Marta Cristhiany Cunha Pinheiro

Analgesic and Anti-Inflammatory Activities of the Isomeric Mixture of Alpha- and Beta-Amyrin from Protium heptaphyllum(Aubl.) March

In the present work, we demonsteated that the mixture of alpha- and beta-amyrin (AMI) from Protium heptaphyllum has anti-nociceptive activity as was evident from the writhing and formalin tests in mice. AMI (10 and 50 mg/kg, i.p.) inhibited writhing in 73 and 94%, respectively, while preferentially inhibiting the 2nd phase of the response (37 and 51; and 60 and 73% inhibitions of the 1st and 2nd phases, respectively) to the formalin test. Naloxone, an opioid antagonist, did not reverse the antinociceptive effect. AMI (50 mg/kg, i.p.) was also active in the hot plate test, increasing the reaction time to thermal stimulus after 30 and 60 min, by 62 and 71%, respectively. A preventive antiedematogenic effect was observed in mice that had a carrageenan-in-duced paw edema. Paw volume was significantly and dose-dependently decreased by 39,42 and 53%, three hours after administration of 10, 25 and 50 mg/kg doses, i.p., respectively. AMI (25 and 50 mg/kg, i.p.) was also able to reverse the edema already induced by carrageenan (curative effect). AMI (10 and 25 mg/kg, i.p.) was equally effective in the dex-tran-induced paw edema (preventive effect), reducing the paw volume by 50 and 60% at the 2nd hour, and by 63 and 73% at the third hour post-dose. AMI (50 mg/kg, i.p.) reverted the edema already formed after the dextran injection (curative effect). In conclusion, AMI demonstrated peripheral and central analgesic effects independent of the opioid system, and also showed a potent anti-inflammatory activity. The anti-inflammatory activity was potentiated by both indomethacin and thalid-omide, suggesting a potential involvement of prostaglandins and TNF-alpha inhibitions.

Trends in schistosomiasis-related mortality in Brazil, 2000-2011.

Schistosomiasis is an important public health problem, with high morbidity and mortality in endemic countries. We analysed the epidemiological characteristics and time trends of schistosomiasis-related mortality in Brazil. We performed a nationwide study based on official mortality data obtained from the Brazilian Mortality Information System. We included all deaths in Brazil between 2000 and 2011, in which schistosomiasis was mentioned on the death certificate as an underlying or associated cause of death (multiple causes of death). We calculated crude and age-adjusted mortality rates (per 100,000 inhabitants), and proportional mortality rates. Trends over time were assessed using joinpoint regression models. Over the 12-year study period, 12,491,280 deaths were recorded in Brazil. Schistosomiasis was mentioned in 8,756 deaths, including in 6,319 (72.2%) as an underlying cause and in 2,437 (27.8%) as an associated cause. The average annual age-adjusted mortality rate was 0.49 deaths/100,000 inhabitants (95% confidence interval: 0.46-0.52) and proportional mortality rate was 0.070% (95% confidence interval: 0.069-0.072). Males (0.53 deaths/100,000 inhabitants), those aged ⩾70years (3.41 deaths/100,000 inhabitants), those of brown race/colour (0.44 deaths/100,000 inhabitants), and residents in the Northeast region of Brazil (1.19 deaths/100,000 inhabitants) had the highest schistosomiasis-related death rates. Age-adjusted mortality rates showed a significant decrease at a national level (Annual Percent Change: -2.8%; 95% confidence interval: -4.2 to -2.4) during the studied period. We observed decreasing mortality rates in the Northeast (Annual Percent Change: -2.5%; 95% confidence interval: -4.2 to -0.8), Southeast (Annual Percent Change: -2.2%; 95% confidence interval: -3.6 to -0.9), and Central-West (Annual Percent Change: -7.9%; 95% confidence interval: -11.3 to -4.3) regions, while the rates remained stable in the North and South regions. Despite the reduced mortality, schistosomiasis is still a neglected cause of death in Brazil, with considerable regional differences. Sustainable control measures should focus on increased coverage, and intensified and tailored control measures, to prevent the occurrence of severe forms of schistosomiasis and associated deaths.

Increased detection of schistosomiasis with Kato-Katz and SWAP-IgG-ELISA in a Northeastern Brazil low-intensity transmission area

INTRODUCTION The laboratory diagnosis of schistosomiasis is based mainly on the detection of parasite eggs in stool samples through the Kato-Katz (KK) technique, reading one slide by test. However, a widely known limitation of parasitological methods is reduced sensitivity, particularly in low endemic areas. METHODS To increase sensitivity, we conducted further slide readings from the same stool sample using the parasitological method associated with a serological test. We used the KK method (three slides) and the IgG anti-Schistosoma mansoni-enzyme-linked immunosorbent assay (ELISA) technique to diagnose schistosomiasis in low endemic areas in the Brazilian State of Ceará. Fecal samples and sera from 250 individuals were analyzed. RESULTS Sixteen percent and 47.2% of samples were positive in parasitological tests and serological tests, respectively. Parasitological methods showed that 32 (80%) individuals tested positive on the first slide, 6 (15%) on the second slide, and 2 (5%) on the third. The performance of the ELISA test in the diagnosis, using the KK method as diagnostic reference, showed a negative predictive value of 100%, with specificity and positive predictive values of 62.8% and 33.9%, respectively. CONCLUSIONS In this study, the increase from one to three slides analyzed per sample using the KK technique was shown to be a useful procedure for increasing the diagnostic sensitivity of this technique.

The combination of three faecal parasitological methods to improve the diagnosis of schistosomiasis mansoni in a low endemic setting in the state of Ceará, Brazil

Laboratory diagnosis of intestinal schistosomiasis mansoni can be accomplished through various methods of stool examination to detect parasites, ranging from the most classic tests (Kato-Katz) to several methods that are still undergoing validation. This study was conducted to assess two new parasite identification methods for diagnosing schistosomiasis mansoni in residents of a low endemic area in the municipality of Maranguape, in the state of Ceará, Brazil using the Kato-Katz method as a reference and serology (enzyme-linked immunosorbent assay) for the screening of patients. The Kato-Katz, the saline gradient method and the Helmintex(®) method parasite identification methods were employed only in subjects who exhibited positive serologic tests. The test results were then analysed and treatment of positive individuals was subsequently performed. After comparing the test results, we observed that the saline gradient method and the Helmintex(®) method were more effective in diagnosing schistosomiasis mansoni in the study area compared with the Kato-Katz method.

Spatiotemporal Patterns of Schistosomiasis-Related Deaths, Brazil, 2000-2011.

We analyzed spatiotemporal patterns of 8,756 schistosomiasis-related deaths in Brazil during 2000–2011 and identified high-risk clusters of deaths, mainly in highly schistosomiasis-endemic areas along the coast of Brazil’s Northeast Region. Schistosomiasis remains a neglected public health problem with a high number of deaths in disease-endemic and emerging focal areas.

A conventional polymerase chain reaction-based method for the diagnosis of human schistosomiasis in stool samples from individuals in a low-endemicity area

The aim of this study was to evaluate the efficacy of a polymerase chain reaction (PCR)-based method to detect Schistosoma mansoni DNA in stool samples from individuals living in a low-endemicity area in Brazil. Of the 125 initial stool samples, 80 were ELISA reactive and eggs were identified in 19 of the samples by parasitological examination. For the PCR evaluations, 56 stool samples were selected and divided into five groups. Groups I-IV were scored negative for S. mansoni eggs by parasitological examination. Groups I and II were ELISA reactive, whereas Groups III and IV were ELISA nonreactive. Groups II and III were positive for other intestinal parasites. PCR testing scored eight samples as positive from these four groups. Group V represented the S. mansoni -positive group and it included ELISA-reactive samples that were scored positive for S. mansoni by one or more parasitological examinations (6/19 were positive by Kato-Katz method, 9/17 by saline gradient and 10/13 by Helmintex®). PCR scored 13 of these 19 samples as positive for S. mansoni . We conclude that while none of these methods yielded 100% sensitivity, a combination of techniques should be effective for improving the detection of S. mansoni infection in low-endemicity areas.

Association between allergic responses and Schistosoma mansoni infection in residents in a low-endemic setting in Brazil

INTRODUCTION Schistosomiasis is endemic in 76 countries and territories. Several studies have found an inverse correlation between parasitic disease and the development of allergies. The purpose of the present study was to determine whether infection with Schistosoma mansoni in subjects with a low parasite load is protective against allergy. The final sample consisted of 39 S. mansoni-positive and 52 S. mansoni-negative residents of a small community in northeastern Brazil. METHODS All subjects were submitted to the Kato-Katz test, anti-S. mansoni IgG measurement, the prick test for aeroallergens, eosinophil counts and serum IgE measurement. RESULTS Subjects who reacted to one or more antigens in the prick test were considered allergic. Only 7 S. mansoni-positive subjects (17.9%) reacted to one or more antigens, whereas 20 S. mansoni-negative subjects (38.5%) tested positive for allergy. CONCLUSIONS Our findings suggest that, in areas of low endemicity, infection with S. mansoni significantly reduces the risk of the development of allergy in subjects with a low parasite load.

Monocyte Chemotactic Protein-1 (MCP-1) in Patients with Chronic Schistosomiasis Mansoni: Evidences of Subclinical Renal Inflammation

The aim of this study is to investigate renal markers and the biomarker MCP-1 in patients with schistosomiasis mansoni. This is a cross-sectional study with 85 patients aged 5 to 48 years, with a confirmed diagnosis of schistosomiasis mansoni through the Kato-Katz method. The patients were divided in three groups: control (G-I); infected by S. mansoni before treatment (G-II) and infected by S. mansoni after treatment (G-III). Renal function was evaluated by tubular and glomerular biomarkers and through urinary MCP-1. Patients’ mean age was 23.2±13 years. There was no statistically significant difference between the groups regarding tubular and glomerular function evaluated through the traditional biomarkers. MCP-1 was higher in G-II and G-III, when compared to G-I; p=0.009 and p=0.007, respectively. There was no difference when comparing groups G-II and G-III (p=0.892). Although it was not different among the groups, there was a significant correlation between albuminuria and MCP-1. There was a significant increase in urinary MCP-1 levels in patients with schistosomiasis mansoni, which was associated with albuminuria. This protein has a role in the recruitment of monocytes to injury and inflammation sites . The increase of MCP-1 in the urine evidences that there is silent renal inflammation in these patients and the inflammatory status is not interrupted by specific treatment of the offending agent. Our findings suggest that urinary MCP-1 can be a sensitive marker of renal injury in patients with schistosomiasis mansoni.

Detection of schistosomiasis in an area directly affected by the São Francisco River large-scale water transposition project in the northeast of Brazil

INTRODUCTION The development of the São Francisco River Integration Project [Projeto de Integração do Rio São Francisco (PISF)] in the State of Ceará, Brazil, has resulted in environmental and socioeconomic changes with potential risks to public health. We aimed to determine the presence of Schistosoma mansoni infections in schoolchildren (aged 7-14 years) and workers from the construction site in an area under the direct influence of the PISF in the municipality of Brejo Santo-CE, to aid in the prevention and control of schistosomiasis. METHODS We conducted a cross-sectional study using two S. mansoni-detection methods: detection of S. mansoni eggs by the Kato-Katz parasitological method in stool samples (assessed in triplicate for each sample) and S. mansoni circulating cathodic antigen by the point-of-care immunochromatographic rapid test (POC-CCA) in urine. RESULTS In general, the positivity rates for S. mansoni detection were 1.9% (2/106) among schoolchildren and 2.9% (4/138) among workers. No child had evidence of S. mansoni eggs in their stools; 1.9% tested positive by the POC-CCA method. Among workers, two (1.4%) tested positive by the Kato-Katz test and three (2.2%) by the POC-CCA test. If the POC-CCA test results that were scored as traces were considered negative, then the positivity rates dropped to 0.9% and 0.7% for schoolchildren and workers, respectively. CONCLUSIONS The active transmission of schistosomiasis in a region covered by the PISF was recognized, reinforcing the necessity to consolidate surveillance and control actions, as well as structural sanitation measures to reverse the social determinants of the disease.