New Malaria Treatment: Researchers Test Single-Dose Approach

Researchers have tested a new single-dose malaria treatment that combines two antimalarial medicines with different mechanisms of action, in an effort to develop alternatives as resistance to existing malaria drugs continues to concern scientists and public-health authorities.

The Phase 2a CAPTURE-1 study evaluated cabamiquine combined with pyronaridine in adults and adolescents with uncomplicated Plasmodium falciparum malaria in Gabon and Uganda. The researchers reported that the combination produced more than 90% PCR-corrected efficacy at Day 28 in both study cohorts, with no serious adverse events or deaths recorded among the 38 participants who received treatment.

The findings were published in The Lancet Infectious Diseases in July 2026. Researchers describe the results as early evidence supporting further clinical development, rather than proof that the treatment is ready to replace existing malaria medicines.

Why researchers are looking for new malaria treatments

Most current first-line treatments for uncomplicated malaria are based on artemisinin combination therapies, commonly known as ACTs.

These medicines have played a major role in reducing malaria deaths and controlling infections. But malaria parasites with reduced susceptibility to artemisinin have emerged in parts of Africa, creating concern that existing treatments could become less effective if resistance spreads.

The World Health Organization and malaria researchers have therefore supported the development of medicines that use different mechanisms from artemisinin-based treatments.

The CAPTURE-1 researchers approached the problem by testing a combination that does not contain an artemisinin derivative.

What is cabamiquine?

Cabamiquine is an investigational antimalarial compound that works differently from currently approved artemisinin-based medicines.

According to the research programme behind the study, cabamiquine targets Plasmodium falciparum elongation factor 2, a molecular target that is not used by currently approved antimalarial medicines.

The researchers combined it with pyronaridine, an established antimalarial with a different mechanism of action and a relatively long half-life.

The idea is that combining medicines with complementary mechanisms could help clear parasites while reducing the opportunity for resistance to develop against the new compound.

The treatment was given as a single dose

One of the most notable features of the approach is the proposed dosing schedule.

Instead of requiring patients to take malaria medicine over several days, CAPTURE-1 investigated a single oral dose of cabamiquine and pyronaridine.

The researchers said a shorter regimen could potentially make treatment easier to complete, particularly in settings where access to healthcare is difficult or where patients may struggle to complete multi-day treatment.

That matters because incomplete treatment can leave parasites in the body and contribute to the selection of drug-resistant parasites.

However, a simpler treatment schedule still has to demonstrate that it is safe, effective and durable before it can be considered for routine use.

What happened in the clinical trial?

CAPTURE-1 was a prospective, multicentre, open-label Phase 2a study.

Participants were between 12 and 55 years old and had uncomplicated P. falciparum malaria confirmed through microscopy.

The study was conducted at five hospitals in four African countries, according to the published study, although the treated participants were reported from sites in Gabon and Uganda.

The trial had two parts.

In the first part, participants received a single oral dose containing 330 milligrams of cabamiquine and 360 milligrams of pyronaridine.

In the second part, participants received a higher, weight-adjusted dose of 660 milligrams of cabamiquine and 720 milligrams of pyronaridine.

The researchers assessed safety, tolerability, drug exposure and the ability of the treatment to clear malaria parasites.

Researchers reported encouraging early efficacy

The study found that PCR-corrected adequate clinical and parasitological response at Day 28 exceeded 90% in both treatment cohorts.

PCR correction is important in malaria trials because a patient can become infected again after treatment with a new parasite strain. Researchers use molecular testing to distinguish a new infection from a recurrence of the original infection.

The CAPTURE-1 results therefore provided an early indication that the treatment could clear the original malaria infection in most participants studied.

The study did not establish long-term effectiveness in a large population.

No serious adverse events were reported

Safety was another major part of the investigation.

The published study reported treatment-emergent adverse events in 25 of the 38 participants, or 65.8%.

Most were classified as mild or moderate.

Importantly, the researchers reported no serious adverse events and no deaths during the study.

This does not mean the treatment has been proven completely safe.

A trial involving only 38 treated participants cannot detect every possible adverse effect, particularly rare events that might become apparent only after much larger numbers of people receive a medicine.

That is one reason why medicines move through several stages of clinical testing before regulatory approval.

The trial was stopped early

The results also came with an important qualification.

The investigators planned additional cohorts, but those cohorts were not initiated.

According to the published study, the trial was stopped early after the researchers observed higher-than-predicted cabamiquine exposure in one cohort. The data monitoring committee also raised concerns about the dosing schedule, while the efficacy observed in the studied groups contributed to the decision to end the trial early.

This means the reported results should not be interpreted as evidence from a large completed Phase 2 programme.

The researchers instead used the available findings to determine whether the combination justified further development.

This was not a trial specifically of resistant malaria

The distinction between drug-resistant malaria and research designed to address the threat of resistance is particularly important.

The CAPTURE-1 participants had uncomplicated P. falciparum malaria, but the study was not a trial specifically enrolling patients whose infections had already been demonstrated to be resistant to existing antimalarial medicines.

Instead, the researchers were testing a treatment that does not rely on artemisinin and could potentially provide another option as resistance to existing therapies becomes more widespread.

That makes the study relevant to the drug-resistance problem without supporting a claim that cabamiquine has already been proven to cure artemisinin-resistant malaria in patients.

Why artemisinin resistance matters

Artemisinin-based combinations remain central to malaria treatment, but partial artemisinin resistance has been documented in Africa.

A 2026 study published in The New England Journal of Medicine, for example, examined intravenous artesunate treatment in Uganda in the context of artemisinin-resistant severe malaria and described the emergence and spread of partial resistance as a public-health concern.

Other research has also documented molecular markers associated with antimalarial resistance in Africa.

A study of malaria samples from northern Nigeria found high frequencies of some molecular markers associated with sulfadoxine-pyrimethamine resistance, while not finding the particular combinations associated with failure of preventive treatment in pregnancy.

These findings illustrate why researchers are looking beyond existing drug combinations rather than waiting until resistance becomes widespread.

Africa is becoming an important centre for new malaria trials

CAPTURE-1 is part of a wider effort to develop new malaria medicines through clinical research in Africa.

In September 2026, the West African Network for Clinical Trials of Antimalarial Drugs launched WANECAM3, an Africa-Europe research programme that will evaluate novel non-artemisinin antimalarial treatments in Phase 2 and Phase 3 trials. The programme aims to investigate potential single-dose treatments for uncomplicated malaria while strengthening clinical research capacity in Africa.

The European and Developing Countries Clinical Trials Partnership describes WANECAM3 as a five-year project focused on novel non-artemisinin combinations and antimicrobial drug resistance.

The wider research pipeline also includes other investigational compounds and combinations being studied for both uncomplicated and severe malaria.

What still needs to be established

The CAPTURE-1 findings do not establish that cabamiquine-pyronaridine is ready for general use.

The study was small, and the researchers ended it before all planned cohorts were completed.

Further trials are needed to determine the appropriate dose, confirm safety in larger populations and establish how well the treatment works over longer follow-up periods.

Researchers also need to study populations that were not adequately represented in the early trial.

The published study specifically points to the need for further development, including evaluation in children and other vulnerable populations.

What the research could mean for malaria treatment

If future clinical trials confirm the early findings, a single-dose non-artemisinin treatment could add another option to the malaria treatment pipeline.

The potential advantage would extend beyond convenience.

A medicine with a different mechanism could help diversify the available treatments and reduce reliance on one major drug class as resistance evolves.

But that potential remains subject to further evidence.

The researchers have not shown that cabamiquine-pyronaridine will replace current malaria treatments, and the study does not establish its effectiveness against every resistant malaria strain.

An early step in the search for new malaria medicines

The CAPTURE-1 study provides early clinical evidence for a new approach to malaria treatment at a time when researchers are increasingly concerned about antimalarial resistance.

The combination of cabamiquine and pyronaridine showed more than 90% PCR-corrected efficacy at Day 28 in the two cohorts studied, and no serious adverse events or deaths were reported among the 38 treated participants.

But the small sample size, early termination and need for additional dosing and population studies mean the findings should be viewed as an early research result rather than a finished treatment breakthrough.

The next phase of research will determine whether the single-dose approach can demonstrate sufficient safety, efficacy and durability in larger and more diverse groups of malaria patients.

For now, the study adds another candidate to the growing pipeline of medicines being investigated to protect malaria treatment from the threat of drug resistance.