Proposal of abolition of the skin sensitivity test before equine rabies immune globulin application

An epizootic outbreak of rabies occurred in 1995 in Ribeirão Preto, SP, with 58 cases of animal rabies (54 dogs, 3 cats and 1 bat) confirmed by the Pasteur Institute of São Paulo, and one human death. The need to provide care to a large number of people for the application of equine rabies immune globulin (ERIG) prevented the execution of the skin sensitivity test (SST) and often also the execution of desensitization, procedures routinely used up to that time at the Emergency Unit of the University Hospital of the Faculty of Medicine of Ribeirão Preto, University of São Paulo (EU-UHFMRP-USP), a reference hospital for the application of heterologous sera. In view of our positive experience of several years with the abolition of SST and of the use of premedication before the application of antivenom sera, we used a similar schedule for ERIG application. Of the 1489 victims of animal bites, 1054 (71%) received ERIG; no patient was submitted to SST and all received intravenously anti-histamines (anti-H1 + anti-H2) and corticosteroids before the procedure. The patients were kept under observation for 60 to 180 minutes and no adverse reaction was observed. On the basis of these results, since December 1995 ERIG application has been decentralized in Ribeirão Preto and has become the responsibility of the Emergency Unit of the University Hospital and the Central Basic Health Unit, where the same routine is used. Since then, 4216 patients have received ERIG (1818 at the Basic Health Unit and 2398 at the EU-UHFMRP), with no problems. The ideal would be the routine use of human rabies immune globulin (HRIG) in public health programs, but this is problematic, because of their high cost. However, while this does not occur, the use of SST is no longer justified at the time of application of ERIG, in view of the clinical evidence of low predictive value and low sensitivity of SST involving the application of heterologous sera. It is very important to point out that a negative SST result may lead the health team to a feeling of false safety that no adverse reaction will occur, but this is not true for the anaphylactoid reactions. The decision to use premedication, which is based on knowledge about anaphylaxis and on the pharmacology of the medication used, is left to the judgment of health professionals, who should always be prepared for eventual untoward events.

Influence of Compound 16.842 on hookworm infections

Compound 16.842 was tried with three different groups of patients in order to evaluate its tolerancy, and efficacy as well, with a view of using the drug in mass campaigns against hookworm. Group I, used for a preliminary trial, consisted of 38 patients attending an out-patient clinic, and living either in the out-skirts or in the various urban areas of the city of Rio de Janeiro, including some inmates of an orphanage. Group II, a field trial, was carried out in two farms, where the drug was administered both to the positive cases (124) and to the rest of the population (nearly 90%). Group III, a field trial was also carried out in a small town where nearly 40% of the total population was treated with the Compound. Tolerability was considered rather satisfactory, mainly among the patients receiving two single doses (50-150mg), according to the age, 4 - 6 weeks apart). These results suggest that 2-4 courses of therapy within a shorter span of time should be the ideal for a mass treatment campaign. Efficacy varied from 26.6% to 76.2% parasitological cure in the various groups, with a wide range of variation also in the percent of mean reduction of eggs for hookworm. The drug showed also some effect against Ascaris lumbricoides giving cure rates between 10,5% and 35.7% in the various groups, with a percentage reduction in mean egg counts of 27% to 83.3% according to the various groups. It was concluded that Compound 16.842 possesses a marked effect on hookworm and a mild effect on A. lumbricoides. The findings indicate the need for more accurate studies to determine the most efficient schedules of treatment and the real value of the drug, as compared to other antihelminthics against the two parasites under study.

Prevalência da doença de Chagas no banco de sangue do Hospital das Clínicas de Goiânia: possibilidade de falha da reação de Guerreiro e Machado na seleção de doadores

Os AA. fazem, inicialmente, breve revisão bibliográfica a respeito do problema da transmissão da doença de Chagas por transfusão de sangue; enfocam aspectos como o alerta dado sobre a possibilidade da ocorrência do fato, confirmação dessa possibilidade no homem, prevalência da infecção chagásica em candidatos à doação em vários Bancos de Sangue e medidas profiláticas adotadas. No Banco de Sangue do Hospital das Clínicas de Goiânia, observaram que a prevalência da infecção chagásica em candidatos a doadores, avaliada através da reação de Guerreiro e Machado, foi de 10,43%. Com vistas à verificação da sensibilidade da reação de Guerreiro e Machado na seleção dos candidatos à doação, repetiram o referido exame em 452 doadores, uma ou mais vezes, em diferentes épocas, sempre por ocasião do comparecimento dos mesmos para nova doação. Observaram resultados concordantes da reação em 427 (94,47%) e discordantes em 25 (5,53%). Ressaltam o risco de se proceder à seleção de doadores de sangue com base na reação de Guerreiro e Machado, mesmo quando repetida mais de uma vez. Terminam considerando que, no momento, o método ideal de prevenção da transmissão da doença de Chagas por transfusão de sangue é representado pela adição de violeta de genciana a todo e qualquer sangue a ser transfundido, tanto em áreas endêmicas como fora delas, desde que o doador apresente antecedente epidemiológico.

Hemocultura: técnica sensível na detecção do Trypanosoma cruzi em pacientes chagásicos na fase crônica da doença de Chagas

A sensibilidade de hemoculturas, realizadas uma ou três vezes, foi estudada em 52 pacientes na fase crônica da doença de Chagas. Modificações foram introduzidas na técnica tais como, diminuição do período de processamento do sangue, homogeneização suave e exame até 120 dias do cultivo. Os resultados mostram alto percentual de positividade, ou seja, 79% e 94% dos pacientes foram positivos, respectivamente, com um ou três testes. A julgar pela número de tubos positivos, em cada paciente, a parasitemia foi baixa em 59% deles, média em 16% e alta em 25%. Não houve diferenças significativas nos resultados positivos em função da idade dos pacientes, que variou de 14 a 82 anos. Nossos resultados demonstram que a hemocultura é uma metodologia sensível para o diagnóstico parasitológico da doença de Chagas e ideal para monitorar cura em pacientes submetidos a tratamento.

Validade interna de ensaios terapêuticos em malária: análise de estudos de avaliação da emergência de resistência in vivo do Plasmodium vivax a doses padronizadas de primaquina

Resistência parasitária pode ser definida como a habilidade da cepa parasitária de sobreviver e/ou multiplicar, a despeito da administração e absorção da medicação dada em doses iguais ou superiores àquelas usualmente recomendadas, porém dentro do limite de tolerância dos indivíduos. Assim sendo, o desenho de estudo ideal para monitorizar a emergência da resistência parasitária aos antimaláricos deveria utilizar controles históricos ou alguma informação prévia (baseline) válida. Além disso, é fundamental que se tenha algum tipo de controle sobre os demais determinantes de falha terapêutica, não diretamente relacionados ao fenômeno biológico da resistência do parasita, os quais poderiam variar através do tempo e teriam potencial de distorcer a interpretação dos resultados de estudos dessa natureza. No presente artigo são feitas considerações sobre a validade interna de estudos que objetivam avaliar a emergência da resistência in vivo do Plasmodium vivax à doses padronizadas de primaquina usadas rotineiramente pelos serviços de saúde. Poucos foram os estudos que atentaram para a necessidade de controlar os determinantes externos da falha terapêutica, ou que se preocuparam em comparar os resultados encontrados com as taxas de cura historicamente observadas em uma dada região geográfica. Assim, recomenda-se que maior ênfase seja dada à validade interna (e limitações) das conclusões de estudos dessa natureza.

Emergent arboviruses in Brazil

Brazil is a large tropical country (8,514,215km²) with 185,360,000 inhabitants. More than one third of its territory is covered by tropical forests or other natural ecosystems. These provide ideal conditions for the existence of many arboviruses, which are maintained in a large variety of zoonotic cycles. The risk that new arboviruses might emerge in Brazil is related to the existence of large, densely populated cities that are infested by mosquitoes such as Culex and the highly anthropophilic Aedes aegypti. Infected humans or animals may come into these cities from ecological-epidemiological settings where arbovirus zoonoses occur. This study analyzes the risk of emergence of the alphaviruses Mayaro, Venezuelan equine encephalitis, Eastern equine encephalitis and Chikungunya; the flaviviruses yellow fever, Rocio, Saint Louis encephalitis and West Nile; and the orthobunyavirus Oropouche.

Estudo clínico-radiológico de crianças e adolescentes indígenas Suruí, Região Amazônica

INTRODUÇÃO: Entre os Suruí de Rondônia foram registradas incidências médias de TB > 2.500/100.000 habitantes, entre 1991-2002. Aproximadamente 50% desses casos foram notificados em < 15 anos. MÉTODOS: Trata-se de um estudo clínico-epidemiológico que teve como objetivo descrever as características clínico-radiológicas em crianças e adolescentes identificados como contatos de doentes de TB. Além disto, aplicar o sistema de pontuação para o diagnóstico de TB na infância e verificar se as condutas adotadas no nível local foram concordantes com as diretrizes nacionais. RESULTADOS: Foram analisados 52 Rx de 37 indígenas. Deste conjunto, 48,1% foram normais e 51,9% anormais. Alguns dos Rx apresentaram duas ou mais alterações, totalizando 36 eventos independentes. Observou-se infiltrados (38,9%), calcificações (38,9%), cavitações (11,1%) e atelectasias/derrame pleural (11,1%). Nas imagens anormais, 22,2% eram TB provavelmente ativa e 33,3% sequelas. A confrontação com as diretrizes constatou 52,6% de condutas discordantes. CONCLUSÕES: A presença da infecção tuberculosa latente (ITBL) e TB ativa, entre crianças e adolescentes, são indicadores de transmissão ativa e continuada do Mycobacterium tuberculosis. Os Rx mostrando alta frequência de infiltrados e calcificações é compatível com primo-infecção em idade precoce. Entretanto, essas alterações não são diferentes daquelas observadas entre outros grupos, não sugerindo comprometimento imunológico. As discordâncias apontadas indicam que o momento ideal para o tratamento da ITBL passou despercebido. Conclui-se que é fundamental a utilização do sistema de pontuação para o correto diagnóstico de TB na infância, assim como a realização de baciloscopia e cultura de escarro em adolescentes capazes de expectorar.

Diagnosis of Leishmania (Leishmania) chagasi infection in dogs and the relationship with environmental and sanitary aspects in the municipality of Palmas, state of Tocantins, Brazil

INTRODUCTION: The aim of the present study was to identify the presence of Leishmania (Leishmania) chagasi infection in dogs in the City of Palmas, Tocantins, Brazil, using the PCR technique to list the hot spots of infected dogs in the city and associate their occurrence to significant environmental changes at capture sites. METHODS: DNA was extracted from blood of dogs, and the PCR were performed with primers RV1/RV2. After screening the population studied, the regions of the city that had the highest occurrence of canine infection were detected. These sites were visited, and ecological parameters denoting anthropogenic disturbance were evaluated. RESULTS: Some important features were listed in the regions visited, such as low urbanization, lack of public collection of sewage, limited garbage collection, vacant lots with tall vegetation, decaying organic matter, and, most importantly, the occurrence of stray dogs and poultry in homes. CONCLUSIONS: The methodology for screening the population was very efficient, especially in evaluating a large number of individuals in a short time, with a high degree of automation. The results indicate an association between the observed parameters and the occurrence of infection in dogs. The model presented in the city is ideal for studies of disease progression and expansion and for the evaluation of control measures adopted for canine VL.

Seroepidemiological monitoring in sentinel animals and vectors as part of arbovirus surveillance in the state of Mato Grosso do Sul, Brazil

INTRODUCTION: From February-September 2010, seroepidemiological surveys were conducted on non-human primates and transmitter vector capture was used to investigate the possible circulation of arboviruses in the municipalities of Bonito, Campo Grande, and Jardim, State of Mato Grosso do Sul, Brazil. METHODS: A total of 65 primates from the wild and captivity were used, and potential vectors were captured using Castro and dip nets. Serum samples were tested at the Instituto Evandro Chagas, State of Pará, using the hemagglutination inhibition test to detect total antibodies against 19 different arboviruses. Virus isolation was attempted from serum samples and arthropod suspensions using newborn mice and the C6/36 cell line clone. In addition, identification of the vector species was conducted. RESULTS: From the 19 serum samples from Campo Grande, 1 sample had a 1:20 titer for Flavivirus. From the 35 samples collected in Bonito, 17 samples had antibodies to arboviruses, 4 (11.4%) were positive for Alphavirus, and 5 (14.2%) were positive for Flavivirus. Monotypic reactions were observed for the Mayaro (n = 10) and Oropouche (n = 5) viruses, and 6 (17.1%) samples had titers for >1 virus. We captured 120 Culicidae individuals that were potential arbovirus transmitters in Jardim; however, all the samples were negative for the viruses. CONCLUSIONS: Mato Grosso do Sul has a variety of vertebrate hosts and transmission vectors, thereby providing ideal conditions for the emergence or reemergence of arboviruses, including some pathogenic to human beings.

Prevalence of influenza and adherence to the anti-flu vaccination among elderly

INTRODUCTION: The flu, a condition that can affect the elderly by increasing the risk of serious complications can be prevented through vaccination. Estimate the prevalence of signs and symptoms suggestive of influenza in a group of elderly either vaccinated or unvaccinated against influenza was the objective this study. METHODS: This is a cross-sectional study performed in a Brazilian City. A structured questionnaire was employed to identify the presence of signs and symptoms of influenza in individuals aged 60 years or over. For analysis of associations between variables the prevalence ratio (PR) and its 95% confidence interval (95% CI) were used. RESULTS: One hundred ninety-six participants were interviewed, of whom 57.7% were female. The average age was 69.7 years. About 25% of the vaccinated and 20% of the unvaccinated in 2009, and 25% of the vaccinated and 22.5% of the unvaccinated in 2010 reported having the flu. Among the vaccinated and unvaccinated in 2009 and 2010, there was no verified association between vaccination and influenza (PR=1.24; [95% CI: 0.63-2.43] and PR=1.11; [95% CI: 0.59-2.09], respectively). CONCLUSIONS: This study suggests that, among the elderly selected, the vaccination coverage for influenza is below the ideal, even with projection of the best indices for 2011 (~ 84%). The data on vaccination and disease protection needs further research; however, the results point to the need for measures to better clarify to this population about the disease, its complications and the benefits of vaccination, in addition to combatting the stigma related to low adherence.

Pharmacokinetic/pharmacodynamic target attainment of intravenous β-lactam regimens against Gram-negative bacteria isolated in a Brazilian teaching hospital

ABSTRACTINTRODUCTION: Monte Carlo simulations have been used for selecting optimal antibiotic regimens for treatment of bacterial infections. The aim of this study was to assess the pharmacokinetic and pharmacodynamic target attainment of intravenous β-lactam regimens commonly used to treat bloodstream infections (BSIs) caused by Gram-negative rod-shaped organisms in a Brazilian teaching hospital.METHODS: In total, 5,000 patients were included in the Monte Carlo simulations of distinct antimicrobial regimens to estimate the likelihood of achieving free drug concentrations above the minimum inhibitory concentration (MIC; fT > MIC) for the requisite periods to clear distinct target organisms. Microbiological data were obtained from blood culture isolates harvested in our hospital from 2008 to 2010.RESULTS: In total, 614 bacterial isolates, including Escherichia coli, Enterobacterspp., Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa, were analyzed Piperacillin/tazobactam failed to achieve a cumulative fraction of response (CFR) > 90% for any of the isolates. While standard dosing (short infusion) of β-lactams achieved target attainment for BSIs caused by E. coliand Enterobacterspp., pharmacodynamic target attainment against K. pneumoniaeisolates was only achieved with ceftazidime and meropenem (prolonged infusion). Lastly, only prolonged infusion of high-dose meropenem approached an ideal CFR against P. aeruginosa; however, no antimicrobial regimen achieved an ideal CFR against A. baumannii.CONCLUSIONS:These data reinforce the use of prolonged infusions of high-dose β-lactam antimicrobials as a reasonable strategy for the treatment of BSIs caused by multidrug resistant Gram-negative bacteria in Brazil.

Effects of circular myotomy on the healing of esophageal suture anastomosis: an experimental study

For esophageal reconstruction in newborns with esophageal atresia, esophageal reunion with an end-to-end anastomosis is the ideal procedure, although it may result in leaks and strictures due to tension on the suture line, mainly in cases with a wide gap between the ends. Circular myotomy (Livaditis' procedure) is the best method to elongate the proximal esophageal pouch and reduce anastomotic tension. This experimental investigation in dogs was undertaken to attempt to verify that circular myotomy decreases the anastomotic leak rate in newborns with wide gap esophageal atresia, and to analyze whether the technique promotes morphologic changes in the anastomotic scar. A pilot study demonstrated that it is necessary to resect more than 8 cm (40% of the total esophageal length) in order to obtain high leak rates. In the experimental project, such resection was performed in dogs divided into two groups (control group, anastomosis only, and experimental group, anastomosis plus circular myotomy in the proximal esophageal segment). The animals were killed in the 14th postoperative day, submitted to autopsy, and were evaluated as to the presence of leaks and strictures, as well as to the features (macroscopic and microscopic aspects) of the anastomosis. Leak rates were the same in both groups. Morphometric analysis revealed that in animals in the experimental group, the anastomotic scar was thinner than the control animals, and the isolated muscular manchette distal to the site of myotomy was replaced by fibrous tissue. Correspondingly, a decreased number of newly formed small vessels were noted in the experimental animals, compared to control animals. We concluded that circular myotomy does not decrease the incidence of anastomotic leaks, and it also promotes deleterious changes in anastomotic healing.

Effectiveness of silver nitrate compared to talc slurry as pleural sclerosing agent in rabbits. Influence of concomitant intrapleural lidocaine

The ideal agent for producing pleurodesis has not been identified. Talc, the most commonly used, poses several problems. Another possibility is silver nitrate, which was widely used in the past. PURPOSE: To determine the influence of the intrapleural instillation of lidocaine in producing a pleurodesis with silver nitrate, to define the effect of lidocaine in the maturation of the collagen fibers, and to confirm that the pleurodesis after silver nitrate is stronger than after talc. METHODS: We studied three groups of 8 rabbits. Two groups received 0.5% silver nitrate; in one we had previously injected 0.5 ml of 2% lidocaine. The third group received 400 mg/kg talc (2 ml). The animals were sacrificed 28 days after the injection, and the pleural spaces were assessed grossly for evidence of pleurodesis and microscopically for evidence of inflammation and fibrosis. The total amount of pleural collagen and the distribution of thick and thin collagen fibers were quantified. Collagen was identified using picrosirius red stain. RESULTS: In the two groups that received silver nitrate (without lidocaine: 3.5 + 03 and with lidocaine: 3.2 + 0.3), the macroscopic pleurodesis (scale 0 -- 4) was significantly (p = 0.001) better than that resulting from talc (1.6 + 0.2). The mean degree of pleural fibrosis induced by silver nitrate (3.5 + 0.2) was significantly (p = 0.004) higher than that induced by talc (1.9 + 0.1). The previous instillation of lidocaine resulted in a tendency for decreased amounts of fibrosis (3.1 + 0.4). The mean amount (10³mm²) of pleural collagen was significantly (p = 0.009) greater in the rabbits that received silver nitrate (116.9 + 22.7) than in those that received talc (10.7 + 3.4). The injection of lidocaine slightly reduced the collagen (80.1 + 30.3). The distribution of collagen fibers did not differ among the groups. CONCLUSION: This rabbit model clearly confirms that intrapleural silver nitrate is more effective than talc for producing pleurodesis. The previous intrapleural instillation of lidocaine results in a decreasing trend in the amount of collagen, but does not change the effectiveness of the pleural fusion or modify the process of collagen maturation.

Monitoring the treatment of sepsis with vancomycin in term newborn infants

A prospective study was conducted to determine if standardized vancomycin doses could produce adequate serum concentrations in 25 term newborn infants with sepsis. Purpose: The therapeutic response of neonatal sepsis by Staphylococcus sp. treated with vancomycin was evaluated through serum concentrations of vancomycin, serum bactericidal titers (SBT), and minimum inhibitory concentration (MIC). METHOD: Vancomycin serum concentrations were determined by the fluorescence polarization immunoassay technique , SBT by the macro-broth dilution method, and MIC by diffusion test in agar . RESULTS: Thirteen newborn infants (59.1%) had adequate peak vancomycin serum concentrations (20--40 mg/mL) and one had peak concentration with potential ototoxicity risk (>40 µg/mL). Only 48% had adequate trough concentrations (5--10 mg/mL), and seven (28%) had a potential nephrotoxicity risk (>10 µg/mL). There was no significant agreement regarding normality for peak and trough vancomycin method (McNemar test : p = 0.7905). Peak serum vancomycin concentrations were compared with the clinical evaluation (good or bad clinical evolution) of the infants, with no significant difference found (U=51.5; p=0.1947). There was also no significant difference between the patients' trough concentrations and good or bad clinical evolution (U = 77.0; p=0.1710). All Staphylococcus isolates were sensitive to vancomycin according to the MIC. Half of the patients with adequate trough SBT (1/8), also had adequate trough vancomycin concentrations and satisfactory clinical evolution. CONCLUSIONS: Recommended vancomycin schedules for term newborn infants with neonatal sepsis should be based on the weight and postconceptual age only to start antimicrobial therapy. There is no ideal pattern of vancomycin dosing; vancomycin dosages must be individualized. SBT interpretation should be made in conjunction with the patient's clinical presentation and vancomycin serum concentrations. Those laboratory and clinical data favor elucidation of the probable cause of patient's bad evolution, which would facilitate drug adjustment and reduce the risk of toxicity or failing to achieve therapeutic doses.