Last data update: May 06, 2024. (Total: 46732 publications since 2009)
Records 1-30 (of 147 Records) |
Query Trace: Staples JE[original query] |
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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
Doshi RH , Mukadi PK , Casey RM , Kizito GM , Gao H , Nguete UB , Laven J , Sabi L , Kaba DK , Muyembe-Tamfum JJ , Hyde TB , Ahuka-Mundeke S , Staples JE . Lancet Infect Dis 2024 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 (PRNT(50)). Participants with a PRNT(50) 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. |
Yellow fever vaccine: recommendations of the Advisory Committee on Immunization Practices (ACIP)
Staples JE , Gershman M , Fischer M . MMWR Recomm Rep 2010 59 1-27 This report updates CDC's recommendations for using yellow fever (YF) vaccine (CDC. Yellow fever vaccine: recommendations of the Advisory Committee on Immunizations Practices: MMWR 2002;51[No. RR-17]). Since the previous YF vaccine recommendations were published in 2002, new or additional information has become available on the epidemiology of YF, safety profile of the vaccine, and health regulations related to the vaccine. This report summarizes the current epidemiology of YF, describes immunogenicity and safety data for the YF vaccine, and provides recommendations for the use of YF vaccine among travelers and laboratory workers. YF is a vectorborne disease resulting from the transmission of yellow fever virus (YFV) to a human from the bite of an infected mosquito. It is endemic to sub-Saharan Africa and tropical South America and is estimated to cause 200,000 cases of clinical disease and 30,000 deaths annually. Infection in humans is capable of producing hemorrhagic fever and is fatal in 20%-50% of persons with severe disease. Because no treatment exists for YF disease, prevention is critical to lower disease risk and mortality. A traveler's risk for acquiring YFV is determined by multiple factors, including immunization status, location of travel, season, duration of exposure, occupational and recreational activities while traveling, and local rate of virus transmission at the time of travel. All travelers to countries in which YF is endemic should be advised of the risks for contracting the disease and available methods to prevent it, including use of personal protective measures and receipt of vaccine. Administration of YF vaccine is recommended for persons aged >or=9 months who are traveling to or living in areas of South America and Africa in which a risk exists for YFV transmission. Because serious adverse events can occur following YF vaccine administration, health-care providers should vaccinate only persons who are at risk for exposure to YFV or who require proof of vaccination for country entry. To minimize the risk for serious adverse events, health-care providers should observe the contraindications, consider the precautions to vaccination before administering vaccine, and issue a medical waiver if indicated. |
Japanese encephalitis vaccines: recommendations of the Advisory Committee on Immunization Practices (ACIP)
Fischer M , Lindsey N , Staples JE , Hills S . MMWR Recomm Rep 2010 59 1-27 This report updates the 1993 recommendations by CDC's Advisory Committee on Immunization Practices (ACIP) regarding the prevention of Japanese encephalitis (JE) among travelers (CDC. Inactivated Japanese encephalitis virus vaccine: recommendations of the Advisory Committee on Immunization Practices [ACIP]. MMWR 1993;42[No. RR-1]). This report summarizes the epidemiology of JE, describes the two JE vaccines that are licensed in the United States, and provides recommendations for their use among travelers and laboratory workers. JE virus (JEV), a mosquito-borne flavivirus, is the most common vaccine-preventable cause of encephalitis in Asia. JE occurs throughout most of Asia and parts of the western Pacific. Among an estimated 35,000-50,000 annual cases, 20%-30% of patients die, and 30%-50% of survivors have neurologic or psychiatric sequelae. No treatment exists. For most travelers to Asia, the risk for JE is very low but varies on the basis of destination, duration, season, and activities. JE vaccine is recommended for travelers who plan to spend a month or longer in endemic areas during the JEV transmission season and for laboratory workers with a potential for exposure to infectious JEV. JE vaccine should be considered for 1) short-term (<1 month) travelers to endemic areas during the JEV transmission season if they plan to travel outside of an urban area and will have an increased risk for JEV exposure; 2) travelers to an area with an ongoing JE outbreak; and 3) travelers to endemic areas who are uncertain of specific destinations, activities, or duration of travel. JE vaccine is not recommended for short-term travelers whose visit will be restricted to urban areas or times outside of a well-defined JEV transmission season. Two JE vaccines are licensed in the United States. An inactivated mouse brain--derived JE vaccine (JE-VAX [JE-MB]) has been licensed since 1992 to prevent JE in persons aged >or=1 year traveling to JE-endemic countries. Supplies of this vaccine are limited because production has ceased. In March 2009, an inactivated Vero cell culture-derived vaccine (IXIARO [JE-VC]) was licensed for use in persons aged >or=17 years. JE-MB is the only JE vaccine available for use in children aged 1-16 years, and remaining supplies will be reserved for use in this group. |
Use of Japanese encephalitis vaccine in children: recommendations of the advisory committee on immunization practices, 2013
Centers for Disease Control and Prevention , Bocchini JA , Rubin L , Fischer M , Hills SL , Staples JE . MMWR Morb Mortal Wkly Rep 2013 62 (45) 898-900 On June 19, 2013, the Advisory Committee on Immunization Practices (ACIP) voted to extend existing recommendations for use of inactivated Vero cell culture-derived Japanese encephalitis (JE) vaccine (JE-VC) (Ixiaro, Intercell Biomedical) to include children aged 2 months through 16 years. The ACIP JE Vaccine Workgroup reviewed the epidemiology of JE in travelers and evaluated published and unpublished data on JE-VC immunogenicity and safety in adults and children. The evidence for benefits and risks associated with JE-VC vaccination of children was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework. This report summarizes the evidence considered by ACIP and outlines the recommendations for use of JE-VC in children traveling to JE-endemic countries. |
Fractional dosing of yellow fever live attenuated 17D vaccine: A perspective
Hansen CA , Staples JE , Barrett ADT . Infect Drug Resist 2023 16 7141-7154 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. |
Multi-model prediction of West Nile virus neuroinvasive disease with machine learning for identification of important regional climatic drivers
Holcomb KM , Staples JE , Nett RJ , Beard CB , Petersen LR , Benjamin SG , Green BW , Jones H , Johansson MA . Geohealth 2023 7 (11) e2023GH000906 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. |
Tick-borne encephalitis vaccine: Recommendations of the Advisory Committee on Immunization Practices, United States, 2023
Hills SL , Poehling KA , Chen WH , Staples JE . MMWR Recomm Rep 2023 72 (5) 1-29 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. |
West Nile virus and other nationally notifiable arboviral diseases - United States, 2021
Fagre AC , Lyons S , Staples JE , Lindsey N . MMWR Morb Mortal Wkly Rep 2023 72 (34) 901-906 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
Gould CV , Free RJ , Bhatnagar J , Soto RA , Royer TL , Maley WR , Moss S , Berk MA , Craig-Shapiro R , Kodiyanplakkal RPL , Westblade LF , Muthukumar T , Puius YA , Raina A , Hadi A , Gyure KA , Trief D , Pereira M , Kuehnert MJ , Ballen V , Kessler DA , Dailey K , Omura C , Doan T , Miller S , Wilson MR , Lehman JA , Ritter JM , Lee E , Silva-Flannery L , Reagan-Steiner S , Velez JO , Laven JJ , Fitzpatrick KA , Panella A , Davis EH , Hughes HR , Brault AC , St George K , Dean AB , Ackelsberg J , Basavaraju SV , Chiu CY , Staples JE . Lancet Microbe 2023 4 (9) e711-e721 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. |
Arboviral vaccines for use in pregnant travelers
Hills SL , Wong JM , Staples JE . Travel Med Infect Dis 2023 55 102624 Pregnant women traveling abroad can be exposed to a variety of arboviruses, primarily spread by mosquitoes or ticks. Some arboviral infections can be of particular concern for pregnant women or their fetuses. Vaccination is one preventive measure that can reduce the risk for infection. Several arboviral vaccines have been licensed for many years and can be used to prevent infection in travelers, namely Japanese encephalitis, yellow fever, and tick-borne encephalitis vaccines. Recommendations on use of these vaccines in pregnancy vary. Other arboviral vaccines have been licensed but are not indicated for use in pregnant travelers (e.g., dengue vaccines) or are in development (e.g., chikungunya, Zika vaccines). This review describes arboviral vaccines for travelers, focusing on women who are pregnant and those planning travel during pregnancy. |
Combating West Nile virus disease - time to revisit vaccination
Gould CV , Staples JE , Huang CY , Brault AC , Nett RJ . N Engl J Med 2023 388 (18) 1633-1636 It is time to revisit the need for human West Nile virus (WNV) vaccines. Since its initial detection in the United States in 1999, WNV has become the leading cause of domestic arthropod-borne viral (arboviral) disease. Spread by infected culex-species mosquitoes, WNV has caused more than 55,000 reported cases of human disease, more than 27,000 of them neuroinvasive, and 2600 deaths between 1999 and 2021, according to data from the Centers for Disease Control and Prevention (CDC). WNV is also an ongoing public health threat in many areas of the world; the largest recorded outbreak in Europe occurred in 2018. |
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
Vizzotti C , Harris JB , Aquino A , Rancaño C , Biscayart C , Bonaventura R , Pontoriero A , Baumeister E , Freire MC , Magariños M , Duarte B , Grant G , Reef S , Laven J , Wannemuehler KA , Alvarez AMR , Staples JE . BMC Infect Dis 2023 23 (1) 165 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 (MMR(1)YF(1)), MMR followed by YF vaccine four weeks later (MMR(1)YF(2)), or YF followed by MMR vaccine four weeks later (YF(1)MMR(2)). 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 MMR(1)YF(1) group versus 96.3% in the MMR(1)YF(2) group, a difference of 1.6% [90% CI -1.5, 4.7]; rubella: 97.9% MMR(1)YF(1) versus 94.7% MMR(1)YF(2), a difference of 3.3% [-0.1, 6.7]; mumps: 96.7% MMR(1)YF(1) versus 97.9% MMR(1)YF(2), a difference of -1.3% [-4.1, 1.5]; and YF: 96.3% MMR(1)YF(1) versus 97.5% YF(1)MMR(2), 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
Soto RA , Baldry E , Vahey GM , Lehman J , Silver M , Panella A , Brault AC , Hughes HR , Fitzpatrick KA , Velez J , Biggerstaff BJ , Wolff B , Randolph J , Ruth LJ , Staples JE , Gould CV . Emerg Infect Dis 2023 29 (3) 561-568 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.
Holcomb KM , Mathis S , Staples JE , Fischer M , Barker CM , Beard CB , Nett RJ , Keyel AC , Marcantonio M , Childs ML , Gorris ME , Rochlin I , Hamins-Puértolas M , Ray EL , Uelmen JA , DeFelice N , Freedman AS , Hollingsworth BD , Das P , Osthus D , Humphreys JM , Nova N , Mordecai EA , Cohnstaedt LW , Kirk D , Kramer LD , Harris MJ , Kain MP , Reed EMX , Johansson MA . Parasit Vectors 2023 16 (1) 11 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). |
Acceptability of a Chikungunya virus vaccine, United States Virgin Islands
Curren EJ , Ellis EM , Hennessey MJ , Delorey MJ , Fischer M , Staples JE . Am J Trop Med Hyg 2022 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. |
Severe arboviral neuroinvasive disease in patients on rituximab therapy: A review
Kapadia RK , Staples JE , Gill CM , Fischer M , Khan E , Laven JJ , Panella A , Velez JO , Hughes HR , Brault A , Pastula DM , Gould CV . Clin Infect Dis 2022 76 (6) 1142-1148 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-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. |
West Nile Virus and other domestic nationally notifiable arboviral diseases - United States, 2020
Soto RA , Hughes ML , Staples JE , Lindsey NP . MMWR Morb Mortal Wkly Rep 2022 71 (18) 628-632 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. |
Comparison of Home Antigen Testing With RT-PCR and Viral Culture During the Course of SARS-CoV-2 Infection.
Chu VT , Schwartz NG , Donnelly MAP , Chuey MR , Soto R , Yousaf AR , Schmitt-Matzen EN , Sleweon S , Ruffin J , Thornburg N , Harcourt JL , Tamin A , Kim G , Folster JM , Hughes LJ , Tong S , Stringer G , Albanese BA , Totten SE , Hudziec MM , Matzinger SR , Dietrich EA , Sheldon SW , Stous S , McDonald EC , Austin B , Beatty ME , Staples JE , Killerby ME , Hsu CH , Tate JE , Kirking HL , Matanock A . JAMA Intern Med 2022 182 (7) 701-709 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. |
Household Transmission and Symptomology of SARS-CoV-2 Alpha Variant Among Children-California and Colorado, 2021.
Waltenburg MA , Whaley MJ , Chancey RJ , Donnelly MAP , Chuey MR , Soto R , Schwartz NG , Chu VT , Sleweon S , McCormick DW , Uehara A , Retchless AC , Tong S , Folster JM , Petway M , Thornburg NJ , Drobeniuc J , Austin B , Hudziec MM , Stringer G , Albanese BA , Totten SE , Matzinger SR , Staples JE , Killerby ME , Hughes LJ , Matanock A , Beatty M , Tate JE , Kirking HL , Hsu CH . J Pediatr 2022 247 29-37 e7 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-April 2021, we prospectively followed households with a SARS-CoV-2 infection. We collected questionnaires, serial nasopharyngeal swabs for RT-PCR 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 [CI 0.51-4.53]). SIRs among pediatric and adult household contacts were 55% and 49%, respectively (OR: 1.01 [CI 0.68-1.50]). Among pediatric contacts, no significant differences in 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. Risk of secondary infection was similar among child and adult household contacts. Among children, household transmission of SARS-CoV-2 and risk of secondary infection was not influenced by lineage. Continued mitigation strategies (e.g., masking, physical distancing, vaccination) are needed to protect at-risk groups regardless of virus lineage circulating in communities. |
Duration of West Nile Virus immunoglobulin m antibodies up to 81 months following West Nile Virus disease onset
Staples JE , Gibney KB , Panella AJ , Prince HE , Basile AJ , Laven J , Sejvar JJ , Fischer M . Am J Trop Med Hyg 2022 106 (6) 1721-4 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
Vahey GM , Wilson N , McDonald E , Fitzpatrick K , Lehman J , Clark S , Lindell K , Pastula DM , Perez S , Rhodes H , Gould CV , Staples JE , Cervantes K , Martin SW . Open Forum Infect Dis 2022 9 (3) ofac023 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. |
Household transmission of SARS-CoV-2 Alpha variant - United States, 2021.
Donnelly MAP , Chuey MR , Soto R , Schwartz NG , Chu VT , Konkle SL , Sleweon S , Ruffin J , Haberling DL , Guagliardo SAJ , Stoddard RA , Anderson RD , Morgan CN , Rossetti R , McCormick DW , Magleby R , Sheldon SW , Dietrich EA , Uehara A , Retchless AC , Tong S , Folster JM , Drobeniuc J , Petway ME , Austin B , Stous S , McDonald E , Jain S , Hudziec MM , Stringer G , Albanese BA , Totten SE , Staples JE , Killerby ME , Hughes L , Matanock A , Beatty M , Tate JE , Kirking HL , Hsu CH . Clin Infect Dis 2022 75 (1) e122-e132 BACKGROUND: In Spring 2021, SARS-CoV-2 B.1.1.7 (Alpha) became the predominant variant in the U.S. Research suggests that Alpha has increased transmissibility compared to non-Alpha lineages. We estimated household secondary infection risk (SIR), assessed characteristics associated with transmission, and compared symptoms of persons with Alpha and non-Alpha infections. METHODS: We followed households with SARS-CoV-2 infection for two weeks in San Diego County and metropolitan Denver, January to April 2021. We collected epidemiologic information and biospecimens for serology, RT-PCR, and whole genome sequencing. We stratified SIR and symptoms by lineage, and identified characteristics associated with transmission using Generalized Estimating Equations. RESULTS: We investigated 127 households with 322 household contacts; 72 households (56.7%) had member(s) with secondary infections. SIRs were not significantly higher for Alpha (61.0% [95% confidence interval (CI) 52.4-69.0%]) than non-Alpha (55.6% [CI 44.7-65.9%], P = 0.49). In households with Alpha, persons who identified as Asian or Hispanic/Latino had significantly higher SIRs than those who identified as White (P = 0.01 and 0.03, respectively). Close contact (e.g., kissing, hugging) with primary cases was associated with increased transmission for all lineages. Persons with Alpha infection were more likely to report constitutional symptoms than persons with non-Alpha (86.9% vs. 76.8%, P = 0.05). CONCLUSIONS: Household SIRs were similar for Alpha and non-Alpha. Comparable SIRs may be due to saturation of transmission risk in households owing to extensive close contact, or true lack of difference in transmission rates. Avoiding close contact within households may reduce SARS-CoV-2 transmission for all lineages among household members. |
West Nile virus transmission by solid organ transplantation and considerations for organ donor screening practices, United States
Soto RA , McDonald E , Annambhotla P , Velez JO , Laven J , Panella AJ , Machesky KD , White JL , Hyun J , Freuck E , Habel J , Oh D , Levi M , Hasz R , Eidbo E , Staples JE , Basavaraju SV , Gould CV . Emerg Infect Dis 2022 28 (2) 403-406 West Nile virus (WNV) is the most common domestic arbovirus in the United States. During 2018, WNV was transmitted through solid organ transplantation to 2 recipients who had neuroinvasive disease develop. Because of increased illness and death in transplant recipients, organ procurement organizations should consider screening during region-specific WNV transmission months. |
Genomic Evaluation of the Genus Coltivirus Indicates Genetic Diversity among Colorado Tick Fever Virus Strains and Demarcation of a New Species.
Hughes HR , Velez JO , Fitzpatrick K , Davis EH , Russell BJ , Lambert AJ , Staples JE , Brault AC . Diseases 2021 9 (4) The type species of the genus Coltivirus, Colorado tick fever virus (CTFV), was discovered in 1943 and is the most common tick-borne viral infection in the Western US. Despite its long history, very little is known about the molecular diversity of viruses classified within the species Colorado tick fever coltivirus. Previous studies have suggested genetic variants and potential serotypes of CTFV, but limited genetic sequence information is available for CTFV strains. To address this knowledge gap, we report herein the full-length genomes of five strains of CTFV, including Salmon River virus and California hare coltivirus (CTFV-Ca). The sequence from the full-length genome of Salmon River virus identified a high genetic identity to the CTFV prototype strain with >90% amino acid identity in all the segments except segment four, suggesting Salmon River virus is a strain of the species Colorado tick fever coltivirus. Additionally, analysis suggests that segment four has been associated with reassortment in at least one strain. The CTFV-Ca full-length genomic sequence was highly variable from the prototype CTFV in all the segments. The genome of CTFV-Ca was most similar to the Eyach virus, including similar segments six and seven. These data suggest that CTFV-Ca is not a strain of CTFV but a unique species. Additional sequence information of CTFV strains will improve the molecular surveillance tools and provide additional taxonomic resolution to this understudied virus. |
Tick-borne encephalitis among US travellers, 2010-20
Hills SL , Broussard KR , Broyhill JC , Shastry LG , Cossaboom CM , White JL , Machesky KD , Kosoy O , Girone K , Klena JD , Backenson BP , Gould CV , Lind L , Hieronimus A , Gaines DN , Wong SJ , Choi MJ , Laven JJ , Staples JE , Fischer M . J Travel Med 2021 29 (2) BACKGROUND: Tick-borne encephalitis (TBE) is an arboviral disease that is focally endemic in parts of Europe and Asia. TBE cases among US travellers are rare, with previous reports of only six cases among civilian travellers through 2009 and nine military-related cases through 2020. A TBE vaccine was licenced in the USA in August 2021. Understanding TBE epidemiology and risks among US travellers can help with the counselling of travellers going to TBE-endemic areas. METHODS: Diagnostic testing for TBE in the USA is typically performed at the Centers for Disease Control and Prevention (CDC) because no commercial testing is available. Diagnostic testing for TBE at CDC since 2010 was reviewed. For individuals with evidence of TBE virus infection, information was gathered on demographics, clinical presentations and risk factors for infection. RESULTS: From 2010-20, six patients with TBE were identified. Cases occurred among both paediatric and adult travellers and all were male. Patients were diagnosed with meningitis (n = 2) or encephalitis (n = 4); none died. Cases had travelled to various countries in Europe or Russia. Three cases reported visiting friends or relatives. Activities reported included hiking, camping, trail running, or working outdoors, and two cases had a recognized tick bite. CONCLUSIONS: TBE cases among US travellers are uncommon, with these six cases being the only known TBE cases among civilian travellers during this 11-year period. Nonetheless, given potential disease severity, pre-travel counselling for travellers to TBE-endemic areas should include information on measures to reduce the risk for TBE and other tick-borne diseases, including possible TBE vaccine use if a traveller's itinerary puts them at higher risk for infection. Clinicians should consider the diagnosis of TBE in a patient with a neurologic or febrile illness recently returned from a TBE-endemic country, particularly if a tick bite or possible tick exposure is reported. |
Risk factors for hospitalization among persons with COVID-19-Colorado.
Vahey GM , McDonald E , Marshall K , Martin SW , Chun H , Herlihy R , Tate JE , Kawasaki B , Midgley CM , Alden N , Killerby ME , Staples JE . PLoS One 2021 16 (9) e0256917 BACKGROUND: Most current evidence on risk factors for hospitalization because of coronavirus disease 2019 (COVID-19) comes from studies using data abstracted primarily from electronic health records, limited to specific populations, or that fail to capture over-the-counter medications and adjust for potential confounding factors. Properly understanding risk factors for hospitalization will help improve clinical management and facilitate targeted prevention messaging and forecasting and prioritization of clinical and public health resource needs. OBJECTIVES: To identify risk factors for hospitalization using patient questionnaires and chart abstraction. METHODS: We randomly selected 600 of 1,738 laboratory-confirmed Colorado COVID-19 cases with known hospitalization status and illness onset during March 9-31, 2020. In April 2020, we collected demographics, social history, and medications taken in the 30 days before illness onset via telephone questionnaire and collected underlying medical conditions in patient questionnaires and medical record abstraction. RESULTS: Overall, 364 patients participated; 128 were hospitalized and 236 were non-hospitalized. In multivariable analysis, chronic hypoxemic respiratory failure with oxygen requirement (adjusted odds ratio [aOR] 14.64; 95% confidence interval [CI] 1.45-147.93), taking opioids (aOR 8.05; CI 1.16-55.77), metabolic syndrome (aOR 5.71; CI 1.18-27.54), obesity (aOR 3.35; CI 1.58-7.09), age ≥65 years (aOR 3.22; CI 1.20-7.97), hypertension (aOR 3.14; CI 1.47-6.71), arrhythmia (aOR 2.95; CI 1.00-8.68), and male sex (aOR 2.65; CI 1.44-4.88), were significantly associated with hospitalization. CONCLUSION: We identified patient characteristics, medications, and medical conditions, including some novel ones, associated with hospitalization. These data can be used to inform clinical and public health resource needs. |
West Nile virus and other domestic nationally notifiable arboviral diseases - United States, 2019
Vahey GM , Mathis S , Martin SW , Gould CV , Staples JE , Lindsey NP . MMWR Morb Mortal Wkly Rep 2021 70 (32) 1069-1074 Arthropod-borne viruses (arboviruses) are transmitted to humans primarily through the bites of infected mosquitoes and ticks. West Nile virus (WNV) is the leading cause of domestically acquired arboviral disease in the United States (1). Other arboviruses, including La Crosse, Jamestown Canyon, Powassan, eastern equine encephalitis, and St. Louis encephalitis viruses, cause sporadic disease and occasional outbreaks. This report summarizes surveillance data for nationally notifiable domestic arboviruses reported to CDC for 2019. For 2019, 47 states and the District of Columbia (DC) reported 1,173 cases of domestic arboviral disease, including 971 (83%) WNV disease cases. Among the WNV disease cases, 633 (65%) were classified as neuroinvasive disease, for a national incidence of 0.19 cases per 100,000 population, 53% lower than the median annual incidence during 2009-2018. More Powassan and eastern equine encephalitis virus disease cases were reported in 2019 than in any previous year. Health care providers should consider arboviral infections in patients with aseptic meningitis or encephalitis, perform recommended diagnostic testing, and promptly report cases to public health authorities. Because arboviral diseases continue to cause serious illness, and annual incidence of individual viruses continues to vary with sporadic outbreaks, maintaining surveillance is important in directing prevention activities. 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.*(,)(†). |
Clinical phenotype in infants with negative Zika virus immunoglobulin M testing born to mothers with confirmed Zika virus infection during pregnancy
Godfred-Cato S , Newton S , Adams L , Valencia-Prado M , Lake-Burger H , Morrison A , Jones AM , Olson SM , Roth NM , Tong VT , Gilboa SM , Meaney Delman D , Honein MA , Staples JE , Moore CA . Birth Defects Res 2021 113 (17) 1267-1274 BACKGROUND: Recommended testing for both infants with Zika-associated birth defects (i.e., microcephaly and selected brain or eye anomalies) and infants without birth defects whose mothers had laboratory evidence of possible Zika virus (ZIKV) infection during pregnancy includes nucleic acid amplification testing (NAAT) and immunoglobulin M (IgM) testing within days after birth. Brain and eye defects highly specific for congenital ZIKV infection have been described; sporadic reports have documented negative ZIKV testing in such infants. METHODS: Infants from the U.S. Zika Pregnancy and Infant Registry and Zika Birth Defects Surveillance with Zika-associated birth defects and maternal and infant laboratory testing for ZIKV and two congenital infections (i.e., cytomegalovirus [CMV] and toxoplasmosis) were reviewed for phenotype and laboratory results. Infants with at least one defect considered highly specific for congenital ZIKV infection were designated as having congenital Zika syndrome (CZS) clinical phenotype for this study. RESULTS: Of 325 liveborn infants with Zika-associated birth defects and laboratory evidence of maternal ZIKV infection, 33 (10%) had CZS clinical phenotype; 171 (53%) had ZIKV IgM testing with negative or no ZIKV NAAT. ZIKV IgM was negative in the remaining 120 infants, and for 90%, testing for CMV and toxoplasmosis was missing/incomplete. Among 11 infants testing negative for ZIKV IgM, CMV, and toxoplasmosis, 2 infants had CZS clinical phenotype. CONCLUSIONS: These data add support to previous reports of negative ZIKV IgM testing in infants with clear maternal and phenotypic evidence of congenital ZIKV infection. Follow-up care consistent with the diagnosis is recommended regardless of infant ZIKV test results. |
Frequency of Zika Virus Immunoglobulin M Antibody in Persons with West Nile Virus Infection
Hills SL , Laven J , Biggerstaff BJ , Kosoy O , Staples JE , Panella A . Vector Borne Zoonotic Dis 2021 21 (10) 817-821 West Nile virus (WNV) and Zika virus (ZIKV) are mosquito-borne viruses in the family Flaviviridae. Residents in, and travelers to, areas where the viruses are circulating are at risk for infection, and both viruses can cause an acute febrile illness. Given known cross-reactivity in flavivirus serologic assays, it is possible a patient with acute WNV infection could be misdiagnosed as having ZIKV infection if appropriate testing is not conducted. To understand how frequently persons with WNV infection have detectable cross-reactive ZIKV immunoglobulin M (IgM) antibody, we used archived serum samples from patients in the United States with recent WNV infection confirmed by a microsphere-based immunoassay test for IgM antibody and neutralizing antibody testing. Samples were tested for ZIKV IgM antibody with the Centers for Disease Control and Prevention (CDC) ZIKV IgM antibody capture enzyme-linked immunosorbent assay. Among 153 sera from patients with acute WNV infection, the ZIKV IgM antibody result was positive in 56 (37%; 95% confidence interval [CI] 29-44%) and equivocal in 28 (18%; 95% CI 13-25%). With 55% of samples having cross-reactive antibodies, it is important for health care providers to request appropriate testing based on the most likely cause of a patient's possible arboviral infection considering their clinical symptoms and signs, travel history, and place of residence. For cases where the epidemiology does not support the preliminary IgM findings, confirmatory neutralizing antibody testing should be performed. These measures will avoid an incorrect diagnosis of ZIKV infection, based on cross-reactive antibodies, in a person truly infected with WNV. |
La Crosse Virus Disease in the United States, 2003-2019
Vahey GM , Lindsey NP , Staples JE , Hills SL . Am J Trop Med Hyg 2021 105 (3) 807-812 La Crosse virus (LACV) is an arthropod-borne virus that can cause a nonspecific febrile illness, meningitis, or encephalitis. We reviewed U.S. LACV surveillance data for 2003-2019, including human disease cases and nonhuman infections. Overall, 318 counties in 27 states, principally in the Great Lakes, mid-Atlantic, and southeastern regions, reported LACV activity. A total of 1,281 human LACV disease cases were reported, including 1,183 (92%) neuroinvasive disease cases. The median age of cases was 8 years (range: 1 month-95 years); 1,130 (88%) were aged < 18 years, and 754 (59%) were male. The most common clinical syndromes were encephalitis (N = 960; 75%) and meningitis (N = 219, 17%). The case fatality rate was 1% (N = 15). A median of 74 cases (range: 35-130) was reported per year. The average annual national incidence of neuroinvasive disease cases was 0.02 per 100,000 persons. West Virginia, North Carolina, Tennessee, and Ohio had the highest average annual state incidences (0.16-0.61 per 100,000), accounting for 80% (N = 1,030) of cases. No animal LACV infections were reported. Nine states reported LACV-positive mosquito pools, including three states with no reported human disease cases. La Crosse virus is the most common cause of pediatric neuroinvasive arboviral disease in the United States. However, surveillance data likely underestimate LACV disease incidence. Healthcare providers should consider LACV disease in patients, especially children, with febrile illness, meningitis, or encephalitis in areas where the virus circulates and advise their patients on ways to prevent mosquito bites. |
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