Genotyping Analysis of Cryptococcus deuterogattii and Correlation with Virulence Factors and Antifungal Susceptibility by the Clinical and Laboratory Standards Institute and the European Committee on Antifungal Susceptibility Testing Methods.

Data about the relationship between their molecular types, virulence factors, clinical presentation, antifungal susceptibility profile, and outcome are still limited for Cryptococcus deuterogattii. This study aimed to evaluate the molecular and phenotypic characteristics of 24 C. deuterogattii isolates from the southeast region of Brazil. The molecular characterization was performed by multilocus sequence typing (MLST). The antifungal susceptibility profile was obtained according to CLSI-M27-A3 and EUCAST-EDef 7.1 methods. The virulence factors were evaluated using classic techniques. The isolates were divided into four populations. The molecular analysis suggests recombinant events in most of the groups evaluated. Resistance and susceptibility dose-dependent to fluconazole were evidenced in four isolates (16%) by EUCAST and in four isolates (16%) by CLSI methods. The agreement at ±two dilutions for both methods was 100% for itraconazole, ketoconazole, and voriconazole, 96% for amphotericin B, and 92% for fluconazole. Significant differences in virulence factor expression and antifungal susceptibility to itraconazole and amphotericin B were found. The mixed infection could be suggested by the presence of variable sequence types, differences in virulence factor production, and decreased antifungal susceptibility in two isolates from the same patient. The data presented herein corroborate previous reports about the molecular diversity of C. deuterogattii around the world.

High genetic variability of clinical and environmental Cryptococcus gattii isolates from Brazil.

Among Cryptococcus gattii genotypes, VGII has gained pivotal relevance in epidemiological, clinical and genetic contexts due to its association with several outbreaks in temperate regions and due to the high variability of this genotype. The aim of this study was to compare 25 isolates of C. gattii from the Southeast region of Brazil with previously described isolates from other regions of the country and around the world. Among the 25 isolates, 24 were VGII and one was VGI. All of them were newly identified. Three new allele types (AT) (AT47 for the URA5 locus, AT56 for the LAC1 locus, and AT96 for the IGS1 region) were also described. Compared with other Brazilian isolates, those from the Southeast region presented the greatest haplotype diversity. In general, the regions presented different sequence types (STs), and only nine STs were found in more than one location. GoeBURST analysis showed two large groups among the Brazilian isolates. The largest group consists of 59 STs predominantly from the North and Northeast regions; the other large group includes 57 STs from the Southeast and Midwest regions. In a global context the South American isolates presented the highest genetic diversity (STs = 145, haplotype diversity (Hd) = 0.999 and π = 0.00464), while the African populations showed the lowest genetic diversity (STs = 3, Hd = 0.667 and π = 0.00225). These results confirm that the Brazilian C. gattii VGII population is highly diverse and reinforce the hypothesis of dispersion of this genotype from South America.

The epidemiology of cryptococcosis and the characterization of Cryptococcus neoformans isolated in a Brazilian University Hospital.

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.

The epidemiology of cryptococcosis and the characterization of Cryptococcus neoformans isolated in a Brazilian University Hospital

ABSTRACT 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.

Evaluation of virulence factors of Candida albicans isolated from HIV-positive individuals using HAART.

The colonization by Candida species is one of the most important factors related to the development of oral candidiasis in HIV-infected individuals. The aim of the study was to evaluate and discuss the phospholipase, proteinase, DNAse and haemolytic activities of Candida albicans isolated from the oral cavity of HIV individuals with high efficiency antiretroviral therapy. Seventy-five isolates of C. albicans obtained from saliva samples of patients with HIV and 41 isolates from HIV-negative individuals were studied. Haemolytic activity was determined in Sabouraud dextrose agar plates containing 3% glucose and 7% sheep red cells. Culture medium containing DNA base-agar, egg yolk, and bovine albumin were used to determine DNase, phospholipase and proteinase activities, respectively. All isolates from the HIV patients group had haemolytic activity, 98% showed phospholipase activity, 92% were positive for proteinase and 32% DNAse activity. Regarding the group of indivídios HIV negative, all 41 isolates presented hemolytic activity, 90.2% showed phospholipase and proteinase activity and 12.2% were positive for DNAse. The phospholipase activity was more intense for the group of HIV positive individuals. DNase production was more frequently observed in the group of HIV-positive individuals. The percentage of isolates having DNAse activity was also significantly different between the groups of patients not using any antiretroviral therapy, those using transcriptase inhibitors and those using transcriptase inhibitor and protease inhibitor in combination.

RELATED FACTORS FOR COLONIZATION BY Candida SPECIES IN THE ORAL CAVITY OF HIV-INFECTED INDIVIDUALS.

UNLABELLED: The colonization of the oral cavity is a prerequisite to the development of oropharyngeal candidiasis. AIMS: The aims of this study were: to evaluate colonization and quantify Candida spp. in the oral cavity; to determine the predisposing factors for colonization; and to correlate the levels of CD4+ cells and viral load with the yeast count of colony forming units per milliliter (CFU/mL) in HIV-positive individuals treated at a University Hospital. Saliva samples were collected from 147 HIV patients and were plated on Sabouraud Dextrose Agar (SDA) and chromogenic agar, and incubated at 30 ºC for 72 h. Colonies with similar morphology in both media were counted and the result expressed in CFU/mL. RESULTS: Of the 147 HIV patients, 89 had positive cultures for Candida spp., with a total of 111 isolates, of which C. albicans was the most frequent species (67.6%), and the mean of colonies counted was 8.8 × 10³ CFU/mL. The main predisposing factors for oral colonization by Candida spp. were the use of antibiotics and oral prostheses. The use of reverse transcriptase inhibitors appears to have a greater protective effect for colonization. A low CD4+ T lymphocyte count is associated with a higher density of yeast in the saliva of HIV patients.

RELATED FACTORS FOR COLONIZATION BY Candida SPECIES IN THE ORAL CAVITY OF HIV-INFECTED INDIVIDUALS / Fatores relacionados a colonização da cavidade bucal de indivíduos portadores do HIV por espécies de Candida

The colonization of the oral cavity is a prerequisite to the development of oropharyngeal candidiasis. Aims: The aims of this study were: to evaluate colonization and quantify Candida spp. in the oral cavity; to determine the predisposing factors for colonization; and to correlate the levels of CD4+ cells and viral load with the yeast count of colony forming units per milliliter (CFU/mL) in HIV-positive individuals treated at a University Hospital. Saliva samples were collected from 147 HIV patients and were plated on Sabouraud Dextrose Agar (SDA) and chromogenic agar, and incubated at 30 ºC for 72 h. Colonies with similar morphology in both media were counted and the result expressed in CFU/mL. Results: Of the 147 HIV patients, 89 had positive cultures for Candida spp., with a total of 111 isolates, of which C. albicans was the most frequent species (67.6%), and the mean of colonies counted was 8.8 × 10³ CFU/mL. The main predisposing factors for oral colonization by Candida spp. were the use of antibiotics and oral prostheses. The use of reverse transcriptase inhibitors appears to have a greater protective effect for colonization. A low CD4+ T lymphocyte count is associated with a higher density of yeast in the saliva of HIV patients.

RESUMO A colonização da cavidade oral pode ser considerada um pré-requisito para o desenvolvimento de candidíase orofaríngea. Os objetivos deste estudo foram: avaliar e quantificar espécies de Candidaisoladas da cavidade oral, para determinar os fatores predisponentes para a colonização, e correlacionar os níveis de células CD4+ e carga viral em indivíduos HIV-positivos atendidos em um hospital universitário. Foram coletadas amostras de saliva de 147 pacientes portadores do HIV, as quais foram semeadas em Ágar Sabouraud Dextrose (ASD) e ágar cromogênico e incubadas a 30 °C por 72 horas. As colônias com morfologia semelhante em ambos os meios foram contadas e o resultado expresso em unidade formadora de colônias por mililitro (UFC/mL). Dos 147 pacientes HIV positivos, 89 apresentaram culturas positivas para Candidaspp., totalizando 111 isolados, e C. albicansfoi a espécie mais frequente (67,6%). A contagem média de colônias foi de 8.8 × 10³ UFC/mL. Os principais fatores predisponentes para colonização oral por Candidaspp. foram a utilização de antibióticos e de próteses orais. O uso de antirretroviral da classe de inibidores da transcriptase reversa pareceu ter maior efeito protetor para a colonização. Baixa contagem de linfócitos T CD4+ está relacionada com maior densidade de leveduras na saliva de indivíduos HIV positivos.

Epidemiological profile of Hepatitis C virus infection in patients from West Region of Minas Gerais State, Brazil / Perfil epidemiológico da infecção pelo vírus da hepatite c em pacientes da região oeste de Minas Gerais, Brasil

Hepatitis C virus (HCV) is a serious public health problem and is the leading cause of liver transplantation due to cirrhosis and hepatocellular carcinoma. In Brazil, it is estimated that there are approximately 2 to 3 million HCV chronic carriers. Few data regarding HCV infection are available in West region of Minas Gerais State. Due to the absence of an effective vaccine against this important human pathogen and the high costs of antiviral treatment, it is important to conduct epidemiological studies with the purpose of carry out the planning and implementation of measures to prevent hepatitis C in different populations. Therefore, the aim of this study is to describe the epidemiological aspects of HCV patients from West region of Minas Gerais State, Brazil. Sociodemographic data and risk factors for HCV infection were determined from 74 HCV patients from Uberlândia city (Minas Gerais State). Reactive anti-HCV sera samples were submitted to HCV RNA and genotype detection. Most of individuals were male (63.5%) with mean age of 51 years and presenting low socioeconomic status. HCV genotype was determined among 40 samples and the frequencies were: genotype 2 (45%), 1 (37.5%) and 3 (17.5%). Hepatitis C virus (HCV) infection was common among male and low socioeconomic status individuals.

O vírus da hepatite C (HCV) é um sério problema de saúde pública e a principal causa de transplante de fígado devido à cirrose e carcinoma hepatocelular. No Brasil, estima-se que há aproximadamente 2 a 3 milhões de portadores crônicos do HCV. Poucos dados sobre a infecção pelo HCV na região oeste do estado de Minas Gerais estão disponíveis. Devido à ausência de vacina eficaz contra esse importante patógeno humano e aos altos custos do tratamento antiviral, é importante realizar estudos epidemiológicos com a finalidade de executar o planejamento e implementação de medidas para prevenir a hepatite C em diferentes populações. Portanto, o objetivo deste estudo é descrever os aspectos epidemiológicos dos pacientes portadores de HCV da região oeste do estado de Minas Gerais, Brasil. Dados sociodemográficos e fatores de risco para a infecção com HCV foram determinados de 74 pacientes portadores de HCV da cidade de Uberlândia, Minas Gerais. Amostras de soro reativas foram submetidas às detecções de HCV RNA e genótipo. A maioria dos indivíduos eram homens (63,5%) com média de idade de 51 anos e baixo nível socioeconômico. O genótipo do HCV foi determinado entre 40 amostras e as frequências foram: genótipo 2 (45%), 1 (37,5%) e 3 (17,5%). A infecção com o vírus da hepatite C foi frequente entre homens e indivíduos de baixo nível socioeconômico.

[Histoplasmosis]. / Histoplasmose.

Histoplasmosis is a fungal infection caused by the dimorphic fungus Histoplasma capsulatum. It is classically considered an endemic mycosis, even though the fungus has an opportunistic behavior in immunocompromised patients. People acquired the infection through the inhalation of conidial forms present in the environmental, such as caves dwelling bats and soils inhabited by chickens. The clinical features may vary from asymptomatic infections to disseminated severe forms that affect patients with acquired immunodeficiency syndrome or hematological malignancies and allograft recipients. The diagnosis is based on the detection of the fungus in organic fluids (sputum, blood, liquor) or tissues (histopathological assays), in the culture of biological samples and serological assays. The treatment of severe chronic respiratory acute or localized forms can be performed with oral azolic (itraconazol) and in the disseminated forms, the amphotericin B (preferentially the lipidic formulations) consists in the elected drug to initiate the therapy. Nowadays, histoplasmosis represents one of the most important systemic mycosis in the Americas, with broad distribution in all regions of Brazil.

Histoplasmose: [revisão] / Histoplasmosis: [review]

A histoplasmose é uma micose causada por fungo dimórfico, o Histoplasma capsulatum. É considerada classicamente uma micose endêmica, embora o fungo tenha um comportamento oportunístico em pacientes com depressão da imunidade celular. O homem adquire a infecção através da inalação de conídeos presentes na natureza (cavernas com morcegos, galinheiros, etc). O quadro clínico pode variar, desde infecções assintomáticas até quadros graves disseminados, que acometem pacientes com Aids, transplantados ou com neoplasias hematológicas. O diagnóstico baseia-se no encontro do fungo em fluidos orgânicos (escarro, sangue, líquor) ou tecidos (histopatologia), na cultura de materiais biológicos e na sorologia. O tratamento das formas agudas graves, respiratória crônica ou de formas localizadas pode ser feito com azólicos orais (itraconazol) e nas disseminadas, a Anfotericina B (preferencialmente as formulações lipídicas) constitui a droga da eleição para iniciar a terapia. A histoplasmose representa, hoje uma das micoses sistêmicas mais importantes nas Américas, com ampla distribuição em todas as regiões do Brasil.

Histoplasmosis is a fungal infection caused by the dimorphic fungus Histoplasma capsulatum. It is classically considered an endemic mycosis, even though the fungus has an opportunistic behavior in immunocompromised patients. People acquired the infection through the inhalation of conidial forms present in the environmental, such as caves dwelling bats and soils inhabited by chickens. The clinical features may vary from asymptomatic infections to disseminated severe forms that affect patients with acquired immunodeficiency syndrome or hematological malignancies and allograft recipients. The diagnosis is based on the detection of the fungus in organic fluids (sputum, blood, liquor) or tissues (histopathological assays), in the culture of biological samples and serological assays. The treatment of severe chronic respiratory acute or localized forms can be performed with oral azolic (itraconazol) and in the disseminated forms, the amphotericin B (preferentially the lipidic formulations) consists in the elected drug to initiate the therapy. Nowadays, histoplasmosis represents one of the most important systemic mycosis in the Americas, with broad distribution in all regions of Brazil.

[Advances in the treatment of hepatitis B]. / Avanços no tratamento da hepatite pelo vírus B.

Over the last years there has been considerable progress in the treatment of chronic hepatitis B. Five drugs are now approved for the treatment of this virosis: interferon alpha, lamivudine, adefovir, entecavir and telbivudine. Interferons (conventional or PEG) were the first medicine used in the treatment of hepatitis being able to lead the persistent response (loss of DNA-HBV and of AgHbe) to up to one third of treated cases. A large number of nucleoside/nucleotide analogues are, at present, available to treat hepatitis B. The efficacy of lamivudine, the first nucleoside analogue used, is limited by the high rate of resistance. Adefovir has efficacy comparable to that of lamivudine, but with low resistance rate. Entecavir and tenofovir have also been particularly active in the control of hepatitis B virus replication and are associated with minimal resistance development, even during long treatment regimens. Other drugs, such as telbivudine, emtricitabine and clevudine, will become new treatment options in the near future. Individuals co-infected with HIV/HBV are particularly difficult to manage and are nowadays able to benefit from combinations of drugs of the HAART therapy, which should be effective towards both viruses. The development of more potent antiviral drugs as well as new drug combinations, together with a better understanding of hepatitis B virus resistance mechanisms are important milestones to improve treatment efficacy and to diminish, in the future, the global burden of hepatitis B virus.

Avanços no tratamento da hepatite pelo vírus B / Advances in the treatment of hepatitis B

Nos últimos anos, houve um grande progresso no tratamento da hepatite B crônica. Cinco drogas são hoje aprovadas para tratamento dessa virose: intérferon alfa, lamivudina, adefovir, entecavir e telbivudina. Os intérferons (convencionais ou peguilados) foram as primeiras drogas utilizadas no tratamento dessas infecções podendo levar a resposta sustentada (perda do DNA-VHB e do AgHbe) em até um terço dos casos tratados. Um grande número de análogos de nucleosídeos/nucleotídeos estão no momento, disponíveis para tratar a hepatite B; a eficácia da lamivudina, o primeiro análogo de nucleosídeo utilizado, é limitada pela elevada incidência de resistência. O adefovir tem eficácia comparável à lamivudina porém baixa freqüência de resistência. Entecavir e tenofovir também se mostram muito ativos em controlar a replicação do vírus da hepatite B, e estão associados com mínimo desenvolvimento de resistência, mesmo em tratamento prolongados. Outras drogas, tais como telbivudina, emtricitabina e clevudine, se tornarão em futuro próximo, novas armas no controle dessa virose. Co-infectados HIV/VHB representam um grupo de doentes de difícil manuseio e que hoje se beneficiam com combinações de drogas no esquema anti-retroviral potente que devem atuar em ambas as viroses. O desenvolvimento de antivirais mais potentes e novas associações de medicamentos, conjuntamente com a melhor compreensão dos mecanismos de resistência do vírus da hepatite B a terapia são importantes conquistas para melhorar a eficácia do tratamento e diminuir no futuro, a carga global de portadores do vírus da hepatite B.

Over the last years there has been considerable progress in the treatment of chronic hepatitis B. Five drugs are now approved for the treatment of this virosis: interferon alpha, lamivudine, adefovir, entecavir and telbivudine. Interferons (conventional or PEG) were the first medicine used in the treatment of hepatitis being able to lead the persistent response (loss of DNA-HBV and of AgHbe) to up to one third of treated cases. A large number of nucleoside/nucleotide analogues are, at present, available to treat hepatitis B. The efficacy of lamivudine, the first nucleoside analogue used, is limited by the high rate of resistance. Adefovir has efficacy comparable to that of lamivudine, but with low resistance rate. Entecavir and tenofovir have also been particularly active in the control of hepatitis B virus replication and are associated with minimal resistance development, even during long treatment regimens. Other drugs, such as telbivudine, emtricitabine and clevudine, will become new treatment options in the near future. Individuals co-infected with HIV/HBV are particularly difficult to manage and are nowadays able to benefit from combinations of drugs of the HAART therapy, which should be effective towards both viruses. The development of more potent antiviral drugs as well as new drug combinations, together with a better understanding of hepatitis B virus resistance mechanisms are important milestones to improve treatment efficacy and to diminish, in the future, the global burden of hepatitis B virus.

[Hantavirus cardiopulmonary syndrome in the Triângulo Mineiro and Alto Paranaíba regions, State of Minas Gerais, 1998-2005: clinical-epidemiological aspects of 23 cases]. / Síndrome cardiopulmonar por hantavírus no Triângulo Mineiro e Alto Paranaíba, Minas Gerais, 1998-2005: aspectos clínico-epidemiológicos de 23 casos.

The epidemiological, clinical, laboratory and treatment findings from 23 cases of hantavirus cardiopulmonary syndrome were analyzed. These cases were identified either serologically or immunohistochemically in hospitals in the municipality of Uberlândia, State of Minas Gerais. Fever (100%), dyspnea (100%) and myalgia (78%) were the symptoms most frequently observed in this sample. The most prevalent physical signs were hypotension (65%) and tachycardia (65%). The most common laboratory findings included thrombocytopenia (96%), hemoconcentration (83%) and leukocytosis (74%). Abnormal values for liver enzymes were found in all the patients tested and abnormalities in chest radiography were very frequent (95.6%). In 55.5% of the patients, orotracheal intubation and hemodynamic support were required. The present study confirmed the seasonal pattern of hantavirus cardiopulmonary syndrome in the Uberlândia region and the involvement of professional groups who are considered to be at low risk of infection, in the transmission cycle of the disease. The high lethality rate (39%) and the severity of the disease observed in this study may be related to attending to these patients at a late stage.

Síndrome cardiopulmonar por hantavírus no Triângulo Mineiro e Alto Paranaíba, Minas Gerais, 1998-2005: aspectos clínico-epidemiológicos de 23 casos / Hantavirus cardiopulmonary syndrome in the Triângulo Mineiro and Alto Paranaíba regions, State of Minas Gerais, 1998-2005: clinical-epidemiological aspects of 23 cases

Foram analisados os achados epidemiológicos, clínicos, laboratoriais e terapêuticos de 23 casos de síndrome cardiopulmonar por hantavírus, identificados sorologicamente ou por imunohistoquímica em hospitais do município de Uberlândia, Minas Gerais. Febre (100 por cento), dispnéia (100 por cento) e mialgias (78 por cento) foram os sintomas mais frequentemente observados nesta casuística. Os sinais físicos mais prevalentes foram hipotensão (65 por cento) e taquicardia (65 por cento). Achados laboratoriais mais comuns incluíram trombocitopenia (96 por cento), hemoconcentração (83 por cento) e leucocitose (74 por cento). Valores anormais de enzimas hepáticas foram encontrados em todos os pacientes testados e alterações em radiografias de tórax foram muito (95,6 por cento) freqüentes. Em 55,5 por cento dos pacientes, foi necessário intubação orotraqueal e suporte hemodinâmico. O presente estudo confirmou o padrão sazonal da síndrome cardiopulmonar por hantavírus na região de Uberlândia e o envolvimento, no ciclo de transmissão da doença, de grupos profissionais considerados de baixo risco de infecção. A alta (39 por cento) taxa de letalidade e a gravidade da doença observadas neste estudo podem estar associadas ao atendimento tardio dos pacientes.

The epidemiological, clinical, laboratory and treatment findings from 23 cases of hantavirus cardiopulmonary syndrome were analyzed. These cases were identified either serologically or immunohistochemically in hospitals in the municipality of Uberlândia, State of Minas Gerais. Fever (100 percent), dyspnea (100 percent) and myalgia (78 percent) were the symptoms most frequently observed in this sample. The most prevalent physical signs were hypotension (65 percent) and tachycardia (65 percent). The most common laboratory findings included thrombocytopenia (96 percent), hemoconcentration (83 percent) and leukocytosis (74 percent). Abnormal values for liver enzymes were found in all the patients tested and abnormalities in chest radiography were very frequent (95.6 percent). In 55.5 percent of the patients, orotracheal intubation and hemodynamic support were required. The present study confirmed the seasonal pattern of hantavirus cardiopulmonary syndrome in the Uberlândia region and the involvement of professional groups who are considered to be at low risk of infection, in the transmission cycle of the disease. The high lethality rate (39 percent) and the severity of the disease observed in this study may be related to attending to these patients at a late stage.

[Cryptococosis: clinical epidemiological laboratorial study and fungi varieties in 96 patients]. / Criptococose: estudo clínico-epidemiológico, laboratorial e das variedades do fungo em 96 pacientes.

Ninety-six patients with cryptococcosis confirmed by clinical and laboratorial diagnosis were assessed in a prospective study in a University Hospital from March 1998 to November 2003; of these, 81.3% were HIV seropositive patients. Cryptococcus neoformans was isolated from different samples, of which the cerebrospinal fluid 74 (77%) was the most frequent. C. neoformans var neoformans was isolated in 89 cases, where as C. neoformans var gattii was isolated in 7. Cryptococcal meningoencephalitis was detected in 56.3% cases. It was the most frequent unique clinical manifestation and the fungus was detected in the bloodstream in 13.5% of the patients. Among the risk factors, AIDS (81.3%) was the most frequently associated with mycosis. Direct examination carried out on 121 samples revealed the microorganism in 98.3% of them, while the culture was positive for all samples. Most of the patients (59.4%) were treated with amphotericin B or with triazoles, however 72.9% of them ended in death, in particular those patients with positive tests for the HIV (62.5%). Nowadays, cryptococcosis has been frequently diagnosed in our region and represents one of the opportunistic diseases with the highest morbidity and mortality rates in patients with AIDS.

Criptococose: estudo clínico-epidemiológico, laboratorial e das variedades do fungo em 96 pacientes / Cryptococosis: clinical epidemiologycal laboratorial study and fungi varieties in 96 patients

Estudo prospectivo foi realizado no Hospital de Clínicas da Universidade Federal de Uberlândia, entre março de 1998 e novembro de 2003, em 96 pacientes com diagnóstico clínico e laboratorial de criptococose, sendo 81,3 por cento portadores de Aids. Cepas de Cryptococcus neoformans foram obtidas de diferentes amostras, sendo 77 por cento em líquido cefalorraquidiano. A var neoformans foi isolada em 89 casos e a var gattii em 7. A meningoencefalite criptocócica (56,3 por cento dos casos), foi a manifestação clínica mais descrita, seguida da fungemia (13,5 por cento). Entre os fatores de risco, a AIDS (81,3 por cento) foi o mais comumente associado à micose. A pesquisa direta do fungo realizada em 121 amostras demonstrou o microrganismo em 98,3 por cento, com cultura (+) em todas. Dos pacientes, 59,4 por cento foram tratados com anfotericina B ou derivados triazólicos, sendo que 72,9 por cento evoluíram para óbito, em particular os portadores de AIDS (62,5 por cento). Atualmente, a criptococose tem sido diagnosticada com muita freqüência em nosso meio e constitui uma das doenças oportunísticas de maior morbidade e mortalidade nos pacientes com AIDS.

[Detection of anti-Toxoplasma gondii IgG, IgM and IgA immunoglobulins in the serum, cerebrospinal fluid and saliva of patients with acquired immunodeficiency syndrome and neurotoxoplasmosis]. / Detecção de imunoglobulinas IgG, IgM e IgA anti-Toxoplasma gondii no soro, líquor e saliva de pacientes com síndrome da imunodeficiência adquirida e neurotoxoplasmose.

We studied 55 patients with acquired immunodeficiency syndrome (AIDS) and neurotoxoplasmosis (group 1), 37 patients with AIDS and neurological involvement due to another etiology (group 2) and 18 anti-HIV-negative individuals with neurological manifestations, by searching for anti-T. gondii IgG, IgA and IgM immunoglobulins in serum, cerebrospinal fluid (CSF)and saliva, using ELISA. The negative predictive value of the test for IgG in serum was 100% and in CSF, 92.4%. There was no difference among the three groups studied regarding IgA in serum. For IgA, in CSF the test reached 72.7% specificity (p<0.05). In saliva, only the detection of IgG was found to be correlated with a diagnosis of neurotoxoplasmosis. We emphasize that the absence of anti-T. gondii IgG antibodies in serum and CSF strongly indicates the absence of a diagnosis of neurotoxoplasmosis and that specific IgA immunoglobulins in CSF and IgG in saliva may represent two auxiliary markers for the differential diagnosis of toxoplasmic encephalitis in AIDS.

Detecção de imunoglobulinas IgG, IgM e IgA anti-Toxoplasma gondii no soro, líquor e saliva de pacientes com síndrome da imunodeficiência adquirida e neurotoxoplasmose / Detection of anti-Toxoplasma gondii IgG, IgM and IgA immunoglobulins in the serum, cerebrospinal fluid and saliva of patients with acquired immunodeficiency syndrome and neurotoxoplasmosis

Estudamos 55 pacientes com sindrome da imunodeficiência adquirida (SIDA) e neurotoxoplasmose (grupo 1); 37 pacientes com SIDA e comprometimento neurológico por outra etiologia (grupo 2) e 18 indivíduos anti-HIV negativos com manifestações neurológicas (grupo 3), pesquisando IgG, IgA e IgM anti-Toxoplasma gondii, no soro, líquor e saliva, utilizando teste ELISA, para fins diagnósticos. O valor preditivo negativo do teste para o encontro de IgG no soro foi 100 por cento e no líquor, 92,4 por cento. Não houve diferença entre os três grupos quanto aos anticorpos IgA neste material. Para IgA, no líquor, o teste alcançou 72,7 por cento de especificidade (p<0,05). Na saliva, apenas o encontro de IgG mostrou correlação com o diagnóstico de neurotoxoplasmose. Enfatizamos que a ausência de anticorpos IgG anti-T. gondii no soro e líquor depõe fortemente contra o diagnóstico de neurotoxoplasmose e que imunoglobulinas IgA específicas no líquor e IgG na saliva podem representar dois marcadores auxiliares para o diagnóstico diferencial da encefalite toxoplásmica na SIDA.

Evaluation of intrathecal synthesis of specific IgG antibodies against Toxoplasma gondii in the diagnosis assessment of presumptive toxoplasma encephalitis in aids patients

O diagnóstico da neurotoxoplasmose em pacientes com síndrome da imunodeficiência adquirida baseia-se fundamentalmente nos achados tomográficos ou de ressonância magnética e na resposta ao tratamento específico. Estudamos 55 pacientes com SIDA e neurotoxoplasmose, de acordo com estes critérios diagnósticos (grupo 1); 37 pacientes com SIDA e comprometimento neurológico por outra etiologia (grupo 2) e 16 indivíduos anti-HIV negativo, com outras doenças neurológicas (grupo 3), pesquisando IgG, anti-T. gondii, no soro e no líquor, utilizando a reação de imunofluorescência indireta. Em 72 casos, determinamos os teores totais destes anticorpos aí presentes, com objetivo de avaliar a produção local, no sistema nervoso central, de anticorpos específicos e correlacionar os títulos com atividade da infecção, em pacientes com SIDA e neurotoxoplasmose. Evidência de produção local destes anticorpos foi detectada em 42,8% dos pacientes do grupo 1, em 29,1% dos pacientes do grupo 2 e em nenhum paciente do grupo 3. O teste apresentou especificidade intermediária (70,8%), porém não foi útil para o diagnóstico diferencial da neurotoxoplasmose em pacientes com SIDA, em nosso estudo. Por outro lado, títulos de IgG no líquor > 1/64 alcançaram 100% de especificidade para o diagnóstico de neurotoxoplasmose na SIDA.

Evaluation of intrathecal synthesis of specific IgG antibodies against Toxoplasma gondii in the diagnosis assessment of presumptive toxoplasma encephalitis in AIDS patients.

The diagnosis of neurotoxoplasmosis in patients with acquired immunodeficiency syndrome is mainly based on tomographic or magnetic resonance findings and on the response to specific treatment. We studied 55 patients with AIDS and neurotoxoplasmosis according to these diagnostic criteria (group 1), 37 patients with AIDS and neurological involvement of other etiology (group 2), and 16 anti-HIV-negative individuals with neurological manifestations (group 3). Serum and cerebrospinal fluid were examined for the presence of anti-T. gondii IgG, by indirect immunofluorescence. In 72 of them, the total amounts of these antibodies were determined in order to assess local production of anti-T. gondii antibodies in the central nervous system and to correlate their titers with infection activity in patients with AIDS and neurotoxoplasmosis. IgG titers > or = 1/64 in cerebrospinal fluid reached 100% specificity for the diagnosis of neurotoxoplasmosis in AIDS. Evidence of local synthesis of these antibodies was detected in 42.8% of patients of group 1, in 29.1% of patients of group 2 and in no patient of group 3. The test showed 70.8% specificity and therefore was not useful in our study for the differential diagnosis of neurotoxoplasmosis in patients with AIDS.