Coccidioidomycosis and Histoplasmosis in Immunocompetent Individuals: A Comprehensive Review of Clinical Features, Diagnosis, and Management.

Coccidioidomycosis and histoplasmosis are endemic mycoses caused by the Coccidioides species and Histoplasma capsulatum, respectively. While these fungal infections are often associated with immunocompromised individuals, they pose significant risks to immunocompetent hosts. This review comprehensively analyzes these infections in immunocompetent individuals, focusing on clinical features, diagnostic approaches, and management strategies. The current understanding of coccidioidomycosis and histoplasmosis in immunocompetent individuals includes their clinical presentations, diagnostic methodologies, and treatment options. A literature review encompassed recent studies, clinical guidelines, and expert opinions. Data were analyzed to highlight critical aspects of the clinical manifestations, diagnostic processes, and management of these infections in immunocompetent patients. Coccidioidomycosis typically presents with pulmonary symptoms that may range from mild to severe and can include chronic and disseminated forms. Histoplasmosis also presents a spectrum of pulmonary symptoms with the potential for extrapulmonary dissemination. Diagnostic approaches for both infections involve clinical evaluation, serological tests, culture, and imaging studies. Management strategies include antifungal therapies such as fluconazole and itraconazole for coccidioidomycosis and itraconazole and amphotericin B for histoplasmosis, with treatment duration and monitoring tailored to the severity of the infection. Coccidioidomycosis and histoplasmosis can significantly affect immunocompetent individuals, with clinical presentations varying widely from mild to severe. Accurate diagnosis and appropriate management are crucial for optimal outcomes. This review underscores the importance of awareness and timely intervention in managing these endemic mycoses and highlights the need for continued research into better diagnostic and therapeutic approaches.

Cryptococcoma in an immunocompetent patient: Unveiling the mystery of a rare rim-enhancing brain lesion.

A 59-year-old immunocompetent male who initially presented with symptoms of stroke was found to have an incidental rim-enhancing lesion on magnetic resonance imaging (MRI) of the brain. This discovery led to a lumbar puncture to analyze the cerebrospinal fluid, resulting in the diagnosis of cryptococcoma. The patient was subsequently managed with liposomal amphotericin B, followed by consolidation and maintenance therapy with fluconazole. The patient achieved a positive outcome, demonstrating the effectiveness of early diagnosis and targeted treatment. The rarity of cryptococcoma in immunocompetent individuals makes this case particularly unusual and noteworthy. It underscores the need for more extensive research to enable prompt diagnosis and effective management.

A lesson from fatal invasive fungal infections after CAR-T cell therapy: a case report and literature review.

CD19 chimeric antigen receptor T (CAR-T) cell therapy represents an effective approach to treating patients with relapsed or refractory B-cell hematologic malignancies. Nevertheless, owing to the immunosuppressive effects of this regimen, patients undergoing CD19 CAR-T cell therapy may face an elevated risk of invasive fungal infections, which involve fungi penetrating the host's tissues or bloodstream, leading to life-threating infectious diseases. Herein, we present the case of a 17-year-old male diagnosed with acute lymphoblastic leukemia, who subsequently experienced a fatal invasive fungal infection following administration of CAR-T cell therapy. Furthermore, we delve into the identification of risk factors, implementation of preventive measures and exploration of therapeutic interventions for invasive fungal infections after CAR-T cell therapy.

A 17-year-old male was diagnosed with acute lymphoblastic leukemia and experienced disease relapse after undergoing multiple chemotherapy treatments. Subsequently, he participated in a clinical trial of CAR-T cell therapy at our institution. Due to a possible lung fungal infection, he was given oral antifungal medicine. Throughout the treatment period, he developed recurrent fever. After receiving immunosuppressive agents, he developed gangrene at the sinuses and was diagnosed with invasive fungal sinusitis. Although antifungal medication was adjusted, it failed to fully eradicate the infection, leading to the patient's recurrent shocks associated with the fungal infection. These findings underscore the importance for physicians to be vigilant regarding potential fungal infections when administering CAR-T cell therapy, particularly in patients with preexisting fungal infections prior to treatment. Likewise, caution should be exercised in the use of immunosuppressive agents, given their potential to increase the risk of fungal infections, among other complications. Early and timely surgical intervention in the presence of invasive fungal infections may be more effective than monotherapy in some patients with invasive fungal infections.

Advances in Dendritic-Cell-Based Vaccines against Respiratory Fungal Infections.

Ever since the discovery of dendritic cells by Ralph Steinman and Zanvil Cohn in 1973, it is increasingly evident that dendritic cells are integral for adaptive immune responses, and there is an undeniable focus on them for vaccines development. Fungal infections, often thought to be innocuous, are becoming significant threats due to an increased immunocompromised or immune-suppressed population and climate change. Further, the recent COVID-19 pandemic unraveled the wrath of fungal infections and devastating outcomes. Invasive fungal infections cause significant case fatality rates ranging from 20% to 90%. Regrettably, no licensed fungal vaccines exist, and there is an urgent need for preventive and therapeutic purposes. In this review, we discuss the ontogeny, subsets, tissue distribution, and functions of lung dendritic cells. In the latter part, we summarize and discuss the studies on the DC-based vaccines against pulmonary fungal infections. Finally, we highlight some emerging potential avenues that can be incorporated for DC-based vaccines against fungal infections.

A New Overview of Sex Bias in Fungal Infections.

Fungal infections often disproportionately affect males over females. Since the NIH mandated in 2016 that researchers test their hypotheses in both biological sexes, numerous other fungal infections/colonizations have been found to exhibit sex-specific patterns. These patterns have been observed in various species, including mice, drosophila, cats, and bats, suggesting significant implications for understanding these diseases and developing treatments. Despite the recognition of this sex bias, primary research explaining its underlying causes or mechanisms remains limited. Current evidence suggests that potential causes might be linked to sex hormones, genetic expression, and evolutionary behaviors. This review consolidates recent data on sex bias in fungal infections or colonizations among different species and proposes future research directions to address existing gaps. Thus, this review advances the comprehension of the intricate relationships between biological sex, fungal infections, and broader health implications.

Review and Current Perspectives on DNA Topoisomerase I and II Enzymes of Fungi as Study Models for the Development of New Antifungal Drugs.

Fungal infections represent a growing public health problem, mainly stemming from two phenomena. Firstly, certain diseases (e.g., AIDS and COVID-19) have emerged that weaken the immune system, leaving patients susceptible to opportunistic pathogens. Secondly, an increasing number of pathogenic fungi are developing multi-drug resistance. Consequently, there is a need for new antifungal drugs with novel therapeutic targets, such as type I and II DNA topoisomerase enzymes of fungal organisms. This contribution summarizes the available information in the literature on the biology, topology, structural characteristics, and genes of topoisomerase (Topo) I and II enzymes in humans, two other mammals, and 29 fungi (including Basidiomycetes and Ascomycetes). The evidence of these enzymes as alternative targets for antifungal therapy is presented, as is a broad spectrum of Topo I and II inhibitors. Research has revealed the genes responsible for encoding the Topo I and II enzymes of fungal organisms and the amino acid residues and nucleotide residues at the active sites of the enzymes that are involved in the binding mode of topoisomerase inhibitors. Such residues are highly conserved. According to molecular docking studies, antifungal Topo I and II inhibitors have good affinity for the active site of the respective enzymes. The evidence presented in the current review supports the proposal of the suitability of Topo I and II enzymes as molecular targets for new antifungal drugs, which may be used in the future in combined therapies for the treatment of infections caused by fungal organisms.

Diversity and Distribution of Fungal Infections in Rwanda: High Risk and Gaps in Knowledge, Policy, and Interventions.

Fungal infections (FIs) are spreading globally, raising a significant public health concern. However, its documentation remains sparse in Africa, particularly in Rwanda. This report provides a comprehensive review of FIs in Rwanda based on a systematic review of reports published between 1972 and 2022. The findings reveal a rich diversity of fungal pathogens, including Blastomyces, Candida, Cryptococcus, Histoplasma, Microsporum, Pneumocystis, Rhinosporidium, and Trichophyton caused human infections. Candida infections predominantly affect the vagina mucosa, while Histoplasma duboisi was linked to disseminated infections. Other pathogens, such as Blastomyces dermatitidis and Rhinosporidium seeberi, were associated with cerebellar and nasal mucosa infections, respectively. The widespread observation of soilborne fungi affecting bean crops highlights the pathogens' threat to agricultural productivity, food security, and socioeconomic stability, as well as potential health impacts on humans, animals, and the environment. Of particular importance is that there is no information about FIs among animals in the country. Moreover, the analysis underscores significant limitations in the detection, reporting, and healthcare services related to FIs in the country, indicating gaps in diagnostic capacity and surveillance systems. This is underscored by the predominant use of traditional diagnostic techniques, including culture, cytology, and histopathology in the absence of integrating more sensitive and specific molecular tools in investigating FIs. Developing the diagnostic capacities and national surveillance systems are urgently needed to improve the health of crops, animals, and humans, as well as food security and socioeconomic stability in Rwanda. Also, it is important to indicate severe gaps in the evidence to inform policymaking, guide strategic planning, and improve healthcare and public health services, underscoring the urgent need to build national capacity in fungal diagnosis, surveillance, and research. Raising awareness among the public, scientific community, healthcare providers, and policymakers remains crucial. Furthermore, this report reveals the threats of FIs on public health and food insecurity in Rwanda. A multisectoral one health strategy is essential in research and intervention to determine and reduce the health and safety impacts of fungal pathogens on humans, animals, and the environment.

Epidemiology and timing of infectious complications from battlefield-related burn injuries.

BACKGROUND: Infections are the most frequent complication and cause of mortality in burn patients. We describe the epidemiology and outcomes of infections among deployed U.S. military personnel with burns. METHODS: Military personnel who sustained a burn injury in Iraq or Afghanistan (2009-2014) and were admitted to the Burn Center at U.S. Army Institute of Surgical Research at Brooke Army Medical Center were included in the analysis. RESULTS: The study population included 144 patients who were primarily young (median 24 years) males (99 %) with combat-related burns (62 %) sustained via a blast (57 %), resulting in a median total body surface area burned (TBSA) of 6 % (IQR 3-14 %). Twenty-six (18 %) patients developed infections, with pneumonia being the predominant initial infection (= 16), followed by skin and soft-tissue infections (SSTI, = 6), bloodstream infections (BSI, = 3), and intra-abdominal infections (IAI, = 1). Initial infections were diagnosed at a median of 4 days (IQR 3-5) post-injury for pneumonia, 7 days (IQR 4-12) for SSTIs, 7 days (IQR 6-7) for BSI, and 17 days for IAI. Patients with infections were more severely injured with greater TBSA (median 31 % vs 5 %), more inhalation injury (38 % vs 12 %), and longer time to definitive surgical management (median of 34 days vs 9) compared to those who did not develop infections (p < 0.001). Among patients with inhalation injury, a higher proportion developed pneumonia (42 %) compared to those without inhalation injury (5 %; p < 0.001). Five patients developed an invasive fungal infection. Gram-negative bacilli were most frequently recovered, with 32 % of Gram-negative isolates being multidrug-resistant. Four patients died, of whom all had ≥ 4 infections. CONCLUSIONS: Military personnel with burn injuries who developed infections were more severely injured with greater TBSA and inhalation injury. Improved understanding of risk factors for burn-related infections in combat casualties is critical for effective management.

Diagnostic and Therapeutic Challenge Caused by Candida albicans and Aspergillus spp. Infections in a Pediatric Patient as a Complication of Acute Lymphoblastic Leukemia Treatment: A Case Report and Literature Review.

Fungal infections constitute a significant challenge and continue to be a predominant cause of treatment failure in pediatric leukemia cases. Despite the implementation of antifungal prophylaxis, these infections contribute to approximately 20% of cases in children undergoing treatment for acute lymphoblastic leukemia (ALL). The aim of this study is to highlight the diagnostic and therapeutic challenges associated with invasive fungal infections (IFIs). We also present a review of the epidemiology, risk factors, treatment, and a clinical presentation of IFI in patients with ALL. This case report details the clinical course of confirmed Candida albicans (C. albicans) and Aspergillus spp. infections during the consolidation phase of ALL treatment in a 5-year-old pediatric patient. This male patient did not experience any complications until Day 28 of protocol II. Then, the patient's condition deteriorated. Blood culture detected the growth of C. albicans. Despite the implementation of targeted therapy, the boy's condition did not show improvement. The appearance of respiratory symptoms necessitated a computed tomography (CT) of the chest, which revealed multiple nodular densities atypical for C. albicans etiology. In spite of ongoing antifungal treatment, the lesions depicted in the CT scans showed no regression. A lung biopsy ultimately identified Aspergillus species as the source of the infection. Overcoming fungal infections poses a considerable challenge; therefore, an accurate diagnosis and the prompt initiation of targeted therapy are crucial in managing these infections in patients with leukemia.

Evaluation of voriconazole therapeutic drug monitoring in malignant hematology patients.

INTRODUCTION: Malignant hematology (MH) patients are susceptible to invasive fungal infections due to prolonged neutropenia and immunosuppressive therapies, which may require voriconazole therapy. Although voriconazole therapeutic drug monitoring (TDM) is common, evidence describing this practice is limited. The primary objective of this study was to describe the current practice of voriconazole TDM in MH patients at the Princess Margaret Cancer Centre (PM). METHODS: A retrospective chart review was conducted for MH inpatients initiated on voriconazole at PM between November 1st, 2019 and November 13th, 2020. Data regarding voriconazole doses, levels, dose changes, and adverse effects were collected. The primary endpoint was the proportion of patients with initial voriconazole levels within therapeutic range (1-5 mg/L). RESULTS: Fifty-six patients were included in the study. The most common reason for starting voriconazole was possible invasive fungal infection (44 patients, 78.6%). Fifty-one patients (91.1%) received a loading dose of voriconazole, averaging 386.5 ± 78.5 mg. The average maintenance dose was 242.1 ± 45.7 mg. An average of 2.6 ± 2.9 levels were drawn per patient with an average level of 3.2 ± 2.4 mg/L. Forty-one patients (73.2%) had an initial voriconazole level within therapeutic range and 90 out of 145 total levels (62.1%) were within therapeutic range. There were 52 dose modifications made; 31 (60.8%) doses adjusted, 12 (23.5%) doses held, and 9 (17.6%) doses discontinued. For the 31 dose adjustments, 26 (83.9%) had a level redrawn and 17 (65.4%) of those levels were within therapeutic range. Twenty-three (41.1%) patients developed adverse effects, 8 (34.8%) of which were associated with supratherapeutic levels. Of these 23 patients, 19 (33.9%) experienced transaminitis, 3 (5.4%) experienced both transaminitis and neurotoxicity, and 1 (1.8%) experienced photopsia. CONCLUSION: Overall, 41 (73.2%) patients achieved an initial voriconazole level within therapeutic range. Of these 41 patients, 30 (73.2%) remained within therapeutic range for the duration of their inpatient voriconazole therapy. These findings suggest that the current practice of voriconazole TDM at our institution is yielding largely positive results, but still has room for improvement.

Precision Detection of Fungal Co-Infections for Enhanced COVID-19 Treatment Strategies Using FESEM Imaging.

The treatment of fungal infections presents significant challenges due to the lack of standardized diagnostic procedures, a restricted range of antifungal treatments, and the risk of harmful interactions between antifungal medications and the immunosuppressive drugs used in anti-inflammatory treatment for critically ill patients with COVID-19. Mucormycosis and aspergillosis are the primary invasive fungal infections in patients with severe COVID-19, occurring singly or in combination. Histopathological examination is a vital diagnostic technique that details the presence and invasion of fungi within tissues and blood vessels, and the body's response to the infection. However, the pathology report omits information on the most common fungi associated with the observed morphology, as well as other potential fungi and parasites that ought to be included in the differential diagnosis. This research marks significance in diagnosing fungal infections, such as mucormycosis and aspergillosis associated to COVID-19 by field emission scanning electron microscopy (FESEM) imaging to examine unstained histopathology slides, allowing for a detailed morphological analysis of the fungus. FESEM provides an unprecedented resolution and detail, surpassing traditional Hematoxylin & Eosin (H&E) and Grocott's Methenamine Silver (GMS) staining methods in identifying and differentiating dual fungal infections and diverse fungal species. The findings underscore the critical need for individualized treatment plans for patients severely affected by COVID-19 and compounded by secondary fungal infections. The high-magnification micrographs reveal specific fungal morphology and reproductive patterns. Current treatment protocols largely depend on broad-spectrum antifungal therapies. However this FESEM guided diagnostic approach can help in targeted patient specific anti fungal therapies. Such precision could lead to more effective early interventions, addressing the complex management required for severe COVID-19 cases with coexisting fungal infections. This approach significantly advances disease management and patient recovery, advocating for personalized, precision medicine in tackling this multifaceted clinical challenge.

Invasive fungal infections are rare in pediatric and young adult autologous hematopoietic stem cell transplant patients.

BACKGROUND: Pediatric and young adult patients undergoing autologous hematopoietic stem cell transplant (auto-HSCT) face a crucial, yet understudied, risk of invasive fungal infections (IFI), especially compared to allogeneic transplants. This gap underscores the need for research in pediatric patients undergoing auto-HSCT. Our objective was to evaluate the incidence of IFI in pediatric and young adult patients during the first year after auto-HSCT. MATERIALS AND METHODS: We conducted a single-center retrospective analysis of 150 pediatric and young adult auto-HSCT patients who underwent transplant from January 2013 to January 2023. We focused on IFI incidence within the first-year post transplant, using the European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) criteria for IFI identification. RESULTS: Among the 150 patients analyzed, with 240 unique transplant episodes, the primary indication was neuroblastoma (37.3%), and micafungin was extensively used for prophylaxis (82.7%). There was an absence of IFI from yeast and mold species, suggesting a low IFI risk in this cohort. The incidence of IFI in pediatric auto-HSCT recipients receiving micafungin primary antifungal prophylaxis is rare. CONCLUSIONS: The findings advocate for further research to refine prophylaxis guidelines and highlight the need for individualized risk assessment to optimize post-transplant care.

Diagnosing fungal infections in clinical practice: a narrative review.

BACKGROUND: Invasive fungal infections (IFI) present a major medical challenge, with an estimated 6.5 million cases annually, resulting in 3.8 million deaths. Pathogens such as Aspergillus spp. Candida spp. Mucorales spp. Cryptococcus spp. and other fungi species contribute to these infections, posing risks to immunocompromised individuals. Early and accurate diagnosis is crucial for effective treatment and better patient outcomes. AREAS COVERED: This narrative review provides an overview of the current methods and challenges associated with diagnosing fungal diseases, including invasive aspergillosis and invasive candidiasis, as well as rare and endemic fungal infections. Various diagnostic techniques, including microscopy, culture, molecular diagnostics, and serological tests, are reviewed, highlighting their respective advantages and limitations and role in clinical guidelines. To illustrate, the need for improved diagnostic strategies to overcome existing challenges, such as the low sensitivity and specificity of current tests and the time-consuming nature of traditional culture-based methods, is addressed. EXPERT OPINION: Current advancements in fungal infection diagnostics have significant implications for healthcare outcomes. Improved strategies like molecular testing and antigen detection promise early detection of fungal pathogens, enhancing patient management. Challenges include global access to advanced technologies and the need for standardized, user-friendly point-of-care diagnostics to improve diagnosis of fungal infections globally.

ISCCM Position Statement on the Management of Invasive Fungal Infections in the Intensive Care Unit.

Rationale: Invasive fungal infections (IFI) in the intensive care unit (ICU) are an emerging problem owing to the use of broad-spectrum antibiotics, immunosuppressive agents, and frequency of indwelling catheters. Timely diagnosis which is imperative to improve outcomes can be challenging. This position statement is aimed at understanding risk factors, providing a rational diagnostic approach, and guiding clinicians to optimize antifungal therapy. Objectives: To update evidence on epidemiology, risk factors, diagnostic approach, antifungal initiation strategy, therapeutic interventions including site-specific infections and role of therapeutic drug monitoring in IFI in ICU and focus on some practice points relevant to these domains. Methodology: A committee comprising critical care specialists across the country was formed and specific aspects of fungal infections and antifungal treatment were assigned to each member. They extensively reviewed the literature including the electronic databases and the international guidelines and cross-references. The information was shared and discussed over several meetings and position statements were framed to ensure their reliability and relevance in critical practice. The draft document was prepared after obtaining inputs and consensus from all the members and was reviewed by an expert in this field. Results: The existing evidence on the management of IFI was updated and practice points were prepared under each subheading to enable critical care practitioners to streamline diagnosis and treatment strategies for patients in the ICU with additional detail on site-specific infections therapeutic drug monitoring. Conclusion: This position statement attempts to address the management of IFI in immunocompetent and non-neutropenic ICU patients. The practice points should guide in optimization of the management of critically ill patients with suspected or proven fungal infections. How to cite this article: Bhattacharya PK, Chakrabarti A, Sinha S, Pande R, Gupta S, Kumar AAK, et al. ISCCM Position Statement on the Management of Invasive Fungal Infections in the Intensive Care Unit. Indian J Crit Care Med 2024;28(S2):S20-S41.

Surgical Management of Complicated Thoracic Fungal Infections: A Case Series from a Tertiary Referral Center.

Although rare in the general population, pulmonary fungal infections usually occur in immunocompromised patients. The mainstay of pulmonary fungal infection treatment is prolonged intravenous antifungal therapy. However, surgical management may be required in cases of complex disease, resistance to medical therapy or percutaneous procedures, or associated complications such as fungal empyema and massive hemoptysis. In this series, we present three patients with complicated thoracic fungal infections who underwent individualized surgical management over a 3-month period in 2022 at our institution. Complicated pulmonary fungal infections require surgical intervention to ensure complete resolution. The choice of operation is dependent on several factors, and surgeons operating on these patients must be privy to the various surgical modalities that may be required to successfully treat these patients.

An unusual Toll/MyD88-mediated Drosophila host defence against Talaromyces marneffei.

Talaromycosis, caused by Talaromyces marneffei (T. marneffei, formerly known as Penicillium marneffei), is an opportunistic invasive mycosis endemic in tropical and subtropical areas of Asia with high mortality rate. Despite various infection models established to study the immunological interaction between T. marneffei and the host, the pathogenicity of this fungus is not yet fully understood. So far, Drosophila melanogaster, a well-established genetic model organism to study innate immunity, has not been used in related research on T. marneffei. In this study, we provide the initial characterization of a systemic infection model of T. marneffei in the D. melanogaster host. Survival curves and fungal loads were tested as well as Toll pathway activation was quantified by RT-qPCR of several antimicrobial peptide (AMP) genes including Drosomycin, Metchnikowin, and Bomanin Short 1. We discovered that whereas most wild-type flies were able to overcome the infection, MyD88 or Toll mutant flies failed to prevent fungal dissemination and proliferation and ultimately succumbed to this challenge. Unexpectedly, the induction of classical Toll pathway activation readouts, Drosomycin and Bomanin Short 1, by live or killed T. marneffei was quite limited in wild-type flies, suggesting that the fungus largely escapes detection by the systemic immune system. This unusual situation of a poor systemic activation of the Toll pathway and a strong susceptibility phenotype of MyD88/Toll might be accounted for by a requirement for this host defence in only specific tissues, a hypothesis that remains to be rigorously tested.

Current and emerging technologies to develop Point-of-Care Diagnostics in medical mycology.

INTRODUCTION: Advances in diagnostic technologies, particularly Point-of-Care Diagnostics (POCDs), have revolutionized clinical practice by providing rapid, user-friendly, and affordable testing at or near the patient's location. POCDs have been increasingly introduced in medical mycology and hold promise to improve patient outcomes in a variety of important human fungal diseases. AREAS COVERED: This review focuses on validated POCDs, particularly lateral flow assays (LFAs), for various fungal diseases. Additionally, we discuss emerging innovative techniques such as body fluid analysis, imaging methods, loop-mediated isothermal amplification (LAMP), microfluidic systems, clustered regularly interspaced short palindromic repeats (CRISPR)-based diagnostics, and the emerging role of artificial intelligence. EXPERT OPINION: Compact and user-friendly POCDs have been increasingly introduced in medical mycology, and some of these tests (e.g. Cryptococcus and Histoplasma antigen LFAs) have become mainstream diagnostics, while others, such as LFA in invasive aspergillosis show promise to become part of our routine diagnostic armamentarium. POCDs offer immense benefits such as timely and accurate diagnostic results, reduced patient discomfort, and lower healthcare costs and might contribute to antifungal stewardship. Integrated fluidics combined with microtechnology having multiplex capabilities will be pivotal in medical mycology.

The Road Ahead: Advancing Antifungal Vaccines and Addressing Fungal Infections in the Post-COVID World.

In impoverished nations, the COVID-19 pandemic has led to a widespread occurrence of deadly fungal diseases like mucormycosis. The limited availability of effective antifungal treatments and the emergence of drug-resistant fungal strains further exacerbate the situation. Factors such as systemic steroid use, intravenous drug misuse, and overutilization of broad-spectrum antimicrobials contribute to the prevalence of hospital-acquired infections caused by drug-resistant fungi. Fungal infections exploit compromised immune status and employ intricate mechanisms to evade immune surveillance. The immune response involves the innate and adaptive immune systems, leading to phagocytic and complement-mediated elimination of fungi. However, resistance to antifungals poses a challenge, highlighting the importance of antifungal prophylaxis and therapeutic vaccination. Understanding the host-fungal immunological interactions and developing vaccines are vital in combating fungal infections. Further research is needed to address the high mortality and morbidity associated with multidrug-resistant fungal pathogens and to develop innovative treatment drugs and vaccines. This review focuses on the global epidemiological burden of fungal infections, host-fungal immunological interactions, recent advancements in vaccine development and the road ahead.