Improving the Cost-efficiency of Preventive Chemotherapy: Impact of New Diagnostics on Stopping Decisions for Control of Schistosomiasis.

BACKGROUND: Control of schistosomiasis (SCH) relies on the regular distribution of preventive chemotherapy (PC) over many years. For the sake of sustainable SCH control, a decision must be made at some stage to scale down or stop PC. These "stopping decisions" are based on population surveys that assess whether infection levels are sufficiently low. However, the limited sensitivity of the currently used diagnostic (Kato-Katz [KK]) to detect low-intensity infections is a concern. Therefore, the use of new, more sensitive, molecular diagnostics has been proposed. METHODS: Through statistical analysis of Schistosoma mansoni egg counts collected from Burundi and a simulation study using an established transmission model for schistosomiasis, we investigated the extent to which more sensitive diagnostics can improve decision making regarding stopping or continuing PC for the control of S. mansoni. RESULTS: We found that KK-based strategies perform reasonably well for determining when to stop PC at a local scale. Use of more sensitive diagnostics leads to a marginally improved health impact (person-years lived with heavy infection) and comes at a cost of continuing PC for longer (up to around 3 years), unless the decision threshold for stopping PC is adapted upward. However, if this threshold is set too high, PC may be stopped prematurely, resulting in a rebound of infection levels and disease burden (+45% person-years of heavy infection). CONCLUSIONS: We conclude that the potential value of more sensitive diagnostics lies more in the reduction of survey-related costs than in the direct health impact of improved parasite control.

Intestinal schistosomiasis-related mortality in Minas Gerais, Brazil, 2000-2019: Temporal trends and spatial patterns for determining priority areas.

OBJECTIVE: To identify priority areas for schistosomiasis control, we analysed the epidemiological characteristics, temporal trends and spatial patterns of schistosomiasis-related mortality in the state of Minas Gerais from 2000 to 2019. METHODS: Ecological and time-series study with spatial analysis techniques on deaths from Schistosomiasis mansoni. A log-linear regression model was used to identify changes in mortality rates. Moran's global index, local indicators of spatial association and a retrospective spatio-temporal permutation model were applied to identify the spatial and temporal distribution of mortality rates and assist in identifying priority areas for interventions. RESULTS: A total of 1290 deaths from schistosomiasis were recorded between 2000 and 2019, with an average mortality rate of 0.33 deaths/100,000. Although the overall mortality rate in the state of Minas Gerais decreased significantly over time (average annual percentage change = -9.6; 95% confidence interval = -14.4 to -4.6; p < 0.001), it increased in the mesoregions of Jequitinhonha, Mucuri Valley, and Rio Doce Valley. Spatial analysis identified the displacement and emergence of high-risk clusters from the central region of the state to the mesoregion of Rio Doce Valley. CONCLUSION: Temporal changes and shifting of high-risk areas from the central region to the mesoregion of Rio Doce Valley may indicate possible failures in early diagnosis and treatment of the schistosomiasis control program in these areas. Our research contributes to a better understanding of the spatio-temporal dynamics of death rates due to schistosomiasis infections and might help health authorities to direct resources most efficiently to avoid serious clinical outcomes in Minas Gerais.

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.

A review of serological tests available in Brazil for intestinal schistosomiasis diagnosis.

The World Health Organization (WHO) roadmap and recommendations for elimination of schistosomiasis were recently updated. With significant reductions in the prevalence and intensity of schistosomiasis infections worldwide, there is a need for more sensitive diagnostic methods. There are a few remaining transmission hotspots in Brazil, although low endemicity settings comprise most of the endemic localities. For the latter, serology may represent a tool for population screening which could help eliminate transmission of schistosomiasis. Here, we review serology tests currently available in Brazil from both public health and private laboratories: immunofluorescent antibody tests (IFATs) on adult worm sections and enzyme-linked immunosorbent assays (ELISAs) with soluble egg and adult worm antigens. Both in-house and commercially available tests have received less than adequate performance evaluations. Our review of immediate basic and operational research goals may help identify local adjustments that can be made to improve control interventions aimed at elimination of schistosomiasis as a public health problem.

Screening of a Library of Recombinant Schistosoma mansoni Proteins With Sera From Murine and Human Controlled Infections Identifies Early Serological Markers.

BACKGROUND: Schistosomiasis is a major global health problem caused by blood-dwelling parasitic worms, which is currently tackled primarily by mass administration of the drug praziquantel. Appropriate drug treatment strategies are informed by diagnostics that establish the prevalence and intensity of infection, which, in regions of low transmission, should be highly sensitive. METHODS: To identify sensitive new serological markers of Schistosoma mansoni infections, we have compiled a recombinant protein library of parasite cell-surface and secreted proteins expressed in mammalian cells. RESULTS: Together with a time series of sera samples from volunteers experimentally infected with a defined number of male parasites, we probed this protein library to identify several markers that can detect primary infections with as low as 10 parasites and as early as 5 weeks postinfection. CONCLUSIONS: These new markers could be further explored as valuable tools to detect ongoing and previous S mansoni infections, including in endemic regions where transmission is low.

Reconciling Egg- and Antigen-Based Estimates of Schistosoma mansoni Clearance and Reinfection: A Modeling Study.

BACKGROUND: Despite decades of interventions, 240 million people have schistosomiasis. Infections cannot be directly observed, and egg-based Kato-Katz thick smears lack sensitivity, affected treatment efficacy and reinfection rate estimates. The point-of-care circulating cathodic antigen (referred to from here as POC-CCA+) test is advocated as an improvement on the Kato-Katz method, but improved estimates are limited by ambiguities in the interpretation of trace results. METHOD: We collected repeated Kato-Katz egg counts from 210 school-aged children and scored POC-CCA tests according to the manufacturer's guidelines (referred to from here as POC-CCA+) and the externally developed G score. We used hidden Markov models parameterized with Kato-Katz; Kato-Katz and POC-CCA+; and Kato-Katz and G-Scores, inferring latent clearance and reinfection probabilities at four timepoints over six-months through a more formal statistical reconciliation of these diagnostics than previously conducted. Our approach required minimal but robust assumptions regarding trace interpretations. RESULTS: Antigen-based models estimated higher infection prevalence across all timepoints compared with the Kato-Katz model, corresponding to lower clearance and higher reinfection estimates. Specifically, pre-treatment prevalence estimates were 85% (Kato-Katz; 95% CI: 79%-92%), 99% (POC-CCA+; 97%-100%) and 98% (G-Score; 95%-100%). Post-treatment, 93% (Kato-Katz; 88%-96%), 72% (POC-CCA+; 64%-79%) and 65% (G-Score; 57%-73%) of those infected were estimated to clear infection. Of those who cleared infection, 35% (Kato-Katz; 27%-42%), 51% (POC-CCA+; 41%-62%) and 44% (G-Score; 33%-55%) were estimated to have been reinfected by 9-weeks. CONCLUSIONS: Treatment impact was shorter-lived than Kato-Katz-based estimates alone suggested, with lower clearance and rapid reinfection. At 3 weeks after treatment, longer-term clearance dynamics are captured. At 9 weeks after treatment, reinfection was captured, but failed clearance could not be distinguished from rapid reinfection. Therefore, frequent sampling is required to understand these important epidemiological dynamics.

Excretion patterns of Schistosoma mansoni antigens CCA and CAA by adult male and female worms, using a mouse model and ex vivo parasite cultures.

Assays which enable the detection of schistosome gut-associated circulating anodic (CAA) and cathodic (CCA) antigen in serum or urine are increasingly used as a diagnostic tool for schistosome infection. However, little is known about the production and clearance of these circulating antigens in relation to the sex and reproductive maturity of the parasite. Here we describe CAA and CCA excretion patterns by exploring a mouse model after exposure to 36 male-only, female-only and mixed (male/female) Schistosoma mansoni cercariae. We found that serum and urine CAA levels, analysed at 3 weeks intervals, peaked at 6 weeks post-infection. Worms recovered after perfusion at 14 weeks were cultured ex vivo. Male parasites excreted more circulating antigens than females, in the mouse model as well as ex vivo. In mixed infections (supporting egg production), serum CAA levels correlated to the number of recovered worms, whereas faecal egg counts or Schistosoma DNA in stool did not. No viable eggs and no inflammation were seen in the livers from mice infected with female worms only. Ex vivo, CAA levels were higher than CCA levels. Our study confirms that CAA levels reflect worm burden and allows detection of low-level single-sex infections.

Evaluation of SmITS1-LAMP performance to diagnosis schistosomiasis in human stool samples from an endemic area in Brazil.

Schistosomiasis is a life-threatening infectious disease categorized by the World Health Organization as a public health issue. New molecular diagnostic alternatives for intestinal schistosomiasis caused by Schistosoma mansoni, such as the loop-mediated isothermal amplification (LAMP), a fast and simple amplification technique, have been proposed for control of this NTD in low-endemicity locations. A LAMP assay was performed to detect the internal transcribed spacer 1 ribosomal gene of S. mansoni (SmITS1-LAMP) in 322 DNA extracted from stool samples from schistosomiasis endemic area in Brazil. Kato-Katz analysis of human stool samples was used as the gold standard test, detecting 144 positive samples. SmITS1-LAMP detection limit achieved a maximum analytical sensitivity of 10 fg/µL using S. mansoni genomic DNA, subsequently detecting 17/144 (11.8%) positive samples. SmITS1-LAMP sensitivity and specificity were 12% (95%CI: 7%-18%) and 93% (95%CI: 89%-96%), respectively. Positive predictive value (PPV) and negative predictive value (NPV) were 59% (95%CI: 39% - 76%); and 57% (95%CI: 51% - 62%), respectively. Most cases involved men (61.8%), predominantly young adults (20-39 years old) in cases diagnosed by Kato-Katz and adults (40-59 years old) in cases diagnosed by LAMP. The low number of eggs per gram of stool (1-99 EPG) was the most frequently identified by both Kato-Katz and LAMP. Further studies are needed to evaluate the applicability of SmMIT-LAMP on Schistosoma mansoni diagnosis and surveillance of schistosome infections.

Performance of loop-mediated isothermal amplification (LAMP) for detection of Schistosoma mansoni infection compared with Kato-Katz and real-time PCR.

The performance of loop-mediated isothermal amplification (LAMP) for detection of Schistosoma mansoni DNA from stool and urine samples in comparison with Kato-Katz and real-time polymerase chain reaction (PCR) was studied. After obtaining informed consent, 50 children participated in the present study and agreed to submit stool and urine samples. Stool samples were examined by Kato-Katz. Both real-time PCR and LAMP techniques were applied on stool and urine samples. The overall prevalence of S. mansoni was 46% in stool and urine samples as detected by the employed techniques, and 90% of cases had light infection intensity. The highest percentage of infection was diagnosed by real-time PCR (44%), followed by Kato-Katz (42%) and LAMP in the stool (36%), while the lowest percentages of infection were diagnosed by real-time PCR and LAMP in urine samples (24% and 14%, respectively). Kato-Katz, real-time PCR and LAMP showed 100% specificity where the sensitivity was 91.3%, 95.7% and 78.3%, respectively, in stool samples. Real-time PCR and LAMP showed lower sensitivity in urine samples. The LAMP assay is a promising technique for S. mansoni diagnosis in endemic countries of moderate and high-intensity infection. Yet, it needs further optimization, particularly in urine samples.

Intestinal schistosomiasis among preschool and school-aged children in a rural setting near Alexandria: initiative for elimination.

OBJECTIVE: To assess the status of intestinal schistosomiasis among preschool-aged (PSAC) and school-aged children (SAC) and to compare the efficacy of praziquantel (PZQ) in both groups. METHODS: The study was conducted on 400 children; 103 PSAC and 297 SAC. Diagnosis of Schistosoma mansoni was based on triplicate Kato-Katz thick smears from a single stool sample. To identify the missed cases by Kato-Katz, 120 randomly selected negative cases (38 PSAC and 82 SAC) were screened by real-time PCR. All S. mansoni-positive cases by Kato-Katz were treated by crushed PZQ tablets. Four weeks after treatment, the cure rate was assessed by Kato-Katz smears and real-time PCR. RESULTS: The prevalence of S. mansoni with Kato-Katz was 7.8% among PSAC and 7.4% among SAC. Most of children (63.3%) had light-intensity infection. The cure rate was 100% among PSAC by both techniques, and 91%, and 77.2% among SAC by Kato-Katz and real-time PCR, respectively. In the 120 stool samples screened by real-time PCR, S. mansoni prevalence was 25%; 15.8% and 29.3% were among PSAC and SAC respectively. Treated cases showed a lower range of Ct values than untreated cases. Two melting temperature ranges (Tm = 83-87°C and 89-93°C) were recognised among uncured cases which may point to S. mansoni genetic variability. CONCLUSION: Continuous monitoring and inclusion of PSAC in schistosomiasis control programmes are crucial. Real-time PCR and other molecular tools are recommended for evaluation of the true prevalence, assessment of cure and further studies on genetic diversity.

Diagnostic comparison of stool exam and point-of-care circulating cathodic antigen (POC-CCA) test for schistosomiasis mansoni diagnosis in a high endemicity area in northeastern Brazil.

This study aimed to evaluate the performance of the point-of-care circulating cathodic antigen (POC-CCA) test in a highly endemic area in Brazil, comparing it to the Kato-Katz (KK) technique for sensitivity, specificity and the intensity of the reaction of the test in relation to the parasitic load. The community in Sergipe, Brazil, participated in the study, providing three stool samples, one of urine (POC-CCA) and fingers tick blood sample was tested by enzyme-linked immunosorbent assay (ELISA). Sensitivity, specificity, positive predictive value, negative predictive value, accuracy, kappa coefficient and Spearman's correlation were calculated for the POC-CCA test using the KK as the reference. The prevalence of schistosomiasis by KK testing was 48.82%; POC-CCA (t+) 66.14%; POC-CCA (t-) 45.24%. ELISA results showed 100% agreement in individuals with high and moderate eggs per gram (EPG). POC-CCA presented good diagnostic performance in individuals with medium and high EPG, but there were a high number of false negatives in individuals with low intensity infections. As observed, POC-CCA-filter test improves accuracy and sensitivity compared to a conventional test.

Primary health care facilities capacity gaps regarding diagnosis, treatment and knowledge of schistosomiasis among healthcare workers in North-western Tanzania: a call to strengthen the horizontal system.

BACKGROUND: The World Health Organization (WHO) calls for schistosomiasis endemic countries to integrate schistosomiasis control measures into the primary health care (PHC) services; however, in Tanzania, little is known about the capacity of the primary health care system to assume this role. The objective of this study was to assess the capacity of the primary health care system to diagnose and treat schistosomiasis in endemic regions of north-western Tanzania. METHODS: A total of 80 randomly-selected primary health care facilities located in the Uyui, Geita and Ukerewe districts of North-western Tanzania participated in the study. At each facility, the in-charge clinician, or any other healthcare worker appointed by the in-charge clinician, participated in the questionnaire survey. A quantitative questionnaire installed in a Data Tool Kit software was used to collect data. Healthcare workers working at various stations (laboratory, pharmacy, data clerks, outpatient section) were interviewed. The questionnaire collected information related to healthcare workers' knowledge about urogenital and intestinal schistosomiasis symptoms, human and material resources, laboratory services, data capture, and anti-schistosomiasis treatment availability. RESULTS: A total of 80 healthcare workers were interviewed. Bloody stool (78.3 %) and haematuria (98.7 %) were the most common symptoms of intestinal and urogenital schistosomiasis mentioned by healthcare workers. Knowledge on the chronic symptoms such as hepatosplenomegaly and hematemesis for intestinal schistosomiasis, and oliguria and dysuria for urogenital schistosomiasis, were inadequate. Laboratory services were only available in 33.8 % (27/80) of the health facilities and direct wet preparation was the most common diagnostic technique used for both urine and stool samples. All healthcare workers knew that praziquantel was the drug of choice for the treatment of schistosomiasis and the drug was available in 91.3 % (73/80) of the health facilities. CONCLUSIONS: The capacity of the primary health care facilities included in the current study is inadequate in terms of diagnosis, treatment, reporting and healthcare workers' knowledge of schistosomiasis. Thus, the integration of schistosomiasis control activities into the primary healthcare system requires these gaps to be addressed.

Dot blot platform as a novel diagnostic kit: rapid, accurate, and on-site detection of Schistosoma mansoni in urine samples of hard to detect individuals.

Rapid diagnostics provide actionable information for patient care at the time and site of an encounter with the health care system. The mainstay of infectious diseases care is early detection (case finding) and treatment completion, but for many, it is hard to identify positive individuals, as is the case of infection with low burden in schistosomiasis, a parasitic disease common in the tropics and subtropics. We developed a new, accurate, and fast Dot blot methodology (iDot) to indirectly detect Schistosoma mansoni in individuals with very low parasite burden using urine samples. Accuracy of 0.74 was obtained with a significant difference between negative and positive patients and a substantial agreement was found when iDot was compared with five available methods. Our analysis also revealed the superiority of iDot in detecting negative individuals from non-endemic sites, thus, presenting the lowest rate of false positives. This new method called iDot is convenient and suitable for qualitative and quantitative detection of schistosomiasis in individuals with low parasite burden.

Immunogenicity, antibody responses and vaccine efficacy of recombinant annexin B30 against Schistosoma mansoni.

AIMS: Schistosomes infect approximately 250 million people worldwide. To date, there is no effective vaccine available for the prevention of schistosome infection in endemic regions. There remains a need to develop means to confer long-term protection of individuals against reinfection. In this study, an annexin, namely annexin B30, which is highly expressed in the tegument of Schistosoma mansoni was selected to evaluate its immunogenicity and protective efficacy in a mouse model. METHODS AND RESULTS: Bioinformatics analysis showed that there were three potential linear B-cell epitopes and four conformational B-cell epitopes predicted from annexin B30, respectively. Full-length annexin B30 was cloned and expressed in Escherichia coli BL21(DE3). In the presence of adjuvants, the soluble recombinant protein was evaluated for its protective efficacy in two independent vaccine trials. Immunization of CBA mice with recombinant annexin B30 formulated either in alum only or alum/CpG induced a mixed Th1/Th2 cytokine profile but no significant protection against schistosome infection was detected. CONCLUSION: Recombinant annexin B30 did not confer significant protection against the parasite. The molecule may not be suitable for vaccine development. However, it could be an ideal biomarker recommended for immunodiagnostics development.

Detecting Schistosoma mansoni infections among pre-school-aged children in southern Ghana: a diagnostic comparison of urine-CCA, real-time PCR and Kato-Katz assays.

BACKGROUND: In Ghana, pre-school-aged children (PSAC) are at risk of intestinal schistosomiasis and are living in need of praziquantel treatment. To better assess the infection burden within this vulnerable demographic group, we have provided a comparative assessment of the prevalence of Schistosoma mansoni in pre-school-aged children by urine circulating cathodic antigen (CCA) dipsticks, real-time PCR Taqman® faecal assays and Kato-Katz coproscopy. METHODS: In all, 190 pre-school-aged children were sampled from three endemic communities (viz. Tomefa, Torgahkope/Adakope, and Manheam) around Weija dam, Southern Ghana. Fresh stool and urine samples were collected from all participants for diagnosis. RESULTS: Among all the three communities, the urine-CCA assay recorded the highest prevalence values of 90.5% (95% CI 80.4-96.4), 87.9% (95% CI 76.7-95), and 81.2% (95% CI 69.9-89.6) in Tomefa, Torgahkope/Adakope, and Manheam respectively. Prevalence by real-time PCR was 50% (95% CI 35.5-64.5), 8% (95% CI 2.2-19.2) and 16.7% (95% CI 8.3-28.5), while by Kato-Katz was 55.6% (95% CI 42.5-68.1), 8.6% (95% CI 2.9-19) and 11.6% (95% CI 5.1-21.6) respectively. Children aged 1 year and over were found to be positive with the urine-CCA assay; by the ages of 3-4, over 50% were urine-CCA patent. The sensitivity and specificity of the POC-CCA dipsticks, when compared against the combined results of Kato-Katz/TaqMan results was found to be 84.1% (95% CI = 72.7-92.1) and 12.9% (95% CI = 6.6-22) respectively. CONCLUSIONS: We propose that the urine-CCA dipstick may be a useful rapid diagnostic tool to estimate the prevalence of intestinal schistosomiasis in PSAC, particularly in rapid identification of at-risk areas. However, our assessment has shown that it possible to record false positives when compared to combined Kato-Katz and qPCR results. To guide PSAC praziquantel treatment needs, we propose the urine CCA assay should be included in routine surveillance of intestinal schistosomiasis alongside other diagnostics such as Kato-Katz and urine filtration.

Schistosoma mansoni PCR+ -infected individuals in the Sudan present elevated systemic levels of chemokines when compared to uninfected and egg+ cohorts.

Infections with Schistosoma mansoni remain a major health problem in the Sudan where endemic communities, such as those in Kassala and Khartoum states, continue to face severe social-economic difficulties. Our previous immunoepidemiological findings revealed different immune [cytokine and S. mansoni egg (SEA) antibody] profiles in individuals with active infections (eggs in stool n = 110), individuals positive for S. mansoni via polymerase chain reaction (PCR) using sera (SmPCR+ n = 63) and those uninfected (Sm uninf). As antibody responses to eggs and worms are known to change during infection, we have expanded the profiling further by determining levels of adult worm (SWA) antibodies and nine chemokines in the serum of each individual in the three different cohorts. With the exception of C-C motif chemokine ligand (CCL)2, all measured chemokines were significantly higher in SmPCR+ individuals when compared to the egg+ group and in addition they also presented elevated levels of SWA-specific immunoglobulin (Ig)G2. Multivariable regression analysis further revealed that infection per se was strongly linked to SWA-specific IgG3 levels and CCL5 was strongly associated with a SmPCR+ diagnostic state. In the absence of PCR diagnostics that recognize juvenile worms or schistosomulae motives, identifying schistosome-specific traits should provide better insights into current prevalence rates in endemic communities and, in doing so, take into consideration PCR+ non-egg+ individuals in current treatment programmes.

TF-Test Quantified: a new technique for diagnosis of Schistosoma mansoni eggs.

OBJECTIVES: Laboratory diagnosis of Schistosoma mansoni eggs is routinely performed by conventional quantitative techniques through the parasitological examination of human faeces. However, the diagnostic sensitivity of this type of exam varies from low to moderate. We aimed to develop a new parasitological technique called TF-Test Quantified (TFT-Quant), for the quantitative detection of S. mansoni eggs in human faeces. METHODS: Four study stages were performed using 43 mice infected by S. mansoni cercariae. These experiments allowed the definition of an operational protocol for TFT-Quant and a comparison of this new technique to the conventional Helm-Teste technique. RESULTS: The results show a good diagnostic efficacy of TFT-Quant, which reached 100% in sensitivity and specificity, indicating an 'Almost Perfect' Kappa (k) agreement. CONCLUSIONS: This new technique provided a quantitative gain in the detection of S. mansoni eggs, largely free of faecal debris. The next stage of this study is the field validation of the TFT-Quant technique with the use of human faecal samples from an endemic region for mansonic schistosomiasis in Brazil (Microregion Jequitinhonha, State of Minas Gerais). In parallel to this validation, computational algorithms will be developed to allow the automated quantitative diagnosis of S. mansoni eggs.

OBJECTIFS: Le diagnostic en laboratoire des œufs de Schistosoma mansoni est systématiquement effectué à l'aide de techniques quantitatives conventionnelles faisant appel à l'examen parasitologique de selles humaines. Cependant, la sensibilité diagnostique de ce type d'examen varie de faible à modérée. Nous avons voulu développer une nouvelle technique parasitologique appelée TF-Test Quantified (TFT-Quant), pour la détection quantitative des œufs de S. mansoni dans les selles humaines. MÉTHODES: Quatre étapes de l'étude ont été réalisées sur 43 souris infectées par des cercaires de S. mansoni. Ces expériences ont permis de définir un protocole opérationnel pour TFT-Quant et de comparer cette nouvelle technique à la technique classique Helm-Teste. RÉSULTATS: Les résultats montrent une bonne efficacité diagnostique de TFT-Quant, dont la sensibilité et la spécificité ont atteint 100%, ce qui indique une concordance kappa (k) «presque parfaite¼. CONCLUSIONS: Cette nouvelle technique a permis un gain quantitatif dans la détection des œufs de S. mansoni, largement exempts de débris fécaux. La prochaine étape de cette étude est la validation sur le terrain de la technique TFT-Quant avec l'utilisation d'échantillons de selles humaines provenant d'une région endémique pour la schistosomiase mansonique au Brésil (Microregion Jequitinhonha, dans l'Etat de Minas Gerais). Parallèlement à cette validation, des algorithmes informatiques de calcul seront développés pour permettre le diagnostic quantitatif automatisé des œufs de S. mansoni.

Association between Schistosoma mansoni infection and access to improved water and sanitation facilities in Mwea, Kirinyaga County, Kenya.

BACKGROUND: Schistosomiasis remains a public health problem in Central Kenya despite concerted control efforts. Access to improved water and sanitation has been emphasized as important control measures. Few studies have assessed the association between access to improved water sources and sanitation facilities with Schistosoma mansoni infection in different environmental settings. This study assessed the association between S. mansoni infection and household access to improved water sources and sanitation facilities in Mwea, Kirinyaga County, Kenya. METHODS: A cross sectional study was conducted between the months of August and October 2017. A total of 905 household heads from seven villages were interviewed and their stool samples screened for S. mansoni using the Kato Katz technique. Comparisons of demographic factors by S. mansoni infection were tested for significance using the chi-square test (χ2) or the Fisher exact test for categorical variables. Variables associated with S. mansoni infection were analyzed using univariable analysis and the strength of the association measured as odds ratio (OR) using mixed effects logistic regression at 95% CI, with values considered significant at p < 0.05. RESULTS: The overall prevalence of S. mansoni was, 23.1% (95% CI: 20.5-26.0%), with majority of the infections being of light intensity. Rurumi village had the highest prevalence at 33.3%, with Kirogo village having the least prevalence at 7.0%. Majority (84.1%) of the households lacked access to improved water sources but had access to improved sanitation facilities (75%). Households with access to piped water had the lowest S. mansoni infections. However, there was no significant association between S. mansoni infections with either the main source of water in the household (Odds Ratio (OR) =0.782 (95% CI: 0.497-1.229) p = 0.285 or sanitation facilities (OR = 1.018 (95% CI: 0.705-1.469) p = 0.926. CONCLUSION: Our study suggests that S. mansoni is still a public health problem among all age groups in Mwea irrigation scheme, Kirinyaga County, Central Kenya. Majority of the households lacks access to improved water sources but have access to improved sanitation facilities. This study recommends initiatives to ensure adequate provision of improved water sources, and the inclusion of the adult community in preventive chemotherapy programs.

Elevation of C-reactive protein, P-selectin and Resistin as potential inflammatory biomarkers of urogenital Schistosomiasis exposure in preschool children.

BACKGROUND: Schistosomiasis is known to induce inflammatory immune responses. C-reactive protein (CRP), resistin and P-selectin are serological inflammatory markers that rise during the acute stages of infection. Here, we propose such inflammatory biomarkers have a potential for use in urogenital schistosomiasis diagnostic screening for exposure and infection in preschool-aged children. METHODS: As part of a larger study on urogenital schistosomiasis, 299 preschool children aged 1-5 years were included in this cross-sectional study. Parasitological diagnosis was conducted using urine filtration for Schistosoma haemtobium infection, and Kato Katz for S. mansoni infection. Serum levels of P-selectin, resistin, CRP, and antibodies against S. haematobium cercarial antigen preparation (CAP) and soluble worm antigen preparation (SWAP) were measured by ELISA. RESULTS: Of the 299 participants, 14% were egg positive for S. haematobium. Serology showed 46 and 9% of the participants to have been exposed to S. haematobium cercarial antigens and adult worm antigens, respectively. Levels of P-selectin were significantly higher in participants infected with S. haematobium (egg-positive) than in uninfected participants (p = 0.001). Levels of P-selectin were also higher in those exposed to cercarial antigen than in unexposed participants (p = 0.019). There was a positive correlation between P-selectin and infection intensity (r = 0.172; p = 0.002), as well as with IgM responses to CAP and SWAP (r = 0.183; p = 0.001); (r = 0.333; p < 0.0001) respectively. CRP significantly correlated with IgM responses to CAP (r = 0.133; p = 0.029) while resistin correlated with IgM responses to CAP and SWAP (r = 0.127; p = 0.016); (r = 0.197; p = 0.0004). CRP levels were higher in those exposed to cercarial and adult worm antigens than unexposed participants (p = 0.035); (p = 0.002) respectively, while resistin was higher in participants exposed to cercarial antigen than unexposed participants (p = 0.024). CONCLUSION: In this preschool population, P-selectin is significantly associated with urogenital schistosome infection and intensity; hence a potential biomarker for infection diagnosis and disease monitoring. The inflammatory biomarkers (P-selectin, Resistin and CRP) were significantly higher in participants exposed to cercarial antigens than unexposed individuals indicating an underlying inflammatory environment.

Diagnosis of Schistosoma mansoni infections: what are the choices in Brazilian low-endemic areas?

The population of Brazil is currently characterised by many individuals harbouring low-intensity Schistosoma mansoni infections. The Kato-Katz technique is the diagnostic method recommended by the World Health Organization (WHO) to assess these infections, but this method is not sensitive enough in the context of low egg excretion. In this regard, potential alternatives are being employed to overcome the limits of the Kato-Katz technique. In the present review, we evaluated the performance of parasitological and immunological approaches adopted in Brazilian areas. Currently, the diagnostic choices involve a combination of strategies, including the utilisation of antibody methods to screen individuals and then subsequent confirmation of positive cases by intensive parasitological investigations.