The usual suspect—malaria? Diagnostic challenges in post-artesunate delayed haemolysis: a clinical laboratory perspective through a case report

(2025) 24:360 Molnar et al. Malaria Journal https://doi.org/10.1186/s12936-025-05450-2 Malaria Journal Open Access CASE REPORT The usual suspect—malaria? Diagnostic challenges in post‑artesunate delayed haemolysis: a clinical laboratory perspective through a case report Eva Molnar1,2*, Pedro M. Cabral1,2, Francisco Portal3, André Rodrigues Guimarães4,5, Lurdes Santos4,5 and João Tiago Guimarães1,2,6 Abstract Malaria, a potentially fatal infectious disease, remains a significant global health concern, mainly in tropical regions. In Europe, its incidence is currently low and predominantly travel-related. Thus, a timely diagnosis requires healthcare teams to consider malaria in their differential diagnoses and obtain a thorough travel history. In medical laboratories, despite the present low case numbers, professionals must maintain a high diagnostic proficiency through continuous training and adherence to quality assurance programmes. First-line anti-malarial treatment with artemisinin derivatives is highly effective when implemented in a timely manner. However, as a consequence of their efficacy, a predictable haemolytic phenomenon may occur in some cases, which may be difficult to distinguish from manifestations of the disease itself. This mini review examines a case of travel-associated malaria to highlight diagnostic challenges from a medical laboratory perspective, with a particular focus on post-artesunate delayed haemolysis (PADH), a rare but potentially severe complication of malaria treatment. *Correspondence: Eva Molnar 1 Serviço de Patologia Clínica, Hospital Universitário de São João, Unidade Local de Saúde São João, Alameda Prof. Hernâni Monteiro, 4200‑319 Porto, Portugal 2 Departamento de Biomedicina, Faculdade de Medicina, Universidade do Porto, Alameda Prof. Hernâni Monteiro, 4200‑319 Porto, Portugal 3 Unidade de Farmacologia Clínica, Hospital Universitário de São João, Unidade Local de Saúde de São João, Alameda Prof. Hernâni Monteiro, 4200‑319 Porto, Portugal 4 Serviço de Doenças Infeciosas, Hospital Universitário de São João, Unidade Local de Saúde de São João, Alameda Prof. Hernâni Monteiro, 4200‑319 Porto, Portugal 5 Departamento de Medicina, Faculdade de Medicina, Universidade do Porto, Alameda Prof. Hernâni Monteiro, 4200‑319 Porto, Portugal 6 Unidade de Investigação em Epidemiologia, Instituto de Saúde Pública da Universidade do Porto, Rua das Taipas 135, 4050‑600 Porto, Portugal Case presentation A 59-year-old man with no relevant medical history presented to the Emergency Department at night, coming straight from the airport, reporting asthenia and jaundice. The patient disclosed a recent travel to Angola, where he had received treatment for malaria and reported engaging in unprotected sexual activity during his stay. Upon further questioning, the patient revealed that he had been hospitalized for six-days with a malaria infection and treated with intravenous artesunate. On discharge, a three-day course of oral artemether-lumefantrine was prescribed. At follow-up (third and sixth days after discharge), he showed worsening anaemia (Hb 74 and 59 g/L, respectively). Concerned about his deteriorating condition, the patient decided to leave Angola and travelled directly to Portugal, presenting to the Emergency Department upon arrival. © The Author(s) 2025. 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To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/. Molnar et al. Malaria Journal (2025) 24:360 On initial assessment, his vital signs included a heart rate of 127 bpm, blood pressure of 120/52 mmHg, oxygen saturation of 99% on room air, and normal respiratory rate. He was afebrile. Cardiac and pulmonary examinations were unremarkable. Abdominal evaluation revealed tenderness in the right upper quadrant and hepatomegaly, with the liver palpable 4–5 cm below the costal margin. Pitting oedema was noted in both lower limbs. Laboratory tests—including blood gas analysis, malaria testing and acute viral hepatitis panel—along with a chest x-ray and an abdominal ultrasound were promptly ordered. The blood gas analysis showed slight respiratory alkalosis (pH 7.48, p CO2 28.4 mmHg) and profound anaemia (haemoglobin [Hb] 48 g/L). The abdominal ultrasound detected hepatosplenomegaly. The chest x-ray revealed no abnormalities. The complete blood count confirmed the severe anaemia (Hb 44 g/dL), revealed a high reticulocyte count (21% or 279 × 109/L) and normal thrombocyte count (365 × 109/L). The chemistry panel showed slightly elevated aspartate aminotransferase (43 U/L) and bilirubin levels (38.65 μmol/L total and 11.29 μmol/L direct bilirubin), markedly elevated lactate dehydrogenase (1332 U/L) and decreased haptoglobin (< 70 mg/L). The acute viral hepatitis panel (HBsAg, anti-HBs, anti-HBc, anti-HCV and HIV-1/2 Ag/Ab) came back negative. Coagulation studies were within normal limits. The direct antiglobulin test (Coombs test) was positive. Malaria testing included an Abbott BinaxNOW immunochromatographic rapid diagnostic test (RDT) and evaluation of the peripheral blood smear. The RDT came back positive for Plasmodium falciparum infection (PfHRP2 positive). The peripheral blood smear was prepared on the Sysmex SP-50, digital imaging was obtained by the Sysmex DI-60 system. The slide was evaluated using light microscopy (Nikon Eclypse E400) by the on duty clinical pathologist. The peripheral smear showed anisocytosis and polychromasia. No malaria parasites were observed. Given the clinical presentation and the laboratory finding, a presumptive diagnosis of post-artesunate delayed haemolysis (PADH) was established. The patient was admitted to the Infectious Diseases Intensive Care Unit and treatment with intravenous prednisolone was promptly initiated. During his five-day hospital stay, he received multiple blood transfusions. He was discharged with increasing levels of haemoglobin and decreasing levels of cytolytic markers (Fig. 1). Follow-up care was provided for a period of one year after the completion of corticotherapy. Page 2 of 7 Mala (...truncated)