Disease progression in Plasmodium knowlesi malaria is linked to variation in invasion gene family members
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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.
Ahmed , A M , Monsanto Pinheiro , M , Divis , P C , Siner , A , Zainudin , R , Wong , I T , Lu , C W , Singh-Khaira , S K , Millar , S B , Lynch , S , Willmann , M , Singh , B , Krishna , S & Cox Singh , J 2014 , ' Disease progression in Plasmodium knowlesi malaria is linked to variation in invasion gene family members ' PLoS Neglected Tropical Diseases , vol 8 , no. 8 , e3086 . DOI: 10.1371/journal.pntd.0003086
PLoS Neglected Tropical Diseases
Copyright 2014 Ahmed et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
This study was funded by The Medical Research Council (MRC) UK; Grant number G0801971. MMP is supported by The Wellcome Trust (ISSF 097831/Z/11/Z)