A Ugandan malaria haplotype dulls three drugs while pooled digoxin trials cut admissions
A peer-reviewed Nature Medicine study links a spreading Ugandan Plasmodium haplotype to lower susceptibility to three antimalarials, while pooled Dutch trials tie low-dose digoxin to a 25 percent drop in heart-failure hospitalisations.
Science··Evening
PX1 haplotype spreads and dulls three antimalarials
Whole-genome sequencing of 157 Plasmodium falciparum samples from Uganda put the strongest recent selection signal on chromosome 7, at the phosphoinositide-binding protein PX1. The haplotype, three mutations plus two deletions, was first seen in 2008 and passed 50 per cent prevalence in northern Uganda by 2016 and in eastern Uganda by 2023. The peer-reviewed study appeared in Nature Medicine. Parasites carrying the haplotype showed significantly lower ex vivo susceptibility to lumefantrine, mefloquine and dihydroartemisinin, the active metabolite of artemether. Disrupting px1 in vitro left a parasite strain more susceptible to all three. Artemether-lumefantrine is the most widely used first-line artemisinin-based combination therapy in Africa; the authors report the ex vivo result as a susceptibility signal and leave clinical outcomes to further study.[1]
Low-dose digoxin trims admissions once three trials merge
UMCG cardiologists randomised about 1,000 heart-failure patients at 43 centres in the Netherlands to low-dose digoxin or placebo on top of standard care for an average of three years. Cardiovascular death and worsening heart failure fell by 19 percent in the digoxin arm, a result that did not reach statistical significance on its own. Pooling the trial with two earlier studies produced a significant reduction of about 25 percent in heart-failure hospitalisations. The studies, led by Dirk Jan van Veldhuisen, Kevin Damman and Peter van der Meer, report that the pooled benefit held in patients already taking all four standard drugs. Standard heart-failure care now rests on four drugs, and the question the team set out to answer was whether digoxin, in use for centuries and costing less than ten cents a day, is worth adding as a fifth. The results were also presented at the ESC Heart Failure Congress in Barcelona. More than 500,000 people in the Netherlands are estimated to live with heart failure.[2]
Uganda adopted artemether-lumefantrine two years before PX1 arose
Artemether-lumefantrine became Uganda's first-line treatment for uncomplicated malaria in 2006, two years before the PX1-linked PIN haplotype was first recorded in 2008. Uganda sits among the epicenters where artemisinin partial resistance and declining lumefantrine susceptibility are emerging in African surveillance; the Nature Medicine paper cites lumefantrine's mechanism as still unknown. A follow-on arm tracked roughly 600 of the original digoxin trial participants after treatment stopped; among 288 patients who had been on digoxin, 14 were hospitalized or died in the first six weeks after withdrawal. Digoxin now reaches only about 15 percent of heart-failure patients in the Netherlands, and the pooled analysis reports low-dose treatment as generally safe and relatively easy to use.[1], [2]
