Long-term survival and cause-specific mortality of patients newly diagnosed with tuberculosis in São Paulo state, Brazil, 2010-15: a population-based, longitudinal study.

BACKGROUND: Long-term survival and cause-specific mortality of patients who start tuberculosis treatment is rarely described. We aimed to assess the long-term survival of these patients and evaluate the association between vulnerable conditions (social, health behaviours, and comorbidities) and cause-specific mortality in a country with a high burden of tuberculosis. METHODS: In this population-based, longitudinal study in São Paulo state, Brazil, we described the 5-year survival of patients who were newly diagnosed with tuberculosis in 2010. We included patients with newly-diagnosed tuberculosis, aged 15 years or older, and notified to the São Paulo State Tuberculosis Program in 2010. We excluded patients whose diagnosis had changed during follow-up (ie, they did not have tuberculosis) and patients who had multidrug-resistant (MDR) tuberculosis. We selected our population with tuberculosis from the dedicated electronic system TBweb. Our primary objective was to estimate the excess mortality over 5 years and within the group who survived the first year, compared with the general São Paulo state population. We also estimated the association between social vulnerability (imprisonment and homelessness), health behaviours (alcohol and drug use), and comorbidities (diabetes and mental disorders) with all-cause and cause-specific mortality. We used the competing risk analysis framework, estimating cause-specific hazard ratios (HRs) adjusted for potential confounding factors. FINDINGS: In 2010, there were 19 252 notifications of tuberculosis cases. We excluded 550 cases as patients were younger than 15 years, 556 cases that were not tuberculosis, 2597 retreatments, and 48 cases of MDR tuberculosis, resulting in a final cohort of 15 501 patients with tuberculosis. Over a period of 5 years from tuberculosis diagnosis, 2660 (17%) of 15 501 patients died. Compared with the source population, matched by age, sex, and calendar year, the standardised mortality ratio was 6·47 (95% CI 6·22-6·73) over 5 years and 3·93 (3·71-4·17) among those who survived the first year. 1197 (45%) of 2660 deaths were due to infection. Homelessness and alcohol and drug use were associated with death from infection (adjusted cause-specific HR 1·60, 95% CI 1·39-1·85), cardiovascular (1·43, 1·06-1·95), and external or ill-defined causes of death (1·80, 1·37-2·36). Diabetes was associated with deaths from cardiovascular causes (1·70, 1·23-2·35). INTERPRETATION: Patients newly diagnosed with tuberculosis were at a higher risk of death than were the source population, even after tuberculosis treatment. Post-tuberculosis sequelae and vulnerability are associated with excess mortality and must be addressed to mitigate the tuberculosis burden worldwide. FUNDING: Wellcome Trust.

Comparison of clinical tools for dengue diagnosis in a pediatric population-based cohort.

BACKGROUND: We aimed to estimate and compare the ability of clinical tools for dengue diagnosis in a pediatric population. METHODS: We prospectively evaluated episodes of acute febrile syndrome identified during the follow-up of a population-based cohort of children and adolescents residing in a dengue endemic city. We estimated the area under the receiver operating characteristic curve (AU-ROC) for dengue diagnosis of three clinical tools: the summation of manifestations of the WHO case definition, a predefined clinical scale and a logistic regression model obtained in this study. RESULTS: We compared 219 dengue cases (confirmed by laboratory) and 286 patients with other febrile illnesses. In a multiple model, variables independently associated with dengue included the duration of fever, sleepiness and exanthema. Rhinorrhea, cough and minimal leukocyte count were inversely associated with dengue. This model reached an accuracy of 84.2% (for a cut-off of >0.5, sensitivity: 79.5%, specificity: 87.9%, positive predictive value: 83.7%, negative predictive value: 84.6%). The AU-ROC of this model (89.8%) was significantly higher than that obtained with either the predefined scale (82.1%) or the WHO definition manifestations (77%). CONCLUSION: We validated a predefined scale and identified a multiple model suitable for the clinical diagnosis of dengue in the pediatric population.

Long-term survival and cause-specific mortality of patients newly diagnosed with tuberculosis in São Paulo state, Brazil, 2010­15: a population-based, longitudinal study

Background Long-term survival and cause-specific mortality of patients who start tuberculosis treatment is rarely described. We aimed to assess the long-term survival of these patients and evaluate the association between vulnerable conditions (social, health behaviours, and comorbidities) and cause-specific mortality in a country with a high burden of tuberculosis. Methods In this population-based, longitudinal study in São Paulo state, Brazil, we described the 5-year survival of patients who were newly diagnosed with tuberculosis in 2010. We included patients with newly-diagnosed tuberculosis, aged 15 years or older, and notified to the São Paulo State Tuberculosis Program in 2010. We excluded patients whose diagnosis had changed during follow-up (ie, they did not have tuberculosis) and patients who had multidrug-resistant (MDR) tuberculosis. We selected our population with tuberculosis from the dedicated electronic system TBweb. Our primary objective was to estimate the excess mortality over 5 years and within the group who survived the first year, compared with the general São Paulo state population. We also estimated the association between social vulnerability (imprisonment and homelessness), health behaviours (alcohol and drug use), and comorbidities (diabetes and mental disorders) with all-cause and cause-specific mortality. We used the competing risk analysis framework, estimating cause-specific hazard ratios (HRs) adjusted for potential confounding factors. Findings In 2010, there were 19 252 notifications of tuberculosis cases. We excluded 550 cases as patients were younger than 15 years, 556 cases that were not tuberculosis, 2597 retreatments, and 48 cases of MDR tuberculosis, resulting in a final cohort of 15 501 patients with tuberculosis. Over a period of 5 years from tuberculosis diagnosis, 2660 (17%) of 15 501 patients died. Compared with the source population, matched by age, sex, and calendar year, the standardised mortality ratio was 6·47 (95% CI 6·22­6·73) over 5 years and 3·93 (3·71­4·17) among those who survived the first year. 1197 (45%) of 2660 deaths were due to infection. Homelessness and alcohol and drug use were associated with death from infection (adjusted cause-specific HR 1·60, 95% CI 1·39­1·85), cardiovascular (1·43, 1·06­1·95), and external or ill-defined causes of death (1·80, 1·37­2·36). Diabetes was associated with deaths from cardiovascular causes (1·70, 1·23­2·35). Interpretation Patients newly diagnosed with tuberculosis were at a higher risk of death than were the source population, even after tuberculosis treatment. Post-tuberculosis sequelae and vulnerability are associated with excess mortality and must be addressed to mitigate the tuberculosis burden worldwide.

Estimating the impact of tuberculosis anatomical classification on treatment outcomes: A patient and surveillance perspective analysis.

INTRODUCTION: Tuberculosis anatomical classification is inconsistent in the literature, which limits current tuberculosis knowledge and control. We aimed to evaluate whether tuberculosis classification impacts on treatment outcomes at patient and aggregate level. METHODS: We analyzed adults from São Paulo State, Brazil with newly diagnosed tuberculosis from 2010-2013. We used an extended clinical classification of tuberculosis, categorizing cases as pulmonary, pulmonary and extrapulmonary, extrapulmonary and miliary/disseminated. Our primary outcome was unsuccessful outcome of treatment. To investigate the reported treatment outcome at the aggregate level, we sampled 500 different "countries" from the dataset and compared the impact of pulmonary and extrapulmonary classifications on the reported treatment success. RESULTS: Of 62,178 patients, 49,999 (80.4%) were pulmonary, 9,026 (14.5%) extrapulmonary, 1,651 (2.7%) pulmonary-extrapulmonary and 1,502 (2.4%) miliary/disseminated. Pulmonary-extrapulmonary cases had similar unsuccessful outcome of treatment compared with pulmonary (adjusted-OR 1.00, 95%CI, 0.88-1.13, p = 0.941), while extrapulmonary were associated with better (adjusted-OR 0.65, 95%CI, 0.60-0.71, p<0.001) and miliary/disseminated with worse outcomes (adjusted-OR 1.51, 95%CI, 1.33-1.71, p<0.001). We found that 60 (12%) countries would report a difference ≥10% in treatment success depending on whether they reported all clinical forms together (current WHO recommendation) or pulmonary forms alone, overestimating the treatment success of pulmonary forms. CONCLUSIONS: The expanded anatomical classification of tuberculosis was strongly associated with treatment outcomes at the patient level. Remarkably, pulmonary with concomitant extrapulmonary forms had similar treatment outcomes compared with pulmonary forms after adjustment for potential confounders. At the aggregate level, reporting treatment success for all clinical forms together might hide differences in progress between pulmonary and extrapulmonary tuberculosis control.

The impact of being homeless on the unsuccessful outcome of treatment of pulmonary TB in São Paulo State, Brazil.

BACKGROUND: Tuberculosis (TB) is a major public health problem requiring complex treatment, the success of which depends on biological, social, and institutional factors. São Paulo State (SPS), in Brazil, has a high TB burden. Because of high socioeconomic heterogeneity and chaotic urbanisation, homelessness might play an important role in the TB burden in SPS. Our aim was to determine the association between homelessness and outcome of treatment of pulmonary TB (PTB) in SPS. METHODS: A historical cohort from the routine SPS TB database for 2009-2013 was analysed. The study population was newly diagnosed adult patients with PTB. Homelessness was ascertained at notification or when treatment started. Our outcome was unsuccessful outcome of treatment. We used logistic regression to adjust for potential confounders and multiple imputation for missing data. RESULTS: We analysed 61,817 patients; 1726 (2.8 %, 95%CI 2.7-2.9 %) were homeless. Homeless patients were concentrated in bigger cities, were more frequently middle-aged males, had black/brown skin colour, and had received less education (P < 0.001, for all). Alcohol and drug use was three times more frequent in homeless patients (43.2 % vs 14.4 %, 30.2 % vs. 9.4 %, P < 0.001, respectively). HIV testing was less common among the homeless, of whom 17.3 % were HIV positive compared with 8.5 % among the not homeless population (P < 0.001). Microbiologic confirmation was more frequent among the homeless (91.6 % vs. 84.8 %, P < 0.001). Unsuccessful outcome of treatment was 57.3 % among the homeless and 17.5 % among the not homeless (OR = 6.32, 95%CI 5.73-6.97, P < 0.001), mainly due to loss to follow-up (39 %) and death (10.5 %). After full-adjustment for potential confounders, homelessness remained strongly associated with lower treatment success (aOR = 4.96, 95 % CI 4.27-5.76, P < 0.001). HIV status interacted with homelessness: among HIV-infected patients, the aOR was 2.45 (95%CI 1.90-3.16, Pinteraction < 0.001). The population attributable fraction for the joint effect of homelessness, alcohol and drug use was almost 20 %. CONCLUSIONS: Confirming our hypothesis, homelessness led to a marked reduction in the successful treatment of newly diagnosed pulmonary tuberculosis. Homelessness and associated conditions were important contributors to lack of treatment success in pulmonary tuberculosis in São Paulo. A multifaceted intervention must be implemented to target this vulnerable population.

Serodiagnosis as adjunct assay for pertussis infection in São Paulo, Brazil.

Pertussis remains an important public health problem in many countries despite extensive immunization. Cultures and real-time PCR (RT-PCR) assays are the recommended pertussis diagnostic tests, but they lack sensitivity at the later stage of the disease. This study introduces the IgG anti-pertussis toxin enzyme-linked immunosorbent assay (PT ELISA) in our routine diagnosis to improve disease burden estimation. Serum samples and nasopharyngeal swabs (n = 503) were collected at the same time from patients presenting with cough illness suspected of being pertussis and tested by the PT ELISA and culture and/or RT-PCR, respectively. Patients were separated into three age groups: group 1, <1 year (n = 260; mean age, 3 months), group 2, 1 to 6 years (n = 81; mean age, 3 years), and group 3, ≥7 years (n = 162; mean age, 26 years). The times (means) from cough onset to specimen collection were 16, 24, and 26 days, respectively. In group 1, 83 (82.2%) of 101 positive cases were positive for pertussis by culture/RT-PCR, while 40 (39.6%) tested positive by PT ELISA. In group 2, 6 (19.4%) of 31 positive cases were culture/RT-PCR positive, and 29 (93.6%) were seropositive. In group 3, 13 (13.8%) of 94 positive cases were positive by culture/RT-PCR and 91 (96.8%) were positive by serology. Culture/RT-PCR detected more cases of pertussis in infants (P < 0.0001), whereas the PT ELISA detected more cases in adolescents and adults (P < 0.0001). The timing between cough onset and specimen collection or recent vaccination may have partially affected our results. Serology is a suitable, cost-effective, and complementary pertussis diagnostic tool, especially among older children, adolescents, and adults during the later disease phase.

Equity in health: tuberculosis in the Bolivian immigrant community of São Paulo, Brazil.

OBJECTIVES: To analyse the profile of tuberculosis (TB) among Bolivian immigrants, investigate the impact that this population has on the trends of TB and assess equity in access to TB treatment, in the city of São Paulo, Brazil. METHODS: Descriptive study of the epidemiological profile of TB in four city districts with large Bolivian populations, comparing cases among Brazilians and Bolivians, during the 1998-2008 period was carried out. We used logistic regression to adjust the treatment outcome for potential confounders. RESULTS: We identified 2056 new TB cases: 65.7% in Brazilians, 32.1% in Bolivians and 2.2% among other nationalities. Although TB incidence remained stable (high) over the study period, the annual proportion of cases among Bolivians increased from 15.0% to 53.0%. In comparison with the Brazilians, the Bolivians were younger (median age, 24 vs. 40 years; P < 0.0001) and presented a lower unemployment rate (3.1%vs. 11.6%; P < 0.0001), a lower rate of HIV co-infection (1.5%vs. 28.5%; P< 0.001), a higher proportion of individuals receiving supervised treatment (81.5%vs. 62.0%; P < 0.0001) and a higher proportion of cures (71.6%vs. 63.2%; P< 0.0001). After having been adjusted for potential confounder, cure after treatment was not associated with nationality. CONCLUSIONS: Bolivian immigrants influenced the incidence but not the trends of TB among Brazilians in the study area. We found no significant differences between Bolivians and Brazilians regarding healthcare access or treatment outcome. Guaranteed universal health care access for all, including undocumented individuals, contributes to health equity. Specific intervention strategies are warranted for immigrants with tuberculosis.

Incorporation of real-time PCR into routine public health surveillance of culture negative bacterial meningitis in São Paulo, Brazil.

Real-time (RT)-PCR increases diagnostic yield for bacterial meningitis and is ideal for incorporation into routine surveillance in a developing country. We validated a multiplex RT-PCR assay for Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae in Brazil. Risk factors for being culture-negative, RT-PCR positive were determined. The sensitivity of RT-PCR in cerebrospinal fluid (CSF) was 100% (95% confidence limits, 96.0%-100%) for N. meningitidis, 97.8% (85.5%-99.9%) for S. pneumoniae, and 66.7% (9.4%-99.2%) for H. influenzae. Specificity ranged from 98.9% to 100%. Addition of RT-PCR to routine microbiologic methods increased the yield for detection of S. pneumoniae, N. meningitidis, and H. influenzae cases by 52%, 85%, and 20%, respectively. The main risk factor for being culture negative and RT-PCR positive was presence of antibiotic in CSF (odds ratio 12.2, 95% CI 5.9-25.0). RT-PCR using CSF was highly sensitive and specific and substantially added to measures of meningitis disease burden when incorporated into routine public health surveillance in Brazil.

Incorporation of real-time PCR into routine public health Surveillance of culture negative bacterial meningitis in Sao Paulo, Brazil

Real-time (RT)-PCR increases diagnostic yield for bacterial meningitis and is ideal for incorporation into routine surveillance in a developing country. We validated a multiplex RT-PCR assay for Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae in Brazil. Risk factors for being culture-negative, RT-PCR positive were determined. The sensitivity of RT-PCR in cerebrospinal fluid (CSF) was 100% (95% confidence limits, 96.0%–100%) for N. meningitidis, 97.8% (85.5%–99.9%) for S. pneumoniae, and 66.7% (9.4%–99.2%) for H. influenzae. Specificity ranged from 98.9% to 100%. Addition of RT-PCR to routine microbiologic methods increased the yield for detection of S. pneumoniae, N. meningitidis, and H. influenzae cases by52%, 85%, and 20%, respectively. The main risk factor for being culture negative and RT-PCR positive was presence of antibiotic in CSF (odds ratio 12.2, 95% CI 5.9-25.0). RT-PCR using CSF was highly sensitive and specific and substantially added to measures of meningitis disease burden when incorporated into routine public health surveillance in Brazil

Tendência temporal e desigualdades na mortalidade por diarreias em menores de 5 anos / Temporal trends and inequality in under-5 mortality from diarrhea

Objetivo: Analisar a tendência da mortalidade por diarreia entre menores de 5 anos, no município de Osasco (SP), entre 1980 e 2000. Métodos: Trata-se de estudo observacional com dois delineamentos. Um descritivo, que toma o indivíduo como unidade do estudo, e outro ecológico, analisando agregado populacional que incluiu análise de séries temporais. A fonte de dados foi o sistema de informação de mortalidade do Estado de São Paulo e censos de 1980, 1991 e 2000. Descreveu-se a variação sazonal e para a análise de tendência aplicaram-se modelos log lineares de regressão polinomiais, utilizando-se variáveis sociodemográficas da criança e da mãe. Foram analisadas a evolução de indicadores sociodemográficos do município de 1980 a 2000, as taxas médias de mortalidade por diarreia nos menores de 5 anos e seus diferenciais por distrito nos anos 90. Resultados: Dos 1.360 óbitos, 94,3 e 75,3% atingiram, respectivamente, menores de 1 ano e de 6 meses. O declínio da mortalidade foi de 98,3%, com deslocamento da sazonalidade do verão para o outono. A mediana da idade elevou-se de 2 meses nos primeiros períodos para 3 meses no último. O resíduo de óbitos manteve-se entre filhos de mães de 20 a 29 anos e escolaridade < 8 anos. O risco relativo entre o distrito mais atingido e a taxa média do município diminuiu de 3,4 para 1,3 do primeiro para o segundo quinquénio dos anos 90. Conclusão: Nossos resultados apontam uma elevação da idade mais vulnerável e a provável mudança do agente mais frequentemente associado ao óbito por diarreia.

Objective: To analyze the trend in mortality due to diarrhea among children under 5 in the town of Osasco (SP), Brazil, between 1980 and 2000. Methods: This is a descriptive observational study with two different designs, the first using individuais as the unit of study, and the other ecológica!, using groups of individuais as units of observation and including time series analysis. Data were obtained from the state of São Paulo information system of deaths and the results of the 1980, 1991 and 2000 censuses. Seasonal variations were described and log linear polynomial regres sion models were employed to analyze trends, using the sociodemographic characteristies of mothers and their children. Analyses were carried out of the changes in the town's sociodemographic indicators from 1980 to 2000, the average mortality rates among under-5s due to diarrhea and the differences between districts during the 1990s. Results: There were a total of 1,360 deaths, 94.3% of which were before 1 year of age and 75.3% of which were before 6 months. There was a 98.3% reduction in mortality and the period of peak mortality shifted from summer to autumn/fall. The median age at death increased from 2 months at the first three quinquenium of study to 3 months at the last. The residual deaths were among the children of mothers aged 20 to 29 years and of mothers who had spent less than 8 years in education. The relative risk between the worst-affected district and the average rate for the townreduced from 3.4 to 1.3 from the first 5 years of the 1990s to the second half of the decade. Conclusions: Our results demonstrate an increase in the age of greatest vulnerability and indicate that it is probable that the agent most often linked with mortality due to diarrhea has changed.

Tendência temporal e desigualdades na mortalidade por diarreias em menores de 5 anos / Temporal trends and inequality in under-5 mortality from diarrhea

OBJETIVO: Analisar a tendência da mortalidade por diarreia entre menores de 5 anos, no município de Osasco (SP), entre 1980 e 2000. MÉTODOS: Trata-se de estudo observacional com dois delineamentos. Um descritivo, que toma o indivíduo como unidade do estudo, e outro ecológico, analisando agregado populacional que incluiu análise de séries temporais. A fonte de dados foi o sistema de informação de mortalidade do Estado de São Paulo e censos de 1980, 1991 e 2000. Descreveu-se a variação sazonal e para a análise de tendência aplicaram-se modelos log lineares de regressão polinomiais, utilizando-se variáveis sociodemográficas da criança e da mãe. Foram analisadas a evolução de indicadores sociodemográficos do município de 1980 a 2000, as taxas médias de mortalidade por diarreia nos menores de 5 anos e seus diferenciais por distrito nos anos 90. RESULTADOS: Dos 1.360 óbitos, 94,3 e 75,3 por cento atingiram, respectivamente, menores de 1 ano e de 6 meses. O declínio da mortalidade foi de 98,3 por cento, com deslocamento da sazonalidade do verão para o outono. A mediana da idade elevou-se de 2 meses nos primeiros períodos para 3 meses no último. O resíduo de óbitos manteve-se entre filhos de mães de 20 a 29 anos e escolaridade < 8 anos. O risco relativo entre o distrito mais atingido e a taxa média do município diminuiu de 3,4 para 1,3 do primeiro para o segundo quinquênio dos anos 90. CONCLUSÃO: Nossos resultados apontam uma elevação da idade mais vulnerável e a provável mudança do agente mais frequentemente associado ao óbito por diarreia.

OBJECTIVE: To analyze the trend in mortality due to diarrhea among children under 5 in the town of Osasco (SP), Brazil, between 1980 and 2000. METHODS: This is a descriptive observational study with two different designs, the first using individuals as the unit of study, and the other ecological, using groups of individuals as units of observation and including time series analysis. Data were obtained from the state of São Paulo information system of deaths and the results of the 1980, 1991 and 2000 censuses. Seasonal variations were described and log linear polynomial regression models were employed to analyze trends, using the sociodemographic characteristics of mothers and their children. Analyses were carried out of the changes in the town's sociodemographic indicators from 1980 to 2000, the average mortality rates among under-5s due to diarrhea and the differences between districts during the 1990s. RESULTS: There were a total of 1,360 deaths, 94.3 percent of which were before 1 year of age and 75.3 percent of which were before 6 months. There was a 98.3 percent reduction in mortality and the period of peak mortality shifted from summer to autumn/fall. The median age at death increased from 2 months at the first three quinquenium of study to 3 months at the last. The residual deaths were among the children of mothers aged 20 to 29 years and of mothers who had spent less than 8 years in education. The relative risk between the worst-affected district and the average rate for the town reduced from 3.4 to 1.3 from the first 5 years of the 1990s to the second half of the decade. CONCLUSIONS: Our results demonstrate an increase in the age of greatest vulnerability and indicate that it is probable that the agent most often linked with mortality due to diarrhea has changed.

Temporal trends and inequality in under-5 mortality from diarrhea.

OBJECTIVE: To analyze the trend in mortality due to diarrhea among children under 5 in the town of Osasco (SP), Brazil, between 1980 and 2000. METHODS: This is a descriptive observational study with two different designs, the first using individuals as the unit of study, and the other ecological, using groups of individuals as units of observation and including time series analysis. Data were obtained from the state of São Paulo information system of deaths and the results of the 1980, 1991 and 2000 censuses. Seasonal variations were described and log linear polynomial regression models were employed to analyze trends, using the sociodemographic characteristics of mothers and their children. Analyses were carried out of the changes in the town's sociodemographic indicators from 1980 to 2000, the average mortality rates among under-5s due to diarrhea and the differences between districts during the 1990s. RESULTS: There were a total of 1,360 deaths, 94.3% of which were before 1 year of age and 75.3% of which were before 6 months. There was a 98.3% reduction in mortality and the period of peak mortality shifted from summer to autumn/fall. The median age at death increased from 2 months at the first three quinquenium of study to 3 months at the last. The residual deaths were among the children of mothers aged 20 to 29 years and of mothers who had spent less than 8 years in education. The relative risk between the worst-affected district and the average rate for the town reduced from 3.4 to 1.3 from the first 5 years of the 1990s to the second half of the decade. CONCLUSIONS: Our results demonstrate an increase in the age of greatest vulnerability and indicate that it is probable that the agent most often linked with mortality due to diarrhea has changed.

Economic impact of a rotavirus vaccine in Brazil.

The study was done to evaluate the cost-effectiveness of a national rotavirus vaccination programme in Brazilian children from the healthcare system perspective. A hypothetical annual birth-cohort was followed for a five-year period. Published and national administrative data were incorporated into a model to quantify the consequences of vaccination versus no vaccination. Main outcome measures included the reduction in disease burden, lives saved, and disability-adjusted life-years (DALYs) averted. A rotavirus vaccination programme in Brazil would prevent an estimated 1,804 deaths associated with gastroenteritis due to rotavirus, 91,127 hospitalizations, and 550,198 outpatient visits. Vaccination is likely to reduce 76% of the overall healthcare burden of rotavirus-associated gastroenteritis in Brazil. At a vaccine price of US$ 7-8 per dose, the cost-effectiveness ratio would be US$ 643 per DALY averted. Rotavirus vaccination can reduce the burden of gastroenteritis due to rotavirus at a reasonable cost-effectiveness ratio.

Emergence and disappearance of a virulent clone of Haemophilus influenzae biogroup aegyptius, cause of Brazilian purpuric fever.

SUMMARY: In 1984, children presented to the emergency department of a hospital in the small town of Promissão, São Paulo State, Brazil, with an acute febrile illness that rapidly progressed to death. Local clinicians and public health officials recognized that these children had an unusual illness, which led to outbreak investigations conducted by Brazilian health officials in collaboration with the U.S. Centers for Disease Control and Prevention. The studies that followed are an excellent example of the coordinated and parallel studies that are used to investigate outbreaks of a new disease, which became known as Brazilian purpuric fever (BPF). In the first outbreak investigation, a case-control study confirmed an association between BPF and antecedent conjunctivitis but the etiology of the disease could not be determined. In a subsequent outbreak, children with BPF were found to have bacteremia caused by Haemophilus influenzae biogroup aegyptius (H. aegyptius), an organism previously known mainly to cause self-limited purulent conjunctivitis. Molecular characterization of blood and other isolates demonstrated the clonal nature of the H. aegyptius strains that caused BPF, which were genetically distant from the diverse strains that cause only conjunctivitis. This led to an intense effort to identify the factors causing the unusual invasiveness of the BPF clone, which has yet to definitively identify the virulence factor or factors involved. After a series of outbreaks and sporadic cases through 1993, no additional cases of BPF have been reported.

Presumptive rapid diagnosis of parvovirus infection in patients with Erythema infectiosum-like illness

In September 1987 an outbreak of exanthematous illness ressembling erythma infectiosum occurres at an elementary school of Säo Paulo city. Attempts to isolate virus from the nasofaryngeal secretion and urine and serum samples collected from the ill children in acute phase of illness resulted negative. Nevertheless, parvovirus-like particles of about 24 nm in diameter were observed by negative staining electron microscopy in concentraded urine of seven out of eight ill patients and in nasopharyngeal secretion of one out of four patients. No similar viral particle was observed in concentred urine samples collected on the same occasion from their classmates without evident signs of illness. This is a proposal of an alternative test for a rapid and sensitive presumptive diagnosis of human parvovirus infection

Preliminar characterization of a new virus isolated from the spinal fluid of patients with meningitis in Säo Paulo, Brazil

De dezembro de 1982 a março de 1983 um total de 138 pacientes com idade de 4 meses a 57 anos foram atendidos em diferentes hosptais de Säo Paulo com sintomas de meningite asséptica. Um agente transmissível foi isolado de 35 das 53 amostras de líquor. A replicaçäo desse novo vírus ou de um grupo de vírus relacioandos antigenicamente com características semelhantes foi detectada através do efeito citopático produzido em cultura de células de MDCK. O agente isolado demonstrou ter um diâmtro em torno de 40 nm quando examinado ao microscópio eletrônico através da coloraçäo negativa. Nenhuma atividade hemaglutinante foi detectada em pH 7,2 com hemácias humanas de cobaias ou de galinha e em pH 6,0 - 7,2 com hemácias de ganso. Esse agente näo se mostrou patogênico ao camundongo recém-nascido e adulto, era sensível ao clorofórmio e näo foi inibido pelo BuDR, o que indica conter o genoma RNA

Frequência de anticorpos anti-Cysticercus cellulosae em população de risco para cisticercose e em segmento de população considerado supostamente normal, em regiões do Estado de São Paulo, Brasil / Frequency of anti-cysticercus cellulosae antibodies in high risk population for cysticercosis and in a segment considered as normal population, in areas of Säo Paulo state, Brazil

Examinaram-se, através de reação de fixação de complemento, os soros de 234 pacientes internados em hospital psiquiátrico localizado no município de Presidente Prudente, considerados de risco para infecção cisticercótica, além de 454 soros de gestantes procedentes da Região Administrativa de Santos e 397 soros de indivíduos considerados supostamente normais, procedentes da Região Administrativa de Presidente Prudente. O antígeno utilizado na reação de fixação de complemento foi obtido através de extração metílica, à temperatura ambiente, dos císticercos tratados com acetona. Consideraram-se positivas as reações em que ocorreu fixação de complemento a partir da diluição 1 :2. Dos 1.085 soros testados, 27 apresentaram atividade anticomplementar e 17 (1,6%) mostraram-se reagentes. Todavia, quando se consideraram, separadamente, os grupos procedentes de Santos, Presidente Prudente e os doentes mentais, percebe-se diferença significativa nos resultados: assim, os índices de freqüência foram, respectivamente, 0,88% e 1,00% para os indivíduos procedentes de Santos e Presidente Prudente e considerados supostamente normais e 3,8% para os doentes mentais. Os resultados indicam que não é desprezível a ocorrência de anticorpos anti-Cysticercus cellulosae em nosso meio, especialmente entre pacientes de hospitais psiquiátricos (AU).