Blastomycosis, caused by dimorphic fungi of the Blastomyces genus, is endemic to regions in North America, including the Great Lakes and other parts of Canada and the United States of America. The infection primarily occurs through the inhalation of airborne conidia from contaminated soil and decaying organic matter. Pulmonary involvement is most common, but dissemination to other organs such as the skin and bones can occur, especially in immunocompromised individuals. Diagnosis is challenging due to its clinical overlap with other diseases. Culture remains the gold-standard diagnostic method, but is time-consuming, with sensitivity ranging from 66.4% to 86%. Tissue histopathology offers quicker results but has sensitivities ranging from 36% to 85%. Antigen detection assays show high sensitivity from 76.3% to 91.3% but suffer from cross-reactivity with other fungi. PCR methods offer high specificity, with sensitivity ranging from 67.6% to 100%. In immunocompromised patients, blastomycosis is often more severe, with a mortality rate exceeding 30%. Multi-modal diagnostic approaches are crucial for accurate detection and management.

Invasive fungal diseases (IFDs) represent an escalating global health threat, compounded by the rapid emergence of antifungal resistance (AFR). This review synthesizes the contemporary landscape of AFR from clinical and microbiological perspectives, providing actionable insights for clinical practitioners. We examine the epidemiology of critical pathogens, including Candidozyma auris, clonal Candida parapsilosis, azole-resistant Aspergillus fumigatus, and dissect the underlying molecular mechanisms, from genetic mutations in ERG11 and cyp51A to novel emerging epigenetic and adaptive strategies. We critically appraise the diagnostic gap between phenotypic testing and clinical urgency, highlighting the role of rapid molecular assays and next-generation sequencing. Finally, we evaluate evidence-based therapeutic strategies, including the integration of novel agents such as rezafungin, ibrexafungerp, olorofim, and fosmanogepix), while emphasizing the imperative of antifungal stewardship, infection prevention and control in mitigating resistance, and “One-Health” interventions.

Background: Bedaquiline (BDQ) has transformed the management of multidrug-resistant (MDR) and rifampin-resistant tuberculosis (TB). Unfortunately, the expanded use of BDQ in these regimens has been accompanied by resistance, which is steadily increasing in certain regions of the world. Nonetheless, our understanding of the mechanisms behind BDQ resistance remains poor, limiting the utility of more rapid molecular or genomic-based diagnostics for the detection of BDQ-resistant isolates. Case Summary: We describe an unusual case of a rapid, 2-year evolution of a fully susceptible Mycobacterium tuberculosis strain to extensively drug-resistant TB in a 44-year-old Canadian-born woman with Crohn’s disease. Comparative whole-genome sequencing captured the progressive development of resistance mutations and identified a novel loss-of-function mutation (Glu-177-STOP) in the M. tuberculosis pepQ gene that was associated with treatment failure while on BDQ and phenotypic BDQ/clofazimine (CFZ) cross-resistance. Therapeutic drug monitoring while on MDR therapy (daily ethambutol, pyrazinamide, linezolid, CFZ, and intravenous amikacin) detected low serum levels of CFZ, which was not addressed prior to the addition of BDQ to her 5-drug regimen and may have selected for BDQ/CFZ cross-resistance. Conclusion: This case contributes to the limited clinical data implicating pepQ in BDQ/CFZ cross-resistance and describes a novel loss-of-function mutation associated with resistance. As our understanding of genotypic BDQ resistance remains elementary, when novel drug mutations arise, practitioners should consider their significance in the context of phenotypic drug susceptibility test results and the patient’s clinical response.

While lung cancer remains a lethal disease despite treatment advances, some parasitic infections can demonstrate cancer-modulating roles and exhibit anti-tumor effects. The emergence of hydatid cysts as a potential anti-cancer treatment has sparked optimism for the development of more successful therapies. This research examines the effect of hydatic cysts on the growth and proliferation of lung tumor cells, as well as the underlying molecular mechanisms involved. The laminated layer (LL) of the hydatid cyst antigens was administered to lung cancer cells with varying dosages and durations. The MTT assay was applied to evaluate cell viability. After exposure to different concentrations of LL antigens, the apoptosis, necrosis, cell cycle, and intracellular reactive oxygen species (ROS) of the cell culture were measured using flow cytometry. The expression levels of SOX-9, β-catenin, CD133, and CD44 genes were assessed using Real-Time PCR. Treating A549 cells with varying concentrations of LL antigens resulted in a decrease in viable cells, which depended on both time and dosage. Treatment with cysts led to apoptosis induction and a reduction in necrosis percentage in a dose-dependent manner. The induction of apoptosis correlated with elevated ROS production and a notable decrease in the expression of invasion-related genes (β-catenin, CD133, and CD44) (P < 0.05). However, this reduction in expression was not statistically significant for SOX-9. Exposing lung cancer cells to precise amounts of crude LL antigens resulted in cell death, apoptosis, increased intracellular ROS levels, and reduced expression of genes linked to cancer cell growth and invasion. These results lay the groundwork for further exploring purified Echinococcus granulosus parasite antigens as potential drug targets in cancer treatment.

Given the overlap of epidemiological and clinical presentations of both rickettsioses and malaria infections, diagnostic testing where malaria is confirmed or excluded, without subsequent rickettsial testing, specifically in the case of Plasmodium vivax or P. ovale infection, may mask the possibility of relapse. A lack of clinical suspicion of co-infections, absence of knowledge on the geographic distribution of diseases, and lack of availability of point-of-care diagnostic testing for other tropical diseases can often lead to missed diagnosis or misdiagnosis of common tropical infections, including rickettsioses. We herein describe a case of confirmed intercurrent rickettsial and P. vivax infection, with the former potentially triggering a relapse of the latter in a febrile traveler returning to Canada from South America, and review the literature on tropical coinfections in returning travelers.