Proceedings of the Second International Meeting on Endemic Mycoses of the Americas (IMEMA), and First International Symposium on Implantation Mycoses (ISIM).

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 during September 25-27th, 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 in 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.

Evaluation of an enzyme immunoassay technique on detecting urinary Histoplasma capsulatum antigen in the diagnosis of disseminated histoplasmosis in Argentina.

INTRODUCTION: Histoplasmosis is a systemic mycosis of universal distribution, highly endemic in the Americas. It is caused by a dimorphic fungus Histoplasma capsulatum var. capsulatum. It affects both immunocompetent and immunocompromised individuals where progressive and disseminated forms are observed. A very important risk factor is HIV infection/AIDS, with a mortality rate of 20-40% in Latin America. The diagnosis of this mycosis is made by conventional and molecular methods or by antigen and antibody detection. METHODS: In this retrospective, longitudinal and analytical study, carried out over a period of 2 years, the sensitivity (S) and specificity (E) of a commercial kit for the detection of Histoplasma antigen by EIA technique (HC-Ag) was evaluated in 50 patients with AIDSassociated histoplasmosis. In addition, its performance was compared with that of other diagnostic techniques routinely used in our laboratory. RESULTS: HC-Ag had a S of 94%, E 96%, positive likelihood coefficient (CVP): 20.68 and negative likelihood coefficient (CVN): 0.06. The delay time of the results was 4 days, similar to that of antibody detection and n-PCR and much less than that of blood cultures. The combination of methods improved S to 100%; with similar values in E. CONCLUSION: The HC-Ag method demonstrated its usefulness in the diagnosis of progressive disseminated histoplasmosis and the combination of methods is a good option to increase sensitivity and decrease the time to reach the diagnosis of certainty. This allows improving the strategy in the management of the disease and decreasing its case-fatality rate.

Introducción: La histoplasmosis es una micosis sistémica de distribución universal, altamente endémica en las Américas. Es causada por un hongo dimórfico: Histoplasma capsulatum var. capsulatum. Afecta tanto a inmunocompetentes como a inmunocomprometidos, se observan formas progresivas y diseminadas. Un factor de riesgo muy importante es la infección por HIV/sida, con una tasa de mortalidad del 20-40% en América Latina. El diagnóstico de esta micosis se realiza por métodos convencionales y moleculares o por detección de antígenos y anticuerpos. Métodos: En este estudio retrospectivo, longitudinal y analítico, realizado en un periodo de 2 años, se evaluó la sensibilidad (S) y especificidad (E) de un kit comercial para la detección de antígeno de Histoplasma por técnica de EIA (HC-Ag) en 50 pacientes con histoplasmosis asociada a sida. Además, se comparó su rendimiento con el de otras técnicas diagnósticas utilizadas habitualmente en nuestro laboratorio. Resultados: HC-Ag tuvo una S del 94%, E del 96%, coeficiente de verosimilitud positiva (CVP) de 20.68 y coeficiente de verosimilitud negativa (CVN) de 0.06. El tiempo de demora de los resultados fue de 4 días, similar al de la detección de anticuerpos y n-PCR y mucho menor que el de los hemocultivos. La combinación de métodos mejoró la S a 100%; con valores similares en E. Conclusión: El método HC-Ag demostró su utilidad en el diagnóstico de histoplasmosis diseminada progresiva y la combinación de métodos es una buena opción para aumentar la sensibilidad y disminuir el tiempo para llegar al diagnóstico de certeza. Esto permite mejorar la estrategia en el manejo de la enfermedad y reducir su tasa de letalidad.

Evaluation of an enzyme immunoassay technique on detecting urinary Histoplasma capsulatum antigen in the diagnosis of disseminated histoplasmosis in Argentina / Evaluación de una técnica de inmunoensayo enzimático para la detección del antígeno urinario de Histoplasma capsulatum en el diagnóstico de histoplasmosis diseminada en Argentina

Abstract Introduction : Histoplasmosis is a systemic mycosis of universal distribution, highly endemic in the Americas. It is caused by a dimorphic fungus Histoplasma capsulatum var. capsulatum. It affects both immunocompetent and immunocompromised individuals where progressive and disseminated forms are observed. A very important risk factor is HIV infection/AIDS, with a mortality rate of 20-40% in Latin America. The diagnosis of this mycosis is made by conventional and molecular methods or by antigen and antibody detection. Methods : In this retrospective, longitudinal and ana lytical study, carried out over a period of 2 years, the sensitivity (S) and specificity (E) of a commercial kit for the detection of Histoplasma antigen by EIA technique (HC-Ag) was evaluated in 50 patients with AIDS-associated histoplasmosis. In addition, its performance was compared with that of other diagnostic techniques routinely used in our laboratory. Results : HC-Ag had a S of 94%, E 96%, positive likeli hood coefficient (CVP): 20.68 and negative likelihood coefficient (CVN): 0.06. The delay time of the results was 4 days, similar to that of antibody detection and n-PCR and much less than that of blood cultures. The combination of methods improved S to 100%; with simi lar values in E. Conclusion : The HC-Ag method demonstrated its usefulness in the diagnosis of progressive disseminated histoplasmosis and the combination of methods is a good option to increase sensitivity and decrease the time to reach the diagnosis of certainty. This allows improv ing the strategy in the management of the disease and decreasing its case-fatality rate.

Resumen Introducción : La histoplasmosis es una micosis sis témica de distribución universal, altamente endémica en las Américas. Es causada por un hongo dimórfico: Histoplasma capsulatum var. capsulatum. Afecta tanto a inmunocompetentes como a inmunocomprometidos, se observan formas progresivas y diseminadas. Un factor de riesgo muy importante es la infección por HIV/sida, con una tasa de mortalidad del 20-40% en América Latina. El diagnóstico de esta micosis se realiza por métodos convencionales y moleculares o por detección de antígenos y anticuerpos. Métodos : En este estudio retrospectivo, longitudinal y analítico, realizado en un periodo de 2 años, se evaluó la sensibilidad (S) y especificidad (E) de un kit comercial para la detección de antígeno de Histoplasma por técnica de EIA (HC-Ag) en 50 pacientes con histoplasmosis aso ciada a sida. Además, se comparó su rendimiento con el de otras técnicas diagnósticas utilizadas habitualmente en nuestro laboratorio. Resultados : HC-Ag tuvo una S del 94%, E del 96%, coeficiente de verosimilitud positiva (CVP) de 20.68 y coeficiente de verosimilitud negativa (CVN) de 0.06. El tiempo de demora de los resultados fue de 4 días, simi lar al de la detección de anticuerpos y n-PCR y mucho menor que el de los hemocultivos. La combinación de métodos mejoró la S a 100%; con valores similares en E. Conclusión : El método HC-Ag demostró su utilidad en el diagnóstico de histoplasmosis diseminada progresiva y la combinación de métodos es una buena opción para aumentar la sensibilidad y disminuir el tiempo para llegar al diagnóstico de certeza. Esto permite mejorar la estrategia en el manejo de la enfermedad y reducir su tasa de letalidad.

[Clinical problems in Medical Mycology: Problem number 56]. / Problemas clínicos en Micología Médica: problema número 56.

We present the case of a twenty six year-old woman with rheumatoid arthritis, treated with certolizumab. She sought medical attention due to cough, fever and night sweats. X-ray exam showed a miliary pneumonia. She was treated for tuberculosis and 50days later she presented with aphasia. Magnetic nuclear resonance revealed brain lesions. Histoplasma capsulatum PCR test and urinary antigen were positive, so an antifungal treatment with voriconazole was started. Visual adverse effects forced to change the antifungal schedule in both the length of treatment and the antifungal drug. With this measure the patient progressed favorably. The test of urinary Histoplasma capsulatum antigen and PCR amplification were key to make a diagnosis and also for a follow-up.

High-Throughput Microsatellite Markers Development for Genetic Characterization of Emerging Sporothrix Species.

Sporotrichosis is the main subcutaneous mycosis worldwide transmitted by animal or plant vectors and often escalates to outbreaks or epidemics. The current cat-transmitted sporotrichosis driven by Sporothrix brasiliensis has become a significant public health issue in South America. Transmission dynamics remain enigmatic due to the lack of development of polymorphic markers for molecular epidemiological analysis. This study used a high-throughput mining strategy to characterize simple sequence repeat (SSR) markers from Sporothrix genomes. A total of 118,140-143,912 SSR loci were identified (82,841-98,369 unique markers), with a 3651.55-3804.65 SSR/Mb density and a majority of dinucleotides motifs (GC/CG). We developed a panel of 15 highly polymorphic SSR markers suitable for genotyping S. brasiliensis, S. schenckii, and S. globosa. PCR amplification revealed 240 alleles in 180 Sporothrix isolates with excellent polymorphic information content (PIC = 0.9101), expected heterozygosity (H = 0.9159), and discriminating power (D = 0.7127), supporting the effectiveness of SSR markers in uncovering cryptic genetic diversity. A systematic population genetic study estimated three clusters, corresponding to S. brasiliensis (population 1, n = 97), S. schenckii (population 2, n = 49), and S. globosa (population 3, n = 34), with a weak signature of mixed ancestry between populations 1 and 2 or 3 and 2. Partitioning of genetic variation via AMOVA revealed highly structured populations (ΦPT = 0.539; Nm = 0.213; p < 0.0001), with approximately equivalent genetic variability within (46%) and between (54%) populations. Analysis of SSR diversity supports Rio de Janeiro (RJ) as the center of origin for contemporary S. brasiliensis infections. The recent emergence of cat-transmitted sporotrichosis in northeastern Brazil indicates an RJ-Northeast migration resulting in founder effects during the introduction of diseased animals into sporotrichosis-free areas. Our results demonstrated high cross-species transferability, reproducibility, and informativeness of SSR genetic markers, helping dissect deep and fine-scale genetic structures and guiding decision making to mitigate the harmful effects of the expansion of cat-transmitted sporotrichosis.

Características clínicas, métodos diagnósticos y evolución de la criptococosis extrameníngea en personas viviendo con VIH / Clinical features, diagnosis methods and evolution in non meningeal cryptococcosis in people living with VIH

La criptococosis es una micosis grave que se manifiesta, en el 90% de los casos, como una meningoencefalitis, especialmente en las personas con VIH. El objetivo de este estudio es describir los casos de criptococosis extrameníngea en personas viviendo con VIH y conocer cuántas de estas padecen compromiso meníngeo concomitante. Además, determinar la relación con el título de antígeno polisacárido capsular de Cryptococcus en suero. Se realizó un estudio retrospectivo, observacional y analítico. Se incluyeron personas viviendo con VIH cuyo diagnóstico inicial de criptococosis se había realizado a partir de muestras extrameníngeas en el período comprendido entre 2012 y 2019. Los pacientes se dividieron en dos grupos. Grupo 1, pacientes sin compromiso meníngeo; Grupo 2, aquellos que finalmente tenían compromiso del SNC. De un total de 531 criptococosis registradas en ese período, se incluyeron 113 pacientes (21%), de los cuales en 58 se comprobó el compromiso meníngeo. No se observaron diferencias significativas en cuanto a la mortalidad entre ambos grupos.Ninguno de los pacientes con antigenemia por LFA (antígeno capsular en suero por inmunocromatografía) positiva, pero con antigenemia por aglutinación de partículas de látex (AL) negativa, tuvo compromiso meníngeo. Se observó que títulos de antígeno para Cryptococcus en suero por AL mayor o igual a 1/100 se correlacionaron con un aumento de 30 veces en la posibilidad de padecer meningitis. En todos los casos se debe descartar el compromiso del SNC. La AL sigue siendo una prueba útil y complementaria, debido a que en los casos con AL negativa no se observó compromiso meníngeo

Cryptococcosis is a serious mycosis that manifests itself, in 90% of cases, as meningoencephalitis, especially in AIDS patients. The objective of this study is to describe the extra-meningeal cases of cryptococcosis in people living with HIV and to know how many of them suffer from concomitant meningeal involvement. Also, to determine its relationship with the Cryptococcus capsular polysaccharide antigen titer in serum.A retrospective, observational and analytical study was carried out. HIV-positive patients whose initial diagnosis had been made from extrameningeal samples in the period between 2012 and 2019 were included. The patients were divided into 2 groups. Group 1: patients without meningeal involvement; group 2: those who finally had CNS involvement.Of a total of 531 cryptococcosis registered in this period, 113 patients (21%) were included, of whom meningeal involvement was confirmed in 58. No significant differences were observed in terms of mortality in both groups.None of the patients with positive LFA antigenemia (Capsular antigen detection by lateral Flow assay) but negative latex particle agglutination (LA) antigenemia had meningeal involvement. LFA was found to be highly sensitive and allows early diagnosis, but it does not replace other diagnostic procedures.Serum Cryptococcus antigen titers for by LA greater than or equal to 1/100 were found to correlate with a 30-fold increase in the likelihood of meningitis.In all cases, CNS involvement must be ruled out. LA continues to be a useful and complementary test, because in cases with negative LA, no meningeal involvement was observed

A new duplex PCR assay for the rapid screening of mating-type idiomorphs of pathogenic Sporothrix species.

Sporothrix schenckii and allied species are thermodimorphic fungi widely distributed in nature which causes human and animal sporotrichosis, the most common subcutaneous mycosis globally. Sporotrichosis is acquired after a traumatic inoculation of soil or plant material contaminated with Sporothrix propagules or through bites and scratches from diseased cats. In Ascomycota, the master regulators of sex are MAT genes that lie in a single mating-type locus, in Sporothrix these are determined by two nonhomologous alleles, MAT1-1 and MAT1-2. We assessed the whole-genome sequences of medically relevant Sporothrix to develop a single-tube duplex PCR assay to screen S. brasiliensis, S. schenckii, S. globosa, and S. luriei idiomorphs (MAT1-1 or MAT1-2) and understand the distribution and incidence of mating-type strains from natural populations. Using our duplex PCR assay, a 673 bp amplicon (α-box protein) was consistently amplified from all MAT1-1 isolates, while a 291 bp fragment was only amplified from the isolates harboring MAT1-2 (HMG box). Molecular evidence suggests heterothallism (self-sterility) as the unique mating strategy among the species evaluated. The mating-type identity of 93 isolates revealed a nearly equal distribution (1:1 ratio) of mating type alleles within species but deviating between different outbreak areas. Remarkably, for S. brasiliensis in Rio de Janeiro, we report an overwhelming occurrence of MAT1-2 (1:13 ratio; χ2 = 10.286, P = 0.0013) opposing the high prevalence MAT1-1 in the Rio Grande do Sul (10:1 ratio; χ2 = 7.364, P = 0.0067). Therefore, the population structure of Sporothrix species refers from paucity to regular cycles of sexual recombination in most of the studied regions. Our PCR-based mating-type diagnostic assay is proposed here as an important marker to track the geographical expansion during the long-lasting outbreak of cat-transmitted sporotrichosis driven by S. brasiliensis.

Chronic recurrent vulvovaginitis is not only due to Candida.

BACKGROUND: Recurrent vulvovaginitis is a growing problem that affects millions of women worldwide. In many cases it is treated as vulvovaginal candidiasis, but there is not always microbiological confirmation. AIMS: To determine the etiology of vulvovaginitis in a group of patients. METHODS: This is a cross-sectional study in which the data from the medical records of 316 adult patients who consulted for vulvovaginitis were analyzed. Eighty nine percent of the cases had already suffered previous episodes. RESULTS: The median age was 34 (265 patients were between 16 and 45 years old). Yeasts were isolated in culture from 211 (66.8%) patients, although pseudo-hyphae and yeasts were observed in only 166 samples (52.5%) in the direct microscopic examination. Multiple predisposing factors were found, among which the use of contraceptives or previous antibiotics stand out. Most of the patients (almost 90%) had been treated with antifungals, with or without microbiological confirmation. Candida albicans was isolated in 187 (88.6%) patients, followed by Candida glabrata in 6 (2.8%) patients. Association with bacterial vaginosis was found in 35.1% and with intermediate bacterial microbiota in 33.2% of the cases. A remarkably high proportion of C. albicans isolates resistant to fluconazole (80.1%) and itraconazole (58.8%) was found. CONCLUSIONS: A microbiological analysis is essential to confirm the diagnosis of vulvovaginal candidiasis, whether simple, complicated, or recurrent. Identifying the isolated yeast species and determining its susceptibility to antifungal agents are particularly important.

[Tinea capitis: clinical features and therapeutic alternatives]. / Tinea capitis: aspectos clínicos y alternativas terapéuticas.

A descriptive observational and cross-sectional study was carried out. The clinical characteristics, etiologic agents, treatments and outcome of 33 cases of tinea capitis in the Mycology Unit at Francisco J. Muñiz Hospital of Buenos Aires City between January 2015 and December 2019 were analyzed. The median age of the patients was 7 years, 21 of whom were male, 3 were HIV-positive and 22 had pets. The isolated etiologic agents were the following: Microsporum canis in 22 cases, Trichophyton tonsurans in 8, Nannizzia gypsea in 2 and Trichophyton mentagrophytes in one patient. Suppurative tinea capitis (krion Celsi) was detected in 10 cases and the same number of patients presented other skin locations of their dermatophytosis in addition to those in the scalp. Twenty-one cases were orally treated with griseofulvin and 12 with terbinafine. Those patients with suppurative tinea capitis received drops of betamethasone by mouth besides the antifungal drugs. All patients had good clinical and mycological response to the treatments, all lesions disappeared, and mycological studies turned negative by the end of the treatments. We conclude that both drugs were effective for the treatment of tinea capitis; however, lesions in those cases receiving terbinafine involuted more slowly.

Tongue lesion due to Cryptococcus neoformans as the first finding in an HIV-positive patient.

BACKGROUND: Cryptococcosis is a severe universally distributed mycosis which mainly affects immunocompromised hosts. This mycosis is caused by yeasts of two species complex of the genus Cryptococcus: Cryptococcus neoformans and Cryptococcus gattii. Meningeal cryptococcosis is the most frequent clinical presentation of this disseminated mycosis. The oral mucosa involvement is extremely unusual. CASE REPORT: We present a case of cryptococcosis with an unusual clinical form. The patient was assisted because she had an ulcerated lesion on the lingual mucosa. Encapsulated yeasts compatible with Cryptococcus were found in microscopic exams of wet preparations from lingual ulcer clinical samples obtained for cytodiagnosis and mycological studies. Cryptococcus neoformans (C. neoformans var. grubii VNI) was isolated in culture. This patient did not know her condition of HIV seropositive before the appearance of the tongue lesion. CONCLUSIONS: The involvement of the oral mucosa is uncommon in this fungal infection, but is important to include it in the differential diagnosis in HIV positive patients.

Genomic diversity of the human pathogen Paracoccidioides across the South American continent.

Paracoccidioidomycosis (PCM) is a life-threatening systemic mycosis widely reported in the Gran Chaco ecosystem. The disease is caused by different species from the genus Paracoccidioides, which are all endemic to South and Central America. Here, we sequenced and analyzed 31 isolates of Paracoccidioides across South America, with particular focus on isolates from Argentina and Paraguay. The de novo sequenced isolates were compared with publicly available genomes. Phylogenetics and population genomics revealed that PCM in Argentina and Paraguay is caused by three distinct Paracoccidioides genotypes, P. brasiliensis (S1a and S1b) and P. restrepiensis (PS3). P. brasiliensis S1a isolates from Argentina are frequently associated with chronic forms of the disease. Our results suggest the existence of extensive molecular polymorphism among Paracoccidioides species, and provide a framework to begin to dissect the connection between genotypic differences in the pathogen and the clinical outcomes of the disease.

Inherited CARD9 Deficiency in a Patient with Both Exophiala spinifera and Aspergillus nomius Severe Infections.

PURPOSE: Caspase-associated recruitment domain-9 (CARD9) deficiency is an inborn error of immunity that typically predisposes otherwise healthy patients to single fungal infections and the occurrence of multiple invasive fungal infections is rare. It has been described as the first known condition that predisposes to extrapulmonary Aspergillus infection with preserved lungs. We present a patient that expands the clinical variability of CARD9 deficiency. MATERIALS AND METHODS: Genetic analysis was performed by Sanger sequencing. Neutrophils and mononuclear phagocyte response to fungal stimulation were evaluated through luminol-enhanced chemiluminescence and whole blood production of the proinflammatory mediator interleukin (IL)-6, respectively. RESULTS: We report a 56-year-old Argentinean woman, whose invasive Exophiala spinifera infection at the age of 32 years was unexplained and reported in year 2004. At the age of 49 years, she presented with chronic pulmonary disease due to Aspergillus nomius. After partial improvement following treatment with caspofungin and posaconazole, right pulmonary bilobectomy was performed. Despite administration of multiple courses of antifungals, sustained clinical remission could not be achieved. We recently found that the patient's blood showed an impaired production of IL-6 when stimulated with zymosan. We also found that she is homozygous for a previously reported CARD9 loss-of-function mutation (Q289*). CONCLUSIONS: This is the first report of a patient with inherited CARD9 deficiency and chronic invasive pulmonary aspergillosis (IPA) due to A. nomius. Inherited CARD9 deficiency should be considered in otherwise healthy children and adults with one or more invasive fungal diseases.

Antifungal Resistance in Clinical Isolates of Aspergillus spp.: When Local Epidemiology Breaks the Norm.

Aspergillosis is a set of very frequent and widely distributed opportunistic diseases. Azoles are the first choice for most clinical forms. However, the distribution of azole-resistant strains is not well known around the world, especially in developing countries. The aim of our study was to determine the proportion of non-wild type strains among the clinical isolates of Aspergillus spp. To this end, the minimum inhibitory concentration of three azoles and amphotericin B (used occasionally in severe forms) was studied by broth microdilution. Unexpectedly, it was found that 8.1% of the isolates studied have a diminished susceptibility to itraconazole. This value turned out to be similar to the highest azole resistance rate reported in different countries across the world.

[Clinical problems in medical mycology: problem number 53]. / Problemas clínicos en micología médica: problema número 53.

A 21 year-old man, HIV infected, and with poor adherence to antiretroviral treatment, consulted us due to a papular rash on trunk and extremities, showing simultaneously hypochromic stains on his back. He was afebrile and hemodynamically stable. In the mycological study of the clinical samples taken from different lesions, yeasts compatible with Malassezia were observed. Oral itraconazole was prescribed, with an excellent clinical response. Finding the same etiolologic agent in 2different clinical pictures on a single patient is extremely rare.

[Clinical problems in medical mycology: Problem number 52]. / Problemas clínicos en micología médica: problema número 52.

The case of a 60 year old woman with hemoptysis and a thin-walled cavitary lesion at the upper lobe of the right lung is presented. The woman presented at the Mycology Unit of the Muñiz Hospital in Buenos Aires City 3 months after the beginning of her clinical manifestations. A hyaline micelial fungus with chlamido-arthroconidias was isolated from the bronchoalveolar lavage. Immunodiffusion and counter-immnunoelectrophoresis with coccidioidin and histoplasmin rendered positive results against both antigents, and skin tests with coccidioidin and histoplasmin were also positive with strong reactions. The isolated fungus was identified as Coccidioides posadasii at the National Microbiology Institute Carlos Malbrán, by means of a molecular technique. The patient was treated with itraconazole by oral route at a daily dose of 200mg with good clinical response, but due to the persistence of the lung cavity, a surgical removal of the upper lobe of the right lung had to be scheduled.

[Clinical problems in medical mycology: Problem number 51]. / Problemas clínicos en micología médica: problema número 51.

A 48 year-old immunocompetent woman, who had a nodular lesion in the neck and a dense infiltrate at the lower lobe of the left lung, presented at the Mycology Unit of Muñiz Hospital of Buenos Aires City. The pulmonary infiltrate disappeared spontaneously 3 months later. The histopathological study of the nodular lesion showed capsulated yeasts (mucicarmin and alcian blue positive stains) compatible with Cryptococcus. The mycological study of a new sample, obtained by a nodular puncture, allowed the isolation of yeasts, identified as Cryptococcus gattii (VGII). Latex test for Cryptococcus capsular antigen in serum was positive (1/100). CSF cultures rendered negative results. Fluconazole at a daily dose of 800mg was given during 45 days with partial improvement; as cultures from a new clinical sample were positive for Cryptococcus, the antimycotic was changed to itraconazole 400mg/day for 5 months, with an excellent clinical response.

Cryptococcosis in an Infectious Diseases Hospital of Buenos Aires, Argentina. Revision of 2041 cases: Diagnosis, clinical features and therapeutics.

BACKGROUND: Cryptococcosis is still a life-threatening mycosis that continues to be of serious concern in Latin American countries, especially among HIV+positive population. However, there is not any reliable information about the prevalence of this disease in this region. AIMS: The aim of this study is to report data of 2041 patients with cryptococcosis that were attended at the Infectious Diseases Hospital F. J. Muñiz over a 30 year-period. METHODS: Information about demographic and clinical data, survival time and the applied treatment, was taken from the Mycology Unit database. Mycological exams from different clinical samples were performed. Cryptococcal capsular antigen in serum and cerebrospinal fluid was detected through the latex agglutination technique. Cryptococcus isolates were phenotypically identified and the genotype was determined in some of them. Susceptibility tests were carried out following M27-A3 document. RESULTS: Seventy five percent of HIV+positive patients and 50% of the HIV-negative population were males. Mean ages were 34.1 in HIV+positive patients and 44.8 in the HIV-negative. Cryptococcosis was associated with AIDS in 98% of the cases. Meningeal compromise was seen in 90% of the patients. Although cerebrospinal fluid rendered more positive results, blood culture was the first diagnostic finding in some cases. Cryptococcal antigen showed positive results in 96.2% of the sera samples and in the 93.1% of the cerebrospinal fluid samples. Most of the isolates were Cryptococcus neoformans and belonged to genotype VNI. Minimal inhibitory concentration values were mostly below the epidemiological cutoff values. CONCLUSIONS: We observed that thanks to a high level of clinical suspicion, early diagnosis, combined therapy and intracranial pressure control by daily lumbar punctures, the global mortality rate has markedly decreased through the years in the analyzed period.

[Histoplasmosis in AIDS patients without tegumentary manifestations]. / Histoplasmosis en pacientes con SIDA sin manifestaciones cutáneo-mucosas.

BACKGROUND: Histoplasmosis is a mycosis with a high prevalence in HIV/AIDS patients. Clinical presentation includes a wide spectrum of manifestations and diagnosis usually takes up to several weeks in patients who do not present cutaneous lesions. AIM: To determine the clinical and microbiological characteristics as well as some biochemical parameters in patients with AIDS-associated histoplasmosis without tegumentary lesions, in order to develop a guideline which enables an early empiric treatment in cases of difficult diagnosis. METHODS: Medical records of 86 patients with histoplasmosis were reviewed; 31 patients with diagnosis of AIDS-associated histoplasmosis without cutaneous lesions were analyzed. RESULTS: Fever was the most frequent symptom (96.7%), lung involvement was observed in 22 patients (70.9%), the most commonly radiological pattern was miliary pattern [(12/22), 54.5%]. Nineteen patients presented with splenomegaly. Blood culture sensitivity was 93.3% (28/30) and serology was positive only in 23.5% of the cases. Eight patients died (25.8%). Patients in which CD4+ T cell lymphocytes count was < 50 cells/µl, albumin levels < 2.5 g/dl and who presented with pancytopenia had an unfavorable outcome. CONCLUSIONS: In HIV seropositive patients with fever associated to splenomegaly and bilateral miliar pattern in chest radiography, the empiric treatment with amphotericin B must be considered if signs and symptoms of unfavorable outcome are present and due to the time that it takes to arrive at an accurate diagnosis. In order to confirm the diagnosis, all microbiological samples should be collected prior to initiating therapy.

Histoplasmosis en pacientes con SIDA sin manifestaciones cutáneo-mucosas / Histoplasmosis in AIDS patients without tegumentary manifestations

Resumen Antecedentes: La histoplasmosis es una micosis de gran relevancia en pacientes con SIDA. El cuadro clínico puede ser muy variado y, en enfermos que no desarrollan lesiones cutáneas, el diagnóstico suele demorar varias semanas. Objetivo: Establecer pautas que permitan emplear un tratamiento empírico y precoz en pacientes con histoplasmosis asociada al SIDA sin manifestaciones tegumentarias y determinar las características clínicas, microbiológicas y algunos parámetros bioquímicos en los casos de difícil diagnóstico. Métodos: Se analizaron las historias clínicas de 86 pacientes con histoplasmosis. Fueron seleccionados 31 enfermos con histoplasmosis asociada con SIDA sin lesiones cutáneas. Resultados: La fiebre fue el síntoma más frecuente (96,7%), el compromiso pulmonar se comprobó en 22 enfermos (70,9%). El patrón radiológico más frecuentemente hallado en las radiografías de tórax fue el miliar o micronodulillar bilateral [(12/22), 54,5%]. Diecinueve enfermos presentaron esplenomegalia. Los hemocultivos demostraron una sensibilidad de 93,3% (28/30) y la serología fue positiva en 23,5% de los casos. Fallecieron ocho pacientes (25,8%). Los pacientes con recuentos de linfocitos T CD4+ menores a 50 céls/μl, albúmina menor a 2,5 g/dl y pancitopenia evidenciaron un pronóstico desfavorable. Conclusiones: En los pacientes con infección por VIH, fiebre asociada a esplenomegalia y lesiones micronodulillares bilaterales en la radiografía de tórax debe considerarse el tratamiento empírico con anfotericina B cuando existan signos o síntomas de mal pronóstico, debido al tiempo de demora hasta el diagnóstico definitivo. Previo a iniciar el tratamiento deben tomarse todas las muestras para los estudios microbiológicos que permitan confirmar luego la presunción diagnóstica.

Background: Histoplasmosis is a mycosis with a high prevalence in HIV/AIDS patients. Clinical presentation includes a wide spectrum of manifestations and diagnosis usually takes up to several weeks in patients who do not present cutaneous lesions. Aim: To determine the clinical and microbiological characteristics as well as some biochemical parameters in patients with AIDS-associated histoplasmosis without tegumentary lesions, in order to develop a guideline which enables an early empiric treatment in cases of difficult diagnosis. Methods: Medical records of 86 patients with histoplasmosis were reviewed; 31 patients with diagnosis of AIDS-associated histoplasmosis without cutaneous lesions were analyzed. Results: Fever was the most frequent symptom (96.7%), lung involvement was observed in 22 patients (70.9%), the most commonly radiological pattern was miliary pattern [(12/22), 54.5%]. Nineteen patients presented with splenomegaly. Blood culture sensitivity was 93.3% (28/30) and serology was positive only in 23.5% of the cases. Eight patients died (25.8%). Patients in which CD4+ T cell lymphocytes count was < 50 cells/μl, albumin levels < 2.5 g/dl and who presented with pancytopenia had an unfavorable outcome. Conclusions: In HIV seropositive patients with fever associated to splenomegaly and bilateral miliar pattern in chest radiography, the empiric treatment with amphotericin B must be considered if signs and symptoms of unfavorable outcome are present and due to the time that it takes to arrive at an accurate diagnosis. In order to confirm the diagnosis, all microbiological samples should be collected prior to initiating therapy.