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Papers by James Kazura

Research paper thumbnail of Malaria Induces Anemia through CD8+T Cell-Dependent Parasite Clearance and Erythrocyte Removal in the Spleen

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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Research paper thumbnail of Additional file 1: of A novel approach to identifying patterns of human invasion-inhibitory antibodies guides the design of malaria vaccines incorporating polymorphic antigens

Detailed methods and additional analysis of antibody data. (DOCX 1576 kb)

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Research paper thumbnail of Additional file 1: of Human antibodies activate complement against Plasmodium falciparum sporozoites, and are associated with protection against malaria in children

Supplementary figures: Supporting data. (DOCX 1232Â kb)

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Research paper thumbnail of Sensitivity and Specificity of Ultrasound Detection and Risk Factors for Filarial-Associated Hydroceles

The American Journal of Tropical Medicine and Hygiene, 2003

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Research paper thumbnail of Correlation of High Levels of Antibodies to Multiple Pre-Erythrocytic Plasmodium Falciparum Antigens and Protection from Infection

The American Journal of Tropical Medicine and Hygiene, 2005

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Research paper thumbnail of Patterns of protective associations differ for antibodies to P.falciparum-infected erythrocytes and merozoites in immunity against malaria in children

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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Research paper thumbnail of A novel approach to identifying patterns of human invasion-inhibitory antibodies guides the design of malaria vaccines incorporating polymorphic antigens

BMC Medicine, 2016

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Research paper thumbnail of Results of bivariate analysis to determine significant relative odds of high RVF disease severity according to demographic data, clinical signs, symptoms, and exposure factors

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Research paper thumbnail of Typical peri-domestic landscape in the Sangailu area of Kenya

<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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Research paper thumbnail of Contrasting Patterns of Serologic and Functional Antibody Dynamics to Plasmodium falciparum Antigens in a Kenyan Birth Cohort

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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Research paper thumbnail of Kasehagen AJTMH 2006 FigS1

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Research paper thumbnail of Kasehagen AJTNH 2006 TableS1

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Research paper thumbnail of Exposure Factors and Disease Symptoms of Human Rift Valley Fever in Sangailu, Kenya

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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Research paper thumbnail of Broadly reactive antibodies specific for Plasmodium falciparum MSP-119 are associated with the protection of naturally exposed children against infection

Malaria Journal, 2012

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Research paper thumbnail of Effect of transmission intensity and age on subclass antibody responses to Plasmodium falciparum pre-erythrocytic and blood-stage antigens

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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Research paper thumbnail of Time-to-infection by Plasmodium falciparum is largely determined by random factors

BMC Medicine, 2015

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Research paper thumbnail of Lymphatic filariasis in Papua New Guinea: interdisciplinary research on a national health problem

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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Research paper thumbnail of Absence of ivermectin-associated excess deaths

Transactions of the Royal Society of Tropical Medicine and Hygiene, 1998

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Research paper thumbnail of Insecticidal Bed Nets and Filariasis Transmission in Papua New Guinea

New England Journal of Medicine, 2013

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Research paper thumbnail of Exposure to Holoendemic Malaria Results in Suppression of Epstein‐Barr Virus–Specific T Cell Immunosurveillance in Kenyan Children

The Journal of Infectious Diseases, 2007

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Research paper thumbnail of Malaria Induces Anemia through CD8+T Cell-Dependent Parasite Clearance and Erythrocyte Removal in the Spleen

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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Research paper thumbnail of Additional file 1: of A novel approach to identifying patterns of human invasion-inhibitory antibodies guides the design of malaria vaccines incorporating polymorphic antigens

Detailed methods and additional analysis of antibody data. (DOCX 1576 kb)

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Research paper thumbnail of Additional file 1: of Human antibodies activate complement against Plasmodium falciparum sporozoites, and are associated with protection against malaria in children

Supplementary figures: Supporting data. (DOCX 1232Â kb)

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Research paper thumbnail of Sensitivity and Specificity of Ultrasound Detection and Risk Factors for Filarial-Associated Hydroceles

The American Journal of Tropical Medicine and Hygiene, 2003

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Research paper thumbnail of Correlation of High Levels of Antibodies to Multiple Pre-Erythrocytic Plasmodium Falciparum Antigens and Protection from Infection

The American Journal of Tropical Medicine and Hygiene, 2005

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Research paper thumbnail of Patterns of protective associations differ for antibodies to P.falciparum-infected erythrocytes and merozoites in immunity against malaria in children

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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Research paper thumbnail of A novel approach to identifying patterns of human invasion-inhibitory antibodies guides the design of malaria vaccines incorporating polymorphic antigens

BMC Medicine, 2016

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Research paper thumbnail of Results of bivariate analysis to determine significant relative odds of high RVF disease severity according to demographic data, clinical signs, symptoms, and exposure factors

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Typical peri-domestic landscape in the Sangailu area of Kenya

<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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Research paper thumbnail of Contrasting Patterns of Serologic and Functional Antibody Dynamics to Plasmodium falciparum Antigens in a Kenyan Birth Cohort

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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Research paper thumbnail of Kasehagen AJTMH 2006 FigS1

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Research paper thumbnail of Kasehagen AJTNH 2006 TableS1

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Research paper thumbnail of Exposure Factors and Disease Symptoms of Human Rift Valley Fever in Sangailu, Kenya

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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Research paper thumbnail of Broadly reactive antibodies specific for Plasmodium falciparum MSP-119 are associated with the protection of naturally exposed children against infection

Malaria Journal, 2012

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Research paper thumbnail of Effect of transmission intensity and age on subclass antibody responses to Plasmodium falciparum pre-erythrocytic and blood-stage antigens

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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Research paper thumbnail of Time-to-infection by Plasmodium falciparum is largely determined by random factors

BMC Medicine, 2015

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Research paper thumbnail of Lymphatic filariasis in Papua New Guinea: interdisciplinary research on a national health problem

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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Research paper thumbnail of Absence of ivermectin-associated excess deaths

Transactions of the Royal Society of Tropical Medicine and Hygiene, 1998

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Research paper thumbnail of Insecticidal Bed Nets and Filariasis Transmission in Papua New Guinea

New England Journal of Medicine, 2013

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Research paper thumbnail of Exposure to Holoendemic Malaria Results in Suppression of Epstein‐Barr Virus–Specific T Cell Immunosurveillance in Kenyan Children

The Journal of Infectious Diseases, 2007

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