Human cerebral malaria and Plasmodium falciparum genotypes in Malawi

Danny A. Milner; Jimmy Vareta; Clarissa Valim; Jacqui Montgomery; Rachel F. Daniels; Sarah K. Volkman; Daniel E. Neafsey; Daniel J. Park; Stephen F. Schaffner; Nira C. Mahesh; Kayla Barnes; David M. Rosen; Amanda K. Lukens; Daria Van-Tyne; Roger C. Wiegand; Pardis C. Sabeti; Karl B. Seydel; Simon J. Glover; Steve Kamiza; Malcolm E. Molyneux; Terrie E. Taylor; Dyann F. Wirth

doi:10.1186/1475-2875-11-35

Human cerebral malaria and Plasmodium falciparum genotypes in Malawi

Danny A. Milner, Jimmy Vareta, Clarissa Valim, Jacqui Montgomery, Rachel F. Daniels, Sarah K. Volkman, Daniel E. Neafsey, Daniel J. Park, Stephen F. Schaffner, Nira C. Mahesh, Kayla Barnes, David M. Rosen, Amanda K. Lukens, Daria Van-Tyne, Roger C. Wiegand, Pardis C. Sabeti, Karl B. Seydel, Simon J. Glover, Steve Kamiza, Malcolm E. MolyneuxTerrie E. Taylor, Dyann F. Wirth

Research output: Contribution to journal › Article › peer-review

19 Citations (Scopus)

Abstract

Background

Cerebral malaria, a severe form of Plasmodium falciparum infection, is an important cause of mortality in sub-Saharan African children. A Taqman 24 Single Nucleotide Polymorphisms (SNP) molecular barcode assay was developed for use in laboratory parasites which estimates genotype number and identifies the predominant genotype.

Methods

The 24 SNP assay was used to determine predominant genotypes in blood and tissues from autopsy and clinical patients with cerebral malaria.

Results

Single genotypes were shared between the peripheral blood, the brain, and other tissues of cerebral malaria patients, while malaria-infected patients who died of non-malarial causes had mixed genetic signatures in tissues examined. Children with retinopathy-positive cerebral malaria had significantly less complex infections than those without retinopathy (OR = 3.7, 95% CI [1.51-9.10]).The complexity of infections significantly decreased over the malaria season in retinopathy-positive patients compared to retinopathy-negative patients.

Conclusions

Cerebral malaria patients harbour a single or small set of predominant parasites; patients with incidental parasitaemia sustain infections involving diverse genotypes. Limited diversity in the peripheral blood of cerebral malaria patients and correlation with tissues supports peripheral blood samples as appropriate for genome-wide association studies of parasite determinants of pathogenicity.

Original language	English
Article number	35
Pages (from-to)	e35
Journal	Malaria Journal
Volume	11
DOIs	https://doi.org/10.1186/1475-2875-11-35
Publication status	Published - 7 Feb 2012

Keywords

Autopsy
Cerebral malaria
Genotyping
Histopathology
Molecular barcode
Plasmodium falciparum

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1186/1475-2875-11-35Licence: CC BY

Malaria J 11 35Final published version, 383 KBLicence: CC BY

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Milner, D. A., Vareta, J., Valim, C., Montgomery, J., Daniels, R. F., Volkman, S. K., Neafsey, D. E., Park, D. J., Schaffner, S. F., Mahesh, N. C., Barnes, K., Rosen, D. M., Lukens, A. K., Van-Tyne, D., Wiegand, R. C., Sabeti, P. C., Seydel, K. B., Glover, S. J., Kamiza, S., ... Wirth, D. F. (2012). Human cerebral malaria and Plasmodium falciparum genotypes in Malawi. Malaria Journal, 11, e35. Article 35. https://doi.org/10.1186/1475-2875-11-35

@article{c59d11ecab2048a595eb2417458ff241,

title = "Human cerebral malaria and Plasmodium falciparum genotypes in Malawi",

abstract = "BackgroundCerebral malaria, a severe form of Plasmodium falciparum infection, is an important cause of mortality in sub-Saharan African children. A Taqman 24 Single Nucleotide Polymorphisms (SNP) molecular barcode assay was developed for use in laboratory parasites which estimates genotype number and identifies the predominant genotype.MethodsThe 24 SNP assay was used to determine predominant genotypes in blood and tissues from autopsy and clinical patients with cerebral malaria.ResultsSingle genotypes were shared between the peripheral blood, the brain, and other tissues of cerebral malaria patients, while malaria-infected patients who died of non-malarial causes had mixed genetic signatures in tissues examined. Children with retinopathy-positive cerebral malaria had significantly less complex infections than those without retinopathy (OR = 3.7, 95\% CI [1.51-9.10]).The complexity of infections significantly decreased over the malaria season in retinopathy-positive patients compared to retinopathy-negative patients.ConclusionsCerebral malaria patients harbour a single or small set of predominant parasites; patients with incidental parasitaemia sustain infections involving diverse genotypes. Limited diversity in the peripheral blood of cerebral malaria patients and correlation with tissues supports peripheral blood samples as appropriate for genome-wide association studies of parasite determinants of pathogenicity.",

keywords = "Autopsy, Cerebral malaria, Genotyping, Histopathology, Molecular barcode, Plasmodium falciparum",

author = "Milner, \{Danny A.\} and Jimmy Vareta and Clarissa Valim and Jacqui Montgomery and Daniels, \{Rachel F.\} and Volkman, \{Sarah K.\} and Neafsey, \{Daniel E.\} and Park, \{Daniel J.\} and Schaffner, \{Stephen F.\} and Mahesh, \{Nira C.\} and Kayla Barnes and Rosen, \{David M.\} and Lukens, \{Amanda K.\} and Daria Van-Tyne and Wiegand, \{Roger C.\} and Sabeti, \{Pardis C.\} and Seydel, \{Karl B.\} and Glover, \{Simon J.\} and Steve Kamiza and Molyneux, \{Malcolm E.\} and Taylor, \{Terrie E.\} and Wirth, \{Dyann F.\}",

year = "2012",

month = feb,

day = "7",

doi = "10.1186/1475-2875-11-35",

language = "English",

volume = "11",

pages = "e35",

journal = "Malaria Journal",

issn = "1475-2875",

publisher = "BioMed Central Ltd",

}

Milner, DA, Vareta, J, Valim, C, Montgomery, J, Daniels, RF, Volkman, SK, Neafsey, DE, Park, DJ, Schaffner, SF, Mahesh, NC, Barnes, K, Rosen, DM, Lukens, AK, Van-Tyne, D, Wiegand, RC, Sabeti, PC, Seydel, KB, Glover, SJ, Kamiza, S, Molyneux, ME, Taylor, TE & Wirth, DF 2012, 'Human cerebral malaria and Plasmodium falciparum genotypes in Malawi', Malaria Journal, vol. 11, 35, pp. e35. https://doi.org/10.1186/1475-2875-11-35

TY - JOUR

T1 - Human cerebral malaria and Plasmodium falciparum genotypes in Malawi

AU - Milner, Danny A.

AU - Vareta, Jimmy

AU - Valim, Clarissa

AU - Montgomery, Jacqui

AU - Daniels, Rachel F.

AU - Volkman, Sarah K.

AU - Neafsey, Daniel E.

AU - Park, Daniel J.

AU - Schaffner, Stephen F.

AU - Mahesh, Nira C.

AU - Barnes, Kayla

AU - Rosen, David M.

AU - Lukens, Amanda K.

AU - Van-Tyne, Daria

AU - Wiegand, Roger C.

AU - Sabeti, Pardis C.

AU - Seydel, Karl B.

AU - Glover, Simon J.

AU - Kamiza, Steve

AU - Molyneux, Malcolm E.

AU - Taylor, Terrie E.

AU - Wirth, Dyann F.

PY - 2012/2/7

Y1 - 2012/2/7

N2 - BackgroundCerebral malaria, a severe form of Plasmodium falciparum infection, is an important cause of mortality in sub-Saharan African children. A Taqman 24 Single Nucleotide Polymorphisms (SNP) molecular barcode assay was developed for use in laboratory parasites which estimates genotype number and identifies the predominant genotype.MethodsThe 24 SNP assay was used to determine predominant genotypes in blood and tissues from autopsy and clinical patients with cerebral malaria.ResultsSingle genotypes were shared between the peripheral blood, the brain, and other tissues of cerebral malaria patients, while malaria-infected patients who died of non-malarial causes had mixed genetic signatures in tissues examined. Children with retinopathy-positive cerebral malaria had significantly less complex infections than those without retinopathy (OR = 3.7, 95% CI [1.51-9.10]).The complexity of infections significantly decreased over the malaria season in retinopathy-positive patients compared to retinopathy-negative patients.ConclusionsCerebral malaria patients harbour a single or small set of predominant parasites; patients with incidental parasitaemia sustain infections involving diverse genotypes. Limited diversity in the peripheral blood of cerebral malaria patients and correlation with tissues supports peripheral blood samples as appropriate for genome-wide association studies of parasite determinants of pathogenicity.

AB - BackgroundCerebral malaria, a severe form of Plasmodium falciparum infection, is an important cause of mortality in sub-Saharan African children. A Taqman 24 Single Nucleotide Polymorphisms (SNP) molecular barcode assay was developed for use in laboratory parasites which estimates genotype number and identifies the predominant genotype.MethodsThe 24 SNP assay was used to determine predominant genotypes in blood and tissues from autopsy and clinical patients with cerebral malaria.ResultsSingle genotypes were shared between the peripheral blood, the brain, and other tissues of cerebral malaria patients, while malaria-infected patients who died of non-malarial causes had mixed genetic signatures in tissues examined. Children with retinopathy-positive cerebral malaria had significantly less complex infections than those without retinopathy (OR = 3.7, 95% CI [1.51-9.10]).The complexity of infections significantly decreased over the malaria season in retinopathy-positive patients compared to retinopathy-negative patients.ConclusionsCerebral malaria patients harbour a single or small set of predominant parasites; patients with incidental parasitaemia sustain infections involving diverse genotypes. Limited diversity in the peripheral blood of cerebral malaria patients and correlation with tissues supports peripheral blood samples as appropriate for genome-wide association studies of parasite determinants of pathogenicity.

KW - Autopsy

KW - Cerebral malaria

KW - Genotyping

KW - Histopathology

KW - Molecular barcode

KW - Plasmodium falciparum

U2 - 10.1186/1475-2875-11-35

DO - 10.1186/1475-2875-11-35

M3 - Article

SN - 1475-2875

VL - 11

SP - e35

JO - Malaria Journal

JF - Malaria Journal

M1 - 35

ER -

Human cerebral malaria and Plasmodium falciparum genotypes in Malawi

Abstract

Keywords

UN SDGs

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