Relapsing Malaria

Relapsing malaria is recurrent malaria caused by reactivation of dormant liver hypnozoites of Plasmodium vivax or P. ovale after clearing of the blood stage. It should be distinguished from recrudescence (incomplete clearance of blood stage parasites, mainly P. falciparum or P. malariae) and from reinfection.

• Relapse interval: weeks to several months (P. vivax tropical strains 3 to 5 weeks), up to years.
• Relapse is more likely without radical cure with an 8 aminoquinoline.

Recurrent fever with chills and sweats, headache and malaise, usually milder than the primary attack, with splenomegaly and anaemia.

• Occurs without mosquito exposure and after a symptom free interval.
• Differential diagnosis: reinfection, recrudescent falciparum malaria, P. malariae recrudescence (even years later), bacterial infection, typhoid, dengue, brucellosis, tuberculosis, leishmaniasis, lymphoma.
• Complications: recurrent anaemia, splenomegaly and rupture, growth faltering, miscarriage and low birth weight in pregnancy, nephrotic syndrome (P. malariae), repeated hospitalisation.

Confirm species and timing.

• Blood film and PCR to identify P. vivax or P. ovale; rapid antigen tests that detect pLDH or aldolase; consider mixed infection.
• G6PD quantitative testing before 8 aminoquinoline therapy; haemoglobin, platelets, pregnancy test.
• History: timing since first illness, previous radical cure, travel, adherence.

Treat the blood stage again, then give radical cure.

• Supportive: antipyretic, hydration, nutrition, correction of anaemia, adherence counselling, nets.
• Pharmacological: blood stage: chloroquine 25 mg base/kg over 3 days (10, 10, then 5 mg/kg) where susceptible, or artemether lumefantrine in weight band doses for 3 days (35 kg and over 4 tablets per dose at 0, 8, 24, 36, 48 and 60 hours). Radical cure for P. vivax and P. ovale: primaquine 0.25 to 0.5 mg/kg base daily (adults 15 to 30 mg) for 14 days with food, once G6PD testing is normal; or tafenoquine 300 mg once in adults (G6PD activity over 70 percent). Repeat full course in confirmed relapse after previous low dose primaquine, using the higher dose (0.5 mg/kg). Mild to intermediate G6PD deficiency: primaquine 0.75 mg/kg base weekly for 8 weeks. Recrudescent falciparum malaria: use an alternative artemisinin combination (dihydroartemisinin piperaquine) or artesunate plus clindamycin or quinine plus doxycycline, and treat severe cases with IV artesunate.
• Procedures: none.
• Special groups: pregnancy and breastfeeding, chloroquine weekly 300 mg base prophylaxis until delivery after treatment, primaquine after delivery with normal G6PD; infants under 6 months, no primaquine; severe G6PD deficiency, no primaquine; HIV, review interactions.
• Red flags: dark urine and falling haemoglobin during primaquine (stop at once), severe anaemia, high parasitaemia, recurrence in under 28 days (drug failure), pregnancy.
• Follow-up: films at days 3, 7 and 28; haemoglobin at day 7 on primaquine; repeat review at 3 and 6 months; relapse prevention counselling.