Blastomycosis in 64 Wisconsin Children: Unanticipated Infection Risk and Severity in Urban Residents.

BACKGROUND: Blastomycosis, an endemic mycosis of immunocompetent individuals, is typically seen after exposure to waterways within rural wooded regions. It is not considered a disease of urban environments. Infection can be solely pneumonic or disseminate to skin, bone or central nervous system. Unknown factors influence disease acquisition and severity in children. METHODS: We analyzed acquisition risks and disease characteristics of blastomycosis in children seen at a tertiary care center from 1998 to 2018 to identify potential exposure sources, measure disease severity and assess the effect of race upon disease severity. RESULTS: Of 64 infected children, mean age was 12.9 years, with median time to diagnosis 38.5 days. About 72% were male, 38% resided in urban counties and 50% had typical environmental exposure. Isolated pulmonary infection occurred in 33 (52%). The remainder had evidence of dissemination to skin (N = 13), bone (N = 16; 7 clinically silent) and cranium (N = 7; 3 clinically silent). Infection was moderate/severe in 19 (30%). Two children (3%) died. About 79% of children with moderate/severe disease (P = 0.008) and 71% of urban children (P = 0.007) lacked typical environmental exposure. Comparing children from urban counties to other residences, 63% versus 5% were black (P < 0.001) and 71% versus 35% developed extrapulmonary dissemination (P = 0.006). Moderate/severe disease was seen in 7/17 (42%) black children but only 12/47 (26%) children of other races (P = 0.23). CONCLUSIONS: Blastomycosis, can be endemic in urban children in the absence of typical exposure history, have frequent, sometimes clinically silent, extrapulmonary dissemination and possibly produces more severe disease in black children.

Investigation of Genetic Susceptibility to Blastomycosis Reveals Interleukin-6 as a Potential Susceptibility Locus.

Genetic differences are hypothesized to underlie ethnic disparities in incidence rates of the endemic systemic mycoses, including blastomycosis. Individuals of Hmong ancestry display elevated risk for this serious fungal infection. Here, we interrogated the genomes of Wisconsin (WI) Hmong blastomycosis patients using homozygosity mapping to uncover regions of the genome that are likely shared among the greater Hmong population and filtered for variants with high potential to affect disease susceptibility. This approach uncovered 113 candidate susceptibility variants, and among the most promising are those in genes involved in the interleukin-17 (IL-17) response. In particular, we identified 25 linked variants near the gene encoding IL-6 (IL6). We validated differences in cytokine production between Hmong and European volunteers and formally demonstrated a critical role for IL-6 in the development of adaptive immunity to Blastomyces dermatitidis Our findings suggest that the dysregulation of IL-17 responses underlies a recently reported and poorly understood ethnic health disparity.IMPORTANCE Blastomycosis is a potentially life-threatening infection caused by the fungus Blastomyces dermatitidis As with related fungal diseases, blastomycosis is noted to affect some populations more than others. These patterns of illness are often not related to predisposing conditions or exposure risks; thus, genetic differences are thought to underlie these health disparities. People of Hmong ancestry in Wisconsin are at elevated risk of blastomycosis compared to the general population. We studied the genetic codes of Hmong blastomycosis patients and identified candidate sites in their genomes that may explain their susceptibility to this infection. We further studied one particular region of the genome that is involved with the immune processes that fight B. dermatitidis Our work revealed population differences in the response to fungi. A better understanding of the genetic underpinnings of susceptibility to infectious diseases has broader implications for community health, especially in the paradigm of personalized medicine.

Blastomycosis and pregnancy.

Blastomycosis is an exceedingly uncommon complication of pregnancy, rarely encountered by the practicing obstetrician. However, recognizing its presence during pregnancy and expeditiously initiating appropriate therapy is of critical importance to the mother and fetus. Mississippi has the highest prevalence of blastomycosis in North America. Nevertheless, there have been only three pregnancies complicated by this fungal disease at the University of Mississippi Medical Center (Jackson, MS) during two decades. During the same time frame there were another 120 blastomycotic patients treated at the University of Mississippi Medical Center. As a condition of partial immunodepression, a nonobligatory opportunistic fungal disease like blastomycosis can complicate pregnancy. From data on our three patients and 16 other published cases, it seems that fetal risk exceeds maternal risk. There were a total of 20 babies born from mothers with blastomycosis. Only two babies (10%) had transplacental infection and both succumbed to blastomycosis. None of the 18 affected mothers for whom data was available died of the disease. Furthermore, there was never progression in the mothers, with 14 complete cures and considerable postpartum regressions of lesions in the other four women. Even the three women who received no treatment had either noticeable improvement or total regression of the disease after delivery. One of the two stillborns with blastomycosis was born to an untreated mother.

Epidemiology and clinical spectrum of blastomycosis diagnosed at Manitoba hospitals.

Blastomyces dermatitidis is a dimorphic fungus endemic to Canada and the United States. Few reports regarding blastomycosis in Canada have been published. We retrospectively reviewed the medical charts of 143 patients with confirmed cases of blastomycosis diagnosed in hospitals in Manitoba, Canada, from 1988 through 1999. The annual incidence rate of blastomycosis in Manitoba was 0.62 cases per 100,000 population, compared with 7.11 cases per 100,000 population in the Kenora, Ontario district. The average age of patients was 38.0 years, and males accounted for 65.0% of cases. An increased incidence of blastomycosis was observed in the Aboriginal subpopulation. Organ systems involved were as follows: respiratory system (93.0% of cases), skin (21.0%), bone (13.3%), genitourinary tract (1.4%), and the central nervous system (1.4%); 6.3% of patients died, and death was associated with a short clinical course. This study provides a summary of the current status of blastomycosis in this area of endemicity in Canada.