hypnozoites

Hypnozoites are dormant liver-stage forms of certain malaria parasites that can reactivate and cause relapse infections. They most commonly occur in Plasmodium vivax and Plasmodium ovale infections, though not in Plasmodium falciparum. After a mosquito bite, sporozoites travel to hepatocytes; most develop into liver schizonts that release merozoites, but a subset remains dormant as hypnozoites, sometimes for weeks to years.

During blood-stage infection, relapse occurs when hypnozoites reactivate and initiate a new cycle of merozoite release independent of re-exposure to mosquitoes. Relapses can occur despite clearance of the initial blood infection and can sustain transmission in endemic areas.

Diagnosis is challenging; hypnozoites cannot be detected by routine blood smears or standard diagnostics. Clinically, relapse malaria is distinguished from reinfection by exposure history and regional patterns, but differentiation is not always possible.

Treatment and prevention: Radical cure requires agents that eliminate liver hypnozoites in addition to treating blood-stage parasites. The 8-aminoquinoline primaquine has long been used to eradicate hypnozoites with a typical 14-day course, while tafenoquine provides a longer-acting option; both require screening for glucose-6-phosphate dehydrogenase (G6PD) deficiency due to risk of hemolysis, and are generally avoided in pregnancy. G6PD testing is essential before initiating therapy.

Clinical significance: Hypnozoites explain relapse patterns in vivax and ovale malaria and present challenges for malaria elimination. Research continues to clarify triggers for hypnozoite activation and to improve monitoring and safety of radical-curative regimens.