Link Between pfmdr1 Copy Number and Malaria Treatment Failure in Cambodia
Author Information
Author(s): Lim Pharath, Alker Alisa P, Khim Nimol, Shah Naman K, Incardona Sandra, Doung Socheat, Yi Poravuth, Bouth Denis Mey, Bouchier Christiane, Puijalon Odile Mercereau, Meshnick Steven R, Wongsrichanalai Chansuda, Fandeur Thierry, Le Bras Jacques, Ringwald Pascal, Ariey Frédéric
Primary Institution: Institut Pasteur in Cambodia
Hypothesis
Is there a link between pfmdr1 copy number and treatment failure in falciparum malaria?
Conclusion
Increased pfmdr1 copy number is associated with treatment failure in artesunate-mefloquine therapy but not in artemether-lumefantrine therapy.
Supporting Evidence
- Parasites with increased pfmdr1 copy number had significantly reduced in vitro susceptibility to mefloquine, lumefantrine, and artesunate.
- The presence of three or more copies of pfmdr1 was associated with recrudescence in artesunate-mefloquine treated patients.
- Pfmdr1 copy number was lower in subjects with adequate clinical response compared to those with treatment failure.
Takeaway
This study found that having more copies of a specific gene (pfmdr1) can make malaria treatment with one medicine less effective, but it doesn't affect another type of treatment.
Methodology
Blood samples were collected from malaria-infected patients and analyzed for pfmdr1 copy number and drug susceptibility.
Potential Biases
Potential bias due to low quality of some samples affecting in vitro testing results.
Limitations
In vitro drug sensitivity was successfully assayed in only 44% of samples due to low parasite counts.
Participant Demographics
Patients were over six years old with confirmed Plasmodium falciparum mono-infection.
Statistical Information
P-Value
p<0.001
Confidence Interval
95%CI: 2.09–29.10
Statistical Significance
p<0.001
Digital Object Identifier (DOI)
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