Plasma levels of innate immune mediators are associated with liver fibrosis in low parasite burden Schistosoma mansoni-infected individuals.

In the murine model, it was demonstrated that pro-inflammatory cytokines and chemokines are essential to the formation and modulation of Schistosoma-induced granulomatous inflammation. However, the relationship of these immune mediators and disease severity is hard to be established in naturally infected individuals. The current study evaluates the association between plasma concentrations of MIF, sTNF-R1, CCL3, CCL7 and CCL24 and schistosomiasis morbidity in Schistosoma mansoni-infected patients with a low parasite burden. For this propose, 97 S. mansoni-infected individuals were subjected to abdominal ultrasound analysis and clinical examination. Among them, 88 had plasma concentration of immune mediators estimated by ELISA assay. Multivariate linear regression models were used to evaluate the relationship between the plasma concentration of immune mediators and the variables investigated. Although most individuals presented low parasite burden, over 30% of them showed signs of fibrosis defined by ultrasound measurements and 2 patients had a severe form of schistosomiasis. No association between parasite burden and the plasma levels of chemokine/cytokines or disease severity was observed. There was a positive association between plasma concentration of CCL4, sTNF-R1, CCL3 and MIF with gall bladder thickness and/or with portal vein thickness that are liver fibrosis markers. In contrast, no association was found between CCL7 plasma concentrations with any of the schistosomiasis morbidity parameters evaluated. The data showed that CCL24, sTNFR1, MIF and CCL3 can be detected in plasma of S. mansoni-infected individuals and their concentration would be used as prognostic makers of Schistosoma-induced liver fibrosis, even in individuals with low parasite burden.

Predictors of the short- and long-term survival of HIV-infected patients admitted to a Brazilian intensive care unit.

The outcomes of HIV-infected patients requiring critical care have improved. However, in developing countries, information about HIV-infected patients admitted to intensive care units (ICUs) is scarce. We describe the prognosis of HIV-infected patients admitted to a Brazilian ICU and the factors predictive of short- and long-term survival. A historical cohort study, including HIV-infected patients admitted to a Brazilian ICU at an HIV/AIDS reference hospital, was conducted. Survivors were followed up for 24 months after ICU discharge. Demographic, clinical and laboratory data, disease severity scores and mortality were evaluated. Data were analysed using survival and regression models. One hundred and twenty-five patients were studied. In-ICU and in-hospital mortality rates were 46.4% and 68.0%, respectively. Multivariate analysis showed that the in-ICU mortality was significantly associated with APACHE (Acute Physiology and Chronic Health Evaluation) II scores (odds ratio [OR], 1.11; 95% confidence interval [CI], 1.03-1.11), mechanical ventilation (OR, 6.39; 95% CI, 1.29-31.76), tuberculosis treatment (OR, 2.62; 95% CI, 1.03-6.71), use of antiretroviral therapy (OR, 0.19; 95% CI, 0.05-0.77) and septic shock (OR, 4.38; 95% CI, 1.78-10.76). Septic shock was also associated with long-term survival (hazard ratio, 3.0; 95% CI, 1.31-6.90). In-hospital and in-ICU mortality were higher than those reported for developed countries. ICU admission mostly due to AIDS-related diseases may explain these differences.

Serum and cerebral spinal fluid levels of chemokines and Th2 cytokines in Schistosoma mansoni myeloradiculopathy.

Schistosomal myeloradiculopathy (SMR) is the most common neurological form of Schistosoma mansoni infection. In this study we investigated the expression of chemokines and Th2 cytokines in serum and cerebral spinal fluid (CSF) of SMR patients. SMR patients presented increased serum levels of CCL11/eotaxin and CCL24/eotaxin-2 when compared to controls. SMR patients also had higher levels of IL-13 in CSF. Thus, SMR patients present enhancement of both IL-13 and CCR3 acting chemokines, both of which may facilitate the expression of a Th2 response and Th2-dependent damage to the spinal cord. As this cytokine is responsible for promoting Th2 responses, this finding is in accordance to the view that Th2 cells are important in the immunological process against the S. mansoni.

The use and misuse of the "impact factor" as a parameter for evaluation of scientific publication quality: a proposal to rationalize its application.

We present a critical analysis of the generalized use of the "impact factor". By means of the Kruskal-Wallis test, it was shown that it is not possible to compare distinct disciplines using the impact factor without adjustments. After assigning the median journal the value of one (1.000), the impact factor value for each journal was calculated by the rule of three. The adjusted values were homogeneous, thus permitting comparison among distinct disciplines.

The use and misuse of the "impact factor" as a parameter for evaluation of scientific publication quality: a proposal to rationalize its application

We present a critical analysis of the generalized use of the "impact factor". By means of the Kruskal-Wallis test, it was shown that it is not possible to compare distinct disciplines using the impact factor without adjustments. After assigning the median journal the value of one (1.000), the impact factor value for each journal was calculated by the rule of three. The adjusted values were homogeneous, thus permitting comparison among distinct disciplines.

Efficacy of oxamniquine and praziquantel in the treatment of Schistosoma mansoni infection: a controlled trial.

OBJECTIVE: To evaluate the therapeutic efficacy of oxamniquine and praziquantel, the two most clinically important schistosomicide drugs, and to compare the accuracy of faecal examination with the accuracy of oogram in testing for Schistosoma mansoni infection. METHODS: In a triple-masked and randomized controlled trial, 106 patients infected with S. mansoni were randomly allocated to one of three statistically homogeneous groups. One group was given 60 mg/kg praziquantel per day for three consecutive days, another was given two daily doses of 10 mg/kg oxamniquine, and the placebo group received starch. Faecal examinations (days 15, 30, 60, 90, 120, 150, and 180 after treatment) and biopsy of rectal mucosa by quantitative oogram (days 30, 60, 120, and 180) were used for the initial diagnosis and for evaluating the degree of cure. The chi2 test and the Kruskal-Wallis test were used to compare variables in the three groups. Survival analysis (Kaplan-Meier) and the log-rank test were used to evaluate the efficacy of the treatments. FINDINGS: The sensitivity of stool examinations ranged from 88.9% to 94.4% when patients presented with >5000 S. mansoni eggs per gram of tissue (oogram); when the number of eggs dropped to <1000 eggs per gram, sensitivity was reduced (range, 22.7-34.0%). When cure was evaluated by stool examination, oxamniquine and praziquantel had cure rates of 90.3% and 100%, respectively. However, when the oogram was used as an indicator of sensitivity, the oxamniquine cure rate dropped dramatically (to 42.4%), whereas the rate for praziquantel remained high, at 96.1%. CONCLUSIONS: Praziquantel was significantly more effective than oxamniquine in treating S. mansoni infection. The oogram was markedly more sensitive than stool examinations in detecting S. mansoni eggs and should be recommended for use in clinical trials with schistosomicides.

Hepatosplenic schistosomiasis in field-based studies: a combined clinical and sonographic definition.

A combined clinical and sonographic classification of hepatosplenic schistosomiasis mansoni to be used in field-based studies is proposed herein. Seven hundred forty one individuals out of 892 (83%), living in an area endemic for schistosomiasis in Brazil, have been submitted to clinical and ultrasound examinations. Based on two stool examinations the overall prevalence for schistosomiasis in this area was 73%. Abdominal palpation was performed with patients in dorsal decubit, during deep breath, by two experienced physicians and a portable ultrasound was used for the evaluation of liver fibrosis, portal collaterals and spleen size. Four groups of individuals were identified using data obtained by abdominal palpation and ultrasound examination: (1) palpable spleen and intense periportal thickening in 9 individuals (1.2%); (2) spleen not palpable and intense periportal thickening in 15 (2%); (3) palpable spleen with light to moderate periportal thickening in 32 (4.3%), and (4) palpable spleen with a normal liver on ultrasound in 30 (4%). The definition of hepatosplenic schistosomiasis in field-based studies as the finding of Schistosoma mansoni eggs in the stools in an individual with splenomegaly is not acceptable anymore. Abdominal ultrasound should be combined with clinical examination to accurately identify hepatosplenics in endemic areas for schistosomiasis.

Nested case-control study in a serological survey to evaluate the effectiveness of a Chagas disease control programme in Brazil.

OBJECTIVE: To identify risk factors associated with Trypanosoma cruzi infections in areas under surveillance in the State of Minas Gerais, Brazil. METHODS: A model using a nested case-control design incorporated within a serological survey of schoolchildren which was employed to evaluate the effectiveness of the Chagas disease control programme. FINDINGS: In a sample of 40,374 schoolchildren (aged 7-14 years) surveyed, 16 children tested positive for T. cruzi antibody (by indirect immunofluorescence and indirect haemagglutination). In the case-control study, each case was randomly matched to three seronegative controls (classroom and age +/- 1 year). Compared to controls, T. cruzi-seropositive children were more likely to have a seropositive mother (odds ratio (OR) = 6.8; 95% confidence interval (CI) = 0.71-63.9) or a seropositive family member (OR = 8.6; 95% CI = 1.0-75.5). CONCLUSION: Use of the nested case-control model in a sero-epidemiological survey to evaluate risk factors for T. cruzi transmission was adequate for assessing the effectiveness of a Chagas disease control programme.

Human toxocariasis and pyogenic liver abscess: a possible association.

OBJECTIVES: To study the role of human toxocariasis in the pathogenesis of pyogenic liver abscess. METHODS: We compared the serology for toxocariasis and serum levels of IgE in 16 patients with pyogenic liver abscess to those in 32 matched (age and gender) controls to define the possible association between these two entities. RESULTS: The serology for toxocariasis was positive in 10 of 16 patients compared with 4 of 32 controls. The relative odds and 95% confidence interval (conditional logistic regression), comparing cases and matched controls, was significant (1.4; 95% confidence interval, 1.1-1.7) for Toxocara serology. Regarding IgE serum levels, there was no difference between cases and controls. CONCLUSIONS: Human toxocariasis can be one of the predisposing causes of pyogenic liver abscess, especially in tropical countries in which this parasitic disease is common. Treatment of human toxocariasis may prevent morbid complications like hepatic abscess and should be considered in patients with clinical and/or serological evidence of Toxocara infection.

[Association between socioeconomic factors and infant deaths due to diarrhea, pneumonia, and malnutrition in a metropolitan area of Southeast Brazil: a case-control study]. / Associação entre fatores sócio-econômicos e mortalidade infantil por diarréia, pneumonia e desnutrição em região metropolitana do Sudeste do Brasil: um estudo caso-controle.

A population-based case-control study was carried out to identify determinant factors for post-neonatal infant deaths due to diarrhea, pneumonia, and malnutrition in Greater Metropolitan Belo Horizonte, Southeast Brazil. From May 1, 1991, to April 30, 1992, 511 post-neonatal deaths due to diarrhea, pneumonia, and malnutrition were selected after investigation of medical records to validate cause of death. Of this total, 396 deaths were compared to a neighborhood control group, matched for age. The study was carried out in a low-income area with a high proportion of families living in shantytowns. The article discusses the methodology and selected socioeconomic factors. Logistic regression analysis indicated that number of household appliances, mother's and father's education, and mother's marital and work status were significantly associated with risk of infant death, i.e., they were determinants of infant deaths due to avoidable causes.

Differential patterns of glucose-induced electrical activity and intracellular calcium responses in single mouse and rat pancreatic islets.

Although isolated rat islets are widely used to study in vitro insulin secretion and the underlying metabolic and ionic processes, knowledge on the properties of glucose-induced electrical activity (GIEA), a key step in glucose-response coupling, has been gathered almost exclusively from microdissected mouse islets. Using a modified intracellular recording technique, we have now compared the patterns of GIEA in collagenase-isolated rat and mouse islets. Resting membrane potentials of rat and mouse beta-cells were approximately -50 and -60 mV, respectively. Both rat and mouse beta-cells displayed prompt membrane depolarizations in response to glucose. However, whereas the latter exhibited a bursting pattern consisting of alternating hyperpolarized and depolarized active phases, rat beta-cells fired action potentials from a nonoscillating membrane potential at all glucose concentrations (8.4-22.0 mmol/l). This was mirrored by changes in the intracellular Ca2+ concentration ([Ca2+]i), which was oscillatory in mouse and nonoscillatory in rat islets. Stimulated rat beta-cells were strongly hyperpolarized by diazoxide, an activator of ATP-dependent K+ channels. Glucose evoked dose-dependent depolarizations and [Ca2+]i increases in both rat (EC50 5.9-6.9 mmol/l) and mouse islets (EC50 8.3-9.5 mmol/l), although it did not affect the burst plateau potential in the latter case. We conclude that there are important differences between beta-cells from both species with respect to early steps in the stimulus-secretion coupling cascade based on the following findings: 1) mouse beta-cells have a larger resting K+ conductance in 2 mmol/l glucose, 2) rat beta-cells lack the compensatory mechanism responsible for generating membrane potential oscillations and holding the depolarized plateau potential in mouse beta-cells, and 3) the electrical and [Ca2+]i dose-response curves in rat beta-cells are shifted toward lower glucose concentrations. Exploring the molecular basis of these differences may clarify several a priori assumptions on the electrophysiological properties of rat beta-cells, which could foster the development of new working models of pancreatic beta-cell function.

Design, implementation, and evaluation at entry of a prospective cohort study of homosexual and bisexual HIV-1-negative men in Belo Horizonte, Brazil: Project Horizonte.

BACKGROUND AND OBJECTIVES: Project Horizonte, an open cohort of homosexual and bisexual HIV-1-negative men, is a component of the Minas Gerais AIDS Vaccine Program of the Federal University of Minas Gerais, Belo Horizonte, Brazil. Its objectives included the evaluation of seroincidence of HIV, to ascertain the role of counseling on behavior modification and to assess their willingness to participate in future HIV vaccine trials. METHODS: Various means of recruitment were used, including pamphlets, notices in community newspapers, radio, and television, at anonymous testing centers, and by word of mouth. RESULTS: From October 1994 to May 1999, 470 volunteers were enrolled. Their mean age was 26 years and over 70% of them had high school or college education. During the follow-up, they were seen every 6 months, when they received counseling and condoms, and when HIV testing was done. Eighteen seroconversions were observed, and the incidence rates estimates were 1.75 per 100 and 1.99 per 100 person-years, for 36 and 48 months of follow-up, respectively. During the entire period, 139 volunteers were lost to follow-up. Among them, 59 (42.4%) never returned after the initial visit and 51 (36.7) came only once after their initial visit. No losses were observed for those observed during follow-up for more than 3 years. At enrollment, 50% of participants said they would participate in a vaccine trial, and 30% said they might participate. CONCLUSIONS: The results obtained up to this moment confirm the feasibility of following this type of cohort for an extended period, estimating HIV incidence rate, and evaluating counseling for safe sexual practices in preparation for clinical trials with candidate HIV vaccines in Brazil.

Sexually transmitted diseases in homosexual and bisexual males from a cohort of human immunodeficiency virus negative volunteers (Project Horizonte), Belo Horizonte, Brazil

Sexually transmitted diseases (STD) are very frequent in the whole world. Males who do not use a condom during their sexual relations are at great risk. We report cases of STD during six months of observation, among homosexual/bisexual males who participate in the Project Horizonte. There were 16 cases of genital warts, 6 cases of human immunodeficiency virus infection, 24 cases of unspecific urethritis, 28 cases of herpes simplex virus infection, 30 cases of syphilis, 58 cases of gonorrhea and 84 cases of pediculosis. We concluded that a condom must be used in all sexual relations and new counseling techniques are needed, to avoid this situation

Sexually transmitted diseases in homosexual and bisexual males from a cohort of human immunodeficiency virus negative volunteers (Project Horizonte), Belo Horizonte, Brazil.

Sexually transmitted diseases (STD) are very frequent in the whole world. Males who do not use a condom during their sexual relations are at great risk. We report cases of STD during six months of observation, among homosexual/bisexual males who participate in the Project Horizonte. There were 16 cases of genital warts, 6 cases of human immunodeficiency virus infection, 24 cases of unspecific urethritis, 28 cases of herpes simplex virus infection, 30 cases of syphilis, 58 cases of gonorrhea and 84 cases of pediculosis. We concluded that a condom must be used in all sexual relations and new counseling techniques are needed, to avoid this situation.

Schistosoma mansoni: assessment of morbidity before and after control.

The literature on the assessment of morbidity due to Schistosoma mansoni infection is updated. Imaging techniques such as ultrasonography, echodoppler cardiography, computerized tomography (CT scan) and magnetic resonance imaging (MRI) introduced a new perspective, and expanded our knowledge on morbidity. Three well-defined syndromes caused by schistosomiasis mansoni have been described: the stage of invasion, acute schistosomiasis (Katayama fever), and chronic schistosomiasis. Complications of the acute and chronic syndromes have also been reported: pulmonary hypertension, neuroschistosomiasis, association with Salmonella, association with Staphylococci, viral hepatitis B, glomerulonephritis. In most individuals with hepatosplenic schistosomiasis the spleen is increased in size. Hepatosplenic schistosomiasis can, however, occur without splenomegaly. The definition of hepatosplenic schistosomiasis in endemic areas as the finding of S. mansoni eggs in the stools in an individual with hepatosplenomegaly is not satisfactory anymore. Many aspects of morbidity are expected to change after schistosomiasis control. Some are expected to change quickly (worm burden, Salmonella bacteremia, hepatosplenic schistosomiasis in children) whereas others shall remain for years (pulmonary hypertension, glomerulonephritis, neuroschistosomiasis). Intestinal schistosomiasis in individuals with low worm burdens is very difficult to diagnose and therefore laborious to control.

The microfilarial periodicity of Wuchereria bancrofti in north-eastern Brazil.

The periodicity of Wuchereria bancrofti microfilariae (mff) in peripheral blood was analysed in 42 microfilaraemics living in Maceió, in Alagoas state, north-eastern Brazil. Nine blood samples were collected from each subject, over a 24-h period, and two quantitative (60-microliter) thick smears were prepared from each sample. Although all the subjects had detectable microfilaraemias from 23.00 hours to 06.00 hours, no mff could be detected in most (71.4%) of the smears prepared from samples collected at 15.00 hours. Samples collected during the day, at 15.00 hours, contained 170 times fewer mff/microliter than those collected at 01.00 hours, when microfilaraemias were generally most intense. For diagnosis of bancroftian filariasis in Maceió, blood samples should be collected between 22.00 and 03.00 hours, when microfilarial counts will be at least 90% of the peak counts. The circadian variation observed was independent of the subject's gender and microfilarial density. Mathematical analysis, using a simple harmonic-wave model, indicated a periodicity index of 127.6 and that maximum microfilarial densities occurred at 00.51 hours, confirming the nocturnal pattern of microfilaraemia in the study area.