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.

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.

Understanding recovery and resilience from natural disasters in hospitality organizations.

Extreme weather events, such as Hurricane María, shed light on the importance of understanding the factors that promote resilience, defined as bouncing back after adverse events. The current study took a qualitative focus group approach toward understanding resilience in employees of the hospitality industry after Hurricane María. The hospitality industry plays an important role in disaster responses due to its role in supporting local and national economies, job stability for vulnerable employees, and in supporting response efforts, eg, housing aid workers. Through a series of in-depth focus groups, employees from San Juan, Puerto Rico and surrounding areas shared their Hurricane María experiences in terms of themselves as individuals, their workplaces, and their community. Major themes focused on the importance of the preparedness phase of the disaster response timeline, measuring impact and response on multiple levels in interdependent systems, creating and promoting awareness of resources, and acknowledging both struggle and strength when conceptualizing transformative potential. These findings can inform actionable strategies for individuals, organizations, and communities.

Barriers and Opportunities for the MCH Workforce to Support Hurricane Preparedness, Response, and Recovery in Florida.

OBJECTIVES: In recent years, catastrophic hurricanes have devastated numerous areas, prompting a need to build resilience particularly in at-risk populations that rely on health care and social services. The Maternal and Child Health (MCH) workforce covers a wide breadth of services to pregnant women, families, and children with special health care needs. Research has noted the need to strengthen this workforce with training and skills to help their patients and clients prepare, respond, and recover from disasters. METHODS: Focus groups and interviews with 35 Florida parents and professionals impacted by Hurricanes Irma, Maria, and Michael were conducted to evaluate the stressors placed on systems of care serving mothers and infants in Florida. Journey mapping was used to explore opportunities for improving MCH training and services. RESULTS: Results highlight the importance of increased communication and collaboration between families and providers, coordination among health care and social services providers, effective public messaging, tailored preparedness materials and processes, and the need for post-disaster mental health services and employment resources. CONCLUSION: Ultimately, hurricane preparation and mitigation are key for improving community resilience and these efforts should be tailored to MCH populations as well as delivered by the providers who know their needs best.

Challenges for the disaster workforce during a compound hurricane-pandemic.

The COVID-19 pandemic has created new workforce considerations for emergency management community in addressing cumulative and cascading disasters. This research identifies how emergency management planning for both the changing dynamics of COVID-19 and the upcoming hurricane season may change under a compound threat. Many jurisdictions have faced challenges in providing adequate staffing of shelters before the pandemic. Now, fatigue among staff further exacerbates these challenges as resources are stretched thin. Six workshops, involving 265 national, state, and local leaders, staff, experts, and advocates from 22 states, and a range of disciplines (disaster planning, public health, social services, academia, and healthcare), were convened to identify concerns and potential strategies to address staffing, training, logistics, and support. Strategies proposed to increase the number and skill set of staff available involve increased reliance upon volunteers and nonprofit organizations. Mental health resources, personal protective equipment, sanitation supplies, and defining roles within emergency shelters were recommended to reduce fatigue and redistribute responsibilities. Findings illuminate additional research avenues regarding assessing the underlying stressors contributing to the planning process and effective means of implementing these interventions to bolster emergency management shelter operations during a prolonged pandemic and in the future.

An Evaluation of Florida's Zika Response Using the WHO Health Systems Framework: Can We Apply These Lessons to COVID-19?

OBJECTIVES: From 2016 to 2018 Florida documented 1471 cases of Zika virus, 299 of which were pregnant women (Florida Department of Health, https://www.floridahealth.gov/diseases-and-conditions/mosquito-bornediseases/surveillance.html , 2019a). Florida's response required unprecedented rapid and continuous cross-sector communication, adaptation, and coordination. Zika tested public health systems in new ways, particularly for maternal child health populations. The systems are now being challenged again, as the Coronavirus COVID-19 pandemic spreads throughout Florida. This qualitative journey mapping evaluation of Florida's response focused on care for pregnant women and families with infants exposed to Zika virus. METHODS: Fifteen focus groups and interviews were conducted with 33 public health and healthcare workers who managed outbreak response, case investigations, and patient care in south Florida. Data were thematically analyzed, and the results were framed by the World Health Organization's (WHO) Healthcare Systems Framework of six building blocks: health service delivery, health workforce, health information systems, access to essential medicines, financing, and leadership and governance (World Health Organization, https://www.who.int/healthsystems/strategy/everybodys_business.pdf , 2007, https://www.who.int/healthinfo/systems/monitoring/en/ , 2010). RESULTS: Results highlighted coordination of resources, essential services and treatment, data collection, communication among public health and healthcare systems, and dissemination of information. Community education, testing accuracy and turnaround time, financing, and continuity of health services were areas of need, and there was room for improvement in all indicator areas. CONCLUSIONS: The WHO Framework encapsulated important infrastructure and process factors relevant to the Florida Zika response as well as future epidemics. In this context, similarities, differences, and implications for the Coronavirus COVID-19 pandemic response are discussed.

Partnerships Involved in Public Health Testing for Zika Virus in Florida, 2016.

The emergence of Zika virus in the Americas in 2015 and its association with birth defects and other adverse health outcomes triggered an unprecedented public health response and a demand for testing. In 2016, when Florida exceeded state public health laboratory capacity for diagnostic testing, the state formed partnerships with federal and commercial laboratories. Eighty-two percent of the testing (n = 33 802 of 41 008 specimens) by the laboratory partners, including Florida's Bureau of Public Health Laboratories (BPHL; n = 13 074), a commercial laboratory (n = 19 214), and the Centers for Disease Control and Prevention (CDC; n = 1514), occurred from July through November 2016, encompassing the peak period of local transmission. These partnerships allowed BPHL to maintain acceptable test turnaround times of 1 to 4 days for nucleic acid testing and 3 to 7 days for serologic testing. Lessons learned from this response to inform future outbreaks included the need for early planning to establish outside partnerships, adding specimen triage strategies to surge plans, and integrating state and CDC information systems.

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.

A CD40 Agonist and PD-1 Antagonist Antibody Reprogram the Microenvironment of Nonimmunogenic Tumors to Allow T-cell-Mediated Anticancer Activity.

In cancers with tumor-infiltrating lymphocytes (TILs), monoclonal antibodies (mAbs) that block immune checkpoints such as CTLA-4 and PD-1/PD-L1 promote antitumor T-cell immunity. Unfortunately, most cancers fail to respond to single-agent immunotherapies. T regulatory cells, myeloid derived suppressor cells (MDSCs), and extensive stromal networks within the tumor microenvironment (TME) dampen antitumor immune responses by preventing T-cell infiltration and/or activation. Few studies have explored combinations of immune-checkpoint antibodies that target multiple suppressive cell populations within the TME, and fewer have studied the combinations of both agonist and antagonist mAbs on changes within the TME. Here, we test the hypothesis that combining a T-cell-inducing vaccine with both a PD-1 antagonist and CD40 agonist mAbs (triple therapy) will induce T-cell priming and TIL activation in mouse models of nonimmunogenic solid malignancies. In an orthotopic breast cancer model and both subcutaneous and metastatic pancreatic cancer mouse models, only triple therapy was able to eradicate most tumors. The survival benefit was accompanied by significant tumor infiltration of IFNγ-, Granzyme B-, and TNFα-secreting effector T cells. Further characterization of immune populations was carried out by high-dimensional flow-cytometric clustering analysis and visualized by t-distributed stochastic neighbor embedding (t-SNE). Triple therapy also resulted in increased infiltration of dendritic cells, maturation of antigen-presenting cells, and a significant decrease in granulocytic MDSCs. These studies reveal that combination CD40 agonist and PD-1 antagonist mAbs reprogram immune resistant tumors in favor of antitumor immunity.

Entinostat Converts Immune-Resistant Breast and Pancreatic Cancers into Checkpoint-Responsive Tumors by Reprogramming Tumor-Infiltrating MDSCs.

Immune-checkpoint inhibition (ICI) has revolutionized treatment in cancers that are naturally immunogenic by enabling infiltration of T cells into the tumor microenvironment (TME) and promoting cytotoxic signaling pathways. Tumors possessing complex immunosuppressive TMEs such as breast and pancreatic cancers present unique therapeutic obstacles as response rates to ICI remain low. Such tumors often recruit myeloid-derived suppressor cells (MDSCs), whose functioning prohibits both T-cell activation and infiltration. We attempted to sensitize these tumors to ICI using epigenetic modulation to target MDSC trafficking and function to foster a less immunosuppressive TME. We showed that combining a histone deacetylase inhibitor, entinostat (ENT), with anti-PD-1, anti-CTLA-4, or both significantly improved tumor-free survival in both the HER2/neu transgenic breast cancer and the Panc02 metastatic pancreatic cancer mouse models. Using flow cytometry, gene-expression profiling, and ex vivo functional assays, we characterized populations of tumor-infiltrating lymphocytes (TILs) and MDSCs, as well as their functional capabilities. We showed that addition of ENT to checkpoint inhibition led to significantly decreased suppression by granulocytic MDSCs in the TME of both tumor types. We also demonstrated an increase in activated granzyme-B-producing CD8+ T effector cells in mice treated with combination therapy. Gene-expression profiling of both MDSCs and TILs identified significant changes in immune-related pathways. In summary, addition of ENT to ICI significantly altered infiltration and function of innate immune cells, allowing for a more robust adaptive immune response. These findings provide a rationale for combination therapy in patients with immune-resistant tumors, including breast and pancreatic cancers.

Effect of endoscopic pyloric therapies for patients with nausea and vomiting and functional obstructive gastroparesis.

Gastroparesis (GP) is associated with loss of interstitial cells of Cajal (ICCs) and gastric dysrhythmias such as tachygastria. We hypothesized that a subset of patients with GP, normal 3cycles per minute (cpm) gastric myoelectrical activity (GMA), and normal upper endoscopy may respond to pyloric therapies. AIMS: To determine the effect of botulinum toxin A (btA) injection or balloon dilation (BD) of the pylorus on symptoms and body weight in patients with GP and 3cpm GMA. METHODS: Patients were identified who had GP, normal 3cpm GMA, and normal endoscopy that excluded mechanical obstruction of the pylorus. Electrogastrograms (EGG) with water load tests (WLT) were recorded to determine GMA. Gastric emptying was measured with 4h scintigraphy. Each patient underwent up to three pyloric treatments with btA or BD. RESULTS: Thirty-three patients (29 women) with an average age of 42years were studied. Seventy-nine percent had idiopathic GP and 21% had diabetic GP. The average percent meal retained at 4h was 42% and each EGG test showed normal 3cpm GMA. Nausea was the major symptom in 76% of patients. Complete or partial symptom response occurred in 75%, 72%, and 88% of patients after the first, second, or third endoscopic pyloric treatment, respectively. Overall, 78% of the 33 patients reported improvement in symptoms and average weight gain was 1.54lb from baseline to final treatment (p<0.04). CONCLUSION: Pyloric therapies appear to be effective treatments in symptomatic patients with GP and 3cpm GMA and controlled trials are warranted.

Local Mosquito-Borne Transmission of Zika Virus - Miami-Dade and Broward Counties, Florida, June-August 2016.

During the first 6 months of 2016, large outbreaks of Zika virus disease caused by local mosquito-borne transmission occurred in Puerto Rico and other U.S. territories, but local mosquito-borne transmission was not identified in the continental United States (1,2). As of July 22, 2016, the Florida Department of Health had identified 321 Zika virus disease cases among Florida residents and visitors, all occurring in either travelers from other countries or territories with ongoing Zika virus transmission or sexual contacts of recent travelers.* During standard case investigation of persons with compatible illness and laboratory evidence of recent Zika virus infection (i.e., a specimen positive by real-time reverse transcription-polymerase chain reaction [rRT-PCR], or positive Zika immunoglobulin M [IgM] with supporting dengue serology [negative for dengue IgM antibodies and positive for dengue IgG antibodies], or confirmation of Zika virus neutralizing antibodies by plaque reduction neutralization testing [PRNT]) (3), four persons were identified in Broward and Miami-Dade counties whose infections were attributed to likely local mosquito-borne transmission. Two of these persons worked within 120 meters (131 yards) of each other but had no other epidemiologic connections, suggesting the possibility of a local community-based outbreak. Further epidemiologic and laboratory investigations of the worksites and surrounding neighborhood identified a total of 29 persons with laboratory evidence of recent Zika virus infection and likely exposure during late June to early August, most within an approximate 6-block area. In response to limited impact on the population of Aedes aegypti mosquito vectors from initial ground-based mosquito control efforts, aerial ultralow volume spraying with the organophosphate insecticide naled was applied over a 10 square-mile area beginning in early August and alternated with aerial larviciding with Bacillus thuringiensis subspecies israelensis (Bti), a group biologic control agent, in a central 2 square-mile area. No additional cases were identified after implementation of this mosquito control strategy. No increases in emergency department (ED) patient visits associated with aerial spraying were reported, including visits for asthma, reactive airway disease, wheezing, shortness of breath, nausea, vomiting, or diarrhea. Local and state health departments serving communities where Ae. aegypti, the primary vector of Zika virus, is found should continue to actively monitor for local transmission of the virus.(†).

Black widow spider envenomation, a rare cause of Horner's syndrome.

Horner's syndrome involves a triad of eyelid ptosis, miosis, and facial anhidrosis that results from disruption of the oculosympathetic pathway. Acquired Horner's syndrome is associated with a variety of medical conditions including Pancoast tumor and carotid dissection. We report the unique case of a 47-year-old man presenting with Horner's syndrome 4 weeks after black widow spider envenomation. Workup did not reveal any alternative explanatory etiology. We hypothesize that late sequelae of black widow spider envenomation secondary to autonomic nerve injury or retrograde axonal transport after mechanical inoculation may have led to an acquired defect in the oculosympathetic pathway resulting in a Horner's syndrome. This case introduces a rare cause of Horner's syndrome and highlights the importance of environmental exposures in the evaluation of these patients.