The yeast genus Tardiomyces gen. nov. with one new species and two new combinations.

PURPOSE: Rare yeasts species are increasingly reported as causative agents of invasive human infection. Proper identification and antifungal therapy are essential to manage these infections. Candida blankii is one of these emerging pathogens and is known for its reduced susceptibility to multiple antifungals. METHODS: To obtain more insight into the characteristics of this species, 26 isolates reported as C. blankii were investigated using genetic and phenotypical approaches. RESULTS: Among the 26 isolates, seven recovered either from blood, sputum, urine, or the oral cavity, displayed substantial genetic and some phenotypical differences compared to the other isolates, which were confirmed as C. blankii. We consider these seven strains to represent a novel species, Tardiomyces depauwii. Phylogenomics assigned C. blankii, C. digboiensis, and the novel species in a distinct branch within the order Dipodascales, for which the novel genus Tardiomyces is erected. The new combinations Tardiomyces blankii and Tardiomyces digboiensis are introduced. Differences with related, strictly environmental genera Sugiyamaella, Crinitomyces, and Diddensiella are enumerated. All three Tardiomyces species share the rare ability to grow up to 42 °C, display slower growth in nutrient-poor media, and show a reduced susceptibility to azoles and echinocandins. Characteristics of T. depauwii include high MIC values with voriconazole and a unique protein pattern. CONCLUSION: We propose the novel yeast species Tardiomyces depauwii and the transfer of C. blankii and C. digboiensis to the novel Tardiomyces genus.

Evaluation of the Vitek 2 system for antifungal susceptibility testing of Candida auris using a representative international panel of clinical isolates: overestimation of amphotericin B resistance and underestimation of fluconazole resistance.

Although the Vitek 2 system is broadly used for antifungal susceptibility testing of Candida spp., its performance against Candida auris has been assessed using limited number of isolates recovered from restricted geographic areas. We therefore compared Vitek 2 system with the reference Clinical and Laboratory Standards Institute (CLSI) broth microdilution method using an international collection of 100 C. auris isolates belonging to different clades. The agreement ±1 twofold dilution between the two methods and the categorical agreement (CA) based on the Centers for Disease Control and Prevention's (CDC's) tentative resistance breakpoints and Vitek 2-specific wild-type upper limit values (WT-ULVs) were determined. The CLSI-Vitek 2 agreement was poor for 5-flucytosine (0%), fluconazole (16%), and amphotericin B (29%), and moderate for voriconazole (61%), micafungin (67%), and caspofungin (81%). Significant interpretation errors were recorded using the CDC breakpoints for amphotericin B (31% CA, 69% major errors; MaEs) and fluconazole (69% CA, 31% very major errors; VmEs), but not for echinocandins (99% CA, 1% MaEs for both micafungin and caspofungin) for which the Vitek 2 allowed correct categorization of echinocandin-resistant FKS1 mutant isolates. Discrepancies were reduced when the Vitek 2 WT-ULV of 16 mg/L for amphotericin B (98% CA, 2% MaEs) and of 4 mg/L for fluconazole (96% CA, 1% MaEs, 3% VmEs) were used. In conclusion, the Vitek 2 system performed well for echinocandin susceptibility testing of C .auris. Resistance to fluconazole was underestimated whereas resistance to amphotericin B was overestimated using the CDC breakpoints of ≥32 and ≥2 mg/L, respectively. Vitek 2 minimun inhibitory concentrations (MICs) >4 mg/L indicated resistance to fluconazole and Vitek 2 MICs ≤16 mg/L indicated non-resistance to amphotericin B.

Sphingolipid diversity in Candida auris: unraveling interclade and drug resistance fingerprints.

In this study, we explored the sphingolipid (SL) landscape in Candida auris, which plays pivotal roles in fungal biology and drug susceptibility. The composition of SLs exhibited substantial variations at both the SL class and molecular species levels among clade isolates. Utilizing principal component analysis, we successfully differentiated the five clades based on their SL class composition. While phytoceramide (PCer) was uniformly the most abundant SL class in all the isolates, other classes showed significant variations. These variations were not limited to SL class level only as the proportion of different molecular species containing variable number of carbons in fatty acid chains also differed between the isolates. Also a comparative analysis revealed abundance of ceramides and glucosylceramides in fluconazole susceptible isolates. Furthermore, by comparing drug-resistant and susceptible isolates within clade IV, we uncovered significant intraclade differences in key SL classes such as high PCer and low long chain base (LCB) content in resistant strains, underscoring the impact of SL heterogeneity on drug resistance development in C. auris. These findings shed light on the multifaceted interplay between genomic diversity, SLs, and drug resistance in this emerging fungal pathogen.

Revised ISHAM-ABPA working group clinical practice guidelines for diagnosing, classifying and treating allergic bronchopulmonary aspergillosis/mycoses.

BACKGROUND: The International Society for Human and Animal Mycology (ISHAM) working group proposed recommendations for managing allergic bronchopulmonary aspergillosis (ABPA) a decade ago. There is a need to update these recommendations due to advances in diagnostics and therapeutics. METHODS: An international expert group was convened to develop guidelines for managing ABPA (caused by Aspergillus spp.) and allergic bronchopulmonary mycosis (ABPM; caused by fungi other than Aspergillus spp.) in adults and children using a modified Delphi method (two online rounds and one in-person meeting). We defined consensus as ≥70% agreement or disagreement. The terms "recommend" and "suggest" are used when the consensus was ≥70% and <70%, respectively. RESULTS: We recommend screening for A. fumigatus sensitisation using fungus-specific IgE in all newly diagnosed asthmatic adults at tertiary care but only difficult-to-treat asthmatic children. We recommend diagnosing ABPA in those with predisposing conditions or compatible clinico-radiological presentation, with a mandatory demonstration of fungal sensitisation and serum total IgE ≥500 IU·mL-1 and two of the following: fungal-specific IgG, peripheral blood eosinophilia or suggestive imaging. ABPM is considered in those with an ABPA-like presentation but normal A. fumigatus-IgE. Additionally, diagnosing ABPM requires repeated growth of the causative fungus from sputum. We do not routinely recommend treating asymptomatic ABPA patients. We recommend oral prednisolone or itraconazole monotherapy for treating acute ABPA (newly diagnosed or exacerbation), with prednisolone and itraconazole combination only for treating recurrent ABPA exacerbations. We have devised an objective multidimensional criterion to assess treatment response. CONCLUSION: We have framed consensus guidelines for diagnosing, classifying and treating ABPA/M for patient care and research.

Genotyping and clonal origin of Sporothrix brasiliensis in human sporotrichosis cases in Argentina.

Sporothrix brasiliensis is considered a highly virulent emerging pathogen that causes sporotrichosis in humans, mainly after zoonotic transmission from infected cats. The epidemic of this zoonosis that originated from Brazil has spread in the last decades, generating hyperendemic regions in Latin America. We present two cases of human sporotrichosis causes by S. brasiliensis in Buenos Aires, Argentina, with good clinical response to differing treatments after contact with sick cats. Using Short tandem repeat (STR) genotyping, the two S. brasiliensis cases appear to be introduced from Brazil and likely originate from the same source.

Molecular typing and antifungal susceptibility profile of Candida krusei bloodstream isolates from Türkiye.

Candida krusei also known as Pichia kudriavzevii is a potentially multidrug-resistant yeast because it is intrinsically resistant to fluconazole and develops acquired resistance to echinocandins and polyenes. Here, we aim to provide a better understanding of the epidemiology and transmission modes of C. krusei infections by comparing invasive bloodstream (n = 35) and non-invasive vaginal (n = 20) C. krusei isolates. The genetic relatedness of the isolates was assessed using a newly described short tandem repeat (STR) analysis and their sensitivity to eight antifungal compounds was evaluated by antifungal susceptibility testing using the CLSI microbroth dilution method. All C. krusei isolates revealed unique STR genotypes, indicating the absence of clonal transmission in the study group. Furthermore, no drug-resistant or non-wild-type isolates were identified. Our findings demonstrated high resolution of STR genotyping for the detection and simultaneous genetic analysis of multiple C. krusei strains in clinical samples and excellent in vitro activity of common antifungal agents against invasive strains.

Skin innate immune response against fungal infections and the potential role of trained immunity.

Fungal skin infections are distributed worldwide and can be associated with economic and social traits. The immune response related to skin cells is complex and its understanding is essential to the comprehension of each cell's role and the discovery of treatment alternatives. The first studies of trained immunity (TI) described the ability of monocytes, macrophages and natural killer (NK) cells to develop a memory-like response. However, the duration of TI does not reflect the shorter lifespan of these cells. These conclusions supported later studies showing that TI can be observed in stem and haematopoietic cells and, more recently, also in non-immune skin cells such as fibroblasts, highlighting the importance of resident cells in response to skin disorders. Besides, the participation of less studied proinflammatory cytokines in the skin immune response, such as IL-36γ, shed light into a new possibility of inflammatory pathway blockade by drugs. In this review, we will discuss the skin immune response associated with fungal infections, the role of TI in skin and clinical evidence supporting opportunities and challenges of TI and other inflammatory responses in the pathogenesis of fungal skin infections.

Disseminated Basidiobolomycosis Caused by Basidiobolus omanensis in a Child with Acute Lymphoblastic Leukemia (ALL). Case Report and Literature Review.

Basidiobolomycosis is an uncommon fungal infection caused by the genus Basidiobolus. In immunocompetent children, it usually causes cutaneous infection and rarely affects the gastrointestinal tract, and it is extremely rare for the disease to spread. The present study reports the first case of disseminated basidiobolomycosis caused by Basidiobolus omanensis in a child with acute lymphoblastic leukemia who died as a result of uncontrolled infection and multi-organ failure despite surgical and antifungal therapy with L-AMB and voriconazole. A review of the literature yielded 76 cases, including the current case with the majority of which were reported as invasive gastrointestinal infection. The median age was 4 years (61 male and 15 female) and the majority of these children were from the Middle East (80%), specifically Saudi Arabia (45%). Most patients were treated with systemic antifungal agents (mostly itraconazole and amphotericin B). Surgical intervention was done in 25% of these patients and the death rate was 12%.

An Autochthonous Susceptible Candida auris Clade I Otomycosis Case in Iran.

Candida auris is a newly emerging multidrug-resistant fungal pathogen considered to be a serious global health threat. Due to diagnostic challenges, there is no precise estimate for the prevalence rate of this pathogen in Iran. Since 2019, only six culture-proven C. auris cases have been reported from Iran, of which, five belonged to clade V and one to clade I. Herein, we report a case of otomycosis due to C. auris from 2017 in a 78-year-old man with diabetes mellitus type II without an epidemiological link to other cases or travel history. Short tandem repeat genotyping and whole genome sequencing (WGS) analysis revealed that this isolate belonged to clade I of C. auris (South Asian Clade). The WGS single nucleotide polymorphism calling demonstrated that the C. auris isolate from 2017 is not related to a previously reported clade I isolate from Iran. The presence of this retrospectively recognized clade I isolate also suggests an early introduction from other regions or an autochthonous presence. Although the majority of reported C. auris isolates worldwide are resistant to fluconazole and, to a lesser extent, to echinocandins and amphotericin B, the reported clade I isolate from Iran was susceptible to all antifungal drugs.

A conceptual framework for nomenclatural stability and validity of medically important fungi: a proposed global consensus guideline for fungal name changes supported by ABP, ASM, CLSI, ECMM, ESCMID-EFISG, EUCAST-AFST, FDLC, IDSA, ISHAM, MMSA, and MSGERC.

The rapid pace of name changes of medically important fungi is creating challenges for clinical laboratories and clinicians involved in patient care. We describe two sources of name change which have different drivers, at the species versus the genus level. Some suggestions are made here to reduce the number of name changes. We urge taxonomists to provide diagnostic markers of taxonomic novelties. Given the instability of phylogenetic trees due to variable taxon sampling, we advocate to maintain genera at the largest possible size. Reporting of identified species in complexes or series should where possible comprise both the name of the overarching species and that of the molecular sibling, often cryptic species. Because the use of different names for the same species will be unavoidable for many years to come, an open access online database of the names of all medically important fungi, with proper nomenclatural designation and synonymy, is essential. We further recommend that while taxonomic discovery continues, the adaptation of new name changes by clinical laboratories and clinicians be reviewed routinely by a standing committee for validation and stability over time, with reference to an open access database, wherein reasons for changes are listed in a transparent way.

The Fourier-transform infrared spectroscopy-based method as a new typing tool for Candida parapsilosis clinical isolates.

The Fourier-transform infrared spectroscopy-based IR Biotyper is a straightforward typing tool for bacterial species, but its use with Candida species is limited. We applied IR Biotyper to Candida parapsilosis, a common cause of nosocomial bloodstream infection (BSI), which is aggravated by the intra-hospital spread of fluconazole-resistant isolates. Of 59 C. parapsilosis isolates studied, n = 56 (48 fluconazole-resistant and 8 fluconazole-susceptible) and n = 3 (2 fluconazole-resistant and 1 fluconazole-susceptible) isolates, respectively, had been recovered from BSI episodes in 2 spatially distant Italian hospitals. The latter isolates served as an outgroup. Of fluconazole-resistant isolates, n = 40 (including one outgroup) harbored the Y132F mutation alone and n = 10 (including one outgroup) harbored both Y132F and R398I mutations in the ERG11-encoded azole-target enzyme. Using a microsatellite typing method, which relies on the amplification of genomic short tandem repeats (STR), two major clusters were obtained based on the mutation(s) (Y132F or Y132F/R398I) present in the isolates. Regarding IR Biotyper, each isolate was analyzed in quintuplicate using an automatic (i.e., proposed by the manufacturer's software) or tentative (i.e., proposed by us) cutoff value. In the first case, four clusters were identified, with clusters I and II formed by Y132F or Y132F/R398I isolates, respectively. In the second case, six subclusters (derived by the split of clusters I and II) were identified. This allowed to separate the outgroup isolates from other isolates and to increase the IR Biotyper typeability. The agreement of IR Biotyper with STR ranged from 47% to 74%, depending on type of cutoff value used in the analysis. IMPORTANCE Establishing relatedness between clinical isolates of Candida parapsilosis is important for implementing rapid measures to control and prevent nosocomial transmission of this Candida species. We evaluated the FTIR-based IR Biotyper, a new typing method in the Candida field, using a collection of fluconazole-resistant C. parapsilosis isolates supposed to be genetically related due to the presence of the Y132F mutation. We showed that IR Biotyper was discriminatory but not as much as the STR method, which is still considered the method of choice. Further studies on larger series of C. parapsilosis isolates or closely related Candida species will be necessary to confirm and/or extend the results from this study.

Whole genome sequencing analysis demonstrates therapy-induced echinocandin resistance in Candida auris isolates.

Candida auris is an emerging, multidrug-resistant yeast, causing outbreaks in healthcare facilities. Echinocandins are the antifungal drugs of choice to treat candidiasis, as they cause few side effects and resistance is rarely found. Previously, immunocompromised patients from Kuwait with C. auris colonisation or infection were treated with echinocandins, and within days to months, resistance was reported in urine isolates. To determine whether the development of echinocandin resistance was due to independent introductions of resistant strains or resulted from intra-patient resistance development, whole genome sequencing (WGS) single-nucleotide polymorphism (SNP) analysis was performed on susceptible (n = 26) and echinocandin-resistant (n = 6) isolates from seven patients. WGS SNP analysis identified three distinct clusters differing 17-127 SNPs from two patients, and the remaining isolates from five patients, respectively. Sequential isolates within patients had a maximum of 11 SNP differences over a time period of 1-10 months. The majority of isolates with reduced susceptibility displayed unique FKS1 substitutions including a novel FKS1M690V substitution, and nearly all were genetically related, ranging from only three to six SNP differences compared to susceptible isolates from the same patient. Resistant isolates from three patients shared the common FKS1S639F substitution; however, WGS analysis did not suggest a common source. These findings strongly indicate that echinocandin resistance is induced during antifungal treatment. Future studies should determine whether such echinocandin-resistant strains are capable of long-term colonisation, cause subsequent breakthrough candidiasis, have a propensity to cross-infect other patients, or remain viable for longer time periods in the hospital environment.

Predictors for Prolonged Hospital Stay Solely to Complete Intravenous Antifungal Treatment in Patients with Candidemia: Results from the ECMM Candida III Multinational European Observational Cohort Study.

BACKGROUND: To date, azoles represent the only viable option for oral treatment of invasive Candida infections, while rates of azole resistance among non-albicans Candida spp. continue to increase. The objective of this sub-analysis of the European multicenter observational cohort study Candida III was to describe demographical and clinical characteristics of the cohort requiring prolonged hospitalization solely to complete intravenous (iv) antifungal treatment (AF Tx). METHODS: Each participating hospital (number of eligible hospitals per country determined by population size) included the first ~ 10 blood culture proven adult candidemia cases occurring consecutively after July 1st, 2018, and treating physicians answered the question on whether hospital stay was prolonged only for completion of intravenous antifungal therapy. Descriptive analyses as well as binary logistic regression was used to assess for predictors of prolonged hospitalization solely to complete iv AF Tx. FINDINGS: Hospital stay was prolonged solely for the completion of iv AF Tx in 16% (100/621) of candidemia cases by a median of 16 days (IQR 8 - 28). In the multivariable model, initial echinocandin treatment was a positive predictor for prolonged hospitalization to complete iv AF Tx (aOR 2.87, 95% CI 1.55 - 5.32, p < 0.001), while (i) neutropenia, (ii) intensive care unit admission, (iii) catheter related candidemia, (iv) total parenteral nutrition, and (v) C. parapsilosis as causative pathogen were found to be negative predictors (aOR 0.22 - 0.45; p < 0.03). INTERPRETATION: Hospital stays were prolonged due to need of iv AF Tx in 16% of patients with candidemia. Those patients were more likely to receive echinocandins as initial treatment and were less severely ill and less likely infected with C. parapsilosis.

In vitro combination of antifungal drugs with tacrolimus (FK506) holds promise against clinical Candida species, including Candida auris.

In vitro interactions between tacrolimus, a calcineurin inhibitor, and fluconazole, itraconazole, caspofungin, or anidulafungin were evaluated against Candida auris, C. albicans, C. parapsilosis, and C. glabrata (each five strains). Tacrolimus-itraconazole, tacrolimus-caspofungin, and tacrolimus-fluconazole combinations resulted in synergistic interactions against 95%, 90%, and 60% of Candida isolates, respectively. However, tacrolimus-anidulafungin resulted in only a 35% synergistic effect. A combination of tacrolimus and itraconazole was most potent with synergy against 100% of C. auris, C. parapsilosis, and C. glabrata isolates. Of note, no antagonistic interaction was found.

Genotyping and susceptibility testing uncovers large azole-resistant Candida tropicalis clade in Alexandria, Egypt.

OBJECTIVES: Candida tropicalis is an emerging medically relevant Candida species. The yeast primarily causes opportunistic infections in intensive care units and is highly prevalent in tropical countries. The genetic diversity within this species is high, and nosocomial transmission has been reported. C. tropicalis genotyping of isolates from low- and middle-income countries is underrepresented when compared with that from high-income countries. Also, in Egypt, only limited genotyping has been conducted for C. tropicalis isolates, while antifungal resistance seems to increase, especially against azoles. METHODS: Antifungal susceptibility testing was performed on 64 C. tropicalis isolates from ICU patients collected from multiple hospitals in Alexandria, Egypt. Genotyping by means of short tandem repeat (STR) and whole genome sequencing (WGS) single nucleotide polymorphism (SNP) analysis was performed. RESULTS: Using antifungal susceptibility testing, fluconazole resistance was observed in 24 isolates (38%), of which 23 harboured an ERG11 G464S substitution, previously shown to cause resistance in Candida albicans. STR genotyping showed that these 23 isolates were related, forming a distinct resistant clade. WGS SNP analysis subsequently confirmed this genetic relationship, although isolates within this clade differed in at least 429 SNPs, suggesting that these were independently introduced. CONCLUSION: Overall, STR and WGS SNP analysis of this collection indicates limited C. tropicalis nosocomial transmission in Alexandria, while the presence of this large azole-resistant C. tropicalis clade within this city hampers the treatment of intensive care unit patients.

Application of Novel Short Tandem Repeat Typing for Wickerhamomyces anomalus Reveals Simultaneous Outbreaks within a Single Hospital.

Wickerhamomyces anomalus, previously known as Candida pelliculosa, occasionally causes candidemia in humans, primarily infecting neonates, and infants. The mortality rate of these invasive infections is high, and isolates with a reduced susceptibility to fluconazole have been reported. W. anomalus outbreaks are regularly reported in healthcare facilities, especially in neonatal intensive care units (NICUs). In order to rapidly genotype isolates with a high-resolution, we developed and applied a short tandem repeat (STR) typing scheme for W. anomalus. Six STR markers were selected and amplified in two multiplex PCRs, M3 and M6, respectively. In total, 90 W. anomalus isolates were typed, leading to the identification of 38 different genotypes. Four large clusters were found, unveiling simultaneous outbreak events spread across multiple units within the same hospital. STR typing results of 11 isolates were compared to whole-genome sequencing (WGS) single nucleotide polymorphism (SNP) calling, and the identified genotypic relationships were highly concordant. We performed antifungal susceptibility testing of these isolates, and a reduced susceptibility to fluconazole was found for two (2.3%) isolates. ERG11 genes of these two isolates were examined using WGS data, which revealed a novel I469L substitution in one isolate. By constructing a homology model for W. anomalus ERG11p, the substitution was found in close proximity to the fluconazole binding site. In summary, we showed multiple W. anomalus outbreak events by applying a novel STR genotyping scheme.

Molecular Characterization and Sterol Profiles Identify Nonsynonymous Mutations in ERG2 as a Major Mechanism Conferring Reduced Susceptibility to Amphotericin B in Candida kefyr.

The molecular basis of reduced susceptibility to amphotericin B (rs-AMB) among any yeasts is poorly defined. Genetic alterations in genes involved in ergosterol biosynthesis and total cell sterols were investigated among clinical Candida kefyr isolates. C. kefyr isolates (n = 81) obtained from 74 patients in Kuwait and identified by phenotypic and molecular methods were analyzed. An Etest was initially used to identify isolates with rs-AMB. Specific mutations in ERG2 and ERG6 involved in ergosterol biosynthesis were detected by PCR sequencing. Twelve selected isolates were also tested by the SensiTitre Yeast One (SYO), and total cell sterols were evaluated by gas chromatography-mass spectrometry and ERG3 and ERG11 sequencing. Eight isolates from 8 patients showed rs-AMB by Etest, including 2 isolates with additional resistance to fluconazole or to all three antifungals. SYO correctly identified 8 of 8 rs-AMB isolates. A nonsynonymous mutation in ERG2 was detected in 6 of 8 rs-AMB isolates but also in 3 of 73 isolates with a wild-type AMB pattern. One rs-AMB isolate contained a deletion (frameshift) mutation in ERG2. One or more nonsynonymous mutations was detected in ERG6 in 11 of 81 isolates with the rs-AMB or wild-type AMB pattern. Among 12 selected isolates, 2 and 2 isolates contained a nonsynonymous mutation(s) in ERG3 and ERG11, respectively. Ergosterol was undetectable in 7 of 8 rs-AMB isolates, and the total cell sterol profiles were consistent with loss of ERG2 function in 6 rs-AMB isolates and loss of ERG3 activity in another rs-AMB isolate. Our data showed that ERG2 is a major target conferring rs-AMB in clinical C. kefyr isolates. IMPORTANCE Some yeast species exhibit intrinsic resistance or rapidly acquire resistance to azole antifungals. Despite >50 years of clinical use, resistance to amphotericin B (AMB) among yeast species has been extremely rarely reported until recently. Reduced susceptibility to AMB (rs-AMB) among yeast species is, therefore, a matter of serious concern due to the availability of only four classes of antifungal drugs. Recent studies in Candida glabrata, Candida lusitaniae, and Candida auris have identified ERG genes involved in ergosterol biosynthesis as the major targets conferring rs-AMB. The results of this study also show that nonsynonymous mutations in ERG2 impair its function, abolish ergosterol from C. kefyr, and confer rs-AMB. Thus, rapid detection of rs-AMB among clinical isolates will help in proper management of invasive C. kefyr infections.

Tackling Histoplasmosis Infection in People Living with HIV from Latin America: From Diagnostic Strategy to Public Health Solutions.

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.