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Disease progression in Plasmodium knowlesi malaria is linked to variation in invasion gene family members

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Author(s)

Atique M. Ahmed, Miguel Monsanto 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

School/Research organisations

Abstract

Plasmodium knowlesi, a parasite of Southeast Asian macaques, has entered the human population. Approximately 10% of P. knowlesi infections are severe, 1–2% are fatal, in Sarawak, Malaysian Borneo. Increase in parasitaemia is associated with disease severity, but little is known about parasite virulence in this newly described human pathogen. Here we present the results of a study on P. knowlesi parasites collected from 147 patients. We use the isolates to produce DNA sequences from a polymorphic (genetically variable) region of two P. knowlesi genes, Pknbpxa and Pknbpxb, that are involved in parasite entry into host red blood cells. We addressed the question that some parasite genotypes may have an invasion advantage leading to severe disease in human infections. We analysed the DNA sequences with matched clinical and laboratory data from the patient cohort (n = 147). We found that specific DNA sequences (Pknbpxa and Pknbpxb alleles) clustered with high parasitaemia and markers of disease severity. Here, for the first time, we provide evidence that variant alleles of the Plasmodium Reticulocyte Binding-Like Protein invasion gene family can influence disease progression in patients with malaria. The biological characteristics of the variants will be studied to aid our understanding of malaria pathophysiology and to inform intervention strategies.

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Details

Original languageEnglish
Article numbere3086
Number of pages14
JournalPLoS Neglected Tropical Diseases
Volume8
Issue number8
DOIs
Publication statusPublished - 14 Aug 2014

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