Subclinical signs of podocyte injury associated with Circulating Anodic Antigen (CAA) in Schistosoma mansoni-infected patients in Brazil.

BACKGROUND: The long-term effects of schistosomiasis on the glomerulus may contribute to the development of chronic kidney disease. This study aimed to investigate baseline Schistosoma mansoni-Circulating Anodic Antigen (CAA) levels and their association with kidney biomarkers related to podocyte injury and inflammation in long-term follow-up after praziquantel (PZQ) treatment. METHODS: Schistosoma infection was diagnosed by detecting CAA in urine using a quantitative assay based on lateral flow using luminescent up-converting phosphor reporter particles. A cutoff threshold of 0.1 pg/mL CAA was used to diagnose Schistosoma infection (baseline) in a low-prevalence area in Ceará, Northeast, Brazil. Two groups were included: CAA-positive and CAA-negative individuals, both of which received a single dose of PZQ at baseline. Urinary samples from 55 individuals were evaluated before (baseline) and at 1, 2, and 3 years after PZQ treatment. At all time points, kidney biomarkers were quantified in urine and adjusted for urinary creatinine levels. RESULTS: CAA-positive patients had increased baseline albuminuria and proteinuria and showed greater associations between kidney biomarkers. CAA levels correlated only with Vascular Endothelial Growth Factor (VEGF) (podocyte injury) levels. Increasing trends were observed for malondialdehyde (oxidative stress), monocyte chemoattractant protein-1 (inflammation marker), and VEGF. In the follow-up analysis, no relevant differences were observed in kidney biomarkers between the groups and different periods. CONCLUSIONS: S. mansoni-infected individuals presented subclinical signs of glomerular damage that may reflect podocyte injury. However, no causal effect on long-term renal function was observed after PZQ treatment.

Subclinical signs of podocyte injury associated with Circulating Anodic Antigen (CAA) in Schistosoma mansoni-infected patients in Brazil

ABSTRACT Background: The long-term effects of schistosomiasis on the glomerulus may contribute to the development of chronic kidney disease. This study aimed to investigate baseline Schistosoma mansoni-Circulating Anodic Antigen (CAA) levels and their association with kidney biomarkers related to podocyte injury and inflammation in long-term follow-up after praziquantel (PZQ) treatment. Methods: Schistosoma infection was diagnosed by detecting CAA in urine using a quantitative assay based on lateral flow using luminescent up-converting phosphor reporter particles. A cutoff threshold of 0.1 pg/mL CAA was used to diagnose Schistosoma infection (baseline) in a low-prevalence area in Ceará, Northeast, Brazil. Two groups were included: CAA-positive and CAA-negative individuals, both of which received a single dose of PZQ at baseline. Urinary samples from 55 individuals were evaluated before (baseline) and at 1, 2, and 3 years after PZQ treatment. At all time points, kidney biomarkers were quantified in urine and adjusted for urinary creatinine levels. Results: CAA-positive patients had increased baseline albuminuria and proteinuria and showed greater associations between kidney biomarkers. CAA levels correlated only with Vascular Endothelial Growth Factor (VEGF) (podocyte injury) levels. Increasing trends were observed for malondialdehyde (oxidative stress), monocyte chemoattractant protein-1 (inflammation marker), and VEGF. In the follow-up analysis, no relevant differences were observed in kidney biomarkers between the groups and different periods. Conclusions: S. mansoni-infected individuals presented subclinical signs of glomerular damage that may reflect podocyte injury. However, no causal effect on long-term renal function was observed after PZQ treatment.

Burden of schistosomiasis-related mortality in Brazil: epidemiological patterns and spatial-temporal distribution, 2003-2018.

OBJECTIVE: To characterise the epidemiological patterns and the spatial-temporal distribution of schistosomiasis-related mortality in Brazil from 2003 to 2018. METHODS: A national population-based ecological study that used official data from the Mortality Information System. The data included all deaths recorded in Brazil from 2003 to 2018 in which schistosomiasis was mentioned in the death certificate as an underlying or associated cause of death (multiple causes). The municipalities of residence were used as units of geographic analysis, and standardised and smoothed mortality rates (per 100 000 inhabitants) were calculated using the local empirical Bayes method. Spatial autocorrelation was evaluated using global and local Moran indexes. To analyse the spatial dependence, the Getis-Ord G and Gi* statistics were used. RESULTS: During the study period, 18 421 113 deaths were recorded in Brazil. Schistosomiasis was mentioned in 11 487 deaths (proportional mortality: 0.06%); for 8141 deaths (70.87%), it was listed as the underlying cause, and for 3346 deaths (29.13%), it was listed as an associated cause. The mean mortality rate was 0.38 deaths/100 000 inhabitants. Individuals ≥ 70 years of age (RR: 115.34, 95% CI: 68.56-194.03) and residents in the Northeast region (RR: 10.81, 95% CI: 5.95-19.66) presented higher risks related to schistosomiasis. Municipalities with high mortality rates were identified in all regions, and high-risk clusters were found in municipalities located in the Northeast and Southeast regions of the country. CONCLUSIONS: Schistosomiasis remains an important cause of death in persistently endemic areas in Brazil, particularly in those with a high prevalence of the disease and a marked parasite load.

OBJECTIF: Caractériser les profils épidémiologiques et la distribution spatio-temporelle de la mortalité liée à la schistosomiase au Brésil de 2003 à 2018. MÉTHODES: Une étude écologique nationale basée sur la population qui a utilisé les données officielles du système d'information sur la mortalité. Les données incluaient tous les décès enregistrés au Brésil de 2003 à 2018 dans lesquels la schistosomiase était mentionnée dans le certificat de décès comme cause sous-jacente ou associée (causes multiples) de décès. Les municipalités de résidence ont été utilisées comme unités d'analyse géographique et les taux de mortalité normalisés et lissés (pour 100.000 habitants) ont été calculés à l'aide de la méthode empirique locale de Bayes. L'autocorrélation spatiale a été évaluée à l'aide d'indices de Moran globaux et locaux. Pour analyser la dépendance spatiale, les statistiques de Getis-Ord G et Gi* ont été utilisées. RÉSULTATS: Au cours de la période d'étude, 18.421.113 décès ont été enregistrés au Brésil. La schistosomiase a été mentionnée dans 11.487 décès (mortalité proportionnelle: 0,06%); pour 8.141 décès (70,87%), elle a été répertoriée comme la cause sous-jacente et pour 3.346 décès (29,13%), comme cause associée. Le taux de mortalité moyen était de 0,38 décès/100.000 habitants. Les personnes âgées de ≥70 ans (RR: 115,34 ; IC95%: 68,56 à 194,03) et les résidents de la région du Nord-Est (RR: 10,81 ; IC95%: 5,95 à 19,66) présentaient des risques plus élevés liés à la schistosomiase. Des municipalités présentant des taux de mortalité élevés ont été identifiées dans toutes les régions et des grappes à haut risque ont été trouvées dans des municipalités situées dans les régions du nord-est et du sud-est du pays. CONCLUSIONS: La schistosomiase reste une cause importante de mortalité dans les zones d'endémie persistante du Brésil, en particulier dans celles à forte prévalence de la maladie et à forte charge parasitaire.

Epidemiology and predictors of occurrence of SCHISTOSOMA MANSONI infection in a low-endemicity area in northeast Brazil

In Latin America 96% of the cases of schistosomiasis occur in Brazil in low-socioeconomic status populations. The epidemiological characteristics and occurrence predictors of Schistosoma mansoni infection were determined in the Bananeiras community, located in Capistrano, a town in Ceará state, Brazil. Sanitary, environmental, socioeconomic, and behavioral data were collected using a semi-structured questionnaire. An investigation to assess S. mansoni infection was conducted using the Kato-Katz and Point-of-Care Circulating Cathodic Antigen (POC-CCA) methods. From the 258 subjects were analyzed, 54.3% (n=140) were women, median age 30 years. Thirty-three (12.8%) individuals were positive by either egg- and/or CCA-positivity. The highest positivity rate was found in the 30-39 year old group. There was no piped water supply, sewage network or municipal refuse collection service. Most individuals were illiterate or had not finished elementary school (66.3%). About 29.1% of the families had a monthly income below one Brazilian minimum wage and 91.1% reported contact with natural water sources. We found an association between infection and age group of 20-40 years, illiteracy, household with 7 inhabitants or more, household with up to 3 rooms and an outhouse. Contrarily, being 40 years old or older and household with up to 6 inhabitants were not risk factors. Schistosomiasis remains a public health problem in this municipality, evidencing a strong association with low socioeconomic conditions and high vulnerability. These findings reinforce the importance of identifying the factors associated with the infection for more effective guidance in actions in control programs targeting schistosomiasis prevention and control.

Performance of an Ultra-Sensitive Assay Targeting the Circulating Anodic Antigen (CAA) for Detection of Schistosoma mansoni Infection in a Low Endemic Area in Brazil.

Techniques with high sensitivity and specificity are required for an accurate diagnosis in low-transmission settings, where the conventional parasitological methods are insensitive. We determined the accuracy of an up-converting phosphor-lateral flow circulating anodic antigen (UCP-LF CAA) assay in urine and serum for Schistosoma mansoni diagnosis in low-prevalence settings in Ceará, Brazil, before and after praziquantel treatment. Clinical samples of a total of 258 individuals were investigated by UCP-LF CAA, point-of-care-circulating cathodic antigen (POC-CCA), soluble worm antigen preparation (SWAP)-ELISA and Kato-Katz (KK); a selection of 128 stools by real-time PCR technique. Three and 6-weeks after treatment, samples were collected and evaluated by detection Schistosoma circulating antigens (CAA and CCA). The UCP-LF CAA assays detected 80 positives (31%) with urine and 82 positives (31.8%) with serum. The urine POC-CCA and serum SWAP-ELISA assays detected 30 (11.6%) and 107 (40.7%) positives, respectively. The Kato-Katz technique revealed only 4 positive stool samples (1.6%). Among the 128 individuals with complete data records, 19 cases were identified by PCR (14.8%); Sensitivities and specificities of the UCP-LF CAA assays, determined versus a combined reference standard based on CCA/KK/PCR positivity, ranged from 60-68% to 68-77%, respectively. In addition only for comparative purposes, sensitivities of the different assays were determined vs. a comparative reference based on CAA/KK/PCR positivity, showing the highest sensitivity for the urine CAA assay (80%), followed by the serum CAA (70.9%), SWAP-ELISA (43.6%), PCR (34.5%), POC-CCA (29.1%), whilst triplicate Kato-Katz thick smears had a very low sensitivity (3.6%). CAA concentrations were higher in serum than in urine and were significantly correlated. There was a significant decrease in urine and serum CAA levels 3 and 6-weeks after treatment. The UCP-LF CAA assays revealed 33 and 28 S. mansoni-infected patients at the 3- and 6-week post-treatment follow-up, respectively. The UCP-LF CAA assays show high sensitivity for the diagnosis of S. mansoni in low-endemicity settings. It detects a considerably higher number of infections than microscopy, POC-CCA or PCR. Also it shows to be very useful for evaluating cure rates after treatment. Hence, the UCP-LF CAA assay is a robust and promising diagnostic approach in low-transmission settings.

Identification of Biomphalaria sp. and other freshwater snails in the large-scale water transposition project in the Northeast of Brazil.

The wide eco-bio-social intervention generated by the SaoFrancisco River Integration Project (PISF) may contribute to the dispersion or introduction of schistosomiasis intermediate hosts in areas without prior recording. The objective was to characterize the limnic malacofauna and its distribution along watersheds involved in the PISF. A cross-sectional study based on the collection of mollusks from 33 water bodies, from Aurora, Brejo Santo, Jaguaretama, Jaguaribara, Jati e Mauriti municipalities in the Ceara (CE) State was developed. The conchological characteristics were used to identify snails at the genus level. The snails of the genus Biomphalaria were analyzed for the presence of Schistosoma mansoni cercariae and the molecular identification (only mollusks from Brejo Santo-CE) for differentiation between species. The following species were found: Biomphalaria sp.; Drepanotrema sp.; Melanoides sp.; Physa sp.; and Pomacea sp. Pomacea sp. (75.8%) and Biomphalaria sp. (72.7%) were the most prevalent species. All municipalities showed Biomphalaria sp. Biomphalaria straminea (Porcos Stream) and Biomphalaria kuhniana was identified in the Boi 1 and Cipo reservoirs (Brejo Santo). The evaluated municipalities under the influence of the PISF present areas with potential for schistosomiasis transmission. It is necessary to intensify control actions and health surveillance in these areas.

Evaluating a point-of-care circulating cathodic antigen test (POC-CCA) to detect Schistosoma mansoni infections in a low endemic area in north-eastern Brazil.

Schistosomiasis is still a public health problem in Brazil. The Kato-Katz test is the most frequently used diagnostic method for Schistosoma mansoni infection. However, it lacks sensitivity in areas of low prevalence. We have assessed the positivity rate of S. mansoni infection in Bananeiras, a village on Capistrano, Ceara, Brazil by performing a point-of-care test in urine to determine the circulating cathodic antigens (POC-CCA), and we compared the findings with those of the Kato-Katz technique for egg detection in stool and an enzyme-linked immunosorbent assay for specific antibodies against adult worms (SWAP-ELISA) in serum before treatment (baseline). Additionally, the POC-CCA and Kato-Katz test results were compared at one and two years post-treatment, and only POC-CCA strips were utilised for follow-up testing on urine samples at 3-6 weeks. Only one sample of stool and urine was collected per event. Overall, 258 individuals were investigated at the baseline. The POC-CCA test detected 10 (3.9%) positive cases; however, this amount increased to 30 (11.6%) when considering trace readings as positive (t + ), whereas the Kato-Katz method found only 4 (1.6%) positive cases and the SWAP-ELISA detected 105 (40.7%) positive cases. The consistency observed between a single POC-CCA (t + ) or (t-) and the Kato-Katz (three slides) was poor (Kappa indexes <0.20). The highest positivity rate as determined by CCA and Kato-Katz was found in adults. At the baseline, a praziquantel treatment was administered to all individuals regardless of their infection status. According to the POC-CCA test, 93% of the previous positive cases became negative by the third week after the treatment; this rate reached 100% at the sixth week assessment. The follow-up showed that of the 175 individuals evaluated at one year post-treatment, only one (0.6%) showed 'trace' results, and all the individuals were negative for eggs in the stool. At two years, all 185 examined individuals were negative by the Kato-Katz method, and 11 (5.9%) presented traces by POC-CCA. Our results indicate that a single POC-CCA test reveals a significantly higher number of positive cases than the Kato-Katz technique for diagnosing S. mansoni in a low endemic setting, when trace results are considered as positive cases. Nevertheless, the true significance of the trace is not clear. These findings reinforce the need to associate different tools for improved schistosomiasis diagnosis in individuals with low parasite burdens.

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.

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

Abstract 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.