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.

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.

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.

Knowledge gaps in the epidemiology of severe dengue impede vaccine evaluation.

The most severe consequences of dengue virus infection include shock, haemorrhage, and major organ failure; however, the frequency of these manifestations varies, and the relative contribution of pre-existing anti-dengue virus antibodies, virus characteristics, and host factors (including age and comorbidities) are not well understood. Reliable characterisation of the epidemiology of severe dengue first depends on the use of consistent definitions of disease severity. As vaccine trials have shown, severe dengue is a crucial interventional endpoint, yet the infrequency of its occurrence necessitates the inclusion of thousands of study participants to appropriately compare its frequency among participants who have and have not been vaccinated. Hospital admission is frequently used as a proxy for severe dengue; however, lack of specificity and variability in clinical practices limit the reliability of this approach. Although previous infection with a dengue virus is the best characterised risk factor for developing severe dengue, the influence of the timing between dengue virus infections and the sequence of dengue virus infections on disease severity is only beginning to be elucidated. To improve our understanding of the diverse factors that shape the clinical spectrum of disease resulting from dengue virus infection, prospective, community-based and clinic-based immunological, virological, genetic, and clinical studies across a range of ages and geographical regions are needed.

Cost-effectiveness of dengue vaccination in Puerto Rico.

An effective and widely used vaccine could reduce the burden of dengue virus (DENV) around the world. DENV is endemic in Puerto Rico, where the dengue vaccine CYD-TDV is currently under consideration as a control measure. CYD-TDV has demonstrated efficacy in clinical trials in vaccinees who had prior dengue virus infection. However, in vaccinees who had no prior dengue virus infection, the vaccine had a modestly elevated risk of hospitalization and severe disease. The WHO therefore recommended a strategy of pre-vaccination screening and vaccination of seropositive persons. To estimate the cost-effectiveness and benefits of this intervention (i.e., screening and vaccination of seropositive persons) in Puerto Rico, we simulated 10 years of the intervention in 9-year-olds using an agent-based model. Across the entire population, we found that 5.5% (4.6%-6.3%) of dengue hospitalizations could be averted. However, we also found that 0.057 (0.045-0.073) additional hospitalizations could occur for every 1,000 people in Puerto Rico due to DENV-naïve children who were vaccinated following a false-positive test results for prior exposure. The ratio of the averted hospitalizations among all vaccinees to additional hospitalizations among DENV-naïve vaccinees was estimated to be 19 (13-24). At a base case cost of vaccination of 382 USD, we found an incremental cost-effectiveness ratio of 122,000 USD per QALY gained. Our estimates can provide information for considerations to introduce the CYD-TDV vaccine in Puerto Rico.

Dengue Vaccine: Recommendations of the Advisory Committee on Immunization Practices, United States, 2021.

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.

Epidemiologic and spatiotemporal trends of Zika Virus disease during the 2016 epidemic in Puerto Rico.

BACKGROUND: After Zika virus (ZIKV) emerged in the Americas, laboratory-based surveillance for arboviral diseases in Puerto Rico was adapted to include ZIKV disease. METHODS AND FINDINGS: Suspected cases of arboviral disease reported to Puerto Rico Department of Health were tested for evidence of infection with Zika, dengue, and chikungunya viruses by RT-PCR and IgM ELISA. To describe spatiotemporal trends among confirmed ZIKV disease cases, we analyzed the relationship between municipality-level socio-demographic, climatic, and spatial factors, and both time to detection of the first ZIKV disease case and the midpoint of the outbreak. During November 2015-December 2016, a total of 71,618 suspected arboviral disease cases were reported, of which 39,717 (55.5%; 1.1 cases per 100 residents) tested positive for ZIKV infection. The epidemic peaked in August 2016, when 71.5% of arboviral disease cases reported weekly tested positive for ZIKV infection. Incidence of ZIKV disease was highest among 20-29-year-olds (1.6 cases per 100 residents), and most (62.3%) cases were female. The most frequently reported symptoms were rash (83.0%), headache (64.6%), and myalgia (63.3%). Few patients were hospitalized (1.2%), and 13 (<0.1%) died. Early detection of ZIKV disease cases was associated with increased population size (log hazard ratio [HR]: -0.22 [95% confidence interval -0.29, -0.14]), eastern longitude (log HR: -1.04 [-1.17, -0.91]), and proximity to a city (spline estimated degrees of freedom [edf] = 2.0). Earlier midpoints of the outbreak were associated with northern latitude (log HR: -0.30 [-0.32, -0.29]), eastern longitude (spline edf = 6.5), and higher mean monthly temperature (log HR: -0.04 [-0.05, -0.03]). Higher incidence of ZIKV disease was associated with lower mean precipitation, but not socioeconomic factors. CONCLUSIONS: During the ZIKV epidemic in Puerto Rico, 1% of residents were reported to public health authorities and had laboratory evidence of ZIKV disease. Transmission was first detected in urban areas of eastern Puerto Rico, where transmission also peaked earlier. These trends suggest that ZIKV was first introduced to Puerto Rico in the east before disseminating throughout the island.

Entomological Investigation Detects Dengue Virus Type 1 in Aedes (Stegomyia) albopictus (Skuse) during the 2015-16 Outbreak in Hawaii.

A dengue outbreak occurred on Hawaii Island between September 2015 and March 2016. Entomological investigations were undertaken between December 2015 and February 2016 to determine which Aedes mosquito species were responsible for the outbreak. A total of 3,259 mosquitoes were collected using a combination of CDC autocidal gravid ovitraps, Biogents BG-Sentinel traps, and hand-nets; immature mosquitoes were collected during environmental surveys. The composition of species was Aedes albopictus (58%), Aedes aegypti (25%), Wyeomyia mitchelli (7%), Aedes vexans (5%), Culex quinquefasciatus (4%), and Aedes japonicus (1%). Adult mosquitoes were analyzed by real-time reverse transcription polymerase chain reaction (PCR) for the presence of dengue virus (DENV) RNA. Of the 185 pools of female mosquitoes tested, 15 containing Ae. albopictus were positive for the presence of DENV type 1 RNA. No virus was detected in pools of the remaining species. Phylogenetic analysis showed the virus strain belonged to genotype I and was closely related to strains that were circulating in the Pacific between 2008 and 2014. This is the first report of detection of DENV in Ae. albopictus from Hawaii.

Travel-Associated and Locally Acquired Dengue Cases - United States, 2010-2017.

Dengue is a potentially fatal acute febrile illness caused by any of four mosquito-transmitted dengue viruses (DENV-1 to DENV-4) belonging to the family Flaviviridae and endemic throughout the tropics. Competent mosquito vectors of DENV are present in approximately one half of all U.S. counties. To describe epidemiologic trends in travel-associated and locally acquired dengue cases in the United States, CDC analyzed cases reported from the 50 states and District of Columbia to the national arboviral surveillance system (ArboNET). Cases are confirmed by detection of 1) virus RNA by reverse transcription-polymerase chain reaction (RT-PCR) in any body fluid or tissue, 2) DENV antigen in tissue by a validated assay, 3) DENV nonstructural protein 1 (NS1) antigen, or 4) immunoglobulin M (IgM) anti-DENV antibody if the patient did not report travel to an area with other circulating flaviviruses. When travel to an area with other flaviviruses was reported, IgM-positive cases were defined as probable. During 2010-2017, totals of 5,009 (93%) travel-associated and 378 (7%) locally acquired confirmed or probable dengue cases were reported to ArboNET. Cases were equally distributed between males and females, and median age was 41 years. Eighteen (three per 1,000) fatal cases were reported, all among travelers. Travelers should review country-specific recommendations (https://wwwnc.cdc.gov/travel/notices/watch/dengue-asia) for reducing their risk for DENV infection, including using insect repellent and staying in residences with air conditioning or screens on windows and doors.

Comparing vector and human surveillance strategies to detect arbovirus transmission: A simulation study for Zika virus detection in Puerto Rico.

BACKGROUND: Detecting and monitoring the transmission of arboviruses such as Zika virus (ZIKV), dengue virus, and chikungunya virus is critical for prevention and control activities. Previous work has compared the ability of different human-focused surveillance strategies to detect ZIKV transmission in U.S. counties where no known transmission had occurred, but whether virological surveillance in mosquitoes could represent an effective surveillance system is unclear. OBJECTIVES: We leveraged a unique set of data from human and virological surveillance in Ae. aegypti during the 2016 ZIKV epidemic in Caguas, Puerto Rico, to compare alternative strategies for detecting and monitoring ZIKV activity. METHODS: We developed a simulation model for mosquito and human surveillance strategies and simulated different transmission scenarios with varying infection rates and mosquito trap densities. We then calculated the expected weekly number of detected infections, the probability of detecting transmission, and the number of tests needed and compared the simulations with observed data from Caguas. RESULTS: In simulated high transmission scenarios (1 infection per 1,000 people per week), the models demonstrated that both approaches had estimated probabilities of detection of greater than 78%. In simulated low incidence scenarios, vector surveillance had higher sensitivity than human surveillance and sensitivity increased with more traps, more trapping effort, and testing. In contrast, the actual data from Caguas indicated that human virological surveillance was more sensitive than vector virological surveillance during periods of both high and low transmission. CONCLUSION: In scenarios where human surveillance is not possible or when transmission intensity is very low, virological surveillance in Ae. aegypti may be able to detect and monitor ZIKV epidemic activity. However, surveillance for humans seeking care for Zika-like symptoms likely provides an equivalent or more sensitive indicator of transmission intensity in most circumstances.

Lessons Learned from Dengue Surveillance and Research, Puerto Rico, 1899-2013.

Dengue was first reported in Puerto Rico in 1899 and sporadically thereafter. Following outbreaks in 1963 and 1969, the Centers for Disease Control and Prevention has worked closely with the Puerto Rico Department of Health to monitor and reduce the public health burden of dengue. During that time, evolving epidemiologic scenarios have provided opportunities to establish, improve, and expand disease surveillance and interventional research projects. These initiatives have enriched the tools available to the global public health community to understand and combat dengue, including diagnostic tests, methods for disease and vector surveillance, and vector control techniques. Our review serves as a guide to organizations seeking to establish dengue surveillance and research programs by highlighting accomplishments, challenges, and lessons learned during more than a century of dengue surveillance and research conducted in Puerto Rico.

Autocidal gravid ovitraps protect humans from chikungunya virus infection by reducing Aedes aegypti mosquito populations.

BACKGROUND: Public health responses to outbreaks of dengue, chikungunya, and Zika virus have been stymied by the inability to control the primary vector, Aedes aegypti mosquitos. Consequently, the need for novel approaches to Aedes vector control is urgent. Placement of three autocidal gravid ovitraps (AGO traps) in ~85% of homes in a community was previously shown to sustainably reduce the density of female Ae. aegypti by >80%. Following the introduction of chikungunya virus (CHIKV) to Puerto Rico, we conducted a seroprevalence survey to estimate the prevalence of CHIKV infection in communities with and without AGO traps and evaluate their effect on reducing CHIKV transmission. METHODS AND FINDINGS: Multivariate models that calculated adjusted prevalence ratios (aPR) showed that among 175 and 152 residents of communities with and without AGO traps, respectively, an estimated 26.1% and 43.8% had been infected with CHIKV (aPR = 0.50, 95% CI: 0.37-0.91). After stratification by time spent in their community, protection from CHIKV infection was strongest among residents who reported spending many or all weekly daytime hours in their community:10.3% seropositive in communities with AGO traps vs. 48.7% in communities without (PR = 0.21, 95% CI: 0.11-0.41). The age-adjusted rate of fever with arthralgia attributable to CHIKV infection was 58% (95% CI: 46-66%). The monthly number of CHIKV-infected mosquitos and symptomatic residents were diminished in communities with AGO traps compared to those without. CONCLUSIONS: These findings indicate that AGO traps are an effective tool that protects humans from infection with a virus transmitted by Ae. aegypti mosquitos. Future studies should evaluate their protective effectiveness in large, urban communities.

Dengue and Zika Virus Diagnostic Testing for Patients with a Clinically Compatible Illness and Risk for Infection with Both Viruses.

Dengue and Zika viruses are closely related mosquitoborne flaviviruses with similar transmission cycles, distribution throughout the tropics and subtropics, and disease manifestations including fever, rash, myalgia, and arthralgia. For patients with suspected dengue or Zika virus disease, nucleic acid amplification tests (NAATs) are the preferred method of diagnosis. Immunoglobulin M (IgM) antibody testing can identify additional infections and remains an important tool for the diagnosis of these diseases, but interpreting the results is complicated by cross-reactivity, and determining the specific timing of infection can be difficult. These limitations are a particular challenge for pregnant women in determining whether Zika virus infection occurred during or before the pregnancy.This report summarizes existing and new guidance on dengue and Zika virus diagnostic testing for patients with a clinically compatible illness who live in or recently traveled to an area where there is risk for infection with both viruses. CDC recommendations for screening of asymptomatic pregnant women with possible Zika virus exposure are unchanged. For symptomatic nonpregnant persons, dengue and Zika virus NAATs should be performed on serum collected ≤7 days after symptom onset. Dengue and Zika virus IgM antibody testing should be performed on NAAT-negative serum specimens or serum collected >7 days after onset of symptoms. For symptomatic pregnant women, serum and urine specimens should be collected as soon as possible within 12 weeks of symptom onset for concurrent dengue and Zika virus NAATs and IgM antibody testing. Positive IgM antibody test results with negative NAAT results should be confirmed by neutralizing antibody tests when clinically or epidemiologically indicated, including for all pregnant women. Data on the epidemiology of viruses known to be circulating at the location of exposure and clinical findings should be considered when deciding which tests to perform and for interpreting results.Patients with clinically suspected dengue should receive appropriate management to monitor and treat shock and hemorrhage. Women with laboratory evidence of possible Zika virus infection during pregnancy and their infants should be evaluated and managed for possible adverse outcomes. Dengue and Zika virus disease are nationally notifiable conditions, and cases should be reported to public health authorities.

Impacts of Hurricanes Irma and Maria on Aedes aegypti Populations, Aquatic Habitats, and Mosquito Infections with Dengue, Chikungunya, and Zika Viruses in Puerto Rico.

Puerto Rico was severely impacted by Hurricanes Irma and Maria in September 2017. The island has been endemic for dengue viruses (DENV) and recently suffered epidemics of chikungunya (CHIKV 2014) and Zika (ZIKV 2016) viruses. Although severe storms tend to increase the number of vector and nuisance mosquitoes, we do not know how they influence Aedes aegypti populations and arboviral transmission. We compared the abundance of female Ae. aegypti in autocidal gravid ovitraps (AGO traps), container habitats, and presence of RNA of DENV, CHIKV, and ZIKV in this vector before and after the hurricanes in Caguas city and in four communities in southern Puerto Rico. Two of these communities were under vector control using mass AGO trapping and the other two nearby communities were not. We also investigated mosquito species composition and relative abundance (females/trap) using Biogents traps (BG-2 traps) in 59 sites in metropolitan San Juan city after the hurricanes. Mosquitoes sharply increased 5 weeks after Hurricane Maria. Ensuing abundance of Ae. aegypti was higher in Caguas and in one of the southern communities without vector control. Aedes aegypti did not significantly change in the two areas with vector control. The most abundant mosquitoes among the 26 species identified in San Juan were Culex (Melanoconion) spp., Culex quinquefasciatus, Culex nigripalpus, and Ae. aegypti. No arboviruses were detected in Ae. aegypti following the hurricanes, in contrast with observations from the previous year, so that the potential for Aedes-borne arboviral outbreaks following the storms in 2017 was low.

Citywide Control of Aedes aegypti (Diptera: Culicidae) during the 2016 Zika Epidemic by Integrating Community Awareness, Education, Source Reduction, Larvicides, and Mass Mosquito Trapping.

This investigation was initiated to control Aedes aegypti and Zika virus transmission in Caguas City, Puerto Rico, during the 2016 epidemic using Integrated Vector Management (IVM), which included community awareness and education, source reduction, larviciding, and mass-trapping with autocidal gravid ovitraps (AGO). The epidemic peaked in August to October 2016 and waned after April 2017. There was a preintervention period in October/November 2016 and IVM lasted until August 2017. The area under treatment (23.1 km2) had 61,511 inhabitants and 25,363 buildings. The city was divided into eight even clusters and treated following a cluster randomized stepped-wedge design. We analyzed pools of female Ae. aegypti adults for RNA detection of dengue (DENV), chikungunya (CHIKV), and Zika (ZIKV) viruses using 360 surveillance AGO traps every week. Rainfall, temperature, and relative humidity were monitored in each cluster. Mosquito density significantly changed (generalized linear mixed model; F8, 14,588 = 296; P < 0.001) from 8.0 ± 0.1 females per trap per week before the intervention to 2.1 ± 0.04 after the percentage of buildings treated with traps was 60% and to 1.4 ± 0.04 when coverage was above 80%. Out of a total 12,081 mosquito pools, there were 1 DENV-, 7 CHIKV-, and 49 ZIKV-positive pools from October 2016 to March 2017. Afterward, we found only one positive pool of DENV in July 2017. This investigation demonstrated that it was possible to scale up effective Ae. aegypti control to a medium-size city through IVM that included mass trapping of gravid Ae. aegypti females.

Incidence and Outcome of Severe and Nonsevere Thrombocytopenia Associated With Zika Virus Infection-Puerto Rico, 2016.

BACKGROUND: Zika virus (ZIKV) infection has been associated with severe thrombocytopenia. We describe the incidence, clinical manifestations, and outcomes of patients with ZIKV infection and thrombocytopenia. METHODS: We reviewed medical records of patients with ZIKV infection and thrombocytopenia (platelet count <100 ×109 cells/L) in Puerto Rico during 2016. Severe thrombocytopenia was defined by platelet count <20 ×109/L or a platelet count <50 ×109/L and treatment for immune thrombocytopenia (ITP). RESULTS: Of 37 878 patients with ZIKV infection, 47 (0.1%) had thrombocytopenia in the absence of an alternative etiology (1.4 cases/100 000 population), including 12 with severe thrombocytopenia. Most patients with thrombocytopenia were adult (77%) and male (53%). Platelet nadir occurred a median (range) of 6 (1-16) and 5 (0-34) days after symptom onset for patients with severe and nonsevere thrombocytopenia, respectively. Among patients with severe thrombocytopenia, all had bleeding, 33% were admitted to the intensive care unit, and 8% died; 50% were treated for ITP. Among 5 patients with severe thrombocytopenia who received intravenous immunoglobulin, the median platelet count increase (range) was 112 (65-202) ×109/L. In contrast, among 4 patients who received platelet transfusion, the median increase in platelet count (range) was 8.5 (-6 to 52) ×109/L. CONCLUSIONS: Patients with severe thrombocytopenia and ZIKV infection experienced prominent acute morbidity. Consistent with recommended management, administration of ITP treatments to such patients may be more efficacious than platelet transfusion in resolving thrombocytopenia. Severe thrombocytopenia should be considered a rare outcome of ZIKV infection.

Implementation and Evaluation of Guillain-Barré Syndrome Surveillance in Puerto Rico during the 2016 Zika Virus Epidemic.

OBJECTIVE: Guillain-Barré syndrome (GBS) is an uncommon autoimmune disorder that follows infection or vaccination, and increased incidence has been reported during Zika virus (ZIKV) transmission. During the 2016 ZIKV epidemic, the Puerto Rico Department of Health (PRDH) implemented the Enhanced GBS Surveillance System (EGBSSS). Here, we describe EGBSSS implementation and evaluate completeness, validity, and timeliness. METHODS: GBS cases were identified using passive surveillance and discharge diagnostic code for GBS. Completeness was evaluated by capture-recapture methods. Sensitivity and positive predictive value (PPV) for confirmed GBS cases were calculated for both case identification methods. Median time to completion of key time steps were compared by quarter (Q1-4) and hospital size. RESULTS: A total of 122 confirmed GBS cases with onset of neurologic illness in 2016 were identified. Capture-recapture methodology estimated that four confirmed GBS cases were missed by both identification methods. Identification of cases by diagnostic code had a higher sensitivity than passive surveillance (89% vs. 80%), but a lower PPV (60% vs. 72%). There was a significant decrease from Q1 to Q3 in median time from hospital admission to case reporting (11 days vs. 2 days, p = 0.032) and from Q2 to Q3 in median time from specimen receipt to arbovirus laboratory test reporting (35 days vs. 26 days, p = 0.004). CONCLUSION: EGBSSS provided complete, valid, and increasingly timely surveillance data, which guided public health action and supported healthcare providers during the ZIKV epidemic. This evaluation provides programmatic lessons for GBS surveillance and emergency response surveillance.

Vital Signs: Trends in Reported Vectorborne Disease Cases - United States and Territories, 2004-2016.

INTRODUCTION: Vectorborne diseases are major causes of death and illness worldwide. In the United States, the most common vectorborne pathogens are transmitted by ticks or mosquitoes, including those causing Lyme disease; Rocky Mountain spotted fever; and West Nile, dengue, and Zika virus diseases. This report examines trends in occurrence of nationally reportable vectorborne diseases during 2004-2016. METHODS: Data reported to the National Notifiable Diseases Surveillance System for 16 notifiable vectorborne diseases during 2004-2016 were analyzed; findings were tabulated by disease, vector type, location, and year. RESULTS: A total 642,602 cases were reported. The number of annual reports of tickborne bacterial and protozoan diseases more than doubled during this period, from >22,000 in 2004 to >48,000 in 2016. Lyme disease accounted for 82% of all tickborne disease reports during 2004-2016. The occurrence of mosquitoborne diseases was marked by virus epidemics. Transmission in Puerto Rico, the U.S. Virgin Islands, and American Samoa accounted for most reports of dengue, chikungunya, and Zika virus diseases; West Nile virus was endemic, and periodically epidemic, in the continental United States. CONCLUSIONS AND IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: Vectorborne diseases are a large and growing public health problem in the United States, characterized by geographic specificity and frequent pathogen emergence and introduction. Differences in distribution and transmission dynamics of tickborne and mosquitoborne diseases are often rooted in biologic differences of the vectors. To effectively reduce transmission and respond to outbreaks will require major national improvement of surveillance, diagnostics, reporting, and vector control, as well as new tools, including vaccines.