Last data update: May 06, 2024. (Total: 46732 publications since 2009)
Records 1-23 (of 23 Records) |
Query Trace: Feldmann K[original query] |
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Perspectives on advancing countermeasures for filovirus disease: Report from a multi-sector meeting
Sprecher A , Cross R , Marzi A , Martins KA , Wolfe D , Montgomery JM , Spiropoulou CF , Cihlar T , Ahuka-Mundeke S , Nyhuis T , Teicher C , Crozier I , Strong J , Kobinger G , Woolsey C , Geisbert TW , Feldmann H , Muyembe JJ . J Infect Dis 2023 228 S474-S478 Although there are now approved treatments and vaccines for Ebola virus disease (EVD), the case fatality of EVD remains unacceptably high even when treated with the newly approved therapeutics; furthermore, these countermeasures are not expected to be effective against disease caused by other filoviruses. A meeting of subject matter experts from public health, research, and countermeasure development agencies and manufacturers was held during the 10th International Filovirus Symposium to discuss strategies to address these gaps, including how newer countermeasures could be advanced for field readiness. Several investigational therapeutics, vaccine candidates, and combination strategies were presented. In all, a common theme emerged: the greatest challenge to completing development was the implementation of well-designed clinical trials of safety and efficacy during filovirus disease outbreaks. These outbreaks are usually of short duration, providing but a brief opportunity for trials to be launched, and have too few cases to allow for full enrollment during a single outbreak, so clinical trials will necessarily need to span multiple outbreaks which may occur in a number of at-risk countries. Preparing for this will require agreed-upon common protocols for trials intended to bridge multiple outbreaks across all at-risk countries. A multi-national research consortium including, and led by, at-risk countries would be an ideal mechanism to negotiate agreement on protocol design and coordinate preparation. Discussion participants recommended a follow-up meeting be held in Africa with national public health and research agencies from at-risk countries to establish such a consortium. |
Late remdesivir treatment initiation partially protects African green monkeys from lethal Nipah virus infection
de Wit E , Williamson BN , Feldmann F , Goldin K , Lo MK , Okumura A , Lovaglio J , Bunyan E , Porter DP , Cihlar T , Saturday G , Spiropoulou CF , Feldmann H . Antiviral Res 2023 216 105658 Remdesivir is a nucleotide prodrug with preclinical efficacy against lethal Nipah virus infection in African green monkeys when administered 1 day post inoculation (dpi) (Lo et al., 2019). Here, we determined whether remdesivir treatment was still effective when treatment administration initiation was delayed until 3 dpi. Three groups of six African green monkeys were inoculated with a lethal dose of Nipah virus, genotype Bangladesh. On 3 dpi, one group received a loading dose of 10 mg/kg remdesivir followed by daily dosing with 5 mg/kg for 11 days, one group received 10 mg/kg on 12 consecutive days, and the remaining group received an equivalent volume of vehicle solution. Remdesivir treatment initiation on 3 dpi provided partial protection from severe Nipah virus disease that was dose dependent, with 67% of animals in the high dose group surviving the challenge. However, remdesivir treatment did not prevent clinical disease, and surviving animals showed histologic lesions in the brain. Thus, early administration seems critical for effective remdesivir treatment during Nipah virus infection. |
Pathogenicity of Lloviu and Bombali viruses in IFNAR-/- mice
Fletcher P , Feldmann F , Takada A , Crossland NA , Hume AJ , Albariño C , Kemenesi G , Feldmann H , Mühlberger E , Marzi A . J Infect Dis 2023 228 S548-S553 Type I interferon receptor knockout (IFNAR-/-) mice are not able to generate a complete innate immune response, therefore, these mice are often considered to assess the pathogenicity of emerging viruses. We sought to assess the pathogenicity of emerging wildtype filovirus infections in IFNAR-/- mice since filovirus models using immunocompetent mice require a mouse-adapted viral strain. We infected IFNAR-/- mice with a low or high dose of Lloviu virus (LLOV) or Bombali virus (BOMV) by the intranasal (i.n.) or intraperitoneal (i.p.) route and compared virus loads at early and late timepoints after infection. No signs of disease and no viral RNA were detected after i.n. infection regardless of LLOV dose. In contrast, i.p. infections resulted in increased viral loads in the high-dose LLOV and BOMV groups at the early timepoint. The low-dose LLOV and BOMV groups achieved higher viral loads at the late timepoint. However, there was 100% survival in all groups and no signs of disease. In conclusion, our results indicate a limited value of the IFNAR-/- mouse model for investigation of the pathogenicity of LLOV and BOMV. |
Epidemiologic Investigation of Two Welder's Anthrax Cases Caused by Bacillus Cereus Group Bacteria: Occupational Link Established by Environmental Detection.
Dawson P , Salzer JS , Schrodt CA , Feldmann K , Kolton CB , Gee JE , Marston CK , Gulvik CA , Elrod MG , Villarma A , Traxler RM , Negrón ME , Hendricks KA , Moulton-Meissner H , Rose LJ , Byers P , Taylor K , Ware D , Balsamo GA , Sokol T , Barrett B , Payne E , Zaheer S , Jung GO , Long S , Quijano R , LeBouf L , O'Sullivan B , Swaney E , Antonini JM , Perio MA , Weiner Z , Bower WA , Hoffmaster AR . Pathogens 2022 11 (8) Abstract Bacillus cereus group bacteria containing the anthrax toxin genes can cause fatal anthrax pneumonia in welders. Two welder's anthrax cases identified in 2020 were investigated to determine the source of each patient's exposure. Environmental sampling was performed at locations where each patient had recent exposure to soil and dust. Samples were tested for the anthrax toxin genes by real-time PCR, and culture was performed on positive samples to identify whether any environmental isolates matched the patient's clinical isolate. A total of 185 environmental samples were collected in investigation A for patient A and 108 samples in investigation B for patient B. All samples from investigation B were real-time PCR-negative, but 14 (8%) samples from investigation A were positive, including 10 from patient A's worksite and 4 from his work-related clothing and gear. An isolate genetically matching the one recovered from patient A was successfully cultured from a worksite soil sample. All welder's anthrax cases should be investigated to determine the source of exposure, which may be linked to their worksite. Welding and metalworking employers should consider conducting a workplace hazard assessment and implementing controls to reduce the risk of occupationally associated illnesses including welder's anthrax. |
Welders anthrax: A review of an occupational disease
de Perio MA , Hendricks KA , Dowell CH , Bower WA , Burton NC , Dawson P , Schrodt CA , Salzer JS , Marston CK , Feldmann K , Hoffmaster AR , Antonini JM . Pathogens 2022 11 (4) Since 1997, nine cases of severe pneumonia, caused by species within the B. cereus group and with a presentation similar to that of inhalation anthrax, were reported in seemingly immunocompetent metalworkers, with most being welders. In seven of the cases, isolates were found to harbor a plasmid similar to the B. anthracis pXO1 that encodes anthrax toxins. In this paper, we review the literature on the B. cereus group spp. pneumonia among welders and other metalworkers, which we term welder’s anthrax. We describe the epidemiology, including more information on two cases of welder’s anthrax in 2020. We also describe the health risks associated with welding, potential mechanisms of infection and pathological damage, prevention measures according to the hierarchy of controls, and clinical and public health considerations. Considering occupational risk factors and controlling exposure to welding fumes and gases among workers, according to the hierarchy of controls, should help prevent disease transmission in the workplace. © 2022 by the authors. Licensee MDPI, Basel, Switzerland. |
Notes from the Field: Fatal Anthrax Pneumonia in Welders and Other Metalworkers Caused by Bacillus cereus Group Bacteria Containing Anthrax Toxin Genes - U.S. Gulf Coast States, 1994-2020.
Dawson P , Schrodt CA , Feldmann K , Traxler RM , Gee JE , Kolton CB , Marston CK , Gulvik CA , Antonini JM , Negrón ME , McQuiston JR , Hendricks K , Weiner Z , Balsamo GA , Sokol T , Byers P , Taylor K , Zaheer S , Long S , O'Sullivan B , de Perio MA , Hoffmaster AR , Salzer JS , Bower WA . MMWR Morb Mortal Wkly Rep 2021 70 (41) 1453-1454 In 2020, CDC confirmed two cases of pneumonia (one fatal) in welders caused by rare Bacillus cereus group bacteria containing anthrax toxin genes typically associated with Bacillus anthracis. B. cereus group bacteria are gram-positive facultative anaerobes, often toxin-producing, that are ubiquitous in the environment and reside naturally in soil and dust (1). B. cereus can also be found in food, and although infection typically causes illnesses characterized by diarrhea or vomiting, B. cereus can have other clinical manifestations (e.g., pulmonary, ocular, or cutaneous). Among seven persons in the United States reported to be infected with B. cereus group bacteria containing anthrax toxin genes resulting in pneumonia since 1994, five patients died and two had critical illness with prolonged hospitalization and recovery (2–5). All persons with pneumonia were welders or other metalworkers who had worked in Louisiana or Texas (Table). In addition to the seven pneumonia cases, a cutaneous infection with B. cereus group bacteria containing anthrax toxin genes has been reported in a patient with an anthrax eschar in Florida.† |
Remdesivir (GS-5734) protects African green monkeys from Nipah virus challenge
Lo MK , Feldmann F , Gary JM , Jordan R , Bannister R , Cronin J , Patel NR , Klena JD , Nichol ST , Cihlar T , Zaki SR , Feldmann H , Spiropoulou CF , de Wit E . Sci Transl Med 2019 11 (494) Nipah virus is an emerging pathogen in the Paramyxoviridae family. Upon transmission of Nipah virus from its natural reservoir, Pteropus spp. fruit bats, to humans, it causes respiratory and neurological disease with a case-fatality rate about 70%. Human-to-human transmission has been observed during Nipah virus outbreaks in Bangladesh and India. A therapeutic treatment for Nipah virus disease is urgently needed. Here, we tested the efficacy of remdesivir (GS-5734), a broad-acting antiviral nucleotide prodrug, against Nipah virus Bangladesh genotype in African green monkeys. Animals were inoculated with a lethal dose of Nipah virus, and a once-daily intravenous remdesivir treatment was initiated 24 hours later and continued for 12 days. Mild respiratory signs were observed in two of four treated animals, whereas all control animals developed severe respiratory disease signs. In contrast to control animals, which all succumbed to the infection, all remsdesivir-treated animals survived the lethal challenge, indicating that remdesivir represents a promising antiviral treatment for Nipah virus infection. |
A cynomolgus macaque model for Crimean-Congo haemorrhagic fever
Haddock E , Feldmann F , Hawman DW , Zivcec M , Hanley PW , Saturday G , Scott DP , Thomas T , Korva M , Avsic-Zupanc T , Safronetz D , Feldmann H . Nat Microbiol 2018 3 (5) 556-562 Crimean-Congo haemorrhagic fever (CCHF) is the most medically significant tick-borne disease, being widespread in the Middle East, Asia, Africa and parts of Europe (1) . Increasing case numbers, westerly movement and broadly ranging case fatality rates substantiate the concern of CCHF as a public health threat. Ixodid ticks of the genus Hyalomma are the vector for CCHF virus (CCHFV), an arbovirus in the genus Orthonairovirus of the family Nairoviridae. CCHFV naturally infects numerous wild and domestic animals via tick bite without causing obvious disease(2,3). Severe disease occurs only in humans and transmission usually happens through tick bite or contact with infected animals or humans. The only CCHF disease model is a subset of immunocompromised mice(4-6). Here, we show that following CCHFV infection, cynomolgus macaques exhibited hallmark signs of human CCHF with remarkably similar viral dissemination, organ pathology and disease progression. Histopathology showed infection of hepatocytes, endothelial cells and monocytes and fatal outcome seemed associated with endothelial dysfunction manifesting in a clinical shock syndrome with coagulopathy. This non-human primate model will be an invaluable asset for CCHFV countermeasures development. |
Assessing occupational erionite and respirable crystalline silica exposure among outdoor workers in Wyoming, South Dakota, and Montana
Beaucham C , King B , Feldmann K , Harper M , Dozier A . J Occup Environ Hyg 2018 15 (6) 1-33 Erionite is a naturally occurring fibrous mineral found in many parts of the world, including the western United States. Inhalational exposure to erionite fibers in some localities is associated with health effects similar to those caused by asbestos exposure, including malignant mesothelioma. Therefore, there is concern regarding occupational exposures in the western United States. Currently there are no standard sampling and analytical methods for airborne erionite fibers, as well as no established occupational exposure limits. Due to the potential adverse health effects, characterizing and minimizing exposures is prudent. Crystalline silica also occurs naturally in areas where erionite is found, principally as the mineral quartz. Work activities involving rocks containing quartz and soils derived from those rocks can lead to exposure to respirable crystalline silica (RCS). The typically dry and dusty environment of the western United States can increase the likelihood of exposures to aerosolized rocks and soils, but inhalation exposure is also possible in more humid conditions. In this case study, we describe several outdoor occupational environments with potential exposures to erionite and RCS. We describe our method for evaluating those exposures and demonstrate: (1) the occurrence of occupational exposures to airborne erionite and RCS, (2) that the chemical make-up of the erionite mineral can be determined, and (3) that effective dust control practices are needed to reduce employee exposures to these minerals. |
Severity of disease in humanized mice infected with Ebola virus or reston virus is associated with magnitude of early viral replication in liver
Spengler JR , Saturday G , Lavender KJ , Martellaro C , Keck JG , Nichol ST , Spiropoulou CF , Feldmann H , Prescott J . J Infect Dis 2017 217 (1) 58-63 Both Ebola virus (EBOV) and Reston virus (RESTV) cause disease in non-human primates, yet only EBOV causes disease in humans. To investigate differences in viral pathogenicity, humanized mice (hu-NSG-SGM3) were inoculated with EBOV or RESTV. Consistent with differences in disease in human infection, pronounced weight loss and markers of hepatic damage and disease were observed exclusively in EBOV-infected mice. These abnormalities were associated with significantly higher EBOV replication in the liver but not in the spleen, suggesting that in this model, efficiency of viral replication in select tissues early in infection may contribute to differences in viral pathogenicity. |
The pathogenesis of Ebola virus disease
Baseler L , Chertow DS , Johnson KM , Feldmann H , Morens DM . Annu Rev Pathol 2017 12 387-418 For almost 50 years, ebolaviruses and related filoviruses have been repeatedly reemerging across the vast equatorial belt of the African continent to cause epidemics of highly fatal hemorrhagic fever. The 2013-2015 West African epidemic, by far the most geographically extensive, most fatal, and longest lasting epidemic in Ebola's history, presented an enormous international public health challenge, but it also provided insights into Ebola's pathogenesis and natural history, clinical expression, treatment, prevention, and control. Growing understanding of ebolavirus pathogenetic mechanisms and important new clinical observations of the disease course provide fresh clues about prevention and treatment approaches. Although viral cytopathology and immune-mediated cell damage in ebolavirus disease often result in severe compromise of multiple organs, tissue repair and organ function recovery can be expected if patients receive supportive care with fluids and electrolytes; maintenance of oxygenation and tissue perfusion; and respiratory, renal, and cardiovascular support. Major challenges for managing future Ebola epidemics include establishment of early and aggressive epidemic control and earlier and better patient care and treatment in remote, resource-poor areas where Ebola typically reemerges. In addition, it will be important to further develop Ebola vaccines and to adopt policies for their use in epidemic and pre-epidemic situations. |
Human immune system mouse models of Ebola virus infection
Spengler JR , Prescott J , Feldmann H , Spiropoulou CF . Curr Opin Virol 2017 25 90-96 Human immune system (HIS) mice, immunodeficient mice engrafted with human cells (with or without donor-matched tissue), offer a unique opportunity to study pathogens that cause disease predominantly or exclusively in humans. Several HIS mouse models have recently been used to study Ebola virus (EBOV) infection and disease. The results of these studies are encouraging and support further development and use of these models in Ebola research. HIS mice provide a small animal model to study EBOV isolates, investigate early viral interactions with human immune cells, screen vaccines and therapeutics that modulate the immune system, and investigate sequelae in survivors. Here we review existing models, discuss their use in pathogenesis studies and therapeutic screening, and highlight considerations for study design and analysis. Finally, we point out caveats to current models, and recommend future efforts for modeling EBOV infection in HIS mice. |
Ebola Virus Replication and Disease Without Immunopathology in Mice Expressing Transgenes to Support Human Myeloid and Lymphoid Cell Engraftment.
Spengler JR , Lavender KJ , Martellaro C , Carmody A , Kurth A , Keck JG , Saturday G , Scott DP , Nichol ST , Hasenkrug KJ , Spiropoulou CF , Feldmann H , Prescott J . J Infect Dis 2016 214 S308-S318 The study of Ebola virus (EBOV) pathogenesis in vivo has been limited to nonhuman primate models or use of an adapted virus to cause disease in rodent models. Herein we describe wild-type EBOV (Makona variant) infection of mice engrafted with human hematopoietic CD34+ stem cells (Hu-NSG-SGM3 mice; hereafter referred to as SGM3 HuMice). SGM3 HuMice support increased development of myeloid immune cells, which are primary EBOV targets. In SGM3 HuMice, EBOV replicated to high levels, and disease was observed following either intraperitoneal or intramuscular inoculation. Despite the high levels of viral antigen and inflammatory cell infiltration in the liver, the characteristic histopathology of Ebola virus disease was not observed, and this absence of severe immunopathology may have contributed to the recovery and survival of some of the animals. Future investigations into the underlying mechanisms of the atypical disease presentation in SGM3 HuMice will provide additional insights into the immunopathogenesis of severe EBOV disease. |
Ebola virus is unlikely to become endemic in West Africa
Sprecher A , Feldmann H , Hensley LE , Kobinger G , Nichol ST , Strong J , Van Herp M . Nat Microbiol 2016 1 (3) 16007 Concern over Ebola becoming endemic in West Africa has appeared in the medical and lay media. Routes of transmission, rates of viral evolution, suitability of humans as hosts and rarity of spillover events make this very unlikely. Without evidence that endemic Ebola is likely, ending epidemics should remain the focus. |
Plasmodium Parasitemia Associated With Increased Survival in Ebola Virus-Infected Patients.
Rosenke K , Adjemian J , Munster VJ , Marzi A , Falzarano D , Onyango CO , Ochieng M , Juma B , Fischer RJ , Prescott JB , Safronetz D , Omballa V , Owuor C , Hoenen T , Groseth A , Martellaro C , van Doremalen N , Zemtsova G , Self J , Bushmaker T , McNally K , Rowe T , Emery SL , Feldmann F , Williamson BN , Best SM , Nyenswah TG , Grolla A , Strong JE , Kobinger G , Bolay FK , Zoon KC , Stassijns J , Giuliani R , de Smet M , Nichol ST , Fields B , Sprecher A , Massaquoi M , Feldmann H , de Wit E . Clin Infect Dis 2016 63 (8) 1026-33 BACKGROUND: The ongoing Ebola outbreak in West Africa has resulted in 28 646 suspected, probable, and confirmed Ebola virus infections. Nevertheless, malaria remains a large public health burden in the region affected by the outbreak. A joint Centers for Disease Control and Prevention/National Institutes of Health diagnostic laboratory was established in Monrovia, Liberia, in August 2014, to provide laboratory diagnostics for Ebola virus. METHODS: All blood samples from suspected Ebola virus-infected patients admitted to the Medecins Sans Frontieres ELWA3 Ebola treatment unit in Monrovia were tested by quantitative real-time polymerase chain reaction for the presence of Ebola virus and Plasmodium species RNA. Clinical outcome in laboratory-confirmed Ebola virus-infected patients was analyzed as a function of age, sex, Ebola viremia, and Plasmodium species parasitemia. RESULTS: The case fatality rate of 1182 patients with laboratory-confirmed Ebola virus infections was 52%. The probability of surviving decreased with increasing age and decreased with increasing Ebola viral load. Ebola virus-infected patients were 20% more likely to survive when Plasmodium species parasitemia was detected, even after controlling for Ebola viral load and age; those with the highest levels of parasitemia had a survival rate of 83%. This effect was independent of treatment with antimalarials, as this was provided to all patients. Moreover, treatment with antimalarials did not affect survival in the Ebola virus mouse model. CONCLUSIONS: Plasmodium species parasitemia is associated with an increase in the probability of surviving Ebola virus infection. More research is needed to understand the molecular mechanism underlying this remarkable phenomenon and translate it into treatment options for Ebola virus infection. |
Ebola laboratory response at the Eternal Love Winning Africa Campus, Monrovia, Liberia, 2014-2015
de Wit E , Rosenke K , Fischer RJ , Marzi A , Prescott J , Bushmaker T , van Doremalen N , Emery SL , Falzarano D , Feldmann F , Groseth A , Hoenen T , Juma B , McNally KL , Ochieng M , Omballa V , Onyango CO , Owuor C , Rowe T , Safronetz D , Self J , Williamson BN , Zemtsova G , Grolla A , Kobinger G , Rayfield M , Stroher U , Strong JE , Best SM , Ebihara H , Zoon KC , Nichol ST , Nyenswah TG , Bolay FK , Massaquoi M , Feldmann H , Fields B . J Infect Dis 2016 214 S169-S176 West Africa experienced the first epidemic of Ebola virus infection, with by far the greatest number of cases in Guinea, Sierra Leone, and Liberia. The unprecedented epidemic triggered an unparalleled response, including the deployment of multiple Ebola treatment units and mobile/field diagnostic laboratories. The National Institute of Allergy and Infectious Diseases and the Centers for Disease Control and Prevention deployed a joint laboratory to Monrovia, Liberia, in August 2014 to support the newly founded Ebola treatment unit at the Eternal Love Winning Africa (ELWA) campus. The laboratory operated initially out of a tent structure but quickly moved into a fixed-wall building owing to severe weather conditions, the need for increased security, and the high sample volume. Until May 2015, when the laboratory closed, the site handled close to 6000 clinical specimens for Ebola virus diagnosis and supported the medical staff in case patient management. Laboratory operation and safety, as well as Ebola virus diagnostic assays, are described and discussed; in addition, lessons learned for future deployments are reviewed. |
The merits of malaria diagnostics during an Ebola virus disease outbreak
de Wit E , Falzarano D , Onyango C , Rosenke K , Marzi A , Ochieng M , Juma B , Fischer RJ , Prescott JB , Safronetz D , Omballa V , Owuor C , Hoenen T , Groseth A , van Doremalen N , Zemtsova G , Self J , Bushmaker T , McNally K , Rowe T , Emery SL , Feldmann F , Williamson B , Nyenswah TG , Grolla A , Strong JE , Kobinger G , Stroeher U , Rayfield M , Bolay FK , Zoon KC , Stassijns J , Tampellini L , de Smet M , Nichol ST , Fields B , Sprecher A , Feldmann H , Massaquoi M , Munster VJ . Emerg Infect Dis 2016 22 (2) 323-6 Malaria is a major public health concern in the countries affected by the Ebola virus disease epidemic in West Africa. We determined the feasibility of using molecular malaria diagnostics during an Ebola virus disease outbreak and report the incidence of Plasmodium spp. parasitemia in persons with suspected Ebola virus infection. |
Nanopore Sequencing as a Rapidly Deployable Ebola Outbreak Tool.
Hoenen T , Groseth A , Rosenke K , Fischer RJ , Hoenen A , Judson SD , Martellaro C , Falzarano D , Marzi A , Squires RB , Wollenberg KR , de Wit E , Prescott J , Safronetz D , van Doremalen N , Bushmaker T , Feldmann F , McNally K , Bolay FK , Fields B , Sealy T , Rayfield M , Nichol ST , Zoon KC , Massaquoi M , Munster VJ , Feldmann H . Emerg Infect Dis 2016 22 (2) 331-4 Rapid sequencing of RNA/DNA from pathogen samples obtained during disease outbreaks provides critical scientific and public health information. However, challenges exist for exporting samples to laboratories or establishing conventional sequencers in remote outbreak regions. We successfully used a novel, pocket-sized nanopore sequencer at a field diagnostic laboratory in Liberia during the current Ebola virus outbreak. |
Personal protective equipment for filovirus epidemics: a call for better evidence
Sprecher AG , Caluwaerts A , Draper M , Feldmann H , Frey CP , Funk RH , Kobinger G , Le Duc JW , Spiropoulou C , Williams WJ . J Infect Dis 2015 212 Suppl 2 S98-S100 Personal protective equipment (PPE) is an important part of worker protection during filovirus outbreaks. The need to protect against a highly virulent fluid-borne pathogen in the tropical environment imposes a heat stress on the wearer that is itself a safety risk. No evidence supports the choice of PPE employed in recent outbreaks, and standard testing procedures employed by the protective garment industry do not well simulate filovirus exposure. Further research is needed to determine the appropriate PPE for filoviruses and the heat stress that it imposes. |
Emergency postexposure vaccination with vesicular stomatitis virus-vectored Ebola vaccine after needlestick.
Lai L , Davey R , Beck A , Xu Y , Suffredini AF , Palmore T , Kabbani S , Rogers S , Kobinger G , Alimonti J , Link CJ Jr , Rubinson L , Stroher U , Wolcott M , Dorman W , Uyeki TM , Feldmann H , Lane HC , Mulligan MJ . JAMA 2015 313 (12) 1249-55 IMPORTANCE: Safe and effective vaccines and drugs are needed for the prevention and treatment of Ebola virus disease, including following a potentially high-risk exposure such as a needlestick. OBJECTIVE: To assess response to postexposure vaccination in a health care worker who was exposed to the Ebola virus. DESIGN AND SETTING: Case report of a physician who experienced a needlestick while working in an Ebola treatment unit in Sierra Leone on September 26, 2014. Medical evacuation to the United States was rapidly initiated. Given the concern about potentially lethal Ebola virus disease, the patient was offered, and provided his consent for, postexposure vaccination with an experimental vaccine available through an emergency Investigational New Drug application. He was vaccinated on September 28, 2014. INTERVENTIONS: The vaccine used was VSVDeltaG-ZEBOV, a replicating, attenuated, recombinant vesicular stomatitis virus (serotype Indiana) whose surface glycoprotein gene was replaced by the Zaire Ebola virus glycoprotein gene. This vaccine has entered a clinical trial for the prevention of Ebola in West Africa. RESULTS: The vaccine was administered 43 hours after the needlestick occurred. Fever and moderate to severe symptoms developed 12 hours after vaccination and diminished over 3 to 4 days. The real-time reverse transcription polymerase chain reaction results were transiently positive for vesicular stomatitis virus nucleoprotein gene and Ebola virus glycoprotein gene (both included in the vaccine) but consistently negative for Ebola virus nucleoprotein gene (not in the vaccine). Early postvaccination cytokine secretion and T lymphocyte and plasmablast activation were detected. Subsequently, Ebola virus glycoprotein-specific antibodies and T cells became detectable, but antibodies against Ebola viral matrix protein 40 (not in the vaccine) were not detected. CONCLUSIONS AND RELEVANCE: It is unknown if VSVDeltaG-ZEBOV is safe or effective for postexposure vaccination in humans who have experienced a high-risk occupational exposure to the Ebola virus, such as a needlestick. In this patient, postexposure vaccination with VSVDeltaG-ZEBOV induced a self-limited febrile syndrome that was associated with transient detection of the recombinant vesicular stomatitis vaccine virus in blood. Strong innate and Ebola-specific adaptive immune responses were detected after vaccination. The clinical syndrome and laboratory evidence were consistent with vaccination response, and no evidence of Ebola virus infection was detected. |
Transmission studies resume for avian flu
Fouchier RA , Garcia-Sastre A , Kawaoka Y , Barclay WS , Bouvier NM , Brown IH , Capua I , Chen H , Compans RW , Couch RB , Cox NJ , Doherty PC , Donis RO , Feldmann H , Guan Y , Katz JM , Kiselev OI , Klenk HD , Kobinger G , Liu J , Liu X , Lowen A , Mettenleiter TC , Osterhaus AD , Palese P , Peiris JS , Perez DR , Richt JA , Schultz-Cherry S , Steel J , Subbarao K , Swayne DE , Takimoto T , Tashiro M , Taubenberger JK , Thomas PG , Tripp RA , Tumpey TM , Webby RJ , Webster RG . Science 2013 339 (6119) 520-1 In January 2012, influenza virus researchers from around the world announced a voluntary pause of 60 days on any research involving highly pathogenic avian influenza H5N1 viruses leading to the generation of viruses that are more transmissible in mammals (1). We declared a pause to this important research to provide time to explain the public health benefits of this work, to describe the measures in place to minimize possible risks, and to enable organizations and governments around the world to review their policies (for example, on biosafety, biosecurity, oversight, and communication) regarding these experiments. | During the past year, the benefits of this important research have been explained clearly in publications (2-7) and meetings (8-10). Measures to mitigate possible risks of the work have been detailed (11-13). The World Health Organization has released recommendations on laboratory biosafety for those conducting this research (14), and relevant authorities in several countries have reviewed the biosafety, biosecurity, and funding conditions under which further research would be conducted on the laboratory-modified H5N1 viruses (10, 15-17). Thus, acknowledging that the aims of the voluntary moratorium have been met in some countries and are close to being met in others, we declare an end to the voluntary moratorium on avian flu transmission studies. |
Pause on avian flu transmission research
Fouchier RA , Garcia-Sastre A , Kawaoka Y , Barclay WS , Bouvier NM , Brown IH , Capua I , Chen H , Compans RW , Couch RB , Cox NJ , Doherty PC , Donis RO , Feldmann H , Guan Y , Katz J , Klenk HD , Kobinger G , Liu J , Liu X , Lowen A , Mettenleiter TC , Osterhaus AD , Palese P , Peiris JS , Perez DR , Richt JA , Schultz-Cherry S , Steel J , Subbarao K , Swayne DE , Takimoto T , Tashiro M , Taubenberger JK , Thomas PG , Tripp RA , Tumpey TM , Webby RJ , Webster RG . Science 2012 335 (6067) 400-1 THE CONTINUOUS THREAT OF AN INFLUENZA PANDEMIC REPRESENTS ONE OF THE BIGGEST CHALlenges in public health. Influenza pandemics are known to be caused by viruses that evolve from animal reservoirs, such as in birds and pigs, and can acquire genetic changes that increase their ability to transmit in humans. Pandemic preparedness plans have been implemented worldwide to mitigate the impact of influenza pandemics. A major obstacle in preventing influenza pandemics is that little is known regarding what makes an influenza virus transmissible in humans. As a consequence, the potential pandemic risk associated with the many different influenza viruses of animals cannot be assessed with any certainty. | Recent research breakthroughs identified specific determinants of transmission of H5N1 influenza viruses in ferrets. Responsible research on influenza virus transmission using different animal models is conducted by multiple laboratories in the world using the highest international standards of biosafety and biosecurity practices that effectively prevent the release of transmissible viruses from the laboratory. These standards are regulated and monitored closely by the relevant authorities. This statement is being made by the principal investigators of these laboratories. |
Potential impact of a 2-person security rule on BioSafety Level 4 laboratory workers
LeDuc JW , Anderson K , Bloom ME , Carrion R Jr , Feldmann H , Fitch JP , Geisbert JB , Geisbert TW , Holbrook MR , Jahrling PB , Ksiazek TG , Patterson J , Rollin PE . Emerg Infect Dis 2009 15 (7) e1 Directors of all major BioSafety Level 4 (BSL-4) laboratories in the United States met in 2008 to review the current status of biocontainment laboratory operations and to discuss the potential impact of a proposed 2-person security rule on maximum-containment laboratory operations. Special attention was paid to the value and risks that would result from a requirement that 2 persons be physically present in the laboratory at all times. A consensus emerged indicating that a video monitoring system represents a more efficient, economical standard; provides greater assurance that pathogens are properly manipulated; and offers an increased margin of employee safety and institutional security. The 2-person security rule (1 to work and 1 to observe) may decrease compliance with dual responsibilities of safety and security by placing undue pressure on the person being observed to quickly finish the work, and by placing the observer in the containment environment unnecessarily. |
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