Last data update: Dec 02, 2024. (Total: 48272 publications since 2009)
Records 1-30 (of 31 Records) |
Query Trace: Rabe I[original query] |
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Wastewater surveillance for influenza A virus and H5 subtype concurrent with the highly pathogenic avian influenza A(H5N1) virus outbreak in cattle and poultry and associated human cases - United States, May 12-July 13, 2024
Louis S , Mark-Carew M , Biggerstaff M , Yoder J , Boehm AB , Wolfe MK , Flood M , Peters S , Stobierski MG , Coyle J , Leslie MT , Sinner M , Nims D , Salinas V , Lustri L , Bojes H , Shetty V , Burnor E , Rabe A , Ellison-Giles G , Yu AT , Bell A , Meyer S , Lynfield R , Sutton M , Scholz R , Falender R , Matzinger S , Wheeler A , Ahmed FS , Anderson J , Harris K , Walkins A , Bohra S , O'Dell V , Guidry VT , Christensen A , Moore Z , Wilson E , Clayton JL , Parsons H , Kniss K , Budd A , Mercante JW , Reese HE , Welton M , Bias M , Webb J , Cornforth D , Santibañez S , Soelaeman RH , Kaur M , Kirby AE , Barnes JR , Fehrenbach N , Olsen SJ , Honein MA . MMWR Morb Mortal Wkly Rep 2024 73 (37) 804-809 As part of the response to the highly pathogenic avian influenza A(H5N1) virus outbreak in U.S. cattle and poultry and the associated human cases, CDC and partners are monitoring influenza A virus levels and detection of the H5 subtype in wastewater. Among 48 states and the District of Columbia that performed influenza A testing of wastewater during May 12-July 13, 2024, a weekly average of 309 sites in 38 states had sufficient data for analysis, and 11 sites in four states reported high levels of influenza A virus. H5 subtype testing was conducted at 203 sites in 41 states, with H5 detections at 24 sites in nine states. For each detection or high level, CDC and state and local health departments evaluated data from other influenza surveillance systems and partnered with wastewater utilities and agriculture departments to investigate potential sources. Among the four states with high influenza A virus levels detected in wastewater, three states had corresponding evidence of human influenza activity from other influenza surveillance systems. Among the 24 sites with H5 detections, 15 identified animal sources within the sewershed or adjacent county, including eight milk-processing inputs. Data from these early investigations can help health officials optimize the use of wastewater surveillance during the upcoming respiratory illness season. |
A systematic review of the data, methods and environmental covariates used to map Aedes-borne arbovirus transmission risk
Lim AY , Jafari Y , Caldwell JM , Clapham HE , Gaythorpe KAM , Hussain-Alkhateeb L , Johansson MA , Kraemer MUG , Maude RJ , McCormack CP , Messina JP , Mordecai EA , Rabe IB , Reiner RC Jr , Ryan SJ , Salje H , Semenza JC , Rojas DP , Brady OJ . BMC Infect Dis 2023 23 (1) 708 BACKGROUND: Aedes (Stegomyia)-borne diseases are an expanding global threat, but gaps in surveillance make comprehensive and comparable risk assessments challenging. Geostatistical models combine data from multiple locations and use links with environmental and socioeconomic factors to make predictive risk maps. Here we systematically review past approaches to map risk for different Aedes-borne arboviruses from local to global scales, identifying differences and similarities in the data types, covariates, and modelling approaches used. METHODS: We searched on-line databases for predictive risk mapping studies for dengue, Zika, chikungunya, and yellow fever with no geographical or date restrictions. We included studies that needed to parameterise or fit their model to real-world epidemiological data and make predictions to new spatial locations of some measure of population-level risk of viral transmission (e.g. incidence, occurrence, suitability, etc.). RESULTS: We found a growing number of arbovirus risk mapping studies across all endemic regions and arboviral diseases, with a total of 176 papers published 2002-2022 with the largest increases shortly following major epidemics. Three dominant use cases emerged: (i) global maps to identify limits of transmission, estimate burden and assess impacts of future global change, (ii) regional models used to predict the spread of major epidemics between countries and (iii) national and sub-national models that use local datasets to better understand transmission dynamics to improve outbreak detection and response. Temperature and rainfall were the most popular choice of covariates (included in 50% and 40% of studies respectively) but variables such as human mobility are increasingly being included. Surprisingly, few studies (22%, 31/144) robustly tested combinations of covariates from different domains (e.g. climatic, sociodemographic, ecological, etc.) and only 49% of studies assessed predictive performance via out-of-sample validation procedures. CONCLUSIONS: Here we show that approaches to map risk for different arboviruses have diversified in response to changing use cases, epidemiology and data availability. We identify key differences in mapping approaches between different arboviral diseases, discuss future research needs and outline specific recommendations for future arbovirus mapping. |
A systematic review of the data, methods and environmental covariates used to map Aedes-borne arbovirus transmission risk (preprint)
Lim AY , Jafari Y , Caldwell JM , Clapham HE , Gaythorpe KAM , Hussain-Alkhateeb L , Johansson MA , Kraemer MUG , Maude RJ , McCormack CP , Messina JP , Mordecai EA , Rabe IB , Reiner RC , Ryan SJ , Salje H , Semenza JC , Rojas DP , Brady OJ . medRxiv 2023 20 Background Aedes (Stegomyia)-borne diseases are an expanding global threat, but gaps in surveillance make comprehensive and comparable risk assessments challenging. Geostatistical models combine data from multiple locations and use links with environmental and socioeconomic factors to make predictive risk maps. Here we systematically review past approaches to map risk for different Aedesborne arboviruses from local to global scales, identifying differences and similarities in the data types, covariates, and modelling approaches used. Methods We searched on-line databases for predictive risk mapping studies for dengue, Zika, chikungunya, and yellow fever with no geographical or date restrictions. We included studies that needed to parameterise or fit their model to real-world epidemiological data and make predictions to new spatial locations of some measure of population-level risk of viral transmission (e.g. incidence, occurrence, suitability, etc). Results We found a growing number of arbovirus risk mapping studies across all endemic regions and arboviral diseases, with a total of 183 papers published 2002-2022 with the largest increases shortly following major epidemics. Three dominant use cases emerged: i) global maps to identify limits of transmission, estimate burden and assess impacts of future global change, ii) regional models used to predict the spread of major epidemics between countries and iii) national and sub-national models that use local datasets to better understand transmission dynamics to improve outbreak detection and response. Temperature and rainfall were the most popular choice of covariates (included in 50% and 40% of studies respectively) but variables such as human mobility are increasingly being included. Surprisingly, few studies (22%, 33/148) robustly tested combinations of covariates from different domains (e.g. climatic, sociodemographic, ecological, etc) and only 48% of studies assessed predictive performance via out-of-sample validation procedures. Conclusions Here we show that approaches to map risk for different arboviruses have diversified in response to changing use cases, epidemiology and data availability. We outline specific recommendations for future studies regarding aims and data choice, covariate selection, model formulation and evaluation. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
Humoral and cellular immune responses to recombinant herpes zoster vaccine in patients with chronic lymphocytic leukemia and monoclonal B cell lymphocytosis
Muchtar E , Koehler AB , Johnson MJ , Rabe KG , Ding W , Call TG , Leis JF , Kenderian SS , Hayman SR , Wang Y , Hampel PJ , Holets MA , Darby HC , Slager SL , Kay NE , Miao C , Canniff J , Whitaker JA , Levin MJ , Schmid DS , Kennedy RB , Weinberg A , Parikh SA . Am J Hematol 2021 97 (1) 90-98 Monoclonal B cell lymphocytosis (MBL) and chronic lymphocytic leukemia (CLL) are clonal B cell disorders associated with increased risk of infections and impaired vaccination responses. We investigated the immunogenicity of recombinant zoster vaccine (RZV) in these patients. Individuals with MBL/untreated CLL and Bruton tyrosine kinase inhibitor (BTKi)-treated CLL patients were given two doses of RZV separated by two months. Responses assessed at 3-months and 12-months from the first dose of RZV by an anti-glycoprotein E ELISA antibody assay and by dual-color IFN-γ and IL-2 FLUOROSPOT assays were compared to historic controls matched by age and sex. Sixty-two patients (37 MBL/untreated CLL and 25 BTKi-treated CLL) were enrolled with a median age of 68 years at vaccination. An antibody response at 3 months was seen in 45% of participants, which was significantly lower compared to historic controls (63%, P=0.03). The antibody response did not significantly differ between MBL/untreated CLL and BTKi-treated CLL (51% vs 36%, respectively, P=0.23). The CD4+ T cell response to vaccination was significantly lower in study participants compared to controls (54% vs 96%, P<0.001), mainly due to lower responses among BTKi-treated patients compared to untreated MBL/CLL (32% vs 73%, P=0.008). Overall, only 29% of participants achieved combined antibody and cellular responses to RZV. Among participants with response assessment at 12 months (n=47), 24% had antibody titers below response threshold. Hypogammaglobulinemia and BTKi therapy were associated with reduced T cell responses in a univariate analysis. Strategies to improve vaccine response to RZV among MBL/CLL patients are needed. This article is protected by copyright. All rights reserved. |
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. |
Investigation of Heartland Virus Disease throughout the United States, 2013-2017
Staples JE , Pastula DM , Panella AJ , Rabe IB , Kosoy OI , Walker WL , Velez JO , Lambert AJ , Fischer M . Open Forum Infect Dis 2020 7 (5) ofaa125 Background: Heartland virus (HRTV) was first described as a human pathogen in 2012. From 2013 to 2017, the Centers for Disease Control and Prevention (CDC) implemented a national protocol to evaluate patients for HRTV disease, better define its geographic distribution, epidemiology, and clinical characteristics, and develop diagnostic assays for this novel virus. Methods: Individuals aged >/=12 years whose clinicians contacted state health departments or the CDC about testing for HRTV infections were screened for recent onset of fever with leukopenia and thrombocytopenia. A questionnaire was administered to collect data on demographics, risk factors, and signs and symptoms; blood samples were tested for the presence of HRTV RNA and neutralizing antibodies. Results: Of 85 individuals enrolled and tested, 16 (19%) had evidence of acute HRTV infection, 1 (1%) had past infection, and 68 (80%) had no infection. Patients with acute HRTV disease were residents of 7 states, 12 (75%) were male, and the median age (range) was 71 (43-80) years. Illness onset occurred from April to September. The majority reported fatigue, anorexia, nausea, headache, confusion, arthralgia, or myalgia. Fourteen (88%) cases were hospitalized; 2 (13%) died. Fourteen (88%) participants reported finding a tick on themselves in the 2 weeks before illness onset. HRTV-infected individuals were significantly older (P < .001) and more likely to report an attached tick (P = .03) than uninfected individuals. Conclusions: Health care providers should consider HRTV disease testing in patients with an acute febrile illness with either leukopenia or thrombocytopenia not explained by another condition or who were suspected to have a tickborne disease but did not improve following appropriate treatment. |
Patients with laboratory evidence of West Nile virus disease without reported fever
Landry K , Rabe IB , Messenger SL , Hacker JK , Salas ML , Scott-Waldron C , Haydel D , Rider E , Simonson S , Brown CM , Smole SC , Neitzel DF , Schiffman EK , Strain AK , Vetter S , Fischer M , Lindsey NP . Epidemiol Infect 2019 147 e219 In 2013, the national surveillance case definition for West Nile virus (WNV) disease was revised to remove fever as a criterion for neuroinvasive disease and require at most subjective fever for non-neuroinvasive disease. The aims of this project were to determine how often afebrile WNV disease occurs and assess differences among patients with and without fever. We included cases with laboratory evidence of WNV disease reported from four states in 2014. We compared demographics, clinical symptoms and laboratory evidence for patients with and without fever and stratified the analysis by neuroinvasive and non-neuroinvasive presentations. Among 956 included patients, 39 (4%) had no fever; this proportion was similar among patients with and without neuroinvasive disease symptoms. For neuroinvasive and non-neuroinvasive patients, there were no differences in age, sex, or laboratory evidence between febrile and afebrile patients, but hospitalisations were more common among patients with fever (P < 0.01). The only significant difference in symptoms was for ataxia, which was more common in neuroinvasive patients without fever (P = 0.04). Only 5% of non-neuroinvasive patients did not meet the WNV case definition due to lack of fever. The evidence presented here supports the changes made to the national case definition in 2013. |
Expanded Molecular Testing on Patients with Suspected West Nile Virus Disease.
Lindsey NP , Messenger SL , Hacker JK , Salas ML , Scott-Waldron C , Haydel D , Rider E , Simonson S , Brown CM , Patel P , Smole SC , Neitzel DF , Schiffman EK , Palm J , Strain AK , Vetter SM , Nefzger B , Fischer M , Rabe IB . Vector Borne Zoonotic Dis 2019 19 (9) 690-693 Most diagnostic testing for West Nile virus (WNV) disease is accomplished using serologic testing, which is subject to cross-reactivity, may require cumbersome confirmatory testing, and may fail to detect infection in specimens collected early in the course of illness. The objective of this project was to determine whether a combination of molecular and serologic testing would increase detection of WNV disease cases in acute serum samples. A total of 380 serum specimens collected </=7 days after onset of symptoms and submitted to four state public health laboratories for WNV diagnostic testing in 2014 and 2015 were tested. WNV immunoglobulin M (IgM) antibody and RT-PCR tests were performed on specimens collected </=3 days after symptom onset. WNV IgM antibody testing was performed on specimens collected 4-7 days after onset and RT-PCR was performed on IgM-positive specimens. A patient was considered to have laboratory evidence of WNV infection if they had detectable WNV IgM antibodies or WNV RNA in the submitted serum specimen. Of specimens collected </=3 days after symptom onset, 19/158 (12%) had laboratory evidence of WNV infection, including 16 positive for only WNV IgM antibodies, 1 positive for only WNV RNA, and 2 positive for both. Of specimens collected 4-7 days after onset, 21/222 (9%) were positive for WNV IgM antibodies; none had detectable WNV RNA. These findings suggest that routinely performing WNV RT-PCR on acute serum specimens submitted for WNV diagnostic testing is unlikely to identify a substantial number of additional cases beyond IgM antibody testing alone. |
West Nile virus and other nationally notifiable arboviral diseases - United States, 2017
Curren EJ , Lehman J , Kolsin J , Walker WL , Martin SW , Staples JE , Hills SL , Gould CV , Rabe IB , Fischer M , Lindsey NP . MMWR Morb Mortal Wkly Rep 2018 67 (41) 1137-1142 Arthropodborne viruses (arboviruses) are transmitted to humans primarily through the bites of infected mosquitoes or ticks. West Nile virus (WNV) is the leading cause of domestically acquired arboviral disease in the continental United States (1). Other arboviruses, including Jamestown Canyon, La Crosse, Powassan, St. Louis encephalitis, and eastern equine encephalitis viruses, cause sporadic cases of disease and occasional outbreaks. This report summarizes surveillance data reported to CDC from U.S. states in 2017 for nationally notifiable arboviruses. It excludes dengue, chikungunya, and Zika viruses because, in the continental United States, these viruses are acquired primarily through travel. In 2017, 48 states and the District of Columbia (DC) reported 2,291 cases of domestic arboviral disease, including 2,097 (92%) WNV disease cases. Among the WNV disease cases, 1,425 (68%) were classified as neuroinvasive disease (e.g., meningitis, encephalitis, or acute flaccid paralysis), for a national rate of 0.44 cases per 100,000 population. More Jamestown Canyon and Powassan virus disease cases were reported in 2017 than in any previous year. Because arboviral diseases continue to cause serious illness, maintaining surveillance is important to direct and promote prevention activities. |
Adverse events following vaccination with an inactivated, Vero cell culture-derived Japanese encephalitis vaccine in the United States, 2012-2016
Walker WL , Hills SL , Miller ER , Fischer M , Rabe IB . Vaccine 2018 36 (29) 4369-4374 BACKGROUND: In March 2009, the U.S. Food and Drug Administration licensed an inactivated Vero cell culture-derived Japanese encephalitis vaccine (JE-VC [IXIARO(R)]) for use in persons aged >/=17years. In 2013, licensure was extended to include children aged >/=2months. A previous analysis reviewed adverse events reported to the U.S. Vaccine Adverse Event Reporting System (VAERS) from May 2009 through April 2012. METHODS: We reviewed adverse events reported to VAERS following JE-VC administered from May 1, 2012 through April 30, 2016. Adverse event reporting rates were calculated using 802,229 doses distributed. RESULTS: During the 4-year period, 119 adverse event reports were received for a reporting rate of 14.8 per 100,000 doses distributed. Nine (8%) adverse events were classified as serious for a reporting rate of 1.1 per 100,000 distributed. The most commonly reported event was hypersensitivity (n=24; 20%) for a rate of 3.0 per 100,000 doses distributed; 1 anaphylaxis event was reported. Ten (8%) neurologic events were reported for a rate of 1.2 per 100,000 doses distributed; 2 events were classified as seizures. Sixty-three (53%) adverse events occurred after a first dose of JE-VC. Eighty (67%) adverse events occurred after administration of JE-VC with other vaccines. Eleven (9%) adverse events were reported in children; 1 was considered serious. CONCLUSIONS: These data continue to support the generally favorable safety profile of JE-VC. Reporting rates of adverse events were similar to those of the previous analysis. Although reporting rates of adverse events in children could not be calculated, there were low numbers of reported events in this age group. Post-licensure adverse event surveillance for this relatively new vaccine continues to be important to monitor adverse event reporting rates and identify possible rare serious events. |
Update: Noncongenital Zika virus disease cases - 50 U.S. states and the District of Columbia, 2016
Hall V , Walker WL , Lindsey NP , Lehman JA , Kolsin J , Landry K , Rabe IB , Hills SL , Fischer M , Staples JE , Gould CV , Martin SW . MMWR Morb Mortal Wkly Rep 2018 67 (9) 265-269 Zika virus is a flavivirus primarily transmitted to humans by Aedes aegypti mosquitoes (1). Zika virus infections also have been documented through intrauterine transmission resulting in congenital infection; intrapartum transmission from a viremic mother to her newborn; sexual transmission; blood transfusion; and laboratory exposure (1-3). Most Zika virus infections are asymptomatic or result in mild clinical illness, characterized by acute onset of fever, maculopapular rash, arthralgia, or nonpurulent conjunctivitis; Guillain-Barre syndrome, meningoencephalitis, and severe thrombocytopenia rarely have been associated with Zika virus infection (1). However, congenital Zika virus infection can result in fetal loss, microcephaly, and other birth defects (1,2). In 2016, a total of 5,168 noncongenital Zika virus disease cases were reported from U.S. states and the District of Columbia. Most cases (4,897, 95%) were in travelers returning from Zika virus-affected areas. A total of 224 (4%) cases were acquired through presumed local mosquitoborne transmission, and 47 (1%) were acquired by other routes. It is important that providers in the United States continue to test symptomatic patients who live in or recently traveled to areas with ongoing Zika virus transmission or had unprotected sex with someone who lives in or traveled to those areas. All pregnant women and their partners should take measures to prevent Zika virus infection during pregnancy. A list of affected areas and specific recommendations on how to prevent Zika virus infection during pregnancy are available at https://www.cdc.gov/pregnancy/zika/protect-yourself.html. |
Modes of transmission of Zika virus
Gregory CJ , Oduyebo T , Brault AC , Brooks JT , Chung KW , Hills S , Kuehnert MJ , Mead P , Meaney-Delman D , Rabe I , Staples E , Petersen LR . J Infect Dis 2017 216 S875-s883 For >60 years, Zika virus (ZIKV) has been recognized as an arthropod-borne virus with Aedes species mosquitoes as the primary vector. However in the past 10 years, multiple alternative routes of ZIKV transmission have been identified. We review the available data on vector and non-vector-borne modes of transmission and interventions undertaken, to date, to reduce the risk of human infection through these routes. Although much has been learned during the outbreak in the Americas on the underlying mechanisms and pathogenesis of non-vector-borne ZIKV infections, significant gaps remain in our understanding of the relative incidence of, and risk from, these modes compared to mosquito transmission. Additional research is urgently needed on the risk, pathogenesis, and effectiveness of measures to mitigate non-vector-borne ZIKV transmission. |
Ability to serologically confirm recent Zika virus infection in areas with varying past incidence of dengue virus infection in the United States and U.S. territories in 2016
Lindsey NP , Staples JE , Powell K , Rabe IB , Fischer M , Powers AM , Kosoy OI , Mossel EC , Munoz-Jordan JL , Beltran M , Hancock WT , Toews KE , Ellis EM , Ellis BR , Panella AJ , Basile AJ , Calvert AE , Laven J , Goodman CH , Gould CV , Martin SW , Thomas JD , Villanueva J , Mataia ML , Sciulli R , Gose R , Whelen AC , Hills SL . J Clin Microbiol 2017 56 (1) Background. Cross-reactivity within flavivirus antibody assays, produced by shared epitopes in the envelope proteins, can complicate serological diagnosis of Zika virus (ZIKAV) infection. We assessed the utility of the plaque reduction neutralization test (PRNT) to confirm recent ZIKAV infections and rule out misleading positive IgM results in areas with varying past dengue virus (DENV) infection incidence. Methods. We reviewed PRNT results of sera collected for diagnosis of ZIKAV infection from January 1 through August 31, 2016 with positive ZIKAV IgM results and ZIKAV and DENV PRNT performed. PRNT result interpretations included ZIKAV, unspecified flavivirus, DENV infection, or negative. For this analysis, ZIKAV IgM was considered false-positive for samples interpreted as DENV infection or negative. Results. In US states, 208 (27%) of 759 IgM positives were confirmed as ZIKAV, compared to 11 (21%) of 52 in the US Virgin Islands (USVI), 15 (15%) of 103 in American Samoa, and 13 (11%) of 123 in Puerto Rico. In American Samoa and Puerto Rico, more than 80% of IgM positives were unspecified flavivirus infections. The false-positivity rate was 27% in US states, 18% in USVI, 2% in American Samoa, and 6% in Puerto Rico. Conclusions. In US states, PRNT provided a virus-specific diagnosis or ruled out infection in the majority of IgM positive samples. Almost a third of ZIKAV IgM positive results did not confirm; therefore, providers and patients must understand that IgM results are preliminary. In territories with historically higher DENV transmission, PRNT usually could not differentiate between ZIKAV and DENV infections. |
St. Louis encephalitis virus possibly transmitted through blood transfusion - Arizona, 2015
Venkat H , Adams L , Sunenshine R , Krow-Lucal E , Levy C , Kafenbaum T , Sylvester T , Smith K , Townsend J , Dosmann M , Kamel H , Patron R , Kuehnert M , Annambhotla P , Basavaraju SV , Rabe IB . Transfusion 2017 57 (12) 2987-2994 BACKGROUND: St. Louis encephalitis virus is a mosquito-borne flavivirus that infrequently causes epidemic central nervous system infections. In the United States, blood donors are not screened for St. Louis encephalitis virus infection, and transmission through blood transfusion has not been reported. During September 2015, St. Louis encephalitis virus infection was confirmed in an Arizona kidney transplant recipient. An investigation was initiated to determine the infection source. STUDY DESIGN AND METHODS: The patient was interviewed, and medical records were reviewed. To determine the likelihood of mosquito-borne infection, mosquito surveillance data collected at patient and blood donor residences in timeframes consistent with their possible exposure periods were reviewed. To investigate other routes of exposure, organ and blood donor and recipient specimens were obtained and tested for evidence of St. Louis encephalitis virus infection. RESULTS: The patient presented with symptoms of central nervous system infection. Recent St. Louis encephalitis virus infection was serologically confirmed. The organ donor and three other organ recipients showed no laboratory or clinical evidence of St. Louis encephalitis virus infection. Among four donors of blood products received by the patient via transfusion, one donor had a serologically confirmed, recent St. Louis encephalitis virus infection. Exposure to an infected mosquito was unlikely based on the patient's minimal outdoor exposure. In addition, no St. Louis encephalitis virus-infected mosquito pools were identified around the patient's residence. CONCLUSION: This investigation provides evidence of the first reported possible case of St. Louis encephalitis virus transmission through blood product transfusion. Health care providers and public health professionals should maintain heightened awareness for St. Louis encephalitis virus transmission through blood transfusion in settings where outbreaks are identified. |
Update: Interim guidance for health care providers caring for pregnant women with possible Zika virus exposure - United States (including U.S. territories), July 2017
Oduyebo T , Polen KD , Walke HT , Reagan-Steiner S , Lathrop E , Rabe IB , Kuhnert-Tallman WL , Martin SW , Walker AT , Gregory CJ , Ades EW , Carroll DS , Rivera M , Perez-Padilla J , Gould C , Nemhauser JB , Ben Beard C , Harcourt JL , Viens L , Johansson M , Ellington SR , Petersen E , Smith LA , Reichard J , Munoz-Jordan J , Beach MJ , Rose DA , Barzilay E , Noonan-Smith M , Jamieson DJ , Zaki SR , Petersen LR , Honein MA , Meaney-Delman D . MMWR Morb Mortal Wkly Rep 2017 66 (29) 781-793 CDC has updated the interim guidance for U.S. health care providers caring for pregnant women with possible Zika virus exposure in response to 1) declining prevalence of Zika virus disease in the World Health Organization's Region of the Americas (Americas) and 2) emerging evidence indicating prolonged detection of Zika virus immunoglobulin M (IgM) antibodies. Zika virus cases were first reported in the Americas during 2015-2016; however, the incidence of Zika virus disease has since declined. As the prevalence of Zika virus disease declines, the likelihood of false-positive test results increases. In addition, emerging epidemiologic and laboratory data indicate that, as is the case with other flaviviruses, Zika virus IgM antibodies can persist beyond 12 weeks after infection. Therefore, IgM test results cannot always reliably distinguish between an infection that occurred during the current pregnancy and one that occurred before the current pregnancy, particularly for women with possible Zika virus exposure before the current pregnancy. These limitations should be considered when counseling pregnant women about the risks and benefits of testing for Zika virus infection during pregnancy. This updated guidance emphasizes a shared decision-making model for testing and screening pregnant women, one in which patients and providers work together to make decisions about testing and care plans based on patient preferences and values, clinical judgment, and a balanced assessment of risks and expected outcomes. |
Evaluation of placental and fetal tissue specimens for Zika virus infection - 50 states and District of Columbia, January-December, 2016
Reagan-Steiner S , Simeone R , Simon E , Bhatnagar J , Oduyebo T , Free R , Denison AM , Rabeneck DB , Ellington S , Petersen E , Gary J , Hale G , Keating MK , Martines RB , Muehlenbachs A , Ritter J , Lee E , Davidson A , Conners E , Scotland S , Sandhu K , Bingham A , Kassens E , Smith L , St George K , Ahmad N , Tanner M , Beavers S , Miers B , VanMaldeghem K , Khan S , Rabe I , Gould C , Meaney-Delman D , Honein MA , Shieh WJ , Jamieson DJ , Fischer M , Zaki SR . MMWR Morb Mortal Wkly Rep 2017 66 (24) 636-643 Zika virus infection during pregnancy can cause congenital microcephaly and brain abnormalities (1), and detection of Zika virus RNA in clinical and tissue specimens can provide definitive laboratory evidence of recent Zika virus infection. Whereas duration of viremia is typically short, prolonged detection of Zika virus RNA in placental, fetal, and neonatal brain tissue has been reported and can provide key diagnostic information by confirming recent Zika virus infection (2). In accordance with recent guidance (3,4), CDC provides Zika virus testing of placental and fetal tissues in clinical situations where this information could add diagnostic value. This report describes the evaluation of formalin-fixed paraffin-embedded (FFPE) tissue specimens tested for Zika virus infection in 2016 and the contribution of this testing to the public health response. Among 546 live births with possible maternal Zika virus exposure, for which placental tissues were submitted by the 50 states and District of Columbia (DC), 60 (11%) were positive by Zika virus reverse transcription-polymerase chain reaction (RT-PCR). Among 81 pregnancy losses for which placental and/or fetal tissues were submitted, 18 (22%) were positive by Zika virus RT-PCR. Zika virus RT-PCR was positive on placental tissues from 38/363 (10%) live births with maternal serologic evidence of recent unspecified flavivirus infection and from 9/86 (10%) with negative maternal Zika virus immunoglobulin M (IgM) where possible maternal exposure occurred >12 weeks before serum collection. These results demonstrate that Zika virus RT-PCR testing of tissue specimens can provide a confirmed diagnosis of recent maternal Zika virus infection. |
Zika virus: Common questions and answers
Igbinosa II , Rabe IB , Oduyebo T , Rasmussen SA . Am Fam Physician 2017 95 (8) 507-513 Since local mosquito-borne transmission of Zika virus was first reported in Brazil in early 2015, the virus has spread rapidly, with active transmission reported in at least 61 countries and territories worldwide, including the United States. Zika virus infection during pregnancy is a cause of microcephaly and other severe brain anomalies. The virus is transmitted primarily through the bite of an infected Aedes mosquito, but other routes of transmission include sexual, mother-to-fetus during pregnancy, mother-to-infant at delivery, laboratory exposure, and, possibly, transfusion of blood products. Most persons with Zika virus infection are asymptomatic or have only mild symptoms; hospitalizations and deaths are rare. When symptoms are present, maculopapular rash, fever, arthralgia, and conjunctivitis are most common. Zika virus testing is recommended for persons with possible exposure (those who have traveled to or live in an area with active transmission, or persons who had sex without a condom with a person with possible exposure) if they have symptoms consistent with Zika virus disease. Testing is also recommended for pregnant women with possible exposure, regardless of whether symptoms are present. Treatment is supportive, and no vaccine is currently available. The primary methods of prevention include avoiding bites of infected Aedes mosquitoes and reducing the risk of sexual transmission. Pregnant women should not travel to areas with active Zika virus transmission, and men and women who are planning to conceive in the near future should consider avoiding nonessential travel to these areas. Condoms can reduce the risk of sexual transmission. |
Update: Interim guidance for preconception counseling and prevention of sexual transmission of Zika virus for persons with possible Zika virus exposure - United States, September 2016
Petersen EE , Meaney-Delman D , Neblett-Fanfair R , Havers F , Oduyebo T , Hills SL , Rabe IB , Lambert A , Abercrombie J , Martin SW , Gould CV , Oussayef N , Polen KN , Kuehnert MJ , Pillai SK , Petersen LR , Honein MA , Jamieson DJ , Brooks JT . MMWR Morb Mortal Wkly Rep 2016 65 (39) 1077-1081 CDC has updated its interim guidance for persons with possible Zika virus exposure who are planning to conceive and interim guidance to prevent transmission of Zika virus through sexual contact, now combined into a single document. Guidance for care for pregnant women with possible Zika virus exposure was previously published. Possible Zika virus exposure is defined as travel to or residence in an area of active Zika virus transmission (http://www.cdc.gov/zika/geo/index.html), or sex without a condom with a partner who traveled to or lived in an area of active transmission. Based on new though limited data, CDC now recommends that all men with possible Zika virus exposure who are considering attempting conception with their partner, regardless of symptom status, section sign wait to conceive until at least 6 months after symptom onset (if symptomatic) or last possible Zika virus exposure (if asymptomatic). Recommendations for women planning to conceive remain unchanged: women with possible Zika virus exposure are recommended to wait to conceive until at least 8 weeks after symptom onset (if symptomatic) or last possible Zika virus exposure (if asymptomatic). Couples with possible Zika virus exposure, who are not pregnant and do not plan to become pregnant, who want to minimize their risk for sexual transmission of Zika virus should use a condom or abstain from sex for the same periods for men and women described above. Women of reproductive age who have had or anticipate future Zika virus exposure who do not want to become pregnant should use the most effective contraceptive method that can be used correctly and consistently. These recommendations will be further updated when additional data become available. |
Zika virus disease cases - 50 states and the District of Columbia, January 1-July 31, 2016
Walker WL , Lindsey NP , Lehman JA , Krow-Lucal ER , Rabe IB , Hills SL , Martin SW , Fischer M , Staples JE . MMWR Morb Mortal Wkly Rep 2016 65 (36) 983-986 Zika virus is a mosquito-borne flavivirus primarily transmitted to humans by Aedes aegypti mosquitoes. Zika virus infections have also been documented through intrauterine transmission resulting in congenital infection; intrapartum transmission from a viremic mother to her newborn; sexual transmission; blood transfusion; and laboratory exposure. Most Zika virus infections are asymptomatic. Clinical illness, when it occurs, is generally mild and characterized by acute onset of fever, maculopapular rash, arthralgia, or nonpurulent conjunctivitis. However, Zika virus infection during pregnancy can cause adverse outcomes such as fetal loss, and microcephaly and other serious brain anomalies. Guillain-Barre syndrome, a rare autoimmune condition affecting the peripheral nervous system, also has been associated with Zika virus infection. Following the identification of local transmission of Zika virus in Brazil in May 2015, the virus has continued to spread throughout the Region of the Americas, and travel-associated cases have increased. In 2016, Zika virus disease and congenital infections became nationally notifiable conditions in the United States (8). As of September 3, 2016, a total of 2,382 confirmed and probable cases of Zika virus disease with symptom onset during January 1-July 31, 2016, had been reported from 48 of 50 U.S. states and the District of Columbia. Most cases (2,354; 99%) were travel-associated, with either direct travel or an epidemiologic link to a traveler to a Zika virus-affected area. Twenty-eight (1%) cases were reported as locally acquired, including 26 associated with mosquito-borne transmission, one acquired in a laboratory, and one with an unknown mode of transmission. Zika virus disease should be considered in patients with compatible clinical signs or symptoms who traveled to or reside in areas with ongoing Zika virus transmission or who had unprotected sex with someone who traveled to those areas. Health care providers should continue to educate patients, especially pregnant women, about the importance of avoiding infection with Zika virus, and all pregnant women should be assessed for possible Zika virus exposure at each prenatal visit. |
Adverse event reports following yellow fever vaccination, 2007-13
Lindsey NP , Rabe IB , Miller ER , Fischer M , Staples JE . J Travel Med 2016 23 (5) BACKGROUND: Yellow fever (YF) vaccines have been available since the 1930s and are generally considered safe and effective. However, rare reports of serious adverse events (SAE) following vaccination have prompted the Advisory Committee for Immunization Practices to periodically expand the list of conditions considered contraindications and precautions to vaccination. METHODS: We describe adverse events following YF vaccination reported to the U.S. Vaccine Adverse Event Reporting System (VAERS) from 2007 through 2013 and calculate age- and sex-specific reporting rates of all SAE, anaphylaxis, YF vaccine-associated neurologic disease (YEL-AND) and YF vaccine-associated viscerotropic disease (YEL-AVD). RESULTS: There were 938 adverse events following YF vaccination reported to VAERS from 2007 through 2013. Of these, 84 (9%) were classified as SAEs for a rate of 3.8 per 100 000 doses distributed. Reporting rates of SAEs increased with increasing age with a rate of 6.5 per 100 000 in persons aged 60-69 years and 10.3 for ≥70 years. The reporting rate for anaphylaxis was 1.3 per 100 000 doses distributed and was highest in persons ≤18 years (2.7 per 100 000). Reporting rates of YEL-AND and YEL-AVD were 0.8 and 0.3 per 100 000 doses distributed, respectively; both rates increased with increasing age. CONCLUSIONS: These findings reinforce the generally acceptable safety profile of YF vaccine, but highlight the importance of continued physician and traveller education regarding the risks and benefits of YF vaccination, particularly for older travellers. |
Interim guidance for interpretation of Zika virus antibody test results
Rabe IB , Staples JE , Villanueva J , Hummel KB , Johnson JA , Rose L , Hills S , Wasley A , Fischer M , Powers AM . MMWR Morb Mortal Wkly Rep 2016 65 (21) 543-6 Zika virus is a single-stranded RNA virus in the genus Flavivirus and is closely related to dengue, West Nile, Japanese encephalitis, and yellow fever viruses (1,2). Among flaviviruses, Zika and dengue virus share similar symptoms of infection, transmission cycles, and geographic distribution. Diagnostic testing for Zika virus infection can be accomplished using both molecular and serologic methods. For persons with suspected Zika virus disease, a positive real-time reverse transcription-polymerase chain reaction (rRT-PCR) result confirms Zika virus infection, but a negative rRT-PCR result does not exclude infection (3-7). In these cases, immunoglobulin (Ig) M and neutralizing antibody testing can identify additional recent Zika virus infections (6,7). However, Zika virus antibody test results can be difficult to interpret because of cross-reactivity with other flaviviruses, which can preclude identification of the specific infecting virus, especially when the person previously was infected with or vaccinated against a related flavivirus (8). This is important because the results of Zika and dengue virus testing will guide clinical management. Pregnant women with laboratory evidence of Zika virus infection should be evaluated and managed for possible adverse pregnancy outcomes and be reported to the U.S. Zika Pregnancy Registry or the Puerto Rico Zika Active Pregnancy Surveillance System for clinical follow-up (9,10). All patients with clinically suspected dengue should have proper management to reduce the risk for hemorrhage and shock (11). If serologic testing indicates recent flavivirus infection that could be caused by either Zika or dengue virus, patients should be clinically managed for both infections because they might have been infected with either virus. |
Travel-associated Zika virus disease cases among U.S. residents - United States, January 2015-February 2016
Armstrong P , Hennessey M , Adams M , Cherry C , Chiu S , Harrist A , Kwit N , Lewis L , McGuire DO , Oduyebo T , Russell K , Talley P , Tanner M , Williams C , Basile J , Brandvold J , Calvert A , Cohn A , Fischer M , Goldman-Israelow B , Goodenough D , Goodman C , Hills S , Kosoy O , Lambert A , Lanciotti R , Laven J , Ledermann J , Lehman J , Lindsey N , Mead P , Mossel E , Nelson C , Nichols M , O'Leary D , Panella A , Powers A , Rabe I , Reagan-Steiner S , Staples JE , Velez J . MMWR Morb Mortal Wkly Rep 2016 65 (11) 286-9 Zika virus is an emerging mosquito-borne flavivirus. Recent outbreaks of Zika virus disease in the Pacific Islands and the Region of the Americas have identified new modes of transmission and clinical manifestations, including adverse pregnancy outcomes. However, data on the epidemiology and clinical findings of laboratory-confirmed Zika virus disease remain limited. During January 1, 2015-February 26, 2016, a total of 116 residents of 33 U.S. states and the District of Columbia had laboratory evidence of recent Zika virus infection based on testing performed at CDC. Cases include one congenital infection and 115 persons who reported recent travel to areas with active Zika virus transmission (n = 110) or sexual contact with such a traveler (n = 5). All 115 patients had clinical illness, with the most common signs and symptoms being rash (98%; n = 113), fever (82%; 94), and arthralgia (66%; 76). Health care providers should educate patients, particularly pregnant women, about the risks for, and measures to prevent, infection with Zika virus and other mosquito-borne viruses. Zika virus disease should be considered in patients with acute onset of fever, rash, arthralgia, or conjunctivitis, who traveled to areas with ongoing Zika virus transmission (http://www.cdc.gov/zika/geo/index.html) or who had unprotected sex with a person who traveled to one of those areas and developed compatible symptoms within 2 weeks of returning. |
Zika virus infection among U.S. pregnant travelers - August 2015-February 2016
Meaney-Delman D , Hills SL , Williams C , Galang RR , Iyengar P , Hennenfent AK , Rabe IB , Panella A , Oduyebo T , Honein MA , Zaki S , Lindsey N , Lehman JA , Kwit N , Bertolli J , Ellington S , Igbinosa I , Minta AA , Petersen EE , Mead P , Rasmussen SA , Jamieson DJ . MMWR Morb Mortal Wkly Rep 2016 65 (8) 211-4 After reports of microcephaly and other adverse pregnancy outcomes in infants of mothers infected with Zika virus during pregnancy, CDC issued a travel alert on January 15, 2016, advising pregnant women to consider postponing travel to areas with active transmission of Zika virus. On January 19, CDC released interim guidelines for U.S. health care providers caring for pregnant women with travel to an affected area (1), and an update was released on February 5 (2). As of February 17, CDC had received reports of nine pregnant travelers with laboratory-confirmed Zika virus disease; 10 additional reports of Zika virus disease among pregnant women are currently under investigation. No Zika virus-related hospitalizations or deaths among pregnant women were reported. Pregnancy outcomes among the nine confirmed cases included two early pregnancy losses, two elective terminations, and three live births (two apparently healthy infants and one infant with severe microcephaly); two pregnancies (approximately 18 weeks' and 34 weeks' gestation) are continuing without known complications. Confirmed cases of Zika virus infection were reported among women who had traveled to one or more of the following nine areas with ongoing local transmission of Zika virus: American Samoa, Brazil, El Salvador, Guatemala, Haiti, Honduras, Mexico, Puerto Rico, and Samoa. This report summarizes findings from the nine women with confirmed Zika virus infection during pregnancy, including case reports for four women with various clinical outcomes. U.S. health care providers caring for pregnant women with possible Zika virus exposure during pregnancy should follow CDC guidelines for patient evaluation and management (1,2). Zika virus disease is a nationally notifiable condition. CDC has developed a voluntary registry to collect information about U.S. pregnant women with confirmed Zika virus infection and their infants. Information about the registry is in preparation and will be available on the CDC website. |
Serological survey for antibodies to mosquito-borne bunyaviruses among US National Park Service and US Forest Service employees
Kosoy O , Rabe I , Geissler A , Adjemian J , Panella A , Laven J , Basile AJ , Velez J , Griffith K , Wong D , Fischer M , Lanciotti RS . Vector Borne Zoonotic Dis 2016 16 (3) 191-8 Serum samples from 295 employees of Great Smoky Mountains National Park (GRSM), Rocky Mountain National Park (ROMO), and Grand Teton National Park with adjacent Bridger-Teton National Forest (GRTE-BTNF) were subjected to serological analysis for mosquito-borne bunyaviruses. The sera were analyzed for neutralizing antibodies against six orthobunyaviruses: La Crosse virus (LACV), Jamestown Canyon virus (JCV), snowshoe hare virus (SSHV), California encephalitis virus, and Trivittatus virus (TVTV) belonging to the California serogroup and Cache Valley virus (CVV) belonging to the Bunyamwera serogroup. Sera were also tested for immunoglobulin (Ig) G antibodies against LACV and JCV by enzyme-linked immunosorbent assay (ELISA). The proportion of employees with neutralizing antibodies to any California serogroup bunyavirus was similar in all three sites, with the prevalence ranging from 28% to 36%. The study demonstrated a seroprevalence of 3% to CVV across the three parks. However, proportions of persons with antibodies to specific viruses differed between parks. Participants residing in the eastern regions had a higher seroprevalence to LACV, with 24% (18/75) GRSM employees being seropositive. In contrast, SSHV seroprevalence was limited to employees from the western sites, with 1.7% (1/60) ROMO and 3.8% (6/160) GRTE-BTNF employees being positive. Seroprevalence to JCV was noted in employees from all sites at rates of 6.7% in GRSM, 21.7% in ROMO, and 15.6% in GRTE-BTNF. One employee each from ROMO (1.7%) and GRTE-BTNF (1.9%) were positive for TVTV. This study also has illustrated the greater sensitivity and specificity of plaque reduction neutralization test compared to IgG ELISA in conducting serosurveys for LACV and JCV. |
Characterization of large structural genetic mosaicism in human autosomes.
Machiela MJ , Zhou W , Sampson JN , Dean MC , Jacobs KB , Black A , Brinton LA , Chang IS , Chen C , Chen C , Chen K , Cook LS , Crous Bou M , De Vivo I , Doherty J , Friedenreich CM , Gaudet MM , Haiman CA , Hankinson SE , Hartge P , Henderson BE , Hong YC , Hosgood HD 3rd , Hsiung CA , Hu W , Hunter DJ , Jessop L , Kim HN , Kim YH , Kim YT , Klein R , Kraft P , Lan Q , Lin D , Liu J , Le Marchand L , Liang X , Lissowska J , Lu L , Magliocco AM , Matsuo K , Olson SH , Orlow I , Park JY , Pooler L , Prescott J , Rastogi R , Risch HA , Schumacher F , Seow A , Setiawan VW , Shen H , Sheng X , Shin MH , Shu XO , VanDen Berg D , Wang JC , Wentzensen N , Wong MP , Wu C , Wu T , Wu YL , Xia L , Yang HP , Yang PC , Zheng W , Zhou B , Abnet CC , Albanes D , Aldrich MC , Amos C , Amundadottir LT , Berndt SI , Blot WJ , Bock CH , Bracci PM , Burdett L , Buring JE , Butler MA , Carreon T , Chatterjee N , Chung CC , Cook MB , Cullen M , Davis FG , Ding T , Duell EJ , Epstein CG , Fan JH , Figueroa JD , Fraumeni JF Jr , Freedman ND , Fuchs CS , Gao YT , Gapstur SM , Patino-Garcia A , Garcia-Closas M , Gaziano JM , Giles GG , Gillanders EM , Giovannucci EL , Goldin L , Goldstein AM , Greene MH , Hallmans G , Harris CC , Henriksson R , Holly EA , Hoover RN , Hu N , Hutchinson A , Jenab M , Johansen C , Khaw KT , Koh WP , Kolonel LN , Kooperberg C , Krogh V , Kurtz RC , LaCroix A , Landgren A , Landi MT , Li D , Liao LM , Malats N , McGlynn KA , McNeill LH , McWilliams RR , Melin BS , Mirabello L , Peplonska B , Peters U , Petersen GM , Prokunina-Olsson L , Purdue M , Qiao YL , Rabe KG , Rajaraman P , Real FX , Riboli E , Rodriguez-Santiago B , Rothman N , Ruder AM , Savage SA , Schwartz AG , Schwartz KL , Sesso HD , Severi G , Silverman DT , Spitz MR , Stevens VL , Stolzenberg-Solomon R , Stram D , Tang ZZ , Taylor PR , Teras LR , Tobias GS , Viswanathan K , Wacholder S , Wang Z , Weinstein SJ , Wheeler W , White E , Wiencke JK , Wolpin BM , Wu X , Wunder JS , Yu K , Zanetti KA , Zeleniuch-Jacquotte A , Ziegler RG , de Andrade M , Barnes KC , Beaty TH , Bierut LJ , Desch KC , Doheny KF , Feenstra B , Ginsburg D , Heit JA , Kang JH , Laurie CA , Li JZ , Lowe WL , Marazita ML , Melbye M , Mirel DB , Murray JC , Nelson SC , Pasquale LR , Rice K , Wiggs JL , Wise A , Tucker M , Perez-Jurado LA , Laurie CC , Caporaso NE , Yeager M , Chanock SJ . Am J Hum Genet 2015 96 (3) 487-97 Analyses of genome-wide association study (GWAS) data have revealed that detectable genetic mosaicism involving large (>2 Mb) structural autosomal alterations occurs in a fraction of individuals. We present results for a set of 24,849 genotyped individuals (total GWAS set II [TGSII]) in whom 341 large autosomal abnormalities were observed in 168 (0.68%) individuals. Merging data from the new TGSII set with data from two prior reports (the Gene-Environment Association Studies and the total GWAS set I) generated a large dataset of 127,179 individuals; we then conducted a meta-analysis to investigate the patterns of detectable autosomal mosaicism (n = 1,315 events in 925 [0.73%] individuals). Restricting to events >2 Mb in size, we observed an increase in event frequency as event size decreased. The combined results underscore that the rate of detectable mosaicism increases with age (p value = 5.5 x 10(-31)) and is higher in men (p value = 0.002) but lower in participants of African ancestry (p value = 0.003). In a subset of 47 individuals from whom serial samples were collected up to 6 years apart, complex changes were noted over time and showed an overall increase in the proportion of mosaic cells as age increased. Our large combined sample allowed for a unique ability to characterize detectable genetic mosaicism involving large structural events and strengthens the emerging evidence of non-random erosion of the genome in the aging population. |
Adverse events following vaccination with an inactivated, Vero cell culture-derived Japanese encephalitis vaccine in the United States, 2009-2012
Rabe IB , Miller E , Fischer M , Hills S . Vaccine 2014 33 (5) 708-12 BACKGROUND: In March 2009, the U.S. Food and Drug Administration licensed an inactivated, Vero cell culture-derived Japanese encephalitis vaccine (JE-VC [Ixiaro]) for use in adults. The vaccine was licensed based on clinical trial safety data in 3558 JE-VC recipients. It is essential to monitor post-licensure surveillance data to evaluate the safety of JE-VC because rare adverse events may not be detected until the vaccine is administered to a larger population. METHODS: We reviewed adverse events reported to the U.S. Vaccine Adverse Event Reporting System (VAERS) for adults (≥17 years) who received JE-VC from May 2009 through April 2012. Adverse event reporting rates were calculated using 275,848 JE-VC doses distributed. RESULTS: Over the 3 year period, 42 adverse events following vaccination with JE-VC were reported to VAERS for an overall reporting rate of 15.2 adverse events per 100,000 doses distributed. Of the 42 total reports, 5 (12%) were classified as serious for a reporting rate of 1.8 per 100,000 doses distributed; there were no deaths. Hypersensitivity reactions (N=12) were the most commonly reported type of adverse event, with a rate of 4.4 per 100,000 doses distributed; no cases of anaphylaxis were reported. Three adverse events of the central nervous system were reported (one case of encephalitis and two seizures) for a rate of 1.1 per 100,000; all occurred after receipt of JE-VC with other vaccines. CONCLUSIONS: These post-marketing surveillance data suggest a good safety profile for JE-VC consistent with findings from pre-licensure clinical trials. Post-licensure safety data should continue to be monitored for any evidence of rare serious or neurologic adverse events. |
Donor-derived West Nile virus infection in solid organ transplant recipients: report of four additional cases and review of clinical, diagnostic, and therapeutic features.
Winston DJ , Vikram HR , Rabe IB , Dhillon G , Mulligan D , Hong JC , Busuttil RW , Nowicki MJ , Mone T , Civen R , Tecle SA , Trivedi KK , Hocevar SN . Transplantation 2014 97 (9) 881-9 We describe four solid-organ transplant recipients with donor-derived West Nile virus (WNV) infection (encephalitis 3, asymptomatic 1) from a common donor residing in a region of increased WNV activity. All four transplant recipients had molecular evidence of WNV infection in their serum and/or cerebrospinal fluid (CSF) by reverse transcription polymerase chain reaction (RT-PCR) testing. Serum from the organ donor was positive for WNV IgM but negative for WNV RNA, whereas his lymph node and spleen tissues tested positive for WNV by RT-PCR. Combination therapy included intravenous immunoglobulin (4 cases), interferon (3 cases), fresh frozen plasma with WNV IgG (2 cases), and ribavirin (1 case). Two of the four transplant recipients survived.Review of the 20 published cases of organ-derived WNV infection found that this infection is associated with a high incidence of neuroinvasive disease (70%) and severe morbidity and mortality (30%). Median time to onset of symptomatic WNV infection was 13 days after transplantation (range 5-37 days). Initial unexplained fever unresponsive to antibiotic therapy followed by rapid onset of neurologic deficits was the most common clinical presentation. Confirmation of infection was made by testing serum and CSF for both WNV RNA by RT-PCR and WNV IgM by serological assays. Treatment usually included supportive care, reduction of immunosuppression, and frequent intravenous immunoglobulin. The often negative results for WNV by current RT-PCR and serological assays and the absence of clinical signs of acute infection in donors contribute to the sporadic occurrence of donor-derived WNV infection. Potential organ donors should be assessed for unexplained fever and neurological symptoms, particularly if they reside in areas of increased WNV activity. |
Fatal transplant-associated West Nile virus encephalitis and public health investigation-California, 2010
Rabe IB , Schwartz BS , Farnon EC , Josephson SA , Webber AB , Roberts JP , de Mattos AM , Gallay BJ , van Slyck S , Messenger SL , Yen CJ , Bloch EM , Drew CP , Fischer M , Glaser CA . Transplantation 2013 96 (5) 463-8 BACKGROUND: In December 2010, a case of West Nile virus (WNV) encephalitis occurring in a kidney recipient shortly after organ transplantation was identified. METHODS: A public health investigation was initiated to determine the likely route of transmission, detect potential WNV infections among recipients from the same organ donor, and remove any potentially infected blood products or tissues. Available serum, cerebrospinal fluid, and urine samples from the organ donor and recipients were tested for WNV infection by nucleic acid testing and serology. RESULTS: Two additional recipients from the same organ donor were identified, their clinical and exposure histories were reviewed, and samples were obtained. WNV RNA was retrospectively detected in the organ donor's serum. After transplantation, the left kidney recipient had serologic and molecular evidence of WNV infection and the right kidney recipient had prolonged but clinically inapparent WNV viremia. The liver recipient showed no clinical signs of infection but had flavivirus IgG antibodies; however, insufficient samples were available to determine the timing of infection. No remaining infectious products or tissues were identified. CONCLUSIONS: Clinicians should suspect WNV as a cause of encephalitis in organ transplant recipients and report cases to public health departments for prompt investigation of the source of infection. Increased use of molecular testing and retaining pretransplantation sera may improve the ability to detect and diagnose transplant-associated WNV infection in organ transplant recipients. |
Detectable clonal mosaicism and its relationship to aging and cancer.
Jacobs KB , Yeager M , Zhou W , Wacholder S , Wang Z , Rodriguez-Santiago B , Hutchinson A , Deng X , Liu C , Horner MJ , Cullen M , Epstein CG , Burdett L , Dean MC , Chatterjee N , Sampson J , Chung CC , Kovaks J , Gapstur SM , Stevens VL , Teras LT , Gaudet MM , Albanes D , Weinstein SJ , Virtamo J , Taylor PR , Freedman ND , Abnet CC , Goldstein AM , Hu N , Yu K , Yuan JM , Liao L , Ding T , Qiao YL , Gao YT , Koh WP , Xiang YB , Tang ZZ , Fan JH , Aldrich MC , Amos C , Blot WJ , Bock CH , Gillanders EM , Harris CC , Haiman CA , Henderson BE , Kolonel LN , Le Marchand L , McNeill LH , Rybicki BA , Schwartz AG , Signorello LB , Spitz MR , Wiencke JK , Wrensch M , Wu X , Zanetti KA , Ziegler RG , Figueroa JD , Garcia-Closas M , Malats N , Marenne G , Prokunina-Olsson L , Baris D , Schwenn M , Johnson A , Landi MT , Goldin L , Consonni D , Bertazzi PA , Rotunno M , Rajaraman P , Andersson U , Freeman LE , Berg CD , Buring JE , Butler MA , Carreon T , Feychting M , Ahlbom A , Gaziano JM , Giles GG , Hallmans G , Hankinson SE , Hartge P , Henriksson R , Inskip PD , Johansen C , Landgren A , McKean-Cowdin R , Michaud DS , Melin BS , Peters U , Ruder AM , Sesso HD , Severi G , Shu XO , Visvanathan K , White E , Wolk A , Zeleniuch-Jacquotte A , Zheng W , Silverman DT , Kogevinas M , Gonzalez JR , Villa O , Li D , Duell EJ , Risch HA , Olson SH , Kooperberg C , Wolpin BM , Jiao L , Hassan M , Wheeler W , Arslan AA , Bueno-de-Mesquita HB , Fuchs CS , Gallinger S , Gross MD , Holly EA , Klein AP , LaCroix A , Mandelson MT , Petersen G , Boutron-Ruault MC , Bracci PM , Canzian F , Chang K , Cotterchio M , Giovannucci EL , Goggins M , Hoffman Bolton JA , Jenab M , Khaw KT , Krogh V , Kurtz RC , McWilliams RR , Mendelsohn JB , Rabe KG , Riboli E , Tjønneland A , Tobias GS , Trichopoulos D , Elena JW , Yu H , Amundadottir L , Stolzenberg-Solomon RZ , Kraft P , Schumacher F , Stram D , Savage SA , Mirabello L , Andrulis IL , Wunder JS , Patiño García A , Sierrasesúmaga L , Barkauskas DA , Gorlick RG , Purdue M , Chow WH , Moore LE , Schwartz KL , Davis FG , Hsing AW , Berndt SI , Black A , Wentzensen N , Brinton LA , Lissowska J , Peplonska B , McGlynn KA , Cook MB , Graubard BI , Kratz CP , Greene MH , Erickson RL , Hunter DJ , Thomas G , Hoover RN , Real FX , Fraumeni JF Jr , Caporaso NE , Tucker M , Rothman N , Pérez-Jurado LA , Chanock SJ . Nat Genet 2012 44 (6) 651-8 In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of >2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 x 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 x 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases. |
Safe and sustained vaginal delivery of pyrimidinedione HIV-1 inhibitors from polyurethane intravaginal rings
Johnson TJ , Srinivasan P , Albright TH , Watson-Buckheit K , Rabe L , Martin A , Pau CP , Hendry RM , Otten R , McNicholl J , Buckheit R Jr , Smith J , Kiser PF . Antimicrob Agents Chemother 2012 56 (3) 1291-9 The potent antiretroviral pyrimidinediones IQP-0528 (PYD1) and IQP-0532 (PYD2) were formulated in polyurethane intravaginal rings (IVRs) as prophylactic drug delivery systems to prevent the sexual transmission of HIV-1. To aid in the selection of a pyrimidinedione candidate and the optimal loading of the drug in the IVR delivery system, four pyrimidinedione IVR formulations (PYD1 at 0.5 wt% [PYD1(0.5wt%)], PYD1(1wt%), PYD2(4wt%), and PYD2(14wt%)) were evaluated in pigtail macaques over 28 days for safety and pyrimidinedione vaginal biodistribution. Kinetic analysis of vaginal proinflammatory cytokines, native microflora, and drug levels suggested that all formulations were safe, but only the high-loaded PYD2(14wt%) IVR demonstrated consistently high pyrimidinedione vaginal fluid and tissue levels over the 28-day study. This formulation delivered drug in excess of 10 mug/ml to vaginal fluid and 1 mug/g to vaginal tissue, a level over 1,000 times the in vitro 50% effective concentration. The in vitro release of PYD1 and PYD2 under nonsink conditions correlated well with in vivo release, both in amount and in kinetic profile, and therefore may serve as a more biologically relevant means of evaluating release in vitro than typically employed sink conditions. Lastly, the pyrimidinediones in the IVR formulation were chemically stable after 90 days of storage at elevated temperature, and the potent nanomolar-level antiviral activity of both molecules was retained after in vitro release. Altogether, these results point to the successful IVR formulation and vaginal biodistribution of the pyrimidinediones and demonstrate the usefulness of the pigtail macaque model in evaluating and screening antiretroviral IVR formulations prior to preclinical and clinical evaluation. |
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