Travel Surveillance and Genomics Uncover a Hidden Zika Outbreak during the Waning Epidemic.

The Zika epidemic in the Americas has challenged surveillance and control. As the epidemic appears to be waning, it is unclear whether transmission is still ongoing, which is exacerbated by discrepancies in reporting. To uncover locations with lingering outbreaks, we investigated travel-associated Zika cases to identify transmission not captured by reporting. We uncovered an unreported outbreak in Cuba during 2017, a year after peak transmission in neighboring islands. By sequencing Zika virus, we show that the establishment of the virus was delayed by a year and that the ensuing outbreak was sparked by long-lived lineages of Zika virus from other Caribbean islands. Our data suggest that, although mosquito control in Cuba may initially have been effective at mitigating Zika virus transmission, such measures need to be maintained to be effective. Our study highlights how Zika virus may still be "silently" spreading and provides a framework for understanding outbreak dynamics. VIDEO ABSTRACT.

DengueSeq: a pan-serotype whole genome amplicon sequencing protocol for dengue virus.

BACKGROUND: The increasing burden of dengue virus on public health due to more explosive and frequent outbreaks highlights the need for improved surveillance and control. Genomic surveillance of dengue virus not only provides important insights into the emergence and spread of genetically diverse serotypes and genotypes, but it is also critical to monitor the effectiveness of newly implemented control strategies. Here, we present DengueSeq, an amplicon sequencing protocol, which enables whole-genome sequencing of all four dengue virus serotypes. RESULTS: We developed primer schemes for the four dengue virus serotypes, which can be combined into a pan-serotype approach. We validated both approaches using genetically diverse virus stocks and clinical specimens that contained a range of virus copies. High genome coverage (>95%) was achieved for all genotypes, except DENV2 (genotype VI) and DENV 4 (genotype IV) sylvatics, with similar performance of the serotype-specific and pan-serotype approaches. The limit of detection to reach 70% coverage was 10-100 RNA copies/µL for all four serotypes, which is similar to other commonly used primer schemes. DengueSeq facilitates the sequencing of samples without known serotypes, allows the detection of multiple serotypes in the same sample, and can be used with a variety of library prep kits and sequencing instruments. CONCLUSIONS: DengueSeq was systematically evaluated with virus stocks and clinical specimens spanning the genetic diversity within each of the four dengue virus serotypes. The primer schemes can be plugged into existing amplicon sequencing workflows to facilitate the global need for expanded dengue virus genomic surveillance.

Autochthonous Plasmodium vivax Infections, Florida, USA, 2023.

During May-July 2023, a cluster of 7 patients at local hospitals in Florida, USA, received a diagnosis of Plasmodium vivax malaria. Whole-genome sequencing of the organism from 4 patients and phylogenetic analysis with worldwide representative P. vivax genomes indicated probable single parasite introduction from Central/South America.

Introduction and Spread of Dengue Virus 3, Florida, USA, May 2022-April 2023.

During May 2022-April 2023, dengue virus serotype 3 was identified among 601 travel-associated and 61 locally acquired dengue cases in Florida, USA. All 203 sequenced genomes belonged to the same genotype III lineage and revealed potential transmission chains in which most locally acquired cases occurred shortly after introduction, with little sustained transmission.

Dengue Outbreak Response during COVID-19 Pandemic, Key Largo, Florida, USA, 2020.

We report a dengue outbreak in Key Largo, Florida, USA, from February through August 2020, during the COVID-19 pandemic. Successful community engagement resulted in 61% of case-patients self-reporting. We also describe COVID-19 pandemic effects on the dengue outbreak investigation and the need to increase clinician awareness of dengue testing recommendations.

Reemergence of Dengue Virus Serotype 3, Brazil, 2023.

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

Outbreak of Locally Acquired Mosquito-Transmitted (Autochthonous) Malaria - Florida and Texas, May-July 2023.

Eight cases of locally acquired, mosquito-transmitted (i.e., autochthonous) Plasmodium vivax malaria, which has not been reported in the United States since 2003, were reported to CDC from state health departments in Florida and Texas during May 18-July 17, 2023. As of August 4, 2023, case surveillance, mosquito surveillance and control activities, and public outreach and education activities continue in both states. U.S. clinicians need to consider a malaria diagnosis in patients with unexplained fever, especially in areas where autochthonous malaria has been recently reported, although the risk for autochthonous malaria in the United States remains very low. Prompt diagnosis and treatment of malaria can prevent severe disease or death and limit ongoing transmission to local Anopheles mosquitoes and other persons. Preventing mosquito bites and controlling mosquitoes at home can prevent mosquitoborne diseases, including malaria. Before traveling internationally to areas with endemic malaria, travelers should consult with a health care provider regarding recommended malaria prevention measures, including potentially taking malaria prophylaxis. Malaria is a nationally notifiable disease; continued reporting of malaria cases to jurisdictional health departments and CDC will also help ensure robust surveillance to detect and prevent autochthonous malaria in the United States.

Using Comic-Based Concussion Discharge Instructions to Address Caregiver Health Literacy in the Emergency Department.

INTRODUCTION: This study compared the effectiveness of comic-based with text-based concussion discharge instructions on improving caregiver knowledge. This study also examined the role of social determinants of health on comprehension instructions. METHODS: This was an observational study of the caregivers of pediatric concussion patients. Caregivers' health literacy and demographics related socioeconomic factors were obtained. After the patients' evaluation in the emergency department, caregivers were given printed comic-based concussion discharge instructions. Caregivers were contacted 3 days later and tested overall knowledge of discharge instructions' content. These survey results were compared with historical controls who received text-based instructions. RESULTS: A total of 120 participants were recruited, and 86 participants completed follow-up procedures. When comparing the caregivers' recall ability with a comic-based vs traditional text-based instructions, caregivers with comic-based content were more likely to accurately recall overall discharge instructions (77.5% vs 44%, P < .001), particularly physical rest and activity restrictions (86.5% vs 63%, P < .001). Caregivers also were less likely to misidentify a red flag symptom (7.5% vs 19%, P < .04). Comic-based instructions did not increase recall of cognitive rest instructions or postconcussive symptoms. When examining demographic factors, caregivers who could not recall 3 postconcussive symptoms were more likely to be Hispanic or Black, less likely to be college educated, and more likely to have low health literacy. DISCUSSION: Novel methods should be explored to adequately prepare caregivers for continuing postconcussive care at home. Discharge instructions must be tailored to address caregivers' baseline health literacy and how caregivers digest and retain information.

Case Series of Laboratory-Associated Zika Virus Disease, United States, 2016-2019.

Zika virus diagnostic testing and laboratory research increased considerably when Zika virus began spreading through the Americas in 2015, increasing the risk for potential Zika virus exposure of laboratory workers and biomedical researchers. We report 4 cases of laboratory-associated Zika virus disease in the United States during 2016-2019. Of these, 2 were associated with needlestick injuries; for the other 2 cases, the route of transmission was undetermined. In laboratories in which work with Zika virus is performed, good laboratory biosafety practices must be implemented and practiced to reduce the risk for infection among laboratory personnel.

COVID-19 in Correctional and Detention Facilities - United States, February-April 2020.

An estimated 2.1 million U.S. adults are housed within approximately 5,000 correctional and detention facilities† on any given day (1). Many facilities face significant challenges in controlling the spread of highly infectious pathogens such as SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19). Such challenges include crowded dormitories, shared lavatories, limited medical and isolation resources, daily entry and exit of staff members and visitors, continual introduction of newly incarcerated or detained persons, and transport of incarcerated or detained persons in multiperson vehicles for court-related, medical, or security reasons (2,3). During April 22-28, 2020, aggregate data on COVID-19 cases were reported to CDC by 37 of 54 state and territorial health department jurisdictions. Thirty-two (86%) jurisdictions reported at least one laboratory-confirmed case from a total of 420 correctional and detention facilities. Among these facilities, COVID-19 was diagnosed in 4,893 incarcerated or detained persons and 2,778 facility staff members, resulting in 88 deaths in incarcerated or detained persons and 15 deaths among staff members. Prompt identification of COVID-19 cases and consistent application of prevention measures, such as symptom screening and quarantine, are critical to protecting incarcerated and detained persons and staff members.

Randomized Controlled Trial of Acute Illness Educational Intervention in the Pediatric Emergency Department: Written Versus Application-Based Education.

OBJECTIVES: The aim of this study was to determine the (1) feasibility, (2) demand, (3) acceptability, and (4) usefulness of a mobile health (mHealth) application (app) compared with a written intervention distributed in a pediatric emergency department (ED). METHODS: This was a randomized controlled trial with parents of children 12 years or younger presenting to the ED for nonurgent complaints. Parents were randomized to receive a (1) low literacy pediatric health book with video, (2) pediatric mHealth app, (3) both 1 and 2, or (4) car-seat safety video and handout (control). Demand, acceptability, and usefulness were assessed at 1-, 3-, and 6-month follow-ups. Modified intention-to-treat analysis was completed for proportional data. RESULTS: Ninety-eight parents completed randomization (83% approached). One or more follow-up was completed for 80.6% of parents. Only 57.1% downloaded the app. Parents used the app less than the book (35.1% vs 73.0%, P < 0.01), found the app to be harder to understand (26.0% vs 94.6%, P < 0.001) and less useful (37.8% vs 70.3%, P < 0.01), and were less likely to recommend the app to others (48.7% vs 100%, P < 0.01). No parent who received both book and app would prefer to have only the app; 88.9% of parents wanted either the book or both. CONCLUSIONS: There was low demand for an mHealth app with parents who prefer, accept, and use the book more. Giving written health information to vulnerable populations in a pediatric ED has the capacity to empower parents with knowledge to care for a child and potentially decrease future nonurgent ED use with translation into a larger study.

Health Literacy: Implications for Child Health.

Health literacy is an important issue to consider in the provision of health-care to children. Similar to the adult population, most parents face health literacy challenges. Of particular concern, 1 in 4 parents have low health literacy, greatly affecting their ability to use health information to make health decisions for their child. High expectations are placed on parents and children to achieve effective disease management and positive health outcomes in the context of complex health-care systems and disease treatment regimens. Low health literacy affects parent acquisition of knowledge, attitudes, and behaviors, as well as child health outcomes across the domains of disease prevention, acute illness care, and chronic illness care. The effect of low health literacy is wide ranging, including 1) poor nutrition knowledge and behaviors, 2) higher obesity rates, 3) more medication errors, 4) more emergency department use, and 5) poor asthma knowledge, behaviors, and outcomes. Health-care providers can mitigate the effects of health literacy by seeking to align health-care demands with the health literacy skills of families. Effective health literacy-informed interventions provide insights into methods that can be used by providers and health systems to improve health outcomes. Health literacy-informed communication strategies should be used with all families in a "universal precautions approach" because all parents likely benefit from clear communication. As scientific advances are made in disease prevention and management, unless families understand how to follow provider recommendations, the benefit of these advances will not be realized and disparities in outcomes will be exacerbated.

Parents' pain medication underdosing is associated with more emergency department visits in sickle cell disease.

OBJECTIVE: To determine the association between health literacy, medication knowledge, and pain treatment skills with emergency department (ED) use of parents of children with sickle cell disease (SCD). METHODS: Parents of children 1- to 12-years-old with SCD were enrolled. Health literacy was assessed using the Newest Vital Sign. Parents completed a structured interview assessing knowledge of the dosage and frequency of home pain medications and an applied skills task requiring them to dose a prescribed pain medication. Underdosage was defined by too small a dose (dosage error) or too infrequent a dose (frequency error). The association between medication knowledge and applied skills with ED visits for pain over the past year was evaluated using Poisson regression adjusting for genotype. RESULTS: One hundred parent/child pairs were included; 50% of parents had low health literacy. Low health literacy was associated with more underdose frequency errors (38% vs. 19%, P = 0.02) on the skills task. On medication knowledge, underdose dosage errors (adjusted incidence rate ratio [aIRR] 2.0, 95% confidence interval [CI] 1.3-3.0) and underdose frequency errors (aIRR, 1.7, 95% CI 1.2-2.6) were associated with a higher rate of ED visits for pain. On the skills task, underdose dosage errors (aIRR 1.6, 95% CI 1.1-2-.4) and underdose frequency errors were associated with more ED visits (aIRR 1.5, 95% CI 1.1-2.1). CONCLUSIONS: For medication knowledge and skills tasks, children of parents who underdosed pain medication had a higher rate of ED visits for pain. Health literate strategies to improve parents' medication skills may improve pain treatment at home and decrease healthcare utilization.

Health literacy affects likelihood of radiology testing in the pediatric emergency department.

OBJECTIVE: To test the hypothesis that the effect of race/ethnicity on decreased radiologic testing in the pediatric emergency department (ED) varies by caregiver health literacy. STUDY DESIGN: This was a secondary analysis of a cross-sectional study of caregivers accompanying children ≤ 12 years to a pediatric ED. Caregiver health literacy was measured using the Newest Vital Sign. A blinded chart review determined whether radiologic testing was utilized. Bivariate and multivariate analyses, adjusting for ED triage level, child insurance, and chronic illness were used to determine the relationship between race/ethnicity, health literacy, and radiologic testing. Stratified analyses by caregiver health literacy were conducted. RESULTS: Five hundred four caregivers participated; the median age was 31 years, 47% were white, 37% black, 10% Hispanic, and 49% had low health literacy. Black race and low health literacy were associated with less radiologic testing (P < .01). In stratified analysis, minority race was associated with less radiologic testing only if a caregiver had low health literacy (aOR 0.5; 95% CI 0.3-0.9), and no difference existed in those with adequate health literacy (aOR 0.7; 95% CI 0.4-1.3). CONCLUSIONS: Caregiver low health literacy modifies whether minority race/ethnicity is associated with decreased radiologic testing, with only children of minority caregivers with low health literacy receiving fewer radiologic studies. Future interventions to eliminate disparities in healthcare resource utilization should consider health literacy as a mutable factor.

Travel surveillance uncovers dengue virus dynamics and introductions in the Caribbean.

Dengue is the most prevalent mosquito-borne viral disease in humans, and cases are continuing to rise globally. In particular, islands in the Caribbean have experienced more frequent outbreaks, and all four dengue virus (DENV) serotypes have been reported in the region, leading to hyperendemicity and increased rates of severe disease. However, there is significant variability regarding virus surveillance and reporting between islands, making it difficult to obtain an accurate understanding of the epidemiological patterns in the Caribbean. To investigate this, we used travel surveillance and genomic epidemiology to reconstruct outbreak dynamics, DENV serotype turnover, and patterns of spread within the region from 2009-2022. We uncovered two recent DENV-3 introductions from Asia, one of which resulted in a large outbreak in Cuba, which was previously under-reported. We also show that while outbreaks can be synchronized between islands, they are often caused by different serotypes. Our study highlights the importance of surveillance of infected travelers to provide a snapshot of local introductions and transmission in areas with limited local surveillance and suggests that the recent DENV-3 introductions may pose a major public health threat in the region.

DengueSeq: A pan-serotype whole genome amplicon sequencing protocol for dengue virus.

Background: The increasing burden of dengue virus on public health due to more explosive and frequent outbreaks highlights the need for improved surveillance and control. Genomic surveillance of dengue virus not only provides important insights into the emergence and spread of genetically diverse serotypes and genotypes, but it is also critical to monitor the effectiveness of newly implemented control strategies. Here, we present DengueSeq, an amplicon sequencing protocol, which enables whole-genome sequencing of all four dengue virus serotypes. Results: We developed primer schemes for the four dengue virus serotypes, which can be combined into a pan-serotype approach. We validated both approaches using genetically diverse virus stocks and clinical specimens that contained a range of virus copies. High genome coverage (>95%) was achieved for all genotypes, except DENV2 (genotype VI) and DENV 4 (genotype IV) sylvatics, with similar performance of the serotype-specific and pan-serotype approaches. The limit of detection to reach 70% coverage was 101-102 RNA copies/µL for all four serotypes, which is similar to other commonly used primer schemes. DengueSeq facilitates the sequencing of samples without known serotypes, allows the detection of multiple serotypes in the same sample, and can be used with a variety of library prep kits and sequencing instruments. Conclusions: DengueSeq was systematically evaluated with virus stocks and clinical specimens spanning the genetic diversity within each of the four dengue virus serotypes. The primer schemes can be plugged into existing amplicon sequencing workflows to facilitate the global need for expanded dengue virus genomic surveillance.

Impact of SARS-CoV-2 Infection on the Association Between Laboratory Tests and Severe Outcomes Among Hospitalized Children.

Background: To assist clinicians with identifying children at risk of severe outcomes, we assessed the association between laboratory findings and severe outcomes among severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected children and determined if SARS-CoV-2 test result status modified the associations. Methods: We conducted a cross-sectional analysis of participants tested for SARS-CoV-2 infection in 41 pediatric emergency departments in 10 countries. Participants were hospitalized, had laboratory testing performed, and completed 14-day follow-up. The primary objective was to assess the associations between laboratory findings and severe outcomes. The secondary objective was to determine if the SARS-CoV-2 test result modified the associations. Results: We included 1817 participants; 522 (28.7%) SARS-CoV-2 test-positive and 1295 (71.3%) test-negative. Seventy-five (14.4%) test-positive and 174 (13.4%) test-negative children experienced severe outcomes. In regression analysis, we found that among SARS-CoV-2-positive children, procalcitonin ≥0.5 ng/mL (adjusted odds ratio [aOR], 9.14; 95% CI, 2.90-28.80), ferritin >500 ng/mL (aOR, 7.95; 95% CI, 1.89-33.44), D-dimer ≥1500 ng/mL (aOR, 4.57; 95% CI, 1.12-18.68), serum glucose ≥120 mg/dL (aOR, 2.01; 95% CI, 1.06-3.81), lymphocyte count <1.0 × 109/L (aOR, 3.21; 95% CI, 1.34-7.69), and platelet count <150 × 109/L (aOR, 2.82; 95% CI, 1.31-6.07) were associated with severe outcomes. Evaluation of the interaction term revealed that a positive SARS-CoV-2 result increased the associations with severe outcomes for elevated procalcitonin, C-reactive protein (CRP), D-dimer, and for reduced lymphocyte and platelet counts. Conclusions: Specific laboratory parameters are associated with severe outcomes in SARS-CoV-2-infected children, and elevated serum procalcitonin, CRP, and D-dimer and low absolute lymphocyte and platelet counts were more strongly associated with severe outcomes in children testing positive compared with those testing negative.

Travel surveillance uncovers dengue virus dynamics and introductions in the Caribbean.

Dengue is the most prevalent mosquito-borne viral disease in humans, and cases are continuing to rise globally. In particular, islands in the Caribbean have experienced more frequent outbreaks, and all four dengue virus (DENV) serotypes have been reported in the region, leading to hyperendemicity and increased rates of severe disease. However, there is significant variability regarding virus surveillance and reporting between islands, making it difficult to obtain an accurate understanding of the epidemiological patterns in the Caribbean. To investigate this, we used travel surveillance and genomic epidemiology to reconstruct outbreak dynamics, DENV serotype turnover, and patterns of spread within the region from 2009-2022. We uncovered two recent DENV-3 introductions from Asia, one of which resulted in a large outbreak in Cuba, which was previously under-reported. We also show that while outbreaks can be synchronized between islands, they are often caused by different serotypes. Our study highlights the importance of surveillance of infected travelers to provide a snapshot of local introductions and transmission in areas with limited local surveillance and suggests that the recent DENV-3 introductions may pose a major public health threat in the region.