Secondary Hemophagocytic Lymphohistiocytosis Triggered by Mixed Plasmodium spp. and SARS-CoV-2 Coinfection

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome that may be triggered by infectious diseases, including malaria and viral infections. A case of mixed Plasmodium vivax and Plasmodium falciparum infection concomitant with severe acute respiratory syndrome coronavirus 2 in a patient who developed secondary HLH is described in the present study. Malaria was acquired in the endemic state of Mato Grosso, Brazil, but diagnosed in Macaé, Rio de Janeiro, a nonendemic region. The patient presented with high fever, pancytopenia, hypertriglyceridemia, and hyperferritinemia. Bone marrow aspirate revealed hemophagocytosis. The patient met six of the eight HLH-2004 criteria and had an HScore indicating a high probability of secondary HLH. Recovery was achieved after the initiation of antimalarial and corticosteroid therapies. This case suggests that parasitic and viral infections may synergistically trigger immunologic "second hits," promoting macrophage hyperactivation. Recognition of overlapping infections, particularly outside endemic areas, may facilitate earlier diagnosis and timely management of secondary HLH.