Severe falciparum malaria treated with artesunate complicated by delayed onset haemolysis and acute kidney injury

Abstract

Background: Severe falciparum malaria may be complicated by haemolysis after parasite clearance, however the mechanisms remain unclear. Recent reports describe a pattern of delayed onset haemolysis among non-immune travellers with hyperparasitaemia treated with intravenous artesunate, termed post-artesunate delayed haemolysis (PADH). The occurrence and clinical impact of PADH following severe malaria infections in areas of unstable transmission are unknown.

Case: A 45-year-old Bangladeshi male was initially admitted to a local hospital with severe falciparum malaria complicated by hyperparasitaemia and treated with intravenous artesunate. Twenty days from his first presentation he was readmitted with delayed onset haemolytic anaemia and acute kidney injury. Multiple blood transfusions and haemodialysis were required. Renal biopsy revealed acute tubular injury and haem pigment nephropathy. His haemoglobin and renal function recovered to baseline after 62 days from his second admission.

Discussion: This case highlights the differential diagnosis of post-malaria delayed onset haemolysis, including the recently described syndrome of post-artemisinin delayed haemolysis. The pathophysiology contributing to acute kidney injury in this patient and the limited treatment options are discussed.

Conclusions: This report describes PADH complicated by acute kidney injury in an adult patient living in a malaria hypoendemic region who subsequently required blood transfusions and haemodialysis. This case emphasizes the importance of routine follow up of haemoglobin and renal function in artesunate-treated patients who have recovered from severe malaria.

Figure 1

Haemoglobin, haematocrit, creatinine, and lactate dehydrogenase profiles from both hospital admissions. The first admission for severe malaria with hyperparasitaemia and hyperbilirubinaemia from day 0 to day 8; second hospital admission for severe haemolytic anaemia and acute kidney injury from day 20 to day 44. a Haemoglobin and haematocrit profile during hospital admissions. Haematocrit was stable during first hospital admission. Haemoglobin dropped by 57 and 65% on days 14 and 20, respectively, and recovered by day 81. Arrows indicate timing of whole blood transfusions on days 20 and 21; b haemoglobin and lactate dehydrogenase (LDH) profile during hospital admissions; c haemoglobin and creatinine profile during hospital admissions. Acute kidney injury, with a creatinine increase by 21× on second hospital admission, classified as stage 3 according to AKIN criteria and ‘failure’ by RIFLE criteria. Presumed baseline creatinine from day 1 was 74 μmol/L. His creatinine returned close to baseline by day 81 (106 μmol/L). Asterisks indicate haemodialysis on days 20, 21, 23, 25, and 30; ‘B’ indicates renal biopsy on day 27. AKIN acute kidney injury network, RIFLE risk, injury, failure, loss, end-stage kidney disease.

Figure 2

Renal biopsy. Left kidney ultrasound guided biopsy performed on day 27. Photomicrographs to show histopathological findings; a acute tubular necrosis with dilation, epithelial thinning, tubular cell necrosis and regeneration, interstitial oedema, and minimal inflammation (haematoxylin and eosin stain ×200); b acute tubular injury with PAS staining showing loss of brush border in the dilated injured proximal tubules (Periodic acid Schiff ×200); c a normal glomerulus (×400 Jones methanamine silver stain), and d a Perls stain for iron showing particulate and diffuse staining in damaged proximal tubules (×400). Specialized PAS, methanamine, and Perls straining were performed in Bangkok, Thailand since only haematoxylin and eosin stain was available in Bangladesh.