1. Introduction
Invasive fungal infections (IFIs) are a significant cause of morbidity and mortality in hospitalized patients and the immunocompromised populations. Candidemia, invasive aspergillosis, mucormycosis, cryptococcosis, and
2. Aspergillosis
The genus
The major risk factors for infection include prolonged neutropenia, HSCT, SOT, corticosteroid therapy, chronic granulomatous disease, immunosuppressive treatment for malignancies, hematologic malignancy, myelodysplastic syndrome or aplastic anemia, advanced stage of human immunodeficiency virus (HIV) infection (facilitated by low CD4+ cell counts), previous infections (such as cytomegalovirus infection), and patients with critical illness [4, 6]. The spectrum of disease is determined by the host’s immune status and the virulence of
In immunocompetent hosts, aspergillosis causes mainly allergic symptoms without invasion and destruction of the host’s tissues and chronic pulmonary aspergillosis. Allergic bronchopulmonary aspergillosis (ABPA) is a syndrome that arises from a hypersensitivity reaction to antigens from
In immunocompromised patients, invasive aspergillosis (IA) can be a rapidly, progressive and frequently fatal disease. Invasive pulmonary aspergillosis (IPA) and rhinocerebral aspergillosis are the most common clinical forms of IA. Other clinical conditions included tracheobronchitis, invasive
3. Candidiasis
As opportunistic pathogens,
The incidence of
4. Cryptococcosis
HIV infection, idiopathic CD4+ lymphopenia, corticosteroid treatment, SOT, malignant and lymphoproliferative disorders, sarcoidosis, treatment with some monoclonal antibodies (such as alemtuzumab, infliximab, etanercept, adalimumab, or anti-GM CSF), rheumatologic diseases (such as systemic lupus erythematosus and rheumatoid arthritis), chronic liver disease, renal failure and/or peritoneal dialysis, hyper-IgM syndrome or hyper-IgE syndrome are the main risk factors for cryptococcosis [31, 33, 34].
In HIV-negative individuals, cryptococcosis occurs in transplant recipients and other patients with primary or acquired defects in cell-mediated immunity [32]. In a recently multicenter, longitudinal cohort study in the United States [40], the demographics of 145 HIV-negative patients with cryptococcosis demonstrated that SOT (49 cases, 33.8%) was the main underlying disease, followed by autoimmune syndromes (15.9%), hematologic malignancy (11.7%), decompensated liver disease (9.7%), solid tumor (5.6%), primary immunodeficiency (2.1%), and HSCT (2.8%). Glucocorticoid therapy and cytotoxic chemotherapy were the immunosuppressive medications described for more than 40% of patients. CNS involvement was observed in 71 patients (49%).
5. Mucormycosis
Uncontrolled diabetes, hematological malignancy, malnutrition, solid organ transplantation, hematopoietic stem cell transplant, and liver disease are the primary underlying conditions associated with mucormycosis. Predisposing factors include corticosteroid use, neutropenia, trauma, anticancer therapy, use of calcineurin inhibitors, biological and renal replacement therapies, prior antifungal prophylaxis (e.g., voriconazole), iron overload and deferoxamine therapy [41, 42, 44].
Rhinocerebral, pulmonary, cutaneous, gastrointestinal, and disseminated mucormycosis are the common types of disease described. The mortality and morbidity rates are dependent on affected organ, Mucorales species, and medical status of the patient. Mucormycosis can be an extremely aggressive disease, and mortality rates can reach 46% in sinus infection, 73% in mucormycosis after exposure to voriconazole, 76% in pulmonary disease, and 96% in disseminated infections [42, 45].
Based on autopsy reports [46], mucormycosis is the third most common cause of invasive fungal infection, after candidiasis and aspergillosis. In developed countries, hematologic malignancies and hematopoietic stem cell transplantation are the leading underlying conditions in mucormycosis cases while in developing countries, particularly in India, the major causes of the disease are associated with uncontrolled diabetes or trauma [43, 47]. Data from Transplant-Associated Infection Surveillance Network show that mucormycosis (formerly zygomycosis) was the third most common IFI (8%) in HSCT [11] and sixth most common IFI (2%) among organ transplant recipients [22].
6. Pneumocystis
Despite the genus
The occurrence of
7. Conclusions
The changes in the spectrum of the fungal infections associated with new risk factors and the emergence of resistant fungi highlight the necessity of a continuous update on knowledge of the epidemiology of fungal infections. Besides, the reduction of mortality among patients with IFIs must be accompanied by research that allows the development of new antifungal treatment strategies and earlier diagnosis by traditional and non-culture-based molecular tests.
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