Cracking the Code: Malaria Gene Mutations & Drug Resistance
Malaria is a disease caused by a parasite called Plasmodium falciparum, which is transmitted to humans through the bite of infected female Anopheles mosquitoes. In Ghana, the primary malaria vectors are Anopheles gambiae sensu stricto and Anopheles funestus, two species known for their efficiency in spreading malaria.
In Ghana and many parts of Africa, malaria is treated with a group of medicines called artemisinin-based combination therapies (ACTs). But sometimes, these treatments don’t work as well as they should. One major reason is that the parasite can develop resistance through changes in its genes—what scientists call mutations.
In this blog post, we’ll break down the important mutations that help the parasite survive even when drugs are used. We'll also explain how these changes work, what their names mean, and how malaria is currently treated.
Watch the video here:
What Are the Recommended Treatments for Malaria in Ghana?
The first choice treatment in Ghana for uncomplicated malaria is Artemisinin-based Combination Therapy (ACT). This means the medicine combines:
An artemisinin derivative (which kills parasites fast),
Plus a partner drug (which stays longer in the body to kill leftover parasites).
Common ACTs used in Ghana include:
Artemether-Lumefantrine (AL)
Artesunate-Amodiaquine (AS-AQ)
There’s also Sulfadoxine-Pyrimethamine (SP), which is used mainly for prevention during pregnancy (called IPTp).
Why Do We Use Partner Drugs with Artemisinin?
Artemisinin works very fast, clearing most parasites in about 48 hours, but it leaves the body quickly. Without a partner drug to clean up the rest, some parasites might survive and multiply again.
Partner drugs:
Kill the remaining parasites after artemisinin finishes,
Help prevent the parasite from becoming resistant to artemisinin,
Lower the chance of the infection coming back (called recrudescence).
What Are Gene Mutations?
Mutations are small changes in the DNA of an organism. In malaria parasites, some mutations change the shape or behavior of proteins that drugs target. This means the drugs can no longer kill the parasite effectively.
Each mutation has a special code to describe it. For example:
K76T means:
K: The normal amino acid is lysine.
76: The change happens at position 76 of the protein.
T: The amino acid changes to threonine.
Important Genes and Mutations in Malaria Resistance
1. Chloroquine Resistance
pfcrt gene: The key mutation is K76T.
pfmdr1 gene: Other changes include N86Y, Y184F, and D1246Y.
These mutations make it harder for chloroquine to kill the parasite.
2. Sulfadoxine-Pyrimethamine (SP) Resistance
SP is a mix of two drugs that block folate synthesis in the parasite.
pfdhfr gene: Mutations like N51I, C59R, and S108N make pyrimethamine less effective.
pfdhps gene: Changes like A437G and K540E reduce the power of sulfadoxine.
When multiple mutations happen together (especially 3 in pfdhfr and 2 in pfdhps), the treatment may not work at all. This is called quintuple resistance.
3. Artemisinin Partial Resistance
pfkelch13 gene: Changes like C580Y, R561H, and Y493H are signs that artemisinin might not clear the parasite quickly.
These mutations don't stop artemisinin completely but slow down how fast the parasite is removed from the body.
What Are Haplotypes?
A haplotype is a group of mutations that are often found together in a parasite. For example:
CVIET is a haplotype found in chloroquine-resistant parasites. It shows changes at positions 72 to 76 in the pfcrt gene.
The wild-type (non-mutated) version is called CVMNK. The mutant version CVIET includes the important K76T mutation.
Summary Table
Why This Matters
Knowing these mutations helps scientists and health workers:
Monitor which drugs are still working
Plan better treatments
Prevent resistance from spreading
Conclusion
As a student learning about malaria, it’s important to understand not just how the disease is treated but also how the parasite can fight back. By studying gene mutations and resistance patterns, we can help protect future treatments and save lives.
If you want to learn more, explore topics like molecular epidemiology, PCR testing for resistance, and how these studies shape malaria policies in Ghana and beyond!
Bibliography
WHO. 2019. World malaria report 2019. https://www.who.int/publications -detail/world-malaria-report-2019. Accessed 9 December 2019.
WHO. 2009. Anti-malaria drug policy for Ghana, 2nd revised version 2009. http://apps.who.int/medicinedocs/en/d/Js18072en/.
Mensah, B. A., Aydemir, O., Myers-Hansen, J. L., Opoku, M., Hathaway, N. J., Marsh, P. W., Anto, F., Bailey, J., Abuaku, B., & Ghansah, A. (2020). Antimalarial Drug Resistance Profiling of Plasmodium falciparum Infections in Ghana Using Molecular Inversion Probes and Next-Generation Sequencing. Antimicrobial Agents and Chemotherapy, 64(4), e01423-19.
Mensah, B. A., Akyea-Bobi, N. E., & Ghansah, A. (2022). Genomic approaches for monitoring transmission dynamics of malaria: A case for malaria molecular surveillance in Sub–Saharan Africa. Frontiers in Epidemiology, 2, Article 939291. https://doi.org/10.3389/fepid.2022.939291
Verity, R., Aydemir, O., Brazeau, N. F., et al. (2020). The impact of antimalarial resistance on the genetic structure of Plasmodium falciparum in the DRC. Nature Communications, 11, Article 2107. https://doi.org/10.1038/s41467-020-15779-8
Wei, X., Brashear, A., Siddiqui, F., Agyekum, G., Lucky, A., Chim-Ong, A., Afrane, Y., Miao, J., Wang, C., Amoah, L., & Cui, L. (2025). Plasmodium falciparum genetic diversity and multiplicity of infection in northern and southern Ghana assessed by amplicon sequencing. Infection, Genetics and Evolution, 131, 105754.
Ghansah, A., Tiedje, K. E., Argyropoulos, D. C., Onwona, C. O., Deed, S. L., Labbé, F., Oduro, A. R., Koram, K. A., Pascual, M., & Day, K. P. (2023). Comparison of molecular surveillance methods to assess changes in the population genetics of Plasmodium falciparum in high transmission. Frontiers in Parasitology, 2, Article 1067966. https://doi.org/10.3389/fpara.2023.1067966
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