Specific environmental factors are associated with increased rates of invasive mucormycosis infections in patients with acute leukemia and myelodysplastic syndrome Free

Climate change has significant impacts on fungal disease, including geographic expansion of endemic mycoses and emergence of new fungal pathogens. Prior research has demonstrated an association between high ambient temperature and invasive mucormycosis infections (IMI), yet the impact of climate change on IMIs is not well understood. In this study, we performed a single-center analysis of the relationship between specific environmental factors—temperature, precipitation, humidity, and particulate matter 2.5 (PM_2.5) levels—and IMI incidence in patients with hematologic malignancies over an 11-year period.

We included patients who had a diagnosis of acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), acute lymphoblastic leukemia (ALL), or mixed phenotype acute leukemia (MPAL) and a positive PCR test for IMI at Fred Hutchinson Cancer Center or University of Washington Medical Center (UWMC) in Seattle, WA between January 1, 2013 and December 31, 2023. We captured demographic and clinical characteristics from medical records and excluded those with detection of non-pathogenic Mucorales species (e.g. M. racemosus) or whose infection was deemed by the clinical team to represent colonization rather than invasive disease. IMI diagnosis date was defined as the sample collection date for the first positive PCR test. For our denominator, we calculated total number of inpatient-days for all patients (with or without IMI) who had ≥1 inpatient admission with ICD codes for the above diagnoses or allogeneic hematopoietic stem cell transplant (HCT) at UWMC during the study period. We compiled aggregate monthly data and divided total number of IMI cases by total inpatient-days to compute monthly IMI incidence rates. Monthly King County mean ambient temperature, total precipitation levels, and relative humidity data were obtained from the National Oceanic and Atmospheric Administration National Centers for Environmental Information, and maximum PM_2.5levels from the Environmental Protection Agency air quality tool. Poisson regression with number of IMI cases as the dependent variable and the logarithm of inpatient-days as an offset was used to test for associations between environmental variables and incidence rates of IMI, in separate models. Restricted cubic splines were used to accommodate non-linear patterns.

During the 11-year study period, 75 patients with acute leukemia or MDS were diagnosed with IMI. Median age was 60 years (range 22-89), 39% were female; the majority had AML (52, 69%), while 10 (13%) had MDS, 10 (13%) had ALL, and 3 (4%) had MPAL. Eighteen (24%) patients had prior allogeneic HCT a median of 176 days before IMI (range 15-1624 days). Most IMI cases had pulmonary involvement (68/75, 91%), 11 of which had ≥1 additional site of infection. 30- and 90-day all-cause mortality rates following IMI diagnosis were 48% and 59%, respectively.

Overall, IMI incidence rate was 4.2 per 10,000 inpatient-days (95% confidence interval 3.3-5.3), based on a total of 176,841 inpatient-days during the study period. Incidence rates did not increase consistently during the study period, but varied by season (p<.001), with highest rates in summer months July-September (7.8-8.5/10,000 inpatient-days) and lowest rates in winter months December-March (0-2.8/10,000 inpatient-days). Higher mean temperature was significantly associated with higher IMI incidence rate, with a steady increase from 5 to 20°C (p<.001). Lower levels of precipitation (p=.003) and humidity (p<.001 for minimum, p=.002 for maximum) were associated with higher IMI incidence rate, with a pattern of steady decrease from the first to third quartile of precipitation and humidity levels and a plateau thereafter. Months with higher PM_2.5 levels had higher IMI incidence rates, though this was not significant (p=.10) and mainly driven by several values >100.

ConclusionsIn our study of patients with acute leukemia or MDS between 2013 and 2023, high ambient temperature, low precipitation, and low humidity were associated with increased IMI incidence rates. Our findings underscore the potential role of the environment in IMIs and raise the question of whether clinical decision-making, such as when to modify antifungal prophylaxis, should incorporate real-time environmental data. As climate change intensifies, additional research on the intersection of climate change and fungal disease in patients with hematologic malignancies is imperative.