Visceral Mycoses as a Cause of Severe HIV Infection and Death

<b><i>Introduction:</i></b> In recent years, there has been an increase in the number of systemic fungal infections among HIV-infected individuals. The article aimed to examine the frequency of invasive mycoses among the HIV-infected patients at the time of their urgent and/or planned admission to a specialized hospital. <b><i>Methods:</i></b> The diagnostic methods used in this study involved physical examination, laboratory testing, bacteriological examination, immunological examination, molecular genetic testing, and radiological imaging. The study was conducted under the ethical guidelines for retrospective studies and does not disclose data on individual patients. <b><i>Results:</i></b> Between 2016 and 2018, 85 HIV patients who died with HIV history underwent a series of clinical and pathomorphological examinations at the Novgorod Regional Infectious Diseases Hospital. Systemic mycoses frequently occur in the respiratory system and less often in the brain. Their incidence is severe and the mortality rates associated with it are high. In this study, PCP was the most common cause of death provoked by mycoses. <b><i>Discussion/Conclusion:</i></b> Systemic fungal disease can be diagnosed through a combination of diagnostic methods. A crucial factor in the reduction of mortality rates for systemic mycosis is the early diagnosis and intensive antimicrobial therapy.

Invasive fungal infections in children with rheumatic diseases

Introduction. In children with rheumatic diseases, severe fungal infections (invasive mycoses – IM) are not well understood.Objectives. To analyze risk factors, disease course of IM in children with systemic rheumatic diseases.Materials and methods. For diagnosis of IM were used criteria EORTC/MSGERC, 2019. We reviewed the literature over the past 15 years on IM in children with rheumatic diseases from the international databases Pubmed and Web of Science.Results. In retrospective multicenter study were included 8 children with IM and systemic rheumatic diseases: ANCA-associated vasculitis (n=4), systemic lupus erythematosus (n=3), juvenile rheumatoid arthritis (n=1). Median age was 13,5 (8-17) y., boys – 67%. Invasive aspergillosis was diagnosed in 5 patients and invasive candidiasis – 3. The risk factors of invasive mycoses were high rheumatic disease activity (100%), corticosteroids (prednisolone ≥ 0,3 mg/kg/d) use for ≥21 d (87,5%), immunosuppressive therapy (87,5%), recent (≤ 2 weeks) pulse steroid therapy (75%), hemophagocytic lymphohistiocytosis (62,5%), prolonged (≥ 10 days) severe neutropenia (≤ 0,5х109/l) (62,5%), and prolonged (≥10 days lymphopenia (≤ 1,0х109/l) (37,5%). In patients with invasive aspergillosis the involved organ was the lung, in patients with invasive candidiasis a candidemia was diagnoses. All patients received antifungal therapy. The overall 30 days survival rate was 37,5%.Сonclusions. Children with high rheumatic diseases activity and intensive treatment with immunosuppressive agents should be considered as patients with a high risk of invasive mycoses with a high mortality.

Analysis of regulatory T lymphocytes in fungal infections

Morbidity and mortality rates in invasive mycoses determine the need to improve methods for their timely diagnosis by assessment the patients’ immune status. Evaluation of individual immune status allows the clinician to predict the development and course of fungal infections. At the same time, identification of opportunistic mycosis in immunocompetent patients should require a search for some hidden immune deficiency. Determining the cause of such immune defects can help develop an effective strategy for both etiotropic and immune therapy of patients with invasive mycoses. Currently, the functions of regulatory T lymphocytes that support immunological tolerance in fungal infections remain to be incompletely studied. In this review, we present experimental works which suggest that the regulatory T lymphocytes are able to suppress immune responses to fungi by stimulating the immunosuppressive environment. It was shown that regulatory T lymphocytes use Toll-like receptor 2 to achieve immunosuppression in Candida infections. The balance between the number and function of regulatory T lymphocytes is essential for elimination of fungal pathogens and protection against post-infectious immunopathological conditions. It was found that the regulatory T lymphocytes provide protection at an early stage of Candida infection, since, due to IL-2 suppression, they enhance Th17 differentiation and clearance of fungi. Moreover, at the later stages of infection, the regulatory T lymphocytes have an inhibitory effect. The balance between Th17 and regulatory T lymphocytes in mucosal lining is considered the main factor for distinguishing between commensal carriage and Candida albicans infection. The study is presented which indicate that disseminated candidiasis associated with expansion of regulatory T lymphocytes stimulates a Th17-cell response that controls the course of the disease. The mechanisms that control regulatory T lymphocytes homeostasis are essential for providing effective protection against pathogens, as well as for controlling the immunopathological conditions associated with Candida infection. The review presents data that have established the role of TGF-β1 in increasing the viability of regulatory T lymphocytes, which is correlated with the pronounced immunomodulating role of these cells at the later phase of Candida infections of the mucous membrane. It has been also demonstrated that the pulmonary regulatory Tlymphocytes are induced during cryptococcal infection, which predominantly suppresses Th2 cells, thereby supporting its course. Expansion of the regulatory T lymphocytes upon administration of IL-2/antiIL-2 complex during cryptococcal infection led to a decrease in IgE production and a decrease in allergic airway inflammation. It should be noted that refinement of prognostic value of the regulatory T lymphocytes in human fungal infections may substantiate the basic principles of targeted immunotherapy.

Mucormycosis following COVID19: clinical case and literature review

Mucormycosis is one of the most aggressive invasive mycoses. The mortality rate of patients with mucormycosis, depending on clinical form and background disease, varies from 30% to 100%. This article provides the first description of mucormycosis in Russia after infection caused by SARS-CoV-2, as well as a review of literature reports on mucormycosis in patients with COVID-19 (as of September 2021).

Species distribution and antifungal susceptibility of Aspergillus clinical isolates in Lebanon

Aim: We sought to provide first insights into the epidemiology and antifungal susceptibility patterns of the aspergilli in Lebanon. Materials & methods: After species identification, antifungal susceptibility was investigated according to EUCAST recommendations. CYP51A gene was sequenced in resistant isolates and its expression level was evaluated by Reverse transcription-quantitative PCR. Results: Among the 73 Aspergillus isolates studied (mostly from ears), the predominant species was Aspergillus niger (54.8%). The overall drug resistance was highest for amphotericin B (38.4%), followed by itraconazole (31.5%), posaconazole (30.1%) and voriconazole (23.3%). In addition, CYP51A gene mutations were not the major cause of azole resistance among these isolates. Conclusion: Our findings indicate the paramount need for an integral One Health strategy and a national reference center for invasive mycoses and antifungals.

Immunotherapy against Systemic Fungal Infections Based on Monoclonal Antibodies

The increasing incidence in systemic fungal infections in humans has increased focus for the development of fungal vaccines and use of monoclonal antibodies. Invasive mycoses are generally difficult to treat, as most occur in vulnerable individuals, with compromised innate and adaptive immune responses. Mortality rates in the setting of our current antifungal drugs remain excessively high. Moreover, systemic mycoses require prolonged durations of antifungal treatment and side effects frequently occur, particularly drug-induced liver and/or kidney injury. The use of monoclonal antibodies with or without concomitant administration of antifungal drugs emerges as a potentially efficient treatment modality to improve outcomes and reduce chemotherapy toxicities. In this review, we focus on the use of monoclonal antibodies with experimental evidence on the reduction of fungal burden and prolongation of survival in in vivo disease models. Presently, there are no licensed monoclonal antibodies for use in the treatment of systemic mycoses, although the potential of such a vaccine is very high as indicated by the substantial promising results from several experimental models.

The current place of echinocandins in the treatment and prophylaxis of invasive fungal infections

Invasive fungal infections continue to show steady growth among various patient populations, accompanied by high rates of both morbidity and attributive mortality. For the treatment of invasive mycoses, a few number of drugs are currently available, which include polyenes, azoles, echinocandins, allylamines and flucytosine. Among these groups, echinocandins – anidulafungin, caspofungin and mycafungin – represent a key class of antifungal drugs, primarily for the treatment of the most common form of systemic fungal infections – Invasive candidiasis. Possessing a unique mechanism of action that determines fungicidal activity against yeast pathogens, a predictable pharmacokinetics profile, and good safety profile, echinocandins have firmly taken the lead in the treatment of infections caused by Candida species. In addition, they are used in the treatment of refractory cases of invasive aspergillosis and for the prevention of invasive mycoses in selected patient populations. In this brief review, the main clinical and pharmacological characteristics of echinocandins and their positioning within the current versions of practical recommendations will be presented.