Giardiasis in the Immunocompromised: A Case Series Highlighting Diagnostic Pitfalls and Treatment Challenges

<i>Giardia lamblia</i> (<i>G. lamblia</i>) is a leading cause of protozoal intestinal infection worldwide, typically presenting as a self-limiting diarrheal illness in immunocompetent hosts. In immunocompromised patients, however, giardiasis may be severe, recurrent, or refractory to standard therapy, leading to diagnostic confusion due to overlapping conditions such as chemotherapy-related diarrhea or gastrointestinal graft-versus-host disease (GVHD). We report three cases of giardiasis in patients with leukemia, each highlighting distinct clinical challenges: neutropenic fever complicated by colitis and partial bowel obstruction, recurrent refractory disease in the setting of profound hypogammaglobulinemia, and post-transplant giardiasis mimicking gastrointestinal GVHD. These cases emphasize the limitations of stool microscopy, the value of multiplex polymerase chain reaction (PCR) and immunoassays, and the increasing recognition of metronidazole treatment failure. Alternative agents such as nitazoxanide, tinidazole, or combination regimens may be required, and intravenous immunoglobulin (IVIG) can support clearance in patients with antibody deficiency. Chronic giardiasis carries significant risks of malabsorption, malnutrition, and poor oncologic outcomes, underscoring the importance of early diagnosis, tailored therapy, and supportive care in this vulnerable population.