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Hypnozoites: Dormant Malaria Parasites Explained

Hypnozoites are dormant liver-stage forms of certain malaria parasites that can remain in the body for years after infection and cause late relapses of malaria.

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Things worth knowing about "Hypnozoites"

Hypnozoites are dormant liver-stage forms of certain malaria parasites that can remain in the body for years after infection and cause late relapses of malaria.

What Are Hypnozoites?

Hypnozoites are a dormant, inactive form of certain malaria-causing parasites. The term comes from the Greek words hypnos (sleep) and zoion (living being). These are resting stages of Plasmodium parasites that lodge inside the liver cells of an infected person, where they can survive for months or even years without causing any symptoms.

Which Parasites Form Hypnozoites?

Not all malaria parasites are capable of forming hypnozoites. Only two of the five human-pathogenic Plasmodium species produce them:

Plasmodium vivax: The most common cause of malaria relapses worldwide.
Plasmodium ovale: Less widespread, but also capable of forming hypnozoites.

Plasmodium falciparum, the most dangerous malaria parasite, does not form hypnozoites and therefore does not cause true late relapses.

How Do Hypnozoites Develop and What Do They Do?

When an infected Anopheles mosquito bites a person, it transmits sporozoites into the bloodstream. These travel to the liver and infect liver cells. While most sporozoites begin multiplying immediately, some develop into hypnozoites: they enter a dormant, metabolically inactive state, effectively hiding from both the immune system and most medications.

Under certain internal or external triggers – such as stress, fever, another infection, or a weakened immune system – hypnozoites can reactivate. They then begin to multiply, exit the liver, and re-enter the bloodstream, causing a new episode of blood-stage malaria. This process is known as a relapse and can occur months to years after the original infection.

Clinical Significance

Hypnozoites pose a major medical challenge because they:

are responsible for unexpectedly late malaria relapses, even long after leaving an endemic region,
cannot be eliminated by standard malaria treatments such as chloroquine,
make complete cure of malaria infections more difficult, and
contribute to the ongoing transmission of malaria in endemic areas.

Diagnosis

Hypnozoites cannot be directly detected with currently available diagnostic tools, as they remain hidden inside liver cells and cause no symptoms during their dormant phase. Standard malaria blood tests (blood smear or rapid diagnostic tests) do not detect them. The clinical diagnosis of a relapse is based on recurrence of symptoms and detection of parasites in the blood.

Treatment: Radical Cure Therapy

To eliminate hypnozoites and prevent future relapses, specific medications are required:

Primaquine: The standard drug for eliminating hypnozoites in P. vivax and P. ovale infections. It is taken over a 14-day course. Important: In individuals with G6PD deficiency (glucose-6-phosphate dehydrogenase deficiency), primaquine can trigger severe haemolysis (destruction of red blood cells).
Tafenoquine: A newer medication available as a single-dose treatment, but also contraindicated in people with G6PD deficiency.

This treatment approach is known as radical cure or anti-relapse therapy and is a critical step in fully treating vivax malaria (P. vivax) and ovale malaria (P. ovale).

References

World Health Organization (WHO): Guidelines for the treatment of malaria, 3rd edition, 2015. Available at: https://www.who.int/publications/i/item/9789241549127
White NJ: Plasmodium vivax infections. Trends in Parasitology, 2011. PubMed PMID: 21190884.
Commons RJ et al.: Estimating the proportion of Plasmodium vivax relapses attributable to the hypnozoite reservoir. PLOS Medicine, 2019. DOI: 10.1371/journal.pmed.1002945.

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