Disease progression in Plasmodium knowlesi malaria is linked to variation in invasion gene family members.
Emerging pathogens undermine initiatives to control the global health impact of infectious diseases. Zoonotic malaria is no exception. Plasmodium knowlesi, a malaria parasite of Southeast Asian macaques, has entered the human population. P. knowlesi, like Plasmodium falciparum, can reach high parasi...
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ftdoajarticles:oai:doaj.org/article:e900c886b08148f6b09dffa7bd0c496a 2023-05-15T15:14:13+02:00 Disease progression in Plasmodium knowlesi malaria is linked to variation in invasion gene family members. Atique M Ahmed Miguel M Pinheiro Paul C Divis Angela Siner Ramlah Zainudin Ing Tien Wong Chan Woon Lu Sarina K Singh-Khaira Scott B Millar Sean Lynch Matthias Willmann Balbir Singh Sanjeev Krishna Janet Cox-Singh 2014-08-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0003086 https://doaj.org/article/e900c886b08148f6b09dffa7bd0c496a EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC4133233?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0003086 https://doaj.org/article/e900c886b08148f6b09dffa7bd0c496a PLoS Neglected Tropical Diseases, Vol 8, Iss 8, p e3086 (2014) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2014 ftdoajarticles https://doi.org/10.1371/journal.pntd.0003086 2022-12-31T03:39:06Z Emerging pathogens undermine initiatives to control the global health impact of infectious diseases. Zoonotic malaria is no exception. Plasmodium knowlesi, a malaria parasite of Southeast Asian macaques, has entered the human population. P. knowlesi, like Plasmodium falciparum, can reach high parasitaemia in human infections, and the World Health Organization guidelines for severe malaria list hyperparasitaemia among the measures of severe malaria in both infections. Not all patients with P. knowlesi infections develop hyperparasitaemia, and it is important to determine why. Between isolate variability in erythrocyte invasion, efficiency seems key. Here we investigate the idea that particular alleles of two P. knowlesi erythrocyte invasion genes, P. knowlesi normocyte binding protein Pknbpxa and Pknbpxb, influence parasitaemia and human disease progression. Pknbpxa and Pknbpxb reference DNA sequences were generated from five geographically and temporally distinct P. knowlesi patient isolates. Polymorphic regions of each gene (approximately 800 bp) were identified by haplotyping 147 patient isolates at each locus. Parasitaemia in the study cohort was associated with markers of disease severity including liver and renal dysfunction, haemoglobin, platelets and lactate, (r = ≥ 0.34, p = <0.0001 for all). Seventy-five and 51 Pknbpxa and Pknbpxb haplotypes were resolved in 138 (94%) and 134 (92%) patient isolates respectively. The haplotypes formed twelve Pknbpxa and two Pknbpxb allelic groups. Patients infected with parasites with particular Pknbpxa and Pknbpxb alleles within the groups had significantly higher parasitaemia and other markers of disease severity. Our study strongly suggests that P. knowlesi invasion gene variants contribute to parasite virulence. We focused on two invasion genes, and we anticipate that additional virulent loci will be identified in pathogen genome-wide studies. The multiple sustained entries of this diverse pathogen into the human population must give cause for concern to malaria ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLoS Neglected Tropical Diseases 8 8 e3086 |
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Directory of Open Access Journals: DOAJ Articles |
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English |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Atique M Ahmed Miguel M Pinheiro Paul C Divis Angela Siner Ramlah Zainudin Ing Tien Wong Chan Woon Lu Sarina K Singh-Khaira Scott B Millar Sean Lynch Matthias Willmann Balbir Singh Sanjeev Krishna Janet Cox-Singh Disease progression in Plasmodium knowlesi malaria is linked to variation in invasion gene family members. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Emerging pathogens undermine initiatives to control the global health impact of infectious diseases. Zoonotic malaria is no exception. Plasmodium knowlesi, a malaria parasite of Southeast Asian macaques, has entered the human population. P. knowlesi, like Plasmodium falciparum, can reach high parasitaemia in human infections, and the World Health Organization guidelines for severe malaria list hyperparasitaemia among the measures of severe malaria in both infections. Not all patients with P. knowlesi infections develop hyperparasitaemia, and it is important to determine why. Between isolate variability in erythrocyte invasion, efficiency seems key. Here we investigate the idea that particular alleles of two P. knowlesi erythrocyte invasion genes, P. knowlesi normocyte binding protein Pknbpxa and Pknbpxb, influence parasitaemia and human disease progression. Pknbpxa and Pknbpxb reference DNA sequences were generated from five geographically and temporally distinct P. knowlesi patient isolates. Polymorphic regions of each gene (approximately 800 bp) were identified by haplotyping 147 patient isolates at each locus. Parasitaemia in the study cohort was associated with markers of disease severity including liver and renal dysfunction, haemoglobin, platelets and lactate, (r = ≥ 0.34, p = <0.0001 for all). Seventy-five and 51 Pknbpxa and Pknbpxb haplotypes were resolved in 138 (94%) and 134 (92%) patient isolates respectively. The haplotypes formed twelve Pknbpxa and two Pknbpxb allelic groups. Patients infected with parasites with particular Pknbpxa and Pknbpxb alleles within the groups had significantly higher parasitaemia and other markers of disease severity. Our study strongly suggests that P. knowlesi invasion gene variants contribute to parasite virulence. We focused on two invasion genes, and we anticipate that additional virulent loci will be identified in pathogen genome-wide studies. The multiple sustained entries of this diverse pathogen into the human population must give cause for concern to malaria ... |
format |
Article in Journal/Newspaper |
author |
Atique M Ahmed Miguel M Pinheiro Paul C Divis Angela Siner Ramlah Zainudin Ing Tien Wong Chan Woon Lu Sarina K Singh-Khaira Scott B Millar Sean Lynch Matthias Willmann Balbir Singh Sanjeev Krishna Janet Cox-Singh |
author_facet |
Atique M Ahmed Miguel M Pinheiro Paul C Divis Angela Siner Ramlah Zainudin Ing Tien Wong Chan Woon Lu Sarina K Singh-Khaira Scott B Millar Sean Lynch Matthias Willmann Balbir Singh Sanjeev Krishna Janet Cox-Singh |
author_sort |
Atique M Ahmed |
title |
Disease progression in Plasmodium knowlesi malaria is linked to variation in invasion gene family members. |
title_short |
Disease progression in Plasmodium knowlesi malaria is linked to variation in invasion gene family members. |
title_full |
Disease progression in Plasmodium knowlesi malaria is linked to variation in invasion gene family members. |
title_fullStr |
Disease progression in Plasmodium knowlesi malaria is linked to variation in invasion gene family members. |
title_full_unstemmed |
Disease progression in Plasmodium knowlesi malaria is linked to variation in invasion gene family members. |
title_sort |
disease progression in plasmodium knowlesi malaria is linked to variation in invasion gene family members. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2014 |
url |
https://doi.org/10.1371/journal.pntd.0003086 https://doaj.org/article/e900c886b08148f6b09dffa7bd0c496a |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 8, Iss 8, p e3086 (2014) |
op_relation |
http://europepmc.org/articles/PMC4133233?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0003086 https://doaj.org/article/e900c886b08148f6b09dffa7bd0c496a |
op_doi |
https://doi.org/10.1371/journal.pntd.0003086 |
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PLoS Neglected Tropical Diseases |
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8 |
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8 |
container_start_page |
e3086 |
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