Mutation Research-fundamental and Molecular Mechanisms of Mutagenesis, 2002
The human mannose-binding lectin (MBL) is an important protein of the innate immune system. MBL i... more The human mannose-binding lectin (MBL) is an important protein of the innate immune system. MBL is able to eliminate potential pathogens by activating the complement cascade or by opsonisation. We investigated the gene and promoter region of MBL in a population from Papua New Guinea infected with Plasmodium falciparum parasites and measured the appropriate serum concentrations of these individuals. Their
The American journal of tropical medicine and hygiene, 2007
Levels of C-reactive protein (CRP), a classic marker for the acute phase response (APR), were mea... more Levels of C-reactive protein (CRP), a classic marker for the acute phase response (APR), were measured in children with asymptomatic malaria infection in the Amele region of Papua New Guinea (PNG). Despite the presence of parasitemia, the prevalence of CRP levels consistent with an APR (CRP > 10 microg/mL) was very low (< 10%). Splenomegaly was significantly associated with increased parasitemia (P < 0.001) and CRP levels (P < 0.001), highlighting the importance of splenomegaly as an indicator of recent high density infection in this population. Multivariate analysis showed that CRP levels were significantly associated with splenomegaly, fever, hemoglobin, and age (P < or = 0.002). CRP levels also increased with increasing parasitemia (P < 0.001) but remained < 3.5 microg/mL. The low levels of CRP indicate that children in the Amele modulate inflammation associated with malaria.
The American journal of tropical medicine and hygiene, 2004
The ecology and behavior of most of the 11 known members of the Anopheles punctulatus group remai... more The ecology and behavior of most of the 11 known members of the Anopheles punctulatus group remain unresolved and only the morphologic species An. farauti, An. koliensis, and An. punctulatus are known as vectors of malaria in Papua New Guinea. Of 1,582 mosquitoes examined morphologically, 737 were identified as An. farauti s.l., 719 as An. koliensis, and 126 as An. punctulatus. All specimens identified morphologically as An. punctulatus were shown to be An. punctulatus by polymerase chain reaction-restriction fragment length polymorphism analysis, but the An. farauti and An. koliensis morphotypes consisted of three or more species including An. farauti s.s., An. farauti No. 2, and An. farauti No. 4. The biting cycles and role in malaria transmission of some of these species are described here for the first time. We also show evidence that An. koliensis could be a sub-complex of two or more species. The epidemiologic implications of our findings are discussed.
Adherence of Plasmodium falciparum-infected erythrocytes to cerebral postcapillary venular endoth... more Adherence of Plasmodium falciparum-infected erythrocytes to cerebral postcapillary venular endothelium is believed to be a critical step in the development of cerebral malaria. Some of the possible receptors mediating adherence have been identified, but the process of adherence in vivo is poorly understood. We investigated the role of carbohydrate ligands in adherence, and we identified chondroitin sulfate (CS) as a specific receptor for P. falciparum-infected erythrocytes. Parasitized cells bound to Chinese hamster ovary (CHO) cells and C32 melanoma cells in a chondroitin sulfate-dependent manner, whereas glycosylation mutants lacking chondroitin sulfate A (CSA) supported little or no binding. Chondroitinase treatment of wild-type CHO cells reduced binding by up to 90%. Soluble CSA inhibited binding to CHO cells by 99.2 +/- 0.2% at 10 mg/ml and by 72.5 +/- 3.8% at 1 mg/ml, whereas a range of other glycosaminoglycans such as heparan sulfate had no effect. Parasite lines selected for increased binding to CHO cells and most patient isolates bound specifically to immobilized CSA. We conclude that P. falciparum can express or expose proteins at the surface of the infected erythrocyte that mediate specific binding to CSA. This mechanism of adherence may contribute to the pathogenesis of P. falciparum malaria, but has wider implications as an example of an infectious agent with the capacity to bind specifically to cell-associated or immobilized CS.
... Page 8. Conclusions This study of polymorphism, diversity and selection of Pf38 in two P. fal... more ... Page 8. Conclusions This study of polymorphism, diversity and selection of Pf38 in two P. falciparum populations in PNG, con-firmed the findings of Tetteh et al. [9] in the Gambia that Pf38 is a modestly polymorphic antigen gene that shows some evidence of balancing selection. ...
Plasmodium falciparum malaria is responsible for 2 million deaths each year. Even in endemic regi... more Plasmodium falciparum malaria is responsible for 2 million deaths each year. Even in endemic regions, immunity to malaria builds slowly and is rarely complete. Strategies such as antigenic variation and antigenic diversity are critical to a parasite&#39;s ability to evade the host immune response and infect previously exposed individuals. In this short review, the phenomenon of antigenic variation is discussed in relation to immune evasion and its impact on parasite pathogenesis. Recent advances in the understanding of the underlying molecular mechanisms of antigenic variation are examined and questions posed for future research.
Large-scale studies of genomic variation could assist efforts to eliminate malaria. But there are... more Large-scale studies of genomic variation could assist efforts to eliminate malaria. But there are scientific, ethical and practical challenges to carrying out such studies in developing countries, where the burden of disease is greatest. The Malaria Genomic Epidemiology Network (MalariaGEN) is now working to overcome these obstacles, using a consortial approach that brings together researchers from 21 countries.
Mutation Research-fundamental and Molecular Mechanisms of Mutagenesis, 2002
The human mannose-binding lectin (MBL) is an important protein of the innate immune system. MBL i... more The human mannose-binding lectin (MBL) is an important protein of the innate immune system. MBL is able to eliminate potential pathogens by activating the complement cascade or by opsonisation. We investigated the gene and promoter region of MBL in a population from Papua New Guinea infected with Plasmodium falciparum parasites and measured the appropriate serum concentrations of these individuals. Their
The American journal of tropical medicine and hygiene, 2007
Levels of C-reactive protein (CRP), a classic marker for the acute phase response (APR), were mea... more Levels of C-reactive protein (CRP), a classic marker for the acute phase response (APR), were measured in children with asymptomatic malaria infection in the Amele region of Papua New Guinea (PNG). Despite the presence of parasitemia, the prevalence of CRP levels consistent with an APR (CRP > 10 microg/mL) was very low (< 10%). Splenomegaly was significantly associated with increased parasitemia (P < 0.001) and CRP levels (P < 0.001), highlighting the importance of splenomegaly as an indicator of recent high density infection in this population. Multivariate analysis showed that CRP levels were significantly associated with splenomegaly, fever, hemoglobin, and age (P < or = 0.002). CRP levels also increased with increasing parasitemia (P < 0.001) but remained < 3.5 microg/mL. The low levels of CRP indicate that children in the Amele modulate inflammation associated with malaria.
The American journal of tropical medicine and hygiene, 2004
The ecology and behavior of most of the 11 known members of the Anopheles punctulatus group remai... more The ecology and behavior of most of the 11 known members of the Anopheles punctulatus group remain unresolved and only the morphologic species An. farauti, An. koliensis, and An. punctulatus are known as vectors of malaria in Papua New Guinea. Of 1,582 mosquitoes examined morphologically, 737 were identified as An. farauti s.l., 719 as An. koliensis, and 126 as An. punctulatus. All specimens identified morphologically as An. punctulatus were shown to be An. punctulatus by polymerase chain reaction-restriction fragment length polymorphism analysis, but the An. farauti and An. koliensis morphotypes consisted of three or more species including An. farauti s.s., An. farauti No. 2, and An. farauti No. 4. The biting cycles and role in malaria transmission of some of these species are described here for the first time. We also show evidence that An. koliensis could be a sub-complex of two or more species. The epidemiologic implications of our findings are discussed.
Adherence of Plasmodium falciparum-infected erythrocytes to cerebral postcapillary venular endoth... more Adherence of Plasmodium falciparum-infected erythrocytes to cerebral postcapillary venular endothelium is believed to be a critical step in the development of cerebral malaria. Some of the possible receptors mediating adherence have been identified, but the process of adherence in vivo is poorly understood. We investigated the role of carbohydrate ligands in adherence, and we identified chondroitin sulfate (CS) as a specific receptor for P. falciparum-infected erythrocytes. Parasitized cells bound to Chinese hamster ovary (CHO) cells and C32 melanoma cells in a chondroitin sulfate-dependent manner, whereas glycosylation mutants lacking chondroitin sulfate A (CSA) supported little or no binding. Chondroitinase treatment of wild-type CHO cells reduced binding by up to 90%. Soluble CSA inhibited binding to CHO cells by 99.2 +/- 0.2% at 10 mg/ml and by 72.5 +/- 3.8% at 1 mg/ml, whereas a range of other glycosaminoglycans such as heparan sulfate had no effect. Parasite lines selected for increased binding to CHO cells and most patient isolates bound specifically to immobilized CSA. We conclude that P. falciparum can express or expose proteins at the surface of the infected erythrocyte that mediate specific binding to CSA. This mechanism of adherence may contribute to the pathogenesis of P. falciparum malaria, but has wider implications as an example of an infectious agent with the capacity to bind specifically to cell-associated or immobilized CS.
... Page 8. Conclusions This study of polymorphism, diversity and selection of Pf38 in two P. fal... more ... Page 8. Conclusions This study of polymorphism, diversity and selection of Pf38 in two P. falciparum populations in PNG, con-firmed the findings of Tetteh et al. [9] in the Gambia that Pf38 is a modestly polymorphic antigen gene that shows some evidence of balancing selection. ...
Plasmodium falciparum malaria is responsible for 2 million deaths each year. Even in endemic regi... more Plasmodium falciparum malaria is responsible for 2 million deaths each year. Even in endemic regions, immunity to malaria builds slowly and is rarely complete. Strategies such as antigenic variation and antigenic diversity are critical to a parasite&#39;s ability to evade the host immune response and infect previously exposed individuals. In this short review, the phenomenon of antigenic variation is discussed in relation to immune evasion and its impact on parasite pathogenesis. Recent advances in the understanding of the underlying molecular mechanisms of antigenic variation are examined and questions posed for future research.
Large-scale studies of genomic variation could assist efforts to eliminate malaria. But there are... more Large-scale studies of genomic variation could assist efforts to eliminate malaria. But there are scientific, ethical and practical challenges to carrying out such studies in developing countries, where the burden of disease is greatest. The Malaria Genomic Epidemiology Network (MalariaGEN) is now working to overcome these obstacles, using a consortial approach that brings together researchers from 21 countries.
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