Enhancing Eastern Equine Encephalitis Virus Surveillance in New Jersey: Optimized Collection of Culiseta Melanura.

Eastern equine encephalitis virus (EEEV) causes the most clinically severe neuroinvasive arboviral disease in the United States. The virus is endemic in eastern and Gulf Coast states and the Great Lakes region, causing cases annually. To detect EEEV circulation in its enzootic cycle before the virus infects humans and other mammals, mosquito control agencies in New Jersey have conducted mosquito surveillance using a series of permanent wooden resting box sites since 1975. We conducted 2 field studies, 1 evaluating resting traps and 1 evaluating efficacy of CO2 lures, to optimize collection of Culiseta melanura, the primary enzootic vector of EEEV. Resulting mosquito samples were subjected to molecular analysis to determine EEEV infection rates. Corrugated plastic boxes trapped more bloodfed Cs. melanura than other resting trap types (resting boxes, Centers for Disease Control and Prevention [CDC] resting traps, or fiber pots) and were similar to resting boxes in total number of female Cs. melanura caught. Further, non-baited CDC light traps were more successful in trapping host-seeking Cs. melanura than those baited with dry ice, a CO2 lure. The EEEV RNA was identified in Cs. melanura, Aedes vexans, Anopheles quadrimaculatus, and Uranotaenia sapphirina. Our findings indicate that corrugated plastic boxes and non-CO2 baited traps could improve detection of Cs. melanura. Mosquito control agencies are encouraged to periodically assess their surveillance strategy for EEEV.

Immunological response to fractional-dose yellow fever vaccine administered during an outbreak in Kinshasa, Democratic Republic of the Congo: results 5 years after vaccination from a prospective cohort study.

BACKGROUND: In 2016, outbreaks of yellow fever in Angola and the Democratic Republic of the Congo led to a global vaccine shortage. A fractional dose of 17DD yellow fever vaccine (containing one-fifth [0·1 ml] of the standard dose) was used during a pre-emptive mass campaign in August, 2016, in Kinshasa, Democratic Republic of the Congo among children aged 2 years and older and non-pregnant adults (ie, those aged 18 years and older). 1 year following vaccination, 97% of participants were seropositive; however, the long-term durability of the immune response is unknown. We aimed to conduct a prospective cohort study and invited participants enrolled in the previous evaluation to return 5 years after vaccination to assess durability of the immune response. METHODS: Participants returned to one of six health facilities in Kinshasa in 2021, where study staff collected a brief medical history and blood specimen. We assessed neutralising antibody titres against yellow fever virus using a plaque reduction neutralisation test with a 50% cutoff (PRNT50). Participants with a PRNT50 titre of 10 or higher were considered seropositive. The primary outcome was the proportion of participants seropositive at 5 years. FINDINGS: Among the 764 participants enrolled, 566 (74%) completed the 5-year visit. 5 years after vaccination, 539 (95·2%, 95% CI 93·2-96·7) participants were seropositive, including 361 (94·3%, 91·5-96·2) of 383 who were seronegative and 178 (97·3%, 93·8-98·8) of 183 who were seropositive at baseline. Geometric mean titres (GMTs) differed significantly across age groups for those who were initially seronegative with the lowest GMT among those aged 2-5 years and highest among those aged 13 years and older. INTERPRETATION: A fractional dose of the 17DD yellow fever vaccine induced an immunologic response with detectable titres at 5 years among the majority of participants in the Democratic Republic of the Congo. These findings support the use of fractional-dose vaccination for outbreak prevention with the potential for sustained immunity. FUNDING: Gavi, the Vaccine Alliance through the CDC Foundation. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Tick-Borne Encephalitis Vaccine: Recommendations of the Advisory Committee on Immunization Practices, United States, 2023.

Tick-borne encephalitis (TBE) virus is focally endemic in parts of Europe and Asia. The virus is primarily transmitted to humans by the bites of infected: Ixodes species ticks but can also be acquired less frequently by alimentary transmission. Other rare modes of transmission include through breastfeeding, blood transfusion, solid organ transplantation, and slaughtering of viremic animals. TBE virus can cause acute neurologic disease, which usually results in hospitalization, often permanent neurologic or cognitive sequelae, and sometimes death. TBE virus infection is a risk for certain travelers and for laboratory workers who work with the virus. In August 2021, the Food and Drug Administration approved Ticovac TBE vaccine for use among persons aged ≥1 year. This report summarizes the epidemiology of and risks for infection with TBE virus, provides information on the immunogenicity and safety of TBE vaccine, and summarizes the recommendations of the Advisory Committee on Immunization Practices (ACIP) for use of TBE vaccine among U.S. travelers and laboratory workers.

Multi-Model Prediction of West Nile Virus Neuroinvasive Disease With Machine Learning for Identification of Important Regional Climatic Drivers.

West Nile virus (WNV) is the leading cause of mosquito-borne illness in the continental United States (CONUS). Spatial heterogeneity in historical incidence, environmental factors, and complex ecology make prediction of spatiotemporal variation in WNV transmission challenging. Machine learning provides promising tools for identification of important variables in such situations. To predict annual WNV neuroinvasive disease (WNND) cases in CONUS (2015-2021), we fitted 10 probabilistic models with variation in complexity from naïve to machine learning algorithm and an ensemble. We made predictions in each of nine climate regions on a hexagonal grid and evaluated each model's predictive accuracy. Using the machine learning models (random forest and neural network), we identified the relative importance and variation in ranking of predictors (historical WNND cases, climate anomalies, human demographics, and land use) across regions. We found that historical WNND cases and population density were among the most important factors while anomalies in temperature and precipitation often had relatively low importance. While the relative performance of each model varied across climatic regions, the magnitude of difference between models was small. All models except the naïve model had non-significant differences in performance relative to the baseline model (negative binomial model fit per hexagon). No model, including the ensemble or more complex machine learning models, outperformed models based on historical case counts on the hexagon or region level; these models are good forecasting benchmarks. Further work is needed to assess if predictive capacity can be improved beyond that of these historical baselines.

Fractional Dosing of Yellow Fever Live Attenuated 17D Vaccine: A Perspective.

Yellow fever virus (YFV) is a mosquito-borne flavivirus that causes over 109,000 severe infections and over 51,000 deaths annually in endemic areas of sub-Saharan Africa and tropical South America. The virus has a transmission cycle involving mosquitoes and humans or non-human primates (NHPs) as the vertebrate hosts. Although yellow fever (YF) is prevented by a live attenuated vaccine (strain 17D), recent epidemics in Angola, the Democratic Republic of the Congo (DRC), and Brazil put great pressure on vaccine stockpiles. This resulted in the World Health Organization (WHO) and Pan American Health Organization (PAHO) implementing, on an emergency basis only, off-label dose-sparing techniques and policies during 2016-2018 to protect as many people in DRC and Brazil as possible from disease during unexpected large outbreaks of YF. Subsequently non-inferiority studies involving full doses compared to fractional doses indicated promising results, leading some policy-makers and scientists to consider utilizing YF vaccine fractional doses in non-emergency scenarios. Although the additional data on the immunogenicity and safety of fractional doses are promising, there are several questions and considerations that remain regarding the use of fractional doses, including differences in the initial antibody kinetics, differences in the immune response in certain populations, and durability of the immune response to fractional doses compared to full doses. Until the remaining knowledge gaps are addressed, full doses instead of fractional doses should continue to be used unless there are insufficient doses of the vaccine available to control outbreaks of YF.

West Nile Virus and Other Nationally Notifiable Arboviral Diseases - United States, 2021.

Arthropod-borne viruses (arboviruses) are transmitted to humans primarily through the bites of infected mosquitoes or ticks, and in the continental United States, West Nile virus (WNV) is the leading cause of domestically acquired arboviral disease. Other arboviruses cause sporadic cases of disease as well as occasional outbreaks. This report summarizes 2021 surveillance data reported to CDC by U.S. jurisdictions for nationally notifiable arboviruses; the report excludes chikungunya, dengue, yellow fever, and Zika virus disease cases, because these infections were acquired primarily through travel during 2021. Forty-nine states and the District of Columbia reported 3,035 cases of domestic arboviral disease, including those caused by West Nile (2,911), La Crosse (40), Jamestown Canyon (32), Powassan (24), St. Louis encephalitis (17), unspecified California serogroup (six), and eastern equine encephalitis (five) viruses. Among the WNV disease cases, 2,008 (69%) were classified as neuroinvasive disease, for a national incidence of 0.61 cases per 100,000 population. Because arboviral diseases continue to cause serious illness, maintaining surveillance programs to monitor their transmission and prevalence is important to the direction and promotion of prevention activities. Health care providers should consider arboviral infections in the differential diagnosis of aseptic meningitis and encephalitis, obtain appropriate specimens for laboratory testing, and promptly report cases to public health authorities. Prevention depends on community and household efforts to reduce vector populations and personal protective measures to prevent mosquito and tick bites, such as use of Environmental Protection Agency-registered insect repellent and wearing protective clothing.

Transmission of yellow fever vaccine virus through blood transfusion and organ transplantation in the USA in 2021: report of an investigation.

BACKGROUND: In 2021, four patients who had received solid organ transplants in the USA developed encephalitis beginning 2-6 weeks after transplantation from a common organ donor. We describe an investigation into the cause of encephalitis in these patients. METHODS: From Nov 7, 2021, to Feb 24, 2022, we conducted a public health investigation involving 15 agencies and medical centres in the USA. We tested various specimens (blood, cerebrospinal fluid, intraocular fluid, serum, and tissues) from the organ donor and recipients by serology, RT-PCR, immunohistochemistry, metagenomic next-generation sequencing, and host gene expression, and conducted a traceback of blood transfusions received by the organ donor. FINDINGS: We identified one read from yellow fever virus in cerebrospinal fluid from the recipient of a kidney using metagenomic next-generation sequencing. Recent infection with yellow fever virus was confirmed in all four organ recipients by identification of yellow fever virus RNA consistent with the 17D vaccine strain in brain tissue from one recipient and seroconversion after transplantation in three recipients. Two patients recovered and two patients had no neurological recovery and died. 3 days before organ procurement, the organ donor received a blood transfusion from a donor who had received a yellow fever vaccine 6 days before blood donation. INTERPRETATION: This investigation substantiates the use of metagenomic next-generation sequencing for the broad-based detection of rare or unexpected pathogens. Health-care workers providing vaccinations should inform patients of the need to defer blood donation for at least 2 weeks after receiving a yellow fever vaccine. Despite mitigation strategies and safety interventions, a low risk of transfusion-transmitted infections remains. FUNDING: US Centers for Disease Control and Prevention (CDC), the Biomedical Advanced Research and Development Authority, and the CDC Epidemiology and Laboratory Capacity Cooperative Agreement for Infectious Diseases.

Immune response to co-administration of measles, mumps, and rubella (MMR), and yellow fever vaccines: a randomized non-inferiority trial among one-year-old children in Argentina.

BACKGROUND: In yellow fever (YF) endemic areas, measles, mumps, and rubella (MMR), and YF vaccines are often co-administered in childhood vaccination schedules. Because these are live vaccines, we assessed potential immune interference that could result from co-administration. METHODS: We conducted an open-label, randomized non-inferiority trial among healthy 1-year-olds in Misiones Province, Argentina. Children were randomized to one of three groups (1:1:1): Co-administration of MMR and YF vaccines (MMR1YF1), MMR followed by YF vaccine four weeks later (MMR1YF2), or YF followed by MMR vaccine four weeks later (YF1MMR2). Blood samples obtained pre-vaccination and 28 days post-vaccination were tested for immunoglobulin G antibodies against measles, mumps, and rubella, and for YF virus-specific neutralizing antibodies. Non-inferiority in seroconversion was assessed using a -5% non-inferiority margin. Antibody concentrations were compared with Kruskal-Wallis tests. RESULTS: Of 851 randomized children, 738 were correctly vaccinated, had ≥ 1 follow-up sample, and were included in the intention-to-treat population. Non-inferior seroconversion was observed for all antigens (measles seroconversion: 97.9% in the MMR1YF1 group versus 96.3% in the MMR1YF2 group, a difference of 1.6% [90% CI -1.5, 4.7]; rubella: 97.9% MMR1YF1 versus 94.7% MMR1YF2, a difference of 3.3% [-0.1, 6.7]; mumps: 96.7% MMR1YF1 versus 97.9% MMR1YF2, a difference of -1.3% [-4.1, 1.5]; and YF: 96.3% MMR1YF1 versus 97.5% YF1MMR2, a difference of -1.2% [-4.2, 1.7]). Rubella antibody concentrations and YF titers were significantly lower following co-administration; measles and mumps concentrations were not impacted. CONCLUSION: Effective seroconversion was achieved and was not impacted by the co-administration, although antibody levels for two antigens were lower. The impact of lower antibody levels needs to be weighed against missed opportunities for vaccination to determine optimal timing for MMR and YF vaccine administration. TRIAL REGISTRATION: The study was retrospectively registered in ClinicalTrials.gov (NCT03368495) on 11/12/2017.

Increase in Colorado Tick Fever Virus Disease Cases and Effect of COVID-19 Pandemic on Behaviors and Testing Practices, Montana, 2020.

In 2020, Montana, USA, reported a large increase in Colorado tick fever (CTF) cases. To investigate potential causes of the increase, we conducted a case-control study of Montana residents who tested positive or negative for CTF during 2020, assessed healthcare providers' CTF awareness and testing practices, and reviewed CTF testing methods. Case-patients reported more time recreating outdoors on weekends, and all reported finding a tick on themselves before illness. No consistent changes were identified in provider practices. Previously, only CTF serologic testing was used in Montana. In 2020, because of SARS-CoV-2 testing needs, the state laboratory sent specimens for CTF testing to the Centers for Disease Control and Prevention, where more sensitive molecular methods are used. This change in testing probably increased the number of CTF cases detected. Molecular testing is optimal for CTF diagnosis during acute illness. Tick bite prevention measures should continue to be advised for persons doing outdoor activities.

Evaluation of an open forecasting challenge to assess skill of West Nile virus neuroinvasive disease prediction.

BACKGROUND: West Nile virus (WNV) is the leading cause of mosquito-borne illness in the continental USA. WNV occurrence has high spatiotemporal variation, and current approaches to targeted control of the virus are limited, making forecasting a public health priority. However, little research has been done to compare strengths and weaknesses of WNV disease forecasting approaches on the national scale. We used forecasts submitted to the 2020 WNV Forecasting Challenge, an open challenge organized by the Centers for Disease Control and Prevention, to assess the status of WNV neuroinvasive disease (WNND) prediction and identify avenues for improvement. METHODS: We performed a multi-model comparative assessment of probabilistic forecasts submitted by 15 teams for annual WNND cases in US counties for 2020 and assessed forecast accuracy, calibration, and discriminatory power. In the evaluation, we included forecasts produced by comparison models of varying complexity as benchmarks of forecast performance. We also used regression analysis to identify modeling approaches and contextual factors that were associated with forecast skill. RESULTS: Simple models based on historical WNND cases generally scored better than more complex models and combined higher discriminatory power with better calibration of uncertainty. Forecast skill improved across updated forecast submissions submitted during the 2020 season. Among models using additional data, inclusion of climate or human demographic data was associated with higher skill, while inclusion of mosquito or land use data was associated with lower skill. We also identified population size, extreme minimum winter temperature, and interannual variation in WNND cases as county-level characteristics associated with variation in forecast skill. CONCLUSIONS: Historical WNND cases were strong predictors of future cases with minimal increase in skill achieved by models that included other factors. Although opportunities might exist to specifically improve predictions for areas with large populations and low or high winter temperatures, areas with high case-count variability are intrinsically more difficult to predict. Also, the prediction of outbreaks, which are outliers relative to typical case numbers, remains difficult. Further improvements to prediction could be obtained with improved calibration of forecast uncertainty and access to real-time data streams (e.g. current weather and preliminary human cases).

Severe Arboviral Neuroinvasive Disease in Patients on Rituximab Therapy: A Review.

With increasing use of rituximab and other B-cell depleting monoclonal antibodies for multiple indications, infectious complications are being recognized. We summarize clinical findings of patients on rituximab with arboviral diseases identified through literature review or consultation with the Centers for Disease Control and Prevention. We identified 21 patients on recent rituximab therapy who were diagnosed with an arboviral disease caused by West Nile, tick-borne encephalitis, eastern equine encephalitis, Cache Valley, Jamestown Canyon, and Powassan viruses. All reported patients had neuroinvasive disease. The diagnosis of arboviral infection required molecular testing in 20 (95%) patients. Median illness duration was 36 days (range, 12 days to 1 year), and 15/19 (79%) patients died from their illness. Patients on rituximab with arboviral disease can have a severe or prolonged course with an absence of serologic response. Patients should be counseled about mosquito and tick bite prevention when receiving rituximab and other B-cell depleting therapies.

Transfusion-Transmitted Cache Valley Virus Infection in a Kidney Transplant Recipient With Meningoencephalitis.

BACKGROUND: Cache Valley virus (CVV) is a mosquito-borne virus that is a rare cause of disease in humans. In the fall of 2020, a patient developed encephalitis 6 weeks following kidney transplantation and receipt of multiple blood transfusions. METHODS: After ruling out more common etiologies, metagenomic next-generation sequencing (mNGS) of cerebrospinal fluid (CSF) was performed. We reviewed the medical histories of the index kidney recipient, organ donor, and recipients of other organs from the same donor and conducted a blood traceback investigation to evaluate blood transfusion as a possible source of infection in the kidney recipient. We tested patient specimens using reverse-transcription polymerase chain reaction (RT-PCR), the plaque reduction neutralization test, cell culture, and whole-genome sequencing. RESULTS: CVV was detected in CSF from the index patient by mNGS, and this result was confirmed by RT-PCR, viral culture, and additional whole-genome sequencing. The organ donor and other organ recipients had no evidence of infection with CVV by molecular or serologic testing. Neutralizing antibodies against CVV were detected in serum from a donor of red blood cells received by the index patient immediately prior to transplant. CVV neutralizing antibodies were also detected in serum from a patient who received the co-component plasma from the same blood donation. CONCLUSIONS: Our investigation demonstrates probable CVV transmission through blood transfusion. Clinicians should consider arboviral infections in unexplained meningoencephalitis after blood transfusion or organ transplantation. The use of mNGS might facilitate detection of rare, unexpected infections, particularly in immunocompromised patients.

Acceptability of a Chikungunya Virus Vaccine, United States Virgin Islands.

Chikungunya virus, a mosquito-borne alphavirus, causes acute febrile illness with polyarthralgia. Groups at risk for severe disease include neonates, people with underlying medical conditions, and those aged ≥ 65 years. Several chikungunya vaccines are in late clinical development with licensure expected in the United States during 2023. We administered a questionnaire to randomly selected households in the U.S. Virgin Islands (USVI) to assess interest in a hypothetical chikungunya vaccine. Estimates were calibrated to age and sex of USVI population, and univariate and multivariable analyses were performed. Of 966 participants, 520 (adjusted 56%, 95% CI = 51-60%) were interested in receiving the vaccine. Of 446 participants not interested in vaccination, 203 (adjusted 47%, 95% CI = 41-52%) cited safety concerns as the reason. Educational efforts addressing vaccine safety concerns and risk factors for severe disease would likely improve vaccine acceptability and uptake among those most at risk.

COVID-19 Case Investigations Among Federally Quarantined Evacuees From Wuhan, China, and Exposed Personnel at a US Military Base, United States, February 5-21, 2020.

In February 2020, during the early days of the COVID-19 pandemic, 232 evacuees from Wuhan, China, were placed under federal 14-day quarantine upon arrival at a US military base in San Diego, California. We describe the monitoring of evacuees and responders for symptoms of COVID-19, case and contact investigations, infection control procedures, and lessons learned to inform future quarantine protocols for evacuated people from a hot spot resulting from a novel pathogen. Thirteen (5.6%) evacuees had COVID-19-compatible symptoms and 2 (0.9%) had laboratory-confirmed SARS-CoV-2. Two case investigations identified 43 contacts; 3 (7.0%) contacts had symptoms but tested negative for SARS-CoV-2 infection. Daily symptom and temperature screening of evacuees and enacted infection control procedures resulted in rapid case identification and isolation and no detected secondary transmission among evacuees or responders. Lessons learned highlight the challenges associated with public health response to a novel pathogen and the evolution of mitigation strategies as knowledge of the pathogen evolves.

West Nile Virus and Other Domestic Nationally Notifiable Arboviral Diseases - United States, 2020.

Arthropod-borne viruses (arboviruses) are transmitted to humans primarily through the bite of infected mosquitoes and ticks. West Nile virus (WNV), mainly transmitted by Culex species mosquitos, is the leading cause of domestically acquired arboviral disease in the United States (1). Other arboviruses cause sporadic cases of disease and occasional outbreaks. This report summarizes passive data for nationally notifiable domestic arboviruses in the United States reported to CDC for 2020. Forty-four states reported 884 cases of domestic arboviral disease, including those caused by West Nile (731), La Crosse (88), Powassan (21), St. Louis encephalitis (16), eastern equine encephalitis (13), Jamestown Canyon (13), and unspecified California serogroup (2) viruses. A total of 559 cases of neuroinvasive WNV disease were reported, for a national incidence of 0.17 cases per 100,000 population. Because arboviral diseases continue to cause serious illness and the locations of outbreaks vary annually, health care providers should consider arboviral infections in patients with aseptic meningitis or encephalitis that occur during periods when ticks and mosquitoes are active, perform recommended diagnostic testing, and promptly report cases to public health authorities to guide prevention strategies and messaging.

Household Transmission and Symptomology of Severe Acute Respiratory Syndrome Coronavirus 2 Alpha Variant among Children-California and Colorado, 2021.

OBJECTIVE: To assess the household secondary infection risk (SIR) of B.1.1.7 (Alpha) and non-Alpha lineages of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among children. STUDY DESIGN: During January to April 2021, we prospectively followed households with a SARS-CoV-2 infection. We collected questionnaires, serial nasopharyngeal swabs for reverse transcription polymerase chain reaction testing and whole genome sequencing, and serial blood samples for serology testing. We calculated SIRs by primary case age (pediatric vs adult), household contact age, and viral lineage. We evaluated risk factors associated with transmission and described symptom profiles among children. RESULTS: Among 36 households with pediatric primary cases, 21 (58%) had secondary infections. Among 91 households with adult primary cases, 51 (56%) had secondary infections. SIRs among pediatric and adult primary cases were 45% and 54%, respectively (OR, 0.79; 95% CI, 0.41-1.54). SIRs among pediatric primary cases with Alpha and non-Alpha lineage were 55% and 46%, respectively (OR, 1.52; 95% CI, 0.51-4.53). SIRs among pediatric and adult household contacts were 55% and 49%, respectively (OR, 1.01; 95% CI, 0.68-1.50). Among pediatric contacts, no significant differences in the odds of acquiring infection by demographic or household characteristics were observed. CONCLUSIONS: Household transmission of SARS-CoV-2 from children and adult primary cases to household members was frequent. The risk of secondary infection was similar among child and adult household contacts. Among children, household transmission of SARS-CoV-2 and the risk of secondary infection was not influenced by lineage. Continued mitigation strategies (eg, masking, physical distancing, vaccination) are needed to protect at-risk groups regardless of virus lineage circulating in communities.

Comparison of Home Antigen Testing With RT-PCR and Viral Culture During the Course of SARS-CoV-2 Infection.

Importance: As self-collected home antigen tests become widely available, a better understanding of their performance during the course of SARS-CoV-2 infection is needed. Objective: To evaluate the diagnostic performance of home antigen tests compared with reverse transcription-polymerase chain reaction (RT-PCR) and viral culture by days from illness onset, as well as user acceptability. Design, Setting, and Participants: This prospective cohort study was conducted from January to May 2021 in San Diego County, California, and metropolitan Denver, Colorado. The convenience sample included adults and children with RT-PCR-confirmed infection who used self-collected home antigen tests for 15 days and underwent at least 1 nasopharyngeal swab for RT-PCR, viral culture, and sequencing. Exposures: SARS-CoV-2 infection. Main Outcomes and Measures: The primary outcome was the daily sensitivity of home antigen tests to detect RT-PCR-confirmed cases. Secondary outcomes included the daily percentage of antigen test, RT-PCR, and viral culture results that were positive, and antigen test sensitivity compared with same-day RT-PCR and cultures. Antigen test use errors and acceptability were assessed for a subset of participants. Results: This study enrolled 225 persons with RT-PCR-confirmed infection (median [range] age, 29 [1-83] years; 117 female participants [52%]; 10 [4%] Asian, 6 [3%] Black or African American, 50 [22%] Hispanic or Latino, 3 [1%] Native Hawaiian or Other Pacific Islander, 145 [64%] White, and 11 [5%] multiracial individuals) who completed 3044 antigen tests and 642 nasopharyngeal swabs. Antigen test sensitivity was 50% (95% CI, 45%-55%) during the infectious period, 64% (95% CI, 56%-70%) compared with same-day RT-PCR, and 84% (95% CI, 75%-90%) compared with same-day cultures. Antigen test sensitivity peaked 4 days after illness onset at 77% (95% CI, 69%-83%). Antigen test sensitivity improved with a second antigen test 1 to 2 days later, particularly early in the infection. Six days after illness onset, antigen test result positivity was 61% (95% CI, 53%-68%). Almost all (216 [96%]) surveyed individuals reported that they would be more likely to get tested for SARS-CoV-2 infection if home antigen tests were available over the counter. Conclusions and Relevance: The results of this cohort study of home antigen tests suggest that sensitivity for SARS-CoV-2 was moderate compared with RT-PCR and high compared with viral culture. The results also suggest that symptomatic individuals with an initial negative home antigen test result for SARS-CoV-2 infection should test again 1 to 2 days later because test sensitivity peaked several days after illness onset and improved with repeated testing.

Duration of West Nile Virus Immunoglobulin M Antibodies up to 81 Months Following West Nile Virus Disease Onset.

West Nile virus (WNV) IgM antibodies typically indicate a recent infection. However, WNV IgM antibodies can remain detectable for months to years following illness onset. We found that 23% (11/47) of samples tested with a WNV ELISA and 43% (20/47) of samples tested with WNV microsphere immunoassay (MIA) at 16-19 months following WNV illness onset were positive for IgM antibodies. The proportion of samples testing positive for WNV IgM by ELISA decreased over time, but 5% (2/44) of individuals remained positive at 60-63 months after their acute illness and 4% (2/50) were WNV IgM equivocal at 72-81 months. Testing by MIA showed the same general trend of decreased proportion positive over time though the rates of positivity were higher at most time points compared with the ELISA, including 6% (3/50) of participant's samples identified as IgM positive by MIA at 72-81 months post their acute illness. With the MIA, there also was a high proportion of samples with nonspecific results at each time point; average of 23% across all time points. Clinicians and public health officials should consider these findings along with clinical and epidemiologic data when interpreting WNV IgM antibody test results.

Seroprevalence of Powassan Virus Infection in an Area Experiencing a Cluster of Disease Cases: Sussex County, New Jersey, 2019.

In 2019, a geographically focal cluster of 3 Powassan virus neuroinvasive disease cases occurred in New Jersey. We conducted a serosurvey of 273 adult area residents and estimated that immunoglobulin M seroprevalence was 0.31% (95% confidence interval [CI], .04%-1.00%) and 23% (95% CI, 7%-100%) of infections result in neuroinvasive disease.