What is Malaria Relapse?
Malaria relapse refers to the recurrence of malaria symptoms after a period of apparent recovery from an initial infection. This happens when Plasmodium parasites remain dormant in the liver after the initial infection and later reactivate to cause new episodes of illness. Relapse is most commonly associated with Plasmodium vivax and Plasmodium ovale infections, which have a liver stage that can remain dormant for months or even years.

What causes Malaria Relapse?
Malaria relapse occurs when hypnozoites, the dormant form of the parasite, are left in the liver after the initial infection. These hypnozoites can remain inactive for weeks, months, or even years before becoming active again. When they reactivate, they re-enter the bloodstream and infect red blood cells, causing a recurrence of symptoms.

• Plasmodium vivax and Plasmodium ovale are the species most commonly associated with relapse, due to their ability to form hypnozoites in the liver.
• Plasmodium falciparum and Plasmodium malariae do not form hypnozoites and are less likely to cause relapse, although reinfection can still occur.

Who is at risk for Malaria Relapse?
Individuals who have been previously infected with Plasmodium vivax or Plasmodium ovale are at risk of relapse. People living in or traveling to malaria-endemic areas, particularly those in sub-Saharan Africa, Southeast Asia, and South America, are more likely to experience relapse if they do not receive appropriate treatment. Factors that increase the risk of relapse include:

• Inadequate treatment of the initial malaria infection, which may not completely eradicate hypnozoites from the liver
• Reinfection with malaria parasites, which can occur even after successful treatment of a previous episode
• Immunocompromised states, such as HIV infection, that can affect the body’s ability to mount an effective immune response to malaria

What are the symptoms of Malaria Relapse?
Symptoms of malaria relapse are similar to those of the initial infection and may include:

• Fever (often cyclical or intermittent)
• Chills
• Fatigue and general malaise
• Headache
• Muscle aches
• Nausea and vomiting
• Anemia (due to the destruction of red blood cells)
• Jaundice (yellowing of the skin and eyes, in severe cases)
• Abdominal pain
• Dark-colored urine (hemoglobinuria) in severe cases

These symptoms generally appear weeks or months after the initial infection, as the hypnozoites become active again and cause a new round of infection.

How is Malaria Relapse diagnosed?
The diagnosis of malaria relapse typically involves:

• Blood tests – to detect the presence of Plasmodium parasites in the bloodstream. Blood smears are examined under a microscope to identify the specific species of Plasmodium.
• Rapid diagnostic tests (RDTs) – quick tests to detect specific antigens produced by the malaria parasite.
• Polymerase chain reaction (PCR) – used to identify the species of Plasmodium and confirm relapse.
• Liver function tests – in some cases, to evaluate the effect of the relapse on the liver.

Relapse is often suspected when a person who has previously been treated for malaria begins to experience symptoms after an asymptomatic period.

Is Malaria Relapse treatable?
Yes, malaria relapse is treatable. The treatment for relapse typically involves:

• Primaquine – This drug is used to kill the dormant hypnozoites in the liver, preventing relapse. It is especially effective for Plasmodium vivax and Plasmodium ovale. However, primaquine should be used cautiously in people with G6PD deficiency, as it can cause hemolysis (destruction of red blood cells).
• Chloroquine – Often used in combination with primaquine for the treatment of Plasmodium vivax relapse, as it targets the blood stage of the parasite.
• Artemisinin-based combination therapies (ACTs) – These are used for the blood stage of the infection and can help treat any Plasmodium falciparum or Plasmodium vivax that may be present.
• Mefloquine or quinine – may be used in cases of severe malaria relapse, particularly if the individual is unable to tolerate primaquine.

Can Malaria Relapse be prevented?
While relapse cannot always be entirely prevented, steps can be taken to reduce the risk:

• Complete treatment for malaria infections, including the use of primaquine, to eradicate hypnozoites and reduce the chances of relapse
• Intermittent preventive treatment (IPT) – for pregnant women, children, or travelers in malaria-endemic areas, which involves taking antimalarial drugs periodically to reduce the risk of relapse
• Mosquito bite prevention – using insecticide-treated bed nets (ITNs), insect repellents, and indoor spraying to prevent new infections and reduce the overall malaria burden
• Surveillance and early treatment – monitoring individuals who have had malaria to ensure prompt diagnosis and treatment of any relapses

What is the outlook for someone with Malaria Relapse?
The outlook for malaria relapse depends on the promptness of diagnosis and treatment. If treated early with primaquine and other antimalarial drugs, most individuals recover fully from relapse. However, untreated relapse can lead to severe complications such as severe anemia, organ failure, and in rare cases, death. Frequent relapse can also contribute to the development of antimalarial drug resistance, which may complicate future treatment efforts.