In the absence of acute febrile illness and without a confirmatory test, malaria is assumed when other etiologies for splenomegaly have been excluded, and, generally, the individual responds to the treatment for malaria (e.g., decreased spleen size and decreased total IgM titers).6 Splenomegaly itself is associated with other morbidities, such as chronic hematologic and hepatic abnormalities and splenic rupture. Here, CD40LG is linked to malaria.