YELLOW FEVER PREVENTION STRATEGIES AWARENESS AMONG HIV-INFECTED PATIENTS IN SÃO PAULO, BRAZIL

Introduction: Vaccination is the main preventive strategy against Yellow Fever (YF), which is a public health concern in Brazil. However, HIV-infected patients might have insufficient knowledge regarding YF, YF prevention, and vaccines in general. Methods: In this questionnaire-based study, data from 158 HIV-infected individuals were addressed in three distinct outpatient clinics in São Paulo. Information was collected on demographic and clinical characteristics, as well as patients' knowledge of vaccines, YF and YF preventive strategies. In addition, individual YF vaccine recommendations and vaccine status were investigated. Results: Although most participants adequately ascertain the vaccine as the main prevention strategy against YF, few participants were aware of the severity and lack of specific treatment for YF. Discrepancy in YF vaccine (patients who should have taken the vaccine, but did not) was observed in 18.8% of participants. Conclusion: YF is an important and preventable public health concern, and these results demonstrate that more information is necessary for the HIV-infected population.

Echocardiographic parameters associated with pulmonary congestion in Chagas cardiomyopathy

INTRODUCTION: Discrepancy between the intensity of pulmonary congestion and the grade of cardiomegaly seems to be a common finding of Chagas cardiomyopathy, in spite of significant systolic dysfunction of the left ventricle. Its mechanism has not been established. The aim of this study was to investigate pulmonary congestion and to analyze if it correlated with Doppler echocardiographic parameters in patients with Chagas dilated cardiomyopathy. METHODS: Fifty-five patients with positive serology tests for Trypanosoma cruzi and Chagas dilated cardiomyopathy were studied. Chest x-rays, Doppler echocardiogram and plasmatic brain natriuretic peptide levels were obtained in all patients. The degree of pulmonary venous vessels changes on chest x-ray was graded using a pulmonary congestion score, and then compared to Doppler echocardiographic parameters. RESULTS: Mean age was 48.5 ± 11.2 years and 29% were women. The majority (95%) of patients were in NYHA functional class I and II. Mild pulmonary congestion by chest x-ray was found in 80% of the patients. In a multivariate analysis, left ventricular ejection fraction, right ventricular TEI index and the color M-mode velocity correlated with the degree of pulmonary congestion. CONCLUSIONS: Pulmonary venous changes on chest x-rays are frequent, but usually mild in patients with Chagas dilated cardiomyopathy. The degree of pulmonary congestion correlates with Doppler echocardiographic left and right ventricular dysfunction and with color M-mode velocity.

Measuring male infertility: epidemiological aspects

Evidence suggests that human semen quality may have been deteriorating in recent years. Most of the evidence is retrospective, based on analysis of data sets collected for other purposes. Measures of male infertility are needed if we want to monitor the biological capacity for males to reproduce over time or between different populations. We also need these measures in analytical epidemiology if we want to identify risk indicators, risk factors, or even causes of an impaired male fecundity-that is, the male component in the biological ability to reproduce. The most direct evaluation of fecundity is to measure the time it takes to conceive. Since the time of conception may be missed in the case of an early abortion, time to get pregnant is often measured as the time it takes to obtain a conception that survives until a clinically recognized pregnancy or even a pregnancy that ends with a live born child occurs. A prolonged time required to produce pregnancy may therefore be due to a failure to conceive or a failure to maintain a pregnancy until clinical recognition. Studies that focus on quantitative changes in fecundity (that does not cause sterility) should in principle be possible in a pregnancy sample. The most important limitation in fertility studies is that the design requires equal persistency in trying to become pregnant and rather similar fertility desires and family planning methods in the groups to be compared. This design is probably achievable in exposure studies that make comparisons with reasonable comparable groups concerning social conditions and use of contraceptive methods.

Proton magnetic resonance spectroscopy of the frontal lobe in schizophrenics: a critical review of the methodology

Schizophrenic patients undergoing proton magnetic resonance spectroscopy show alterations in N-acetyl aspartate levels in several brain regions, indicating neuronal dysfunction. The present review focuses on the main proton magnetic resonance spectroscopy studies in the frontal lobe of schizophrenics. A MEDLINE search, from 1991 to March 2004, was carried out using the key-words spectroscopy and schizophrenia and proton and frontal. In addition, articles cited in the reference list of the studies obtained through MEDLINE were included. As a result, 27 articles were selected. The results were inconsistent, 19 papers reporting changes in the N-acetyl aspartate levels, while 8 reported no change. Methodological analysis led to the conclusion that the discrepancy may be due the following factors: (i) number of participants; (ii) variation in the clinical and demographic characteristics of the groups; (iii) little standardization of the acquisition parameters of spectroscopy. Overall, studies that fulfill strict methodological criteria show N-acetyl aspartate decrease in the frontal lobe of male schizophrenics.

Body Mass Index: A Scientific Evidence-Based Inquiry

OBJECTVE: To objectively and critically assess body mass index and to propose alternatives for relating body weight and height that are evidence-based and that eliminate or reduce the limitations of the body mass index. METHODS: To analyze the relations involving weight and height, we used 2 databases as follows: 1) children and adolescents from Brazil, the United States, and Switzerland; and 2) 538 university students. We performed mathematical simulations with height data ranging from 115 to 190 cm and weight data ranging from 25 to 105 kg. We selected 3 methods to analyze the relation of weight and height as follows: body mass index - weight (kg)/height (m²); reciprocal of the ponderal index - height (cm)/weight1/3 (kg); and ectomorphy. Using the normal range from 20 to 25 kg/m² for the body mass index in the reference height of 170 cm, we identified the corresponding ranges of 41 to 44 cm/kg1/3 for the reciprocal of the ponderal index, and of 1.45 to 3.60 for ectomorphy. RESULTS: The mathematical simulations showed a strong association among the 3 methods with an absolute concordance to a height of 170 cm, but with a tendency towards discrepancy in the normal ranges, which had already been observed for the heights of 165 and 175 cm. This made the direct convertibility between the indices unfeasible. The reciprocal of the ponderal index and ectomorphy with their cut points comprised a larger age range in children and adolescents and a wider and more central range in the university students, both for the reported (current) and desired weights. CONCLUSION: The reciprocal of the ponderal index and ectomorphy are stronger and are more mathematically logical than body mass index; in addition, they may be applied with the same cut points for normal from the age of 5 ½ years on.

Cell-matrix interactions in Schistosomal portal fibrosis: a dynamic event

In recent years, one of the most significant progress in the understanding of liver diseases was the demonstration that liver fibrosis is a dynamic process resulting from a balance between synthesis and degradation of several matrix components, collagen in particular. Thus, fibrosis has been found to be a very early event during liver diseases, be it of toxic, viral or parasitic origin, and to be spontaneously reversible, either partially or totally. In liver fibrosis cell matrix interactions are dependent on the existence of the many factors (sometimes acting in combination) which produce the same events at the cellular and molecular levels. These events are: (i) the recruitment of fiber-producing cells, (ii) their proliferation, (iii) the secretion of matrix constituents of the extracellular matrix, and (iv) the remodeling and degradation of the newly formed matrix. All these events represent, at least in principle, a target for a therapeutic intervention aimed at influencing the experimentally induced hepatic fibrosis. In this context, hepatosplenic schistosomiasis is of particular interest, being an immune cell-mediated granulomatous disease and a model of liver fibrosis allowing extensive studies in human and animals as well as providing original in vitro models.

Chemical and pharmacological investigation of Solanum species of Brazil: a search for solasodine and other potentially useful therapeutic agents

A systematic search for solasodine, an important staring material for the partial synthesis of steroidal hormones as well as other potentially bioactive constituents of various Solanum species of Brazil has been undertaken. Thus, the fruits of S. paludosum, S. asperum, S. sessiliforum and Solanum sp. were found to contain significant amounts of solasodine. The root bark of S. paludosum which showe durare like activity yelded tomatidenol and another yet unidentified alkaloid responsible for the biological activity. The fruits of S. asperum yelded a new spirosolane alkaloid, solaparnaine. The stem bark of S. pseudo-quina showed convulsive and exitatory activity from which (25S)-isosolafloridine was identified as the active principle. In addition, the latter alkaloid was also found to show antimicrobial activity.

The value of ultrasonography in assessment of portal hypertension in hepatosplenic schistosomiasis

Ultrasonography can reveal most of the manifestations of portal hypertension complicating hepatosplenic, schistosomiasis. However, direct demonstration of gastroesophageal varices by ultrasonography is still very difficult. An attempt was done to correlate sonographic features of portal hypertension with the degree of fibrosis to screen patients having varices and predicting their chance of bleeding. The results obtained were found to be consistent with the esophagogastric endoscopy and with history of hematemesis. Four parameters were used, size of spleen, degree of periportal fibrosis, presence of collaterals and portal vein diameter. A pilot field survey was also done adopting the same principle.

T lymphocytes and iron overload: novel correlations of possible significance to the biology of the immunological system

This paper is written in the context of our changing preception of the immunological system as a system with possible biological roles exceding the prevailung view of a system concerned principally with the defense against external pathogens. The view discussed here relates the immunological system inextricably to the metabolism of iron, the circulation of the blood and the resolution of the evolutionary paradox created by oxygen and iron. Indirect evidence for this inextricable relationship between the two systems can be derived from the discrepancy between the theoretical quasi-impossibility of the existence of an iron deficiency state in the adult and the reality of the WHO numbers of people in the world with iron deficiency anemia. With mounting evidence that TNF, IL-1, and T lymphocyte cytokines affect hemopoieisis and iron metabolism it is possible that the reported discrepancy is a reflection of that inextricable interdependence between the two systems in the face of infection. Further direct evidence for a relationship between T cell subset numbers and iron metabolism is presented from the results of a study of T cell populations in patients with hereditary hemochromatosis. The recent finding of a correlation between low CD8+ lymphocite numbers, liver demage associated with HCVpositivity and severity of iron overload in B-thalassemia major patients (umpublished data of RW Grandy; P. Giardina, M. Hilgartner) concludes this review.

Molluscicide control of snail vectors of schistosomiasis

A review of the methodology recommended by the World Health Organization for the use of molluscicides for the control of snail vectors of schistosomiasis is presented. Discussion of the principle molluscicides used, their advantages and disadvantages, the techniques and equipment required for their application and evaluation of effect as well as the biological control of snails is included.

Schistosomiasis vaccine development: progress and prospects

The undisputed, worldwide success of chemotherapy notwithstanding, schistosomiasis continues to defy control efforts in as much rapid reinfection demands repeated treatment, sometimes as often as once a year. There is thus a need for a complementary tool with effect for the longer term, notably a vaccine. International efforts in this direction have been ongoing for several decades but, until the recombinant DNA techniques were introduced, antigen production remained an unsurmountable bottleneck. Although animal experiments have been highly productive and are still much needed, they probably do not reflect the human situation adequately and real progress can not be expected until more is known about human immune responses to schistosome infection. It is well-known that irradiated cercariae consistently produce high levels of protection in experimental animals but, for various reasons, this proof of principle cannot be directly exploited. Research has instead been focussed on the identification and testing of specific schistosome antigens. This work has been quite successful and is already at the stage where clinical trials are called for. Preliminary results from coordinated in vitro laboratory and field epidemiological studies regarding the protective potential of several antigens support the initiation of such trials. A series of meetings, organized earlier this year in Cairo, Egypt, reviewed recent progress, selecteded suitable vaccine candidates and made firm recommendations for future action including pledging support for large-scale production according to good manufacturing practice (GMP) and Phase I trials. Scientists at the American Centers for Disease Control and Prevention (CDC) have drawn up a detailed research plan. The major financial support will come from USAID, Cairo, which has established a scientific advisory group of Egyptian scientists and representatives from current and previous international donors such as WHO, NIAID, the European Union and the Edna McConnell Clark Foundation.

A comparative study on IgG-ELISA, IgM-IFT and Kato-Katz methods for epidemiological purposes in a low endemic area for schistosomiasis

The high sensitivity and the possibility of automation of the enzyme-linked-immunosorbent-assay (ELISA) has indicated this technique as one of the most useful serological test for epidemiological studies. In the present study, an ELISA for detection of IgG antibodies against adult worm antigens (IgG-ELISA) was investigated for epidemiological purposes, in a rural area of the municipality of Itariri (São Paulo, Brazil). Blood on filter paper (1,180 samples) from about 650 schoolchildren were submitted to ELISA and the data compared to the results of the parasitological method of Kato-Katz and also to the IgM-IFT (immunofluorescence test for IgM antibodies to gut associated antigens). The prevalence rates respectively of 8.5%, 43.0%, and 56.2% by the Kato-Katz, IgG-ELISA, and IgM-IFT methods suggest the poor sensitivity of the parasitological method for detection of Schistosoma mansoni eggs in individuals with low worm burden, situation commonly observed in low endemic areas. These results can partially explain the poor degree of agreement between the IgG-ELISA and the Kato-Katz, as suggested by the Kappa index of 0.170. Otherwise, the Kappa index of 0.675 showed substantial agreement between the two serological tests. Some discrepancy of results between the two serological techniques must be better investigated.

Oviposition response of the mosquito, Culex quinquefasciatus to the secondary metabolite(s) of the fungus, Trichoderma viride

Secondary metabolites produced by Trichoderma viride, a deuteromycetes fungus, under submerged culture condition were formulated and evaluated for oviposition attractancy against gravid females of Culex quinquefasciatus mosquito. At a concentration of 10 µg ml-1 the formulation showed remarkable attractancy with an oviposition active index (OAI) of +0.52. When the oviposition attractancy of the formulation was compared with a known oviposition attractant, p-cresol, both at 10 µg ml-1, the former was found to be more attractive to result in 70% egg laying than the later with 30% egg laying. Thin layer chromatography fractions of the secondary metabolites showed that a fraction with Rf value of 0.88 was highly active as oviposition attractant with an OAI of +0.65. Further work on identification of the active principle(s) of the microbial formulation might lead to an oviposition attractant useful in mosquito vector management.

Larvicidal activity of the essential oil from Lippia sidoides cham. against Aedes aegypti linn

The aim of this work was to study the larvicidal activity of Lippia sidoides essential oil against Aedes aegypti larvae. The essential oil and its hydrolate (saturated solution of essential oil in water) were obtained by vapor extraction and their chemical composition determined by GL-chromatography coupled to mass spectroscopy. Bioassays were run with the essential oil, pure and diluted hydrolate and with their main constituents thymol and carvacrol. The results obtained showed that L. sidoides essential oil and its hydrolate have larvicidal action against the mosquito A. aegypti, causing an almost instantaneous mortality. Thymol, an alkylated phenol derivative and one of the major components of L. sidoides essential oil, was identified as the active principle responsible for the larvicidal action, causing 100% larval mortality at the lowest tested concentration of 0.017% (w/v). These results suggest that the essential oil of L. sidoides is promising as larvicide against A. aegypti and could be useful in the search of newer, more selective, and biodegradable larvicidal natural compounds to be used in official combat programs and at home.

From genomes to vaccines via the proteome

An effective vaccine against schistosomiasis mansoni would be a valuable control tool and the high levels of protection elicited in rodents and primates by radiation-attenuated cercariae provide proof of principle. A major obstacle to vaccine development is the difficulty of identifying the antigens that mediate protection, not least because of the size of the genome at 280Mb DNA encoding 14,000 to 20,000 genes. The technologies collectively called proteomics, including 2D electrophoresis, liquid chromatography and mass spectrometry, now permit any protein to be identified provided there is extensive DNA data, and preferably a genome sequence. Applied to soluble (cytosolic) proteins from schistosomes, proteomics reveals the great similarity in composition between life cycle stages, with several WHO vaccine candidates amongst the most abundant constituents. The proteomic approach has been successfully applied to identify the secretions used by cercaria to penetrate host skin, the gut secretions of adult worms and the proteins exposed on the tegument surface. Soluble proteins can also be separated by 2D electrophoresis before western blotting to identify the full range of antigenic targets present in a parasite preparation. The next step is to discover which target proteins represent the weak points in the worm's defences.