On April 24, 2023, the American Samoa Department of Health (ASDoH) declared a public health emergency amid concern about a possible measles outbreak given low 2-dose vaccination coverage at the time. ASDoH had received two positive measles immunoglobulin (Ig) M test results after Flag Day festivities 1 week earlier from vaccinated children. ASDoH performed active case finding, took actions to mitigate transmission, and requested technical assistance from CDC. ASDoH implemented a vaccination campaign to improve suboptimal coverage. Confirmatory molecular testing of specimens from these initial persons under investigation (PUIs) was not possible, but subsequent testing of specimens from additional PUIs by Hawaii State Laboratories Division and CDC ruled out measles. In settings with low measles prevalence, measles antibody testing results have low positive predictive value and can lead to difficulties with interpreting results. Testing for additional pathogens revealed a variety of viruses known to cause common childhood viral exanthems. Both molecular and serologic testing should be performed for all suspected measles cases. To decrease the probability of false-positive IgM results, testing should be reserved for cases that meet the Council of State and Territorial Epidemiologists measles case definition, especially those in persons with no evidence of immunity and with a history of recent international travel. In addition, maintaining high measles vaccination coverage can prevent future outbreaks.

IMPORTANCE: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has evolved through multiple phases in the United States, with significant differences in patient centered outcomes with improvements in hospital strain, medical countermeasures, and overall understanding of the disease. We describe how patient characteristics changed and care progressed over the various pandemic phases; we also emphasize the need for an ongoing clinical network to improve the understanding of known and novel respiratory viral diseases. OBJECTIVES: To describe how patient characteristics and care evolved across the various COVID-19 pandemic periods in those hospitalized with viral severe acute respiratory infection (SARI). DESIGN: Severe Acute Respiratory Infection-Preparedness (SARI-PREP) is a Centers for Disease Control and Prevention Foundation-funded, Society of Critical Care Medicine Discovery-housed, longitudinal multicenter cohort study of viral pneumonia. We defined SARI patients as those hospitalized with laboratory-confirmed respiratory viral infection and an acute syndrome of fever, cough, and radiographic infiltrates or hypoxemia. We collected patient-level data including demographic characteristics, comorbidities, acute physiologic measures, serum and respiratory specimens, therapeutics, and outcomes. Outcomes were described across four pandemic variant periods based on a SARS-CoV-2 sequenced subsample: pre-Delta, Delta, Omicron BA.1, and Omicron post-BA.1. SETTING: Multicenter cohort of adult patients admitted to an acute care ward or ICU from seven hospitals representing diverse geographic regions across the United States. PARTICIPANTS: Patients with SARI caused by infection with respiratory viruses. MAIN OUTCOMES AND RESULTS: Eight hundred seventy-four adult patients with SARI were enrolled at seven study hospitals between March 2020 and April 2023. Most patients (780, 89%) had SARS-CoV-2 infection. Across the COVID-19 cohort, median age was 60 years (interquartile range, 48.0-71.0 yr) and 66% were male. Almost half (430, 49%) of the study population belonged to underserved communities. Most patients (76.5%) were admitted to the ICU, 52.5% received mechanical ventilation, and observed hospital mortality was 25.5%. As the pandemic progressed, we observed decreases in ICU utilization (94% to 58%), hospital length of stay (median, 26.0 to 8.5 d), and hospital mortality (32% to 12%), while the number of comorbid conditions increased. CONCLUSIONS AND RELEVANCE: We describe increasing comorbidities but improved outcomes across pandemic variant periods, in the setting of multiple factors, including evolving care delivery, countermeasures, and viral variants. An understanding of patient-level factors may inform treatment options for subsequent variants and future novel pathogens.

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.

OBJECTIVES: The COVID-19 pandemic threatened standard hospital operations. We sought to understand how this stress was perceived and manifested within individual hospitals and in relation to local viral activity. DESIGN: Prospective weekly hospital stress survey, November 2020-June 2022. SETTING: Society of Critical Care Medicine's Discovery Severe Acute Respiratory Infection-Preparedness multicenter cohort study. SUBJECTS: Thirteen hospitals across seven U.S. health systems. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We analyzed 839 hospital-weeks of data over 85 pandemic weeks and five viral surges. Perceived overall hospital, ICU, and emergency department (ED) stress due to severe acute respiratory infection patients during the pandemic were reported by a mean of 43% (sd, 36%), 32% (30%), and 14% (22%) of hospitals per week, respectively, and perceived care deviations in a mean of 36% (33%). Overall hospital stress was highly correlated with ICU stress (ρ = 0.82; p < 0.0001) but only moderately correlated with ED stress (ρ = 0.52; p < 0.0001). A county increase in 10 severe acute respiratory syndrome coronavirus 2 cases per 100,000 residents was associated with an increase in the odds of overall hospital, ICU, and ED stress by 9% (95% CI, 5-12%), 7% (3-10%), and 4% (2-6%), respectively. During the Delta variant surge, overall hospital stress persisted for a median of 11.5 weeks (interquartile range, 9-14 wk) after local case peak. ICU stress had a similar pattern of resolution (median 11 wk [6-14 wk] after local case peak; p = 0.59) while the resolution of ED stress (median 6 wk [5-6 wk] after local case peak; p = 0.003) was earlier. There was a similar but attenuated pattern during the Omicron BA.1 subvariant surge. CONCLUSIONS: During the COVID-19 pandemic, perceived care deviations were common and potentially avoidable patient harm was rare. Perceived hospital stress persisted for weeks after surges peaked.

Vascular dysfunction and capillary leak are common in critically ill COVID-19 patients, but identification of endothelial pathways involved in COVID-19 pathogenesis has been limited. Angiopoietin-like 4 (ANGPTL4) is a protein secreted in response to hypoxic and nutrient-poor conditions that has a variety of biological effects including vascular injury and capillary leak. OBJECTIVES: To assess the role of ANGPTL4 in COVID-19-related outcomes. DESIGN SETTING AND PARTICIPANTS: Two hundred twenty-five COVID-19 ICU patients were enrolled from April 2020 to May 2021 in a prospective, multicenter cohort study from three different medical centers, University of Washington, University of Southern California and New York University. MAIN OUTCOMES AND MEASURES: Plasma ANGPTL4 was measured on days 1, 7, and 14 after ICU admission. We used previously published tissue proteomic data and lung single nucleus RNA (snRNA) sequencing data from specimens collected from COVID-19 patients to determine the tissues and cells that produce ANGPTL4. RESULTS: Higher plasma ANGPTL4 concentrations were significantly associated with worse hospital mortality (adjusted odds ratio per log(2) increase, 1.53; 95% CI, 1.17-2.00; p = 0.002). Higher ANGPTL4 concentrations were also associated with higher proportions of venous thromboembolism and acute respiratory distress syndrome. Longitudinal ANGPTL4 concentrations were significantly different during the first 2 weeks of hospitalization in patients who subsequently died compared with survivors (p for interaction = 8.1 × 10(-5)). Proteomics analysis demonstrated abundance of ANGPTL4 in lung tissue compared with other organs in COVID-19. ANGPTL4 single-nuclear RNA gene expression was significantly increased in pulmonary alveolar type 2 epithelial cells and fibroblasts in COVID-19 lung tissue compared with controls. CONCLUSIONS AND RELEVANCE: ANGPTL4 is expressed in pulmonary epithelial cells and fibroblasts and is associated with clinical prognosis in critically ill COVID-19 patients.

Respiratory virus infections cause significant morbidity and mortality ranging from mild uncomplicated acute respiratory illness to severe complications, such as acute respiratory distress syndrome, multiple organ failure, and death during epidemics and pandemics. We present a protocol to systematically study patients with severe acute respiratory infection (SARI), including severe acute respiratory syndrome coronavirus 2, due to respiratory viral pathogens to evaluate the natural history, prognostic biomarkers, and characteristics, including hospital stress, associated with clinical outcomes and severity. DESIGN: Prospective cohort study. SETTING: Multicenter cohort of patients admitted to an acute care ward or ICU from at least 15 hospitals representing diverse geographic regions across the United States. PATIENTS: Patients with SARI caused by infection with respiratory viruses that can cause outbreaks, epidemics, and pandemics. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Measurements include patient demographics, signs, symptoms, and medications; microbiology, imaging, and associated tests; mechanical ventilation, hospital procedures, and other interventions; and clinical outcomes and hospital stress, with specimens collected on days 0, 3, and 7-14 after enrollment and at discharge. The primary outcome measure is the number of consecutive days alive and free of mechanical ventilation (VFD) in the first 30 days after hospital admission. Important secondary outcomes include organ failure-free days before acute kidney injury, shock, hepatic failure, disseminated intravascular coagulation, 28-day mortality, adaptive immunity, as well as immunologic and microbiologic outcomes. CONCLUSIONS: SARI-Preparedness is a multicenter study under the collaboration of the Society of Critical Care Medicine Discovery, Resilience Intelligence Network, and National Emerging Special Pathogen Training and Education Center, which seeks to improve understanding of prognostic factors associated with worse outcomes and increased resource utilization. This can lead to interventions to mitigate the clinical impact of respiratory virus infections associated with SARI.

BACKGROUND: Passive reporting to the Centers for Disease Control and Prevention has identified carbapenemase-producing organisms (CPOs) among solid organ transplant (SOT) recipients, potentially representing an emerging source of spread. We analyzed CPO prevalence in wards where SOT recipients receive inpatient care to inform public health action to prevent transmission. METHODS: From September 2019 to June 2020, five U.S. hospitals conducted consecutive point prevalence surveys (PPS) of all consenting patients admitted to transplant units, regardless of transplant status. We used the Cepheid Xpert® Carba-R assay to identify carbapenemase genes (bla(KPC) , bla(NDM) , bla(VIM) , bla(IMP) , bla(OXA-48) ) from rectal swabs. Laboratory-developed molecular tests were used to retrospectively test for a wider range of bla(IMP) and bla(OXA) variants. RESULTS: In total, 154 patients were screened and 92 (60%) were SOT recipients. CPOs were detected among 7 (8%) SOT recipients, from two of five screened hospitals: 4 bla(KPC) , 1 bla(NDM) , 2 blaOXA(-23) . CPOs were detected in 2 (3%) of 62 non-transplant patients. In three of five participating hospitals, CPOs were not identified among any patients admitted to transplant units. CONCLUSIONS: Longitudinal surveillance in transplant units, as well as PPS in areas with diverse CPO epidemiology, may inform the utility of routine screening in SOT units to prevent the spread of CPOs. This article is protected by copyright. All rights reserved.

The U.S. territory of American Samoa has experienced recent outbreaks of illnesses caused by viruses transmitted by Aedes species mosquitoes, including dengue, chikungunya, and Zika virus. In November 2016, a traveler from the Solomon Islands tested positive for infection with dengue virus type 2 (DENV-2). Additional dengue cases were identified in the subsequent weeks through passive and active surveillance. Suspected dengue cases were tested locally with a dengue rapid diagnostic test (RDT) for DENV nonstructural protein 1 (NS1). Specimens from RDT-positive cases and patients meeting the dengue case definition were tested by real-time reverse transcription-polymerase chain reaction (real-time RT-PCR) at Hawaii State Laboratories. During November 2016-October 2018, a total of 3,240 patients were tested for evidence of DENV infection (118 by RDT-NS1 alone, 1,089 by real-time RT-PCR alone, and 2,033 by both methods), 1,081 (33.4%) of whom tested positive for dengue (19.5 per 1,000 population). All 941 real-time RT-PCR-positive specimens were positive for DENV-2. The monthly number of laboratory-confirmed cases peaked at 120 during December 2017. Among laboratory-confirmed dengue cases, 380 (35.2%) patients were hospitalized; one patient, who was transferred to American Samoa for care late in his illness, died. The public health response to this outbreak included disposal of solid waste to remove mosquito breeding sites, indoor residual spraying of pesticides in schools, reinforcement of dengue patient management education, and public education on mosquito avoidance and seeking medical care for symptoms of dengue.

Pregnant women living in or traveling to areas with local mosquito-borne Zika virus transmission are at risk for Zika virus infection, which can lead to severe fetal and infant brain abnormalities and microcephaly (1). In February 2016, CDC recommended 1) routine testing for Zika virus infection of asymptomatic pregnant women living in areas with ongoing local Zika virus transmission at the first prenatal care visit, 2) retesting during the second trimester for women who initially test negative, and 3) testing of pregnant women with signs or symptoms consistent with Zika virus disease (e.g., fever, rash, arthralgia, or conjunctivitis) at any time during pregnancy (2). To collect information about pregnant women with laboratory evidence of recent possible Zika virus infection* and outcomes in their fetuses and infants, CDC established pregnancy and infant registries (3). During January 1, 2016-April 25, 2017, U.S. territoriesdagger with local transmission of Zika virus reported 2,549 completed pregnancies section sign (live births and pregnancy losses at any gestational age) with laboratory evidence of recent possible Zika virus infection; 5% of fetuses or infants resulting from these pregnancies had birth defects potentially associated with Zika virus infection paragraph sign (4,5). Among completed pregnancies with positive nucleic acid tests confirming Zika infection identified in the first, second, and third trimesters, the percentage of fetuses or infants with possible Zika-associated birth defects was 8%, 5%, and 4%, respectively. Among liveborn infants, 59% had Zika laboratory testing results reported to the pregnancy and infant registries. Identification and follow-up of infants born to women with laboratory evidence of recent possible Zika virus infection during pregnancy permits timely and appropriate clinical intervention services (6).

The first patients with laboratory-confirmed cases of Zika virus disease in American Samoa had symptom onset in January 2016. In response, the American Samoa Department of Health (ASDoH) implemented mosquito control measures, strategies to protect pregnant women, syndromic surveillance based on electronic health record (EHR) reports, Zika virus testing of persons with one or more signs or symptoms of Zika virus disease (fever, rash, arthralgia, or conjunctivitis), and routine testing of all asymptomatic pregnant women in accordance with CDC guidance. All collected blood and urine specimens were shipped to the Hawaii Department of Health Laboratory for Zika virus testing and to CDC for confirmatory testing. Early in the response, collection and testing of specimens from pregnant women was prioritized over the collection from symptomatic nonpregnant patients because of limited testing and shipping capacity. The weekly numbers of suspected Zika virus disease cases declined from an average of six per week in January-February 2016 to one per week in May 2016. By August, the EHR-based syndromic surveillance indicated a return to pre-outbreak levels. The last Zika virus disease case detected by real-time, reverse transcription-polymerase chain reaction (rRT-PCR) occurred in a patient who had symptom onset on June 19, 2016. In August 2016, ASDoH requested CDC support in assessing whether local transmission had been reduced or interrupted and in proposing a timeline for discontinuation of routine testing of asymptomatic pregnant women. An end date (October 15, 2016) was determined for active mosquito-borne transmission of Zika virus and a timeline was developed for discontinuation of routine screening of asymptomatic pregnant women in American Samoa (conception after December 10, 2016, with permissive testing for asymptomatic women who conceive through April 15, 2017).

Zika virus is a cause of microcephaly and brain abnormalities (1), and it is the first known mosquito-borne infection to cause congenital anomalies in humans. The establishment of a comprehensive surveillance system to monitor pregnant women with Zika virus infection will provide data to further elucidate the full range of potential outcomes for fetuses and infants of mothers with asymptomatic and symptomatic Zika virus infection during pregnancy. In February 2016, Zika virus disease and congenital Zika virus infections became nationally notifiable conditions in the United States (2). Cases in pregnant women with laboratory evidence of Zika virus infection who have either 1) symptomatic infection or 2) asymptomatic infection with diagnosed complications of pregnancy can be reported as cases of Zika virus disease to ArboNET* (2), CDC's national arboviral diseases surveillance system. Under existing interim guidelines from the Council for State and Territorial Epidemiologists (CSTE), asymptomatic Zika virus infections in pregnant women who do not have known pregnancy complications are not reportable. ArboNET does not currently include pregnancy surveillance information (e.g., gestational age or pregnancy exposures) or pregnancy outcomes. To understand the full impact of infection on the fetus and neonate, other systems are needed for reporting and active monitoring of pregnant women with laboratory evidence of possible Zika virus infection during pregnancy. Thus, in collaboration with state, local, tribal, and territorial health departments, CDC established two surveillance systems to monitor pregnancies and congenital outcomes among women with laboratory evidence of Zika virus infection(dagger) in the United States and territories: 1) the U.S. Zika Pregnancy Registry (USZPR),( section sign) which monitors pregnant women residing in U.S. states and all U.S. territories except Puerto Rico, and 2) the Zika Active Pregnancy Surveillance System (ZAPSS), which monitors pregnant women residing in Puerto Rico. As of May 12, 2016, the surveillance systems were monitoring 157 and 122 pregnant women with laboratory evidence of possible Zika virus infection from participating U.S. states and territories, respectively. Tracking and monitoring clinical presentation of Zika virus infection, all prenatal testing, and adverse consequences of Zika virus infection during pregnancy are critical to better characterize the risk for congenital infection, the performance of prenatal diagnostic testing, and the spectrum of adverse congenital outcomes. These data will improve clinical guidance, inform counseling messages for pregnant women, and facilitate planning for clinical and public health services for affected families.