Medical School

Postgraduate research profiles

Contact

Rina Wong

Phone: (+61 8) 9431 2358
Fax: (+61 8) 9431 2977


Supervisors

Start date

Jan 2007

Submission date

Dec 2009

Links

Curriculum vitae

Rina Wong CV
[application/rtf, 104.91 kb]
Updated 02 Sep 2009

Rina Wong

Rina Wong profile photo

Thesis

Resistance of Plasmodium falciparum to anti-malarial in Papua New Guinea: Associations between in vitro drug sensitivity, genetic mutations and clinical outcome.

Summary

Malaria is a resurgent disease causing 500 million cases, 2 million deaths and threatening half the world’s population each year. Papua New Guinea (PNG) is endemic to four species Plasmodium, with P. falciparum being predominant. It is the most dangerous species, being responsible for the highest mortality and cerebral malaria. Young children and pregnant women carry the brunt of the burden. P. falciparum has developed resistance to most available antimalarial drugs, hampering the multifaceted efforts in malaria control and eradication.

This project introduced the use of an enzyme based assay plasmodium lactate dehydrogenase (pLDH) to monitor in vitro drug sensitivity of P. falciparum field isolates from PNG. This method is less time consuming and less labour intensive compared to the traditional microscopic quantification of schizont maturation. The in vitro sensitivity to nine conventional (chloroquine, amodiaquine and its metabolite) and novel drugs (lumefantrine, mefloquine, piperaquine, naphthoquine, dihydroartemisinin, azithromycin) are reported and cross resistance between these drugs are also examined. The above field component was carried out in collaboration of the PNG Institution of Medical Research, Madang, PNG. In addition, we have characterised the underlying genotypes associated with drug resistance. In particular, we examined 28 single nucleotide polymorphisms (SNPs) in four drug resistant genes in the parasite genome, namely P. falciparum chloroquine transporter (pfcrt), P.falciparum dihydrofolate reductase (pfdhfr), P. falciparum dihydropteorate synthetase (pfdhps) and P. falciparum multidrug resistance 1 (pfmdr1) genes. The technique employed was based on a post PCR ligase detection reaction fluorescence microsphere assay (LDR-FMA), with a novel component for pfmdr1 evaluation developed as part of this thesis. This technique was originally developed at the Centre for Global Health and Diseases, Case Western Reserve University, Cleveland, Ohio, where this part of the study was carried out . The in vitro and molecular data will be matched with known clinical treatment outcomes from the WHO and NHMRC sponsored ‘standard treatment trial’ conducted in PNG. These data will be collated for the development of a statistical model that will identify predictors of treatment failure.

Secondary aims include investigating the use of statins and fibrates as antimalarial drugs by means of in vitro growth inhibition assays and bioassays. Isobologram studies were also performed to identify interactions between these with conventional antimalarials with the view of their potential use in adjunctive therapy.

Why my research is important

Our efforts contribute to an important part of the global fight against malaria.

Funding

  • APA Scholarship
  • AdHoc Scholarship, School of Medicine and Pharmacology, UWA
  • Postgraduate Travel Award, UWA