Fungal Infections in Phagocytic Defects

Delineating the infection susceptibility of primary immunodeficiencies allows insight into host immunity. Filamentous mold infections are seen most frequently in chronic granulomatous disease, a neutrophil disorder characterized by impaired superoxide production. Mucocutaneous candidiasis occurs in disorders of impaired interleukin (IL)-17 and IL-22 signaling, such as seen in autosomal dominant hyper-IgE (Job’s) syndrome and in disorders with autoantibodies to these cytokines. The endemic dimorphic fungi are in part controlled by disorders of the IL-12/interferon (IFN)-γ pathway, such as IFN-γ receptor and STAT1 defects. Understanding the pathways involved in these primary immunodeficiency disorders will also provide insight into these infections in secondary immunodeficiencies and allow guidance for novel therapies.     

Donor-Derived Fungal Infections in Transplant Patients

Fungal infection can occur in transplant patients via one of four mechanisms: donor-derived infections, contamination during the transplantation period, reactivation of latent infection in the host, or new infection during the posttransplantation period. Distinguishing between these mechanisms is often difficult and as a result, donor-derived fungal infections may be under-recognized with few data on its prevalence. We review published reports of donor-derived fungal infections and discuss the role of donor screening and the importance of establishing a national reporting, tracking, and notification system for transplant-transmitted infections.     

Combination Therapy for Invasive Fungal Infections

The purpose of this review is to summarize and evaluate relevant literature on combination antifungal therapy for invasive fungal infections (IFIs). Cryptococcal meningitis has the largest body and highest quality in support of combination therapy with amphotericin B and flucytosine. More recent data in treatment of invasive aspergillosis suggest combination therapy with voriconazole and echinocandins may be effective in select patients. Quality studies are needed to define combination therapy in rare mold infections. Multiple strategies have been employed to optimize treatment of the growing incidence of IFIs. With exceptions as noted above, justification for the use of combination antifungal therapy is most often based on uncontrolled and/or underpowered studies, in vitro data, and case reports.     

Diverse Honeydew-Consuming Fungal Communities Associated with Scale Insects

Sooty mould fungi are ubiquitous, abundant consumers of insect-honeydew that have been little-studied. They form a complex of unrelated fungi that coexist and compete for honeydew, which is a chemically complex resource. In this study, we used scanning electron microscopy in combination with T-RFLP community profiling and ITS-based tag-pyrosequencing to extensively describe the sooty mould community associated with the honeydews of two ecologically important New Zealand coelostomidiid scale insects, Coelostomidia wairoensis and Ultracoelostoma brittini. We tested the influence of host plant on the community composition of associated sooty moulds, and undertook limited analyses to examine the influence of scale insect species and geographic location. We report here a previously unknown degree of fungal diversity present in this complex, with pyrosequencing detecting on average 243 operational taxonomic units across the different sooty mould samples. In contrast, T-RFLP detected only a total of 24 different “species” (unique peaks). Nevertheless, both techniques identified similar patterns of diversity suggesting that either method is appropriate for community profiling. The composition of the microbial community associated with individual scale insect species varied although the differences may in part reflect variation in host preference and site. Scanning electron microscopy visualised an intertwined mass of fungal hyphae and fruiting bodies in near-intact physical condition, but was unable to distinguish between the different fungal communities on a morphological level, highlighting the need for molecular research. The substantial diversity revealed for the first time by pyrosequencing and our inability to identify two-thirds of the diversity to further than the fungal division highlights the significant gap in our knowledge of these fungal groups. This study provides a first extensive look at the community diversity of the fungal community closely associated with the keystone insect-honeydew systems of New Zealand’s native forests and suggests there is much to learn about sooty mould communities.     

Breakthrough Invasive Fungal Infections in Patients with Acute Myeloid Leukemia

Mycopathologia - We sought to determine the occurrence, risk factors, effect of antifungal prophylaxis, and outcomes of invasive fungal infections (IFIs) in patients with acute myeloid leukemia...     

Invasive Fungal Infections in the Child with Chronic Granulomatous Disease

Invasive fungal infections (IFI) are a major threat for patients with chronic granulomatous disease (CGD) which is an inherited disorder of NADPH oxidase. The absence of a functional NADPH oxidase complex affects the display of an efficient antimicrobial effect as well as a controlled inflammatory response. Invasive aspergillosis caused by either Aspergillus fumigatus or A. nidulans is the most common IFI. Aspergillus nidulans infections seem to display a unique interaction with the CGD host and are seldom reported in other immunocompromised hosts. The occurrence of mucormycosis in the CGD host is mainly noted in the setting of treatment of inflammatory complications with immunosuppressive drugs. Candida infections are infrequently seen and show an age-dependent clinical presentation mainly affecting infants and young children. Furthermore, the child with CGD is susceptible to a wide range of fungal pathogens, indicating the need to determine the causative fungus, often by invasive diagnostic approaches, to guide optimal and rational treatment. Currently, it is becoming more and more clear that the exaggerated inflammatory response to fungal infection in the CGD host is leading in the pathogenesis, and antiinflammatory treatment might become as important as antifungal treatment in this specific host.     

Tumor Necrosis Factor Inhibitors and Fungal Infections

The number of commercially available tumor necrosis factor (TNF)-α inhibitors has been increasing, including two new agents licensed since 2008. In addition to an expanding number of agents, there are also increasing licensed and “off label” clinical applications for the TNF inhibitors for the treatment of a variety of inflammatory or granulomatous disorders. Unfortunately, use of the TNF inhibitors has been associated with a wide variety of opportunistic infections, including fungal infections. Higher rates of morbidity and mortality from fungal infection in TNF inhibitor-treated patients have been observed, likely due to a delay in the diagnosis of invasive fungal infections and a tendency for these patients to develop severe and disseminated disease. Therefore, the US Food and Drug Administration issued a “black box” warning for clinicians in September 2008 to alert providers to the risks of fungal infections in patients treated with TNF-α inhibitors.     

Genetic Susceptibility to Fungal Infections in Humans

Most fungal infections in humans occur in the setting of iatrogenic immunosuppression or HIV infection. In the absence of these factors, fungi cause mild, self-limited infections that typically involve mucocutaneous surfaces. Hence, when persistent or recurrent mucocutaneous infections (chronic mucocutaneous candidiasis [CMC]) or invasive fungal infections (IFIs) develop in a “normal” host, they are indicative of genetic defects causing innate or adaptive immune dysfunction. In this review, recent developments concerning genetic and immunologic factors that affect the risk for IFIs and CMC are critically discussed.     

Invasive Pulmonary Fungal Infections in Cystic Fibrosis

Invasive pulmonary mycosis is after allergic bronchopulmonary aspergillosis (ABPA) a frequent and severe complication of CF lung disease. Among CF caregivers, there is an insecurity when and how to treat infections of the lung parenchyma caused by different fungi in patients with CF. This case series provides a multicenter experience on diagnostic, manifestation, and treatment of non-ABPA cases of pulmonary. Non-ABPA cases of pulmonary mycoses in patients with CF have been collected from the CF Centers in Berlin, Essen, Worms, Frankfurt (Germany), Leeds (UK), and Barcelona (Spain). Non-ABPA was defined as total serum IgE level <500 kU/L. Scedosporium and Lomentospora species seem to be more virulent in patients with CF and have been successfully treated with triple antifungal drug regimens in several cases. Rare fungi including yeasts can have pathogenic potential in CF. In this series, antibiotic treatment failure was the main indicator for the initiation of antifungal treatment. For an early and effective treatment of pulmonary mycoses in CF, the identification of biomarkers and of risk factors beyond antibiotic treatment failure is crucial and urgently needed. Furthermore, treatment efficacy studies are necessary for the different causative agents of these infections.     

Pathogenesis of Fungal Infections in Cystic Fibrosis

For a long time, the microbiology of cystic fibrosis has been focussed on Pseudomonas aeruginosa and associated Gram-negative pathogens. An increasing body of evidence has been compiled demonstrating an important role for moulds and yeasts within this complex patient group. Whether or not fungi are active participants, spectators or transient passersby remain to be elucidated. However, functionally, they do appear to play a contributory role in pathogenesis, albeit we do not know if this is a direct or indirect effect. The following review examines some of the key evidence for the role of fungi in CF pathogenesis.     

Trade-related Infections: Global Traffic and Microbial Travel

Science is only beginning to understand the interplay between global trade and human infectious diseases. The reported frequency of the emergence of new human pathogens has been increasing, coincident with the burgeoning of global trade. This report examines the phenomenon of trade related infections which are infections whose emergence, or dissemination and transmission may be driven by global trade in commodities, or whose occurrence cause major economic impact through trade disruption. Through four case studies, the interplay between global trade and the emergence and dissemination of new human infections is described. The examples are drawn from three distinct types of emergent infections: human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) and the trade in blood clotting derivatives, enteric disease and fresh produce, and prion infections and beef. The observations from these studies are then placed in the global policy framework for the control of infectious diseases and the regulation of trade. This framework is embodied in the World Health Organization and the World Trade Organization. While increasing discourse is occurring between the sectors of health and trade at the level of international organizations, such discourse at the national and local level is largely absent. A more complete evidence base for policy decision making is sorely needed to foster a global trading system which also maintains the public safety from emergent infectious diseases.     

Fungal Infections in COVID-19 Intensive Care Patients

Opportunistic fungal infections increase morbidity and mortality in COVID-19 patients monitored in intensive care units (ICU). As patients’ hospitalization days in the ICU and intubation period increase, opportunistic infections also increase, which prolongs hospital stay days and elevates costs. The study aimed to describe the profile of fungal infections and identify the risk factors associated with mortality in COVID-19 intensive care patients. The records of 627 patients hospitalized in ICU with the diagnosis of COVID-19 were investigated from electronic health records and hospitalization files. The demographic characteristics (age, gender), the number of ICU hospitalization days and mortality rates, APACHE II scores, accompanying diseases, antibiotic-steroid treatments taken during hospitalization, and microbiological results (blood, urine, tracheal aspirate samples) of the patients were recorded. Opportunistic fungal infection was detected in 32 patients (5.10%) of 627 patients monitored in ICU with a COVID-19 diagnosis. The average APACHE II score of the patients was 28 ± 6. While 25 of the patients (78.12%) died, seven (21.87%) were discharged from the ICU. Candida parapsilosis (43.7%) was the opportunistic fungal agent isolated from most blood samples taken from COVID-19 positive patients. The mortality rate of COVID-19 positive patients with candidemia was 80%. While two out of the three patients (66.6%) for whom fungi were grown from their tracheal aspirate died, one patient (33.3%) was transferred to the ward. Opportunistic fungal infections increase the mortality rate of COVID-19-positive patients. In addition to the risk factors that we cannot change, invasive procedures should be avoided, constant blood sugar regulation should be applied, and unnecessary antibiotics use should be avoided.     

Epidemiology of Invasive Fungal Infections in Latin America

The pathogenic role of invasive fungal infections (IFIs) has increased during the past two decades in Latin America and worldwide, and the number of patients at risk has risen dramatically. Working habits and leisure activities have also been a focus of attention by public health officials, as endemic mycoses have provoked a number of outbreaks. An extensive search of medical literature from Latin America suggests that the incidence of IFIs from both endemic and opportunistic fungi has increased. The increase in endemic mycoses is probably related to population changes (migration, tourism, and increased population growth), whereas the increase in opportunistic mycoses may be associated with the greater number of people at risk. In both cases, the early and appropriate use of diagnostic procedures has improved diagnosis and outcome.