Safety and Efficacy of Rifampin or Isoniazid Among People With Mycobacterium tuberculosis Infection and Living With Human Immunodeficiency Virus or Other Health Conditions: Post Hoc Analysis of 2 Randomized Trials.

BACKGROUND: The safety and efficacy of rifampin among people living with human immunodeficiency virus (PLHIV) or other health conditions is uncertain. We assessed completion, safety, and efficacy of 4 months of rifampin vs 9 months of isoniazid among PLHIV or other health conditions. METHODS: We conducted post hoc analysis of 2 randomized trials that included 6859 adult participants with Mycobacterium tuberculosis infection. Participants were randomized 1:1 to 10 mg/kg/d rifampin or 5 mg/kg/d isoniazid. We report completion, drug-related adverse events (AE), and active tuberculosis incidence among people living with HIV; with renal failure or receiving immunosuppressants; using drugs or with hepatitis; with diabetes mellitus; consuming >1 alcoholic drink per week or current/former smokers; and with no health condition. RESULTS: Overall, 270 (3.9%) people were living with HIV (135 receiving antiretroviral therapy), 2012 (29.3%) had another health condition, and 4577 (66.8%) had no condition. Rifampin was more often or similarly completed to isoniazid in all populations. AEs were less common with rifampin than isoniazid among PLHIV (risk difference, -2.1%; 95% confidence interval [CI], -5.9 to 1.6). This was consistent for others except people with renal failure or on immunosuppressants (2.1%; 95% CI, -7.2 to 11.3). Tuberculosis incidence was similar among people receiving rifampin or isoniazid. Among participants receiving rifampin living with HIV, incidence was comparable to those with no health condition (rate difference, 4.1 per 1000 person-years; 95% CI, -6.4 to 14.7). CONCLUSIONS: Rifampin appears to be safe and as effective as isoniazid across many populations with health conditions, including HIV. CLINICAL TRIALS REGISTRATION: NCT00170209; NCT00931736.

Knowledge about tuberculosis transmission and prevention and perceptions of health service utilization among index cases and contacts in Brazil: Understanding losses in the latent tuberculosis cascade of care.

INTRODUCTION: Tuberculosis contacts are candidates for active and latent tuberculosis infection screening and eventual treatment. However, many losses occur in the different steps of the contacts' cascade of care. Reasons for this are poorly understood. OBJECTIVE: To describe the different steps where losses in the contact cascade occur and to explore knowledge and attitudes regarding tuberculosis transmission/prevention and perceptions about tuberculosis services in order to understand the reasons for losses from the tuberculosis service users' perspective. DESIGN: We collected routine data from the index case and contact registry books and from patients' records to build the cascade of care of contacts in 12 health facilities in three Brazilian cities with high tuberculosis incidence rates. During a knowledge, attitudes and practices (KAP) survey, trained interviewers administered a semi-structured questionnaire to 138 index cases and 98 contacts. RESULTS: Most of the losses in the cascade occurred in the first two steps (contact identification, 43% and tuberculin skin testing placement, 91% of the identified contacts). Among KAP-interviewed contacts, 67% knew how tuberculosis is transmitted, 87% knew its key symptoms and 81% declared they would take preventive therapy if prescribed. Among KAP-interviewed index cases, 67% knew they could spread tuberculosis, 70% feared for the health of their families and 88% would like their family to be evaluated in the same services. CONCLUSION: Only a small proportion of contacts are evaluated for active and latent tuberculosis, despite their-and their index cases'-reasonable knowledge, positive attitudes towards prevention and satisfaction with tuberculosis services. In these services, education of service users would not be a sufficient solution. Healthcare workers' and managers' perspective, not explored in this study, may bring more light to this subject.

Shortened first-line TB treatment in Brazil: potential cost savings for patients and health services.

BACKGROUND: Shortened treatment regimens for tuberculosis are under development to improve treatment outcomes and reduce costs. We estimated potential savings from a societal perspective in Brazil following the introduction of a hypothetical four-month regimen for tuberculosis treatment. METHODS: Data were gathered in ten randomly selected health facilities in Rio de Janeiro. Health service costs were estimated using an ingredient approach. Patient costs were estimated from a questionnaire administered to 126 patients. Costs per visits and per case treated were analysed according to the type of therapy: self-administered treatment (SAT), community- and facility-directly observed treatment (community-DOT, facility-DOT). RESULTS: During the last 2 months of treatment, the largest savings could be expected for community-DOT; on average USD 17,351-18,203 and USD 43,660-45,856 (bottom-up and top-down estimates) per clinic. Savings to patients could also be expected as the median (interquartile range) patient-related costs during the two last months were USD 108 (13-291), USD 93 (36-239) and USD 11 (7-126), respectively for SAT, facility-DOT and community-DOT. CONCLUSION: Introducing a four-month regimen may result in significant cost savings for both the health service and patients, especially the poorest. In particular, a community-DOT strategy, including treatment at home, could maximise health services savings while limiting patient costs. Our cost estimates are likely to be conservative because a 4-month regimen could hypothetically increase the proportion of patients cured by reducing the number of patients defaulting and we did not include the possible cost benefits from the subsequent prevention of costs due to downstream transmission averted and rapid clinical improvement with less side effects in the last two months.

Lesões molusco-símiles em paciente com esporotricose / Molluscum-like lesions in a patient with sporotrichosis

Esporotricose é uma infecção fúngica subcutânea, adquirida por inoculação direta, causada pelo Sporothrix schenckii. Embora a apresentação clássica linfocutânea represente a maioria dos casos, as formas clínicas atípicas e graves têm aumentado em ocorrência. Esporotricose sistêmica e esporotricose cutânea disseminada são variantes raras, usualmente associadas à imunodeficiência celular ou a estados debilitantes. Relatamos o primeiro caso na literatura de lesões molusco-símiles em esporotricose cutaneomucosa múltipla. Os exames micológico direto e histopatológico apresentavam-se ricos em células leveduriformes.

Sporotrichosis is a subcutaneous fungal infection caused by Sporothrix schenckii and acquired by direct inoculation. Although the majority of cases consist of the classic lymphocutaneous presentation, the frequency of atypical and severe clinical forms of the disease has increased progressively. Systemic and disseminated cutaneous sporotrichosis constitute rare variants and such cases are generally associated with cellular immunodeficiency or debilitated states. The present paper describes the first published case of molluscum-like lesions in disseminated mucocutaneous sporotrichosis. Direct mycological examination and histopathology revealed numerous yeast cells.

Molluscum-like lesions in a patient with sporotrichosis.

Sporotrichosis is a subcutaneous fungal infection caused by Sporothrix schenckii and acquired by direct inoculation. Although the majority of cases consist of the classic lymphocutaneous presentation, the frequency of atypical and severe clinical forms of the disease has increased progressively. Systemic and disseminated cutaneous sporotrichosis constitute rare variants and such cases are generally associated with cellular immunodeficiency or debilitated states. The present paper describes the first published case of molluscum-like lesions in disseminated mucocutaneous sporotrichosis. Direct mycological examination and histopathology revealed numerous yeast cells.

Tuberculosis and gender in a priority city in the state of Rio de Janeiro, Brazil.

The objective of this study was to compare gender differences among tuberculosis patients in a city with a high incidence of tuberculosis. This was a cross-sectional questionnaire-based study involving 560 tuberculosis patients (373 males and 187 females). Sociodemographic and clinical data, as well as data related to diagnostic criteria and treatment outcome, were collected (from the questionnaires and medical records) and subsequently compared between the genders. The median time from symptom onset to diagnosis was 90 days. There were no differences between the genders regarding the clinical presentation, diagnostic criteria, previous noncompliance with treatment, time from symptom onset, number of medical appointments prior to diagnosis, or treatment outcome. Gender-specific approaches are not a priority in Brazil. However, regardless of patient gender, the delay in diagnosis is a major concern.

Tuberculose e gênero em um município prioritário no estado do Rio de Janeiro / Tuberculosis and gender in a priority city in the state of Rio de Janeiro, Brazil

O objetivo deste estudo foi comparar diferenças entre os gêneros nos pacientes com tuberculose em uma cidade com alta incidência da doença. Este foi um estudo transversal com base em questionário envolvendo 560 pacientes com tuberculose (373 homens e 187 mulheres). Características sociodemográficas e clínicas, assim como critérios diagnósticos e desfecho do tratamento, foram coletados dos questionários e fichas médicas e posteriormente comparados entre os gêneros. A mediana do tempo do surgimento de sintomas até o diagnóstico foi de 90 dias. Não foram encontradas diferenças entre os gêneros relativas à apresentação clínica, critério diagnóstico, abandono prévio de tratamento, tempo do surgimento de sintomas, número de consultas antes do diagnóstico ou desfecho do tratamento. A abordagem diferenciada para os gêneros não é uma prioridade no Brasil. A demora no diagnóstico, no entanto, é um problema maior a despeito do gênero.

The objective of this study was to compare gender differences among tuberculosis patients in a city with a high incidence of tuberculosis. This was a cross-sectional questionnaire-based study involving 560 tuberculosis patients (373 males and 187 females). Sociodemographic and clinical data, as well as data related to diagnostic criteria and treatment outcome, were collected (from the questionnaires and medical records) and subsequently compared between the genders. The median time from symptom onset to diagnosis was 90 days. There were no differences between the genders regarding the clinical presentation, diagnostic criteria, previous noncompliance with treatment, time from symptom onset, number of medical appointments prior to diagnosis, or treatment outcome. Gender-specific approaches are not a priority in Brazil. However, regardless of patient gender, the delay in diagnosis is a major concern.

Choosing incentives to stimulate tuberculosis treatment compliance in a poor county in Rio de Janeiro state, Brazil.

BACKGROUND: Tuberculosis (TB) treatment default is a major constraint of TB control, resulting in continued disease transmission and possibly the emergence of multidrug resistance. Marginalized populations may abandon treatment before being cured. The objective of this study was to evaluate the socioeconomic status (SES) of TB patients and identify potential incentives for improving treatment compliance by SES. MATERIAL AND METHODS: A cross-sectional survey was conducted in a public health unit in Duque de Caxias, a county with one of the lowest per capita incomes in Rio de Janeiro state. From November 2003 to March 2004, 305 TB patients answered an anonymous questionnaire on socio-demographic aspects, household items and family income, history of previous treatment default, and on incentives for improving treatment adherence. Incentives were classified as economic, administrative, health service support, and habits, and scored as fundamental (3), important (2), desirable (1), or irrelevant (0). RESULTS: Health service support incentives had the highest scores overall. The aggregate economic incentive score correlated with SES (r = -0.191, p = 0.001). Among the 20% poorest patients, 16.7% had a previous history of default vs. 1.6% among the wealthiest (p = 0.004). Patients with a history of treatment default were significantly more likely to choose health service support incentives than other patients (r = -0.263, p = 0.039). CONCLUSIONS: Professional commitment will be needed to effect the necessary changes in health service support. Financial support for food and transportation subsidies may be required to improve treatment compliance among the poorest TB patients, i.e. those most likely to have previously defaulted from treatment.

[A rare case of intrapulmonary fetus-in-fetu]. / Um raro caso de fetus-in-fetu intrapulmonar.

Fetus-in-fetu (FIF) is a rare pathological condition, which presents as a congenital tumor, usually in the abdomen or retroperitoneum. A few cases have been reported in the cranial cavity, cervical spine, ovarium, scrotum and liver. We presently report a case of intrapulmonary FIF in a 12-year-old girl who was on treatment for pulmonary tuberculosis and had no symptoms related to the tumor. To our knowledge this is the first reported case of FIF with pulmonary presentation.

Obitos atribuídos à tuberculose no Estado do Rio de Janeiro / Deaths attributed to tuberculosis in the State of Rio de Janeiro

INTRODUÇAO:Em 1998, o Rio de Janeiro era o estado de maior incidência e mortalidade por tuberculose do Brasil. O Sistema de Informação de Agravos de Notificação em Tuberculose (SINAN-TB-RJ) não era confiável. OBJETIVO: Utilizar o estudo dos óbitos por tuberculose como instrumento de avaliação do programa de controle de tuberculose. MÉTODO: Foram realizados estudos descritivos do SINAN-TB-RJ e do Sistema de Informação de Mortalidade em tuberculose do Rio de Janeiro (SIM-TB-RJ) e os dois bancos de dados foram cruzados utilizando-se o programa Reclink. Foi também realizado um estudo baseado em prontuários dos cinco hospitais onde ocorreu o maior número de óbitos por tuberculose. RESULTADOS: Em 1998 foram registrados no SINAN-TB-RJ 16.567 casos de tuberculose em maiores de 14 anos. A forma pulmonar estava presente em 13.989 (84,5 por cento) casos, dos quais 8.223 (56,8 por cento) tiveram baciloscopia positiva. A sorologia anti-HIV, recomendada para todos os pacientes com tuberculose, foi solicitada em apenas 4.141 (25 por cento) casos. No SIM-TB-RJ foram registrados 1.146 óbitos, dos quais 478 (41,7 por cento) casos haviam sido notificados no SINAN-TB-RJ, entre 1995 e 1998. Dos 302 prontuários estudados, em 154 (50,9 por cento) o período de internação foi inferior a 10 dias. O tempo entre o início dos sintomas e o diagnóstico foi superior a 60 dias em 143 (47,3 por cento) pacientes. Dos 125 pacientes em re-tratamento, para apenas 43 (34,4 por cento) foi prescrito o esquema RHZE recomendado pelo Ministério da Saúde. CONCLUSAO: O estudo demonstra que a tuberculose é sub-notificada, o diagnóstico é tardio, a utilização dos exames laboratoriais recomendados é baixa e as normas do Ministério da Saúde não são cumpridas.

Knowledge about STD/AIDS and sexual behavior among high school students in Rio de Janeiro, Brazil.

The incidence of AIDS and other sexually transmitted diseases (STDs) is increasing among adolescents. In order to better understand high-risk sexual behavior among students, a cross-sectional study based on a self-answered anonymous questionnaire was conducted in 10 public and private high schools in Rio de Janeiro, Brazil. Data were obtained on sociodemographics, knowledge of STD/AIDS, and sexual behavior. Among 945 students aged 13-21, 59% were sexually initiated, and the median age at first sexual intercourse was 15 years (range: 7-19). Although 94% reported being aware of the need for condom use for protection, only 34% informed always using condoms during sex. Low family income was associated with unsatisfactory knowledge (OR = 9.40; 95% CI = 6.05-14.60) and inconsistent condom use (OR = 11.60; 95% CI = 5.54-24.30). However, unsatisfactory knowledge was not associated with inconsistent condom use. School-based educational programs should focus on sexual behavior more than on transmission of knowledge, as well as targeting low-income students.

Knowledge about STD/AIDS and sexual behavior among high school students in Rio de Janeiro, Brazil

The incidence of AIDS and other sexually transmitted diseases (STDs) is increasing among adolescents. In order to better understand high-risk sexual behavior among students, a cross-sectional study based on a self-answered anonymous questionnaire was conducted in 10 public and private high schools in Rio de Janeiro, Brazil. Data were obtained on sociodemographics, knowledge of STD/AIDS, and sexual behavior. Among 945 students aged 13-21, 59 percent were sexually initiated, and the median age at first sexual intercourse was 15 years (range: 7-19). Although 94 percent reported being aware of the need for condom use for protection, only 34 percent informed always using condoms during sex. Low family income was associated with unsatisfactory knowledge (OR = 9.40; 95 percent CI = 6.05-14.60) and inconsistent condom use (OR = 11.60; 95 percent CI = 5.54-24.30). However, unsatisfactory knowledge was not associated with inconsistent condom use. School-based educational programs should focus on sexual behavior more than on transmission of knowledge, as well as targeting low-income students

Perfil de citocinas e células imunológicas em pacientes com tuberculose pleural co-infectados ou não pelo HIV / Cytokine and immune cell profile pleural tuberculosis in patients with and without HIV co-infection

Introdução: a tuberculose pleural tem uma evolução benigna, mesmo quando associada à infecção pelo HIV. Com o objetivo de compreender os mecanismos imunológicos envolvidos neste fenômeno, nós comparamos as concentrações de citocinas e subgrupos de células imunológicas no líquido e tecido pleural de pacientes com tuberculose pleural com e sem infecção pelo HIV. Material e métodos: foram incluídos 42 pacientes com o diagnóstico de tuberculose pleural dos quais 12 infectados pelo HIV. A análise imunohistoquímica do tecido pleural foi realizada em 21 pacientes utilizando os seguintes anticorpos monoclonais: anti-CD4, anti-CD8, anti-delta TCR, anti-perforina e anti-fasL. A concentração de citocinas (IL-2,IL-4, IL-10, IL-12 e IFN-) foi medida pelo método ELISA no líquido pleural de 29 pacientes. Resultados: a mediana das proporções de células CD8+ e perforina+ foi superior nos pacientes infectados pelo HIV. A proporção de células CD4+, FasL+ e delta-TCR+ foram semelhantes nos dois grupos. A IL-4 foi indetectável em todos os pacientes. Três de nove pacientes infectados pelo HIV apresentaram uma concentração de IL-2 superior a 40 pg/ml (p=0,02). Conclusões: as concentrações de IFN-, IL-10 e IL-12 foram semelhantes nos dois grupos. A citotoxicidade mediada pela perforina e a IL-2 parecem ter um papel importante na proteção contra Mycobacterium tuberculosis nos estádios iniciais da infecção pelo HIV. As células CD8+ do tecido pleural podem ser uma fonte alternativa de síntese de IFN- em pacientes com tuberculose pleural co-infectados pelo HIV.

Introduction: pleural tuberculosis (TB) has a benign course whether associated or not to HIV infection. To understand the immune mechanisms involved in this phenomenon, we compared cytokine concentrations and subsets of immune cells in the pleural fluid/tissue from patients with TB pleurisy with and without HIV co-infection. Material and methods: forty-two patients diagnosed with pleural TB were included, twelve of whom were HIV-infected. Immunohistochemical analysis of pleural tissue was performed in 21 patients with TB pleurisy with and without HIV co-infection. Material and methods: forty-two patients diagnosed with pleural TB were included, twelve of whom were HIV-infected. Immunohistochemical analysis of pleural tissue was performed in 21 patients using the following monoclonal antibodies: anti-CD4, anti CD-8, anti-delta TCR, anti-perforin and anti FasL. Cytokine (IL-2, OÇ-4, IL-10, IL-12 amd IFN-) concentration was measured by the ELISA method in the pleural fluid of 29 patients. Results: the median proportions of CD8+ and perforin + cells were higher in HIV-infected patients. The proportions of CD4+, FasL+ and delta-TCR+ cells were similar in both groups. IL-4 was undetectable in all patients. Three out of nine HIV-infected patients had IL-2 concentration ouver 40pg/ml (p=0.02). Conclusion: the concentrations of IFN-, IL-10 and IL-12 were similar in both groups. Perforin-mediated cytotoxicity and IL-2 may play an important role in protection against Mycobacterium tuberculosis in the early stages of HIV infection. Pleural CD8+ cells may be an alternative source for IFN- in HIV-infected patients with tuberculosis.

Valor diagnóstico da punçäo-biópsia pleural: experiência em um serviço de clínica médica / Efficacy of thoracentesis and pleura biopsy in the diagnosis of pleural inflamatory diseases: experience in an internal medicine ward

OBJETIVO: Avaliar o valor da punçäo-biópsia pleural no diagnóstico das doenças inflamatórias da pleura. MÉTODO: Foi feito um estudo retrospectivo de 82 toracocenteses realizadas durante um período de 42 meses em uma enfermaria de clínica médica no Rio de Janeiro. Os aspectos bioquímico, citológico e bacteriológico do líquido pleural e o exame histopatológico do fragmento pleural foram correlacionados com o diagnóstico final. A sensibilidade e os valores preditivos da concentraçäo protéica e da percentagem de linfócitos no líquido pleural foram calculados utilizando diferentes valores de corte. RESULTADOS: Dos 82 pacientes, 73 (89 por cento) tinham tuberculose. Todos os pacientes com menos de 35 anos tinham tuberculose. O valor preditivo negativo para o diagnóstico de tuberculose aumentou de 17,1 por cento para 66,7 por cento utilizando 4,5g/dL e 2,5g/dL, respectivamente, como valores de corte para a concentraçäo de protéina no líquido pleural. O valor preditivo positivo, de 94,2 por cento. A pesquisa de BAAR no líquido pleural foi negativa nas 82 amostras. A sensibilidade do exame histopatológico da pleura foi de 69,2 por cento para o diagnóstico de tuberculose. CONCLUSÄO: A tuberculose foi a causa mais comum de derrame pleural em todos as faizas etárias. O exame que mais contribuiu para confirmar este diagnóstico foi a análise histopatológica. Os autores sugerem que a punçäo pleural e a biópsia sejam realizadas simultaneamente nas populaçöes em que a tuberculose tenha alta prevalência

Testagem Anti-hiv nos pacientes com tuberculose no estado do Rio de Janeiro / Hiv screening among tuberculosis patients in Rio de Janeiro State

Introdução: Embora a identificação da infecção pelo HIV em pacientes com tuberculose tenha implicações práticas relevantes, muito destes pacientes não são testados. Nós avaliamos a frequencia da testagem para a infecção pelo HIV em pacientes com tuberculose, comparando dois períodos diferentes. Métodos: Foram estudados pacientes com tuberculose notificados a Secretaria de Estado de Saúde do Rio de Janeiro (SES-RJ). A frequência de testagem anti-HIV foi avaliada nos anos de 1996 e 1998 de acordo com: sexo, faixa etária, sítio de acometimento da tuberculose e município de atendimento. Os dados foram obtidos nos bancos de dados de tuberculose da SES-RJ. Resultados: Foram notificados 17.356 adultos (³15 anos) em 1996 e 15.175 em 1998. A porcentagem de pacientes testados foi de 22% e de 26,1% respectivamente. A probabilidade de testagem foi maior em homens (OR=1,23; IC95%:1,14-11,33 em 1996 e OR=1,49; IC95%:1,38-1,62 em 1998), na faixa etária de 20-49 anos, principalmente nas formas miliar, meníngea e ganglionar. Os pacientes atendidos no município do Rio de Janeiro tiveram uma probabilidade maior de serem testados quando comparados aos de outros municípios. Conclusão: O rastreamento da infecção pelo HIV nos pacientes com tuberculose no Rio de Janeiro permanece insatisfatório. A testagem é mais frequente quando a co-infecção é mais provável. Oferecer a testagem a todos os pacientes deve ser uma das prioridades dos programas de aids e de tuberculose.

Introduction: Althoug the identification of HIV infection in patients with tuberculosis has relevant pratical implications, in Brazil many patients with tuberculosis remain untested. We evaluated the frequency of HIV screening in patients with tuberculosis, comparing two different periods. Methods: Patients with tuberculosis reported to the Rio de Janeiro State Department of Health were studied. The frequency os HIV testing was analyzed according to: gender, are group, clinical forms of tuberculosis an county where the patients were assisted. Data were obtained on the database system of the Rio de Janeiro State Health Department. Results: A total of 17,356 adult (>15 years) tuberculosis patients were reported in 1996 and 15,175 in 1998. The percentage of tested patients was 22% and 26.1 % respectively. The probability of being tested was higher in men (OR=1.23; 95%CI:1.14-1.33 in 1996 and OR=1.49; 95%CI:1.38-1.62 in 1998), in the age group 20 to 49 years, when tuberculosis was extrapulmonary (OR=2.06; 95%CI:1.86-2.28 in 1996 and OR=1.99; 95%CI:1.79-2.22 in 1998), specially in miliary, meningeal and lymph node tuberculosis, and when patients were assisted in the county of Rio de Janeiro (capital to the state of Rio de Janeiro). Conclusions: HIV screening in tuberculosis patients in Rio de Janeiro remains unsatisfactory. Testing is more frequent in when HIV co-infection is more likely. To offer testing and counseling to all tuberculosis patients should be one of the priorities of both AIDS and tuberculosis programs.

Clinical patterns of diarrhea in AIDS: a retrospective study at the Federal University Hospital, Rio de Janeiro

Three hundred and fifty two medical records of AIDS inpatients were analysed in a retrospective study to establish the frequency, clinical patterns and etiology of AIDS-related diarrhea. Diarrhea was observed in 58.8 per cent of the patients, being a chronic symptom in 65.7 per cent, and the first complaint in 24.6 per cent. The most common cause of diarrhea was coccidea and the etiology remained unknown in 56.1 per cent of the patients. Routine stool examination was the most sensitive method in the diagnosis of diarrhea. In countries with limited resources, the use of stool examinations seems to provide appropriate clinical management. The implementation of an objective protocol could improve the etiologic diagnosis of AIDS-related diarrhea without the burden of more complex and invasive technologies.