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.     

A 12-year study of fungal infections in Rio Grande do Sul,Southern Brazil

BackgroundThe number of fungal infections has increased in recent years in Rio Grande do Sul (RS), Brazil. Epidemiological studies are important for proper control of infections.AimsTo evaluate the etiology of fungal infections in patients in RS, from 2003 to 2015.MethodsThis is a retrospective and longitudinal study carried out at Mycology Department of Central Laboratory of RS; 13,707 samples were evaluated. The variables sex, age, site of infection, and etiologic agent were analyzed. Susceptibility of Candida to fluconazole was tested in isolates from samples collected in 2015 from 51 outpatients.ResultsOf the 13,707 samples, 840 cases (6.12%) of fungal infections were found and included in the analyses; female gender accounted for the 55.9% of the cases. The main fungus was Candida albicans (450 cases, 53.38%; p < 0.001). Onychomycosis was the most frequent infection in superficial mycoses. Systemic mycoses accounted for 54.05% of the cases, from which 68.8% occurred in males, mainly HIV-positive (33.11%), and the main etiologic agent in these cases was Cryptococcus neoformans (73.13%). Among 51 samples tested for susceptibility to fluconazole, 78.43% of Candida isolates were susceptible; 5.88% were susceptible in a dose-dependent manner, and 15.69% were resistant.ConclusionsC. albicans is a common cause of fungal infections in RS, accounting for half of the cases; resistance to antifungals was found in non-hospitalized patients. In addition, women seem to be more susceptible to fungal infections than men, however men show more systemic mycoses than women. The nails are the most common site of infection.     

Opportunistic invasive mycoses in AIDS. An autopsy study of 211 cases.

The opportunistic mycoses are an important cause of morbidity-mortality among patients with severe immunosuppression provoked by HIV. We present a study of 211 serial autopsies of patients with HIV/AIDS infection carried out by our service in a period of 10 years, observing frequency of invasive mycoses of the 44.1%. Pneumocystis carinii infection was the most frequent (32%) with a prevalence of lung affection. Candidiasis follows it in order of frequency with 31.1%, predominantly the oropharyngeal manifestation. Systemic or cerebromeningeal cryptococcosis were serious and common disorder (29%). Diseminated histoplasmosis occurred in 9.6% and in three cases (3.2%) pulmonary aspergillosis was diagnosed as a postmortem discovery in cavity lesions. In our series, other less common HIV-associated were not identified.     

Aspectos actuales de las enfermedades invasivas por hongos filamentosos

Invasive fungal infections have become a major cause of morbimortality in intensive care patients, persons suffering from cancer or immune deficiencies, and other diseases with impaired immunity. Candida albicans remains the most frequent fungal pathogen, but advances in the diagnosis, prevention and treatment of invasive candidiasis are leading to important etiological changes. Among the emerging invasive mycoses, are those caused by filamentous fungi, such as Aspergillus, Lomentospora/Scedosporium, Fusarium or the Mucorales. Invasive aspergillosis is difficult to diagnose, and although there are diagnostic tools available, their use is not widespread, and their effectiveness vary depending on the group of patients. Clinical suspicion in high-risk patients, radiological diagnosis and the use of biomarkers, such as 1,3-β-D-glucan and galactomannan, can be of great help. However, diagnostic resources are limited in other mycoses, but radiology, pathological studies and the microbiological diagnosis can be useful. The high mortality of these mycoses requires early empirical antifungal treatment in many cases. Voriconazole is the first choice for treatment of the majority of aspergillosis, scedosporiasis, fusariosis and other hyalohyphomycoses. The treatment of mucormycoses, Lomentospora prolificans infections or mycoses by dematiaceous fungi are more complicated. Amphotericin B is active against many mucoralean fungi, but the combination of two or more antifungal agents could be a therapeutic alternative in many amphotericin B-refractory mycoses. Current clinical challenges include improving the diagnosis and the treatment of these mycoses, along with improving the adequate prevention in patients at high risk of suffering from them.     

Onychomycosis in Rome,Italy

This report presents the results of a study conducted between 1985 and 1994 on onychomycosis observed in the city of Rome. Six thousand six hundred and eighty eight patients were examined during this period. Among them 1,762 (26.3%) were affected by fungal nail infections. Because the etiologic agents could not be isolated in 105 cases (6%), the results refer to 1,657 subjects (24.8% of the total), presenting with positive microscopic and cultural examinations. Thirty eight patients (2.3%) had onychomycosis of both their hands and feet.From an etiological point of view, 59.1% of the nail infections were caused by yeasts, 23.2% were infected with dermatophytes and 17.6% by non-dermatophytic fungi. The etiology of onychomycosis of the hands differed from that of the feet. Yeasts were primarily responsible for onychomycosis of the hands (86.2%), while dermatophytes caused tinea unguium peduum (48%). Fungal fingernail infections by Candida spp. were the most common (50.3%), followed by those of the feet by dermatophytes (20%). Candida albicans was responsible for 70.6% of the hand infections but for only 15.9% of those of the feet. Trichophyton rubrum and T mentagrophytes were the most common dermatophytes, mainly causing toenail infections (23.4% and 21%, respectively), while Aspergillus spp., Scopulariopsis brevicaulis, Acremonium spp. and Aspergillus niger were the most common non-dermatophytes observed.With regard to sex, the fungal nail infections were more widespread in women (72.1%) and in subjects of both sexes over the age of 50.     

Environmental Isolates of Fungi from Aquarium Pools Housing Killer Whales (Orcinus orca)

Systemic mycoses in killer whales (Orcinus orca) are rare diseases, but have been reported. Two killer whales died by fungal infections at the Port of Nagoya Public Aquarium in Japan. In this study, the fungal flora of the pool environment at the aquarium was characterized. Alternaria spp., Aspergillus spp. (A. fumigatus, A. niger, A. versicolor), Fusarium spp. and Penicillium spp. were isolated from the air and the pool surroundings. The other isolates were identified as fungal species non-pathogenic for mammals. However, the species of fungi isolated from the environmental samples in this study were not the same as those isolated from the cases of disease in killer whales previously reported.     

Epidemiology of Invasive Fungal Infections in Patients with Acquired Immunodeficiency Syndrome at a Reference Hospital for Infectious Diseases in Brazil

Invasive fungal infections (IFIs) represent one of the main causes of morbimortality in immunocompromised patients. Pneumocystosis, cryptococcosis and histoplasmosis are the most frequently occurring IFIs in patients with acquired immunodeficiency syndrome (AIDS). Fungi, such as Candida spp. and Aspergillus spp., may cause severe diseases during the course of an HIV infection. Following the introduction of highly active anti-retroviral therapy, there has been a marked reduction of opportunistic fungal infections, which today is 20–25 % of the number of infections observed in the mid-1990s. This study is an observational and retrospective study aimed at the characterising IFI incidence and describing the epidemiology, clinical diagnostic and therapeutic features and denouement in HIV/AIDS patients. In HIV/AIDS patients, the IFI incidence is 54.3/1,000 hospitalisation/year, with a lethality of 37.7 %. Cryptococcosis represents the main opportunistic IFI in the population, followed by histoplasmosis. Nosocomial pathogenic yeast infections are caused principally by Candida spp., with a higher candidemia incidence at our institution compared to other Brazilian centres.     

Advances and limitations in the early diagnosis of invasive yeast infections

In the last years, the main advances in the serological diagnosis of mycoses caused by yeasts have occurred in the area of antibody and (1-3)-beta-D-glucan detection. Commercialization of the Candida albicans IFA IgG test and detection of antibodies against recombinant antigens Hwp1 and enolase are the most important contributions to the first area. Detection of (1-3)-beta-D-glucan confirms its usefulness as a good marker for the diagnosis of invasive candidiasis. The most recent studies suggest that combination of two tests to detect antígen, antibodies, (1-3)-beta-D-glucan and DNA will be needed to optimize the diagnosis of systemic yeast infections.     

Las micosis en Venezuela: casuística de los Grupos de Trabajo en Micología (1984-2010)

BackgroundIn 1984 the Venezuelan Work Groups in Mycology (VWGM) were created introducing an innovative approach to the study of the mycoses in Venezuela.AimTo study the occurrence of the mycoses in Venezuela.MethodsReview the reported cases of mycoses by the newsletter Boletín Informativo Las Micosis en Venezuela (VWGM) from 1984 to 2010.ResultsThe data collected showed 36,968 reported cases of superficial mycoses, 1,989 of deep systemic cases, and 822 of localized mycoses. Pityriasis dermatophytosis was the most common superficial infection, and paracoccidioidomycosis and histoplasmosis the most frequent deep systemic infection. Chromoblastomycosis was the most frequently diagnosed subcutaneous infection. The data provided showed the distribution by geographical area for each of the fungal infections studied, which may help to establish the endemic areas.DiscussionSuperficial mycosis is a public health problem due to its high morbidity and is probably responsible for some of the outbreaks in high-risk groups. Paracoccidioidomycosis and histoplasmosis were reported more often, which agrees with earlier reports prior to the formation of the VWGM. Cases of sporotrichosis and chromoblastomycosis in Venezuela can be considered unique due to the high number of cases. This study highlights the contribution of the VWGM to the behavior of the mycoses in Venezuela, its incidence, prevalence, and the recognition of these infections as a problem of public health importance. The VWGM should keep working in this endeavor, not only reporting new cases, but also unifying the clinical and epidemiological criteria, in order to properly monitor the evolving epidemiological changes reported in these types of infections.     

The fungal cell wall as a target for the development of new antifungal therapies

In the past three decades invasive mycoses have globally emerged as a persistent source of healthcare-associated infections. The cell wall surrounding the fungal cell opposes the turgor pressure that otherwise could produce cell lysis. Thus, the cell wall is essential for maintaining fungal cell shape and integrity. Given that this structure is absent in host mammalian cells, it stands as an important target when developing selective compounds for the treatment of fungal infections. Consequently, treatment with echinocandins, a family of antifungal agents that specifically inhibits the biosynthesis of cell wall (1-3)β-D-glucan, has been established as an alternative and effective antifungal therapy. However, the existence of many pathogenic fungi resistant to single or multiple antifungal families, together with the limited arsenal of available antifungal compounds, critically affects the effectiveness of treatments against these life-threatening infections. Thus, new antifungal therapies are required. Here we review the fungal cell wall and its relevance in biotechnology as a target for the development of new antifungal compounds, disclosing the most promising cell wall inhibitors that are currently in experimental or clinical development for the treatment of some invasive mycoses.     

A Case of Rhinoorbital Mucormycosis in a Leukemic Patient with a Literature Review from Turkey

Mucormycosis (Zygomycosis) is a rare, invasive, opportunistic fungal infection of the paranasal sinuses, caused by a fungus of the order Mucorales. We report a case of rhinoorbital mucormycosis caused by Rhizopus oryzae in an acute lymphoblastic leukemia patient and review the 79 Mucormycosis cases reported in the last decade from Turkey. In our case, the diagnosis was made with endoscopic appearance, computerized tomography of the paranasal sinuses, and culture of the surgical materials. Following aggressive surgical debridement and parenteral amphotericin B therapy, the patient recovered completely. In Turkish literature, rhinocerebral manifestations were the most common form of the mucormycosis (64 cases), followed by pulmonary form (6 cases). The most common risk factor was hematologic malignancies (32 cases) and diabetes mellitus (32 cases), similar to those reported from the rest of the world. The etiologic agents responsible for the review cases were Rhizopus sp., Mucor spp., Rhizomucor spp., Rhizopus oryzae, Mucor circinelloides, and Lichtheimia corymbifera. Although various treatment modalities were used, amphotericin B was the mainstay of therapy. Mortality rate was found to be 49.4% in review cases. It seems that strong clinical suspicion and early diagnosis, along with aggressive antifungal therapy and endoscopic sinus surgery, have great importance for better prognosis in mucormycosis.     

Therapeutic DNA vaccine encoding peptide P10 against experimental paracoccidioidomycosis

Paracoccidioidomycosis (PCM), caused by Paracoccidioides brasiliensis, is the most prevalent invasive fungal disease in South America. Systemic mycoses are the 10th most common cause of death among infectious diseases in Brazil and PCM is responsible for more than 50% of deaths due to fungal infections. PCM is typically treated with sulfonamides, amphotericin B or azoles, although complete eradication of the fungus may not occur and relapsing disease is frequently reported. A 15-mer peptide from the major diagnostic antigen gp43, named P10, can induce a strong T-CD4+ helper-1 immune response in mice. The TEPITOPE algorithm and experimental data have confirmed that most HLA-DR molecules can present P10, which suggests that P10 is a candidate antigen for a PCM vaccine. In the current work, the therapeutic efficacy of plasmid immunization with P10 and/or IL-12 inserts was tested in murine models of PCM. When given prior to or after infection with P. brasiliensis virulent Pb 18 isolate, plasmid-vaccination with P10 and/or IL-12 inserts successfully reduced the fungal burden in lungs of infected mice. In fact, intramuscular administration of a combination of plasmids expressing P10 and IL-12 given weekly for one month, followed by single injections every month for 3 months restored normal lung architecture and eradicated the fungus in mice that were infected one month prior to treatment. The data indicate that immunization with these plasmids is a powerful procedure for prevention and treatment of experimental PCM, with the perspective of being also effective in human patients.     

Present and future of voriconazole in the treatment of invasive mycoses: the inseparable binomial diagnosis-treatment

Two milestones have characterized the last decades in Medical Mycology: the continuous increase in incidence of invasive mycoses and the discovery of new antifungal drugs that have allowed the successful treatment of these severe infections. This monography presents the most relevant studies on the present situation of invasive mycoses, its diagnosis and treatment, as well as data confirming the important role of voriconazole in their treatment.     

Serodiagnosis of Mycoses Using Recombinant Antigens

The early diagnosis of mycoses is important for the institution of an effective antifungal therapy. Detection of antibodies against crude antigenic extracts is one of the standard techniques for the diagnosis of most mycoses. However, while these crude antigenic extracts are relatively easy to obtain, they usually show low reproducibility and are not very specific, since antibodies from patients with different mycoses may show cross-reactivity. The application of molecular biology techniques to the study of fungal antigens has allowed the production of recombinant antigens that may help to solve these problems. The purpose of this review is to discuss the use of recombinant fungal antigens in the diagnosis of mycoses.     

Histopathological diagnosis of mycoses in veterinary pathology

Histopathological analysis demonstrates the morphology of the fungi and shows their relationship with tissue lesions, which is a valuable information in the diagnosis of veterinary mycoses, especially in superficial infections where reservoirs make difficult the diagnosis using other techniques. On the other hand, histopathological analysis should be complementary to other methods such as culture, immunohistochemistry, serology, PCR, etc. In this work, the most relevant histopathological features of some of the most common mycoses of domestic animals, some of which have zoonotic potential, are described and their differential diagnosis is discussed. To facilitate the discussion of the differential diagnoses, mycoses have been grouped by the sites of the infections and by the nature of the fungi (dimorphic and filamentous). Mycoses included in the study were 1) Superficial and deep infections: dermatophytosis, dermatophytic pseudomycetoma, eumycotic mycetoma, phaeohyphomycosis and malasezziasis. 2) Systemic mycoses: aspergillosis and zygomycosis. 3) Mycoses due to dimorphic fungi: candidiasis, cryptococcosis, blastomycosis, sporotrichosis, coccidioidomycosis and histoplasmosis. 4) Infections by algae and other fungi: protothecosis and pneumocystosis.     

Onychomycosis in Cali,Colombia

This study presents the epidemiological and mycological aspects of 299 patients with nail lesions who were referred to three diagnostic laboratories in the city of Cali. The diagnosis of mycoses was established through visualization of mycotic structures in a direct microscopic examination of skin scrapings and by isolation. Onychomycosis was found in 183 cases (61.2%), of which 141 were in toenails (44 in males and 97 in females), 38 in fingernails (9 males and 29 females), and 4 cases in toenails and fingernails simultaneously (all females). No statistically significant relation was found between sex and onychomycosis. Yeasts accounted for 40.7% of the mycoses, dermatophytes for 38%, nondermatophyte molds for 14% and the etiology was mixed in the remaining cases (7.3%). Candida albicans was the most commonly isolated yeast species; the most common dermatophyte was Trichophyton rubrum and Fusarium spp. and Scytalidium dimidiatum were the most common nondermatophytic molds. Them common fungi found in fingernails were yeasts; in toenails dermatophytes were more prevalent (chi2 with Yates' correction = 19.75, P= 0.000088). Yeasts were observed more frequently in females while dermatophytes were more common in males. The difference between these two etiologic groups was statistically significant (chi2 with Yates' correction = 7.43, P = 0.0064); no relation was observed according to age.     

A global view on fungal infections in humans and animals: infections caused by dimorphic fungi and dermatophytoses

Fungal infections are still underappreciated and their prevalence is underestimated, which renders them a serious public health problem. Realistic discussions about their distribution, symptoms, and control can improve management and diagnosis and contribute to refinement of preventive actions using currently available tools. This article represents an overview of dermatophytes and endemic fungi that cause infections in humans and animals. In addition, the impact of climate change on the fungal spread is discussed. The endemic fungal infections characterized in this article include coccidioidomycosis, histoplasmosis, blastomycosis, lobomycosis, emergomycosis and sporotrichosis. Moreover the geographic distribution of these fungi, which are known to be climate sensitive and/or limited to endemic tropical and subtropical areas, is highlighted. In turn, dermatophytes cause superficial fungal infections of skin, hairs and nails, which are the most prevalent mycoses worldwide with a high economic burden. Therefore, the possibility of causing zoonoses and reverse zoonoses by dermatophytes is highly important. In conclusion, the article illustrates the current issues of the epidemiology and distribution of fungal diseases, emphasizing the lack of public programmes for prevention and control of these types of infection.     

重型肝炎患者肝移植术后真菌感染临床分析

目的分析重型肝炎肝移植受体术后真菌感染情况,进一步探讨其易感因素和防治措施。方法回顾性分析我院器官移植中心2003年3月至2006年2月间89例重型肝炎肝移植患者的临床资料并进行讨论。结果89例重型肝炎肝移植患者中21例出现术后真菌感染,感染率为23.6%,较其他病种肝移植更高,其中12例为白念珠菌(57.1%),6例为光滑念珠菌(28.6%),1例为近平滑念珠菌,1例为克柔念珠菌,1例为热带念珠菌。真菌感染多发生在术后1周内,感染部位以呼吸系统为主。结论重型肝炎肝移植患者术后真菌感染以念珠菌属的早期呼吸道感染为主。术前肝性脑病与术后发生真菌感染之间存在相关关系。而一般的白念珠菌感染不会显著地影响重型肝炎肝移植患者的预后。预防性使用抗真菌药物在重型肝炎肝移植术后真菌感染的治疗中具有重要意义。     

Antifungal Therapy for Invasive Fungal Diseases in Allogeneic Stem Cell Transplant Recipients: An Update

Invasive fungal diseases (IFDs) remain a major cause of morbidity and mortality in allogeneic stem cell transplant (SCT) recipients. While the most common pathogens are Candida spp. and Aspergillus spp., the incidence of infections caused by non-albicans Candida species as well as molds such as Zygomycetes has increased. For many years, amphotericin B deoxycholate (AMB-D) was the only available antifungal for the treatment of IFDs. Within the past decade, there has been a surge of new antifungal agents developed and added to the therapeutic armamentarium. Lipid-based formulations of amphotericin B provide an effective and less nephrotoxic alternative to AMB-D. Voriconazole has now replaced AMB-D as first choice for primary therapy of invasive aspergillosis (IA). Another extended-spectrum triazole, posaconazole, also appears to be a promising agent in the management of zygomycosis, refractory aspergillosis, and for prophylaxis. Members of the newest antifungal class, the echinocandins, are attractive agents in select infections due to their safety profile, and are a more attractive option compared to AMB-D as initial treatment for invasive candidiasis and (based on one study) challenge fluconazole for superiority in management with this mycoses. However, challenges do exist among these newer agents in very high-risk individuals like allogeneic SCT recipients, which may include adverse drug events, drug–drug interactions, variability in oral absorption, and availability of alternative formulations. The addition of newer agents has also stimulated interest in the potential application of combination therapy in serious, life-threatening infections. However, adequate studies are not available for most IFDs; thus, the clinical use of combination therapy is not evidenced based on most cases and preciseness in its use is uncertain. Finally, therapeutic drug monitoring of select antifungals (notably posaconazole and voriconazole) may play an increasing role due to significant interpatient variability in serum concentrations after standard doses.     

Epidemiological characteristics of infections caused by Bacteroides, Prevotella and Fusobacterium species: a prospective observational study

In order to investigate differences among infections due to Gram-negative anaerobic bacteria (Bacteroides, Prevotella and Fusobacterium spp.), clinical, epidemiological, and microbiological data were collected and evaluated from 206 anaerobic infections. The most frequently isolated species was Bacteroides fragilis. The majority of the cases were intra-abdominal infections (49%) followed by skin and soft tissue infections (24.7%). Logistic regression analysis showed that Bacteroides spp. strains were more often isolated from intra-abdominal infections (p?=?0.002), whereas Prevotella spp. were isolated more frequently from cases with shorter duration of hospitalization (p?=?0.026), and less frequently from bloodstream infections (p?=?0.049). In addition, Bacteroides spp. were associated with coinfection due to Enterobacteriaceae species (p?=?0.007), whereas Prevotella spp. were associated with coinfection due to Staphylococcus spp. (p?=?0.002). Patients with an infection due to B.?fragilis, were more frequently admitted in a general surgical ward (p?=?0.017), or have been treated with a 2nd generation cephalosporin before anaerobic infection onset (p?=?0.05). Total mortality was 10.9% and was associated with bacteremia (p?=?0.026), and hematological (p?=?0.028), or solid organ malignancy (p?=?0.007). Metronidazole resistance was detected only among Prevotella spp. (16.2%) and B. fragilis group (0.8%) isolates. In conclusion, this study indicated differences between infections due to the most frequently isolated Gram-negative anaerobic species, differences that may affect the design and implementation of empirical antimicrobial chemotherapy guidelines.