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NIH grant 1R21AI202558-01: Investigating a positively-selected chromosome 7 haplotype associated with decreased susceptibility of Plasmodium falciparum to artemisinin and lumefantrine in Africa
Institute: {'code': 'AI', 'abbreviation': 'NIAID', 'name': 'National Institute of Allergy and Infectious Diseases', 'admin_org_id': '12500003', 'admin_funding_url': ''}. PI: JEFFREY A. BAILEY. Award: $251562.
Start: 2026-09-18T00:00:00.
ABSTRACT
Malaria remains a deadly global health threat, especially in Africa, where the most effective
treatments—artemisinin combination therapies (ACTs)—appear to be starting to fail. These therapies combine
a fast-acting drug (artemisinin-derivative) with a longer-acting partner drug. Artemether-lumefantrine is the
most widespread ACT, used in 85% of African malaria cases. Unfortunately, malaria parasites in Africa are
developing resistance to artemisinin, and there are now signs that lumefantrine is failing. Our research in
Uganda has pinpointed a specific, fast-spreading segment of the genome (a haplotype) on chromosome 7 of
the malaria parasite (Plasmodium falciparum) centered on a gene called PX1 that is strongly linked to this
decreased susceptibility of the parasite to artemisinin and lumefantrine. In this project, we will first map the
spread of this new resistance marker (PX1 PIN haplotype) across sub-Saharan Africa using thousands of
samples to determine how widespread the threat is beyond Uganda where we think it originated. Second, we
will use lab-based studies, including gene-editing techniques like CRISPR-Cas9, to definitively prove that the
changes in the PX1 gene are the direct cause of the drug resistance and to precisely define how this
resistance works. This work is crucial for understanding the extent of this emerging drug resistance threat and
for developing urgent new strategies to keep ACTs working and save lives.
This research project has two main goals to address the threat of emerging drug resistance in malaria:
Aim 1: Track the Spread of Resistance: We will use advanced DNA sequencing on thousands of malaria
samples from across Africa to determine how widely this new drug resistance marker (PX1 PIN haplotype) has
spread and if it is evolving alongside other resistance genes.
Aim 2: Confirm the Cause of Resistance: We will perform controlled laboratory tests using existing and
gene-edited parasites to definitively prove that the changes in the PX1 gene are the cause of the decreased
drug sensitivity, specifically to artemisinin and lumefantrine. We will also determine the exact life stage(s) of the
parasite that is most resistant
Together this will give us initial insight into the causative mutations and help inform us of the extent and degree
of the danger posed by the PX1 PIN markerdocument fetched 2026-09-27 02:45