Studies on human anti-rabies immunization in Brazil: I - Evaluation of the 3 + 1 pre-exposure vaccination schedule under field conditions

The currently used pre-exposure anti-rabies immunization schedule in Brazil is the one called 3+1, employing suckling mouse brain vaccine (3 doses on alternate days and the last one on day 30). Although satisfactory results were obtained in well controlled experimental groups using this immunization schedule, in our routine practice, VNA levels lower than 0.5 IU/ml are frequently found. We studied the pre-exposure 3+1 schedule under field conditions in different cities on the State of São Paulo, Brazil, under variable and sometimes adverse circumstances, such as the use of different batches of vaccine with different titers, delivered, stored and administered under local conditions. Fifty out of 256 serum samples (19.5%) showed VNA titers lower than 0.5 IU/ml, but they were not distributed homogeneously among the localities studied. While in some cities the results were completely satisfactory, in others almost 40% did not attain the minimum VNA titer required. The results presented here, considered separately, question our currently used procedures for human pre-exposure anti-rabies immunization. The reasons determining this situation are discussed.

Studies on human anti-rabies immunization in Brazil: II - Preliminary evaluation of the 2-1-1 schedule for human pre-exposure anti-rabies immunization, employing suckling mouse brain vaccine

This study reports preliminary results of virus neutralizing antibody (VNA) titers obtained on different days in the course of human anti-rabies immunization with the 2-1-1 schedule (one dose is given in the right arm and one dose in the left arm at day 0, and one dose is apllied on days 7 and 21), recommended by WHO for post-exposure treatment with cell culture vaccines. A variant schedule (double dose on day zero and another on day 14) was also tested, both employing suckling mouse brain vaccine. A complete seroconversion rate was obtained after only 3 vaccine doses, and almost all patients (11 of 12) presented titers higher than 1.0 IU/ml. Both neutralizing response and seroconversion rates were lower in the group receiving only 3 doses, regardless of the sample collecting day. Although our results are lower than those found with cell culture vaccines, the geometry mean of VNA is fully satisfactory, overcoming the lower limit recommended by WHO of 0.5 IU/ml. The 2-1-1 schedule could be an alternative one for pre exposure immunization, shorter than the classical 3+1 regimen (one dose on days 0, 2, 4 and 30) with only three visits to the doctor, instead of four.

The influence of pre-departure training on expatriate adjustment: an empirical investigation with portuguese international assignees

This chapter examines the cross-cultural influence of training on the adjustment of international assignees. We focus on the pre-departure training (PDT) before an international assignment. It is an important topic because in the globalized world of today more and more expatriations are needed. The absence of PDT may generate the failure of the expatriation experience. Companies may neglect PDT due to cost reduction practices and ignorance of the need for it. Data were collected through semi-structured interviews to 42 Portuguese international assignees and 18 organizational representatives from nine Portuguese companies. The results suggest that companies should develop PDT programs, particularly when the cultural distance to the host country is bigger and when there is no previous experience of expatriation to that country in the company. The study is original because it details in depth the methods of PDT, its problems, and consequences. Some limitations linked to the research design and detailed in the conclusion should be overcome in future studies.

Candidin: comparison of two antigens for cutaneous delayed hypersensitivity testing

A candidin, which is a suspension of killed yeast cells, is commonly used for intradermal tests of delayed hypersensitivity, to evaluate the immunological cellular competence of the patient, when the test is applied along with other similar tests. When working with a cellular antigen, the histopathology of positive skin tests reveals a cellular infiltrate which not only presents a characteristic hypersensitivity reaction but also a neutrophilic abscess in the central part. This research presents the results of a comparison between the yeast cell suspension and the polysaccharide antigens, both obtained from the same strains of Candida albicans. The results obtained by skin tests in one hundred individuals were 61.0% with the polysaccharide antigen and 69.0% with the yeast cell suspension antigen. Concordant results concerning the two antigens were observed in 82.0% of the individuals. The discussion section presents an assumption to explain the differences of positivity obtained with the two antigens. We conclude that the polysaccharide antigen can be utilized in the intradermal test of delayed hypersensitivity to Candida albicans.

In vitro susceptibility testing of Fonsecaea pedrosoi to antifungals

Based on the difficulties experienced in the treatment of chromoblastomycosis, 12 primary human isolates of F. pedrosoi, were tested for their in vitro susceptibility to various antimycotics. We adapted the recommendations of the NCCLS for yeasts and followed the indications for mold testing from other authors in order to determine their MIC’s and the MLC’s. It was found that a significant proportion of the isolates were resistant to 3 of the 4 antimycotics tested, as revealed by high MIC values, as follows: 33% were resistant to amphotericin B (AMB), 58.3% to 5 fluocytosine (5 FC) and 66.7% to fluconazole (FLU). Contrarywise, none of the isolates proved resistant to itraconazole (ITZ). Determination of the MLC’s revealed that a larger proportion of the isolates were not killed by AMB, 5 FC (91.7%), FLU (100%) or even, ITZ (41.7%). These data indicate that it would be desirable to determine the susceptibility of F. pedrosoi before initiating therapy, in order to choose the more effective antifungal and avoid clinical failure

Massive shift in the pneumococcal nasopharyngeal flora after the 7-valent conjugate vaccine: epidemiological studies and testing pathogenic potential in animal models

Dissertation presented to obtain the PhD degree in Biology/Molecular Biology by Universidade Nova de Lisboa, Instituto de Tecnologia Química e Biológica

Evaluation of Etest and macrodilution broth method for antifungal susceptibility testing of Candida sp strains isolated from oral cavities of AIDS patients

A comparison of the Etest and the reference broth macrodilution susceptibility test for fluconazole, ketoconazole, itraconazole and amphotericin B was performed with 59 of Candida species isolated from the oral cavities of AIDS patients. The Etest method was performed according to the manufacturer's instructions, and the reference method was performed according to National Committee for Clinical Laboratory Standards document M27-A guidelines. Our data showed that there was a good correlation between the MICs obtained by the Etest and broth dilution methods. When only the MIC results at ± 2 dilutions for both methods were considered, the agreement rates were 90.4% for itraconazole, ketoconazole and amphotericin B and 84.6% for fluconazole of the C. albicans tested. In contrast, to the reference method, the Etest method classified as susceptible three fluconazole-resistant isolates and one itraconazole-resistant isolate, representing four very major errors. These results indicate that Etest could be considered useful for antifungal sensitivity evaluation of yeasts in clinical laboratories.

Global and Partitioned Multiprocessor Fixed Priority Scheduling with Deferred Pre-emption

This article introduces schedulability analysis for global fixed priority scheduling with deferred preemption (gFPDS) for homogeneous multiprocessor systems. gFPDS is a superset of global fixed priority pre-emptive scheduling (gFPPS) and global fixed priority non-pre-emptive scheduling (gFPNS). We show how schedulability can be improved using gFPDS via appropriate choice of priority assignment and final non-pre-emptive region lengths, and provide algorithms which optimize schedulability in this way. Via an experimental evaluation we compare the performance of multiprocessor scheduling using global approaches: gFPDS, gFPPS, and gFPNS, and also partitioned approaches employing FPDS, FPPS, and FPNS on each processor.

Evolution of genotypes of Group A streptococci from colonization and infection

Dissertação para obtenção do Grau de Doutor em Biologia

Screening for pulmonary tuberculosis in Teresópolis, RJ, Brazil: the search for respiratory symptomatic patients in emergency service of "Hospital das Clínicas de Teresópolis Costantino Ottaviano, Fundação Educacional Serra dos Órgãos"

The aim of the present study was to investigate the detection percentage of tuberculosis among patients that are respiratory symptomatic (TB suspects). In this work, we present the preliminary results of research carried out at "Hospital das Clínicas de Teresópolis Costantino Ottaviano da Fundação Educacional Serra dos Órgãos (FESO)" from November 2003 to April 2004. Among the 40 respiratory symptomatic individuals identified and referred to the Tuberculosis Control Program in Teresópolis, two (5.0%) were characterized as smear-positive. These results confirm reports in the literature and underscore the need for and importance of this strategy.

Rapid turnover of Plasmodium falciparum var gene transcripts and genotypes during natural non-symptomatic infections

The var genes of Plasmodium falciparum code for the antigenically variant erythrocyte membrane proteins 1 (PfEMP1), a major factor for cytoadherence and immune escape of the parasite. Herein, we analyzed the var gene transcript turnover in two ongoing, non-symptomatic infections at sequential time points during two weeks. The number of different circulating genomes was estimated by microsatellite analyses. In both infections, we observed a rapid turnover of plasmodial genotypes and var transcripts. The rapidly changing repertoire of var transcripts could have been caused either by swift elimination of circulating var-transcribing parasites stemming from different or identical genetic backgrounds, or by accelerated switching of var gene transcription itself.

Head-Up Tilt Testing with Different Nitroglycerin Dosages: Experience in Elderly Patients with Unexplained Syncope

AIMS: Protocols using sublingual nitrates have been increasingly used to improve diagnostic accuracy of head-up tilt testing (HUT). Nevertheless, exaggerated responses to nitrates have been frequently described, particularly in elderly patients. The aim of this article is to evaluate, in an elderly population with unexplained syncope, whether the impact of sublingual nitroglycerin (NTG) used as a provocative agent is dose-dependent. METHODS AND RESULTS: One hundred and twenty consecutive elderly patients submitted to HUT using NTG after an asymptomatic drug-free phase were studied. Patients were divided into three groups according to the NTG dosage: 500, 375 and 250 microg. The test was considered positive when there was reproduction of symptoms with bradycardia and/or arterial hypotension. A gradual decrease in the blood pressure after NTG was considered an exaggerated response to nitrates. There were no differences in the clinical characteristics of the different subgroups. A positive test was obtained in 50% of the patients in each group. The rate of exaggerated responses was identical in all groups and ranged between 15 and 17%. CONCLUSION: In an elderly population with syncope of unknown origin submitted to HUT, the response to NTG is not dose-dependent, and no difference was found in the rate of exaggerated responses to nitrates with different NTG dosages.

Primary screening of blood donors by nat testing for HCV-RNA: development of an "in-house" method and results

An "in-house" RT-PCR method was developed that allows the simultaneous detection of the RNA of the Hepatitis C Virus (HCV) and an artificial RNA employed as an external control. Samples were analyzed in pools of 6-12 donations, each donation included in two pools, one horizontal and one vertical, permitting the immediate identification of a reactive donation, obviating the need for pool dismembering. The whole process took 6-8 hours per day and results were issued in parallel to serology. The method was shown to detect all six HCV genotypes and a sensitivity of 500 IU/mL was achieved (95% hit rate). Until July 2005, 139,678 donations were tested and 315 (0.23%) were found reactive for HCV-RNA. Except for five false-positives, all 310 presented the corresponding antibody as well, so the yield of NAT-only donations was zero, presenting a specificity of 99.83%. Detection of a window period donation, in the population studied, will probably demand testing of a larger number of donations. International experience is showing a rate of 1:200,000 - 1:500,000 of isolated HCV-RNA reactive donations.

In vitro susceptibility testing of dermatophytes isolated from pediatric cases in Nigeria against five antifungals

The antifungal activities of itraconazole, ketoconazole, fluconazole, terbinafine and griseofulvin were tested by broth microdilution methods against 71 isolates of dermatophytes isolated from Nigerian children. Most drugs were very active against all the dermatophytes and the MIC 90 ranged from 0.03 to 8.0 µg/mL. This appears to be the first documented data on the antifungal susceptibility testing of isolates of dermatophytes from Nigerian children.