Mutations in Malaria Parasite Gene Linked to Treatment Delays
Author Information
Author(s): Colin J Sutherland, Matt Laundy, Nicholas Price, Martina Burke, Quinton L Fivelman, Geoffrey Pasvol, John L Klein, Peter L Chiodini
Primary Institution: London School of Hygiene & Tropical Medicine
Hypothesis
Are mutations in the Plasmodium falciparum cytochrome b gene associated with delayed parasite recrudescence in malaria patients treated with atovaquone-proguanil?
Conclusion
Genetically-determined parasite resistance to atovaquone is associated with delayed recrudescence of resistant parasites three weeks or more after initial clearance of parasitaemia by atovaquone/proguanil therapy.
Supporting Evidence
- Parasites with pfcyt-b mutations were found in five patients with delayed symptoms after treatment.
- The mean time to recrudescence for mutated parasites was estimated at 28.0 days.
- Four patients carried the Tyr268Cys mutation, previously reported in other cases.
Takeaway
Some malaria patients who took a specific treatment had their symptoms come back weeks later because the parasites had changed in a way that made the treatment less effective.
Methodology
DNA sequencing analysis was performed on P. falciparum cyt-b genes from malaria patients with recurrent parasitaemia following treatment with atovaquone-proguanil.
Potential Biases
Potential bias due to the small sample size and reliance on patient self-reporting for treatment adherence.
Limitations
The study may not account for all treatment failures, as some patients may have sought treatment elsewhere.
Participant Demographics
Patients included both males and females, with ages ranging from 5 to 60 years, and varied ethnic backgrounds.
Statistical Information
P-Value
p<0.05
Confidence Interval
95% C.I. 23.0 – 33.0 days
Statistical Significance
p<0.05
Digital Object Identifier (DOI)
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