This report describes a single case of Acanthamoeba encephalitis in a patient with chronic lymphocytic leukemia (CLL) and a retrospective review of US cases reported to the Centers for Disease Control and Prevention (CDC) Free-Living Ameba (FLA) database from 1956 through 2023. The objective was to characterize the frequency of Acanthamoeba infection among patients with CLL and to compare clinical features and outcomes between patients with CLL and those with other malignancies.
The CDC reviewed the database as a surveillance activity consistent with applicable federal law and policy. Data available in the FLA database informed age, sex, malignancy type, site of infection (CNS versus non-CNS), and survival outcomes when reported.
A 71-year-old man with known CLL who was receiving the Bruton tyrosine-kinase inhibitor ibrutinib presented with fever, encephalopathy, and focal right-sided weakness. Neuroimaging demonstrated a rapidly enlarging left frontal lesion with surrounding edema. Routine testing for bacterial, viral, and parasitic pathogens was unremarkable. Brain biopsy showed necrosis, inflammation, and rare Periodic acid–Schiff–positive organisms. CDC testing confirmed Acanthamoeba infection.
Treatment included azithromycin, sulfadiazine, flucytosine, fluconazole, and miltefosine; despite therapy the patient died 23 days after symptom onset. The authors note that GAE is typically considered subacute to chronic but may present with rapid onset and progression, as occurred in this case and in two other reported CLL cases that resulted in death within days to weeks after hospital presentation.
The authors examined all US Acanthamoeba cases reported to the CDC FLA database from 1956–2023 to evaluate malignancy types and outcomes. Across the dataset, the mean age at diagnosis for all case-patients was 48 years; the mean age in the CLL subgroup was 68 years. Among the 16 CLL cases with known sex, 14 were male and 2 female; the database overall included more male than female patients in many subgroups.
A total of 18 reported patients with CLL were identified since 1956, including the present case. At the time of Acanthamoeba diagnosis, 56 patients in the broader dataset had one or more malignancies: 16 had CLL alone, 1 had CLL plus non-Hodgkin lymphoma, and 30 had other hematologic malignancies (including acute lymphoblastic leukemia, acute myeloid leukemia, chronic myeloid leukemia, and lymphoma). Twelve patients had one or more nonhematologic malignancies.
Of 17 CLL patients with available site-of-infection data, 8 had central nervous system (CNS) involvement: 3 had granulomatous amebic encephalitis (GAE) alone and 5 had GAE with disseminated disease. Nine CLL patients had non-CNS Acanthamoeba infections: 5 had cutaneous disease, 1 rhinosinusitis, and 3 had non-CNS disseminated disease.
Survival data for the 17 CLL cases showed 8 survivors, 3 deaths, and 6 with unknown outcome. All three deaths in the CLL group had GAE; among the eight CLL survivors, one had GAE. In contrast, among patients with non-CLL malignancies and known survival outcome (n = 33), 31 died and 2 survived; neither of the two non-CLL survivors had GAE. GAE was present in 28 of 31 non-CLL patients who died.
Statistical comparison indicated lower odds for death from Acanthamoeba infection in patients with CLL compared with patients with non-CLL malignancies (odds ratio [OR] 0.03; 95% CI 0.003–0.18; p<0.0001). The authors attribute this finding at least in part to the lower frequency of CNS involvement among CLL patients in the dataset. Across all cancer patients, presence of GAE was associated with markedly increased odds of death (OR 68.6; 95% CI 9.0–2,075.9; p<0.0001). The authors also report that overall cohort data showed 30% of cases had non-CNS infections, whereas among CLL patients 53% had non-CNS Acanthamoeba infection.
The authors discuss that CLL is associated with immune dysfunction from the disease itself and from immunosuppressive treatments. Mechanisms include hypogammaglobulinemia, impairments in complement activity and cell-mediated immunity, and neutrophil dysfunction. These immune abnormalities could predispose to infection with free-living amebae such as Acanthamoeba. The 5-year risk for severe infections in CLL patients can be high when IgG levels are low, and immunoglobulin replacement is suggested as a possible mitigator, though specific therapeutic effects were not assessed in this dataset.
Ibrutinib, an immunomodulatory Bruton tyrosine-kinase inhibitor used to treat CLL, is noted to increase risk for invasive infections by impairing innate immune function; the authors report that more than four of the 18 CLL patients in the series had been treated with ibrutinib since its US introduction in 2012. They highlight uncertainty about whether ibrutinib exposure may increase risk for Acanthamoeba infection or for a more acute clinical course and recommend further monitoring.
The study is limited by incomplete and variable data in the CDC FLA database. Detailed clinical and laboratory data, comprehensive treatment histories, methods of Acanthamoeba diagnosis, and timing of death after diagnosis were often not available. Survival status was unknown for several patients. Additionally, the FLA database contains only US cases, which limits generalizability to other settings.
Including the reported patient, 18 Acanthamoeba infections have been identified in patients with CLL since 1956. CLL emerged as the most common malignancy among patients with invasive Acanthamoeba infections in the US database. Patients with CLL had higher proportions of non-CNS disease and significantly better survival odds than patients with other malignancies in this dataset, a finding likely linked to lower frequency of GAE among CLL cases. GAE carries a very high mortality risk across malignancy types. The case and retrospective review underscore that CLL and exposure to immunomodulatory therapies such as ibrutinib may be important considerations in risk assessment for Acanthamoeba infection, but incomplete surveillance data limit definitive conclusions and further monitoring is needed.