Last data update: Jul 11, 2025. (Total: 49561 publications since 2009)
Records 1-30 (of 68 Records) |
Query Trace: Gould CV[original query] |
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West Nile Virus: A Review
Gould CV , Staples JE , Guagliardo SAJ , Martin SW , Lyons S , Hills SL , Nett RJ , Petersen LR . Jama 2025 ![]() IMPORTANCE: West Nile virus (WNV), a neurotropic flavivirus spread by Culex species mosquitoes, is the leading cause of mosquito-borne disease in the contiguous US. From 2014 to 2023, a mean of 1298 WNV neuroinvasive disease cases and 129 deaths were reported annually in the US. OBSERVATIONS: Almost all WNV infection occurs via mosquito bites, but transmission can rarely occur via blood transfusion, organ transplantation, and transplacental, perinatal, breastmilk, percutaneous, and conjunctival exposure. Since 2018, large WNV outbreaks have been reported in Europe, Tunisia, Israel, and the US. In 2021, the largest county-level US outbreak occurred in Arizona, with 1487 disease cases and 101 deaths reported. Based on seroprevalence surveys, approximately 80% of human WNV infections are asymptomatic, 20% cause a febrile illness (West Nile fever), and less than 1% cause neuroinvasive disease (eg, meningitis, encephalitis, acute flaccid myelitis). Mortality of patients with neuroinvasive disease is approximately 10% overall but is 20% in individuals 70 years or older and 30% to 40% in patients with hematologic malignancies, solid organ transplants, and those receiving B-cell-depleting monoclonal antibodies. Among patients hospitalized for WNV disease, 30% to 40% are discharged to long-term care facilities, and more than 50% have long-term sequelae such as fatigue, weakness, myalgia, memory loss, and depression. WNV transmission during solid organ transplantation was identified in 14 clusters in the US and Italy from 2002 to 2023. Since WNV screening of the US blood supply began in 2003, 14 cases of WNV transmission through blood transfusion have been reported. For patients with fever or neurologic symptoms during summer and fall months, WNV should be considered; IgM testing of serum and/or cerebrospinal fluid is recommended, followed by confirmatory neutralizing antibody testing in cases of possible exposure to cross-reacting flaviviruses, atypical presentation or death, or suspected unusual transmission modes such as organ transplantation. Reverse transcription-polymerase chain reaction testing is often more sensitive than IgM testing in patients with severe immunocompromise. There are no evidence-based therapies or human vaccines for WNV disease. Preventive methods include personal protective behaviors, such as using Environmental Protection Agency-registered mosquito repellents, wearing protective clothing, and limiting outdoor exposure from dusk to dawn, and community mosquito control measures. CONCLUSIONS AND RELEVANCE: WNV causes more than 1200 neuroinvasive disease cases and 120 deaths annually in the US. People who are older or immunocompromised are at higher risk of severe disease and death. Since there are no therapies or human vaccines, prevention relies on personal protective measures, WNV surveillance, and mosquito control interventions. |
Eastern Equine Encephalitis in the US
Staples JE , Gould CV . Jama 2025 ![]() This JAMA Insights examines the epidemiology, diagnosis, and management of eastern equine encephalitis virus disease in the US following a recent increase in reported cases. | eng |
Meningoencephalitis Caused by Tick-Borne Encephalitis Virus in a Returning Traveler, United States, 2023
Ogilvy AJ , Hills SL , Gould CV , Fitzpatrick KA , Erinstaples J , Lehman JA , Palmore TN , Lucar J . An Intern Med, Clin Cases 2025 4 (5) We describe a case of meningoencephalitis caused by tick-borne encephalitis (TBE) virus in a traveler returning to the United States presenting with fever, headaches, neck stiffness, encephalopathy, and aphasia. This case highlights the importance of obtaining a travel history and use of the TBE vaccine as appropriate for patients who are at risk for TBE. © 2025 Authors. Published in partnership by the American College of Physicians and American Heart Association. |
West Nile Virus and Other Nationally Notifiable Arboviral Diseases - United States, 2023
Padda H , Jacobs D , Gould CV , Sutter R , Lehman J , Staples JE , Lyons S . MMWR Morb Mortal Wkly Rep 2025 74 (21) 358-364 In the United States, arthropodborne viruses (arboviruses) are primarily transmitted by infected mosquitoes or ticks. Most infections are asymptomatic; symptomatic infections range from mild febrile illness to severe neuroinvasive disease. This report summarizes 2023 data for nationally notifiable domestic arboviral diseases. Forty-eight states and the District of Columbia reported 2,770 human arboviral disease cases, including 2,022 (73%) hospitalizations and 208 (8%) deaths. As in previous years, West Nile virus (WNV) was the most commonly reported domestic arboviral disease in 2023, accounting for 2,628 (95%) of all reported cases. A majority (91%) of case onsets occurred during July-September. Three WNV disease cases among patients infected though organ transplantation from two donors were reported in 2023. Powassan virus disease case reports were the second most common (n = 49), having increased from the previous record high in 2022, with onsets evenly distributed during April-December. La Crosse virus was the most common cause of arboviral disease among children, with most cases classified as neuroinvasive. Variations in annual arboviral disease incidence, distribution, and seasonal temporality highlight the importance of high-quality and timely surveillance. Clinicians should consider arboviral testing in patients with acute febrile or neurologic illness when mosquitoes and ticks are active and report positive test results to their health department. Reducing arboviral disease morbidity and mortality relies on population use of personal protective measures (e.g., insect repellent and protective clothing), implementing vector control efforts, and screening blood and organ donors for WNV. |
Estimation of Incubation Period for Oropouche Virus Disease among Travel-Associated Cases, 2024-2025
Guagliardo SAJ , Martin S , Gould CV , Sutter R , Jacobs D , O'Laughlin K , Huits R , Castilletti C , Staples JE . Emerg Infect Dis 2025 31 (7) Determining the incubation period of Oropouche virus disease can inform clinical and public health practice. We analyzed data from 97 travel-associated cases identified by the Centers for Disease Control and Prevention (n = 74) or the GeoSentinel Network (n = 13) and 10 cases from published literature. Using log-normal interval-censored survival analysis, we estimated the median incubation period to be 3.2 (95% CI 2.5-3.9) days. Symptoms developed by 1.1 (95% CI 0.6-1.5) days for 5% of patients, 9.7 (95% CI 6.9-12.5) days for 95% of patients, and 15.4 (95% CI 9.6-21.3) days for 99% of patients. The estimated incubation period range of 1-10 days can be used to assess timing and potential source of exposure in patients with Oropouche symptoms. For patients with symptom onset >2 weeks after travel, clinicians and public health responders should consider the possibility of local vectorborne transmission or alternative modes of transmission. |
Powassan and Eastern Equine Encephalitis Virus Seroprevalence in Endemic Areas, United States, 2019-2020
Padda H , Huang CY , Grimm K , Biggerstaff BJ , Ledermann JP , Raetz J , Boroughs K , Mossel EC , Martin SW , Lehman JA , Townsend RL , Krysztof D , Saá P , Dinh ETN , Stobierski MG , Esponda-Morrison B , Wolujewicz KAA , Osborne M , Brown CM , Hopkins B , Schiffman EK , Garvin A , Lee X , Osborn RA , Wozniak RJ , Brault AC , Basavaraju SV , Stramer SL , Staples JE , Gould CV . Emerg Infect Dis 2025 31 (5) 929-936 Powassan virus (POWV) and Eastern equine encephalitis virus (EEEV) are regionally endemic arboviruses in the United States that can cause neuroinvasive disease and death. Recent identification of EEEV transmission through organ transplantation and POWV transmission through blood transfusion have increased concerns about infection risk. After historically high numbers of cases of both viruses were reported in 2019, we conducted a seroprevalence survey using blood donation samples from selected endemic counties. Specimens were screened for virus-specific neutralizing antibodies, and population seroprevalence was estimated using weights calibrated to county population census data. For POWV, median county seroprevalence in 4 states was 0.84%, ranging from 0% (95% CI 0%-2.28%) to 11.5% (95% CI 0.82%-40.9%). EEEV infection was identified in a single county (estimated seroprevalence 1.62% [95% CI 0.04%-8.75%]). Although seroprevalence estimates in sampled areas were generally low, additional investigation of higher-prevalence areas could inform risk for transmission from asymptomatic blood and organ donors. |
Jamestown Canyon virus seroprevalence in endemic regions and implications for diagnostic testing
Sutter RA , Calvert AE , Grimm K , Biggerstaff BJ , Thrasher E , Mossel EC , Martin SW , Lehman J , Saa P , Townsend R , Krysztof D , Brown CM , Osborne M , Hopkins B , Osborn R , Lee X , Schiffman EK , Brault AC , Basavaraju SV , Stramer SL , Staples JE , Gould CV . Clin Infect Dis 2025 ![]() ![]() BACKGROUND: Jamestown Canyon virus, a mosquito-borne virus, can cause asymptomatic infection, febrile illness, or neuroinvasive disease in humans. Previous studies have found Jamestown Canyon virus-specific antibodies in a 4-54% of people in various U.S. regions. To understand baseline seroprevalence in regions with the highest number of reported disease cases, we performed a serosurvey among blood donors. METHODS: We randomly selected blood donation specimens collected during December 2019-April 2020 from residents of counties reporting ≥2 disease cases in 2019 or one case in 2019 and ≥1 case during 2010-2018. Specimens were screened for Jamestown Canyon virus-specific neutralizing antibodies and, if positive, tested for IgM antibodies. We estimated county population seroprevalence by calibrating sample weights to population census data. RESULTS: Fourteen counties in three states, Massachusetts, Minnesota, and Wisconsin, met the inclusion criteria. Within each state, average county seroprevalence ranged from 16.8% (95% CI: 9.3%-27.0%) to 18.8% (95% CI: 14.0%-24.4%) for Jamestown Canyon virus neutralizing antibodies and from 7.6% (95% CI: 4.2%-12.5%) to 13.5% (95% CI: 9.6%-18.3%) for both neutralizing and IgM antibodies. CONCLUSIONS: Estimated Jamestown Canyon virus seroprevalence, including for IgM antibodies, is elevated in endemic areas, complicating the interpretation of serologic testing in diagnosing acute disease in symptomatic individuals. Diagnosing Jamestown Canyon virus disease requires a high degree of clinical suspicion, ruling out other possible causes of illness, and if possible, collecting acute and convalescent samples. New assays to detect acute infection could improve diagnosis and public health surveillance for Jamestown Canyon virus disease. |
Reemergence of Oropouche virus in the Americas and risk for spread in the United States and its territories, 2024
Guagliardo SAJ , Connelly CR , Lyons S , Martin SW , Sutter R , Hughes HR , Brault AC , Lambert AJ , Gould CV , Staples JE . Emerg Infect Dis 2024 30 (11) 2241-2249 Oropouche virus has recently caused outbreaks in South America and the Caribbean, expanding into areas to which the virus was previously not endemic. This geographic range expansion, in conjunction with the identification of vertical transmission and reports of deaths, has raised concerns about the broader threat this virus represents to the Americas. We review information on Oropouche virus, factors influencing its spread, transmission risk in the United States, and current status of public health response tools. On the basis of available data, the risk for sustained local transmission in the continental United States is considered low because of differences in vector ecology and in human-vector interactions when compared with Oropouche virus-endemic areas. However, more information is needed about the drivers for the current outbreak to clarify the risk for further expansion of this virus. Timely detection and control of this emerging pathogen should be prioritized to mitigate disease burden and stop its spread. |
Oropouche virus disease among U.S. travelers - United States, 2024
Morrison A , White JL , Hughes HR , Guagliardo SAJ , Velez JO , Fitzpatrick KA , Davis EH , Stanek D , Kopp E , Dumoulin P , Locksmith T , Heberlein L , Zimler R , Lassen J , Bestard C , Rico E , Mejia-Echeverri A , Edwards-Taylor KA , Holt D , Halphen D , Peters K , Adams C , Nichols AM , Ciota AT , Dupuis AP 2nd , Backenson PB , Lehman JA , Lyons S , Padda H , Connelly RC , Tong VT , Martin SW , Lambert AJ , Brault AC , Blackmore C , Staples JE , Gould CV . MMWR Morb Mortal Wkly Rep 2024 73 (35) 769-773 Beginning in late 2023, Oropouche virus was identified as the cause of large outbreaks in Amazon regions with known endemic transmission and in new areas in South America and the Caribbean. The virus is spread to humans by infected biting midges and some mosquito species. Although infection typically causes a self-limited febrile illness, reports of two deaths in patients with Oropouche virus infection and vertical transmission associated with adverse pregnancy outcomes have raised concerns about the threat of this virus to human health. In addition to approximately 8,000 locally acquired cases in the Americas, travel-associated Oropouche virus disease cases have recently been identified in European travelers returning from Cuba and Brazil. As of August 16, 2024, a total of 21 Oropouche virus disease cases were identified among U.S. travelers returning from Cuba. Most patients initially experienced fever, myalgia, and headache, often with other symptoms including arthralgia, diarrhea, nausea or vomiting, and rash. At least three patients had recurrent symptoms after the initial illness, a common characteristic of Oropouche virus disease. Clinicians and public health jurisdictions should be aware of the occurrence of Oropouche virus disease in U.S. travelers and request testing for suspected cases. Travelers should prevent insect bites when traveling, and pregnant persons should consider deferring travel to areas experiencing outbreaks of Oropouche virus disease. |
West Nile Virus and other nationally notifiable arboviral diseases - United States, 2022
Sutter RA , Lyons S , Gould CV , Staples JE , Lindsey NP . MMWR Morb Mortal Wkly Rep 2024 73 (21) 484-488 |
Tick bite risk factors and prevention measures in an area with emerging Powassan virus disease
Wilson N , Vahey GM , McDonald E , Fitzpatrick K , Lehman J , Clark S , Lindell K , Pastula DM , Perez S , Rhodes H , Gould CV , Staples JE , Martin SW , Cervantes K . Public Health Chall 2023 2 (4) BACKGROUND: In the United States (U.S.), Powassan virus is primarily transmitted to humans by the black-legged tick (Ixodes scapularis). Rarely, infections can present as severe neuroinvasive disease. In 2019, four neuroinvasive disease cases were reported in Sussex County, New Jersey, U.S. We administered a survey to county residents to better understand tick bite risk factors and the performance of personal prevention measures. METHODS: A survey was administered in October 2019 to adult residents of randomly selected households. Questions focused on tick bite prevention and risk factors. Crude and adjusted odds ratios (ORs) and 95% confidence intervals were calculated for various outcomes. RESULTS: Of 274 participants, 25% were previously diagnosed with a tick-borne disease, and 42% reported finding an attached tick in 2019. Yardwork and gardening (OR = 7.38) and spending >50 hours outdoors per week (OR = 8.15) were associated with finding an attached tick. Finding an attached tick was inversely associated with the number of prevention measures used, indicating that a layered approach could reduce the risk of tick bites. Those who performed post-outdoor activity prevention measures (e.g., tick checks) were less likely to have a tick attached compared to finding a crawling tick. CONCLUSION: Compliance with prevention recommendations was low, despite a high prevalence of reported tick bites and significant outdoor exposures. Older adults and persons who spend significant time outdoors or engage in yardwork or gardening were at the highest risk of tick bites. Additional research is needed to further understand the barriers to tick bite prevention. |
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. |
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. |
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. |
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. |
Transfusion-Transmitted Cache Valley Virus Infection in a Kidney Transplant Recipient with Meningoencephalitis.
Al-Heeti O , Wu EL , Ison MG , Saluja RK , Ramsey G , Matkovic E , Ha K , Hall S , Banach B , Wilson MR , Miller S , Chiu CY , McCabe M , Bari C , Zimler RA , Babiker H , Freeman D , Popovitch J , Annambhotla P , Lehman JA , Fitzpatrick K , Velez JO , Davis EH , Hughes HR , Panella A , Brault A , Erin Staples J , Gould CV , Tanna S . Clin Infect Dis 2022 76 (3) e1320-e1327 ![]() ![]() 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 six 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 by reverse transcription-polymerase chain reaction (RT-PCR), plaque reduction neutralization test (PRNT), 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. CONCLUSION: 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 testing might facilitate detection of rare, unexpected infections, particularly in immunocompromised patients. |
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. |
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. |
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. |
Estimated US Infection- and Vaccine-Induced SARS-CoV-2 Seroprevalence Based on Blood Donations, July 2020-May 2021.
Jones JM , Stone M , Sulaeman H , Fink RV , Dave H , Levy ME , Di Germanio C , Green V , Notari E , Saa P , Biggerstaff BJ , Strauss D , Kessler D , Vassallo R , Reik R , Rossmann S , Destree M , Nguyen KA , Sayers M , Lough C , Bougie DW , Ritter M , Latoni G , Weales B , Sime S , Gorlin J , Brown NE , Gould CV , Berney K , Benoit TJ , Miller MJ , Freeman D , Kartik D , Fry AM , Azziz-Baumgartner E , Hall AJ , MacNeil A , Gundlapalli AV , Basavaraju SV , Gerber SI , Patton ME , Custer B , Williamson P , Simmons G , Thornburg NJ , Kleinman S , Stramer SL , Opsomer J , Busch MP . JAMA 2021 326 (14) 1400-1409 IMPORTANCE: People who have been infected with or vaccinated against SARS-CoV-2 have reduced risk of subsequent infection, but the proportion of people in the US with SARS-CoV-2 antibodies from infection or vaccination is uncertain. OBJECTIVE: To estimate trends in SARS-CoV-2 seroprevalence related to infection and vaccination in the US population. DESIGN, SETTING, AND PARTICIPANTS: In a repeated cross-sectional study conducted each month during July 2020 through May 2021, 17 blood collection organizations with blood donations from all 50 US states; Washington, DC; and Puerto Rico were organized into 66 study-specific regions, representing a catchment of 74% of the US population. For each study region, specimens from a median of approximately 2000 blood donors were selected and tested each month; a total of 1 594 363 specimens were initially selected and tested. The final date of blood donation collection was May 31, 2021. EXPOSURE: Calendar time. MAIN OUTCOMES AND MEASURES: Proportion of persons with detectable SARS-CoV-2 spike and nucleocapsid antibodies. Seroprevalence was weighted for demographic differences between the blood donor sample and general population. Infection-induced seroprevalence was defined as the prevalence of the population with both spike and nucleocapsid antibodies. Combined infection- and vaccination-induced seroprevalence was defined as the prevalence of the population with spike antibodies. The seroprevalence estimates were compared with cumulative COVID-19 case report incidence rates. RESULTS: Among 1 443 519 specimens included, 733 052 (50.8%) were from women, 174 842 (12.1%) were from persons aged 16 to 29 years, 292 258 (20.2%) were from persons aged 65 years and older, 36 654 (2.5%) were from non-Hispanic Black persons, and 88 773 (6.1%) were from Hispanic persons. The overall infection-induced SARS-CoV-2 seroprevalence estimate increased from 3.5% (95% CI, 3.2%-3.8%) in July 2020 to 20.2% (95% CI, 19.9%-20.6%) in May 2021; the combined infection- and vaccination-induced seroprevalence estimate in May 2021 was 83.3% (95% CI, 82.9%-83.7%). By May 2021, 2.1 SARS-CoV-2 infections (95% CI, 2.0-2.1) per reported COVID-19 case were estimated to have occurred. CONCLUSIONS AND RELEVANCE: Based on a sample of blood donations in the US from July 2020 through May 2021, vaccine- and infection-induced SARS-CoV-2 seroprevalence increased over time and varied by age, race and ethnicity, and geographic region. Despite weighting to adjust for demographic differences, these findings from a national sample of blood donors may not be representative of the entire US population. |
Deaths in Children and Adolescents Associated With COVID-19 and MIS-C in the United States.
McCormick DW , Richardson LC , Young PR , Viens LJ , Gould CV , Kimball A , Pindyck T , Rosenblum HG , Siegel DA , Vu QM , Komatsu K , Venkat H , Openshaw JJ , Kawasaki B , Siniscalchi AJ , Gumke M , Leapley A , Tobin-D'Angelo M , Kauerauf J , Reid H , White K , Ahmed FS , Richardson G , Hand J , Kirkey K , Larson L , Byers P , Garcia A , Ojo M , Zamcheck A , Lash MK , Lee EH , Reilly KH , Wilson E , de Fijter S , Naqvi OH , Harduar-Morano L , Burch AK , Lewis A , Kolsin J , Pont SJ , Barbeau B , Bixler D , Reagan-Steiner S , Koumans EH . Pediatrics 2021 148 (5) OBJECTIVES: To describe the demographics, clinical characteristics, and hospital course among persons <21 years of age with a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-associated death. METHODS: We conducted a retrospective case series of suspected SARS-CoV-2-associated deaths in the United States in persons <21 years of age during February 12 to July 31, 2020. All states and territories were invited to participate. We abstracted demographic and clinical data, including laboratory and treatment details, from medical records. RESULTS: We included 112 SARS-CoV-2-associated deaths from 25 participating jurisdictions. The median age was 17 years (IQR 8.5-19 years). Most decedents were male (71, 63%), 31 (28%) were Black (non-Hispanic) persons, and 52 (46%) were Hispanic persons. Ninety-six decedents (86%) had at least 1 underlying condition; obesity (42%), asthma (29%), and developmental disorders (22%) were most commonly documented. Among 69 hospitalized decedents, common complications included mechanical ventilation (75%) and acute respiratory failure (82%). The sixteen (14%) decedents who met multisystem inflammatory syndrome in children (MIS-C) criteria were similar in age, sex, and race and/or ethnicity to decedents without MIS-C; 11 of 16 (69%) had at least 1 underlying condition. CONCLUSIONS: SARS-CoV-2-associated deaths among persons <21 years of age occurred predominantly among Black (non-Hispanic) and Hispanic persons, male patients, and older adolescents. The most commonly reported underlying conditions were obesity, asthma, and developmental disorders. Decedents with coronavirus disease 2019 were more likely than those with MIS-C to have underlying medical conditions. |
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.*(,)(†). |
Fatal Human Infection with Evidence of Intrahost Variation of Eastern Equine Encephalitis Virus, Alabama, USA, 2019.
Hughes HR , Velez JO , Davis EH , Laven J , Gould CV , Panella AJ , Lambert AJ , Staples JE , Brault AC . Emerg Infect Dis 2021 27 (7) 1886-1892 ![]() ![]() Eastern equine encephalitis virus (EEEV) is an arbovirus in the family Togaviridae, genus Alphavirus, found in North America and associated with freshwater/hardwood swamps in the Atlantic, Gulf Coast, and Great Lakes regions. EEEV disease in humans is rare but causes substantial illness and death. To investigate the molecular epidemiology and microevolution of EEEV from a fatal case in Alabama, USA, in 2019, we used next-generation sequencing of serum and cerebrospinal fluid (CSF). Phylogenetic inference indicated that the infecting strain may be closely related to isolates from Florida detected during 2010-2014, suggesting potential seeding from Florida. EEEV detected in serum displayed a higher degree of variability with more single-nucleotide variants than that detected in the CSF. These data refine our knowledge of EEEV molecular epidemiologic dynamics in the Gulf Coast region and demonstrate potential quasispecies bottlenecking within the central nervous system of a human host. |
Cost effectiveness and impact of a targeted age- and incidence-based West Nile virus vaccine strategy
Curren EJ , Shankar MB , Fischer M , Meltzer MI , Staples JE , Gould CV . Clin Infect Dis 2021 73 (9) 1565-1570 BACKGROUND: West Nile virus (WNV) is the leading cause of arboviral disease in the United States and is associated with significant morbidity and mortality. A previous analysis found that a vaccination program targeting persons aged ≥60 years was more cost effective than universal vaccination, but costs remained high. METHODS: We used a mathematical Markov model to evaluate cost-effectiveness of an age- and incidence-based WNV vaccination program. We grouped states and large counties (≥100,000 persons aged ≥60 years) by median annual WNV incidence rates from 2004 to 2017 for persons aged ≥60 years. We defined WNV incidence thresholds, in increments of 0.5 cases per 100,000 persons ≥60 years. We calculated potential cost per WNV vaccine-prevented case and per quality adjusted life years (QALYs) saved. RESULTS: Vaccinating persons aged ≥60 years in states with an annual incidence of WNV neuroinvasive disease of ≥0.5 per 100,000 resulted in approximately half the cost per health outcome averted compared to vaccinating persons aged ≥60 years in all the contiguous United States. This approach could potentially prevent 37% of all neuroinvasive disease cases and 63% of WNV-related deaths nationally. Employing such a threshold at a county-level further improved cost-effectiveness ratios while preventing 19% and 30% of WNV-related neuroinvasive disease cases and deaths, respectively. CONCLUSIONS: An age- and incidence-based WNV vaccination program could be a more cost-effective strategy than an age-based program while still having a substantial impact on lowering WNV-related morbidity and mortality. |
Fatal Case of Chronic Jamestown Canyon Virus Encephalitis Diagnosed by Metagenomic Sequencing in Patient Receiving Rituximab.
Solomon IH , Ganesh VS , Yu G , Deng XD , Wilson MR , Miller S , Milligan TA , Mukerji SS , Mathewson A , Linxweiler J , Morse D , Ritter JM , Staples JE , Hughes H , Gould CV , Sabeti PC , Chiu CY , Piantadosi A . Emerg Infect Dis 2021 27 (1) 238-42 ![]() A 56-year-old man receiving rituximab who had months of neurologic symptoms was found to have Jamestown Canyon virus in cerebrospinal fluid by clinical metagenomic sequencing. The patient died, and postmortem examination revealed extensive neuropathologic abnormalities. Deep sequencing enabled detailed characterization of viral genomes from the cerebrospinal fluid, cerebellum, and cerebral cortex. |
Transmission of eastern equine encephalitis virus from an organ donor to 3 transplant recipients
Pouch SM , Katugaha SB , Shieh WJ , Annambhotla P , Walker WL , Basavaraju SV , Jones J , Huynh T , Reagan-Steiner S , Bhatnagar J , Grimm K , Stramer SL , Gabel J , Lyon GM , Mehta AK , Kandiah P , Neujahr DC , Javidfar J , Subramanian RM , Parekh SM , Shah P , Cooper L , Psotka MA , Radcliffe R , Williams C , Zaki SR , Staples JE , Fischer M , Panella AJ , Lanciotti RS , Laven JJ , Kosoy O , Rabe IB , Gould CV . Clin Infect Dis 2019 69 (3) 450-458 BACKGROUND: In fall 2017, 3 solid organ transplant (SOT) recipients from a common donor developed encephalitis within 1 week of transplantation, prompting suspicion of transplant-transmitted infection. Eastern equine encephalitis virus (EEEV) infection was identified during testing of endomyocardial tissue from the heart recipient. METHODS: We reviewed medical records of the organ donor and transplant recipients and tested serum, whole blood, cerebrospinal fluid, and tissue from the donor and recipients for evidence of EEEV infection by multiple assays. We investigated blood transfusion as a possible source of organ donor infection by testing remaining components and serum specimens from blood donors. We reviewed data from the pretransplant organ donor evaluation and local EEEV surveillance. RESULTS: We found laboratory evidence of recent EEEV infection in all organ recipients and the common donor. Serum collected from the organ donor upon hospital admission tested negative, but subsequent samples obtained prior to organ recovery were positive for EEEV RNA. There was no evidence of EEEV infection among donors of the 8 blood products transfused into the organ donor or in products derived from these donations. Veterinary and mosquito surveillance showed recent EEEV activity in counties nearby the organ donor's county of residence. Neuroinvasive EEEV infection directly contributed to the death of 1 organ recipient and likely contributed to death in another. CONCLUSIONS: Our investigation demonstrated EEEV transmission through SOT. Mosquito-borne transmission of EEEV to the organ donor was the likely source of infection. Clinicians should be aware of EEEV as a cause of transplant-associated encephalitis. |
Evaluation for arboviral infection among children hospitalized in Colorado with aseptic meningitis and encephalitis
Gould CV , Messacar K , Dominguez SR , Panella A , Tobolowsky F , Fischer M . Pediatr Infect Dis J 2020 39 (11) e382-e384 Among 39 children hospitalized in Colorado with aseptic meningitis or encephalitis, 16 (41%) had an etiology identified, including 2 (5%) with West Nile virus infection. Despite extensive testing, no other arboviral infections were identified. Arboviral infection should be considered in children with neuroinvasive disease during arboviral season with testing directed toward viruses endemic to the region and type of exposure. |
Powassan virus infection likely acquired through blood transfusion presenting as encephalitis in a kidney transplant recipient
Taylor L , Stevens T , Destrampe EM , Brown JA , McGavic J , Gould CV , Chambers TV , Kosoy OI , Burkhalter KL , Annambhotla P , Basavaraju SV , Groves J , Osborn RA , Weiss J , Stramer SL , Misch EA . Clin Infect Dis 2020 72 (6) 1051-1054 A kidney transplant patient without known tick exposure developed encephalitis three weeks after transplantation. During the transplant hospitalization, the patient had received a blood transfusion from an asymptomatic donor later discovered to have been infected with Powassan virus. This report describes a probable instance of transfusion-transmitted Powassan virus infection. |
Implementation of the targeted assessment for prevention strategy in a healthcare system to reduce Clostridioides difficile infection rates
White KA , Soe MM , Osborn A , Walling C , Fike LV , Gould CV , Kuhar DT , Edwards JR , Cochran RL . Infect Control Hosp Epidemiol 2020 41 (3) 1-7 BACKGROUND: Prevention of Clostridioides difficile infection (CDI) is a national priority and may be facilitated by deployment of the Targeted Assessment for Prevention (TAP) Strategy, a quality improvement framework providing a focused approach to infection prevention. This article describes the process and outcomes of TAP Strategy implementation for CDI prevention in a healthcare system. METHODS: Hospital A was identified based on CDI surveillance data indicating an excess burden of infections above the national goal; hospitals B and C participated as part of systemwide deployment. TAP facility assessments were administered to staff to identify infection control gaps and inform CDI prevention interventions. Retrospective analysis was performed using negative-binomial, interrupted time series (ITS) regression to assess overall effect of targeted CDI prevention efforts. Analysis included hospital-onset, laboratory-identified C. difficile event data for 18 months before and after implementation of the TAP facility assessments. RESULTS: The systemwide monthly CDI rate significantly decreased at the intervention (beta2, -44%; P = .017), and the postintervention CDI rate trend showed a sustained decrease (beta1 + beta3; -12% per month; P = .008). At an individual hospital level, the CDI rate trend significantly decreased in the postintervention period at hospital A only (beta1 + beta3, -26% per month; P = .003). CONCLUSIONS: This project demonstrates TAP Strategy implementation in a healthcare system, yielding significant decrease in the laboratory-identified C. difficile rate trend in the postintervention period at the system level and in hospital A. This project highlights the potential benefit of directing prevention efforts to facilities with the highest burden of excess infections to more efficiently reduce CDI rates. |
Reverse Transcription-Polymerase Chain Reaction Testing on Filter Paper-Dried Serum for Laboratory-Based Dengue Surveillance-American Samoa, 2018.
Curren EJ , Tufa AJ , Hancock WT , Biggerstaff BJ , Vaifanua-Leo JS , Montalbo CA , Sharp TM , Fischer M , Hills SL , Gould CV . Am J Trop Med Hyg 2020 102 (3) 622-624 ![]() Laboratory-based surveillance for arboviral diseases is challenging in resource-limited settings. We evaluated the use of filter paper-dried sera for detection of dengue virus (DENV) RNA during an outbreak in American Samoa. Matched liquid and filter paper-dried sera were collected from patients with suspected dengue and shipped to a reference laboratory for diagnostic testing. RNA was extracted from each sample and tested for DENV RNA by real-time reverse transcription-polymerase chain reaction (RT-PCR). Of 18 RT-PCR-positive liquid specimens, 14 matched filter paper-dried specimens were positive for a sensitivity of 78% (95% CI, 55-91%). Of 82 RT-PCR-negative liquid specimens, all filter paper-dried specimens were negative for a specificity of 100% (95% CI, 96-100%). Shipping of filter paper-dried specimens was similarly timely but less expensive than shipping liquid sera. Using filter paper-dried serum or blood can be a cost-effective and sustainable approach to surveillance of dengue and other arboviral diseases in resource-limited settings. |
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