Antivirais incorporados no Brasil para hepatite B cronica: analise de custo-efetividade

OBJETIVO Avaliar o custo-efetividade de diferentes tratamentos medicamentosos para hepatite B crônica entre pacientes adultos. MÉTODOS Utilizando modelo de Markov, construiu-se coorte hipotética de 40 anos para pacientes HBeAg-positivo ou HBeAg-negativo. Foram comparados os usos de adefovir, entecavir, tenofovir e lamivudina (com terapia de resgate em caso de resistência viral) para tratamento de pacientes adultos com hepatite B crônica, virgens de tratamento, com elevados níveis de alanina aminotransferase, sem evidência de cirrose e sem coinfecção por HIV. Valores para custo e efeito foram obtidos da literatura. A medida do efeito foi expressa em anos de vida ganhos (AVG). Taxa de desconto de 5% foi aplicada. Análise de sensibilidade univariada foi conduzida para avaliar incertezas do modelo. RESULTADOS O tratamento inicial com entecavir ou tenofovir apresentou melhores resultados clínicos. As menores razões custo-efetividade foram de entecavir para pacientes HBeAg-positivo (R$ 4.010,84/AVG) e lamivudina para pacientes HBeAg-negativo (R$ 6.205,08/AVG). Para pacientes HBeAg-negativo, a razão custo-efetividade incremental de entecavir (R$ 14.101,05/AVG) está abaixo do limiar recomendado pela Organização Mundial da Saúde. Análise de sensibilidade mostrou que variação nos custos dos medicamentos pode tornar tenofovir alternativa custo-efetiva tanto para pacientes HBeAg-positivo quanto para HBeAg-negativo. CONCLUSÕES Entecavir é alternativa recomendada para iniciar o tratamento de pacientes com hepatite B crônica no Brasil. Contudo, se houver redução no custo de tenofovir, esta pode se tornar alternativa mais custo-efetiva.

Associação da rifampicina à anfotericina B no tratamento da paracoccidioidomicose: resultados em três pacientes tratados

Trabalhos experimentais demonstraram que a anfotericina B, desorganizando funcionalmente a membrana celular fúngica, permite a penetração da rifampicina no citoplasma e sua conseqüente ação contra Histoplasma capsulatum, Blastomyces dermatitidis e Candida albicans. Com metade das doses habituais' de anfotericina B associada à rifampicina conseguem-se melhores resultados do que com a anfotericina B isoladamente em doses plenas. Os Autores discutem as possíveis aplicações desta associação no tratamento da paracoccidioidomi-cose e apresentam 3 casos desta micose em que a inatividade clínica e micológica só foi obtida após o emprego combinado destas drogas.

Aspectos clínicos e sorológicos de 47 pacientes com paracoccidioidomicose tratados pela anfotericina B

In the present study, clinic and serologic aspects of 47 paracoccidioidomycosis patients were reviewed. The clinic-radiologie-laboratorial data of each patient were obtained from the medical chart before, during and after therapy with Amphotericin B. The age of the patients ranged between 13 to 50 years; the ratio male: female was 10:1. The most frequently associated diseases were alcoholism and tabagism; tuberculosis was present in 14.2% of the cases. Most patients came from Botucatu of adjacent towns (central area of the State of São Paulo). Cough with sputum production, dyspnea and anorexia were the most frequent clinic manifestations. All 47 patients, but 5 presented pulmonary involvement which showed the radiologic pattern of interstitial exudate nodular type and fibrocicatritial lesions in 85.7%. There was associated emphysema in 37.7% of the patients. Blood urea, creatinin and kaliemia increased during therapy with Amphotericin B. Clinic-laboratorial follow-up showed electrocardiographic changes in 13, hypertension in 9 and hyperreactivity in Thorn test in 1 patient. Complement fixation was the best serologic test for monitoring patients with paracoccidioidomycosis. Incomplete dosage of Amphotericin B led to therapeutic ineffectivenes.

Acute Hepatitis B in a patient previously positive for antibody to surface antigen (anti-HBs) determined by radioimmunoassay: case report and review of the literature

The determination of anti-HBs as a screening test before vaccination has been advisable in order to encounter immune individuals that don't need to receive vaccine protection. A case-report is presented and three other cases are reviewed from the literature. Anti-HBs was positive in these health-care personnels that developped typical acute B hepatitis. Different subtyping involving the d/y determinants were found in the first case, but false-positive anti-HBs even with high titres, determined by RIA, were found in the other cases. Concomitant determination of anti-HBc or absence of screening tests seem to be more reasonable policies until a low-cost and risk-free vaccine is produced.

Paracoccidioidomicose subaguda progressiva: tratamento de um doente com anfotericina B e nutrição parenteral

Os Autores descrevem um caso de paracoccidioidomicose subaguda progressiva, com quadro clínico sugestivo de síndrome de má absorção, em que o doente não se beneficiara apenas com o tratamento antifúngico convencional. Ao se introduzir como medida auxiliar a nutrição parenteral houve evidente melhora clínica e laboratorial. Desta maneira os Autores propõe o uso associado da nutrição parenteral no tratamento de doentes com esta forma clínica de paracoccidioidomicose.

Efeito da talidomida sobre os níveis séricos de imunoglobulinas IgM e IgA, fator reumatóide e isohemaglutinina anti-A e anti-B em pacientes com lepra lepromatosa: um estudo duplo-cego

Um estudo duplo-cego foi conduzido em pacientes portadores de lepra lepromatosa estável, para avaliar a resposta à administração de talidomida 100 mg por dia, por 18 dias, dos níveis séricos de IgM e IgA e dos títulos de fator reumatóide e isohemaglutininas anti-A e anti-B. Nenhum efeito significativo foi detectado ao fim deste período.

Delayed results of treatment of paracoccidioidomycosis with amphotericin B plus sulfamides versus amphotericin B alone

A delayed evaluation of two groups of patients with paracoccidioidomycosis was carried out. Both groups were treated with amphotericin B, "but one of them was submitted to maintenance treatment with sulfonamides. Statistical analysis showed that treatment is more effective when patients are maintained with sulfonamide drugs.

Prevalence of antibody to hepatitis B virus in an urban population of northeast Brazil

A sample of 1,288 inhabitants of Salvador, Bahia, Brazil, were submitted to the determination of anti-HBs using radioimmunoassay procedure, and analysed according to age, sex and income. Overall prevalence of anti-HBs was 11,8%. ranging from 6,7% among children aged less than three years old to 26,1% among those aged 30 years and older. Males presented prevalence of anti-HBs similar to female individuals, and those with a higher income showed frequencies of anti-HBs greater than those with a lower income level. The following conclusions were drawn: The high prevalence of anti-HBs observed among children suggests early contact with hepatitis B virus, possibly due to vertical transmission and intrafamiliar dissemination of the disease; the frequency of anti-HBs increases with age; the lower prevalence of anti-HBs among those with low income suggests that this group may present higher prevalence of carriers of the hepatitis B virus surface antigen.

Suscetibilidade de biomphalaria glabrata, B. straminea e B. tenagophila a diferentes cepas de schistosoma mansoni

Em condições experimentais foi estudada a suscetibilidade de Biomphalaria glabrata, B. straminea e B. tenagophila a quatro linhagens humanas (MAP, PTH, UPH, e OuH) e duas de roedores silvestres (PTR e VPR) do Schistosoma mansoni. Grupos de 50 moluscos foram expostos individualmente a 10 miracídios e observados durante 70 dias. Avaliou-se a suscetibilidade dos moluscos ao parasito por meio da % de animais com esporocistos, % de moluscos que eliminavam cercárias e mortalidade conjunta dos animais expostos e infectados. Exemplares de B. glabrata mineira infectaram-se com cepa simpátrica (MAP) e com 5 alopátricas do Estado de São Paulo (PTH, VPH, OuH, PTR e VPR). B. glabrata paulista mostrou altas taxas de infecção com as cepas MAP, VPR e OuH do trematódeo. Quatro % dos exemplares B. straminea de São Paulo eliminavam cercárias de cepas simpátricas; com cepa mineira apenas 4% apresentaram esporocistos na vigência de 20 miracídios por molusco; as menores taxas de mortalidade foram registradas com essa espécie de molusco, não sendo maior do que 20%. B. tenagophila paulista foi suscetível apenas às linhagens simpáticas sendo 6% a maior taxa de moluscos que eliminaram cercárias. Os resultados indicam que os movimentos populacionais humanos dentro do território paulista e para fora dele são importantes na disseminação da esquistossomose mansônica.

Seroepidemiology of hepatitis a and b in two urban communities of Rio de Janeiro, Brazil

Hepatitis B markers were determined in 397 individuals from Niterói and 680 from Nova Iguaçu and prevalences of 9.1% (1.0% of HBsAg and 8.1% of anti HBs) and 11.1% (1.8% of HBsAg and 9.3% of antiHBs) were found, respectively. The comparative prevalence of both markers in relation to age showed a higher prevalence of HBsAg in the group 21-50 years old. Considering the antiHBs antibody, it was demostrated a gradual increase with age, reaching 14.9% in Niterói and 29.1% in Nova Iguaçu in individuals over 51 years old. For hepatitis A, in 259 samples from Niterói, equally distributed by age groups, an overall prevalence of 74.5% of anti-HAV antibodies was found. This prevalence increases gradually reaching 90.0% at age over thirty. In 254 samples from Nova Iguaçu analysed, a prevalence of 90.5% of antibodies was encountered when the same criteria of distribution of samples were used. This level of prevalence reached 90.0% already in the age over ten years old. The tests were performed by enzyme immunoassay with reagents prepared in our laboratory.

Radiometric detection of metabolic activity of Paracoccidioides brasiliensis and its susceptibility to amphotericin B and diethylstilbestrol

Paracoccidioidomycosis (South American blastomycosis) is a systemic disease, strikingly more frequent in males, caused by the dimorphic fungus Paracoccidioides brasiliensis. A radiometric assay system has been applied to study the metabolic activity and the effect of drugs on this fungus "in vitro". The Y form of the yeast, grown in liquid Sabouraud medium was inoculated into sterile reaction vials containing the 6B aerobic medium along with 2.0 μCi of 14C-substrates. Control vials, prepared in the same way, contained autoclaved fungi. To study the effects of amphotericin B (AB) (0.1 and 10 μg/ml) and diethylstilbestrol (DSB) (1.0, 5.0 and 10 μg/ml) extra controls with live fungi and no drug were used. All vials were incubated at 35°C and metabolism measured daily with a Bactec instrument. 14CO2 production by P. brasiliensis was slow and could be followed for as long as 50 days. AB at 10mg/ml and DSB at 5 μg/ml inhibited the metabolism and had a cidal effect on this fungus. The results with DSB might explain the low incidence of the disease in females. This technique shows promise for studying metabolic pathways, investi gating more convenient 14C-substrates to expedite radiometric detection and for monitoring the effects of other drugs and factors on the metabolism of P. brasiliensis "in vitro".

Antibody response to heat-inactivated hepatitis B vaccine (CLB-3mg) in hemodialysis patients and occupational risk personnel: a one year follow-up

Immune response against hepatitis B vaccine (CLB 3mg) was evaluated in 59 hemodialysis patients and 20 occupational risk personnel. Seroconversion was induced in 52.5% and 70.0% respectively. Twelve months after the first dose, 37.5% of patients and 60.0% of occupational risk personnel had detectable anti-HBs level. Antibody level was expressed in sample ratio units (SRU). Considering only the responders, in the patients group 38.7% had a low anti-HBs response (2.1-9.9 SRU) 32.3% a medium response (10-99.9 SRU) and 29.0% a high response (>100 SRU) while in occupational risk personnel these values were 14.3%, 64.3% and 21.4% respectively. The authors suggest the use of HBV vaccines with more elevated HBsAg concentration or a reinforced immunization schedule to improve the anti-HBs response not only for patients but also for healthy persons.

Active immunization against hepatitis B virus (HBV) with low-doses of plasma-derived vaccine by intradermal route

Schedule for vaccination against HBV infection has usually been based on three separate injections of 20 meg of the vaccine by intramuscular route. One of the main shortcomings to its use in large scale programs has been its high cost. Ninety out of 300 health workers were submitted to three injections of 2 meg of plasma-derived vaccine (PDV) by intradermal (ID) route on days 0, 30, and 180. Anti-HBs was detected in 74 (82.2%) after the second dose and in 80 (88.9%) after the third dose, a non-significant difference. However, levels above 10 times the cut-off were observed in 29 (32.2%) and 77 (85.5%), respectively (p < 0.001). The results showed that a low-dose schedule is effective when used in health workers and should be tried with other risk groups.