Acute Acalculous Cholecystitis and Post-artesunate Hemolytic Anemia: Two Rare Complications in Severe Malaria

To the Editors: Severe malaria in children continues to represent a major global health concern, particularly in endemic regions, and may present with rare but important complications.1 We report a case of Plasmodium falciparum malaria complicated by acute acalculous cholecystitis and post-artesunate delayed hemolytic anemia (PADH) in a child, emphasizing the need for awareness regarding abdominal symptoms in malaria and follow-up in patients treated with artesunate. A previously healthy 21-month-old girl from Guinea-Bissau, recently arrived in Portugal, presented with a 7-day history of fever, vomiting and prostration. Upon admission, the patient was febrile (38.6ºC), tachycardic (153 bpm) and had a normal blood pressure (99/88 mm Hg). She was pale and lethargic with Glasgow coma scale score of 13. No jaundice, enlarged lymph nodes or hepatosplenomegaly was noted. Laboratory findings revealed P. falciparum hyperparasitemia (15%), metabolic acidosis, anemia (Hb 8.9 g/dL), thrombocytopenia (35 × 109/L), altered renal function (creatinine 0.6 mg/dL, blood urea nitrogen 44 mg/d/L), albumin 30.9 g/L, elevated liver enzymes and high C-reactive protein. She was diagnosed with severe malaria and was treated with intravenous artesunate (3 mg/kg) and ceftriaxone (100 mg/kg), alongside supportive therapy. She completed 2 days of artesunate, followed by 3 days of artemether/lumefantrine, with parasitemia undetectable by day 3. During hospitalization, the child developed hepatomegaly (5 cm), and ultrasound findings were consistent with acute acalculous cholecystitis (Fig. 1). She was managed conservatively with a third-generation cephalosporin, followed by oral cefuroxime during 14 days along with 7 days of metronidazole.FIGURE 1.: Ultrasound with Doppler revealing acute acalculous cholecystitis (on the left) and ultrasound 8 days after reporting total resolution of cholecystitis (on the right).Two weeks postdischarge, the child was less active and looked pale. Severe hemolytic anemia (Hb 5.2 g/dL, reticulocytes 15%, lactate dehydrogenase 2627 U/L, lactate dehydrogenase1.72 mg/dL, haptoglobin 0.7 g/L, with a negative direct coombs test, platelets 113 × 109/L) without malaria recurrence, was diagnosed consistent with PADH. Repeated abdominal ultrasound showed complete resolution of previous findings. The patient received a red blood cell transfusion and began folic acid supplementation. One month later, laboratory studies showed complete hematologic recovery. The pathophysiology of cholecystitis in malaria is unclear but may involve microvascular ischemia caused by parasite sequestration, erythrocyte aggregation, and increased vascular permeability.1 Multiorgan microangiopathy and tissue hypoperfusion in severe malaria may further reduce gallbladder blood flow. Although typically managed conservatively, early recognition and close monitoring are important due to the risk of unfavorable progression.2 One of the possible complications of artesunate is delayed hemolytic anemia, which usually begins 1 week after treatment, particularly in patients with high parasitemia.3,4 It is believed to result from splenic clearance of once-infected erythrocytes that have undergone “pitting,” leading to a shortened red blood cell lifespan. While PADH generally resolves with supportive management, close hematologic monitoring for at least 4 weeks after artesunate therapy is strongly recommended.5 This case highlights 2 uncommon complications of severe P. falciparum malaria (acalculous cholecystitis and PADH) occurring sequentially in the same pediatric patient. Both conditions may be under-recognized but can be effectively managed with early suspicion, appropriate supportive care and close follow-up. Heightened awareness among clinicians in nonendemic regions remains essential as international travel and migration increase the likelihood of imported pediatric malaria cases.