The Experts below are selected from a list of 13218 Experts worldwide ranked by ideXlab platform
Adrian V S Hill - One of the best experts on this subject based on the ideXlab platform.
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thick blood film examination for plasmodium falciparum Malaria has reduced sensitivity and underestimates parasite density
Malaria Journal, 2006Co-Authors: Philip Bejon, Laura Andrews, Angela Huntcooke, Frances Sanderson, Sarah C Gilbert, Adrian V S HillAbstract:Background: Thick blood films are routinely used to diagnose Plasmodium falciparum Malaria. Here, they were used to diagnose volunteers exposed to Experimental Malaria challenge. Methods: The frequency with which blood films were positive at given parasite densities measured by PCR were analysed. The poisson distribution was used to calculate the theoretical likelihood of diagnosis. Further in vitro studies used serial dilutions to prepare thick films from Malaria cultures at known parasitaemia. Results: Even in expert hands, thick blood films were considerably less sensitive than might have been expected from the parasite numbers measured by quantitative PCR. In vitro work showed that thick films prepared from Malaria cultures at known parasitaemia consistently underestimated parasite densities. Conclusion: It appears large numbers of parasites are lost during staining. This limits their sensitivity, and leads to erroneous estimates of parasite density.
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thick blood film examination for plasmodium falciparum Malaria has reduced sensitivity and underestimates parasite density
Malaria Journal, 2006Co-Authors: Philip Bejon, Laura Andrews, Angela Huntcooke, Frances Sanderson, Sarah C Gilbert, Adrian V S HillAbstract:Background Thick blood films are routinely used to diagnose Plasmodium falciparum Malaria. Here, they were used to diagnose volunteers exposed to Experimental Malaria challenge.
Philip Bejon - One of the best experts on this subject based on the ideXlab platform.
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thick blood film examination for plasmodium falciparum Malaria has reduced sensitivity and underestimates parasite density
Malaria Journal, 2006Co-Authors: Philip Bejon, Laura Andrews, Angela Huntcooke, Frances Sanderson, Sarah C Gilbert, Adrian V S HillAbstract:Background: Thick blood films are routinely used to diagnose Plasmodium falciparum Malaria. Here, they were used to diagnose volunteers exposed to Experimental Malaria challenge. Methods: The frequency with which blood films were positive at given parasite densities measured by PCR were analysed. The poisson distribution was used to calculate the theoretical likelihood of diagnosis. Further in vitro studies used serial dilutions to prepare thick films from Malaria cultures at known parasitaemia. Results: Even in expert hands, thick blood films were considerably less sensitive than might have been expected from the parasite numbers measured by quantitative PCR. In vitro work showed that thick films prepared from Malaria cultures at known parasitaemia consistently underestimated parasite densities. Conclusion: It appears large numbers of parasites are lost during staining. This limits their sensitivity, and leads to erroneous estimates of parasite density.
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thick blood film examination for plasmodium falciparum Malaria has reduced sensitivity and underestimates parasite density
Malaria Journal, 2006Co-Authors: Philip Bejon, Laura Andrews, Angela Huntcooke, Frances Sanderson, Sarah C Gilbert, Adrian V S HillAbstract:Background Thick blood films are routinely used to diagnose Plasmodium falciparum Malaria. Here, they were used to diagnose volunteers exposed to Experimental Malaria challenge.
Conrad W Liles - One of the best experts on this subject based on the ideXlab platform.
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b cell intrinsic expression of ifnλ receptor suppresses the acute humoral immune response to Experimental blood stage Malaria
Virulence, 2020Co-Authors: William O Hahn, Marion Pepper, Conrad W LilesAbstract:Antibodies play a critical protective role in the host response to blood-stage Malaria infection. The role of cytokines in shaping the antibody response to blood-stage Malaria is unclear. Interferon lambda (IFNλ), a type III interferon, is a cytokine produced early during blood-stage Malaria infection that has an unknown physiological role during Malaria infection. We demonstrate that B cell-intrinsic IFNλ signals suppress the acute antibody response, acute plasmablast response, and impede acute parasite clearance during a primary blood-stage Malaria infection. Our findings demonstrate a previously unappreciated role for B cell intrinsic IFNλ-signaling in the initiation of the humoral immune response in the host response to Experimental Malaria.
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Experimental Malaria in pregnancy induces neurocognitive injury in uninfected offspring via a c5a c5a receptor dependent pathway
PLOS Pathogens, 2015Co-Authors: Chloe R Mcdonald, Lindsay S Cahill, Jimmy Yang, Hani Kim, Karlee L Silver, Peter A Ward, Howard T J Mount, Conrad W Liles, John G Sled, Kevin C KainAbstract:The in utero environment profoundly impacts childhood neurodevelopment and behaviour. A substantial proportion of pregnancies in Africa are at risk of Malaria in pregnancy (MIP) however the impact of in utero exposure to MIP on fetal neurodevelopment is unknown. Complement activation, in particular C5a, may contribute to neuropathology and adverse outcomes during MIP. We used an Experimental model of MIP and standardized neurocognitive testing, MRI, micro-CT and HPLC analysis of neurotransmitter levels, to test the hypothesis that in utero exposure to Malaria alters neurodevelopment through a C5a-C5aR dependent pathway. We show that Malaria-exposed offspring have persistent neurocognitive deficits in memory and affective-like behaviour compared to unexposed controls. These deficits were associated with reduced regional brain levels of major biogenic amines and BDNF that were rescued by disruption of C5a-C5aR signaling using genetic and functional approaches. Our results demonstrate that Experimental MIP induces neurocognitive deficits in offspring and suggest novel targets for intervention.
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parasite burden and cd36 mediated sequestration are determinants of acute lung injury in an Experimental Malaria model
PLOS Pathogens, 2008Co-Authors: Fiona E Lovegrove, Conrad W Liles, Sina A Gharib, Lourdes Penacastillo, Samir N Patel, John T Ruzinski, Timothy P Hughes, Kevin C KainAbstract:Although acute lung injury (ALI) is a common complication of severe Malaria, little is known about the underlying molecular basis of lung dysfunction. Animal models have provided powerful insights into the pathogenesis of severe Malaria syndromes such as cerebral Malaria (CM); however, no model of Malaria-induced lung injury has been definitively established. This study used bronchoalveolar lavage (BAL), histopathology and gene expression analysis to examine the development of ALI in mice infected with Plasmodium berghei ANKA (PbA). BAL fluid of PbA-infected C57BL/6 mice revealed a significant increase in IgM and total protein prior to the development of CM, indicating disruption of the alveolar–capillary membrane barrier—the physiological hallmark of ALI. In contrast to sepsis-induced ALI, BAL fluid cell counts remained constant with no infiltration of neutrophils. Histopathology showed septal inflammation without cellular transmigration into the alveolar spaces. Microarray analysis of lung tissue from PbA-infected mice identified a significant up-regulation of expressed genes associated with the gene ontology categories of defense and immune response. Severity of Malaria-induced ALI varied in a panel of inbred mouse strains, and development of ALI correlated with peripheral parasite burden but not CM susceptibility. Cd36−/− mice, which have decreased parasite lung sequestration, were relatively protected from ALI. In summary, parasite burden and CD36-mediated sequestration in the lung are primary determinants of ALI in Experimental murine Malaria. Furthermore, differential susceptibility of mouse strains to Malaria-induced ALI and CM suggests that distinct genetic determinants may regulate susceptibility to these two important causes of Malaria-associated morbidity and mortality.
Laura Andrews - One of the best experts on this subject based on the ideXlab platform.
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thick blood film examination for plasmodium falciparum Malaria has reduced sensitivity and underestimates parasite density
Malaria Journal, 2006Co-Authors: Philip Bejon, Laura Andrews, Angela Huntcooke, Frances Sanderson, Sarah C Gilbert, Adrian V S HillAbstract:Background: Thick blood films are routinely used to diagnose Plasmodium falciparum Malaria. Here, they were used to diagnose volunteers exposed to Experimental Malaria challenge. Methods: The frequency with which blood films were positive at given parasite densities measured by PCR were analysed. The poisson distribution was used to calculate the theoretical likelihood of diagnosis. Further in vitro studies used serial dilutions to prepare thick films from Malaria cultures at known parasitaemia. Results: Even in expert hands, thick blood films were considerably less sensitive than might have been expected from the parasite numbers measured by quantitative PCR. In vitro work showed that thick films prepared from Malaria cultures at known parasitaemia consistently underestimated parasite densities. Conclusion: It appears large numbers of parasites are lost during staining. This limits their sensitivity, and leads to erroneous estimates of parasite density.
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thick blood film examination for plasmodium falciparum Malaria has reduced sensitivity and underestimates parasite density
Malaria Journal, 2006Co-Authors: Philip Bejon, Laura Andrews, Angela Huntcooke, Frances Sanderson, Sarah C Gilbert, Adrian V S HillAbstract:Background Thick blood films are routinely used to diagnose Plasmodium falciparum Malaria. Here, they were used to diagnose volunteers exposed to Experimental Malaria challenge.
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enhanced t cell mediated protection against Malaria in human challenges by using the recombinant poxviruses fp9 and modified vaccinia virus ankara
Proceedings of the National Academy of Sciences of the United States of America, 2005Co-Authors: Daniel P Webster, Laura Andrews, Susanna Dunachie, Jenni M Vuola, Tamara Berthoud, Sheila M Keating, Stephen M Laidlaw, Samuel J Mcconkey, Ian D Poulton, Rikke F AndersenAbstract:Malaria is a major global health problem for which an effective vaccine is required urgently. Prime-boost vaccination regimes involving plasmid DNA and recombinant modified vaccinia virus Ankara-encoding liver-stage Malaria antigens have been shown to be powerfully immunogenic for T cells and capable of inducing partial protection against Experimental Malaria challenge in humans, manifested as a delay in time to patent parasitemia. Here, we report that substitution of plasmid DNA as the priming vector with a specific attenuated recombinant fowlpox virus, FP9, vaccine in such prime-boost regimes can elicit complete sterile protection that can last for 20 months. Protection at 20 months was associated with persisting memory but not effector T cell responses. The protective efficacy of various immunization regimes correlated with the magnitude of induced immune responses, supporting the strategy of maximizing durable T cell immunogenicity to develop more effective liver-stage vaccines against Plasmodium falciparum Malaria.
Corazza Danilo - One of the best experts on this subject based on the ideXlab platform.
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Influência da pentoxifilina na infecção pelo Plasmodium berghei ANKA em camundongos susceptíveis ou resistentes às formas graves da malária : aspectos histopatológicos
2015Co-Authors: Corazza DaniloAbstract:A malária ainda é um problema grave para a saúde pública mundial, com bilhões de pessoas vivendo em áreas de risco de infecção, e milhões de pessoas acometidos pela doença, levando a cerca de quase um milhão de mortes anualmente. É uma doença febril aguda e nas formas graves pode apresentar prostração, alteração do estado de consciência, convulsões e edema pulmonar. As manifestações patológicas como o paroxismo febril, malária cerebral e choque, são decorrentes da resposta inflamatória exacerbada, com consequente aumento da adesão de células e o sequestro de eritrócitos principalmente no endotélio das vênulas pós-capilar. A pentoxifilina (PTX) é uma droga com capacidade imunomoduladora, regulando a produção de citocinas inflamatórias como o fator de necrose tumoral (FNT) e com potencial uso para prevenir as formas graves da malária por diminuir a produção do FNT. Este trabalho avaliou a influência da PTX sobre as alterações histopatológicas do cérebro, fígado e pulmão em camundongos susceptíveis ou não as formas graves da malária. Foram estudados camundongos machos com 8 semanas de idade das linhagens C57BL/6, CBA e BALB/c compondo quatro grupos, sendo que dois grupos foram infectados com 106 eritrócitos parasitados com Plasmodium berghei ANKA, tratados a partir do terceiro dia após a infecção, com 8mg/kg/dia de PTX e o outro grupo tratado com NaCl 0,9%. Outros dois grupos não foram infectados porém, seguiram o mesmo tratamento com PTX e NaCl 0,9%. No sexto dia da infecção os camundongos foram sacrificados e após perfusão cardíaca, foram retirados os órgãos (cérebro, fígado e pulmão), e procedido o processamento histológico. As lâminas foram coradas com Hematoxilina-Eosina (HE) e avaliadas em microscopia óptica. Observamos que a PTX foi capaz de diminuir a necrose de neurônios nos modelos CBA e BALB/c, porém, o contrário foi observado no modelo C57BL/6, onde a droga aumentou a necrose de neurônios no cérebro. Observamos também que no córtex cerebral, a PTX aumentou a congestão vascular no modelo C57BL/6, mas diminuiu a congestão vascular nos camundongos CBA e BALB/c. No fígado dos camundongos C57BL/6 e BALB/c dos animais infectados e tratados com a PTX observamos menor número de células de Kupffer com pigmento malárico. No pulmão dos camundongos C57BL/6 observamos aumento da permeabilidade da membrana alvéolo-capilar, que também foi observada nos camundongos CBA e no BALB/c após infecção pelo plasmódio. Contudo, após a administração da PTX, houve redução na congestão vascular. Nossos dados sugerem que as três linhagens de camundongos possuem mecanismos diferentes de resposta em cada órgão, evidenciando a heterogeneidade da influência da droga em camundongos com diferentes bases genéticas, e evidenciando a necessidade de melhor esclarecimento das vias pelas quais a droga age em cada órgão. ______________________________________________________________________________________________ ABSTRACTMalaria is still a major problem for global public health, with billions of people in contamination risk areas, and millions affected by the disease, leading to around nearly one million deaths annually. It is an acute febrile illness and in severe forms can present prostration, altered state of consciousness, seizures and pulmonary edema. Pathological manifestations, as febrile paroxysm, cerebral Malaria and shock, are due to the increased inflammatory response, with consequent increase in cell adhesion and sequestration of erythrocytes mainly in the endothelium of post-capillary venules. Pentoxifylline (PTX) is a drug with immunomodulatory capacity, regulating the production of inflammatory cytokines, such as tumor necrosis factor (TNF), and with a potential use to prevent severe forms of Malaria by reducing the production of TNF. This study evaluated the influence of PTX on the histopathological changes in the brain, liver and lung in mice susceptible or not to severe forms of Malaria. C57BL/6, CBA and BALB/c male mice (8 weeks old) were studied. They comprised four groups, in which two were infected with 106 Plasmodium berghei ANKA parasitized erythrocytes and treated with PTX (8 mg/kg/day) or 0.9% NaCl from the third day after infection onward. The two other remaining groups were not infected, but followed the same treatment, with PTX or 0.9% NaCl. On the sixth day after infection, mice were sacrificed and underwent to a cardiac perfusion, the organs were removed (brain, liver and lung) and carried to a histological processing. The slides were stained with hematoxylin-eosin (HE) and evaluated by light microscopy. We observed that the PTX was able to decrease neuronal necrosis in CBA and BALB/c mice. However, the opposite was observed in C57BL/6 mice, in which PTX increased the neuronal necrosis in brain. We also observed that in the cerebral cortex, PTX increased vascular congestion in C57BL/6 model, but decreased vascular congestion in CBA and BALB/c mice. In the liver of the C57BL/6 and BALB/c mice of infected animals that were treated with PTX, it was observed fewer Kupffer cells showing Malaria pigment. In lungs of C57BL/6 mice, there was an increase in the permeability of the alveolar-capillary membrane, which was also observed in CBA mice after Plasmodium infection. However, after treatment with PTX, there was a reduction in vascular congestion. Our data suggest that the three strains of mice have different mechanisms of response in each organ, showing the heterogeneity of drug influence, and highlighting the need to better understanding of the ways by which the drug acts in each organ from each of these Experimental Malaria models
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Influência da pentoxifilina na infecção pelo Plasmodium berghei ANKA em camundongos susceptíveis ou resistentes às formas graves da malária : aspectos histopatológicos
'Biblioteca Central da UNB', 2015Co-Authors: Corazza DaniloAbstract:Dissertação (mestrado)—Universidade de Brasília, Faculdade de Medicina, Programa de Pós-Graduação em Medicina Tropical, 2015.A malária ainda é um problema grave para a saúde pública mundial, com bilhões de pessoas vivendo em áreas de risco de infecção, e milhões de pessoas acometidos pela doença, levando a cerca de quase um milhão de mortes anualmente. É uma doença febril aguda e nas formas graves pode apresentar prostração, alteração do estado de consciência, convulsões e edema pulmonar. As manifestações patológicas como o paroxismo febril, malária cerebral e choque, são decorrentes da resposta inflamatória exacerbada, com consequente aumento da adesão de células e o sequestro de eritrócitos principalmente no endotélio das vênulas pós-capilar. A pentoxifilina (PTX) é uma droga com capacidade imunomoduladora, regulando a produção de citocinas inflamatórias como o fator de necrose tumoral (FNT) e com potencial uso para prevenir as formas graves da malária por diminuir a produção do FNT. Este trabalho avaliou a influência da PTX sobre as alterações histopatológicas do cérebro, fígado e pulmão em camundongos susceptíveis ou não as formas graves da malária. Foram estudados camundongos machos com 8 semanas de idade das linhagens C57BL/6, CBA e BALB/c compondo quatro grupos, sendo que dois grupos foram infectados com 106 eritrócitos parasitados com Plasmodium berghei ANKA, tratados a partir do terceiro dia após a infecção, com 8mg/kg/dia de PTX e o outro grupo tratado com NaCl 0,9%. Outros dois grupos não foram infectados porém, seguiram o mesmo tratamento com PTX e NaCl 0,9%. No sexto dia da infecção os camundongos foram sacrificados e após perfusão cardíaca, foram retirados os órgãos (cérebro, fígado e pulmão), e procedido o processamento histológico. As lâminas foram coradas com Hematoxilina-Eosina (HE) e avaliadas em microscopia óptica. Observamos que a PTX foi capaz de diminuir a necrose de neurônios nos modelos CBA e BALB/c, porém, o contrário foi observado no modelo C57BL/6, onde a droga aumentou a necrose de neurônios no cérebro. Observamos também que no córtex cerebral, a PTX aumentou a congestão vascular no modelo C57BL/6, mas diminuiu a congestão vascular nos camundongos CBA e BALB/c. No fígado dos camundongos C57BL/6 e BALB/c dos animais infectados e tratados com a PTX observamos menor número de células de Kupffer com pigmento malárico. No pulmão dos camundongos C57BL/6 observamos aumento da permeabilidade da membrana alvéolo-capilar, que também foi observada nos camundongos CBA e no BALB/c após infecção pelo plasmódio. Contudo, após a administração da PTX, houve redução na congestão vascular. Nossos dados sugerem que as três linhagens de camundongos possuem mecanismos diferentes de resposta em cada órgão, evidenciando a heterogeneidade da influência da droga em camundongos com diferentes bases genéticas, e evidenciando a necessidade de melhor esclarecimento das vias pelas quais a droga age em cada órgão.Malaria is still a major problem for global public health, with billions of people in contamination risk areas, and millions affected by the disease, leading to around nearly one million deaths annually. It is an acute febrile illness and in severe forms can present prostration, altered state of consciousness, seizures and pulmonary edema. Pathological manifestations, as febrile paroxysm, cerebral Malaria and shock, are due to the increased inflammatory response, with consequent increase in cell adhesion and sequestration of erythrocytes mainly in the endothelium of post-capillary venules. Pentoxifylline (PTX) is a drug with immunomodulatory capacity, regulating the production of inflammatory cytokines, such as tumor necrosis factor (TNF), and with a potential use to prevent severe forms of Malaria by reducing the production of TNF. This study evaluated the influence of PTX on the histopathological changes in the brain, liver and lung in mice susceptible or not to severe forms of Malaria. C57BL/6, CBA and BALB/c male mice (8 weeks old) were studied. They comprised four groups, in which two were infected with 106 Plasmodium berghei ANKA parasitized erythrocytes and treated with PTX (8 mg/kg/day) or 0.9% NaCl from the third day after infection onward. The two other remaining groups were not infected, but followed the same treatment, with PTX or 0.9% NaCl. On the sixth day after infection, mice were sacrificed and underwent to a cardiac perfusion, the organs were removed (brain, liver and lung) and carried to a histological processing. The slides were stained with hematoxylin-eosin (HE) and evaluated by light microscopy. We observed that the PTX was able to decrease neuronal necrosis in CBA and BALB/c mice. However, the opposite was observed in C57BL/6 mice, in which PTX increased the neuronal necrosis in brain. We also observed that in the cerebral cortex, PTX increased vascular congestion in C57BL/6 model, but decreased vascular congestion in CBA and BALB/c mice. In the liver of the C57BL/6 and BALB/c mice of infected animals that were treated with PTX, it was observed fewer Kupffer cells showing Malaria pigment. In lungs of C57BL/6 mice, there was an increase in the permeability of the alveolar-capillary membrane, which was also observed in CBA mice after Plasmodium infection. However, after treatment with PTX, there was a reduction in vascular congestion. Our data suggest that the three strains of mice have different mechanisms of response in each organ, showing the heterogeneity of drug influence, and highlighting the need to better understanding of the ways by which the drug acts in each organ from each of these Experimental Malaria models
