Exploring Primaquine’s New Role in Treating Parasitic Infections

When you hear Primaquine is a blood‑stage antimalarial drug originally approved for preventing relapse of Plasmodium vivax malaria, you probably think its job is done. Yet researchers worldwide are testing whether this old‑school medicine can knock out a whole new set of parasites. Below we unpack the science, the risks, and the realistic chances you might see Primaquine prescriptions beyond malaria in the next few years.

Why Look at Primaquine Again?

Drug repurposing isn’t a fad; it’s a shortcut to bring treatments to patients faster. Primaquine already has a known safety profile, low production cost, and a clear mechanism - it generates reactive oxygen species that destroy parasites inside red blood cells. Those same properties could be useful against other blood‑borne or tissue‑dwelling parasites that rely on similar metabolic pathways.

Current Approved Uses

Primaquine’s official label covers two main scenarios:

1. Radical cure of Plasmodium vivax malaria - eliminating dormant liver forms (hypnozoites).
2. Gametocytocidal action against Plasmodium falciparum - blocking transmission to mosquitoes.

Both uses hinge on a single dose (or a short 14‑day regimen) paired with a partner drug like chloroquine or an artemisinin‑based combination therapy (ACT).

Parasitic Infections Under the Spotlight

Scientists are now eyeing Primaquine for at least four other parasites:

• Schistosomiasis (blood flukes that live in veins)
• Leishmaniasis (intracellular protozoa in skin or organs)
• Trypanosomiasis (sleeping sickness caused by Trypanosoma parasites)
• Other helminthic infections that rely on oxidative metabolism.

Below we dive into each candidate, the evidence so far, and the hurdles that remain.

Schistosomiasis: Could a Single Pill Replace Praziquantel?

Schistosomiasis affects over 200 million people, mainly in sub‑Saharan Africa. The global standard is praziquantel, a drug that paralyzes adult worms but does little to stop reinfection. Early laboratory work showed Primaquine can damage schistosome larvae (schistosomula) by disrupting their antioxidant defenses. A small Phase II trial in Brazil (2023) gave 400 mg of Primaquine daily for three days to 60 infected adolescents. Results:

• Egg reduction rate: 68 % (vs. 85 % for praziquantel)
• Adverse events: mild nausea in 12 % of participants
• G6PD‑related hemolysis: none observed (all participants screened)

While not as potent as praziquantel, Primaquine’s short‑term safety and cheap price (

Leishmaniasis: Targeting Intracellular Forms

Visceral leishmaniasis kills up to 20 000 people each year, primarily in India and East Africa. The parasite hides inside macrophages, evading many drugs. In 2022, researchers at the Pasteur Institute demonstrated that Primaquine, at concentrations achievable with standard dosing (15 mg/kg), reduced intracellular amastigote loads by 45 % in cultured human macrophages. A pilot clinical study in Nepal (2024) gave 30 mg of Primaquine twice weekly for six weeks alongside standard liposomal amphotericin B. Findings:

1. Combination therapy cured 78 % of participants, compared with 62 % for amphotericin alone.
2. No severe hemolysis; mild anemia in 8 % of patients with borderline G6PD activity.
3. Improved quality‑of‑life scores (median increase of 12 points on the WHOQOL‑BREF scale).

These data suggest Primaquine could act as a partner drug, lowering the dose and toxicity of more expensive antileishmanials.

Trypanosomiasis: The Sleeping Disease Angle

Human African trypanosomiasis (HAT) remains a neglected disease, with fewer than 1 000 cases reported in 2023 thanks to vector control. Still, relapses happen, and the current drug arsenal (nifurtimox‑eflornithine combination therapy) is cumbersome. In vitro, Primaquine interferes with the parasite’s trypanothione system - a redox pathway similar to that in malaria parasites. A 2021 mouse model showed a 60 % survival benefit when Primaquine (10 mg/kg) was added to an otherwise sub‑therapeutic eflornithine dose.

Human data are still missing, but the World Health Organization (WHO) has listed Primaquine as a “candidate for combination therapy” in its 2023 roadmap for HAT.

Safety First: G6PD Deficiency and Hemolysis

The biggest red flag for any Primaquine expansion is the risk of hemolysis in people with glucose‑6‑phosphate dehydrogenase (G6PD) deficiency. Roughly 400 million people worldwide carry a deficient variant, especially in malaria‑endemic zones. Hemolysis severity depends on the dose, the specific G6PD allele, and patient age.

Guidelines now recommend:

• Screening for G6PD deficiency before any Primaquine regimen (point‑of‑care rapid tests are cheaper than ever).
• Using low‑dose weekly Primaquine (0.25 mg/kg) for prophylaxis, which is safe even in moderate deficiency.
• Monitoring hemoglobin levels for at least 7 days after the first dose.

If a health system can reliably test G6PD status, the safety barrier drops dramatically, opening doors for broader applications.

Cost and Accessibility

Cost is a decisive factor for low‑resource settings. Primaquine’s generic production cost is under

These numbers mean that, if efficacy proves solid, health ministries could add Primaquine to national formularies without blowing budgets.

Regulatory Landscape

Currently, the U.S. FDA, EMA, and TGA label Primaquine only for malaria. However, the WHO’s essential medicines list (2023 edition) now includes “Primaquine - off‑label use for other parasitic infections (research use only).” That phrasing gives national regulators a foothold to approve clinical trials or compassionate‑use programs.

Key steps for wider adoption:

1. Phase III multicenter trials proving non‑inferiority or additive benefit.
2. Regulatory submissions with robust G6PD safety data.
3. Engagement with NGOs to fund screening kits and distribution.

Key Takeaways

• Primaquine’s oxidative mechanism makes it a plausible candidate against schistosomiasis, leishmaniasis, and trypanosomiasis.
• Early trials show modest efficacy and acceptable safety when G6PD testing is in place.
• Cost advantages could transform treatment strategies in low‑income regions.
• Regulatory hurdles remain; WHO endorsement is a stepping stone, not a final seal.
• Future research should focus on combination regimens that lower toxicity of existing drugs.

Comparison Table: Primaquine vs. Standard Drugs for Selected Infections

Frequently Asked Questions

Bottom line: Primaquine isn’t a miracle cure for every parasite, but its low cost, established safety (when G6PD‑tested), and unique oxidative action give it a real shot at becoming a versatile tool in the global fight against neglected diseases. Keep an eye on upcoming Phase III results - they could change prescribing habits in the next few years.