCLUSION: If influenza vaccine were to be introduced more broadly in Kenya, effective health messaging will be needed on vaccine side effects and frequency and potential severity of influenza infection.