Geospatial analysis and prevalence of Schistosoma mansoni and soil-transmitted helminth infections in an endemic area in Eastern Brazilian Amazon.

OBJECTIVES: This study evaluated the occurrence of Schistosoma mansoni and soil-transmitted helminths in an endemic area in the Eastern Brazilian Amazon, analysing prevalence and spatial distribution. METHODS: The study was conducted in four localities of Primavera Municipality, in Pará state. Data was obtained from the Decit 40/2012 project and the participants were divided into five age range categories for evaluation: children, adolescents, young adults, adults and elderly individuals. For the diagnostic tests, Kato-Katz slides were prepared to detect S. mansoni and soil-transmitted helminths eggs. The spatial distribution map and the Kernel Density Estimation were performed to assess the presence and location of infections. RESULTS: Stool samples revealed the presence of hookworms, S. mansoni, Ascaris lumbricoides and Trichuris trichiura eggs. Mono-, bi- and poly-parasitic infections were observed, with a significant prevalence of hookworm monoparasitism. CONCLUSIONS: The high frequency of children infected with soil-transmitted helminths confirms their significance as an ongoing public health problem in the poorest municipalities of Brazil. The Geographic Information System plays a crucial role in environmental surveillance and in the control of epidemics and endemic diseases, enabling accurate assessment and informed decision-making for their control.

Epidemiological profile of human toxocariasis in patients examined at Evandro Chagas Institute (IEC/SVSA/MS) between 2014 and 2019.

INTRODUCTION: Toxocariasis is caused by nematodes of Toxocara genus, which infest dogs and cats, with humans serving as paratenic hosts. METHODS: The epidemiological profile of patients examined for toxocariasis between October 2014 and October 2019 at Evandro Chagas Institute (IEC) was outlined. The frequency of anti-T. canis IgG antibodies were evaluated using the Enzyme Linked Immunosorbent Assay (ELISA) method. RESULTS: From a total of 734 samples, 56% were from male (p < 0.05). Regarding age, the group with the most solicitations were from ≤11 years old individuals (p < 0.05). Pará state had the highest number of exams requested (92%), with the majority from residents of urban areas, accounting for 81.5% of samples (p < 0.05). The overall toxocariasis seroprevalence was 41.8%, the male sex being the most frequent with 60.9% (p < 0.05). The most affected age group was ≤11 years old, with a total of 67.8% of positive samples (p < 0.05). CONCLUSION: The high rates obtained emphasize the need for complementary studies on toxocariasis in Brazil, especially in Pará state, contributing to epidemiological surveillance actions in the control of this infection. Besides, health campaigns for domestic and stray animals, also can contribute to a more effective surveillance in controlling parasitic infections and encourages the One Health approach.

FioSchisto's expert perspective on implementing WHO guidelines for schistosomiasis control and transmission elimination in Brazil.

The World Health Organization (WHO) recognizes schistosomiasis as one of the Neglected Tropical Diseases targeted for global elimination in the 2030 Agenda of the Sustainable Development Goals. In Brazil, schistosomiasis mansoni is considered a public health problem, particularly prevalent among vulnerable populations living in areas with poor environmental and sanitary conditions. In 2022, the WHO published a Guideline encompassing recommendations to assist national programs in endemic countries in achieving morbidity control, eliminating schistosomiasis as a public health problem, and advancing towards interrupting transmission. The perspectives presented here, collectively prepared by members of the Oswaldo Cruz Foundation's (Fiocruz) Schistosomiasis Translational Program (FioSchisto), along with invited experts, examine the feasibility of the WHO recommendations for the Brazilian settings, providing appropriate recommendations for public health policies applicable to the epidemiological reality of Brazil, and suggests future research to address relevant issues. In Brazil, the provision of safe water and sanitation should be the key action to achieve schistosomiasis elimination goals. The agencies involved in measures implementation should act together with the Primary Care teams for planning, executing, monitoring, and evaluating actions in priority municipalities based on their epidemiological indicators. Host snails control should prioritize judicious ecological interventions at breeding sites. The Information, Education, and Communication (IEC) strategy should be associated with water and sanitation and other control actions, actively involving school community. To identify infected carriers, FioSchisto recommends a two-stage approach of immunological and molecular tests to verify transmission interruption during the intervention and beyond. Praziquantel administration should be done under medical supervision at the Primary Care level. MDA should be considered in exceptional settings, as a measure of initial attack strategy in locations presenting high endemicity, always integrated with water and sanitation, IEC, and snail control. To assist decision-making, as well as the monitoring and evaluation of strategic actions, there is a need for an Information System. FioSchisto considers this systematization essential to make investments in strategic research to support the improvement of schistosomiasis control actions. Efforts toward schistosomiasis elimination in Brazil will succeed with a paradigm shift from the vertical prescriptive framework to a community-centered approach involving intersectoral and interdisciplinary collaboration.

Experimental infection with Schistosoma mansoni from Belém, Pará, Brazil: Strains newly isolated vs. laboratory maintained.

BACKGROUND: Schistosomiasis is a neglected tropical disease that occurs in locations with inadequate sanitation conditions. The geographic distribution of Schistosoma mansoni trematode depends directly on the presence of its intermediate host, Biomphalaria mollusks. Studies involving recently isolated and laboratory strains are not common due to the difficulty in cycle maintenance. This study evaluated the susceptibility and infectivity responses in intermediate and definitive hosts with strains of S. mansoni, one isolated and kept in laboratory environment for 34 years (BE) and the other recently collected (BE-I) METHODS: For experimental infection, a total of 400 B. glabrata mollusks were divided in four infection groups. Thirty mice were divided in two groups for infection with the two strains. RESULTS: It was possible to notice differences about S. mansoni infection in both strains. The laboratory strain was more harmful to freshly collected mollusks. Differences in the patterns of infection in mice could be observed. CONCLUSION: Particularities occurred in each group of infection by S. mansoni strains, despite having the same geographic origin. Effects from the parasite-host interaction are visible in terms of infection in definitive and intermediate hosts.

Development and evaluation of an indirect ELISA using a multiepitope antigen for the diagnosis of intestinal schistosomiasis.

The laboratory diagnosis of intestinal schistosomiasis, carried out by detecting parasite eggs in feces, has low sensitivity when applied to individuals with low parasitic load. Serological tests can be more sensitive for the diagnosis of the disease. Therefore, the objective of this work was to develop and evaluate an ELISA-based immunoenzymatic assay, using a Schistosoma mansoni multiepitope antigen (ELISA IgG anti-SmME). For this, the amino acid sequences of S. mansoni cathepsin B and asparaginyl endopeptidase were submitted to the prediction of B cell epitopes and, together with peptide sequences obtained from earlier works, were used in the construction of a minigene. The multiepitope protein was expressed in Escherichia coli and the performance of the ELISA IgG anti-SmME for schistosomiasis was evaluated using serum samples from 107 individuals either egg positive or negative. In addition, 11 samples from individuals with other helminth infections were included. The ELISA IgG anti-SmME showed a sensitivity of 81.1% and a specificity of 46.1%. Further analysis revealed a 77.2% sensitivity in diagnosis of individuals with egg counts of ≤12 epg (eggs per gram feces) and 87.5% for individuals with 13­99 epg. It is worth mentioning that, to our knowledge, this was the first study using a multiepitope recombinant antigen in an ELISA for diagnosis of intestinal schistosomiasis, which demonstrated promising results in the diagnosis of individuals with low parasitic loads.

Impaired dynamics of precapillary sphincters and pericytes at first-order capillaries predict reduced neurovascular function in the aging mouse brain.

The microvascular inflow tract, comprising the penetrating arterioles, precapillary sphincters and first-order capillaries, is the bottleneck for brain blood flow and energy supply. Exactly how aging alters the structure and function of the microvascular inflow tract remains unclear. By in vivo four-dimensional two-photon imaging, we reveal an age-dependent decrease in vaso-responsivity accompanied by a decrease in vessel density close to the arterioles and loss of vascular mural cell processes, although the number of mural cell somas and their alpha smooth muscle actin density were preserved. The age-related reduction in vascular reactivity was mostly pronounced at precapillary sphincters, highlighting their crucial role in capillary blood flow regulation. Mathematical modeling revealed impaired pressure and flow control in aged mice during vasoconstriction. Interventions that preserve dynamics of cerebral blood vessels may ameliorate age-related decreases in blood flow and prevent brain frailty.

First report of Biomphalaria tenagophila (d'Orbigny, 1835) (Gastropoda/Planorbidae) in Pará State, Amazon region of Brazil.

INTRODUCTION: Mollusks belonging to Biomphalaria genus are intermediate hosts of Schistosoma mansoni. In the Pará State, Northern Region of Brazil, there are reports of B. glabrata, B. straminea, B. schrammi, B. occidentalis, and B. kuhniana occurrence. Here, we report for the first time the presence of B. tenagophila in Belém, capital of Pará state. METHODS: A total of 79 mollusks were collected and examined to search for possible S. mansoni infection. The specific identification was made by morphological and molecular assays. RESULTS: No specimens parasitized by trematode larvae were detected. For the first time the presence of B. tenagophila in Belém, capital of Pará state, was reported. CONCLUSION: The result increases the knowledge about Biomphalaria mollusks occurrence in the Amazon Region and specifically alerts on the possible role of B. tenagophila in schistosomiasis transmission in Belém.

Accuracy of the urine point-of-care circulating cathodic antigen assay for diagnosing Schistosomiasis mansoni infection in Brazil: A multicenter study.

BACKGROUND: The World Health Organization recommends a market-ready, urine-based point-of-care diagnostic test for circulating cathodic antigens (CCA) to determine the prevalence of S. mansoni. This study evaluated the performance of the URINE CCA (SCHISTO) ECO TESTE® (POC-ECO), which is currently available in Brazil. METHODS: Residents from eight sites with different prevalence estimates provided one urine sample for POC-ECO and one stool sample for Kato-Katz (KK) and Helmintex® (HTX) testing as an egg-detecting reference for infection status. RESULTS: None of the study sites had significantly higher POC-ECO accuracy than KK. CONCLUSIONS: POC-ECO is not currently recommended in Brazilian schistosomiasis elimination programs.

Accuracy of the urine point-of-care circulating cathodic antigen assay for diagnosing Schistosomiasis mansoni infection in Brazil: A multicenter study

ABSTRACT Background: The World Health Organization recommends a market-ready, urine-based point-of-care diagnostic test for circulating cathodic antigens (CCA) to determine the prevalence of S. mansoni. This study evaluated the performance of the URINE CCA (SCHISTO) ECO TESTE® (POC-ECO), which is currently available in Brazil. Methods: Residents from eight sites with different prevalence estimates provided one urine sample for POC-ECO and one stool sample for Kato-Katz (KK) and Helmintex® (HTX) testing as an egg-detecting reference for infection status. Results: None of the study sites had significantly higher POC-ECO accuracy than KK. Conclusions: POC-ECO is not currently recommended in Brazilian schistosomiasis elimination programs.

Reliability of point-of-care circulating cathodic antigen assay for diagnosing schistosomiasis mansoni in urine samples from an endemic area of Brazil after one year of storage at -20 degrees Celsius.

BACKGROUND: The World Health Organization recommends reliable point-of-care (POC) diagnostic testing to eliminate schistosomiasis. Lateral flow immunoassay that detects schistosome circulating cathodic antigen (CCA) in urine to establish prevalence thresholds for intervention in endemic areas is recommended. Stored urine may be useful if surveying at-risk populations is delayed or interrupted by unforeseen circumstances, such as the current COVID-19 pandemic. This study evaluated the manufacturer's claim that Schistosoma mansoni infection can be reliably diagnosed in urine samples stored at -20°C for one year. METHODS: Two-hundred-forty-two subjects from an endemic site in Brazil provided one urine sample each for testing with URINE CCA (SCHISTO) ECO TESTE® (POC-ECO) and one stool sample each for testing with Kato-Katz (KK) and Helmintex® (HTX) as a robust reference standard for infection status. At least 2 ml of urine from each participant was stored at -20°C; after one year, 76 samples were randomly selected for POC-ECO retesting. RESULTS: The POC-ECO agreement between freshly collected and stored urine was inadequate considering trace results as positive (Cohen's kappa coefficient κ = 0.08) and negative (κ = 0.36). POC-ECO accuracy was not significantly greater than that of routine KK (54%; 95% confidence interval: 42.1%-65.5%). CONCLUSIONS: The precision and accuracy of POC-ECO have to be optimized in both freshly collected and stored urine before it can be recommended for use in control programs in Brazil.

RLC score (R status, lymphovascular invasion, C-reactive protein) predicts survival following radical cystectomy for muscle-invasive bladder cancer.

BACKGROUND: CRP-based scoring systems were found to correlate with survival in patients with urooncologic diseases. Our retrospective single-centre study aimed to confirm CRP as a prognostic parameter in patients with bladder cancer (BCa) undergoing radical cystectomy (RC) and, based on the findings, to develop our own outcome score for muscle-invasive bladder cancer (MIBC) patients undergoing RC in order to identify patients with a high risk of mortality. MATERIAL AND METHODS: A total of 254 patients who underwent RC at Hanover Medical School between 1996 and 2007 were reviewed with a follow-up until autumn 2013. The clinicopathologic parameters assessed included age, co-morbidities, pre-/postoperative serum levels of CRP, leukocytes, haemoglobin, creatinine, urinary diversion, tumour grading, staging, lymph node status, lymph node density (LND), lymphovascular invasion (LVI), metastases, and resection margin status. The Chi-square test was used for univariate analyses. Kaplan-Meier estimates and the log-rank test were used for survival analyses. Regarding outcome, overall survival (OS) was assessed. RESULTS: The multivariate analysis excluding lymph node (LN)-positive and metastatic patients at time of RC showed a significant association of R status (R; p < 0.001), LVI (L; p = 0.021) and preoperative CRP level > 5 mg/l (C; p = 0.008) with OS. Based on these parameters, the RLC score was developed. The median OS in the intermediate, high-risk and very high-risk groups according to the RLC score was 62, 22, and 6.5 months, respectively. The score had a high predictive accuracy of 0.752. CONCLUSION: The RLC score identifies BCa patients at a higher risk of overall mortality after RC. Overall, our study supports the role of CRP in prognostic score models for BCa.

Reliability of point-of-care circulating cathodic antigen assay for diagnosing schistosomiasis mansoni in urine samples from an endemic area of Brazil after one year of storage at -20 degrees Celsius

ABSTRACT Background The World Health Organization recommends reliable point-of-care (POC) diagnostic testing to eliminate schistosomiasis. Lateral flow immunoassay that detects schistosome circulating cathodic antigen (CCA) in urine to establish prevalence thresholds for intervention in endemic areas is recommended. Stored urine may be useful if surveying at-risk populations is delayed or interrupted by unforeseen circumstances, such as the current COVID-19 pandemic. This study evaluated the manufacturer's claim that Schistosoma mansoni infection can be reliably diagnosed in urine samples stored at -20°C for one year. Methods Two-hundred-forty-two subjects from an endemic site in Brazil provided one urine sample each for testing with URINE CCA (SCHISTO) ECO TESTE® (POC-ECO) and one stool sample each for testing with Kato-Katz (KK) and Helmintex® (HTX) as a robust reference standard for infection status. At least 2 ml of urine from each participant was stored at -20°C; after one year, 76 samples were randomly selected for POC-ECO retesting. Results: The POC-ECO agreement between freshly collected and stored urine was inadequate considering trace results as positive (Cohen's kappa coefficient κ = 0.08) and negative (κ = 0.36). POC-ECO accuracy was not significantly greater than that of routine KK (54%; 95% confidence interval: 42.1%-65.5%). Conclusions The precision and accuracy of POC-ECO have to be optimized in both freshly collected and stored urine before it can be recommended for use in control programs in Brazil.

Spatial analysis studies of endemic diseases for health surveillance: Application of scan statistics for surveillance of tuberculosis among residents of a metropolitan municipality aged 60 years and above.

Health surveillance aims to monitor adverse health events, and to set disease prevention and control goals, especially for communicable diseases, such as tuberculosis (TB). Older people have a higher risk of TB, due to their specific characteristics, whichpredispose them to infectious disease. Thus, the objective of this study was to demonstrate the importance of scan statistics for detecting spatiotemporal clusters of TB. We conducted a quantitative is an ecological, descriptive study, with a quantitative approach, using the spatial analysis techniques, specifically scan statistics. The study was conducted in the municipality of Belém, Pará, in Brazil using data on 1,134 new cases of TB diagnosed in individuals aged ≥60 years from 2011 to 2015.The data were analyzed using SaTScan software. The analysis of the spatiotemporal dynamics of TB in the municipality showed thatthe high-risk areas includedthe most densely populated neighborhoods, highlighting the priority of theseareas for disease control measures. Spatial analysis can be used to guide more effective interventions according to the characteristics of the location and the local population.

Spatial analysis studies of endemic diseases for health surveillance: Application of scan statistics for surveillance of tuberculosis among residents of a metropolitan municipality aged 60 years and above / Atuação da vigilância em saúde para estudos de análises espaciais de doenças endêmicas: aplicação da técnica de varredura para vigilância de tuberculose em maiores de 60 anos

Abstract Health surveillance aims to monitor adverse health events, and to set disease prevention and control goals, especially for communicable diseases, such as tuberculosis (TB). Older people have a higher risk of TB, due to their specific characteristics, whichpredispose them to infectious disease. Thus, the objective of this study was to demonstrate the importance of scan statistics for detecting spatiotemporal clusters of TB. We conducted a quantitative is an ecological, descriptive study, with a quantitative approach, using the spatial analysis techniques, specifically scan statistics. The study was conducted in the municipality of Belém, Pará, in Brazil using data on 1,134 new cases of TB diagnosed in individuals aged ≥60 years from 2011 to 2015.The data were analyzed using SaTScan software. The analysis of the spatiotemporal dynamics of TB in the municipality showed thatthe high-risk areas includedthe most densely populated neighborhoods, highlighting the priority of theseareas for disease control measures. Spatial analysis can be used to guide more effective interventions according to the characteristics of the location and the local population.

Resumo A vigilância em saúde tem como objetivo o acompanhamento dos eventos adversos à saúde, estabelecendo metas de prevenção e controle, principalmente para as doenças transmissíveis, como a tuberculose. Quando relaciona a tuberculose com a população idosa, tem-se um fatormais agravante, devido as peculiaridades dessa população que favorecem na transmissão da doença. Desse modo, objetivo do trabalho é demonstrar a importância da técnica de varredura (estatística Scan) para detectar as áreas de aglomerados espaço-temporal da TB. Trata-se de um estudo ecológico, descritivo, com abordagem quantitativa, com uso da técnica de análise espacial, em especifico a técnica de varredura. O estudo ocorreu no município de Belém-PA, com 1.134 casos novos de TB em idosos no período de 2011 a 2015. Foi utilizado o programa SaTScan. A dinâmica da tuberculose no município mostrou-se que as áreas de riscos coincidiram com os bairros de maior densidade populacional, evidenciando as áreas prioritárias de maior vulnerabilidade que devem servir para nortear as intervenções mais efetivas de acordo com a característica do local e da sua população.

Improving the continuity and coordination of ambulatory care through feedback and facilitated dialogue-a study protocol for a cluster-randomised trial to evaluate the ACD study (Accountable Care in Germany).

BACKGROUND: Patients in Germany are free to seek care from any office-based physician and can always ask for multiple opinions on a diagnosis or treatment. The high density of physicians and the freedom to choose among them without referrals have led to a need for better coordination between the multiple health professionals treating any given patient. The objectives of this study are to (1) identify informal networks of physicians who treat the same patient population, (2) provide these physicians with feedback on their network and patients, using routine data and (3) give the physicians the opportunity to meet one another in facilitated network meetings. METHODS: The Accountable Care Deutschland (ACD) study is a prospective, non-blinded, cluster-randomised trial comprising a process and economic evaluation of informal networks among 12,525 GPs and office-based specialists and their 1.9 million patients. The units of allocation are the informal networks, which will be randomised either to the intervention (feedback and facilitated meetings) or control group (usual care). The informal networks will be generated by identifying connections between office-based physicians using complete datasets from the Regional Associations of Statutory Health Insurance (SHI) Physicians in Hamburg, Schleswig Holstein, North Rhine and Westphalia Lip, as well as data from three large statutory health insurers in Germany. The physicians will (a) receive feedback on selected indicators of their own treatment activity and that of the colleagues in their network and (b) will be invited to voluntary, facilitated network meetings by their Regional Association of SHI physicians. The primary outcome will be ambulatory-care-sensitive hospitalisations at baseline, at the end of the 2-year intervention period, and at six months and at 12 months after the end of the intervention period. Data will be analysed using the intention-to-treat principle. A pilot study preceded the ACD study. DISCUSSION: Cochrane reviews show that feedback can improve everyday medical practice by shedding light on previously unknown relationships. Providing physicians with information on how they are connected with their colleagues and what the outcomes are of care delivered within their informal networks can help them make these improvements, as well as strengthen their awareness of possible discontinuities in the care they provide. TRIAL REGISTRATION: German Clinical Trials Register DRKS00020884 . Registered on 25 March 2020-retrospectively registered.

Post-capillary venules are the key locus for transcytosis-mediated brain delivery of therapeutic nanoparticles.

Effective treatments of neurodegenerative diseases require drugs to be actively transported across the blood-brain barrier (BBB). However, nanoparticle drug carriers explored for this purpose show negligible brain uptake, and the lack of basic understanding of nanoparticle-BBB interactions underlies many translational failures. Here, using two-photon microscopy in mice, we characterize the receptor-mediated transcytosis of nanoparticles at all steps of delivery to the brain in vivo. We show that transferrin receptor-targeted liposome nanoparticles are sequestered by the endothelium at capillaries and venules, but not at arterioles. The nanoparticles move unobstructed within endothelium, but transcytosis-mediated brain entry occurs mainly at post-capillary venules, and is negligible in capillaries. The vascular location of nanoparticle brain entry corresponds to the presence of perivascular space, which facilitates nanoparticle movement after transcytosis. Thus, post-capillary venules are the point-of-least resistance at the BBB, and compared to capillaries, provide a more feasible route for nanoparticle drug carriers into the brain.

Precapillary sphincters and pericytes at first-order capillaries as key regulators for brain capillary perfusion.

Rises in local neural activity trigger local increases of cerebral blood flow, which is essential to match local energy demands. However, the specific location of microvascular flow control is incompletely understood. Here, we used two-photon microscopy to observe brain microvasculature in vivo. Small spatial movement of a three-dimensional (3D) vasculature makes it challenging to precisely measure vessel diameter at a single x-y plane. To overcome this problem, we carried out four-dimensional (x-y-z-t) imaging of brain microvessels during exposure to vasoactive molecules in order to constrain the impact of brain movements on the recordings. We demonstrate that rises in synaptic activity, acetylcholine, nitric oxide, cyclic guanosine monophosphate, ATP-sensitive potassium channels, and endothelin-1 exert far greater effects on brain precapillary sphincters and first-order capillaries than on penetrating arterioles or downstream capillaries, but with similar kinetics. The high level of responsiveness at precapillary sphincters and first-order capillaries was matched by a higher level of α-smooth muscle actin in pericytes as compared to penetrating arterioles and downstream capillaries. Mathematical modeling based on 3D vasculature reconstruction showed that precapillary sphincters predominantly regulate capillary blood flow and pressure as compared to penetrating arterioles and downstream capillaries. Our results confirm a key role for precapillary sphincters and pericytes on first-order capillaries as sensors and effectors of endothelium- or brain-derived vascular signals.

[Bilateral erythematous swelling of the breasts in a pregnant patient]. / Bilaterale erythematöse Schwellungen der Mammae bei einer schwangeren Patientin.

Mastitis is an infectious or noninfectious inflammation of the mammary glands. The most important differential diagnosis of mastitis is an inflammatory carcinoma, which can be excluded by imaging and a biopsy. Noninfectious mastitis can also occur during pregnancy and knowledge of the possible differential diagnoses is essential for appropriate diagnostics and treatment.