COVID-19 in the US-affiliated Pacific Islands: A timeline of events and lessons learned from March 2020-November 2022.

The US-Affiliated Pacific Islands (USAPIs) experience many health disparities, including high rates of non-communicable disease and limited health resources, making them particularly vulnerable when SARS-CoV-2 began circulating globally in early 2020. Therefore, many USAPIs closed their borders early during the COVID-19 pandemic to give them more time to prepare for community transmission. Routine virtual meetings were established and maintained throughout the pandemic to support preparedness and response efforts and to share information among USAPIs and support partners. Data collected from these regular virtual meetings were gathered and disseminated through routine regional situational reports. These situational reports from March 27, 2020 to November 25, 2022 were reviewed to develop a quantitative dataset with qualitative notes that were used to summarize the COVID-19 response in the USAPIs. The initial surges of COVID-19 in the USAPIs ranged from August 2020 in Guam to August 2022 in the Federated States of Micronesia. This prolonged time between initial surges in the region was due to varying approaches regarding travel requirements, including fully closed borders, repatriation efforts requiring pre-travel quarantine and testing, quarantine requirements upon arrival only, and vaccine mandates. Delaying community transmission allowed USAPIs to establish testing capacity, immunize large proportions of their populations, and use novel COVID-19 therapeutics to reduce severe disease and mortality. Other essential components to support the USAPI regional COVID-19 response efforts included strong partnership and collaboration, regional information sharing and communication efforts, and trust in health leadership among community members. Valuable lessons learned from the USAPIs during the COVID-19 pandemic can be used to continue to strengthen systems within the region and better prepare for future public health emergencies.

Patient Characteristics During Early Transmission of SARS-CoV-2, Palau, January 13-February 24, 2022.

Palau had no reported evidence of COVID-19 community spread until January 2022. We chart reviewed hospitalized patients who had a positive SARS-CoV-2 test result during early community transmission. Booster vaccinations and early outpatient treatment decreased hospitalizations. Inadequate hospital infection control practices contributed to iatrogenic COVID-19 and preventable deaths.

Predictors of Inpatient Racemic Epinephrine Use in Patients Admitted With Croup.

OBJECTIVE: Many patients hospitalized for croup receive no additional racemic epinephrine (RE) postadmission. We analyzed the association between inpatient racemic epinephrine (RE) use and demographic and emergency department (ED) parameters including timing between RE doses with a goal of identifying patients who may be low risk for ED discharge. METHODS: We completed a retrospective cohort study of previously healthy patients ages 2 months to <7 years old who were admitted with a diagnosis of croup from 2016 to 2019 at a freestanding tertiary-care children's hospital. Patients were eligible for this study if they received at least 1 RE treatment before admission. RESULTS: The cohort included 238 patients; 59 (24.7%) patients received additional RE during admission. The number of RE doses in the ED (P = .99) and the median time between RE doses (P = .71) were not different between inpatient RE and no inpatient RE groups. Younger patients (P = .045) and patients with tachypnea for age (odds ratio [OR] 2.33; 95% confidence interval = 1.2-4.4) were more likely to require RE during admission. Median length of hospitalization for patients receiving inpatient RE was significantly longer (38 hours vs 16.7 hours, P < .001), whereas readmit rates were similar between groups (5.1% vs 3.9%, P = .71). CONCLUSIONS: Fewer than 25% of admitted patients received inpatient RE. Age and tachypnea for age were associated with inpatient RE use. Reassessment of admission thresholds for multidose RE use may be warranted to prevent unnecessary hospitalizations.

Two Distinct Illnesses Consistent With MIS-C in a Pediatric Patient.

Multisystem inflammatory syndrome in children (MIS-C) is a severe inflammatory response described in children after infection with severe acute respiratory syndrome coronavirus 2. We present a case of a 9-year-old African American boy with 2 distinct illnesses that were both consistent with MIS-C. He first presented in the early stages of our understanding of MIS-C with predominantly neurologic and gastrointestinal symptoms and demonstrated elevated inflammatory markers consistent with MIS-C. He was treated with intravenous immunoglobulin with complete resolution of signs and symptoms. After 7 months of good health, he returned with a second, distinct illness characterized by fever, rash, gastrointestinal symptoms, and elevated inflammatory markers that met the criteria for MIS-C. In addition, we identified new dilatation of the left anterior descending coronary artery. He improved rapidly after treatment with intravenous immunoglobulin, aspirin, and steroids. Our report highlights the need to achieve a better understanding of this entity's pathogenesis and clinical course and to improve anticipatory guidance for children with MIS-C.

Innovations to maximise impact of a data for decision-making training programme in the Federated States of Micronesia.

Accurate and timely health information is an essential foundation for strengthening health systems. Data for decision making (DDM) is a training curriculum designed to enhance capacity of health department staff to capture and use high-quality data to address priority health issues. In 2013, the Pacific Public Health Surveillance Network adapted and piloted the DDM curriculum as an 'at work, from work, for work' field epidemiology training programme component for low-income and middle-income Pacific Island jurisdictions. Based on lessons learned from the pilot, we made several innovations, including delivery on-site at each district (rather than bringing trainees to a central location), conducting pre-DDM consultations and ongoing contact with health leaders across the programme, taking more care in selecting trainees and enrolling a larger cohort of students from within each health department. The decentralised programme was delivered in-country at four sites (both at national and state levels) in the Federated States of Micronesia. Following delivery, we performed an external evaluation of the programme to assess student outcomes, benefits to the health department and general programme effectiveness. Of the 48 trainees who completed all four classroom modules, 40 trainees participated in the evaluation. Thirty-two of these trainees completed the programme's capstone field project. Eighteen of these projects directly contributed to changes in legislation, revised programme budgets, changes in programme strategy to augment outreach and to target disease and risk factor 'hot spots'.

Emergence of influenza B/Victoria in the Micronesian US-affiliated Pacific Islands, spring 2019.

Data collected through routine syndromic surveillance for influenza-like illness in the Micronesian United States-affiliated Pacific Islands highlighted out-of-season influenza outbreaks in the spring of 2019. This report describes the data collected through the World Health Organization's Pacific Syndromic Surveillance System for the Commonwealth of the Northern Mariana Islands (CNMI), Guam, the Federated States of Micronesia (FSM) and the Republic of the Marshall Islands (RMI). Compared with historical data, more cases of influenza-like illness were observed in all four islands described here, with the highest number reported in Guam in week 9, CNMI and FSM in week 15, and RMI in week 19. The outbreaks predominantly affected those aged < 20 years, with evidence from CNMI and RMI suggesting higher attack rates among those who were unvaccinated. Cases confirmed by laboratory testing suggested that influenza B was predominant, with 83% (99/120) of subtyped specimens classified as influenza B/Victoria during January-May 2019. These outbreaks occurred after the usual influenza season and were consistent with transmission patterns in Eastern Asia rather than those in Oceania or the United States of America, the areas typically associated with the United States-affiliated Pacific Islands due to their geographical proximity to Oceania and political affiliation with the United States of America. A plausible epidemiological route of introduction may be the high levels of international tourism from Eastern Asian countries recorded during these periods of increased influenza B/Victoria circulation. This report demonstrates the value of year-round surveillance for communicable diseases and underscores the importance of seasonal influenza vaccination, particularly among younger age groups.

Impact of program transfer from a non-governmental organization to a district health office: Evaluation of a program integrating water treatment and hygiene kits into reproductive health and HIV services, Machinga District, Malawi, 2010-2012.

BACKGROUND: In September 2009, the Machinga Integrated Antenatal Water Hygiene Kit Program began addressing problems of unsafe water, high infant mortality, and low antenatal care (ANC) attendance in Machinga District, Malawi. In March 2011, the supporting international non-governmental organization transitioned management of the program to the Machinga District Health Office (DHO). We evaluated maternal and HIV service use before and after program transition to the DHO. METHODS: We compared pre- and post-transition periods by examining data recorded in ANC and maternal registries in 15 healthcare facilities (HCFs) by proportion z-tests. We classified HCFs by size, using the median monthly patient volumes as the split for large or small facilities. We used logistic regression to evaluate changes in the use of ANC, maternal, and HIV services and their interactions with HCF size. RESULTS: The percentage of women attending their first ANC visit during the first trimester was similar in the pre-and post-transition periods (9.3% vs 10.2%). Although the percentage of women with ≥4 ANC visits was similar from pre- to post-transition (26.0% vs 24.8%), the odds increased among women in small facilities (OR: 1.37, 95% CI: 1.24-1.51), and decreased among women in large facilities (OR: 0.80, 95% CI: 0.75-0.85). Although a similar percentages of pregnant women were diagnosed with HIV in all HCFs in the pre- and post-transitions periods (6.4% vs 4.8%), a substantially larger proportion of women were not tested for HIV in large HCFs (OR: 6.34, 95% CI: 5.88-6.84). A larger proportion of women gave birth at both small (OR: 1.30, 95% CI: 1.16-1.45) and large HCFs (OR: 1.55, 95% CI: 1.43-1.67) in the post-transition vs. the pre-transition period. CONCLUSIONS: The evaluation results suggest that many positive aspects of this donor-supported program continued following transition of program management from a non-governmental organization to a DHO.

Outbreak of Dengue Virus Type 2 - American Samoa, November 2016-October 2018.

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.

Histone/protein deacetylase inhibitor therapy for enhancement of Foxp3+ T-regulatory cell function posttransplantation.

T-regulatory (Treg) cells are like other cells present throughout the body in being subject to biochemical modifications in response to extracellular signals. An important component of these responses involves changes in posttranslational modifications (PTMs) of histones and many nonhistone proteins, including phosphorylation/dephosphorylation, ubiquitination/deubiquitination, and acetylation/deacetylation. Foxp3, the key transcription factor of Tregs, is constantly being rapidly turned over, and a number of these PTMs determine its level of expression and activity. Of interest in the transplant setting, modulation of the acetylation or deacetylation of key lysine residues in Foxp3 can promote the stability and function, leading to increased Treg production and increased Treg suppressive activity. This mini-review focuses on recent data concerning the roles that histone/protein deacetylases (HDACs) play in control of Treg function, and how small molecule HDAC inhibitors can be used to promote Treg-dependent allograft survival in experimental models. These data are discussed in the light of increasing interest in the identification and clinical evaluation of isoform-selective HDAC inhibitors, and their potential application as tools to modulate Foxp3+ Treg cell numbers and function in transplant recipients.

Ability To Serologically Confirm Recent Zika Virus Infection in Areas with Varying Past Incidence of Dengue Virus Infection in the United States and U.S. Territories in 2016.

Cross-reactivity within flavivirus antibody assays, produced by shared epitopes in the envelope proteins, can complicate the serological diagnosis of Zika virus (ZIKAV) infection. We assessed the utility of the plaque reduction neutralization test (PRNT) to confirm recent ZIKAV infections and rule out misleading positive immunoglobulin M (IgM) results in areas with various levels of past dengue virus (DENV) infection incidence. We reviewed PRNT results of sera collected for diagnosis of ZIKAV infection from 1 January through 31 August 2016 with positive ZIKAV IgM results, and ZIKAV and DENV PRNTs were performed. PRNT result interpretations included ZIKAV, unspecified flavivirus, DENV infection, or negative. For this analysis, ZIKAV IgM was considered false positive for samples interpreted as a DENV infection or negative. In U.S. states, 208 (27%) of 759 IgM-positive results were confirmed to be ZIKAV compared to 11 (21%) of 52 in the U.S. Virgin Islands (USVI), 15 (15%) of 103 in American Samoa, and 13 (11%) of 123 in Puerto Rico. In American Samoa and Puerto Rico, more than 80% of IgM-positive results were unspecified flavivirus infections. The false-positivity rate was 27% in U.S. states, 18% in the USVI, 2% in American Samoa, and 6% in Puerto Rico. In U.S. states, the PRNT provided a virus-specific diagnosis or ruled out infection in the majority of IgM-positive samples. Almost a third of ZIKAV IgM-positive results were not confirmed; therefore, providers and patients must understand that IgM results are preliminary. In territories with historically higher rates of DENV transmission, the PRNT usually could not differentiate between ZIKAV and DENV infections.

Pregnancy Outcomes After Maternal Zika Virus Infection During Pregnancy - U.S. Territories, January 1, 2016-April 25, 2017.

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. territories† with local transmission of Zika virus reported 2,549 completed pregnancies§ (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¶ (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).

Chikungunya virus disease outbreak in Yap State, Federated States of Micronesia.

BACKGROUND: Chikungunya virus is a mosquito-borne alphavirus which causes an acute febrile illness associated with polyarthralgia. Beginning in August 2013, clinicians from the Yap State Department of Health in the Federated States of Micronesia (FSM) identified an unusual cluster of illness which was subsequently confirmed to be chikungunya virus disease. Chikungunya virus disease previously had not been recognized in FSM. METHODOLOGY/PRINCIPAL FINDINGS: Information from patients presenting to healthcare facilities was collected and analyzed. During August 11, 2013, to August 10, 2014, a total of 1,761 clinical cases were reported for an attack rate of 155 clinical cases per 1,000 population. Among residents of Yap Main Island, 3% were hospitalized. There were no deaths. The outbreak began on Yap Main Island and rapidly spread throughout Yap Main Island and to three neighboring islands. CONCLUSIONS/SIGNIFICANCE: Chikungunya virus can cause explosive outbreaks with substantial morbidity. Given the increasing globalization of chikungunya virus, strong surveillance systems and access to laboratory testing are essential to detect outbreaks.

Establishing a Timeline to Discontinue Routine Testing of Asymptomatic Pregnant Women for Zika Virus Infection - American Samoa, 2016-2017.

The first patients with laboratory-confirmed cases of Zika virus disease in American Samoa had symptom onset in January 2016 (1). In response, the American Samoa Department of Health (ASDoH) implemented mosquito control measures (1), strategies to protect pregnant women (1), syndromic surveillance based on electronic health record (EHR) reports (1), Zika virus testing of persons with one or more signs or symptoms of Zika virus disease (fever, rash, arthralgia, or conjunctivitis) (1-3), and routine testing of all asymptomatic pregnant women in accordance with CDC guidance (2,3). 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 (1) 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).

Notes from the Field: Outbreak of Zika Virus Disease - American Samoa, 2016.

During December 2015-January 2016, the American Samoa Department of Health (ASDoH) detected through surveillance an increase in the number of cases of acute febrile rash illness. Concurrently, a case of laboratory-confirmed Zika virus infection, a mosquito-borne flavivirus infection documented to cause microcephaly and other severe brain defects in some infants born to women infected during pregnancy (1,2) was reported in a traveler returning to New Zealand from American Samoa. In the absence of local laboratory capacity to test for Zika virus, ASDoH initiated arboviral disease control measures, including public education and vector source reduction campaigns. On February 1, CDC staff members were deployed to American Samoa to assist ASDoH with testing and surveillance efforts.

Interferometric Scattering Microscopy for the Study of Molecular Motors.

Our understanding of molecular motor function has been greatly improved by the development of imaging modalities, which enable real-time observation of their motion at the single-molecule level. Here, we describe the use of a new method, interferometric scattering microscopy, for the investigation of motor protein dynamics by attaching and tracking the motion of metallic nanoparticle labels as small as 20nm diameter. Using myosin-5, kinesin-1, and dynein as examples, we describe the basic assays, labeling strategies, and principles of data analysis. Our approach is relevant not only for motor protein dynamics but also provides a general tool for single-particle tracking with high spatiotemporal precision, which overcomes the limitations of single-molecule fluorescence methods.

Use of a Rapid Test for Diagnosis of Dengue during Suspected Dengue Outbreaks in Resource-Limited Regions.

Dengue is major public health problem, globally. Timely verification of suspected dengue outbreaks allows for public health response, leading to the initiation of appropriate clinical care. Because the clinical presentation of dengue is nonspecific, dengue diagnosis would benefit from a sensitive rapid diagnostic test (RDT). We evaluated the diagnostic performance of an RDT that detects dengue virus (DENV) nonstructural protein 1 (NS1) and anti-DENV IgM during suspected acute febrile illness (AFI) outbreaks in four countries. Real-time reverse transcription-PCR and anti-DENV IgM enzyme-linked immunosorbent assay were used to verify RDT results. Anti-DENV IgM RDT sensitivity and specificity ranged from 55.3 to 91.7% and 85.3 to 98.5%, respectively, and NS1 sensitivity and specificity ranged from 49.7 to 92.9% and 22.2 to 89.0%, respectively. Sensitivity varied by timing of specimen collection and DENV serotype. Combined test results moderately improved the sensitivity. The use of RDTs identified dengue as the cause of AFI outbreaks where reference diagnostic testing was limited or unavailable.