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01.12.2012 | Research | Ausgabe 1/2012 Open Access

Malaria Journal 1/2012

Human cerebral malaria and Plasmodium falciparum genotypes in Malawi

Zeitschrift:
Malaria Journal > Ausgabe 1/2012
Autoren:
Danny A Milner Jr, 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 G 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
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​1475-2875-11-35) contains supplementary material, which is available to authorized users.

Competing interests

The authors declare that they have no competing interests.

Authors' contributions

DAM designed the study, performed the experiments and statistical analysis, and wrote the manuscript. JV, JM, NCM, KGB, DMR performed the experiments. CV performed the statistical analysis. RFD, SKV, DEN, DJP, SFS, AKL, DVT, RCW, and PCS designed, developed, and validated the barcoding assay. KBS, SJG, SK, MEM, and TET provided clinical care and data collection for all patients. DFW designed the study and edited the manuscript. All authors read and approved the final manuscript.

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.
Zusatzmaterial
Additional file 1: Comparison of the number of msp-1 and - msp- 2 alleles found in peripheral blood and tissues of patients with different diagnosis with the number of heterozygous calls found using the molecular barcode demonstrates low complexity in cerebral malaria. Statistical comparison was made by ANOVA. Comparison of the average number of heterozygous calls found using the molecular barcode in the clinical peripheral blood samples shows a significant difference between retinopathy positive and retinopathy negative. The slightly higher average value of the retinopathy positives is due to the inclusion of patients who may be CM and SMA. Statistical comparison was made by t-test of means. (XLS 20 KB)
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Literatur
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