BACKGROUND: Diagnosis of HIV-associated histoplasmosis remains challenging. Our objective was to compare the performances of (1→3)-β-D-Glucan (BDG) and Aspergillus galactomannan (GM) antigen for the diagnosis of HIV-associated histoplasmosis. METHODS: We performed a diagnostic accuracy study using frozen primary serum specimens issued from consecutive hospitalized people living with HIV (PLWH) and blindly tested for BDG and GM using Fungitell® and PlateliaTM Aspergillus, respectively. RESULTS: We included 121 sera with 92 HIV-associated histoplasmosis cases and 29 negative controls. At thresholds of 150 pg/mL and 0.5 for BDG and GM, sensitivity and specificity were respectively: 95% [85-100] vs 90% [77-100], 52% [34-70] vs 83% [69-97]. ROC curves showed AUCs of 0.82 [0.68-0.91] vs 0.92 [0.80-0.98] for BDG and GM, respectively. Post-test probabilities showed best performances at lowest thresholds for a negative testing of both BDG and GM, and at the 0.7 threshold for a positive GM test. CONCLUSION: If BDG alone may rule out histoplasmosis when negative, GM alone, either positive or negative, showed the best performances for the diagnosis of histoplasmosis. Given poorer performances of BDG and GM compared to Histoplasma antigen detection assays commercially available, they should be considered as an alternative in settings where Histoplasma antigen detection assays remain unavailable. However, this study essentially provides insights in the performances of fungal biomarkers in disseminated histoplasmosis and does not represent recommendations for best practices.

Invasive fungal infections are associated with high mortality, which is exacerbated by the limited antifungal drug armamentarium and increasing antifungal drug resistance. Echinocandins are a frontline antifungal drug class targeting β-glucan synthase (GS), a fungal cell wall biosynthetic enzyme. Echinocandin resistance is generally low but increasing in species like Candida glabrata, an opportunistic yeast pathogen colonizing human mucosal surfaces. Mutations in GS-encoding genes (FKS1 and FKS2 in C. glabrata) are strongly associated with clinical echinocandin failure, but epidemiological studies show that other, as yet unidentified factors also influence echinocandin susceptibility. Furthermore, although the gut is known to be an important reservoir for emergence of drug-resistant strains, the evolution of resistance is not well understood. Here, we studied the evolutionary dynamics of C. glabrata colonizing the gut of immunocompetent mice during treatment with caspofungin, a widely-used echinocandin. Whole genome and amplicon sequencing revealed rapid genetic diversification of this C. glabrata population during treatment and the emergence of both drug target (FKS2) and non-drug target mutations, the latter predominantly in the FEN1 gene encoding a fatty acid elongase functioning in sphingolipid biosynthesis. The fen1 mutants displayed high fitness in the gut specifically during caspofungin treatment and contained high levels of phytosphingosine, whereas genetic depletion of phytosphingosine by deletion of YPC1 gene hypersensitized the wild type strain to caspofungin and was epistatic to fen1Δ. Furthermore, high resolution imaging and mass spectrometry showed that reduced caspofungin susceptibility in fen1Δ cells was associated with reduced caspofungin binding to the plasma membrane. Finally, we identified several different fen1 mutations in clinical C. glabrata isolates, which phenocopied the fen1Δ mutant, causing reduced caspofungin susceptibility. These studies reveal new genetic and molecular determinants of clinical caspofungin susceptibility and illuminate the dynamic evolution of drug target and non-drug target mutations reducing echinocandin efficacy in patients colonized with C. glabrata.

The taxonomy of the Cryptococcus gattii species complex continues to evolve, and has been divided into five pathogenic species. The objective of this systematic review was to summarise the geographical distribution of the C gattii species complex and the species within the C gattii species complex. We searched PubMed for articles related to human, animal, ecological, or laboratory-based studies of C gattii species complex isolates with traceable geographical origin published from January, 1970, until September, 2021. Having extracted their geographical origin, we used ArcMap to construct maps according to the highest degree of resolution allowed by their reported taxonomy, to reflect the most likely area of transmission on the basis of published reports of human isolates. 604 such articles were included in the study. This review indicated that although C gattii species complex isolates have been reported globally, understanding their heterogeneous geographical distribution by species can have implications for researchers and clinicians in formulating research questions and considering diagnostic quandaries.

The second international meeting on endemic mycoses of the Americas (IMEMA) and the first international symposium on implantation mycoses (ISIM) took place in Santiago del Estero, Argentina, on September 25-27, 2023. The conference provided a platform for researchers, clinicians, and experts to discuss the latest developments in the field of endemic and implantation mycoses. Topics included epidemiology, diagnostic advances, treatment strategies, and the impact of environmental factors on the spread of these fungal diseases. IMEMA and ISIM contributed to the regional discourse on the mycoses, emphasizing the importance of international cooperation in addressing these public health challenges. | IMEMA/ISIM, held in Santiago del Estero, Argentina, convened experts to discuss endemic and implantation mycoses, covering topics such as epidemiology, diagnostics, treatment, and advocacy. The event highlighted ongoing efforts in combating these diseases. | eng

BACKGROUND: Opportunistic infections (OIs) are common causes of mortality among people living with HIV (PLHIV). We determined prevalence and 30-day mortality due to histoplasmosis, cryptococcosis, and TB in PLHIV with advanced HIV disease (AHD). METHODS: PLHIV 18 years and older, with a CD4 + T-cell count of less than 350 cells/mm3 newly diagnosed with HIV infection or re-engaged in care after being without ART for more than 90 days (Group A). The second group included symptomatic PLHIV regardless of ART status or CD4 + T-cell count (Group B); all followed for 30 days. Detection of Histoplasma Ag (HisAg) in urine was done by enzyme immunoassay (EIA), Cryptococcus antigen (CrAg) was detected in serum and cerebrospinal fluid (CSF) specimens by lateral flow assay (LFA), and lipoarabinomannan (LAM) detection in urine was by LFA (TB LAM) and in sputum by GeneXpert for diagnosis of Mycobacterium infections. RESULTS: From August 2021 to June 2022, 491 PLHIV were enrolled; 482 (98%) had a CD4 + T-cell result, and 381 patients (79%) were classified with AHD according to CD4 + T-cell count (< 200 CD4/mm(3)). Frequency of an OI was 38% (n = 145/381). Antigen test positivity rate was 16% (72/467) for TB-LAM, 9% (43/464) for HisAg, and 11% (51/484) for CrAg. Twenty-one of 34 (62%) patients receiving CSF CrAg tests were positive, confirming meningitis. Significant differences in 30-day mortality were observed in patients with an OI (16%) vs. no OI (7%) (p = 0.002). Mortality was highest in patients with histoplasmosis (25%), co-infection (22%), cryptococcosis (18% overall; 19% for cryptococcal meningitis), and TB (10%). CONCLUSIONS: TB and fungal OIs, including co-infection, were common in PLHIV in Paraguay and had high associated mortality. Laboratories and health facilities need access to CD4 + T-cell testing and rapid diagnostic assays.

Histoplasma antigen can be detected in people with advanced HIV disease (AHD), allowing for early and accurate diagnosis of histoplasmosis. The aim of this analysis was to assess the cost-effectiveness of routine histoplasmosis screening using antigen detection, among people with AHD. We developed a decision analytic model to evaluate Histoplasma antigen screening among people with AHD. The model estimated the costs, effectiveness, and cost-effectiveness of routine screening for Histoplasma antigen compared to the current practice of no routine Histoplasma antigen screening. The model includes stratification by symptoms of histoplasmosis, severity of presentation, and estimates of 30-day mortality. Data sources were taken from the Pan American Health Organization (PAHO) Strategic Fund databases on public purchases of medicines, and published literature on treatment outcomes. Outcome measures are life years saved (LYS), costs (US dollars), and incremental cost-effectiveness ratios (ICERs). Routine Histoplasma antigen screening avoids an estimated 17% of deaths in persons with advanced HIV disease, and is cost-effective compared to no histoplasmosis screening, with an ICER of $26/LYS. In sensitivity analysis assuming treatment for histoplasmosis with liposomal amphotericin, Histoplasma antigen screening remains cost-effective with an ICER of $607/LYS. Histoplasma antigen screening among people with AHD is a cost-effective strategy and could potentially avert 17% of AIDS-related deaths. Prospective evaluation of histoplasmosis screening is warranted to determine effectiveness and treatment outcomes with this strategy.

Histoplasmosis is a fungal infection caused by the thermally dimorphic fungus Histoplasma capsulatum. This infection causes significant morbidity and mortality in people living with HIV/AIDS, especially in countries with limited resources. Currently used diagnostic tests rely on culture and serology but with some limitations. No molecular assays are commercially available and the results from different reports have been variable. We aimed to evaluate quantitative real-time PCR (qPCR) targeting three protein-coding genes of Histoplasma capsulatum (100-kDa, H and M antigens) for detection of this fungus in formalin-fixed paraffin-embedded (FFPE) samples from patients with proven histoplasmosis. The sensitivity of 100-kDa, H and M qPCR assays were 93.9%, 91% and 57%, respectively. The specificity of 100-kDa qPCR was 93% when compared against samples from patients with other mycoses and other infections, and 100% when samples from patients with non-infectious diseases were used as controls. Our findings demonstrate that real-time PCR assays targeting 100-kDa and H antigen showed the most reliable results and can be successfully used for diagnosing this mycosis when testing FFPE samples.

Histoplasmosis, caused by the thermally dimorphic fungus Histoplasma spp., is a disease with a broad clinical spectrum, presenting from asymptomatic/flu-like symptoms to progressive disseminated disease in people with immunosuppression. In recent years, the concept of histoplasmosis as a disease restricted to the American continent has changed, as now histoplasmosis is reported in many regions around the world. In Latin America, histoplasmosis represents a threat, especially in people with advanced HIV disease (AHD). Diagnosis of histoplasmosis in people living with HIV (PLHIV) is challenging due to the low index of suspicion of the disease, non-specificity of signs and symptoms, and limited access to specific laboratory testing, while the diagnostic delay is significantly associated with mortality. In the last decade, novel diagnostic tests have been developed for the rapid detection of histoplasmosis, such as commercial kits for antigen detection. Furthermore, advocacy groups were created that presented histoplasmosis as a public health problem, with emphasis on patients at risk of progressive disseminated disease. This review aims to discuss the impact of histoplasmosis associated with AHD in Latin America and the strategies employed to tackle histoplasmosis, from the implementation of laboratory testing to disease advocacy and public health interventions.

Histoplasmosis is a major cause of mortality in people living with HIV (PLHIV). Rapid methods to diagnose Histoplasma capsulatum disease could dramatically decrease the time to initiate treatment, resulting in reduced mortality. The aim of this study was to validate a MiraVista(®) Diagnostics (MVD) Histoplasma urine antigen lateral flow assay (MVD LFA) for the detection of H. capsulatum antigen (Ag) in urine and compare this LFA against the MVista(®)&nbsp;Histoplasma Ag quantitative enzyme immunoassays (MVD EIA). We assessed the MVD LFA using a standardized reference panel of urine specimens from Colombia. We tested 100 urine specimens, 26 from PLHIV diagnosed with histoplasmosis, 42 from PLHIV with other infectious diseases, and 32 from non-HIV infected persons without histoplasmosis. Sensitivity and specificity of the MVD LFA was 96%, compared with 96% sensitivity and 77% specificity of the MVD EIA. Concordance analysis between MVD LFA and the MVD EIA displayed an 84% agreement, and a Kappa of 0.656. The MVD LFA evaluated in this study has several advantages, including a turnaround time for results of approximately 40 min, no need for complex laboratory infrastructure or highly trained laboratory personnel, use of urine specimens, and ease of performing.

Fungal respiratory illnesses caused by endemic mycoses can be nonspecific and are often mistaken for viral or bacterial infections. We performed fungal testing on serum specimens from patients hospitalized with acute respiratory illness (ARI) to assess the possible role of endemic fungi as etiologic agents. Patients hospitalized with ARI at a Veterans Affairs hospital in Houston, Texas, during November 2016-August 2017 were enrolled. Epidemiologic and clinical data, nasopharyngeal and oropharyngeal samples for viral testing (PCR), and serum specimens were collected at admission. We retrospectively tested remnant sera from a subset of patients with negative initial viral testing using immunoassays for the detection of Coccidioides and Histoplasma antibodies (Ab) and Cryptococcus, Aspergillus, and Histoplasma antigens (Ag). Of 224 patient serum specimens tested, 49 (22%) had positive results for fungal pathogens, including 30 (13%) by Coccidioides immunodiagnostic assays, 19 (8%) by Histoplasma immunodiagnostic assays, 2 (1%) by Aspergillus Ag, and none by Cryptococcus Ag testing. A high proportion of veterans hospitalized with ARI had positive serological results for fungal pathogens, primarily endemic mycoses, which cause fungal pneumonia. The high proportion of Coccidioides positivity is unexpected as this fungus is not thought to be common in southeastern Texas or metropolitan Houston, though is known to be endemic in southwestern Texas. Although serological testing suffers from low specificity, these results suggest that these fungi may be more common causes of ARI in southeast Texas than commonly appreciated and more increased clinical evaluation may be warranted.

Identification of the emerging multidrug-resistant yeast Candida auris is challenging. Here, we describe the role of the Mexico national reference laboratory Instituto de Diagnóstico y Referencia Epidemiológicos Dr. Manuel Martínez Báez (InDRE) and the Mexican national laboratory network in the identification of C. auris. Reference identification of six suspected isolates was done based on phenotypic and molecular laboratory methods, including growth in special media, evaluation of isolate micromorphology, and species-specific PCR and pan-fungal PCR and sequencing. The four C. auris isolates identified were able to grow on modified Sabouraud agar with 10% NaCl incubated at 42 °C. With one exception, isolates of C. auris were spherical to ovoid yeast-like cells and blastoconidia, with no hyphae or pseudohyphae on cornmeal agar. C. auris isolates were resistant to fluconazole. Species-specific and pan-fungal PCR confirmed isolates as C. auris. Sequence analysis revealed the presence of two different C. auris clades in Mexico, clade I (South Asia) and clade IV (South America).

Coccidioidomycosis is a disease caused by the dimorphic fungi Coccidioides spp., which affects humans and a variety of animal species, including domestic dogs. In dogs, accurate diagnosis could provide a substantial improvement on the quality of canine life, as well as an advancement in the mapping of regions endemic for coccidioidomycosis. The purpose of this study was to compare immunodiagnostic assays for anti-Coccidioides antibody (Ab) detection in dogs' serum. Three commercially available immunodiagnostic assays (IMMY(); Norman, OK, USA) were evaluated, including the sna Coccidioides Ab Lateral Flow Assay (LFA), Coccidioides IDCF immunodiffusion assay (IDCF), and the Clarus Coccidioides Ab Enzyme Immunoassay (EIA). Assays were evaluated using 98 dog serum samples: 29 from dogs with coccidioidomycosis, 15 from dogs diagnosed with histoplasmosis, 10 from dogs diagnosed with blastomycosis, and 44 from dogs without a fungal disease. Using specimens from dogs with coccidioidomycosis, the IDCF had an accuracy of 92% (95% confidence interval [95% CI] = 85-96%), the EIA had an accuracy of 91% (95% CI = 83-96%), and the LFA displayed an accuracy of 82% (95% CI = 73-89%). Using Kappa analysis, the agreement between LFA and EIA was 0.59 (95% CI = 0.42-0.75), that between LFA and IDCF was 0.64 (95% CI = 0.48-0.79), and that between EIA and IDCF was 0.79 (95% CI = 0.64-0.90). Most cross-reactions were observed in dogs with histoplasmosis. Compared with EIA and IDCF, the LFA requires substantially less laboratory equipment and infrastructure and rapidly produces results, offering a substantial improvement for the initial screening of coccidioidomycosis in dogs.

BACKGROUND: The Americas are home to biologically and clinically diverse endemic fungi, including Blastomyces, Coccidioides, Emergomyces, Histoplasma, Paracoccidioides and Sporothrix. In endemic areas with high risk of infection, these fungal pathogens represent an important public health problem. OBJECTIVES: This report aims to summarise the main findings of the regional analysis carried out on the status of the endemic mycoses of the Americas, done at the first International Meeting on Endemic Mycoses of the Americas (IMEMA). METHODS: A regional analysis for the Americas was done, the 27 territories were grouped into nine regions. A SWOT analysis was done. RESULTS: All territories reported availability of microscopy. Seventy percent of territories reported antibody testing, 67% of territories reported availability of Histoplasma antigen testing. None of the territories reported the use of (1-3)--d-glucan. Fifty two percent of territories reported the availability of PCR testing in reference centres (mostly for histoplasmosis). Most of the territories reported access to medications such as trimethoprim-sulfamethoxazole, itraconazole, voriconazole and amphotericin B (AMB) deoxycholate. Many countries had limited access to liposomal formulation of AMB and newer azoles, such as posaconazole and isavuconazole. Surveillance of these fungal diseases was minimal. CONCLUSIONS: A consensus emerged among meeting participants, this group concluded that endemic mycoses are neglected diseases, and due to their severity and lack of resources, the improvement of diagnosis, treatment and surveillance is needed.

On July 15, 2021, the Secretary of Health of Honduras (SHH) was notified of an unexpected number of mucormycosis cases among COVID-19 patients. SHH partnered with the Honduras Field Epidemiology Training Program, the Executive Secretariat of the Council of Ministers of Health of Central America and the Dominican Republic (SE-COMISCA), Pan American Health Organization (PAHO), and CDC to investigate mucormycosis cases at four geographically distinct hospitals in Honduras. | | Mucormycosis is a severe, often fatal disease caused by infection with angioinvasive molds belonging to the order Mucorales. Risk factors for mucormycosis include certain underlying medical conditions (e.g., hematologic malignancy, stem cell or solid organ transplantation, or uncontrolled diabetes) and the use of certain immunosuppressive medications (1). COVID-19 might increase mucormycosis risk because of COVID-19–induced immune dysregulation or associated medical treatments, such as systemic corticosteroids and other immunomodulatory drugs (e.g., tocilizumab), which impair the immune response against mold infections (2). In India, an apparent increase in mucormycosis cases (which was referred to by the misnomer “black fungus”) was attributed to COVID-19 (3).

A sandwich enzyme immunoassay (EIA) for the detection of Histoplasma antigens (Ag) in urine, developed by Optimum Imaging Diagnostics (OIDx) was evaluated. A verification using a standardized reference panel of urine samples found sensitivity of 92%, specificity of 32% and accuracy of 51%. In this study, the OIDx Histoplasma urinary Ag EIA displayed high sensitivity, however, in non-histoplasmosis cases this EIA displayed false-positive results in 68% of specimens tested.

BACKGROUND: Since the first report of Candida auris in 2016, the Colombian Instituto Nacional de Salud (INS) has implemented a national surveillance of the emerging multidrug-resistant fungus. OBJECTIVES: This report summarizes the findings of this laboratory-based surveillance from March 2016 to December 2020. RESULTS: A total of 1,720 C. auris cases were identified, including 393 (23%) colonization cases and 1,327 (77%) clinical cases. Cases were reported in 20 of 32 (62%) Departments of Colombia and involved hospitals from 33 cities. The median age of patients was 34 years; 317 (18%) cases were in children under 16 years, 54% were male. The peak number of cases was observed in 2019 (n=541). In 2020, 379 (94%) of 404 cases reported were clinical cases, including 225 bloodstream infections (BSI) and 154 non-BSI. Among the 404 cases reported in 2020, severe COVID-19 was reported in 122 (30%). Antifungal susceptibility was tested in 379 isolates. Using CDC tentative breakpoints for resistance, 35% of isolates were fluconazole resistant, 33% were amphotericin B resistant, and 0.3% isolate were anidulafungin resistant, 12% were multidrug resistant, and no pan-resistant isolates were identified. CONCLUSION: For five years of surveillance, we observed an increase in the number and geographic spread of clinical cases and an increase in fluconazole resistance. These observations emphasize the need for improved measures to mitigate spread.

Coronavirus disease 2019 (COVID-19), caused by the novel coronavirus SARS-CoV-2, emerged in Wuhan, China, in December 2019 and rapidly spread around the world. Invasive aspergillosis has been reported as a complication of severe influenza pneumonia among intensive care patients. Similarities between COVID-19 and influenza pneumonia, together with limited published case series, suggest that aspergillosis may be an important complication of COVID-19. This report describes a case of ventilator-associated pneumonia involving Aspergillus flavus in a patient with COVID-19 from Buenos Aires, Argentina.

OBJECTIVES: Histoplasmosis and cryptococcosis are important public health problems in people living with HIV (PLHIV) in Central America. Conventional laboratory tests, such as culture and microscopy are not optimal, however, antigen tests are rapid, highly sensitive, and specific for diagnosis of fungal opportunistic infections (OI). The aim of this study was to describe the results of a laboratory-based surveillance system for histoplasmosis and cryptococcosis. METHODS: An observational cross-sectional study based on laboratory surveillance, was carried out in two hospitals in Guatemala and one hospital in El Salvador, between July 2012 to and December 2014. Diagnosis of histoplasmosis and cryptococcosis in PLHIV were performed by culture and antigen test. RESULTS: A total of 160 PLHIV were diagnosed with fungal OI, of which, 96 (60%) were diagnosed with histoplasmosis, 62 (39%) were with cryptococcosis, and two patients (1%) were diagnosed with both fungal diseases. Of the 160 patients analyzed in this study, 94 (59%) were diagnosed using only an antigen assay. CD4 cell count data was available for 136 (85%) patients; 127 (93%) patients had a CD4 count <200 and 90 (66%) had counts <50 CD4 cells per µL. Antiretroviral therapy utilization at diagnosis was low (33%). Seventy-one out of 160 (44%) were co-infected with tuberculosis or other OIs. CONCLUSION: More than half of the patients in this study were diagnosed only by rapid laboratory antigen tests. A high percent of the patients had advanced HIV disease.

OBJECTIVES: Histoplasmosis and cryptococcosis are important public health problems in people living with HIV (PLHIV) in Central America. Conventional laboratory assays, based on microscopy and culture, are not optimal for the diagnosis of either disease. However, antigen (Ag) assays are rapid and highly accurate for the diagnosis of these infections. METHODS: Laboratory surveillance of PLHIV was carried out in four hospitals in Panama, Honduras, and Nicaragua, between 2015 and 2019. Detection of Histoplasma antigens in urine was performed by enzyme immunoassay (EIA), and Cryptococcus antigen detection in sera and cerebrospinal fluid specimens was performed by lateral flow assay (LFA). RESULTS: A total of 4,453 PLHIV with clinical suspicion of histoplasmosis (n=1,343) or cryptococcosis (n=3,110; 2,721 sera and 389 CSF) were tested. Of 1,343 patients suspected of having histoplasmosis, 269 (20%) were Histoplasma Ag positive. Of 3,110 patients tested using the Cryptococcus Ag assay, 329 (11%) were positive. Honduras reported the highest positivity rates (32% for Histoplasma Ag, and 16% for Cryptococcus Ag); Panama reported the largest number of patients testing positive using the Histoplasma Ag assay (n=201); and Nicaragua reported the largest number of patients testing positive using the Cryptococcus Ag assay (n=170). CONCLUSION: Here we show how the implementation of rapid diagnostics assays impacted case detection and were useful for the care of people with advanced HIV. Rapid and accurate diagnosis could reduce mortality associated with histoplasmosis and cryptococcosis in PLHIV.

BACKGROUND: The genus Candida includes about 200 different species, but only a few are able to produce disease in humans. The species responsible for the highest proportion of human infections is Candida albicans. However, in the last two decades there has been an increase in the proportion of infections caused by other Candida species, including C. glabrata (Nakaseomyces glabrata), C. parapsilosis, C. tropicalis, C. krusei (Pichia kudriavzevi) and more recently C. auris. Decolonization of patients has been used as an infection control strategy for bacterial infections, but information about decolonization products used in clinical practice for Candida and other fungal pathogens is limited. Compounds with antimicrobial activity, such as triclosan (TR), boric acid (BA) and zinc oxide (ZO), are mainly used in personal care products. These products can be used for long periods of time without an abrasive skin effect and are a possible alternative for patient decolonization in health care settings. OBJECTIVE: The aim of this study was to evaluate the antifungal activity of boric acid (BA), triclosan (TR) and zinc oxide (ZO), individually and combined, against clinically relevant Candida species. MATERIALS AND METHODS: Compounds to be screened for antifungal activity were evaluated at different concentrations, alone, and combined, using a well diffusion assay. The statistical evaluation was performed using analysis of variance (ANOVA) and a post hoc analysis using the multiple comparisons method. RESULTS: Individually, BA and TR showed antifungal activity against all Candida species evaluated but ZO did not show any antifungal activity. Mixtures of BA [5%] - TR [0.2%]; BA [5%] - TR [0.3%]; BA [5%] - TR [0.2%] - ZO [8.6%]; and BA [5%] - TR [0.2%] - ZO [25%] yielded the highest antifungal activity. An increased antifungal effect was observed in some mixtures when compared with individual compounds. CONCLUSIONS: We demonstrated antifungal activity of BA and TR against multiple Candida species, including against a clade of the emerging healthcare-associated pathogen C. auris. Additionally, this study shows enhancement of the antifungal effect and no antagonism among the mixtures of these compounds. Further research is needed to determine whether these compounds can reduce the burden of Candida on skin.

Endemic fungi are thermally dimorphic fungi that have a limited geographic range and can cause both primary disease and opportunistic infections. The Americas are home to more genera of endemic fungi than anywhere else on earth. These include Coccidioides, Histoplasma, Blastomyces, Paracoccidioides, and Sporothrix. Endemic fungi are found across the Americas and the Caribbean, from Blastomyces gilchristi, which extends into the northeast corners of North America, to Histoplasma capsulatum, which occurs all the way down in the southern regions of South America and into the Caribbean Islands. Symptoms of endemic fungal infection, when present, mimic those of many other diseases and are often diagnosed only after initial treatment for a bacterial or viral disease has failed. Endemic fungi place a significant medical burden on the populations they affect, especially in immunocompromised individuals and in resource-limited settings. This review summarizes the ecology, geographical range, epidemiology, and disease forms of the endemic fungi found in the Americas. An emphasis is placed on new and proposed taxonomic changes, including the assignment of new species names in Histoplasma, Blastomyces, and Paracoccidioides.

Histoplasmosis is a frequent fungal opportunistic infection in people living with HIV (PLHIV), associated every year to a total of 5% to 15% of AIDS-related deaths among this population. In 2020, the first global guidelines for diagnosing and managing disseminated histoplasmosis among PLHIV was published. This document recommends (1) detection of circulating Histoplasma antigens as the recommended laboratory assay to diagnose histoplasmosis among PLHIV; (2) the use of liposomal amphotericin for induction therapy in severe or moderately severe disease, followed by a maintenance therapy with itraconazole for 12 months; a shorter maintenance therapy could be considered if the patient is clinically stable and if immune status has improved; (3) antiretroviral therapy initiation as soon as possible among patients with histoplasmosis without involvement of central nervous system; and (4) that for the treatment of co-infection with histoplasmosis and tuberculosis (TB), treatment of TB should be initiated according to the World Health Organization treatment guidelines. Appropriate health education of providers, supportive supervision, and policy guidance for the care of PLHIV are required.

The disease caused by the new SARS-CoV-2, known as Coronavirus disease 2019 (COVID-19), was first identified in China in December 2019 and rapidly spread around the world. Coinfections with fungal pathogens in patients with COVID-19 add challenges to patient care. We conducted a literature review on fungal coinfections in patients with COVID-19. We describe a report of a patient with disseminated histoplasmosis who was likely infected with SARS-CoV-2 and experienced COVID-19 during hospital care in Buenos Aires, Argentina. This patient presented with advanced HIV disease, a well-known factor for disseminated histoplasmosis; on the other hand, we suspected that COVID-19 was acquired during hospitalization but there is not enough evidence to support this hypothesis. Clinical correlation and the use of specific Histoplasma and COVID-19 rapid diagnostics assays were key to the timely diagnosis of both infections, permitting appropriate treatment and patient care.

Cat-transmitted sporotrichosis caused by Sporothrix brasiliensis has become a major public health concern and presents a distinct divergence from the traditional epidemiology of sporotrichosis. This emerging fungal pathogen spreads readily among cat populations, and human infections occur exclusively via zoonotic transmission. While sporotrichosis is an implantation mycosis that typically manifests as cutaneous lesions in humans and cats, severe extracutaneous manifestations are more common with S. brasiliensis than other Sporothrix species infections. Rapid diagnosis and appropriate treatment regimens are critical for successful clinical resolution of sporotrichosis in both cats and humans. Species-level identification of Sporothrix is possible with molecular diagnostics and necessary for tracking the geographic expansion of S. brasiliensis and better understanding its epidemiology. Combatting cat-transmitted sporotrichosis requires a One Health approach to successfully implement public health control measures.

The fungal kingdom contains an estimated 2.2–3.8 million species [1]. Fungi are ubiquitous and primarily co-exist with plants and animals, creating mutual benefits, including the acquisition of vital nutrients and protection from pathogenic microorganisms. Generally, fungi are beneficial to humankind and are indispensable in the food production chain and in biotechnological processes like the production of chemical compounds and drugs. Approximately 600 species have been reported to cause human disease, mostly due to traumatic introduction into the host. An even smaller number cause serious superficial or invasive disease (https://www.clinicalfungi.org/). The dermatophytes cause superficial infections, but also deep infections, and negatively impact the quality of life of ~ 1 billion people worldwide [2–5]. Globally, Aspergillus, Candida, Cryptococcus, Pneumocystis, and Mucorales infections (the ‘big five’) are important causes of fungal morbidity and mortality, primarily affecting immunocompromised hosts [2, 6, 7]. Among these big five, Candida yeasts cause the largest number of infections, with annual estimates of 134 million mucosal infections, as well as 750,000 life-threatening bloodstream infections associated with mortality rates > 40% [2, 8].

BACKGROUND: Candida auris is an emerging multidrug-resistant yeast that causes outbreaks in healthcare settings around the world. In 2016, clinicians and public health officials identified patients with C. auris bloodstream infections (BSI) in Colombian healthcare facilities. To evaluate potential risk factors and outcomes for these infections, we investigated epidemiologic and clinical features of patients with C. auris and other Candida species BSI. METHODS: We performed a retrospective case-case investigation in four Colombian acute care hospitals, defining a case as Candida spp. isolated from blood culture during January 2015-September 2016. C. auris BSI cases were compared to other Candida species BSI cases. Odds ratio (OR), estimated using logistic regression, was used to assess the association between risk factors and outcomes. RESULTS: We analyzed 90 patients with BSI, including 40 with C. auris and 50 with other Candida species. All had been admitted to the intensive care unit (ICU). No significant demographic differences existed between the two groups. The following variables were independently associated with C. auris BSI: ≥ 15 days of pre-infection ICU stay (OR: 5.62, CI: 2.04-15.5), evidence of severe sepsis (OR: 3.70, CI 1.19-11.48), and diabetes mellitus (OR 5.69, CI 1.01-31.9). CONCLUSION: Patients with C. auris BSI had longer lengths of ICU stay than those with other candidemias, suggesting that infections are acquired during hospitalization. This is different from other Candida infections, which are usually thought to result from autoinfection with host flora.

The recent emergence of a multidrug-resistant yeast, Candida auris, has drawn attention to the closely related species from the Candida haemulonii complex that include C. haemulonii, Candida duobushaemulonii, Candida pseudohaemulonii, and the recently identified Candida vulturna. Here, we used antifungal susceptibility testing and whole-genome sequencing (WGS) to investigate drug resistance and genetic diversity among isolates of C. haemulonii complex from different geographic areas in order to assess population structure and the extent of clonality among strains. Although most isolates of all four species were genetically distinct, we detected evidence of the in-hospital transmission of C. haemulonii and C. duobushaemulonii in one hospital in Panama, indicating that these species are also capable of causing outbreaks in healthcare settings. We also detected evidence of the rising azole resistance among isolates of C. haemulonii and C. duobushaemulonii in Colombia, Panama, and Venezuela linked to substitutions in ERG11 gene as well as amplification of this gene in C. haemulonii in isolates in Colombia suggesting the presence of evolutionary pressure for developing azole resistance in this region. Our results demonstrate that these species need to be monitored as possible causes of outbreaks of invasive infection.

Purpose of Review: This review highlights innovative approaches for histoplasmosis detection using laboratory technologies published in the past 6 years. Recent Findings: Microscopy and culture are the gold standards for confirming the diagnosis of histoplasmosis, but these can be slow, and their sensitivity and specificity can vary. It is well known that rapid diagnosis is necessary to save lives. Newer technologies based on detection of antibodies, antigens, and DNA can enable rapid and accurate clinical diagnosis. Summary: Based on a systematic review of the literature and evaluation of methodologies in five areas, assay accuracy, rapid testing, point of care testing, commercial availability, and use in animal diagnosis and environmental detection, we describe innovative approaches for detection of Histoplasma/histoplasmosis.

Fungal pathogens can affect humans, animals, and plants, and they can be found in the environment or as part of the host microbiome. Fungal diseases present a broad clinical spectrum, ranging from superficial to invasive infections, and can cause outbreaks. During an outbreak investigation, the laboratory plays an essential role in verifying the diagnosis and helping to confirm the source of the outbreak. Immunodiagnostic assays are important tools and often relied upon for the diagnosis of fungal infections, since the gold standard assays of culture and histopathology are time-consuming and often require invasive procedures. Immunodiagnostic assays range from complement fixation and immunodiffusion to enzyme immunoassays and, most recently, to point-of-care lateral flow devices. In general, these assays provide results faster and offer good analytical performance. These characteristics make immunodiagnostic assays good laboratory tools for outbreak investigations. The aim of this review is to describe the principles, advantages, limitations, and availability of immunodiagnostics assays in outbreak investigations, based on the experience of a reference laboratory.

BACKGROUND: Candida auris is an emerging multidrug-resistant yeast that can cause invasive infections and healthcare-associated outbreaks. Here, we describe 34 cases of pediatric C. auris bloodstream infections (BSIs) identified during July 2014-October 2017 in 2 hospitals in Colombia. METHODS: We conducted a retrospective review of microbiology records for possible C. auris cases in 2 hospitals in Barranquilla and Cartagena. BSIs that occurred in patients aged <18 years confirmed as C. auris were included in this analysis. RESULTS: We identified 34 children with C. auris BSIs. Twenty-two (65%) patients were male, 21% were aged <28 days, 47% were aged 29-365 days, and 32% were aged >1 year. Underlying conditions included preterm birth (26%), being malnourished (59%), cancer (12%), solid-organ transplant (3%), and renal disease (3%). Eighty-two percent had a central venous catheter (CVC), 82% were on respiratory support, 56% received total parenteral nutrition (TPN), 15% had a surgical procedure, and 9% received hemodialysis. Preinfection inpatient stay was 22 days (interquartile range, 19-33 days), and in-hospital mortality was 41%. CONCLUSIONS: Candida auris affects children with a variety of medical conditions including prematurity and malignancy, as well as children with CVCs and those who receive TPN. Mortality was high, with nearly half of patients dying before discharge. However, unlike most other Candida species, C. auris can be transmitted in healthcare settings, as suggested by the close clustering of cases in time at each of the hospitals.Candida auris is an emerging multidrug-resistant yeast that can cause invasive infections and healthcare-associated outbreaks. This report describes 34 cases of pediatric C. auris bloodstream infections, identified in two hospitals in Colombia, South America.