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Cryptococcus neoformans is primarily responsible for cases of cryptococcal meningitis in individuals with HIV/AIDS. This study evaluated the susceptibility of C. neoformans obtained from individuals with cryptococcal meningitis associated with HIV/AIDS in Manaus, Amazonas, Brazil, against the action of the antifungals amphotericin B, flucytosine, fluconazole, itraconazole and posaconazole and analyzed it using Multilocus Sequence Typing (MLST) in order to identify the Sequence Types (STs). We analyzed 30 isolates of C. neoformans, from 24 HIV/AIDS patients diagnosed with cryptococcosis from 2017 to 2019 in a reference hospital, in addition to 3 environmental isolates: 1 isolate obtained in the home of a patient and 2 isolates obtained from neighboring homes of patients. 86.6% (n = 26/30) of the clinical isolates were identified as C. neoformans VNI ST93, 6.6% (n = 2/30) as C. neoformans VNI ST5, 3.3% (n = 1/30) as C. neoformans VNI ST32 and 3.3% (n = 1/30) as C. neoformans VNB ST232. The environmental isolates were identified as C. neoformans VNI ST93 (n = 3/3). 96.6% (n = 29/30) isolates were sensitive to amphotericin B, though there was variation in the MIC. 60% (n = 18/30) presented a MIC above the proposed epidemiological cutoff values for one or more antifungals. All environmental isolates were sensitive to the tested antifungals. The MLST showed that there is an important relationship between C. neoformans VNI ST93 and individuals with HIV/AIDS, including in the environmental isolates analyzed. C. neoformans VNB ST232 was observed for the first time in Amazonas. Amphotericin B was proven to be the best drug, but fluconazole and posaconazole also showed relevant action., (© 2024. The Author(s) under exclusive licence to Sociedade Brasileira de Microbiologia.)

Introduction: The present study investigated the impact of immune recovery and the duration of antifungal adherence in the consolidation phase of disseminated histoplasmosis (DH) in acquired immune deficiency syndrome (AIDS) patients living in a hyperendemic area in northeastern Brazil., Material and Methods: Sixty-nine patients with DH/AIDS, admitted to the São José Hospital between 2010 and 2015, who continued histoplasmosis consolidation therapy at the outpatient clinic were studied. The follow-up duration was at least 24 months., Results: Sixty-eight patients used itraconazole 200-400 mg/day or amphotericin B deoxycholate weekly during the consolidation phase, and six patients relapsed during follow-up. The overall median duration of consolidation antifungal use was 250 days [IQR 101 - 372]. Antifungal withdrawal by medical decision occurred in 41 patients (70.7 %) after a median of 293 days [IQR 128 - 372] of use; 16 patients discontinued by their own decision, with a median of 106 days [IQR 37 - 244] of therapy; three patients had no information available, and nine continued on AF therapy. The median CD4+ T-cell count in the group without relapse was 248 cells/µL [IQR 115-355] within 6 months after admission; conversely, in the relapse group, the median cell count remained below 100 cells/µL. Irregular adherence to highly active antiretroviral therapy (HAART) was the leading risk factor associated with relapse and death (p< 0.01)., Discussion: The regular use of HAART, combined with immune recovery, proved to be highly effective in preventing relapses in DH/AIDS patients, suggesting that long-term antifungal therapy may not be necessary., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 SFMM. Published by Elsevier Masson SAS. All rights reserved.)

Histoplasmosis is commonly observed in AIDS patients as a neglected opportunistic disease that has an important relationship with environmental factors. The present study described the clinical characteristics of HIV/AIDS patients diagnosed with disseminated histoplasmosis in a tertiary healthcare facility in Manaus, Amazonas, Brazil, and evaluated the patients' homes and urban environmental samples as a source of exposure to Histoplasma capsulatum. A review of medical records from 2017 to 2019 of patients with HIV/AIDS associated with histoplasmosis was carried out, as well as the collection of environmental samples in the homes of these patients. These samples were subjected to DNA extraction and then subjected to qPCR. A total of 62 patients diagnosed with HIV/AIDS and histoplasmosis were identified, which corresponds to 4.5% (n = 62/1372) of the HIV/AIDS cases detected in the period. Of these, 68% (n = 42/62) were male, with a mean age of 36 years and low education. In 47% (n = 29/62) of the cases, the diagnosis of HIV/AIDS and histoplasmosis occurred simultaneously. Mortality was 45% (n = 28/62), and 68% (n = 42/62) of these patients did not regularly use highly active antiretroviral therapy. The main symptoms found were respiratory, gastrointestinal, and weight loss, and in 81% (n = 50/62), the place of residence was in an urban area. A total of 57 environmental samples were analyzed, and the presence of Histoplasma capsulatum was not detected in any of the analyzed samples. There was a high mortality rate in the studied group of patients with AIDS and histoplasmosis. Most patients reported residing in urban areas of Manaus, with no history of travel to other areas previously known as being high risk for histoplasmosis., (© 2024. The Author(s) under exclusive licence to Sociedade Brasileira de Microbiologia.)

Background: Histoplasmosis is acquired by inhalation of spores of the dimorphic fungus Histoplasma spp. Although this pathogen is distributed worldwide, it is more prevalent in the Americas. However, the real burden of histoplasmosis remains undefined in many endemic regions., Methodology: We conducted a series of 61 autopsies to individuals who died in a hospital in the Brazilian Amazon focused on infectious diseases. We performed a detailed histological and microbiological evaluation with genetic characterization of Histoplasma strains with the aim to evaluate the contribution of histoplasmosis to morbidity and mortality. Additionally, we assessed the clinicopathological correlation., Principal Findings: Evidence of Histoplasma infection was detected in 21 patients (34%). Eight cases were disseminated infections, all of them occurred in HIV-positive patients. Six cases were localized histoplasmosis, limited to the lungs. In seven patients Histoplasma DNA was detected by PCR in patients with no histological lesions. Histoplasma infection was detected in 38% of HIV-positive patients and was a major contributor to death in 22% of them. Lungs, liver and spleen were affected in all cases of disseminated histoplasmosis. Phylogenetic analysis of the strains suggested a high diversity of Histoplasma species circulating in the Brazilian Amazon. Histoplasmosis was clinically missed in 75% of the disseminated infections., Conclusions: The high incidence of histoplasmosis, the low index of clinical suspicion, and the severity of the disseminated disease highlight the need of proactively implementing sensitive routine screening methods for this pathogen in endemic areas. Antifungal prophylaxis against Histoplasma should be encouraged in the severely immunocompromised HIV patients in these areas. In conclusion, substantial mortality is associated with disseminated histoplasmosis among HIV-positive patients in the Brazilian Amazon., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Cryptococcus neoformans is an opportunistic pathogen that causes ∼15% mortality in AIDS patients. Rio Grande City, Rio Grande do Sul (RS), Brazil, has the highest national rate of HIV/AIDS, considering cities with population more than 100,000 habitants., Objective: We aimed to evaluate the clinical and epidemiological profile of cryptococcosis in a reference service for HIV-AIDS patients in the South region of Brazil, over seven years. Material and methods A retrospective study was performed including all cryptococcosis cases diagnosed at the University Hospital, Federal University of Rio Grande (UH-FURG) between January 2010 and December 2016., Results: Seventy cases of cryptococcosis were diagnosis from 2010 to 2016 in the UH-FURG in the seven years of the study. These numbers were responsible for 2.1% to 8.1% of the hospitalizations/year for HIV patients. All were caused by C. neoformans infection (95% C. neoformans var. grubii VNI and 5% C. neoformans var. grubii VNII). Neurocryptococcosis was the major clinical manifestation and cryptococcosis was the HIV- defining condition in 40% of patients. The period of hospitalization was an average of 39.3 days (SD=31.3), and more than half of patients (53%; 37/70) died after a mean of 82 days., Discussion: The present study showed the importance of cryptococcosis as an AIDS-defining disease in HIV-AIDS patients in a tertiary hospital from Southern Brazil. More investment is necessary to reduce the impact of this opportunistic mycosis in HIV-AIDS patients from southern Brazil., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Histoplasmosis is considered the most common invasive opportunistic fungal disease in the Americas, with outbreaks and micro-epidemics reported for over 80 years. In Brazil, this disease has been described since 1946, reaching a remarkable incidence in the population, especially during the HIV-AIDS pandemic. In this study, published and unpublished outbreaks and micro-epidemics of histoplasmosis in Brazil were revisited by accessing different database sources and evaluating epidemiological and clinical features. We have found reports spanning 1946-2017, across 10 Brazilian states and with involvement of 370 humans and 2 dogs, and 13 disseminated cases and 3 deaths were reported. Rio de Janeiro had the largest number of outbreaks (n = 20/40; 50%) reported in this study. The majority of outbreaks and micro-epidemics was reported in caves (n = 21/40; 52.5%), followed by reports in abandoned/deactivated sites (n = 6/40; 15%), mines (n = 5/40; 12.5%), chicken coops (n = 4/40; 10%). Histoplasmosis is a serious health issue in Brazil considering the attractive and growing market of ecotourism throughout more than 7000 caves, and all levels of poultry farming activity are important to raise awareness about how dangerous this neglected disease can be and establish ways to decrease exposure to contaminated environmental sources through adequate preventive measures.

Introduction: We describe the clinical and laboratorial features of oral candidiasis in 66 HIV-positive patients., Methods: Polymerase chain reaction-based techniques were performed for differentiation of Candida spp. isolated from patients at a public teaching hospital in Midwest Brazil., Results: Oral lesions, mainly pseudomembranous, were significantly related to higher levels of immunosuppression. Of 45 Candida isolates, 66.7% were C. albicans. Most of the isolates were susceptible to the antifungal drugs tested., Conclusions: Oral lesions were associated with higher immunosuppression levels. Lower susceptibility to antifungals by non-albicans isolates supports the importance of surveillance studies using susceptibility tests to aid in the treatment.

The purpose of this study was to evaluate the influence of intracranial hypertension in the cerebrospinal fluid (CSF) levels of amphotericin B and fluconazole levels of patients with cryptococcal meningitis. CSF samples and intracranial pressure were obtained by means of routine punctures performed at days 1, 7, and 14 of therapy, respectively. Amphotericin B and fluconazole CSF levels were measured by HPLC method as previously described. The minimum inhibitory concentration for amphotericin B, fluconazole, 5΄flucytosine, and voriconazole of each Cryptococcus isolate was performed according to CLSI. The predominant Cryptococcus species found was C. neoformans, and the major underlying condition was AIDS. Only one CSF sample had a detectable level for amphotericin B during the 14 days of therapy. Fluconazole CSF levels progressively increased from day 1 to day 14 of therapy for most cases. Fluconazole levels in the CSF were above the minimum inhibitory concentrations (MICs) for Cryptococcus during the initial 14 days of antifungal therapy. Variations of intracranial pressure did not affect amphotericin B and fluconazole levels in the CSF. The generalized estimating correlation (GEE) and Spearman correlation test (SCT) showed no significant correlation between the amphotericin B or fluconazole concentrations in the CSF and intracranial pressure (P = .953 and P = .093, respectively for GEE test and P = .477 and P = .847, respectively, for SCT). Combination therapy of amphotericin B with fluconazole was effective in 60% of the patients considering CSF cultures were negative in 9 of 15 patients after 14 days of therapy. Further studies are necessary to evaluate the role of intracranial hypertension on the therapeutic efficacy of different antifungal agents in patients with cryptococcal meningitis.

Objectives: The increase in HIV transmissibility in non-ulcerative sexually transmitted infection is already well-established. It is estimated that symptomatic carriers of N. gonorrhoeae and C. trachomatis have a relative risk of 4.8-fold and 3.6-fold, respectively, for the sexual acquisition of HIV. This type of evaluation for asymptomatic urethritis is necessary to reinforce strategies to combat HIV transmission. This study aims to assess the prevalence of patients with asymptomatic urethritis among men diagnosed with HIV-1 and determine the risk factors associated with this infection., Methods: We enrolled a total of 115 male patients aged 18 years or older who have been diagnosed with HIV infection and have no symptoms of urethritis or other sexually transmitted infections and who have been evaluated between May and August 2015 in a follow-up visit at the Immunology Outpatient Clinic of a Brazilian University Hospital., Results: Four asymptomatic patients were positive for C. trachomatis and were considered asymptomatic carriers of urethritis. Prevalence was 3.47%. Patients who were positive for C. trachomatis urethritis had a lower mean age (p = 0.015)., Conclusion: The presence of asymptomatic sexually transmitted infection is a challenge in clinical practice. We recommend that, in outpatient practice, the habit of inquiring on previous sexual behavior to obtain more information about risks and associations with asymptomatic sexually transmitted infection, a routine physical examination and complementary tests to detect STI pathogens should be performed to discard these conditions. The development of rapid tests for this purpose should also be encouraged.

The majority of HIV-infected patients develop Candida spp-associated clinical oral lesions. Studies have shown that asymptomatic oral colonization of Candida spp may lead to oral lesions or become a source of disseminated infections. The aim of this study was to verify the effects of periodontal conditions on Candida spp prevalence and Candida spp carriage in the oral cavity of HIV-infected patients compared to non-infected patients. Twenty-five patients not infected with HIV and 48 HIV-infected patients were classified according to periodontal conditions as being periodontal healthy or with periodontal disease. Candida spp carriage and classification were performed in oral rinse samples. Viral load and CD4+ T lymphocyte (CD4+L) counts were performed in blood samples from HIV-infected patients. No differences in Candida spp prevalence related to HIV status or periodontal condition were detected. However, Candida spp carriage was increased in periodontally affected HIV-infected patients when compared to periodontally healthy HIV-infected patients (p= 0.04). Periodontally healthy HIV-infected patients presented Candida spp carriage in similar levels as healthy or periodontally affected non-HIV-infected patients. Candida spp carriage was correlated with CD4+L counting in HIV-infected patients. We concluded that periodontal disease is associated with increased Candida spp carriage in HIV-infected patients and may be a predisposing factor to clinical manifestations of candidiasis.

Cryptococcosis, a systemic disease caused by the fungus Cryptococcus neoformans/ Cryptococcus gattii is more severe in immunocompromised individuals. This study aimed to analyze the epidemiology of the disease, the molecular characteristics and the antifungal susceptibility of C. neoformans isolated from patients treated in a Brazilian university hospital. This retrospective study was conducted in the Clinical Hospital, Federal University of Uberlândia, and evaluated cases of cryptococcosis and strains of C. neoformans isolated from 2004 to 2013. We evaluated 41 patients, 85% of whom were diagnosed with AIDS. The fungus was isolated from the cerebrospinal fluid (CSF) of 21 patients (51%); 19.5% had fungemia and in 24% the agent was isolated from the CSF and blood, concurrently. Meningoencephalitis was the most frequent (75%) manifestation of infection. Despite adequate treatment, the mortality of the disease was 58.5%. Most isolates (97.5%) presented the VNI genotype (serotype A, var. grubii) and one isolate was genotyped as C. gattii (VGI); all the isolates were determined as mating type MATa and showed susceptibility to the tested antifungals (fluconazole, voriconazole, amphotericin B and 5-flucytosine). Although AIDS detection rates remain stable, opportunistic infections such as cryptococcosis remain as major causes of morbidity and mortality in these patients.

Cryptococcosis is an important fungal infection in immunocompromised individuals, especially those infected with HIV. In Brazil, despite the free availability of antiretroviral therapy (ART) in the public health system, the mortality rate due to Cryptococcus neoformans meningitis is still high. To obtain a more detailed picture of the population genetic structure of this species in southeast Brazil, we studied 108 clinical isolates from 101 patients and 35 environmental isolates. Among the patients, 59% had a fatal outcome mainly in HIV-positive male patients. All the isolates were found to be C. neoformans var. grubii major molecular type VNI and mating type locus alpha. Twelve were identified as diploid by flow cytometry, being homozygous (AαAα) for the mating type and by PCR screening of the STE20, GPA1, and PAK1 genes. Using the ISHAM consensus multilocus sequence typing (MLST) scheme, 13 sequence types (ST) were identified, with one being newly described. ST93 was identified from 81 (75%) of the clinical isolates, while ST77 and ST93 were identified from 19 (54%) and 10 (29%) environmental isolates, respectively. The southeastern Brazilian isolates had an overwhelming clonal population structure. When compared with populations from different continents based on data extracted from the ISHAM-MLST database (mlst.mycologylab.org) they showed less genetic variability. Two main clusters within C. neoformans var. grubii VNI were identified that diverged from VNB around 0.58 to 4.8 million years ago., Competing Interests: The authors have declared that no competing interests exist.

Background: Infections caused by Chlamydia trachomatis and Neisseria gonorrhoeae are the most common bacterial sexually transmitted infections throughout the world. These sexually transmitted infections are a growing problem in people living with HIV/AIDS. However, the presence of these agents in extra genital sites, remains poorly studied in our country. The objective of this study was to estimate the prevalence of Chlamydia trachomatis and Neisseria gonorrhoeae anal and genital infection in people living with HIV/AIDS followed in a reference center in Salvador, Brazil., Methods: Cross-sectional study, from June 2013 to June 2015. Proven HIV-infected people attending this reference center were invited. Clinical and epidemiological data were obtained through interview with standardized form. Chlamydia trachomatis and Neisseria gonorrhoeae screening was performed using qPCR (COBAS 4800 ® Roche)., Results: The frequency of positive cases of Chlamydia trachomatis and Neisseria gonorrhoeae was 12.3% in total, 9.2% cases amongst women and 17.1% amongst men. We found 14.0% of positive cases in anus and 3.1% in genital region in men, while 5.6% and 3.6%, in women, respectively. Among men, anal infection was associated with age <29 years (p=0.033), report of anal intercourse (p=0.029), pain during anal intercourse (p=0.028). On the other hand, no association between genital infection and other variables were detected in bivariate analysis. Among women, we detected an association between Chlamydia trachomatis genital infection and age <29 years (p<0.001), younger age at first sexual intercourse (p=0.048), pregnancy (p<0.001), viral load >50copies/mL (p=0.020), and no antiretroviral use (p=0.008). Anal infection in women was associated with age <29 years old (p<0.001) and pregnancy (p=0.023), and was not associated with report of anal intercourse (p=0.485)., Conclusion: Missed opportunities for diagnosis in extra genital sites could impact on HIV transmission. The extra genital sites need to be considered to break the HIV and bacterial sexually transmitted infections chain-of-transmission., (Copyright © 2016 Sociedade Brasileira de Infectologia. Published by Elsevier Editora Ltda. All rights reserved.)

A high prevalence of Pneumocystis jirovecii colonization was observed in patients positive for the human immunodeficiency virus (HIV) admitted to a tertiary hospital in southern Brazil between August 2012 and December 2012. Amplification of the mitochondrial large subunit ribosomal RNA gene in oropharyngeal samples through nested polymerase chain reaction identified P. jirovecii colonization in 26 of 58 (44.8%) HIV-positive patients admitted for causes other than Pneumocystis pneumonia. Colonization was more frequent among patients with an absolute CD4 count ≤200 cells/μl. These findings suggest that the HIV-infected population is a major reservoir and source of P. jirovecii infection and that identification of such individuals may contribute to future strategies for improving management of HIV-infected patients., (© The Author 2014. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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

Objectives: This study aimed to evaluate the concentration of lactoferrin in the saliva of HIV infected and healthy children and analyze the associations between lactoferrin levels, Candida sp. colonization, oral manifestations and medical data. Also, the antifungal ability of lactoferrin to inhibit the growth of Candida albicans isolated from saliva of these children was investigated in vitro., Subjects and Methods: Saliva was collected from 70 HIV-infected and 50 healthy children, followed by oral manifestation assessments. The salivary lactoferrin was quantified using an ELISA Kit. The salivary samples were cultured and the Candida spp. colonies counted and then identified by sugar assimilation and fermentation. The antifungal activity of lactoferrin was analyzed in vitro with 10 isolates of C. albicans from each group., Results: The HIV infected children (mean age 9.8 ± 2.8) had higher lactoferrin levels (median 6.13 μg/ml (3.58-7.89)) and were colonized three times more by Candida sp. than the control group (mean age 9.4 ± 2.4) (median 5.74 μg/ml (3.12-6.86)) (p=0.003). Statistical associations were found considering the salivary lactoferrin levels and Candida sp. and oral manifestations between the groups. No associations between lactoferrin concentrations and oral manifestations, immunosuppression, presence of AIDS and use of HAART were observed in the HIV group. The percentage of dead C. albicans due to lactoferrin was inversely proportional to C. albicans cell density for both groups (p<0.001)., Conclusions: HIV-infected children have higher concentrations of lactoferrin and it was associated with Candida sp. colonization but no association with medical data was found. Also, both groups showed similar lactoferrin antifungal activity., (Copyright © 2014. Published by Elsevier Ltd.)

Cryptococcus neoformans is an important cause of morbidity in HIV-infected patients worldwide. In the northern region of Brazil, the prevalence of this infection is poorly known due to a lack of systematic investigations. This study aimed to determine the occurrence of cryptococcosis by detecting antigenaemia in HIV-infected patients in the State of Para, Brazil. A latex Cryptococcus antigen detection kit was used to test 418 serum samples from HIV-infected patients seen at two Infectious Disease Specialized Units in the State of Para. The C. neoformans antigenaemia prevalence was 2.6%, and titres reached 1:8. The cases occurred mainly in asymptomatic females, and 45% presented CD4(+) T lymphocyte counts of fewer than 200 cells/mm(3). These results show the importance of early C. neoformans antigenaemia detection to prevent fungal disease.

Since the beginning of the HIV epidemic, there has been a significant increase in the number of histoplasmosis cases in Ceará, a state in north-east Brazil. The lack of epidemiological data on the genotypes circulating in the north-east region shows the importance of more detailed studies on the molecular epidemiology of Histoplasma capsulatum var. capsulatum in this region. Different molecular techniques have been used to better characterize the genetic profile of H. capsulatum var. capsulatum strains. The aim of this study was to analyse the genetic diversity of H. capsulatum var. capsulatum isolates in Fortaleza, the capital of Ceará, through the sequencing of the internal transcribed spacer (ITS)1-5.8S-ITS2 region, and establish the molecular profile of these isolates, along with strains from south-east Brazil, by RAPD analysis, featuring the different clusters in those regions. The isolates were grouped into two clusters. Cluster 1 included strains from the south-east and north-east regions with separation of isolates into three distinct subgroups (subgroups 1a, 1b and 1c). Cluster 2 included only samples from north-east Brazil. Sequencing of the ITS1-5.8S-ITS2 region allowed the detection of two major clades, which showed geographical correlation between them and their subgroups. Therefore, it can be concluded that the H. capsulatum var. capsulatum isolates from Ceará have a high degree of genetic polymorphism. The molecular data also confirm that populations of this fungus are composed of different genotypes in Brazil and worldwide.

This study contains a descriptive analysis of histoplasmosis in AIDS patients between 2006 and 2010 in the state of Ceará, Brazil. Additionally, the in vitro susceptibility of Histoplasma capsulatum isolates obtained during this period was assessed. We report 208 cases of patients with histoplasmosis and AIDS, describing the epidemiological, clinical, laboratory and therapeutic aspects. The in vitro antifungal susceptibility test was carried out by the microdilution method, according to Clinical and Laboratory Standards Institute, with H. capsulatum in the filamentous and yeast phases, against the antifungals amphotericin B, fluconazole, itraconazole, voriconazole and caspofungin. In 38.9% of the cases, histoplasmosis was the first indicator of AIDS and in 85.8% of the patients the CD4 cell count was lower than 100 cells/mm(3). The lactate dehydrogenase levels were high in all the patients evaluated, with impairment of hepatic and renal function and evolution to death in 42.3% of the cases. The in vitro susceptibility profile demonstrated there was no antifungal resistance among the isolates evaluated. There was a significant increase in the number of histoplasmosis cases in HIV-positive patients during the period surveyed in the state of Ceará, northeastern Brazil, but no antifungal resistance among the recovered isolates of H. capsulatum., (Copyright © 2012 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.)

Introduction: Infections caused by multiresistant Pseudomonas aeruginosa (MR-PA) have been associated with persistent infections and high mortality in acquired immunodeficiency syndrome (AIDS) patients. Therefore, understanding the predisposing factors for infection/colonization by this agent is critical for controlling outbreaks caused by MR-PA in settings with AIDS patients., Objective and Methods: To analyze the presence of factors associated with the acquisition of an epidemic MR-PA strain in a hospital with AIDS-predominant admission. A case-control study was carried out in which cases and controls were gathered from a prospective cohort of all hospitalized patients in an infectious disease hospital during a five-year study period., Results: Multivariate logistic regression analysis demonstrated that enteral nutrition OR = 14.9), parenteral nutrition (OR = 10.7), and use of ciprofloxacin (OR = 8.9) were associated with a significant and independent risk for MR-PA acquisition., Conclusions: Although cross-colonization was likely responsible for the outbreaks, the use of ciprofloxacin was also an important factor associated with the acquisition of an epidemic MR-PA strain. More studies are necessary to determine whether different types of nutrition could lead to modification of gastrointestinal flora, thereby increasing the risk for infection/colonization by MR-PA in this population.

Sporotrichosis is endemic in Rio de Janeiro, Brazil, and cases have been reported to be associated with HIV. This article describes the clinical manifestations and evolution of sporotrichosis in HIV-positive patients and constitutes the largest case series reported to date. There were 21 HIV-positive patients with sporotrichosis diagnosed by the recovery of the etiologic agent from 1999-2009. Sixteen patients (76.2%) were men and five (23.8%) were women, with a mean age of 41.2 years. Seven of these individuals were previously unaware of their HIV infection. Mean CD4 count was 346.4 cells/μl. The most frequent clinical presentations of sporotrichosis in these patients were the lymphocutaneous and disseminated form (seven patients each, 33.3%), followed by the widespread cutaneous form in five (23.8%), and fixed form in the remaining two (9.5%). In patients with the disseminated forms, clinical manifestations involved the skin in six, mucosa (nasal, oral, or conjunctival) in four, bone in two, and meninges in two. Eleven (52.4%) patients received itraconazole and eight (38.1%) amphotericin B contributing to an overall cure rate of 81%. Spontaneous cure was observed in one patient. The clinical forms of sporotrichosis varied according to the patients' immune status. The results demonstrate the importance of sporotrichosis as an opportunistic infection associated with AIDS in countries where the mycosis occurs.

Throughout Brazil, Cryptococcus neoformans is the cause of cryptococcosis, whereas Cryptococcus gattii is endemic to the northern and northeastern states. In this study, the molecular types of 63 cryptococcal isolates recovered from the cerebrospinal fluid of meningitis patients diagnosed between 2008-2010 in Teresina, Piauí, Brazil, were analysed. Out of the 63 patients, 37 (58.7%) were human immunodeficiency virus (HIV)-positive and 26 (41.3%) were HIV-negative. URA5-restriction fragment length polymorphism analysis identified 37/63 (58.7%) isolates as the C. neoformans VNI genotype, predominantly in HIV-positive patients (32/37, 86.5%), and 24/63 (38.1%) as the C. gattii VGII genotype, mostly in HIV-negative patients (21/26, 80.8%). The occurrence of C. gattii VGII in six apparently healthy children and in seven adolescents/young adults in this region reaffirms the endemic occurrence of C. gattii VGII-induced primary cryptococcosis and early cryptococcal infection. Lethality occurred in 18/37 (48.6%) of the HIV-positive subjects and in 13/26 (50%) of the HIV-negative patients. Our results provide new information on the molecular epidemiology of C. neoformans and C. gattii in Brazilian endemic areas.

Background: Vulvovaginal candidiasis (VVC) is the second most common vaginal infection. HIV-infection is a risk factor for this infection., Objective: To determine the frequency of VVC and to describe the main Candida species isolated and their susceptibility to antifungal drugs in HIV-infected patients, compared to HIV-uninfected women in Salvador, Brazil., Methods: Cross-sectional study including a group of 64 HIV-infected women and 76 uninfected women, followed up at the AIDS reference center and at the Gynecological Clinic of Escola Bahiana de Medicina e Saúde Pública (Salvador, Bahia, Brazil)., Results: Frequency of Candida spp. was higher in HIV-infected women (29.7%) than in HIV-uninfected controls (14.5%) (p = 0.02). The odds ratio value for vulvovaginal candidiasis in HIV-infected patients was 2.6 (95% CI: 1.07 - 6.32 p = 0.03). Candida albicans was the most commonly isolated species in both HIV-infected (52.3%) and uninfected women (85.7%), followed by C. parapsolis in 17.6% and 14.3%, respectively. In HIV-infected women, C. glabrata, C. parapsilosis, and a coinfection of C. albicans and C. glabrata were also identified. There was no significant difference between Candida species isolated from the vaginal mucosa of women with VVC and colonization of the vaginal mucosa of HIV-infected and HIV-uninfected women. One C. glabrata isolate from an HIV-infected patient was resistant to fluconazole and other two isolates exhibited a dose-dependent susceptibility., Conclusion: Our results confirm a higher frequency of Candida spp. isolated from the vaginal mucosa of HIV-infected women and a broader spectrum of species involved. Only Candida glabrata isolates showed decreased susceptibility to fluconazole.

Peripheral lymphadenopathy is commonly present in HIV-infected patients and has a wide spectrum of differential diagnoses. We carried out a cross-sectional study of peripheral lymph node biopsies performed from January 2004 to December 2008 in HIV-infected patients who attended a tertiary-care hospital in southern Brazil. Only 60 of 210 peripheral lymph node biopsies performed (28%) were non-diagnostic. The most common diagnoses included: mycobacteriosis (105 cases; 50.2%); lymphoma (19 cases; 9.0%); systemic mycosis (12 cases; 5.7%) including histoplasmosis, cryptococcosis and histoplasmosis; and metastatic cancer (2.9%). Peripheral lymph node biopsy is a simple and useful tool to diagnose opportunistic diseases in HIV-infected patients.

Background: Tuberculous meningitis (TBM) is a growing problem in HIV-infected patients in developing countries, where there is scarce data about this co-infection. Our objectives were to analyze the main features and outcomes of HIV-infected patients with TBM., Methods: This was a retrospective study of HIV-infected Brazilian patients admitted consecutively for TBM. All patients had Mycobacterium tuberculosis isolated from the cerebrospinal fluid (CSF). Presenting clinical and laboratory features were studied. Multivariate analysis was used to identify variables associated with death during hospitalization and at 9 months after diagnosis. Survival was estimated using the Kaplan-Meier method., Results: We included 108 cases (median age 36 years, 72% male). Only 15% had fever, headache, and meningeal signs simultaneously. Forty-eight percent had extrameningeal tuberculosis. The median CD4+ cell count was 65 cells/microl. Among 90 cases, 7% had primary resistance to isoniazid and 9% presented multidrug-resistant strains. The overall mortality during hospitalization was 29% and at 9 months was 41%. Tachycardia and prior highly active antiretroviral therapy (HAART) were associated with 9-month mortality. The 9-month survival rate was 22% (95% confidence interval 12-43%)., Conclusions: Clinical and laboratory manifestations were unspecific. Disseminated tuberculosis and severe immunosuppression were common. Mortality was high and the 9-month survival rate was low. Tachycardia and prior HAART were associated with death within 9 months of diagnosis., (Copyright 2009 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

We molecularly characterized 81 cryptococcal isolates recovered from cerebrospinal fluid samples of 77 patients diagnosed between 1998 and 2007 as having cryptococcal meningitis in Uberaba Minas Gerais, Brazil. Fifty-seven (74%) were male with a mean age 35.6 years. Seventy-two (88.9%) of the isolates were from 68 AIDS patients and cryp-tococcosis was the first AIDS-defining condition in 38 (55.9%) patients. Cryptococcosis and AIDS were simultaneously diagnosed in 25 (65.8%) of these 38 patients. Genotypes were characterized through the use of URA5 restriction fragment length polymorphisms analysis, the genetic variability was determined using PCR-fingerprinting with the minisatellite-specific primer M13, and the mating type and serotypes were established by PCR. Seventy-six of the 81 isolates were Cryptococcus neoformans (93.8%), while the remaining five were C. gattii (6.1%), but all were mating type alpha. C. neoformans isolates were genotype VNI (serotype A), while C. gattii isolates were VGII. Four of the latter isolates were identical, but only two were from AIDS patients. Six of the nine isolates from non-AIDS patients were VNI. PCR fingerprints of the isolates from two of the three AIDS patients with clinical relapse were 100% identical. The predominance of VNI and mating type alpha is in accordance with data from other parts of the world. The occurrence of VGII in Minas Gerais indicates a geographical expansion within Brazil.

Objectives: To evaluate predisposing factors such as orofacial manifestations, immunosuppression status and antiretroviral therapy in relation to oral colonization by Candida spp. in Brazilian HIV-infected children and their uninfected siblings in the era of highly active antiretroviral therapy (HAART)., Methods: Whole stimulated saliva was collected from 65 HIV-infected children (HIV+) and 40 uninfected siblings (HIV-), followed by assessment of orofacial manifestation, caries indexes and the number of cavitated dentinal carious teeth (CDT). The salivary samples were cultured and the colonies were counted. After which they were identified by sugar assimilation and fermentation (API 20C). Data was analyzed using chi-square, Mann-Whitney, Spearman tests and logistic regression., Results: Regarding positive growth, HIV+ presented 80% (52/65) and HIV- 57.5% (23/40) (P = 0.013). Absence of antiretroviral therapy and HAART increased the probability of Candida isolation (P < 0.05). Mean CD4%, immune-status and history of recurrent oral candidiasis (OC) had no influence on Candida isolation. Mixed Candida spp. cultures were observed in HIV+ (40%) and HIV- (52%): C. albicans was more frequently found in both groups, with a higher prevalence in HIV+ (P = 0.05); other non-albicans species were isolated in HIV+ and HIV-. Low prevalence of orofacial manifestations was observed in HIV+ (10.7% of OC). There was an association between means of CDT and Candida growth (P < 0.05) and a positive correlation between number of CDT and Candida cfu-counts in HIV+ and HIV-. Mean CD4% and immune-status had no influence on Candida isolation. Absence of antiretroviral therapy and HAART increased the probability of Candida isolation (P < 0.05)., Conclusions: The HIV infected children had a significantly higher prevalence of oral Candida spp. compared to their uninfected siblings. Absence of HAART and presence of dentinal carious teeth increased significantly Candida spp. colonization in these children.

The authors describe the histopathological necropsy findings of 45 human immunodeficiency virus (HIV)-infected patients with neurocryptococcosis. Systemic cryptococcosis with involvement of multiple organs such as spleen, liver, and lungs was present in all patients. Predominant diffuse meningoencephalitis predominantly in the basal ganglia, thalamus, and mid-brain, with minimal inflammatory infiltrate was seen in 30 AIDS patients (70%). We frequently observed in those patients the presence of multiple gelatinous pseudocysts with abundant Cryptococcus neoformans in the Virchow-Robin spaces and adjacent brain caused by the dissemination of the meningeal infection along the perivascular spaces. Isolated meningeal and cerebral involvement with minimal inflammatory infiltrate with numerous fungal organisms, and occasionally with granulomatous reaction and necrosis, was seen in 15 patients (30%). In addition to involvement of multiple organs by C. neoformans, HIV-infected patients with clinical manifestations of neurocryptococcosis frequently present a widespread involvement of the brain.

Between 2005 and 2008, the prevalence of systemic mycosis among 1,300 HIV/AIDS patients in Cuiabá, Mato Grosso, was 4.6%. The fungus species isolated were Cryptococcus neoformans in 50%, Cryptococcus gattii in 1.6%, Cryptococcus spp in 6.6%, Histoplasma capsulatum in 38.3% and Paracoccidioides brasiliensis in 3.3%. Death was recorded in the cases of 32 patients (53.3%), and cryptococcosis was the main cause. The CD4+ T lymphocyte count was low and similar among patients who survived or died due to systemic mycosis. The factors independently associated with the deaths of these patients were alcoholism (OR: 8.2; 95% CI: 1.4-62.1; p = 0005) and the mean level of lactate dehydrogenase [758 (182) U/l vs. 416 (268) U/l; p < 0001]. The findings showed that systemic mycosis was highly lethal among the patients with HIV/AIDS in Cuiabá and suggested that clinical-laboratory characteristics such as alcoholism and early elevation of lactate dehydrogenase may be factors relating to worse prognosis under these conditions.

The in vitro activities of amphotericin B (AmB) were evaluated against 40 isolates of Cryptococcus neoformans using time-kill curves. The isolates were obtained from 20 AIDS patients with cryptococcal meningitis submitted to AmB therapy. Isolates were exposed in vitro to 1 microg/mL of AmB that represents a serum concentration of AmB, and the viable colony counts were determined over time. AmB exhibited fungicidal activity at 6 and 12 h for 70.6% of isolates, at 24 h for 7.3%, and at 48 h for 22% of isolates, respectively. This effect was not maximized when the test drug concentration was up to 4 times the AmB MIC for the isolates. Regrowth was observed in 17.5% of the isolates after fungicidal endpoint. With standard in vitro susceptibility testing, this tolerance phenomenon could not be assessed, and thus, these tests may underestimate the resistance of C. neoformans to AmB in vivo. AmB is the first-choice drug for the treatment of cryptococcosis in Brazil, and future studies using time-kill methodology are needed to estimate the predictive value of this test in the clinical failure.

Assuming that the IS6110-restriction fragment length polymorphism (RFLP) changes at a constant rate of 3.2 years, this methodology was applied to demonstrate, for the first time, variant patterns of Mycobacterium tuberculosis (MTB) in multiple isolates obtained at short time intervals from sputum and blood of an HIV+ patient with multiple admissions to the Emergency Room and to the multidrug-resistant tuberculosis (MDR-TB) Reference Center of a secondary-care hospital in Rio de Janeiro, Brazil. In sputum, the IS6110-RFLP appeared in isolates with two variant patterns with 10 and 13 IS6110 copies. However, blood presented only the pattern corresponding to 10 copies, suggesting compartmentalization. With regard to the exact match of 10 of 13 bands, this may be a subpopulation with the same clonal origin and this may be related to the IS6110 transposition. A susceptibility test demonstrated an MDR profile (INH(R), RIF(R), SM(R), and EMB(R), with the sputum isolate also exhibiting EMB(S) (R = resistant; S = sensitive). A gene mutation confirmed resistance only to streptomycin. There was agreement between the results of the phenotypic test and the clinical response to MDR-TB treatment, suggesting serious implications with regard to treatment administration based exclusively on molecular methods, and calling attention to the fact that more effective control strategies against the emergence of MDR strains must be implemented by the TB control program to prevent transmission of MDR-MTB strains at health facilities in areas highly endemic for TB.

Objectives: Skin lesions, uncommon in US cases (<10%), occur in 38-85% of cases reported from Latin America. Although these differences may reflect reporting bias, delayed diagnosis, or differences in host immune response among different ethnic groups, they also could result from genetic differences changing the pathobiology of the organism. It is possible that genetic differences among strains of H. capsulatum may influence the pathogenesis and clinical manifestations of histoplasmosis., Methods: We examined the clinical features of patients with mucocutaneous manifestations of histoplasmosis and performed genetic analysis based on nucleotide sequence variations in the internal transcribed spacer regions of rRNA genes of H. capsulatum isolates of patients. Two pairs of PCR primers were designed to develop and amplify the ITS regions of H. capsulatum, 5'-TACCCGGCCACCCTTGTCTA-3' and 5'-AGCGGGTGGCAAAGCCC-3'. These primers were based on the ITS sequence of Ajellomyces capsulatus, the ascomycetous teleomorph form of H. capsulatum, deposited in the GenBank (accession number U18363). Eight patients attending a tertiary-care hospital in southern Brazil were enrolled into the study. All case patients had skin cultures growing H. capsulatum at the mycology laboratory., Results: Six of eight (75%) patients were HIV-positive and presented involvement of multiples organs by H. capsulatum. Two HIV-negative patients did not present evidence of involvement of other organs besides mucosa and skin. ITS sequencing of a DNA H. capsulatum fragment of 485-bp from isolates of 8 patients revealed two distinct strains. The 2 distinct fragments (Hc1, Hc2) differed from each other at 7 positions in the ITS regions. They were identical to strains of H. capsulatum isolated in patients from Colombia and Argentina, but different from strains isolated in US. Hc1 and Hc2 were isolated in 5 patients and 3 patients, respectively, with mucocutaneous manifestations of histoplasmosis. Both Hc1 and Hc2 strains were isolated in HIV-infected and non-HIV-infected patients., Conclusions: Mucocutaneous manifestations of histoplasmosis, which are frequently seen in Brazilian patients were caused by 2 specific strains in our institution. Those strains have been isolated in patients with these particular clinical features of histoplasmosis in Latin America. Our study suggests that unique pathogenic characteristics among the Latin American species of H. capsulatum might explain its increased dermatotropism.

Aims: To report the first eight bone marrow necrosis (BMN) cases related to paracoccidioidomycosis (PCM) from patient autopsies with well-documented bone marrow (BM) histology and cytology., Methods and Results: A retrospective evaluation was performed on BM specimens from eight autopsied patients from Botucatu University Hospital with PCM-related BMN. Relevant BMN literature was searched and analysed., Conclusions: All eight patients had acute PCM. Six had histological only (biopsies) and two cytological only (smears) specimens. Five biopsy specimens revealed severe and one mild coagulation patterned necrotic areas. Five had osteonecrosis. The cytological specimens also showed typical BMN patterns. Paracoccidioides brasiliensis yeast forms were visible within necrotic areas in all cases.

Candida oral flora from 52 Brazilian HIV-infected children was characterized while they received antiviral monotherapy therapy and subsequently, HAART with the use of protease inhibitor. There was a significant increase in non-C. albicans Candida isolates from 9.6-28.8% (P=0.005) after the children were placed on protease inhibitor therapy. Although Candida albicans still remained the most commonly isolated species, relative presence of C. tropicalis (n=9) followed by C. parapsilosis (n=8) markedly increased in association with protease inhibitor therapy. Furthermore, rare Candida species including C. dubliniensis, C. norvegensis, C. humicula and C. rugosa also appeared after the onset of protease inhibitor therapy. Subsequent investigation of the antifungal sensitivity of these diverse isolates, derived during protease inhibitor therapy, demonstrated some variation in antifungal sensitivity. With notable exceptions, the majority were sensitive to amphotericin B while most C. albicans and non-C. albicans Candida isolates were also susceptible to fluconazole, itraconazole and ketoconazole. Amongst exceptions was a single C. tropicalis isolates which was resistant to fluconazole (MIC>64 microl/ml) and one C. albicans-B isolate which showed cross-resistance to all azoles and amphotericin.

The aim of this study was to evaluate the prevalence of Candida spp., and particularly C. dubliniensis, among oral isolates from Brazilian HIV-positive patients correlating these results with CD4 cell counts and viral load. Forty-five individuals (23 female and 22 male) diagnosed as HIV-positive by ELISA and Western-blot, under anti-retroviral therapy for at least 1 year and without oral candidosis signals were included in the study. The control group was constituted by 45 healthy individuals, matched to the test group in relation to age, gender, and oral conditions. Oral rinses were collected and the identification was performed by phenotypic tests. The existence of C. dubliniensis among the isolates was analyzed using a validated multiplex PCR assay. Candida spp. were detected at significantly higher number in the oral cavity of HIV-positive patients in relation to the controls (P = 0.0008). C. albicans was the most frequently isolated species in both groups. In the HIV group, C. glabrata, C. lipolytica, C. krusei, C. guilliermondii, and C. parapsilosis were also identified. In the control group, we additionally identified C. tropicalis and C. dubliniensis. Two isolates (1.9%, 2/108) from control individuals were identified as C. dubliniensis and this species was not verified in the HIV group. Candida spp. counts were statistically lower (P = 0.0230) in the oral cavity of patients with low viral load (<400 copies/mm(3)). Candida spp. counts did not differ statistically among groups with different levels of CD4 cells counts (P = 0.1068).

While many members of the black yeasts genus Cladophialophora have been reported to cause diseases in humans, understanding of their natural niche is frequently lacking. Some species can be recovered from the natural environment by means of selective isolation techniques. The present study focuses on a Cladophialophora strain that caused an interdigital tinea nigra-like lesion in a HIV-positive Brazilian child. The fungal infection was successfully treated with oxiconazole. Similar strains had been recovered from the environment in Brazil, Uruguay and the Netherlands. The strains were characterized by sequencing the Internal Transcribed Spacer (ITS) regions and the small subunit (SSU) of the nuclear ribosomal RNA gene, as well as the elongation factor 1-alpha (EF1alpha) gene. Since no match with any known species was found, it is described as the new species, Cladophialophora saturnica.

Based on combinations of nine variable nucleotides at nine different base positions in the ITS1-5.8S-ITS2 region, Cryptococcus gattii strains were classified into six genotypes. A new genotype of C. gattii, designated as ITS type 8, was isolated from an AIDS patient in Brazil. The ITS type 8 strain is closely related to the ITS type 4 strain, which has been frequently isolated in Brazil and the USA, but which shows ITS-signatured nucleotide difference at each nucleotide position. The ITS type 8 strain is also differentiated from all heretofore reported ITS types of C. gattii strains in the RAPD band patterns and IGS sequence information.

Hemotrophic mycoplasmas infect a variety of mammals. Although infection in humans is rarely reported, an association with an immunocompromised state has been suggested. We report a case of a Mycoplasma haemofelis-like infection in an HIV-positive patient co-infected with Bartonella henselae.

The objective of this article was to evaluate the epidemiology of cryptococcal meningitis in Rio de Janeiro State, Brazil, from 1994 to 2004. Six hundred and ninety-six cases of cryptococcal meningitis were reported, with a mean incidence of 0.45 per 100,000 inhabitants. Patients were predominantly male; mean age was 35.9 years; AIDS was practically the only underlying disease, reported in 61.2% of cases; case-fatality was 51.8%. No decline in incidence was observed during the study period. AIDS is the main predisposing condition for cryptococcal meningitis, and thus the profile of most patients mirrors that of HIV infection. Missing information prevented the evaluation of other underlying diseases.

The purpose of this work was to evaluate the influence of Protease Inhibitors (PI) on the occurrence of oral candidiasis in 111 HIV+ patients under PI therapy (Group A). The controls consisted of 56 patients that were not using PI drugs (Group B) and 26 patients that were not using any drugs for HIV therapy (Group C). The patient's cd4 cell counts were taken in account for the correlations. One hundred and ninety three patients were evaluated. The PI did not affect the prevalence of oral candidiasis (p = 0.158) or the frequency of C. albicans isolates (p = 0.133). Patients with lower cd4 cell counts showed a higher frequency of C. albicans isolates (p = 0.046) and a greater occurrence of oral candidiasis (p = 0.036).

Cryptococcosis is a major opportunistic mycosis which has meningitis as its most frequent clinical presentation and can be fatal in the absence of antifungal therapy. The aetiological agents are Cryptococcus neoformans, which affects mainly immunocompromised subjects, and C. gattii, the aetiologic agent for cryptococcosis in healthy individuals. A recent outbreak of cryptococcosis on Vancouver Island, Canada, raised the level of concern about the epidemiology of this disease. In Brazil, between 1980 and 2002, six per cent of AIDS patients had cryptococcosis in course at the time of diagnosis. To identify the profile of cryptococcal meningitis patients in Rio Grande do Sul (RS), Brazil, a retroactive study was realized using data from patients registered at Laboratório Central de Saúde Pública IPB-LACEN/RS from 2000 to 2005. Most of the patients were men (77.12%), Caucasian (83.5%), median age between thirty and thirty-nine years old (46.24%) and HIV positive (95%).

The objective of this study was to evaluate the incidence, anatomic localization and yeast species isolated from each clinical type of oral candidiasis. The clinical samples were obtained from 67 patients with AIDS with CD4 cell counts below 200 cells/mm(3) and hospitalized in a public hospital (Eduardo de Menezes Hospital) in the city of Belo Horizonte, MG, Brazil. Yeasts were isolated using Chromagar Candida. The results show that 50.7% of these patients had oral candidiasis. The pseudomembranous form was the most frequent clinical manifestation of oral candidiasis, followed by the erythematous and angular cheilite forms. The most common site of these clinical forms of oral candidiasis was the tongue. Candida albicans was the most common yeast species isolated from the lesions. However, other species were also found to be associated with these forms of oral candidiasis.

Histoplasmosis occurs in approximately 5% of acquired immunodeficiency syndrome (AIDS) patients in endemic areas and often evolves to a disseminated picture if diagnosis is delayed and/or CD4 count falls below 150 cells x mm(3) without high active antiretroviral therapy (HAART). This report presents clinical features of patients with histoplasmosis admitted from 1992 to 2005. Of the 57 individuals, 45 (79%) were male, aged 20-40 years; 30 (52.6%) presented histoplasmosis together with HIV diagnosis and 35 (61.4%) referred illness course up to 4 weeks. Fever, hepatomegaly and/or splenomegaly, dyspnea and skin lesions were noticed in 50 (87.7%), 38 (66.7%), 30 (52.6%) and 25 (43.9%) patients respectively. High levels of lactic acid dehydrogenase, X-ray lung interstitial pattern, pancytopenia and CD4 count <100 cells x mm(3) were observed in 48 (84.2%), 35 (66%), 34 (59.6%) and 33 (94%) patients respectively. Mycological diagnosis was performed by one or more methods in all patients. Thirty nine (68.4%) received amphotericin B and/or itraconazole. A cure rate was observed in 76.9% and nine (23.1%) died early during therapy. Otherwise death occurred in 18 (31.6%) before diagnosis was completed. Despite free HAART disposal in public Brazilian health services, histoplasmosis still occurs as the first AIDS baseline condition in patients without antiretroviral therapy, many of whom are not receiving any medical care for HIV infection.

Despite highly active anti-retroviral therapy, cryptococcal meningoencephalitis is the second most prevalent neurological disease in Brazilian AIDS patients, being frequently a defining condition with several episodes. As knowledge of Cryptococcus neoformans isolates in the same episode is critical for understanding why some patients develop several episodes, we investigated the genotype characteristics of C. neoformans isolates in two different situations. By pulsed field gel electrophoresis and random amplified polymorphic DNA analysis, 54 isolates from 12 patients with AIDS and cryptococcosis were analyzed. Group 1 comprised 39 isolates from nine patients with a single episode and hospitalization. Group 2 comprised 15 isolates from three patients with two episodes and hospitalizations. Except for three patients from group 1 probably infected with a single C. neoformans isolate, the other nine patients probably were infected with multiple isolates selected in different collection periods, or the infecting isolate might have underwent mutation to adapt and survive the host immune system and/or the antifungal therapy. However, the three patients from group 2 presented genetic diversity among isolates collected in both hospitalizations, possibly having hosted the initial isolate in both periods. These data, emphasize that Cryptococcus diversity in infection can contribute to strategies of treatment and prevention of cryptococcosis.

This investigation was designed to evaluate the frequency of erythematous candidosis (EC) and Candida species, proteinase and phospholipase exoenzyme production, and to compare clinical features in patients with complete dentures and HIV+/Acquired Immunodeficiency Disease Syndrome (AIDS). Fifty-one patients were selected from a total of 285 with EC: denture wearers (n = 30) and HIV+/AIDS (n = 21). The yeast prevalence and the production of exoenzymes, such as proteinase and phospholipase by Candida species were evaluated by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) electrophoresis. The frequency of Candida albicans was significantly higher (P < 0.05) in both groups although other yeast species (Candida glabrata, Candida krusei, Candida parapsilosis, Candida guilliermondi and Candida tropicalis) were also found. Candida albicans showed greater levels of proteinase production in the denture wearers, when compared with the HIV+/AIDS group. There was no difference between groups with regard to phospholipase production. The protein bands presented similar molecular weights, showing the presence of proteinases in both groups. It could be concluded that the clinical manifestation of EC may be related to its proteinase production capacity. Combination therapies using proteinase inhibitors play an important role in inhibiting exoenzyme production by Candida species, mainly C. albicans.

Since the early 1990s, an increase in Mycobacterium tuberculosis drug resistance has been reported, with high prevalence among HIV+ patients. We evaluated the sensitivity patterns of M. tuberculosis, resistance rate, and predisposing factors among HIV+ patients in Santos, São Vicente, Cubatão, Praia Grande, and Guarujá, São Paulo State, Brazil. The medical charts of 301 patients with positive cultures for M. tuberculosis from 1993 to 2003 were reviewed. Resistance occurred in 57 patients (18.9%), as follows: 32 (10.6%) displayed multidrug-resistant tuberculosis (resistant to at least Rifampicin and Isoniazid); 4 (1.3%) were resistant to two or more drugs; and 21 (7%) were resistant to a single drug. Acquired resistance was observed in 70.1% of cases. Drug resistance was significantly associated with previous tuberculosis treatment, duration of HIV diagnosis, and previous hospitalization. In logistic regression analysis, only previous tuberculosis treatment adjusted by age remained as an independent risk factor (OR = 5.49; 95%CI: 2.60-11.60). Drug resistance to at least one drug in 18.9% and multidrug resistance in 10.6% of cases highlight the relevance of this problem in HIV patients in the Baixada Santista.

Background: Mucocutaneous lesions in human immunodeficiency virus (HIV)-infected patients with disseminated histoplasmosis have a wide spectrum of clinical manifestations, making its diagnosis difficult. Studies have been restricted to case reports and series with small numbers of patients not specifically focusing on the dermatological aspects of histoplasmosis., Aims: To describe the characteristics of mucocutaneous lesions of disseminated histoplasmosis in HIV-infected patients., Methods: A retrospective and prospective study was conducted on 36 HIV-infected patients with mucocutaneous histoplasmosis in a tertiary-care hospital in Brazil., Results: Mucocutaneous histoplasmosis was diagnosed by histopathology in 33 of the 36 patients (91%) and/or culture in 23 (64%). Their CD4+ cell counts ranged from 2 to 103 cells/mm(3). The average number of different morphological types of lesions was three per patient. Despite the variability of the lesions, papules (50%), crusted papules (64%) and oral mucosal erosions and/or ulcers (58%) were the most frequent dermatological lesions. A diffuse pattern of distribution of the skin lesions was found in 58% of the cases. There was significant association between the CD4+ cell counts and the morphological variability of lesions per patient. Variation in the lesions seemed to be associated with higher CD4+ cell counts., Conclusion: Doctors caring for HIV-infected patients should be aware of the wide spectrum of dermatological lesions observed in disseminated histoplasmosis and the importance of detecting and isolating the fungus in mucocutaneous tissues.

We present here the frequency of enteropathogens in an HIV-infected children group and investigate their correlation with clinical and sociodemographic characteristics by collecting 100 stool samples from 55 HIV-seropositive Brazilian children. All specimens were processed according to standard methods for bacterial and yeast detection. A commercially available enzyme-linked immunosorbent assay was used to detect protozoan, and to perform virus detection, molecular tests were applied. Consumption of raw vegetables and fruits and severe immunosuppression were significantly associated with diarrhea. Cryptosporidium parvum was the commonest enteropathogen, followed by Candida albicans, enteropathogenic Escherichia coli, and astrovirus. The number of potential pathogenic agents identified in fecal specimens in asymptomatic HIV-seropositive infants is high, which raises the need for additional investigation in this area as well as in other Brazilian regions.

The antifungal susceptibility profiles and the genetic variability of 83 sequential clinical isolates of Cryptococcus neoformans, including four Cryptococcus gattii isolates, obtained from 38 Sao Paulo AIDS patients with cryptococcal meningitis were assessed by electrophoretic karyotyping and random amplified polymorphic DNA (RAPD) analysis. The majority of the Cryptococcus neoformans isolates were highly susceptible to amphotericin B and fluconazole. Twenty percent of the minimum inhibitory concentration values for amphotericin B varied from 0.5 to 1 micro g mL(-1). For fluconazole, 22% occurred in the range 8-16 mug mL(-1). Sequential isolates from nine patients showed a trend towards lower susceptibility to fluconazole, flucytosine, itraconazole and amphotericin B. The results of molecular typing by electrophoretic karyotyping and RAPD analysis showed the presence of 22 electrophoretic karyotypes (EK) and 15 RAPD profiles that were highly correlated. Our results provided evidence for the occurrence of genetic changes in some strains associated with microevolution during the course of infection. We also observed both microevolution and simultaneous coinfection with two distinct Cryptococcus neoformans strains in one patient. In some patients, we found changed EK- and RAPD patterns in association with increased MIC values.