ABSTRACT Background: We evaluated the association between polymorphisms in the tumor necrosis factor alpha (TNF-α) (-G308A) gene and upper gastrointestinal bleeding (UGIB) in schistosomiasis. Methods: This was a transverse study involving 294 Brazilian patients infected with Schistosoma mansoni. Results: The homozygous A/A genotype in TNF-α (-G308A) showed a risk association (prevalence ratio = 1.90, p = 0.008) with UGIB. There was no statistically significant difference in serum TNF-α levels between the clinical groups. Conclusions: The polymorphic TNF-α (-G308A) can be a risk factor for UGIB, in addition to being a potentially predictive factor for the severity of UGIB in schistosomiasis.

ABSTRACT Background: We analyzed the trends and spatial patterns of schistosomiasis-related mortality in Northeast Brazil in 2000-2019. Methods: A mixed population-based ecological study was conducted, using information on the underlying or associated causes of death. We used Joinpoint regression analysis to calculate the trends. The spatial analysis included rates, spatial moving averages, and standardized mortality rates. The spatial dependence analysis was based on Getis-Ord's G and Gi* indices (Gi star) and local Moran’s index to check for autocorrelation. Results: A total of 5,814,268 deaths were recorded, of which 9,276 (0.16%) were schistosomiasis-related; 51.0% (n=4,732, adjusted rate 0.90/100,000 inhabitants [95% confidence interval (CI) 0.88-0.93]) were males; 40.0% (n=3,715, adjusted rate 7.40/100.000 inhabitants [95%CI: 7.16-7.64]) were ≥70 years old; 54.8% (n=5,087, crude rate 0.80/100,000 inhabitants) were of mixed/Pardo-Brazilian ethnicity; and 77.9% (n=7,229, adjusted rate 0.86/100,000 inhabitants [95%CI: 0.84-0.88]) lived outside state capitals. The highest proportion of deaths was in the state of Pernambuco (53.9%, n=4,996, adjusted rate 2.72/100,000 inhabitants [95%CI: 2.64-2.79]). Increasing mortality rate was verified in the state of Sergipe. On the coast of the state of Rio Grande do Norte and Bahia, there was spatial dependence of spatio-temporal risk patterns with clusters. Throughout the study period, we found positive spatial autocorrelation and cluster formation. Conclusions: In Northeast Brazil, schistosomiasis persists with a high mortality rate, especially in the coastal region, with heterogeneous spatial and temporal patterns. To eliminate schistosomiasis by 2030, it is necessary to strengthen the financing and management of the unified health system (SUS).

Abstract INTRODUCTION: We evaluated the association between genetic polymorphisms in exon 1 (A/O alleles) and promoter regions at positions -550 (H/L variant, rs11003125) and -221 (X/Y variant, rs7096206) MBL2 and periportal fibrosis regression. METHODS: This was a retrospective cohort study involving 114 Brazilians infected with Schistosoma mansoni, who were subjected to follow-up for three years after specific treatment for schistosomiasis to estimate the probability of periportal fibrosis regression. RESULTS: A risk association was observed between polymorphism at the exon 1 MBL2 and periportal fibrosis regression. CONCLUSIONS: This study suggests that the polymorphism of exon 1 MBL2 may potentially be used to predict periportal fibrosis regression in this population.

BACKGROUND Schistosomiasis mansoni is a poverty-related parasitic infection that has a variety of clinical manifestations. We consider the disability and deaths caused by schistosomiasis unacceptable for a tool-ready disease. Its condition in Brazil warrants an analysis that will enable better understanding of the local health losses and contribute to the complex decision-making process. OBJECTIVE This study estimates the cost of schistosomiasis in Brazil in 2015. METHODS We conducted a cost of illness study of schistosomiasis mansoni in Brazil in 2015 based on a prevalence approach and from a societal perspective. The study included 26,499 schistosomiasis carriers, 397 hepatosplenic cases, 48 cases with the neurological form, 284 hospitalisations, and 11,368.26 years of life lost (YLL) of which 5,187 years are attributable to economically active age groups. RESULTS The total cost of schistosomiasis mansoni in Brazil was estimated to be US$ 41,7million in 2015 with 94.61% of this being indirect costs. CONCLUSIONS The economic burden of schistosomiasis mansoni in Brazil is high and results in the loss of productivity. Its persistence in Brazil is a challenge to public health and requires inter-sectorial interventions in areas such as indoor water supply, basic sanitation, and education.

Resumo A ocorrência da esquistossomose mansônica em órgãos do aparelho reprodutor feminino é um evento pouco comum, tendo em vista que o agente etiológico desta doença é um parasito sanguíneo que habita as veias mesentéricas. Neste relato decaso, uma paciente de 45 anos referiu como primeira sintomatologia fortes dores na região ilíaca esquerda há cerca de 2 anos. Uma ultrassonografia pélvica endovaginal identificou aumento do ovário esquerdo, e o laudo sugeriu correlacionar tal achado com dados clínicos e marcadores tumorais. Após passar por vários serviços de saúde, a paciente foi encaminhada para um serviço de oncologia por suspeita de neoplasia, sendo submetida a uma ovariectomia à esquerda. O resultado do exame histopatológico evidenciou a presença de processos inflamatórios granulomatosos em torno de ovos viáveis e calcificados de Schistosoma mansoni. Não houve qualquer evidência de tecido neoplásico. A paciente foi medicada, e seguiu em acompanhamento ambulatorial.

Abstract The occurrence of Manson’s schistosomiasis in organs of the female reproductive tract is an uncommon event, given that the etiological agent for this disease is a blood parasite that inhabits the mesenteric veins. In this case report, a 45-year-old female patient reported that her first symptoms had been strong pain in the left iliac region around two years earlier. An endovaginal pelvic ultrasonography showed that the left ovary was enlarged, and the report suggested that this finding might be correlated with clinical data and tumor markers. After being examined at several healthcare services, the patient was referred to an oncology service due to suspected neoplasia, where she underwent a left ovariectomy. The result from the histopathological examination showed the presence of granulomatous inflammatory processes surrounding both viable and calcified eggs of Schistosoma mansoni. There was no evidence of any neoplastic tissue. The patient was medicated and followed-up as an outpatient.

RESUMO CONTEXTO A fibrose periportal é a maior consequência patológica da infecção pelo Schistosoma mansoni. OBJETIVO Avaliar a acurácia de marcadores séricos e construir um índice para avaliar a fibrose. MÉTODOS Pacientes (n=116) com esquistossomose foram avaliados pela ultrassonografia e dosados os níveis de aminotransferases, γ-glutamil transferase, fosfatase alcalina, ácido hialurônico, citocinas e plaquetas. Imagens de ultrasom foram utilizadas para avaliar a fibrose através de classificação de Niamey e identificados 19 pacientes sem fibrose periportal (padrão A e B), 48 com fibrose média a moderada (C e D) e 49 com fibrose avançada (E e F). RESULTADOS Através de análise multivariada, um modelo foi criado, que envolveu a fosfatase alcalina e plaquetas e conseguiu separar pacientes com diferentes padrões de fibrose periportal. Este índice mostrou um melhor desempenho em separar pacientes sem fibrose dos pacientes com fibrose avançada. O índice biológico mostrou uma área sob a curva ROC de 1,000. Usando valores infereiores e acima do ponto de corte, a presença ou ausência de fibrose avançada pode ser prevista em todos os pacientes. CONCLUSÃO O índice construído pode ser usado para separar os pacientes com diferentes padrões de fibrose periportal, especialmente para prever fibrose avançada em pacientes com esquistossomose.

ABSTRACT BACKGROUND Periportal fibrosis is the major pathological consequence of the Schistosoma mansoni infection. OBJECTIVE To evaluate the accuracy of serum markers and to construct an index to assess fibrosis. METHODS Patients (n=116) with schistosomiasis were evaluated by ultrasound scan and measurements of serum levels of aminotransferases, γ-glutamyl transferase, alkaline phosphatase, hyaluronic acid, cytokines and platelets. Ultrasound images were used to evaluate the fibrosis using Niamey's classification and identified 19 patients without periportal fibrosis (patterns A and B), 48 with mild to moderate fibrosis (C and D) and 49 with advanced fibrosis (E and F). RESULTS Using multivariate analysis, a model was created, which involved alkaline phosphatase and platelets and could separate patients with different patterns of fibrosis. This index showed a better performance in separating patients without fibrosis from with advanced periportal fibrosis. The biological index showed an area under the ROC curve of 1.000. Using values below the lowest or above the highest cut-off point, the presence or absence of advanced fibrosis could be predicted in all patients. CONCLUSION The index constructed can be used to separate patients with different patterns of periportal fibrosis, specially to predict advanced fibrosis in schistosomiasis patients.

Abstract INTRODUCTION: We evaluated the associations between interleukin-10 (IL-10) gene polymorphisms -G1082A/-C819T/-C592A and periportal fibrosis regression after specific treatment for schistosomiasis. METHODS: This retrospective cohort study involved 125 Brazilian patients infected with Schistosomiasis mansoni, who were followed up for 2 years after specific treatment to estimate the probability of periportal fibrosis regression. RESULTS: There was no evidence of associations between IL-10 polymorphisms and periportal fibrosis regression after treatment. CONCLUSIONS: There was no evidence of associations between gene promoter polymorphisms of IL-10 and the regression of periportal fibrosis in this Brazilian population.

INTRODUCTION : We hypothesized higher mannose-binding lectin level and classic factors (i.e., age, sex, alcohol consumption, exposure, and specific treatment) are associated with the severity of periportal fibrosis in schistosomiasis. METHODS : This cross-sectional study involved 79 patients infected with Schistosoma mansoni with severe or mild/moderate periportal fibrosis. Serum concentrations of mannose-binding lectin were obtained by enzyme-linked immunosorbent assay (ELISA). RESULTS: Higher serum level of mannose-binding lectin was significantly associated with advanced periportal fibrosis. CONCLUSIONS: Mannose-binding lectin may contribute to liver pathology in schistosomiasis and may represent a risk factor for advanced periportal fibrosis in the Brazilian population studied.

Contexto Dados em relação às alterações vasculares em pacientes com esquistossomose hepatoesplênica e colopatia hipertensiva portal e suas modificações após cirurgia para atenuação da hipertensão portal são restritos. Objetivo Analisar as alterações da colopatia hipertensiva portal antes e seis a 12 meses após a esplenectomia e desvascularização gástrica. Métodos Foram estudados prospectivamente 12 pacientes com esquistossomose hepatoesplênica e antecedente de hemorragia digestiva alta. Os achados colonoscópicos antes e após 6 a 12 meses após a cirurgia foram analisados. Nesses períodos, biopsias da mucosa do cólon ascendente, sigmóide e reto foram encaminhadas para análise histológica e histomorfométrica. Foi utilizado um grupo controle pela falta de padrão de normalidade das medidas histomorfométricas das vênulas do cólon e reto em indivíduos sem hipertensão portal. O nível de significância crítica adotado em todos os testes foi de probabilidade máxima de erro de 5%. Resultados Não foram encontradas diferenças significantes na intensidade das alterações endoscópicas e histológicas nos vasos da mucosa do cólon e reto após a cirurgia. Entretanto, houve decréscimo estatisticamente significante nas áreas, diâmetros e espessuras dos vasos estudados através da histomorfometria. Conclusão Cirurgia para descompressão da hipertensão portal esquistossomótica tem efeito benéfico na colopatia associada, sendo bem indicada nos pacientes com hemorragia digestive alta e varizes esofágicas.

Context Data on vascular alterations in patients with hepatosplenic schistosomiasis and portal hypertensive colopathy and changes in these after surgery to decrease portal hypertension are limited. Objective The purpose of this study was to analyse the alterations of portal hypertensive colopathy previously and 6-12 months after splenectomy and gastric devascularization. Methods Twelve patients with hepatosplenic schistosomiasis who also had upper gastrointestinal bleeding were studied prospectively. Their endoscopic findings before and 6-12 months after the surgery were analysed. In addition, mucosal biopsies from ascending colon, sigmoid colon and rectum at these time points were subjected to histological and histomorphometric assessment. It was used a control group due to lack of normal pattern of the histomorphometric measures of vessels in individuals without portal hypertension. The critical level of significance adopted in all tests was of a maximum probability error of 5%. Results Surgery did not lead to significant improvement in histological and endoscopic findings. However, on histomorphometry, there was a significant decrease in the area, diameter and thickness of the vessels in mucosa at all colonic sites. Conclusion Surgery for decompression of schistosomal portal hypertension has a beneficial effect on the associated colopathy, being best indicated in patients with gastrointestinal bleeding and esophageal varices.

In this paper, the authors review the literature and share their experience of the principal biological markers of fibrosis for the evaluation of periportal fibrosis (PPF) caused by mansoni schistosomiasis. These biological markers are compared to diagnostic ultrasound (US) scans as means of grading PPF. We also review procollagen type I and III, collagen type IV, laminin, hyaluronic acid (HA), immunoglobulin G, platelets, aspartate aminotransferase to platelet ratio index (APRI) and gamma-glutamyl transpeptidase as markers of the disease. Although there are several good markers for evaluating PPF and portal hypertension, such as HA, platelets or APRI, none can yet replace US. These markers may, however, be used to identify patients at greater risk of developing advanced disease in endemic areas and determine who will need further care and US studies.

Liver biopsy is the gold-standard method to stage fibrosis; however, it is an invasive procedure and is potentially dangerous. The main objective of this study was to evaluate biological markers, such as cytokines IL-13, IFN-γ, TNF-α and TGF-β, platelets, bilirubins (Bil), alanine aminotransferase (ALT) and aspartate aminotransferase (AST), total proteins, γ-glutamil transferase (γ-GT) and alkaline phosphatase (AP), that could be used to predict the severity of hepatic fibrosis in schistosomiasis and hepatitis C (HC) as isolated diseases or co-infections. The following patient groups were selected: HC (n = 39), HC/hepatosplenic schistosomiasis (HSS) (n = 19), HSS (n = 22) and a control group (n = 13). ANOVA and ROC curves were used for statistical analysis. P < 0.05 was considered significant. With HC patients we showed that TNF-α (p = 0.020) and AP (p = 0.005) could differentiate mild and severe fibrosis. With regard to necroinflammatory activity, AST (p = 0.002), γ-GT (p = 0.034) and AP (p = 0.001) were the best markers to differentiate mild and severe activity. In HC + HSS patients, total Bil (p = 0.008) was capable of differentiating between mild and severe fibrosis. In conclusion, our study was able to suggest biological markers that are non-invasive candidates to evaluate fibrosis and necroinflammatory activity in HC and HC + HSS.

The production and regulation of interleukin (IL) IL-13, IL-4 and interferon-gamma (IFN-³) was evaluated in 43 schistosomiasis patients with different clinical forms. Whole-blood cultures cytokine production in response to soluble egg antigen (SEA), soluble worm adult preparation (SWAP), mitogens, neutralizing antibodies or recombinant IL-13 were measured by ELISA. After SWAP stimulation, chronic patients, particularly hepatointestinals, produced higher levels of IL-4 in comparison with acute patients, suggesting the presence of a type 2 cytokine profile in these patients. Following SEA and SWAP stimulation, hepatosplenic (HS) patients showed increased levels of IFN-³ when compared with acute patients, indicating that HS disease in humans is associated with a type 1 cytokine response. The mechanisms of immune regulation are apparently different between the clinical stages of the disease, some of which are antigen-specific.

O relato usual de fibrose hepática em pacientes com esquistossomose mansônica na forma hepato-esplênica não apresenta associação com os parâmetros clínico-hemodinâmicos e de reserva funcional hepática. A histomorfometria adicionou uma nova ferramenta de investigação para medir a densidade da fibrose portal nesses pacientes. Esta investigação teve como objetivo investigar uma possível concordância entre a bem aceita classificação internacional clássica e os graus de densidade da fibrose portal medidos pela histomorfometria. Trinta e cinco crianças e igual número de adultos foram incluídos nesse estudo. Todos os pacientes foram submetidos a esplenectomia e ligadura da veia gástrica esquerda. Os achados histológicos foram avaliados em biópsias hepáticas cirúrgicas coradas pelo tricômico de Masson. O relato histológico oficial (clássico) foi usado como referência. Os estudos histomorfométricos foram feitos por morfometria semi-automática. A percentagem média (X) da fibrose portal ± um desvio padrão (DP) foi classificado como grau II (7,06 até 34,72%); grau I foi até 7,06%; e grau III acima de 34,72%. Embora não alcançando significação estatística ocorreu uma tendência da fibrose ser mais intensa nas crianças que nos adultos (X ± DP - 22,02 ± 13,46% versus 20,63% ± 15,33% "t" = 0,379 p > 0,005). Sete de nove (77,8%) pacientes classificados como grau I, pela morfometria, tiveram a mesma classificação no relato oficial, contudo, dois (22,2%) foram descritos como grau III. Dezesseis de 44 (36,4%) classificados como grau II na morfometria tiveram a mesma classificação na histologia clássica, entretanto, 27 (61,4%) foram classificados como grau III e um (2,3%) como grau I. Quinze (21,4%) de 70 pacientes tiveram grau III em ambas as classificações, mas, dois (11,8%) de dezessete pacientes grau III na morfometria foram grau II na histologia. A medida de concordância kappa (k) entre ambas as classificações foi k=0,319, mostrando uma discreta força de associação. As medidas histomorfométricas da fibrose de Symmers em pacientes cirúrgicos portadores de esquitossomose mansônica dão suporte parcial ao relato oficial do Departamento de Patologia do Hospital das Clínicas - Universidade Federal de Pernambuco. Contudo, existe uma discrepância no grau III. Enquanto na classificação oficial a maioria (62,8%) é constituída por pacientes grau III, na morfometria, a maioria (62,8%) é grau II.

The usual histology report of hepatic fibrosis in patients with hepatosplenic schistosomiasis mansoni presents no association with hemodynamic and clinical liver parameters. Histomorphometry is adding a new tool of investigation for measuring density of portal fibrosis in these patients. This investigation was set up for assessing a possible agreement between the well-accepted international classification and the fibrosis density grades measured by histomorphometry. Thirty-five children and equal number of adults were included in this study. All patients underwent splenectomy and ligature of the left gastric vein. Histology findings were assessed in surgical liver biopsy stained with Masson trichrome. The official histology report was used as reference. The histomorphometric studies were done by semi-automatic morphometry. The mean percentage (X) of portal fibrosis plus or minus one standard deviation (SD) was classified as grade II (7.06% up to 34.72%); grade I was up to 7.06%; and grade III above 34.72%. Although, not reaching statistical significance, there is a tendency of the fibrosis to be more intense in children than adults (X±SD - 22.02±13.46% versus 20.63%±15.33% "t" = 0.379 p>0.05). Seven out of nine (77.8%) patients classified as grade I, by morphometry, had the same result on the official report, however, two (22.2%) were described as grade III. Sixteen out of forty-four (36.4%) classified as grade II on morphometry had the same classification as the histology grade, but, twenty seven (61.4%) were classified as grade III and one (2.3%) as grade I. Fifteen (21.4%) out of 70 patients had grade III on both classifications, but, two (11.8%) out of seventeen G III on morphometry were grade II. The kappa (k) measurement of agreement between both classification was k = 0.319, showing a fair strength of association. The histomorphometric measurements of Symmers fibrosis in surgical patients with mansonic schistosomiasis partially support the report from The Department of Pathology - University Hospital, Federal University of Pernambuco - Brazil. However, there is a discrepancy in grade III. While in the official classification, the majority (62.8%) accounts for this grade, on morphometry only 38.6% represent the same grade. On the contrary, on morphometry, similar majority (62.8%) is grade II.

A group of experts on schistosomiasis and ultrasonography discussed the experiences and results obtained with the Niamey-Belo Horizonte Protocol on Ultrasonography in Schistosomiasis. A series of recomendations about qualitative and quantitative data obtained by ultrasound in studies performed in Africa and Brazil are presented. Imunological, genetic and epidemiological studies must rely on ultrasound for the identification of patients with periportal thickening/fibrosis.

The present work reports on two epidemiological episodes resulting in acute schistosomiasis involving wealthy persons living in the State of Pernambuco, Brazil. The authors discuss the epidemiological, clinical and serologic characteristics of the acute infections and also the way in which the conditions for transmission occurred.