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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%. Author summary: We assessed baseline seroprevalence and risk factors for previous CHIKV or recent ZIKV infection among 4,035 participants in the Communities Organized to Prevent Arboviruses (COPA) study. Participants were recruited among people 1–50 years old living in 38 study clusters in the Ponce municipality of southern Puerto Rico. Among 4,035 participants, 31% had evidence of previous CHIKV infection, and 16% had evidence of recent ZIKV infection. For both viruses, older age was associated with greater risk for infection; male sex was also associated with higher rates of ZIKV infection. Seroprevalence varied by study cluster, with similar patterns between the two viruses. Home screens and air conditioning in the home were significant protective factors against infection in the multivariate analysis for both CHIKV and ZIKV. [ABSTRACT FROM AUTHOR]

We evaluated nucleic acid amplification testing (NAAT) for Zika virus on whole-blood specimens compared with NAAT on serum and urine specimens among asymptomatic pregnant women during the 2015-2016 Puerto Rico Zika outbreak. Using NAAT, more infections were detected in serum and urine than in whole blood specimens. [ABSTRACT FROM AUTHOR]

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. Author summary: During epidemics of Zika virus disease in the Americas in 2015 and 2016, assessment of transmission dynamics was limited by inconsistent laboratory testing of patients with suspected Zika virus disease. This limitation was further complicated by co-circulation of dengue and chikungunya viruses, which cause illnesses clinically similar to Zika virus disease. In Puerto Rico, all reported suspect cases of arboviral disease were tested for Zika, dengue, and chikungunya virus infection throughout the epidemic, which allowed for fine-scale analysis of epidemiologic and spatiotemporal trends. In total, 39,717 cases of Zika virus disease were detected, or roughly 1% of all residents of Puerto Rico. Young adults and females were most affected. Disease was mostly mild, as only 1% of cases were hospitalized. Thirteen patients with Zika virus disease died, most of whom had Guillain-Barré syndrome or severe underlying illnesses. Early detection of Zika virus disease cases was associated with more populated areas of eastern Puerto Rico, where early detection of peak case numbers also occurred, particularly in warmer areas. These trends suggest that, in contrast to prior epidemics of dengue and chikungunya that started in the San Juan metropolitan region, the Zika virus epidemic appears to have begun in eastern Puerto Rico. [ABSTRACT FROM AUTHOR]

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

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. [ABSTRACT FROM AUTHOR]

Chikungunya, a mosquito-borne viral, acute febrile illness (AFI) is associated with polyarthralgia and polyarthritis. Differentiation from other AFI is difficult due to the non-specific presentation and limited availability of diagnostics. This 3-year study identified independent clinical predictors by day post-illness onset (DPO) at presentation and age-group that distinguish chikungunya cases from two groups: other AFI and dengue. Specimens collected from participants with fever ≤7 days were tested for chikungunya, dengue viruses 1–4, and 20 other pathogens. Of 8,996 participants, 18.2% had chikungunya, and 10.8% had dengue. Chikungunya cases were more likely than other groups to be older, report a chronic condition, and present <3 DPO. Regardless of timing of presentation, significant positive predictors for chikungunya versus other AFI were: joint pain, muscle, bone or back pain, skin rash, and red conjunctiva; with dengue as the comparator, red swollen joints (arthritis), joint pain, skin rash, any bleeding, and irritability were predictors. Chikungunya cases were less likely than AFI and dengue to present with thrombocytopenia, signs of poor circulation, diarrhea, headache, and cough. Among participants presenting <3 DPO, predictors for chikungunya versus other AFI included: joint pain, skin rash, and muscle, bone or back pain, and absence of thrombocytopenia, poor circulation and respiratory or gastrointestinal symptoms; when the comparator was dengue, joint pain and arthritis, and absence of thrombocytopenia, leukopenia, and nausea were early predictors. Among all groups presenting 3–5 DPO, pruritic skin became a predictor for chikungunya, joint, muscle, bone or back pain were no longer predictive, while arthritis became predictive in all age-groups. Absence of thrombocytopenia was a significant predictor regardless of DPO or comparison group. This study identified robust clinical indicators such as joint pain, skin rash and absence of thrombocytopenia that can allow early identification of and accurate differentiation between patients with chikungunya and other common causes of AFI. [ABSTRACT FROM AUTHOR]

Drug use disorders (DUDs) can substantially increase the costs of health care, especially when left untreated. Yet, not much is known about the specific types of medical services that give rise to these cost differences. This study aimed to estimate the medical costs of beneficiaries with DUDs enrolled in the Medicaid Managed Care (MMC) program in Puerto Rico using claims data. These were compared to those of a matched group of patients without DUDs. On average, each beneficiary with a DUD incurred in $4539 annually on medical services compared to $2601 in the matched comparison group, a cost differential of $1938. Close to half of these additional medical costs (43.4%) were generated in the physical health services sector. Counts of service claims were also higher for beneficiaries with DUDs than for beneficiaries without DUDs in all service types, except in outpatient and laboratory services for physical health. A host of access strategies and treatment modalities should be tested to assess the extent to which providing adequate access and adequate treatment for a DUD can contribute to cost savings. [ABSTRACT FROM AUTHOR]

The article discusses the identification of passive surveillance and household probes to determine chikungunya cases in Puerto Rico in 2014. Topics covered include the difference of chikungunya and dengue illnesses as well as the similarities in their symptoms. Also mentioned are the symptoms of chikungunya illness such as arthralgia and fever.

Background. The dengue virus serotype 3 (DENV-3) Indian subcontinent strain emerged in Puerto Rico in 1998 after a 21-year absence. The rapid expansion of DENV-3 on the island correlated with the withdrawal of the other serotypes for 7 years. The DENV-3 prevalence declined in 2008 and remains undetected.Methods. We sequenced complete genomes of 92 DENV-3 clinical isolates to characterize the molecular evolution and phylogeography throughout 10 years of continued sampling (1998–2007).Results. We documented 8 distinct lineages that emerged simultaneously and evolved independently. Two of the 8 lineages were highly associated with transient introductions of foreign viruses, and 2 of the 3 endemic lineages covered the entire study period. We found evidence of temporal-geographical clustering only within the 3 endemic lineages. The phylogeography analysis combined with serotype-specific incidence data showed that transmission of a DENV serotype in a given location and time is usually correlated with the absence of the other serotype.Conclusions. Our study shows the cotransmission of DENV-3 lineages through a complex dissemination pattern dissimilar to the evolutionary dynamics of the other serotypes in the island. High virus genetic diversity and a large naive population were underlying factors in the expansion and collapse of DENV-3 in Puerto Rico. [ABSTRACT FROM PUBLISHER]

Background: The incidence and severity of dengue in Latin America has increased substantially in recent decades and data from Puerto Rico suggests an increase in severe cases. Successful clinical management of severe dengue requires early recognition and supportive care. Methods: Fatal cases were identified among suspected dengue cases reported to two disease surveillance systems and from death certificates. To be included, fatal cases had to have specimen submitted for dengue diagnostic testing including nucleic acid amplification for dengue virus (DENV) in serum or tissue, immunohistochemical testing of tissue, and immunoassay detection of anti-DENV IgM from serum. Medical records from laboratory-positive dengue fatal case-patients were reviewed to identify possible determinants for death. Results: Among 10,576 reported dengue cases, 40 suspect fatal cases were identified, of which 11 were laboratory-positive, 14 were laboratory-negative, and 15 laboratory-indeterminate. The median age of laboratory-positive case-patients was 26 years (range 5 months to 78 years), including five children aged <15 years; 7 sought medical care at least once prior to hospital admission, 9 were admitted to hospital and 2 died upon arrival. The nine hospitalized case-patients stayed a mean of 15 hours (range: 3–48 hours) in the emergency department (ED) before inpatient admission. Five of the nine case-patients received intravenous methylprednisolone and four received non-isotonic saline while in shock. Eight case-patients died in the hospital; five had their terminal event on the inpatient ward and six died during a weekend. Dengue was listed on the death certificate in only 5 instances. Conclusions: During a dengue epidemic in an endemic area, none of the 11 laboratory-positive case-patients who died were managed according to current WHO Guidelines. Management issues identified in this case-series included failure to recognize warning signs for severe dengue and shock, prolonged ED stays, and infrequent patient monitoring. Author Summary: Dengue is a major public health problem in the tropics and subtropics; an estimated 50 million cases occur annually and 40 percent of the world's population lives in areas with dengue virus (DENV) transmission. Dengue has a wide range of clinical presentations from an undifferentiated acute febrile illness, classic dengue fever, to severe dengue (i.e., dengue hemorrhagic fever or dengue shock syndrome). About 5% of patients develop severe dengue, which is more common with second or subsequent infections. No vaccines are available to prevent dengue, and there are no specific antiviral treatments for patients with dengue. However, early recognition of shock and intensive supportive therapy can reduce risk of death from ∼10% to less than 1% among severe dengue cases. Reviewing dengue deaths is one means to identify issues in clinical management. These findings can be used to develop healthcare provider education to minimize dengue morbidity and mortality. [ABSTRACT FROM AUTHOR]

To study the evolution of dengue virus (DENV) serotype 2 in Puerto Rico, we examined the genetic composition and diversity of 160 DENV-2 genomes obtained through 22 consecutive years of sampling. A clade replacement took place in 1994-1997 during a period of high incidence of autochthonous DENV-2 and frequent, short-lived reintroductions of foreign DENV-2. This unique clade replacement was complete just before DENV-3 emerged. By temporally and geographically defining DENV-2 lineages, we describe a refuge of this virus through 4 years of low genome diversity. Our analyses may explain the long-term endurance of DENV-2 despite great epidemiologic changes in disease incidence and serotype distribution. [ABSTRACT FROM AUTHOR]

The article reports on the detection of West Nile virus (WNV) in human blood donors in Puerto Rico in 2007. The American Red Cross in Puerto Rico has notified the authorities of three persons whose blood donations were positive of WNV. The human infections and other surveillance for transmission of WNV in Puerto Rico are described. According to the article, the detection of WNV infections indicates that heightened clinical awareness and surveillance are needed to monitor the public health threat posed by WNV.

West Nile virus (WNV) was isolated from a human blood donor, a dead falcon, and mosquitoes in Puerto Rico in 2007. Phylogenetic analysis of the 4 isolates suggests a recent introduction of lineage I WNV that is closely related to WNV currently circulating in North America. [ABSTRACT FROM AUTHOR]

To evaluate potential enhancement of Zika virus (ZIKV) infection among patients with prior dengue virus (DENV) infection, we compared loads of viral RNA among patients infected with ZIKV (n = 1070), DENV-2 (n = 312), or DENV-3 (n = 260). Compared to patients without prior DENV infection, patients with prior DENV infection had significantly higher mean loads of viral RNA if infected with DENV-2 (10.6 vs 11.6 log10 GCE/mL, respectively; t test, P <.0001) or DENV-3 (10.3 vs 10.9 log10 GCE/mL; P <.0001), but not ZIKV (4.7 vs 4.7 log10 GCE/mL; P =.959). These findings provide evidence against in vivo enhancement of ZIKV by anti-DENV antibodies. [ABSTRACT FROM AUTHOR]

Dengue has emerged globally as a major human health problem since the 1950s and is now the most important arboviral disease of humans, infecting nearly 400 million people annually. While some cases are asymptomatic, others can develop a febrile illness (dengue fever) or even progress to severe and fatal dengue. Dengue is caused by any of 4 closely related but distinct viruses, known as Dengue virus serotype 1 to 4 (DENV-1 to DENV-4) which are maintained in endemic transmission to humans in large urban centers of the tropics by Aedes mosquitoes. Since the early 1960s, Puerto Rico, a major metropolitan center in the Caribbean, has experienced increasingly larger and clinically more severe epidemics following the introduction of all four dengue serotypes. The first dengue hemorrhagic fever epidemic in 1986, and a particularly severe outbreak in 1998 were dominated by novel DENV-4 strains that evolved in Puerto Rico, replacing earlier strains and spreading throughout the region. Sequence characterization of 54 complete DENV-4 genomes and their comparative evolution against 74 previously published viral sequences from the region over several decades shows that DENV-4 strains from these periods were genetically distinct based on unique changes in the envelope and non-structural genes. Their replacement of earlier strains in Puerto Rico progressed rapidly, suggesting that strong natural selection played a role in their fixation. This study confirms that DENVs evolve through rapid lineage turnover driven in part by natural selection and genetic drift. [ABSTRACT FROM AUTHOR]