ABSTRACT Optimal management of septic patients requires accurate assessment of both current sever... more ABSTRACT Optimal management of septic patients requires accurate assessment of both current severity status and prognosis. Since the 1990s, substantial advances have been made in the use of circulating biomarkers for such assessments. This summary of the session on “Biomarkers: can they really use guide our daily practice?” presented at the 2021 WEB-CONFERENCE OF THE EUROPEAN SHOCK SOCIETY, 6 November 2021. These biomarkers include ultrasensitive detection of bacteremia, circulating soluble urokina-type plasminogen activator receptor (suPAR), C-reactive protein (CRP) and ferritin and procalcitonin. In addition, the potential application of novel multiwavelength optical biosensor technology allows noninvasive monitoring of multiple metabolites that can be used to assess severity and prognosis in septic patients. The application these biomarkers and improved technologies provide the potential for improved personalized management of septic patients.
The progressive research on yellow fever and the subsequent emergence of the field of arbovirolog... more The progressive research on yellow fever and the subsequent emergence of the field of arbovirology in the 1950s gave rise to the continued development of a global arbovirus surveillance network with a specific focus on human pathogenic arboviruses of the tropical zone. Though unknown at the time, some of the arboviruses studies would emerge within the temperate zone decades later (e.g.: West Nile, Zika, Chikungunya). However, initial research by the surveillance network was heavily focused on the discovery, isolation, and characterization of numerous arbovirus species. Global arboviral surveillance has revealed a cryptic circulation of several arboviruses, mainly in wild cycles of the tropical forest. Although there are more than 500 registered arbovirus species, a mere one third has proved to be pathogenic to humans (CDC, 2015). Indeed, most known arboviruses did not initially demonstrate a pathogenicity to humans or other vertebrates, and were considered “orphans” (i.e. without known of vertebrate hosts). As a part of this global surveillance network, the Institut Pasteur International Network has endeavored to understand the role played by arboviruses in the etiology of febrile syndromes of unknown origin as one of its research missions. Here, we report how The Pasteur Institute of Bangui (Institut Pasteur Bangui, or IPB) in the Central African Republic (CAR) actively participated in this mission and conducted an arbovirus survey from 1973 to 1993 that led to the isolation of 297 virus strains from 409,877 mosquitoes belonging to 78 different species. Ultimately, 24 new virus species were identified among these isolated strains, including two new orphan arboviruses Bozo, Bouboui, and two other unidentified arboviruses (ArB 11266 as a flavivirus-like virus and ArD28542 as a bunyavirus-like virus).The findings of this important, unpublished data from this survey are discussed here and give historical context to the recent global emergence and spread of Zika virus out of Africa. During its long journey from Africa emergence, into Asia, Oceania, and most recently to the Americas, the Zika virus has shown some significant genetic changes to its potential for pathogenicity. The original data presented here suggests that a significant number of other viruses, circulating in a hidden or discrete wild cycle with vertebrate hosts yet to be identified, represent a constant and undetermined risk of emergence among a nonimmune human population with the possibility for similar natural genetic changes. Jean François Saluzzo1, Tom Vincent2, Jay Miller3, Francisco Veas4 and Jean-Paul Gonzalez5* 1Fab’entech, Lyon, France 2O’Neill Institute for National and Global Health Law, Georgetown University Law Center, Washington, DC, USA 3Department of Infectious Disease, Health Security Partners, Washington, DC, USA 4Laboratoire d’Immunophysiopathologie Moléculaire Comparée-UMRMinistère de la Défense3, Institute de Recherche pour le Développement, Montpellier, France 5Center of Excellence for Emerging and Zoonotic Animal Disease, Kansas State University, Manhattan, KS, USA Jean-Paul Gonzalez, et al., Annals of Infectious Disease and Epidemiology Remedy Publications LLC. 2017 | Volume 2 | Issue 3 | Article 1022 2 of infected individuals. Non-human pathogenic viruses, mainly arboviruses, are considered to be orphaned or insect-specific viruses (i.e. without a permissive vertebrate host) [2]. Ultimately, those arboviruses usually pass unnoticed until the moment they emerge in a non-immune population, which reveals hitherto unknown and subsequently unexpected clinical and epidemic patterns. Arbovirus diseases are animal diseases (some are zoonotic), with a sylvatic cycle involving mosquitoes and wild animals [3]. The circulation of these viruses in their sylvatic cycle depends on the frequency of renewal of non-immune monkey populations. Humans are contaminated by penetrating these niches, which are shared with apes. Infections are rare and mainly affect children living in low population densities. The paucity of roads and the subsequent limits on travel help the virus remain confined to an endemic area more or less circumscribed. Once introduced into a non-immune human population, however, as was the case for the chikungunya virus on the island of la Réunion, the spread can be explosive [4]. Among the virus families to which arboviruses belong, it is within the Flaviviridae family (63 virus species) that most of viral species with human pathogenic potential are found. They are often responsible for a broad spectrum of clinical presentations, ranging from sub-clinical infection to deadly hemorrhagic syndrome. Most commonly, infected patients present a benign flu-like infection. These ignored arboviruses with mostly asymptomatic or mildly symptomatic infections can emerge unexpectedly, with improved methods of dispersion. These emergences are complex and difficult to anticipate, as exemplified by recent and original events: West Nile…
IFA titers, a large number had considerably higher total-IFA titers. Further testing with additio... more IFA titers, a large number had considerably higher total-IFA titers. Further testing with additional anti-cat antibodies may elucidate the classes of antibodies and nature of infection in cat populations in which a large proportion exhibits such high titers in the total-IFA test. The authors thank Rimon G. Batshoun for technical advice regarding the IFA tests, Gerald IFA titers, a large number had consid rably higher Van Hoosier, Jr. and Jan Klaassen for review of the manuscript, and Araceli Contreras for editorial assistance. The study was supported in part by a grant from The Lebanese National Council for Scientific Research; the preparation of the manuscript was supported by grant RR01203 from the Division of Research Resources, National Institutes of Health.
Cellular and molecular biology (Noisy-le-Grand, France), 1994
Trichomoniasis is recognised as a major sexually transmitted disease (STD) in the world and may a... more Trichomoniasis is recognised as a major sexually transmitted disease (STD) in the world and may act as an acquired immunodeficiency syndromes (AIDS) co-factor by enhancing the transmission of human immunodeficiency virus (HIV). Diagnosis of Trichomonas vaginalis can be achieved by several methods, but sensitive detection means are still lacking. In this study a 2000-bp repeated DNA fragment of T. vaginalis was cloned. Part of a conserved region of this insert was sequenced, two primers (TVK3 and TVK4) were chosen and a highly sensitive detection by polymerase chain reaction (PCR) was then developed for T. vaginalis. All strains of T. vaginalis analysed with these primers gave the expected 350-bp fragment and a 450-bp additional fragment. Sequence analysis of these PCR amplification products revealed that the 450-bp fragment contained the 350-bp with a 100-bp insertion characterised by a TGG microsatellite. A second primer set, namely TVK3 and TVK7 (determined at the border of the in...
Several anti–severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) monoclonal antibodies (... more Several anti–severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) monoclonal antibodies (mAbs) have received emergency authorization for coronavirus disease 2019 (COVID-19) treatment. However, most of these mAbs are not active against the highly mutated Omicron SARS-CoV-2 subvariants. We have tested a polyclonal approach of equine anti-SARS-CoV-2 F(ab’)2 antibodies that achieved a high level of neutralizing potency against all SARS-CoV-2 variants of concern tested including Omicron BA.1, BA.2, BA.2.12 and BA.4/5. A repertoire of antibodies targeting conserved epitopes in different regions of the spike protein could plausibly account for this remarkable breadth of neutralization. These results warrant the clinical investigation of equine polyclonal F(ab’)2 antibodies as a novel therapeutic strategy against COVID-19.
Background Anakinra may represent an important therapy to improve the prognosis of COVID-19 patie... more Background Anakinra may represent an important therapy to improve the prognosis of COVID-19 patients. This meta-analysis using individual patient data was designed to assess the efficacy and safety of anakinra treatment in patients with COVID-19. Methods Based on a pre-specified protocol (PROSPERO: CRD42020221491), a systematic literature search was performed in MEDLINE (PubMed), Cochrane, medRxiv.org, bioRxiv.org and clinicaltrials.gov databases for trials in COVID-19 comparing administration of anakinra with standard-of-care and/or placebo. Individual patient data from eligible trials were requested. The primary endpoint was the mortality rate and the secondary endpoint was safety. Findings Literature search yielded 209 articles, of which 178 articles fulfilled screening criteria and were full-text assessed. Aggregate data on 1185 patients from 9 studies were analyzed and individual patient data on 895 patients from 6 studies were collected. Most studies used historical controls. ...
ABSTRACT Optimal management of septic patients requires accurate assessment of both current sever... more ABSTRACT Optimal management of septic patients requires accurate assessment of both current severity status and prognosis. Since the 1990s, substantial advances have been made in the use of circulating biomarkers for such assessments. This summary of the session on “Biomarkers: can they really use guide our daily practice?” presented at the 2021 WEB-CONFERENCE OF THE EUROPEAN SHOCK SOCIETY, 6 November 2021. These biomarkers include ultrasensitive detection of bacteremia, circulating soluble urokina-type plasminogen activator receptor (suPAR), C-reactive protein (CRP) and ferritin and procalcitonin. In addition, the potential application of novel multiwavelength optical biosensor technology allows noninvasive monitoring of multiple metabolites that can be used to assess severity and prognosis in septic patients. The application these biomarkers and improved technologies provide the potential for improved personalized management of septic patients.
The progressive research on yellow fever and the subsequent emergence of the field of arbovirolog... more The progressive research on yellow fever and the subsequent emergence of the field of arbovirology in the 1950s gave rise to the continued development of a global arbovirus surveillance network with a specific focus on human pathogenic arboviruses of the tropical zone. Though unknown at the time, some of the arboviruses studies would emerge within the temperate zone decades later (e.g.: West Nile, Zika, Chikungunya). However, initial research by the surveillance network was heavily focused on the discovery, isolation, and characterization of numerous arbovirus species. Global arboviral surveillance has revealed a cryptic circulation of several arboviruses, mainly in wild cycles of the tropical forest. Although there are more than 500 registered arbovirus species, a mere one third has proved to be pathogenic to humans (CDC, 2015). Indeed, most known arboviruses did not initially demonstrate a pathogenicity to humans or other vertebrates, and were considered “orphans” (i.e. without known of vertebrate hosts). As a part of this global surveillance network, the Institut Pasteur International Network has endeavored to understand the role played by arboviruses in the etiology of febrile syndromes of unknown origin as one of its research missions. Here, we report how The Pasteur Institute of Bangui (Institut Pasteur Bangui, or IPB) in the Central African Republic (CAR) actively participated in this mission and conducted an arbovirus survey from 1973 to 1993 that led to the isolation of 297 virus strains from 409,877 mosquitoes belonging to 78 different species. Ultimately, 24 new virus species were identified among these isolated strains, including two new orphan arboviruses Bozo, Bouboui, and two other unidentified arboviruses (ArB 11266 as a flavivirus-like virus and ArD28542 as a bunyavirus-like virus).The findings of this important, unpublished data from this survey are discussed here and give historical context to the recent global emergence and spread of Zika virus out of Africa. During its long journey from Africa emergence, into Asia, Oceania, and most recently to the Americas, the Zika virus has shown some significant genetic changes to its potential for pathogenicity. The original data presented here suggests that a significant number of other viruses, circulating in a hidden or discrete wild cycle with vertebrate hosts yet to be identified, represent a constant and undetermined risk of emergence among a nonimmune human population with the possibility for similar natural genetic changes. Jean François Saluzzo1, Tom Vincent2, Jay Miller3, Francisco Veas4 and Jean-Paul Gonzalez5* 1Fab’entech, Lyon, France 2O’Neill Institute for National and Global Health Law, Georgetown University Law Center, Washington, DC, USA 3Department of Infectious Disease, Health Security Partners, Washington, DC, USA 4Laboratoire d’Immunophysiopathologie Moléculaire Comparée-UMRMinistère de la Défense3, Institute de Recherche pour le Développement, Montpellier, France 5Center of Excellence for Emerging and Zoonotic Animal Disease, Kansas State University, Manhattan, KS, USA Jean-Paul Gonzalez, et al., Annals of Infectious Disease and Epidemiology Remedy Publications LLC. 2017 | Volume 2 | Issue 3 | Article 1022 2 of infected individuals. Non-human pathogenic viruses, mainly arboviruses, are considered to be orphaned or insect-specific viruses (i.e. without a permissive vertebrate host) [2]. Ultimately, those arboviruses usually pass unnoticed until the moment they emerge in a non-immune population, which reveals hitherto unknown and subsequently unexpected clinical and epidemic patterns. Arbovirus diseases are animal diseases (some are zoonotic), with a sylvatic cycle involving mosquitoes and wild animals [3]. The circulation of these viruses in their sylvatic cycle depends on the frequency of renewal of non-immune monkey populations. Humans are contaminated by penetrating these niches, which are shared with apes. Infections are rare and mainly affect children living in low population densities. The paucity of roads and the subsequent limits on travel help the virus remain confined to an endemic area more or less circumscribed. Once introduced into a non-immune human population, however, as was the case for the chikungunya virus on the island of la Réunion, the spread can be explosive [4]. Among the virus families to which arboviruses belong, it is within the Flaviviridae family (63 virus species) that most of viral species with human pathogenic potential are found. They are often responsible for a broad spectrum of clinical presentations, ranging from sub-clinical infection to deadly hemorrhagic syndrome. Most commonly, infected patients present a benign flu-like infection. These ignored arboviruses with mostly asymptomatic or mildly symptomatic infections can emerge unexpectedly, with improved methods of dispersion. These emergences are complex and difficult to anticipate, as exemplified by recent and original events: West Nile…
IFA titers, a large number had considerably higher total-IFA titers. Further testing with additio... more IFA titers, a large number had considerably higher total-IFA titers. Further testing with additional anti-cat antibodies may elucidate the classes of antibodies and nature of infection in cat populations in which a large proportion exhibits such high titers in the total-IFA test. The authors thank Rimon G. Batshoun for technical advice regarding the IFA tests, Gerald IFA titers, a large number had consid rably higher Van Hoosier, Jr. and Jan Klaassen for review of the manuscript, and Araceli Contreras for editorial assistance. The study was supported in part by a grant from The Lebanese National Council for Scientific Research; the preparation of the manuscript was supported by grant RR01203 from the Division of Research Resources, National Institutes of Health.
Cellular and molecular biology (Noisy-le-Grand, France), 1994
Trichomoniasis is recognised as a major sexually transmitted disease (STD) in the world and may a... more Trichomoniasis is recognised as a major sexually transmitted disease (STD) in the world and may act as an acquired immunodeficiency syndromes (AIDS) co-factor by enhancing the transmission of human immunodeficiency virus (HIV). Diagnosis of Trichomonas vaginalis can be achieved by several methods, but sensitive detection means are still lacking. In this study a 2000-bp repeated DNA fragment of T. vaginalis was cloned. Part of a conserved region of this insert was sequenced, two primers (TVK3 and TVK4) were chosen and a highly sensitive detection by polymerase chain reaction (PCR) was then developed for T. vaginalis. All strains of T. vaginalis analysed with these primers gave the expected 350-bp fragment and a 450-bp additional fragment. Sequence analysis of these PCR amplification products revealed that the 450-bp fragment contained the 350-bp with a 100-bp insertion characterised by a TGG microsatellite. A second primer set, namely TVK3 and TVK7 (determined at the border of the in...
Several anti–severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) monoclonal antibodies (... more Several anti–severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) monoclonal antibodies (mAbs) have received emergency authorization for coronavirus disease 2019 (COVID-19) treatment. However, most of these mAbs are not active against the highly mutated Omicron SARS-CoV-2 subvariants. We have tested a polyclonal approach of equine anti-SARS-CoV-2 F(ab’)2 antibodies that achieved a high level of neutralizing potency against all SARS-CoV-2 variants of concern tested including Omicron BA.1, BA.2, BA.2.12 and BA.4/5. A repertoire of antibodies targeting conserved epitopes in different regions of the spike protein could plausibly account for this remarkable breadth of neutralization. These results warrant the clinical investigation of equine polyclonal F(ab’)2 antibodies as a novel therapeutic strategy against COVID-19.
Background Anakinra may represent an important therapy to improve the prognosis of COVID-19 patie... more Background Anakinra may represent an important therapy to improve the prognosis of COVID-19 patients. This meta-analysis using individual patient data was designed to assess the efficacy and safety of anakinra treatment in patients with COVID-19. Methods Based on a pre-specified protocol (PROSPERO: CRD42020221491), a systematic literature search was performed in MEDLINE (PubMed), Cochrane, medRxiv.org, bioRxiv.org and clinicaltrials.gov databases for trials in COVID-19 comparing administration of anakinra with standard-of-care and/or placebo. Individual patient data from eligible trials were requested. The primary endpoint was the mortality rate and the secondary endpoint was safety. Findings Literature search yielded 209 articles, of which 178 articles fulfilled screening criteria and were full-text assessed. Aggregate data on 1185 patients from 9 studies were analyzed and individual patient data on 895 patients from 6 studies were collected. Most studies used historical controls. ...
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