Plasmodium knowlesi malaria in Europe: a new imported case in Spain and a case review

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We present the case of an imported Plasmodium knowlesi infection in a Spanish traveler returning from the Philippines. Conventional microscopy revealed atypical Plasmodium spp. forms, whereas the rapid diagnostic test (RDT) was negative. The diagnosis of P. knowlesi was confirmed using PCR and sequencing, and the patient made a full recovery after three days of artemisinin-based combination therapy with piperaquine tetraphosphate and artenimol. To date, 18 cases of P. knowlesi infection have been reported in Europe. In most cases, microscopy led to misidentification as P. falciparum and/or P. malariae. RDTs often failed to detect acute P. knowlesi, and confirmation relied on molecular techniques in all cases, although some cross-reactivity with P. vivax has been observed previously. All patients received treatment, except for the previously reported Spanish case, and only one case progressed to severe malaria, but no fatalities were described. The diagnosis of P. knowlesi remains challenging. Accurate identification relies on clinical suspicion, a detailed travel history, and microscopic examination, supported by molecular techniques. This approach enables timely diagnosis and appropriate treatment.