James Kazura - Academia.edu (original) (raw)
Papers by James Kazura
mBio, 2015
Severe malarial anemia (SMA) in semi-immune individuals eliminates both infected and uninfected e... more Severe malarial anemia (SMA) in semi-immune individuals eliminates both infected and uninfected erythrocytes and is a frequent fatal complication. It is proportional not to circulating parasitemia but total parasite mass (sequestered) in the organs. Thus, immune responses that clear parasites in organs may trigger changes leading to anemia. Here, we use an outbred-rat model where increasing parasite removal in the spleen escalated uninfected-erythrocyte removal. Splenic parasite clearance was associated with activated CD8+T cells, immunodepletion of which prevented parasite clearance. CD8+T cell repletion and concomitant reduction of the parasite load was associated with exacerbated (40 to 60%) hemoglobin loss and changes in properties of uninfected erythrocytes. Together, these data suggest that CD8+T cell-dependent parasite clearance causes erythrocyte removal in the spleen and thus anemia. In children infected with the human malaria parasite Plasmodium falciparum, elevation of pa...
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Detailed methods and additional analysis of antibody data. (DOCX 1576 kb)
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Supplementary figures: Supporting data. (DOCX 1232Â kb)
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The American Journal of Tropical Medicine and Hygiene, 2003
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The American Journal of Tropical Medicine and Hygiene, 2005
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European journal of immunology, Dec 20, 2017
Acquired antibodies play an important role in immunity to P. falciparum malaria and are typically... more Acquired antibodies play an important role in immunity to P. falciparum malaria and are typically directed towards surface antigens expressed by merozoites and infected erythrocytes (IEs). The importance of specific IE surface antigens as immune targets remains unclear. We evaluated antibodies and protective associations in two cohorts of children in Papua New Guinea. We used genetically-modified P. falciparum to evaluate the importance of PfEMP1 and a P. falciparum isolate with a virulent phenotype. Our findings suggested that PfEMP1 was the dominant target of antibodies to the IE surface, including functional antibodies that promoted opsonic phagocytosis by monocytes. Antibodies were associated with increasing age and concurrent parasitemia, and were higher among children exposed to a higher force-of-infection as determined using molecular detection. Antibodies to IE surface antigens were consistently associated with reduced risk of malaria in both younger and older children. Howe...
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BMC Medicine, 2016
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<p>Shown are traditional wicker and grass-mat domed houses and outbuildings, surrounded by ... more <p>Shown are traditional wicker and grass-mat domed houses and outbuildings, surrounded by a planted compound perimeter and local dense brush vegetation.</p
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Clinical and Vaccine Immunology, 2015
IgG antibodies to Plasmodium falciparum are transferred from the maternal to fetal circulation du... more IgG antibodies to Plasmodium falciparum are transferred from the maternal to fetal circulation during pregnancy, wane after birth, and are subsequently acquired in response to natural infection. We examined the dynamics of malaria antibody responses of 84 Kenyan infants from birth to 36 months of age by (i) serology, (ii) variant surface antigen (VSA) assay, (iii) growth inhibitory activity (GIA), and (iv) invasion inhibition assays (IIA) specific for merozoite surface protein 1 (MSP1) and sialic acid-dependent invasion pathway. Maternal antibodies in each of these four categories were detected in cord blood and decreased to their lowest level by approximately 6 months of age. Serologic antibodies to 3 preerythrocytic and 10 blood-stage antigens subsequently increased, reaching peak prevalence by 36 months. In contrast, antibodies measured by VSA, GIA, and IIA remained low even up to 36 months. Infants sensitized to P. falciparum in utero , defined by cord blood lymphocyte recall re...
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Background: Rift Valley fever virus (RVFV) causes an acute, mosquito-borne viral disease in lives... more Background: Rift Valley fever virus (RVFV) causes an acute, mosquito-borne viral disease in livestock and humans. To determine the exposure factors and range of disease symptoms associated with human RVF, we performed a household cluster survey in six villages in Northeastern Kenya in 2011. Methods: We performed a household cluster survey in six villages in Northeastern Kenya in 2011. 1081 participants were tested via anti-RVFV IgG ELISA. Results: 1081 participants were tested via anti-RVFV IgG ELISA, yielding 16% seroprevalence (95% C.I. 0.1-0.2). No significant differences were found among villages. 31% (154/498) of adults were seropositive vs. 3% of children (≤15 years; 17/583). With each additional year of age, participants were 5% more likely to be seropositive (95% C.I. 1.0-1.1). Documentation of a 3y/o seropositive boy confirmed interepidemic transmission. Males were 2.6 times more likely to be seropositive (p<0.001; 95% C.I. 1.7-3.8); herders were 1.7 times more likely (p...
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Malaria Journal, 2012
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Acta tropica, 2015
Cytophilic immunoglobulin (IgG) subclass responses (IgG1 and IgG3) to Plasmodium falciparum antig... more Cytophilic immunoglobulin (IgG) subclass responses (IgG1 and IgG3) to Plasmodium falciparum antigens have been associated with protection from malaria, yet the relative importance of transmission intensity and age in generation of subclass responses to pre-erythrocytic and blood-stage antigens have not been clearly defined. We analyzed IgG subclass responses to the pre-erythrocytic antigens CSP, LSA-1, and TRAP and the blood-stage antigens AMA-1, EBA-175, and MSP-1 in asymptomatic residents age 2 years or older in stable (n=116) and unstable (n=96) transmission areas in Western Kenya. In the area of stable malaria transmission, a high prevalence of cytophilic (IgG1 and IgG3) antibodies to each antigen was seen in all age groups. Prevalence and levels of cytophilic antibodies to pre-erythrocytic and blood-stage P. falciparum antigens increased with age in the unstable transmission area, yet IgG1 and IgG3 responses to most antigens for all ages in the unstable transmission area were l...
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BMC Medicine, 2015
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Trends in Parasitology, 2003
Bancroftian filariasis is a major public health problem in Papua New Guinea, where the level of t... more Bancroftian filariasis is a major public health problem in Papua New Guinea, where the level of transmission by the mosquito vector, human infection rates and clinical morbidity are among the highest in the world. Coordinated research efforts within the country, involving the disciplines of epidemiology, vector biology, immunology and genetics, have led to new insights into the ecology and pathogenesis of human lymphatic filariasis. Recent work using this knowledge base should be helpful in assessing local and global strategies aimed at eliminating Wuchereria bancrofti and in guiding research that will facilitate achievement of this goal.
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Transactions of the Royal Society of Tropical Medicine and Hygiene, 1998
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New England Journal of Medicine, 2013
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The Journal of Infectious Diseases, 2007
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mBio, 2015
Severe malarial anemia (SMA) in semi-immune individuals eliminates both infected and uninfected e... more Severe malarial anemia (SMA) in semi-immune individuals eliminates both infected and uninfected erythrocytes and is a frequent fatal complication. It is proportional not to circulating parasitemia but total parasite mass (sequestered) in the organs. Thus, immune responses that clear parasites in organs may trigger changes leading to anemia. Here, we use an outbred-rat model where increasing parasite removal in the spleen escalated uninfected-erythrocyte removal. Splenic parasite clearance was associated with activated CD8+T cells, immunodepletion of which prevented parasite clearance. CD8+T cell repletion and concomitant reduction of the parasite load was associated with exacerbated (40 to 60%) hemoglobin loss and changes in properties of uninfected erythrocytes. Together, these data suggest that CD8+T cell-dependent parasite clearance causes erythrocyte removal in the spleen and thus anemia. In children infected with the human malaria parasite Plasmodium falciparum, elevation of pa...
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Detailed methods and additional analysis of antibody data. (DOCX 1576 kb)
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Supplementary figures: Supporting data. (DOCX 1232Â kb)
Bookmarks Related papers MentionsView impact
The American Journal of Tropical Medicine and Hygiene, 2003
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The American Journal of Tropical Medicine and Hygiene, 2005
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European journal of immunology, Dec 20, 2017
Acquired antibodies play an important role in immunity to P. falciparum malaria and are typically... more Acquired antibodies play an important role in immunity to P. falciparum malaria and are typically directed towards surface antigens expressed by merozoites and infected erythrocytes (IEs). The importance of specific IE surface antigens as immune targets remains unclear. We evaluated antibodies and protective associations in two cohorts of children in Papua New Guinea. We used genetically-modified P. falciparum to evaluate the importance of PfEMP1 and a P. falciparum isolate with a virulent phenotype. Our findings suggested that PfEMP1 was the dominant target of antibodies to the IE surface, including functional antibodies that promoted opsonic phagocytosis by monocytes. Antibodies were associated with increasing age and concurrent parasitemia, and were higher among children exposed to a higher force-of-infection as determined using molecular detection. Antibodies to IE surface antigens were consistently associated with reduced risk of malaria in both younger and older children. Howe...
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BMC Medicine, 2016
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<p>Shown are traditional wicker and grass-mat domed houses and outbuildings, surrounded by ... more <p>Shown are traditional wicker and grass-mat domed houses and outbuildings, surrounded by a planted compound perimeter and local dense brush vegetation.</p
Bookmarks Related papers MentionsView impact
Clinical and Vaccine Immunology, 2015
IgG antibodies to Plasmodium falciparum are transferred from the maternal to fetal circulation du... more IgG antibodies to Plasmodium falciparum are transferred from the maternal to fetal circulation during pregnancy, wane after birth, and are subsequently acquired in response to natural infection. We examined the dynamics of malaria antibody responses of 84 Kenyan infants from birth to 36 months of age by (i) serology, (ii) variant surface antigen (VSA) assay, (iii) growth inhibitory activity (GIA), and (iv) invasion inhibition assays (IIA) specific for merozoite surface protein 1 (MSP1) and sialic acid-dependent invasion pathway. Maternal antibodies in each of these four categories were detected in cord blood and decreased to their lowest level by approximately 6 months of age. Serologic antibodies to 3 preerythrocytic and 10 blood-stage antigens subsequently increased, reaching peak prevalence by 36 months. In contrast, antibodies measured by VSA, GIA, and IIA remained low even up to 36 months. Infants sensitized to P. falciparum in utero , defined by cord blood lymphocyte recall re...
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Background: Rift Valley fever virus (RVFV) causes an acute, mosquito-borne viral disease in lives... more Background: Rift Valley fever virus (RVFV) causes an acute, mosquito-borne viral disease in livestock and humans. To determine the exposure factors and range of disease symptoms associated with human RVF, we performed a household cluster survey in six villages in Northeastern Kenya in 2011. Methods: We performed a household cluster survey in six villages in Northeastern Kenya in 2011. 1081 participants were tested via anti-RVFV IgG ELISA. Results: 1081 participants were tested via anti-RVFV IgG ELISA, yielding 16% seroprevalence (95% C.I. 0.1-0.2). No significant differences were found among villages. 31% (154/498) of adults were seropositive vs. 3% of children (≤15 years; 17/583). With each additional year of age, participants were 5% more likely to be seropositive (95% C.I. 1.0-1.1). Documentation of a 3y/o seropositive boy confirmed interepidemic transmission. Males were 2.6 times more likely to be seropositive (p<0.001; 95% C.I. 1.7-3.8); herders were 1.7 times more likely (p...
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Malaria Journal, 2012
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Acta tropica, 2015
Cytophilic immunoglobulin (IgG) subclass responses (IgG1 and IgG3) to Plasmodium falciparum antig... more Cytophilic immunoglobulin (IgG) subclass responses (IgG1 and IgG3) to Plasmodium falciparum antigens have been associated with protection from malaria, yet the relative importance of transmission intensity and age in generation of subclass responses to pre-erythrocytic and blood-stage antigens have not been clearly defined. We analyzed IgG subclass responses to the pre-erythrocytic antigens CSP, LSA-1, and TRAP and the blood-stage antigens AMA-1, EBA-175, and MSP-1 in asymptomatic residents age 2 years or older in stable (n=116) and unstable (n=96) transmission areas in Western Kenya. In the area of stable malaria transmission, a high prevalence of cytophilic (IgG1 and IgG3) antibodies to each antigen was seen in all age groups. Prevalence and levels of cytophilic antibodies to pre-erythrocytic and blood-stage P. falciparum antigens increased with age in the unstable transmission area, yet IgG1 and IgG3 responses to most antigens for all ages in the unstable transmission area were l...
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BMC Medicine, 2015
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Trends in Parasitology, 2003
Bancroftian filariasis is a major public health problem in Papua New Guinea, where the level of t... more Bancroftian filariasis is a major public health problem in Papua New Guinea, where the level of transmission by the mosquito vector, human infection rates and clinical morbidity are among the highest in the world. Coordinated research efforts within the country, involving the disciplines of epidemiology, vector biology, immunology and genetics, have led to new insights into the ecology and pathogenesis of human lymphatic filariasis. Recent work using this knowledge base should be helpful in assessing local and global strategies aimed at eliminating Wuchereria bancrofti and in guiding research that will facilitate achievement of this goal.
Bookmarks Related papers MentionsView impact
Transactions of the Royal Society of Tropical Medicine and Hygiene, 1998
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New England Journal of Medicine, 2013
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The Journal of Infectious Diseases, 2007
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