The Experts below are selected from a list of 3165 Experts worldwide ranked by ideXlab platform
Lisa Oestereich - One of the best experts on this subject based on the ideXlab platform.
-
severe human Lassa Fever is characterized by nonspecific t cell activation and lymphocyte homing to inflamed tissues
Journal of Virology, 2020Co-Authors: Julia R Port, Lisa Oestereich, Elisa Pallasch, David M Wozniak, Beate Beckerziaja, Jonas Muller, Monika Rottstegge, Catherine Olal, Sergio Gomezmedina, Jennifer OyakhliomeAbstract:Lassa Fever (LF) is a zoonotic viral hemorrhagic Fever caused by Lassa virus (LASV), which is endemic to West African countries. Previous studies have suggested an important role for T-cell-mediated immunopathology in LF pathogenesis, but the mechanisms by which T cells influence disease severity and outcome are not well understood. Here, we present a multiparametric analysis of clinical immunology data collected during the 2017-2018 Lassa Fever outbreak in Nigeria. During the acute phase of LF, we observed robust activation of the polyclonal T-cell repertoire, which included LASV-specific and antigenically unrelated T cells. However, severe and fatal LF cases were characterized by poor LASV-specific effector T-cell responses. Severe LF was also characterized by the presence of circulating T cells with homing capacity to inflamed tissues, including the gut mucosa. These findings in LF patients were recapitulated in a mouse model of LASV infection, in which mucosal exposure resulted in remarkably high lethality compared to skin exposure. Taken together, our findings indicate that poor LASV-specific T-cell responses and activation of nonspecific T cells with homing capacity to inflamed tissues are associated with severe LF.IMPORTANCE Lassa Fever may cause severe disease in humans, in particular in areas of endemicity like Sierra Leone and Nigeria. Despite its public health importance, the pathophysiology of Lassa Fever in humans is poorly understood. Here, we present clinical immunology data obtained in the field during the 2018 Lassa Fever outbreak in Nigeria indicating that severe Lassa Fever is associated with activation of T cells antigenically unrelated to Lassa virus and poor Lassa virus-specific effector T-cell responses. Mechanistically, we show that these bystander T cells express defined tissue homing signatures that suggest their recruitment to inflamed tissues and a putative role of these T cells in immunopathology. These findings open a window of opportunity to consider T-cell targeting as a potential postexposure therapeutic strategy against severe Lassa Fever, a hypothesis that could be tested in relevant animal models, such as nonhuman primates.
-
severe human Lassa Fever is characterized by non specific t cell activation and lymphocyte homing to inflamed tissues
Journal of Virology, 2020Co-Authors: Julia R Port, Lisa Oestereich, Elisa Pallasch, David M Wozniak, Beate Beckerziaja, Jonas Muller, Monika Rottstegge, Catherine Olal, Sergio Gomezmedina, Jennifer OyakhliomeAbstract:Lassa Fever (LF) is a zoonotic viral hemorrhagic Fever caused by Lassa virus (LASV), which is endemic to West African countries. Previous studies have suggested an important role for T-cell-mediated immunopathology in LF pathogenesis, but the mechanisms by which T cells influence disease severity and outcome are not well understood. Here, we present a multiparametric analysis of clinical immunology data collected during the 2017-2018 Lassa Fever outbreak in Nigeria. During the acute phase of LF, we observed robust activation of the polyclonal T-cell repertoire, which included LASV-specific and antigenically unrelated T cells. However, severe and fatal LF cases were characterized by poor LASV-specific effector T-cell responses. Severe LF was also characterized by the presence of circulating T cells with homing capacity to inflamed tissues, including the gut mucosa. These findings in LF patients were recapitulated in a mouse model of LASV infection, in which mucosal exposure resulted in remarkably high lethality compared to skin exposure. Taken together, our findings indicate that poor LASV-specific T-cell responses and activation of nonspecific T cells with homing capacity to inflamed tissues are associated with severe LF.IMPORTANCE Lassa Fever may cause severe disease in humans, in particular in areas of endemicity like Sierra Leone and Nigeria. Despite its public health importance, the pathophysiology of Lassa Fever in humans is poorly understood. Here, we present clinical immunology data obtained in the field during the 2018 Lassa Fever outbreak in Nigeria indicating that severe Lassa Fever is associated with activation of T cells antigenically unrelated to Lassa virus and poor Lassa virus-specific effector T-cell responses. Mechanistically, we show that these bystander T cells express defined tissue homing signatures that suggest their recruitment to inflamed tissues and a putative role of these T cells in immunopathology. These findings open a window of opportunity to consider T-cell targeting as a potential postexposure therapeutic strategy against severe Lassa Fever, a hypothesis that could be tested in relevant animal models, such as nonhuman primates.
-
field evaluation of a pan Lassa rapid diagnostic test during the 2018 nigerian Lassa Fever outbreak
Scientific Reports, 2020Co-Authors: Matt L Boisen, Lisa Oestereich, Eghosa Uyigue, John Aiyepada, Katherine J Siddle, Diana K S Nelson, Duane J Bush, Megan M RowlandAbstract:Lassa virus (LASV) is the causative agent of Lassa Fever (LF), an often-fatal hemorrhagic disease. LF is endemic in Nigeria, Sierra Leone and other West African countries. Diagnosis of LASV infection is challenged by the genetic diversity of the virus, which is greatest in Nigeria. The ReLASV Pan-Lassa Antigen Rapid Test (Pan-Lassa RDT) is a point-of-care, in vitro diagnostic test that utilizes a mixture of polyclonal antibodies raised against recombinant nucleoproteins of representative strains from the three most prevalent LASV lineages (II, III and IV). We compared the performance of the Pan-LASV RDT to available quantitative PCR (qPCR) assays during the 2018 LF outbreak in Nigeria. For patients with acute LF (RDT positive, IgG/IgM negative) during initial screening, RDT performance was 83.3% sensitivity and 92.8% specificity when compared to composite results of two qPCR assays. 100% of samples that gave Ct values below 22 on both qPCR assays were positive on the Pan-Lassa RDT. There were significantly elevated case fatality rates and elevated liver transaminase levels in subjects whose samples were RDT positive compared to RDT negative.
-
Lassa Fever in Benin: description of the 2014 and 2016 epidemics and genetic characterization of a new Lassa virus
Emerging microbes & infections, 2020Co-Authors: Anges Yadouleton, Lisa Oestereich, Caroline Picard, Toni Rieger, Frederic Loko, Daniel Cadar, Emile Cossi Kouthon, Emmanuel Obolli Job, Honoré Bankolé, Fernand GbaguidiAbstract:We report two outbreaks of Lassa Fever that occurred in Benin in 2014 and 2016 with 20 confirmed cases and 50% (10/20) mortality. Benin was not previously considered to be an endemic country for Lassa Fever, resulting in a delay to diagnose the disease and its human transmission. Molecular investigations showed the viral genomes to be similar to that of the Togo strain, which is genetically very different from other known strains and confirms the existence of a new lineage. Endemic circulation of Lassa virus in a new territory and the genetic diversity thus confirm that this virus represents a growing threat for West African people. Given the divergence of the Benin strain from the prototypic Josiah Sierra Leone strain frequently used to generate vaccine candidates, the efficacy of vaccine candidates should also be demonstrated with this strain.
-
efficacy of favipiravir alone and in combination with ribavirin in a lethal immunocompetent mouse model of Lassa Fever
The Journal of Infectious Diseases, 2016Co-Authors: Lisa Oestereich, Toni Riege, Anja Ludtke, Paula Ruibal, Elisa Pallasch, Sabrina Ockhol, Susanne Krasema, Cesa MunozfontelaAbstract:Lassa Fever (LF) is a viral hemorrhagic Fever caused by Lassa virus (LASV), an arenavirus endemic in West Africa. Standard of care for LF is the nucleoside analogue ribavirin [1]. However, because of the small therapeutic window [1] and the fact that still one third of patients with LF die despite ribavirin treatment [2], there is a need for more-effective drug therapies against LF. A promising candidate is the broad-spectrum antiviral drug favipiravir (Toyama Chemical) [3], which is approved for emerging influenza virus in Japan. Besides influenza virus, favipiravir shows potent antiviral activity in vitro and in vivo against a wide range of negative-strand RNA viruses, including arenaviruses [3, 4]. We have tested the efficacy of favipiravir alone and in combination with ribavirin in a novel, chimeric mouse model, which is based on lethally irradiated type I interferon receptor knockout (Ifnar–/–) mice transplanted with wild-type bone marrow progenitor cells (termed “Ifnar–/–B6 mice”). Ifnar–/–B6 mice feature a fully functional immune system and are susceptible to wild-type LASV infection (Oestereich et al, unpublished data).
Abdulazeez Imam - One of the best experts on this subject based on the ideXlab platform.
-
fatal case of newborn Lassa Fever virus infection mimicking late onset neonatal sepsis a case report from northern nigeria
Infectious Diseases of Poverty, 2020Co-Authors: Taofik Oluwaseun Ogunkunle, Surajudeen Oyeleke Bello, Chinwe Immaculata Anderson, Rashida Musa, Rasaq Olaosebikan, Abdulazeez ImamAbstract:Lassa Fever is a zoonotic viral infection endemic to the West Africa countries. It is highly fatal during pregnancy and as such reports of neonatal onset Lassa Fever infections are rare in scientific literature. We report a fatal case of Lassa Fever in a 26-day-old neonate mimicking the diagnosis of late-onset neonatal sepsis. The patient is a 26-day-old neonate who was admitted with a day history of Fever, poor feeding, pre-auricular lymphadenopathy and sudden parental death. He was initially evaluated for late onset neonatal sepsis. He later developed abnormal bleeding and multiple convulsions while on admission, prompting the need to evaluate for Lassa Fever using reverse transcription polymerase chain reaction (RT-PCR). He died 31 h into admission and RT-PCR result was positive for Lassa Fever. Neonatal Lassa Fever infection is highly fatal and can mimic neonatal sepsis. High index of suspicion is needed particularly for atypical presentations of neonatal sepsis in Lassa Fever endemic areas.
Augustine Goba - One of the best experts on this subject based on the ideXlab platform.
-
Lassa Fever suspected case definition.
2019Co-Authors: Jeffrey G Shaffer, Augustine Goba, Mambu Momoh, John S. Schieffelin, Michael Gbakie, Foday Alhasan, Nicole B. Roberts, Jessica Randazzo, Troy D. Moon, Lansana KannehAbstract:Lassa Fever suspected case definition.
-
Lassa Fever serostatus results, Kenema Government Hospital, 2008–2016.
2019Co-Authors: Jeffrey G Shaffer, Augustine Goba, Mambu Momoh, John S. Schieffelin, Michael Gbakie, Foday Alhasan, Nicole B. Roberts, Jessica Randazzo, Troy D. Moon, Lansana KannehAbstract:Lassa Fever serostatus results, Kenema Government Hospital, 2008–2016.
-
Data classes and capture sources for Lassa Fever at Kenema Government Hospital.
2019Co-Authors: Jeffrey G Shaffer, Augustine Goba, Mambu Momoh, John S. Schieffelin, Michael Gbakie, Foday Alhasan, Nicole B. Roberts, Jessica Randazzo, Troy D. Moon, Lansana KannehAbstract:Data classes and capture sources for Lassa Fever at Kenema Government Hospital.
-
A medical records and data capture and management system for Lassa Fever in Sierra Leone: Approach, implementation, and challenges
2019Co-Authors: Jeffrey G Shaffer, Augustine Goba, Mambu Momoh, John S. Schieffelin, Michael Gbakie, Foday Alhasan, Nicole B. Roberts, Jessica Randazzo, Troy D. Moon, Lansana KannehAbstract:Situated in southeastern Sierra Leone, Kenema Government Hospital (KGH) maintains one of the world’s only Lassa Fever isolation wards and was a strategic Ebola virus disease (EVD) treatment facility during the 2014 EVD outbreak. Since 2006, the Viral Hemorrhagic Fever Consortium (VHFC) has carried out research activities at KGH, capturing clinical and laboratory data for suspected cases of Lassa Fever. Here we describe the approach, progress, and challenges in designing and maintaining a data capture and management system (DCMS) at KGH to assist infectious disease researchers in building and sustaining DCMS in low-resource environments. Results on screening patterns and case-fatality rates are provided to illustrate the context and scope of the DCMS covered in this study. A medical records system and DCMS was designed and implemented between 2010 and 2016 linking historical and prospective Lassa Fever data sources across KGH Lassa Fever units and its peripheral health units. Data were captured using a case report form (CRF) system, enzyme-linked immunosorbent assay (ELISA) plate readers, polymerase chain reaction (PCR) machines, blood chemistry analyzers, and data auditing procedures. Between 2008 and 2016, blood samples for 4,229 suspected Lassa Fever cases were screened at KGH, ranging from 219 samples in 2008 to a peak of 760 samples in 2011. Lassa Fever case-fatality rates before and following the Ebola outbreak were 65.5% (148/226) and 89.5% (17/19), respectively, suggesting that fewer, but more seriously ill subjects with Lassa Fever presented to KGH following the 2014 EVD outbreak (p = .040). DCMS challenges included weak specificity of the Lassa Fever suspected case definition, limited capture of patient survival outcome data, internet costs, lapses in internet connectivity, low bandwidth, equipment and software maintenance, lack of computer teaching laboratories, and workload fluctuations due to variable screening activity. DCMS are the backbone of international research efforts and additional literature is needed on the topic for establishing benchmarks and driving goal-based approaches for its advancement in developing countries.
-
District of residence for suspected Lassa Fever case screenings at Kenema Government Hospital, 2008–2016.
2019Co-Authors: Jeffrey G Shaffer, Augustine Goba, Mambu Momoh, John S. Schieffelin, Michael Gbakie, Foday Alhasan, Nicole B. Roberts, Jessica Randazzo, Troy D. Moon, Lansana KannehAbstract:District of residence was available for 44.1% (1,866/4,229) of the screened study subjects. Regions with the highest observed Lassa Fever screenings were the Districts of Kenema (n = 1,410), Bo (n = 204), and Kailahun (n = 120).
Taofik Oluwaseun Ogunkunle - One of the best experts on this subject based on the ideXlab platform.
-
fatal case of newborn Lassa Fever virus infection mimicking late onset neonatal sepsis a case report from northern nigeria
Infectious Diseases of Poverty, 2020Co-Authors: Taofik Oluwaseun Ogunkunle, Surajudeen Oyeleke Bello, Chinwe Immaculata Anderson, Rashida Musa, Rasaq Olaosebikan, Abdulazeez ImamAbstract:Lassa Fever is a zoonotic viral infection endemic to the West Africa countries. It is highly fatal during pregnancy and as such reports of neonatal onset Lassa Fever infections are rare in scientific literature. We report a fatal case of Lassa Fever in a 26-day-old neonate mimicking the diagnosis of late-onset neonatal sepsis. The patient is a 26-day-old neonate who was admitted with a day history of Fever, poor feeding, pre-auricular lymphadenopathy and sudden parental death. He was initially evaluated for late onset neonatal sepsis. He later developed abnormal bleeding and multiple convulsions while on admission, prompting the need to evaluate for Lassa Fever using reverse transcription polymerase chain reaction (RT-PCR). He died 31 h into admission and RT-PCR result was positive for Lassa Fever. Neonatal Lassa Fever infection is highly fatal and can mimic neonatal sepsis. High index of suspicion is needed particularly for atypical presentations of neonatal sepsis in Lassa Fever endemic areas.
Elisa Pallasch - One of the best experts on this subject based on the ideXlab platform.
-
severe human Lassa Fever is characterized by non specific t cell activation and lymphocyte homing to inflamed tissues
Journal of Virology, 2020Co-Authors: Julia R Port, Lisa Oestereich, Elisa Pallasch, David M Wozniak, Beate Beckerziaja, Jonas Muller, Monika Rottstegge, Catherine Olal, Sergio Gomezmedina, Jennifer OyakhliomeAbstract:Lassa Fever (LF) is a zoonotic viral hemorrhagic Fever caused by Lassa virus (LASV), which is endemic to West African countries. Previous studies have suggested an important role for T-cell-mediated immunopathology in LF pathogenesis, but the mechanisms by which T cells influence disease severity and outcome are not well understood. Here, we present a multiparametric analysis of clinical immunology data collected during the 2017-2018 Lassa Fever outbreak in Nigeria. During the acute phase of LF, we observed robust activation of the polyclonal T-cell repertoire, which included LASV-specific and antigenically unrelated T cells. However, severe and fatal LF cases were characterized by poor LASV-specific effector T-cell responses. Severe LF was also characterized by the presence of circulating T cells with homing capacity to inflamed tissues, including the gut mucosa. These findings in LF patients were recapitulated in a mouse model of LASV infection, in which mucosal exposure resulted in remarkably high lethality compared to skin exposure. Taken together, our findings indicate that poor LASV-specific T-cell responses and activation of nonspecific T cells with homing capacity to inflamed tissues are associated with severe LF.IMPORTANCE Lassa Fever may cause severe disease in humans, in particular in areas of endemicity like Sierra Leone and Nigeria. Despite its public health importance, the pathophysiology of Lassa Fever in humans is poorly understood. Here, we present clinical immunology data obtained in the field during the 2018 Lassa Fever outbreak in Nigeria indicating that severe Lassa Fever is associated with activation of T cells antigenically unrelated to Lassa virus and poor Lassa virus-specific effector T-cell responses. Mechanistically, we show that these bystander T cells express defined tissue homing signatures that suggest their recruitment to inflamed tissues and a putative role of these T cells in immunopathology. These findings open a window of opportunity to consider T-cell targeting as a potential postexposure therapeutic strategy against severe Lassa Fever, a hypothesis that could be tested in relevant animal models, such as nonhuman primates.
-
severe human Lassa Fever is characterized by nonspecific t cell activation and lymphocyte homing to inflamed tissues
Journal of Virology, 2020Co-Authors: Julia R Port, Lisa Oestereich, Elisa Pallasch, David M Wozniak, Beate Beckerziaja, Jonas Muller, Monika Rottstegge, Catherine Olal, Sergio Gomezmedina, Jennifer OyakhliomeAbstract:Lassa Fever (LF) is a zoonotic viral hemorrhagic Fever caused by Lassa virus (LASV), which is endemic to West African countries. Previous studies have suggested an important role for T-cell-mediated immunopathology in LF pathogenesis, but the mechanisms by which T cells influence disease severity and outcome are not well understood. Here, we present a multiparametric analysis of clinical immunology data collected during the 2017-2018 Lassa Fever outbreak in Nigeria. During the acute phase of LF, we observed robust activation of the polyclonal T-cell repertoire, which included LASV-specific and antigenically unrelated T cells. However, severe and fatal LF cases were characterized by poor LASV-specific effector T-cell responses. Severe LF was also characterized by the presence of circulating T cells with homing capacity to inflamed tissues, including the gut mucosa. These findings in LF patients were recapitulated in a mouse model of LASV infection, in which mucosal exposure resulted in remarkably high lethality compared to skin exposure. Taken together, our findings indicate that poor LASV-specific T-cell responses and activation of nonspecific T cells with homing capacity to inflamed tissues are associated with severe LF.IMPORTANCE Lassa Fever may cause severe disease in humans, in particular in areas of endemicity like Sierra Leone and Nigeria. Despite its public health importance, the pathophysiology of Lassa Fever in humans is poorly understood. Here, we present clinical immunology data obtained in the field during the 2018 Lassa Fever outbreak in Nigeria indicating that severe Lassa Fever is associated with activation of T cells antigenically unrelated to Lassa virus and poor Lassa virus-specific effector T-cell responses. Mechanistically, we show that these bystander T cells express defined tissue homing signatures that suggest their recruitment to inflamed tissues and a putative role of these T cells in immunopathology. These findings open a window of opportunity to consider T-cell targeting as a potential postexposure therapeutic strategy against severe Lassa Fever, a hypothesis that could be tested in relevant animal models, such as nonhuman primates.
-
efficacy of favipiravir alone and in combination with ribavirin in a lethal immunocompetent mouse model of Lassa Fever
The Journal of Infectious Diseases, 2016Co-Authors: Lisa Oestereich, Toni Riege, Anja Ludtke, Paula Ruibal, Elisa Pallasch, Sabrina Ockhol, Susanne Krasema, Cesa MunozfontelaAbstract:Lassa Fever (LF) is a viral hemorrhagic Fever caused by Lassa virus (LASV), an arenavirus endemic in West Africa. Standard of care for LF is the nucleoside analogue ribavirin [1]. However, because of the small therapeutic window [1] and the fact that still one third of patients with LF die despite ribavirin treatment [2], there is a need for more-effective drug therapies against LF. A promising candidate is the broad-spectrum antiviral drug favipiravir (Toyama Chemical) [3], which is approved for emerging influenza virus in Japan. Besides influenza virus, favipiravir shows potent antiviral activity in vitro and in vivo against a wide range of negative-strand RNA viruses, including arenaviruses [3, 4]. We have tested the efficacy of favipiravir alone and in combination with ribavirin in a novel, chimeric mouse model, which is based on lethally irradiated type I interferon receptor knockout (Ifnar–/–) mice transplanted with wild-type bone marrow progenitor cells (termed “Ifnar–/–B6 mice”). Ifnar–/–B6 mice feature a fully functional immune system and are susceptible to wild-type LASV infection (Oestereich et al, unpublished data).
-
efficacy of favipiravir alone and in combination with ribavirin in a lethal immunocompetent mouse model of Lassa Fever
The Journal of Infectious Diseases, 2016Co-Authors: Lisa Oestereich, Anja Ludtke, Paula Ruibal, Elisa Pallasch, Cesa Munozfontela, Toni Rieger, Stephanie Wurr, Sabrina Bockholt, Susanne Krasemann, Stephan GuntherAbstract:We studied the therapeutic potential of favipiravir (T-705) for Lassa Fever, both alone and in combination with ribavirin. Favipiravir suppressed Lassa virus replication in cell culture by 5 log10 units. In a novel lethal mouse model, it lowered the viremia level and the virus load in organs and normalized levels of cell-damage markers. Treatment with 300 mg/kg per day, commenced 4 days after infection, when the viremia level had reached 4 log10 virus particles/mL, rescued 100% of Lassa virus-infected mice. We found a synergistic interaction between favipiravir and ribavirin in vitro and an increased survival rate and extended survival time when combining suboptimal doses in vivo.
