Molecular epidemiology of Paracoccidiodes spp. recovered from patients with paracoccidioidomycosis in a teaching hospital from Minas Gerais State of Brazil.

INTRODUCTION: Paracoccidioidomycosis (PCM) is caused by several species of the Paracoccidioides genus which can be differentiated by interspecific genetic variations, morphology and geographic distribution. Intraspecific variability correlation with clinical and epidemiological aspects of these species still remains unclear. This study aimed to sequence the loci GP43, exon 2 and ARF of 23 clinical isolates of Paracoccidioides spp. from patients in the Southeast Region of Brazil. METHODOLOGY AND MAIN FINDINGS: GenBank was used to compare the present (23) with previous described sequences (151) that included ARF and GP43. It was identified a high polymorphism rate among the 23 isolates in comparison to the other 151. Among the isolates, 22 (95.66%) were S1/P. brasiliensis and 1 (4.34%) was identified as PS2/P. americana. A total of 45 haplotypes were found as follows: 19 from S1/P. brasiliensis (13 from the present study), 15 from P. lutzii, 6 from PS2/P. americana (1 from the present study), 3 from PS3/P. restrepiensis and 2 from PS4/P. venezuelensis. Moreover, exclusive haplotypes according to clinical origin and geographical area were found. S1/P. brasiliensis (HD = 0.655 and K = 4.613) and P. lutzii (HD = 0.649 and K = 2.906) presented the highest rate of polymorphism among all species, from which 12 isolates of the present study were clustered within S1b/P. brasiliensis. The GP43 locus showed a higher variability and was found to be the main reason for the species differentiation. CONCLUSIONS: The results herein decribed show a high intraspecific genetic variability among S1/P. brasiliensis isolates and confirm the predominance of this species in the Southeast region of Brazil. The finding of exclusive haplotypes according to clinical origin and geographical area would suggest correlation between the molecular profile with the clinical form and geographic origin of patients with PCM.

Brazilian Society of Hepatology and Brazilian Society of Infectious Diseases Guidelines for the Diagnosis and Treatment of Hepatitis B.

Chronic hepatitis B is an important health problem that can progress to cirrhosis and complications such as hepatocellular carcinoma. There is approximately 290 million of people with chronic hepatitis B virus (HBV) infection worldwide, however only 10% of patients are currently identified. Most part of Brazil is considered of low prevalence of HBV infection but there are some regions with higher frequency of carriers. Unfortunately, many infected patients are not yet identified nor evaluated for treatment. The Brazilian Society of Infectious Diseases (SBI) and the Brazilian Society of Hepatology worked together to elaborate a guideline for diagnosis and treatment of hepatitis B. The document includes information regarding the population to be tested, diagnostic tools, indications of treatment, therapeutic schemes and also how to handle HBV infection in specific situations (pregnancy, children, immunosuppression, etc). Delta infection is also part of the guideline, since it is an important infection in some parts of the country.

Paracoccidioidomycosis.

Paracoccidioidomycosis is a systemic fungal infection caused by Paracoccidoides brasiliensis. The infection is endemic in subtropical areas of Latin America and has a high prevalence in Brazil. The disease is acquired by airborne inhalation of conidia and is frequently observed in adult male rural workers. The juvenile type of this mycosis is less prevalent (5-10% of clinical cases) and attacks both sexes. This clinical form occurs in children and adolescents and has a subacute course with fever, toxemia, loss of weight, adenopathy, hepatoesplenomegaly, anaemia and eosinophilia. Radiologic abnormalities in the lung fields may be seen. Mucous membrane lesions occasionally occur. The clinical presentation resembles severe tuberculosis, leukaemia or lymphoma. The diagnosis is confirmed by finding yeast-like elements of P. brasiliensis in microscopic examinations of wet preparations of specimens submitted for mycologic studies. The fungus grows slowly (20-30 days) and its isolation is difficult. Histologic and serologic studies may also assist in the diagnosis of this mycosis. Sulfonamides, ketoconazole, itraconazole, fluconazole and amphotericin B have been successfully used in the treatment of paracoccidioidomycosis. Itraconazole is the treatment of choice, being effective in more than 95% of cases. Co-trimoxazole is still frequently used especially in chronic progressive disease and as maintenance after a course of amphotericin B in severe cases of this mycosis.

Serological reactivity of different antigenic preparations of Leishmania (Leishmania) amazonensis and the Leishmania braziliensis complex.

Total antigen from Leishmania (Leishmania) amazonensis and isolates from the Leishmania braziliensis complex, along with their respective antigenic fractions obtained by affinity chromatography on concanavalin-A-Sepharose and jacalin-agarose columns evaluated using immunoenzymatic ELISA assay. For this, serum samples from 229 patients were used, grouped as American tegmental leishmaniasis (n masculine=58), visceral leishmaniasis (n masculine=28), Chagas disease (n masculine=49), malaria (n masculine=32), tuberculosis (n masculine=13) and healthy volunteers (n masculine=49). Samples from American tegmentary leishmaniasis showed higher reactivity with antigens isolated from the Leishmania braziliensis complex than with antigens from Leishmania amazonensis (p<0.001). ELISA assays showed a sensitivity range from 60% to 95% with antigens isolated from the Leishmania braziliensis complex. There was marked nonspecific reactivity among serum samples with the use of antigenic fractions binding with concanavalin-A and jacalin from both Leishmania complexes, in comparison with other antigens (p<0.001). The results presented in this study suggest that the use of homologous antigens increases the efficiency of anti-Leishmania immunoglobulin detection, which may be very valuable for diagnostic purposes.

[Paracoccidioidomycosis at Brasilias university hospital]. / Paracoccidioidomicose no Hospital Universitário de Brasília.

Seventy-six paracoccidioidomycosis patients attended at the university hospital of Brasília from 1984 to 2005 were studied. 82.9% were male and the mean age was 42 years. 54.9% of the patients were engaged in farming activities. Among the patients with the chronic form, 87% were smokers and 55.3% consumed alcohol. Among 71 patients without HIV/AIDS coinfection: a) paracoccidioidomycosis was recurrent in 21 (29.6%); b) the chronic or mixed form affected 77.5% of patients, predominantly in the oropharynx (70.9%) and lungs (67.3%), with lymph node lesions in 29.8%, laryngeal lesions in 27.3% and cutaneous lesions in 16.4%; c) in the acute/subacute form, lymph node lesions predominated (81.3%), followed by cutaneous lesions in 43.8%, which resulted in severe disease in 62.5% and moderate disease in 37.5%. Five patients had HIV/AIDS coinfection and three of them presented disseminated fungal infection together with marked immunosuppression.

Malaria outbreaks in a non-endemic area of Brazil, 2005.

In March 2005, a resident of the municipality of Monte Alegre de Minas, State of Minas Gerais, without any history of traveling to endemic areas for malaria, was diagnosed with Plasmodium vivax infection and local mosquito-borne transmission was suspected. The epidemiological investigation identified another 10 cases with local transmission and all of them were related to the imported malaria case that was detected in this region. The potential exposure site was the banks of the river Tejuco, an area frequented by mineral prospectors. Some of these prospectors were known to have come from states with malaria transmission. In the autochthonous cases, Plasmodium vivax and Plasmodium falciparum were diagnosed. Entomological investigation identified Anopheles (Nyssorhynchus) darlingi, Anopheles (Nyssorhynchus) albitarsis, Anopheles (Nyssorhynchus) triannulatus and Anopheles (Nyssorhynchus) parvus. After the first outbreak, another three autochthonous cases were notified in municipality of Monte Alegre de Minas, in the same year. The occurrence of these outbreaks highlights the importance of surveillance systems in areas that are nonendemic for malaria.

[Brazilian guidelines for the clinical management of paracoccidioidomycosis]. / II Consenso Brasileiro em Paracoccidioidomicose - 2017.

Paracoccidioidomycosis is a systemic fungal disease associated with agricultural activities. Its incidence and prevalence are underestimated because of the lack of reporting in several Brazilian states. If paracoccidiodomycosis is not diagnosed and treated early and adequately, endemic fungal infection may result in serious sequelae. In addition to the Paracoccidioides brasiliensis (P. brasiliensis) complex, the appearance of a new species, Paracoccidioides lutzii (P. lutzii), in Rondônia state, where the disease has reached epidemic levels, and in the country's Midwest region and Pará state, are challenges to diagnosis and to the urgent availability of antigens that are reactive with patients' sera. These guidelines aim to update the first Brazilian consensus on paracoccidioidomycosis by providing evidence-based recommendations for bedside patient management. The guidelines provide data on etiology, epidemiology, immunopathogenesis, diagnosis, treatment and sequelae, with emphasis on diagnosis and treatment, as well as current recommendations and challenges in this field of knowledge.

A paracoccidioidomicose (PCM) é uma micose sistêmica, relacionada às atividades agrícolas, com incidência e prevalência subestimadas, pela ausência de notificação em várias Unidades da Federação (UFs). A evolução insidiosa do quadro clínico pode ter como consequência sequelas graves se o diagnóstico e o tratamento não forem instituídos precoce e adequadamente. Ao lado do complexo Paracoccidioides brasiliensis (P. brasiliensis), a descrição de nova espécie, Paracoccidioides lutzii (P. lutzii), em Rondônia, onde a doença alcançou níveis epidêmicos, bem como na região Centro-Oeste e no Pará, constituem-se em desafios para a instituição do diagnóstico e a urgente disponibilização de antígenos que tenham reatividade com os soros dos pacientes. Este consenso visa atualizar o primeiro consenso brasileiro em PCM, estabelecendo recomendações para o manejo clínico do paciente, com base nas evidências conhecidas. São apresentados dados de etiologia, epidemiologia, imunopatogenia, diagnóstico, terapêutica e sequelas, enfatizando-se o diagnóstico e a terapêutica, bem como recomendações e desafios atuais nessa área do conhecimento.

La paracoccidioidomicosis es una micosis sistémica, relacionada con las actividades agrícolas, con incidencia y prevalencia subestimadas por la ausencia de notificación en varios estados. La evolución insidiosa del cuadro clínico puede tener como consecuencia secuelas graves si el diagnóstico y el tratamiento no se establecen precoz y adecuadamente. Al lado del complejo Paracoccidioides brasiliensis (P. brasiliensis), la descripción de nueva especie, Paracoccidioides lutzii (P. lutzii) en Rondonia, donde la enfermedad alcanzó niveles epidémicos, y en la región Centro Oeste y en Pará, se constituyen en desafíos para la institución del diagnóstico y la urgente puesta a disposición de antígenos que tengan reactividad con los sueros de los pacientes. El presente consenso tiene por objeto actualizar el primer consenso brasileño en paracoccidioidomicosis, estableciendo recomendaciones para el manejo del paciente al borde del lecho, con base en las evidencias conocidas. Se presentan datos de etiología, epidemiología, inmunopatogenia, diagnóstico, terapéutica y secuelas, enfatizando el diagnóstico y terapéutica, así como recomendaciones desafíos y actuales en esta área del conocimiento.

[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.

Abdominal wall protrusion following herpes zoster.

We present the case of a 62-year-old woman with abdominal segmental paresis consequent to radiculopathy caused by zoster, which was confirmed by electroneuromyography. The paresis resolved completely within three months. Recognition of this complication caused by zoster, which is easily misdiagnosed as abdominal herniation, is important for diagnosing this self-limited condition and avoiding unnecessary procedures.

[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.

Brazilian guidelines for the clinical management of paracoccidioidomycosis.

Paracoccidioidomycosis is a systemic fungal disease occurring in Latin America that is associated with rural environments and agricultural activities. However, the incidence and prevalence of paracoccidiodomycosis is underestimated because of the lack of compulsory notification. If paracoccidiodomycosis is not diagnosed and treated early and adequately, the endemic fungal infection could result in serious sequelae. While the Paracoccidioides brasiliensis ( P. brasiliensis ) complex has been known to be the causal agent of paracoccidiodomycosis, a new species, Paracoccidioides lutzii ( P. lutzii ), has been reported in Rondônia, where the disease has reached epidemic levels, and in the Central West and Pará. Accurate diagnoses and availability of antigens that are reactive with the patients' sera remain significant challenges. Therefore, the present guidelines aims to update the first Brazilian consensus on paracoccidioidomycosis by providing evidence-based recommendations for bedside patient management. This consensus summarizes etiological, ecoepidemiological, molecular epidemiological, and immunopathological data, with emphasis on clinical, microbiological, and serological diagnosis and management of clinical forms and sequelae, as well as in patients with comorbidities and immunosuppression. The consensus also includes discussion of outpatient treatments, severe disease forms, disease prevalence among special populations and resource-poor settings, a brief review of prevention and control measures, current challenges and recommendations.

[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.

[Immunoglobulin isotype and IgG subclass profiles in American tegumentary leishmaniasis]. / Perfil de isotipos de imunoglobulinas e subclasses de IgG na leishmaniose tegumentar americana.

The present work investigated the serum antibody profiles in 37 patients with American tegumentary leishmaniasis, who were attended at Hospital de Clinicas - Universidade Federal de Uberlandia, MG, Brazil. The immunoglobulin class and IgG subclass profiles were analyzed by indirect ELISA using Leishmania (Leishmania) amazonensis soluble antigen. The antibody avidity was determined by 6 M urea treatment after incubation with immunoenzymatic conjugate. It was observed that 97% of the serum samples presented anti-Leishmania antibodies for IgE class, 94.6% IgG, 57.5% IgA and 21.5% IgM class. For IgG subclasses the profiles were in the following order of frequency: IgG1>IgG3>IgG2>IgG4. High avidity of anti-Leishmania IgE antibodies was found in 44.4% of the samples. On the other hand, moderate avidity of specific IgG and IgA was observed in 62.8% and 47.8% of samples, respectively. These results indicate a very complex antibody response profile against American tegumentary leishmaniasis.

Brazilian Society of Hepatology and Brazilian Society of Infectious Diseases Guidelines for the Diagnosis and Treatment of Hepatitis B

Abstract Chronic hepatitis B is an important health problem that can progress to cirrhosis and complications such as hepatocellular carcinoma. There is approximately 290 million of people with chronic hepatitis B virus (HBV) infection worldwide, however only 10% of patients are currently identified.Most part of Brazil is considered of low prevalence of HBV infection but there are some regions with higher frequency of carriers. Unfortunately, many infected patients are not yet identified nor evaluated for treatment.The Brazilian Society of Infectious Diseases (SBI) and the Brazilian Society of Hepatology worked together to elaborate a guideline for diagnosis and treatment of hepatitis B. The document includes information regarding the population to be tested, diagnostic tools, indications of treatment, therapeutic schemes and also how to handle HBV infection in specific situations (pregnancy, children, immunosuppression, etc).Delta infection is also part of the guideline, since it is an important infection in some parts of the country.

Oral histoplasmosis in Brazil.

OBJECTIVE: We report 10 cases of histoplasmosis with oral manifestations seen in a teaching hospital in Brazil. STUDY DESIGN: This is a retrospective study of the sociodemographic, clinicopathologic, and treatment data of these cases. RESULTS: Overall, 8 of 10 cases were seropositive for human immunodeficiency virus (HIV), whereas 2 were negative. The predominant oral manifestations found in HIV-seropositive patients were ulcers, oral pain, and odynophagia; both of the HIV-seronegative patients were symptom-free. HIV infection was suspected in 7 cases because of the presence of oral lesions of histoplasmosis. Asthenia, fever, weight loss, lymphadenopathy, and hepatosplenomegaly were found only in HIV-seropositive patients. Radiographs in 3 out of 10 patients suggested pulmonary involvement. Amphotericin B was the antifungal therapy chosen, and clinical remission of oral lesions occurred in an average of 30 days (accumulated doses: 500-1500 mg). Itraconazole was very effective as a follow-up treatment in terms of prevention of recurrence. CONCLUSION: Histoplasmosis only rarely affects HIV-seronegative patients; however, the possibility of hidden immunodepression should be considered when oral manifestations of histoplasmosis are present.

[Hantaviruses]. / Hantaviroses.

Hantaviruses are zoonotic diseases that affect humans and have a worldwide distribution. The hemorrhagic fever associated with renal syndrome occurs endemically in the Asian and European continents affecting housauds of people every year. Hantavirus cardiopulmonary syndrome, recognized as a clinical entity since 1993, represents the prototype of emerging diseases and is distributed in countries of the American continent, including Brazil. Both diseases are transmitted to man through the inhalation of viral particles, which are shed in feces and urine of wild and domestic rodents. They comprise a group of febrile diseases that can affect many organs, particularly the kidneys in the hemorrhagic fever associated with renal syndrome and the lungs and heart in the hantavirus cardiopulmonary syndrome. The lethality of American hantaviroses reaches 50%. The diagnosis of these diseases is performed using serological tests such as immunoenzymatic assays which detect specific antibodies of the IgG and IgM classes. There is no specific treatment. Therefore, special attention should be directed to restore and maintain fluid balance, timely indication of dialysis for renal failure and administration of vasoactive drugs during periods of hypotension and shock. The administration of corticosteroids and/or ribavirin are under evaluation. The number of cases of hantavirus infection has been increasing in Brazil year after year, and it is important to alert health personnel to the occurrence of these entities throughout the country. Awareness of their presence should improve the quality of medical care.

[Skin diseases in patients with AIDS: study in 55 cases in Uberlândia, MG, Brazil]. / Dermatoses em pacientes com AIDS: estudo de 55 casos. Uberlândia, MG, Brasil.

UNLABELLED: Fifty-five patients with acquired immunodeficiency syndrome (AIDS) seen at the Dermatology outpatient clinic and who had mucocutaneous diseases were studied. These diseases, some of them opportunistic, are common but difficult to diagnose given the atypical features of the lesions. OBJECTIVES: The aim of this study was to analyse the frequency and clinical presentation of dermatoses related to Aids seen at the Dermatology outpatient clinic. METHODS: Fifty-five patients with Aids and mucocutaneous lesions were examined from 1995 to 1997 in a cross-sectional study carried out at the Dermatology outpatient clinic of the Universidade Federal de Uberlândia (Minas Gerais, Brazil). Biopsies and cultures were undertaken for laboratory diagnosis. RESULTS: One hundred sixteen dermatoses were diagnosed. Fungal infections (78%) were the commonest among them, followed by viral infections (40%), papulosquamous disorders (27%), papular eruptions (18%), adverse drug reactions (10%), tumors (9%) and a variety of others (7%). The majority of the patients (67%) had more than one type of skin disorder. CONCLUSIONS: In agreement with previous literature data fungal and viral infections were confirmed as the most frequent skin disorders in HIV-positive patients. Dermatological examination, laboratory tests and skin biopsy for histopathological study are necessary for appropriate diagnostic investigation of HIV-related mucocutaneous diseases considering that atypical presentation occurs in a large proportion of the patients.

Plasmodium ovale malaria in Brazil: report of an imported case with a prolonged incubation period.

We report the first case of imported Plasmodium ovale in Brazil, confirmed using both conventional microscopy and PCR-based protocols. The patient was a 36-year-old Brazilian male who had been working as a miner in Cabinda Province, Angola. Based on his travel history, the parasite was dormant for at least two years. The relatively long period of incubation of P. ovale may obscure the link between exposure and disease. The recent increase in the number of people travelling to regions where P. ovale is endemic, suggests that a PCR-based protocol should be included as a complementary tool for malaria reference laboratories.