Abstract
To monitor drug resistance in Plasmodium vivax, a multidrug resistance 1 (Pvmdr1) gene and a putative transporter protein (Pvcrt-o) gene were used as molecular markers for chloroquine resistance. The biomarkers, the dihydrofolate reductase (Pvdhfr) gene and the dihydropteroate synthetase (Pvdhps) gene, were also used for the detection of resistance to sulphadoxine-pyrimethamine (SP); this drug is often accidentally used to treat P. vivax infections. Clinical blood samples (n = 120) were collected from patients who had been to one of eight malaria-endemic countries and diagnosed with P. vivax infection. The chloroquine resistance marker, the Pvmdr1 gene, showed F976:L1076 mutations and L1076 mutation. A K10 insertion in the Pvcrt-o gene was also found among the samples successfully sequenced. A combination of L/I57:R58:M61:T117 mutations in the Pvdhfr gene and G383:G553 mutations in the Pvdhps gene were also observed. Mutations found in these genes indicate that drug resistance is present in these eight countries. Whether or not countries are using chloroquine to treat P. vivax, there appears to be an increase in mutation numbers in resistance gene markers. The detected changes in mutation rates of these genes do suggest that there is still a trend towards increasing P. vivax resistance to chloroquine. The presence of the mutations associated with SP resistance indicates that P. vivax has had exposure to SP and this may be a consequence of either misdiagnosis or coinfections with P. falciparum in the past.
Highlights
In Australia, about 500 malaria cases are reported each year [1] and just under half of them are diagnosed with Plasmodium vivax [2]
Chloroquine resistance in P. vivax was found around the late 1980s and resistance was first reported in Australian travellers, who were diagnosed with P. vivax infection after returning from Papua New Guinea (PNG) [7,8]
Pvcrt-o genes were used as they are orthologous to P. falciparum multidrug-resistant transporter-1 (Pfmdr1) and P. falciparum chloroquine resistance transporter (Pfcrt) genes, which are associated with chloroquine resistance in P. falciparum [6]
Summary
In Australia, about 500 malaria cases are reported each year [1] and just under half of them are diagnosed with Plasmodium vivax [2]. Chloroquine resistance in P. vivax was found around the late 1980s and resistance was first reported in Australian travellers, who were diagnosed with P. vivax infection after returning from Papua New Guinea (PNG) [7,8]. These travellers failed to clear the parasitemia by the standard chloroquine dose [3,6,9,10]. During this period, other reports of chloroquine-resistant P. vivax arose from Asian and South American countries [9]
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