Given the relatively recent discovery of its impact on
human health, there is comparatively little information
on the underlying biological mechanisms of pathogenesis
in P. knowlesi. Furthermore, little is known of the degree of
parasite genetic diversity in naturally acquired human infections. A recent study on the association between P.
knowlesi genotype and disease progression involved the
analysis of the DNA sequences of Pknbpxa and Pknbpxb
invasion gene candidates to determine whether they were
polymorphic in human infections (Box 1). This was found to
be the case, with Pknbpxa being more diverse than
Pkbnpxb [1]. DNA sequences were then generated from
polymorphic fragments of Pknbpxa and Pknbpxb from
138 and 134 patient isolates, respectively. The researchers
found 12 Pknbpxa DNA sequence groups and two Pknbpxb
groups in the patient cohort. Parasite isolates within each
group had additional polymorphisms that constituted two
or three allelic types. The alleles with matched patient
clinical and laboratory data were analysed and statistically
significant clustering of particular alleles with clinical and
laboratory measures of disease progression was found,
including parasitaemia [1]. This report showed that some
P. knowlesi parasites may be more virulent in the human
host, and that this virulence is associated with certain
parasite genotypes. These findings can now be taken forward
in proof-of-principle testing using in vitro invasion
assays.
Given the relatively recent discovery of its impact onhuman health, there is comparatively little informationon the underlying biological mechanisms of pathogenesisin P. knowlesi. Furthermore, little is known of the degree ofparasite genetic diversity in naturally acquired human infections. A recent study on the association between P.knowlesi genotype and disease progression involved theanalysis of the DNA sequences of Pknbpxa and Pknbpxbinvasion gene candidates to determine whether they werepolymorphic in human infections (Box 1). This was found tobe the case, with Pknbpxa being more diverse thanPkbnpxb [1]. DNA sequences were then generated frompolymorphic fragments of Pknbpxa and Pknbpxb from138 and 134 patient isolates, respectively. The researchersfound 12 Pknbpxa DNA sequence groups and two Pknbpxbgroups in the patient cohort. Parasite isolates within eachgroup had additional polymorphisms that constituted twoor three allelic types. The alleles with matched patientclinical and laboratory data were analysed and statisticallysignificant clustering of particular alleles with clinical andlaboratory measures of disease progression was found,including parasitaemia [1]. This report showed that someP. knowlesi parasites may be more virulent in the humanhost, and that this virulence is associated with certainparasite genotypes. These findings can now be taken forwardin proof-of-principle testing using in vitro invasionassays.
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