21 SEP 2026 — Starve the malaria parasite, warm it to a fever, or dose it with the front-line drug, and it does the same thing in response to all three: it starts making the forms that infect mosquitoes. A team at the Barcelona Institute for Global Health has found the switch those three signals run through, a protein called AP2-HS, and shown that deleting the gene behind it stops the process entirely.
The parasite that cannot make those forms is still lethal to the person carrying it. It simply cannot get out.
What the parasite is answering
Plasmodium falciparum spends most of its time in the blood multiplying asexually. A small fraction of each generation becomes gametocytes, the sexual stage, and gametocytes are the only form a mosquito can pick up. Onward transmission depends on that conversion rate.
It has been known for years that stress raises the rate. What was missing was the machinery. The study, published in Nature Microbiology on 17 September, tested three stresses: nutrient limitation, a simulated fever episode, and treatment with dihydroartemisinin, the artemisinin derivative at the centre of current malaria therapy.
All three converge on one protein.
The switch and its brake
AP2-HS works as the control hub. It detects the stressed condition and activates expression of a gene called gdv1, which is the established trigger for gametocyte conversion.
The mechanism is not just transcription. The response also reorganises heterochromatin, the packed form of DNA that holds particular genes silent, which is a slower and more structural change than switching genes on alone.
When GDV1 is activated, it simultaneously drives production of gdv1-as, an RNA that represses gdv1 itself. The switch turns on its own off-switch. The researchers describe the loop as a braking system. It permits a fast response to stress while preventing GDV1 from staying active longer than needed, which would otherwise be lethal to the parasite.
The deletion result
The strongest evidence is the knockout. "When we deleted the ap2-hs gene, the parasites completely lost their ability to develop into gametocytes, even under stressful conditions," said Elisabet Tintó, the study's lead author.
That is a clean result, and it makes AP2-HS a target rather than a curiosity. A compound that blocked it would not cure anyone. It would stop the parasite in a treated person from becoming infectious to the next mosquito. That is a public health objective rather than a therapeutic one.
Why the drug condition matters
Of the three stresses tested, the result for dihydroartemisinin is the most pointed. The drug used to clear the infection is also, in culture, one of the conditions that raises conversion toward the transmissible stage.
That is worth stating carefully, because the obvious inference runs ahead of the evidence. This was an experiment in cultured parasites, not a study of treated patients, and the researchers draw no conclusion about treatment practice. The work establishes the mechanism and the switch, not a clinical effect.
Where this lands for the region
Artemisinin-based therapy is the front line across the Greater Mekong, and reduced susceptibility to it has been tracked in the region for years. A mechanism linking exposure to that drug class with the parasite's sexual conversion is therefore directly relevant to the region. The research team did not make that connection; it is ours, and it is a reason to watch the follow-up work rather than a finding.
The study was led by Alfred Cortés, an ICREA researcher at ISGlobal, with Tintó as first author, and was funded by the "la Caixa" Foundation, Spain's Ministerio de Ciencia and Agencia Estatal de Investigación, and the European Regional Development Fund.
View author profile → · Editorial policy
