Malaria, a disease primarily associated with acute illness, presents a persistent challenge in certain forms due to a hidden stage of the parasite. Some types of the disease can linger, posing a threat long after initial recovery. This continued risk stems from dormant forms of the malaria parasite known as hypnozoites. These parasites represent a significant hurdle in controlling and ultimately eradicating malaria globally.
What Are Hypnozoites?
Hypnozoites are dormant, liver-stage forms of Plasmodium parasites, specifically associated with Plasmodium vivax and Plasmodium ovale species. When an infected mosquito bites a human, it injects sporozoites, which travel to the liver. While some sporozoites develop immediately into a multiplying form that leads to acute illness, a proportion of them transform into inactive hypnozoites within liver cells.
These dormant forms can remain in the liver for weeks, months, or even years without causing any symptoms. Unlike other parasite stages that progress directly to the bloodstream, hypnozoites are characterized by their arrested development. They are believed to be small, spherical, and non-dividing forms within the host’s liver cells. The exact biological mechanisms that govern their entry into dormancy and subsequent activation are still under investigation.
How Hypnozoites Cause Malaria Relapse
The clinical significance of hypnozoites lies in their ability to reactivate from their dormant state in the liver. When activated, these hypnozoites mature and release new parasites into the bloodstream, leading to recurrent episodes of malaria, known as relapses. These relapses can occur weeks, months, or even years after the initial infection has been treated and the patient has recovered.
Relapses cause repeated bouts of illness and chronic symptoms for individuals. From a public health perspective, relapses contribute to continued malaria transmission, even in areas where active cases are being managed. It is important to distinguish a “relapse,” which originates from these dormant liver-stage hypnozoites, from a “recrudescence,” which refers to the re-emergence of blood-stage parasites due to an inadequately treated initial infection. The factors triggering hypnozoite activation are not fully understood, but a new malaria infection or other febrile illnesses may play a role.
Treating and Eliminating Hypnozoites
Targeting hypnozoites is a focus in malaria treatment and elimination efforts. The primary anti-malarial drugs effective against these dormant liver stages are primaquine and tafenoquine, both belonging to the 8-aminoquinoline class. These medications are often referred to as hypnozoitocidal drugs due to their ability to clear the liver-stage parasites, preventing future relapses.
A notable challenge with primaquine and tafenoquine is the requirement for glucose-6-phosphate dehydrogenase (G6PD) deficiency testing before administration. Individuals with G6PD deficiency can experience severe side effects, such as acute hemolytic anemia, when taking these drugs. Therefore, testing for this genetic condition is a necessary step to ensure patient safety. Eliminating hypnozoites helps achieve a complete cure for patients and disrupts the cycle of malaria transmission, supporting global malaria eradication initiatives. Research continues to explore new drug candidates and strategies to overcome the limitations of current treatments and improve the efficacy of hypnozoite clearance.