Mansoni Endemic Area Research Articles

Development, validation, and pilot application of a high throughput molecular xenomonitoring assay to detect Schistosoma mansoni and other trematode species within Biomphalaria freshwater snail hosts

Schistosomiasis is a neglected tropical disease (NTD) caused by infection with parasitic trematodes of the genus Schistosoma that can lead to debilitating morbidity and mortality. The World Health Organization recommend molecular xenomonitoring of Biomphalaria spp. freshwater snail intermediate hosts of Schistosoma mansoni to identify highly focal intestinal schistosomiasis transmission sites and monitor disease transmission, particularly in low-endemicity areas. A standardised protocol to do this, however, is needed. Here, two previously published primer sets were selected to develop and validate a multiplex molecular xenomonitoring end-point PCR assay capable of detecting S. mansoni infections within individual Biomphalaria spp. missed by cercarial shedding. The assay proved highly sensitive and highly specific in detecting and amplifying S. mansoni DNA and also proved highly sensitive in detecting and amplifying non-S. mansoni trematode DNA. The optimised assay was then used to screen Biomphalaria spp. collected from a S. mansoni-endemic area for infection and successfully detected S. mansoni infections missed by cercarial shedding as well as infections with non-S. mansoni trematodes. The continued development and use of molecular xenomonitoring assays such as this will aid in improving disease control efforts, significantly reducing disease-related morbidities experienced by those in schistosomiasis-endemic areas.

Reproducibility matters: intra- and inter-sample variation of the point-of-care circulating cathodic antigen test in two Schistosoma mansoni endemic areas in Uganda.

Over 240 million people are infected with schistosomiasis. Detecting Schistosoma mansoni eggs in stool using Kato-Katz thick smears (Kato-Katzs) is highly specific but lacks sensitivity. The urine-based point-of-care circulating cathodic antigen test (POC-CCA) has higher sensitivity, but issues include specificity, discrepancy between batches and interpretation of trace results. A semi-quantitative G-score and latent class analyses making no assumptions about trace readings have helped address some of these issues. However, intra-sample and inter-sample variation remains unknown for POC-CCAs. We collected 3 days of stool and urine from 349 and 621 participants, from high- and moderate-endemicity areas, respectively. We performed duplicate Kato-Katzs and one POC-CCA per sample. In the high-endemicity community, we also performed three POC-CCA technical replicates on one urine sampleperparticipant. Latent class analysis was performed to estimate the relative contribution of intra- (test technical reproducibility) and inter-sample (day-to-day) variation on sensitivity and specificity. Within-sample variation for Kato-Katzs was higher than between-sample, with the oppositetrue for POC-CCAs. A POC-CCA G3 threshold most accurately assesses individual infections. However, to reach the WHO target product profile of the required 95% specificity for prevalence and monitoring and evaluation, a threshold of G4 is needed, but at the cost of reducing sensitivity. This article is part of the theme issue 'Challenges and opportunities in the fight against neglected tropical diseases: a decade from the London Declaration on NTDs'.

Effect of treatment on school-aged children's hemoglobin levels in a Schistosoma mansoni endemic area of Minas Gerais, Brazil.

Effect of treatment on school-aged children's hemoglobin levels in a Schistosoma mansoni endemic area of Minas Gerais, Brazil.

Increased ShTAL1 IgE responses post-Praziquantel treatment may be associated with a reduced risk to re-infection in a Ghanaian S. haematobium-endemic community.

BackgroundEvidence from recent studies in Schistosoma mansoni-endemic areas show an age-associated immunity that is positively correlated with IgE titres to Schistosoma mansoni-specific tegumental allergen-like protein 1 (SmTAL1). The structural homology between SmTAL1 and the S. haematobium-specific TAL1 (ShTAL1) has been verified, yet it remains unclear whether similar age- and immune-associated trends characterize ShTAL1. This community-based intervention study was conducted to assess whether ShTAL1IgE responses post-treatment with praziquantel (PZQ) might be associated with a reduced risk to re-infection with S. haematobium.Methodology/Principal findingsThis study was conducted at Agona Abodom, Central Region, Ghana, and involved 114 participants aged 6 to 55 years. EDTA blood samples were collected at baseline and 7 weeks after PZQ treatment (Follow-up). Baseline and Follow-up titres of specific IgG1, IgG4, and IgE antibodies to the S. haematobium-specific adult worm antigen (ShAWA), the Sh-specific soluble egg antigen (ShSEA), and the Sh-specific tegumental-allergen-like 1 protein (ShTAL1) in plasma samples were measured using sandwich ELISA. Participants at both time points also provided stool and urine for helminth egg detection by microscopy. Prevalence of S. haematobium at baseline was 22.80%, and decreased to 3.50% at Follow-up. The egg reduction rate (ERR) was 99.87%. Overall plasma levels of ShTAL1-IgE increased 7 weeks post-PZQ treatment, and with increasing age; whiles S. haematobium infection prevalence and intensity decreased. For S. haematobium-infected participants who were egg-negative at Follow-up (N = 23), minimal median levels of ShTAL1-IgE were observed for all age groups prior to treatment, whilst median levels increased considerably among participants aged 12 years and older at Follow-up; and remained minimal among participants aged 11 years or less. In the univariate analysis, being aged 12 years or older implied an increased likelihood for ShTAL1-IgE positivity [12–14 years (cOR = 9.64, 95% CI = 2.09–44.51; p = 0.004); 15+ years (cOR = 14.26, 95% CI = 3.10–65.51; p = 0.001)], and this remained significant after adjusting for confounders [12–14 years (aOR = 22.34, 95% CI = 2.77–180.14; p = 0.004); ≥15 years (aOR = 51.82, 95% CI = 6.44–417.17; p < 0.001)]. Conversely, median ShTAL1-IgG4 titres were hardly detectible at Follow-up.Conclusions/SignificanceThese findings demonstrate that increased IgE levels to ShTAL1 7 weeks after PZQ treatment could be associated with a reduced risk to re-infection, and adds to the large body of evidence suggesting a protective role of the treatment-induced ShTAL1 antigen in schistosomiasis infections. It was also quite clear from this work that apart from being persistently S. haematobium-positive, elevated ShTAL1-IgG4 levels at Follow-up could be indicative of susceptibility to re-infection. These outcomes have important implications in vaccine development, and in shifting the paradigm in mass chemotherapy programmes from a ‘one-size-fits-all’ approach to more sub-group-/participant-specific strategies in endemic areas.

Candidate gene family-based and case-control studies of susceptibility to high Schistosoma mansoni worm burden in African children: a protocol.

Background: Approximately 25% of the risk of Schistosoma mansoni is associated with host genetic variation. We will test 24 candidate genes, mainly in the T h2 and T h17 pathways, for association with S. mansoni infection intensity in four African countries, using family based and case-control approaches. Methods: Children aged 5-15 years will be recruited in S. mansoni endemic areas of Ivory Coast, Cameroon, Uganda and the Democratic Republic of Congo (DRC). We will use family based (study 1) and case-control (study 2) designs. Study 1 will take place in Ivory Coast, Cameroon, Uganda and the DRC. We aim to recruit 100 high worm burden families from each country except Uganda, where a previous study recruited at least 40 families. For phenotyping, cases will be defined as the 20% of children in each community with heaviest worm burdens as measured by the circulating cathodic antigen (CCA) assay. Study 2 will take place in Uganda. We will recruit 500 children in a highly endemic community. For phenotyping, cases will be defined as the 20% of children with heaviest worm burdens as measured by the CAA assay, while controls will be the 20% of infected children with the lightest worm burdens. Deoxyribonucleic acid (DNA) will be genotyped on the Illumina H3Africa SNP (single nucleotide polymorphisms) chip and genotypes will be converted to sets of haplotypes that span the gene region for analysis. We have selected 24 genes for genotyping that are mainly in the Th2 and Th17 pathways and that have variants that have been demonstrated to be or could be associated with Schistosoma infection intensity. Analysis: In the family-based design, we will identify SNP haplotypes disproportionately transmitted to children with high worm burden. Case-control analysis will detect overrepresentation of haplotypes in extreme phenotypes with correction for relatedness by using whole genome principal components.

Candidate gene family-based and case-control studies of susceptibility to high Schistosoma mansoni worm burden in African children: a protocol

Background: Approximately 25% of the risk of Schistosoma mansoni is associated with host genetic variation. We will test 24 candidate genes, mainly in the T h2 and T h17 pathways, for association with S. mansoni infection intensity in four African countries, using family based and case-control approaches. Methods: Children aged 5-15 years will be recruited in S. mansoni endemic areas of Ivory Coast, Cameroon, Uganda and the Democratic Republic of Congo (DRC). We will use family based (study 1) and case-control (study 2) designs. Study 1 will take place in Ivory Coast, Cameroon, Uganda and the DRC. We aim to recruit 100 high worm burden families from each country except Uganda, where a previous study recruited at least 40 families. For phenotyping, cases will be defined as the 20% of children in each community with heaviest worm burdens as measured by the circulating cathodic antigen (CCA) assay. Study 2 will take place in Uganda. We will recruit 500 children in a highly endemic community. For phenotyping, cases will be defined as the 20% of children with heaviest worm burdens as measured by the CAA assay, while controls will be the 20% of infected children with the lightest worm burdens. Deoxyribonucleic acid (DNA) will be genotyped on the Illumina H3Africa SNP (single nucleotide polymorphisms) chip and genotypes will be converted to sets of haplotypes that span the gene region for analysis. We have selected 24 genes for genotyping that are mainly in the Th2 and Th17 pathways and that have variants that have been demonstrated to be or could be associated with Schistosoma infection intensity. Analysis: In the family-based design, we will identify SNP haplotypes disproportionately transmitted to children with high worm burden. Case-control analysis will detect overrepresentation of haplotypes in extreme phenotypes with correction for relatedness by using whole genome principal components.

Environmental Drivers and Potential Distribution of Schistosoma mansoni Endemic Areas in Ethiopia.

In Ethiopia, human schistosomiasis is caused by two species of schistosome, Schistosoma mansoni and S. haematobium, with the former being dominant in the country, causing infections of more than 5 million people and more than 37 million at risk of infection. What is more, new transmission foci for S. mansoni have been reported over the past years in the country, raising concerns over the potential impacts of environmental changes (e.g., climate change) on the disease spread. Knowledge on the distribution of schistosomiasis endemic areas and associated drivers is much needed for surveillance and control programs in the country. Here we report a study that aims to examine environmental determinants underlying the distribution and suitability of S. mansoni endemic areas at the national scale of Ethiopia. The study identified that, among five physical environmental factors examined, soil property, elevation, and climatic factors (e.g., precipitation and temperature) are key factors associated with the distribution of S. mansoni endemic areas. The model predicted that the suitable areas for schistosomiasis transmission are largely distributed in northern, central, and western parts of the country, suggesting a potentially wide distribution of S. mansoni endemic areas. The findings of this study are potentially instrumental to inform public health surveillance, intervention, and future research on schistosomiasis in Ethiopia. The modeling approaches employed in this study may be extended to other schistosomiasis endemic regions and to other vector-borne diseases.

Candidate gene family-based and case-control studies of susceptibility to high Schistosoma mansoni worm burden in African children: a protocol

Background: Approximately 25% of the risk of Schistosoma mansoni is associated with host genetic variation. We will test 24 candidate genes, mainly in the Th2 and Th17 pathways, for association with S. mansoni infection intensity in four African countries, using family based and case-control approaches. Methods: Children aged 5-15 years will be recruited in S. mansoni endemic areas of Ivory Coast, Cameroon, Uganda and the Democratic Republic of Congo (DRC). We will use family based (study 1) and case-control (study 2) designs. Study 1 will take place in Ivory Coast, Cameroon, Uganda and the DRC. We aim to recruit 100 high worm burden families from each country except Uganda, where a previous study recruited at least 40 families. For phenotyping, cases will be defined as the 20% of children in each community with heaviest worm burdens as measured by the circulating cathodic antigen (CCA) assay. Study 2 will take place in Uganda. We will recruit 500 children in a highly endemic community. For phenotyping, cases will be defined as the 20% of children with heaviest worm burdens as measured by the CAA assay, while controls will be the 20% of infected children with the lightest worm burdens. Deoxyribonucleic acid (DNA) will be genotyped on the Illumina H3Africa SNP (single nucleotide polymorphisms) chip and genotypes will be converted to sets of haplotypes that span the gene region for analysis. We have selected 24 genes for genotyping that are mainly in the Th2 and Th17 pathways and that have variants that have been demonstrated to be or could be associated with Schistosoma infection intensity. Analysis: In the family-based design, we will identify SNP haplotypes disproportionately transmitted to children with high worm burden. Case-control analysis will detect overrepresentation of haplotypes in extreme phenotypes with correction for relatedness by using whole genome principal components.

Biogeographical characteristics of Schistosoma mansoni endemic areas in Ethiopia: a systematic review and meta analysis

BackgroundIn Ethiopia, schistosomiasis is caused by Schistosoma mansoni and S. haematobium with the former being widespread and more than 4 million people are estimated to be infected by S. mansoni annually with 35 million at risk of infection. Although many school- and community-based epidemiological surveys were conducted over the past decades, the national distribution of schistosomiasis endemic areas and associated socio-environmental determinants remain less well understood. In this paper, we review S. mansoni prevalence of infections and describe key biogeographical characteristics in the endemic areas in Ethiopia.MethodsWe developed a database of S. mansoni infection surveys in Ethiopia through a systematic review by searching articles published between 1975 and 2019 on electronic online databases including PubMed, ScienceDirect, and Web of Science. A total of 62 studies involving 95 survey locations were included in the analysis. We estimated adjusted prevalence of infection from each survey by considering sensitivity and specificity of diagnostic tests using Bayesian approach. All survey locations were georeferenced and associated environmental and geographical characteristics (e.g. elevation, normalized difference vegetation index, soil properties, wealth index, and climatic data) were described using descriptive statistics and meta-analysis.ResultsThe results showed that the surveys exhibited a wide range of adjusted prevalence of infections from 0.5% to 99.5%, and 36.8% of the survey sites had adjusted prevalence of infection higher than 50%. S. mansoni endemic areas were distributed in six regional states with the majority of surveys being in Amhara and Oromia. Endemic sites were found at altitudes from 847.6 to 3141.8 m above sea level, annual mean temperatures between 17.9 and 29.8 ℃, annual cumulative precipitation between 1400 and 1898 mm, normalized difference vegetation index between 0.03 and 0.8, wealth index score between –68 857 and 179 756; and sand, silt, and clay fraction in soil between 19.1–47.2, 23.0–36.7, and 20.0–52.8 g/100 g, respectively.ConclusionsThe distribution of S. mansoni endemic areas and prevalence of infections exhibit remarked environmental and ecological heterogeneities. Future research is needed to understand how much these heterogeneities drive the parasite distribution and transmission in the region.Graphic

Current status of Schistosoma mansoni infection among previously treated rural communities in the Abbey and Didessa Valleys, Western Ethiopia: Implications for sustainable control.

BackgroundSchistosoma constitutes a major public health problem and developmental challenges in the majority of developing and subtropical regions. The World Health Organization has set guidelines for the control and elimination of schistosomiasis. Ethiopia is providing school-based Mass Drug Administration (MDA) at the study areas of the Abbey and Didessa Valleys of western Ethiopian since 2015. Moreover, mass treatment was already done in the same villages 30 years ago. However, the current Schistosoma mansoni infection status among humans and snails in the study areas is not known. Hence, the present study aims to determine the current status.MethodsA community-based cross-sectional study was conducted in the three communities; Chessega, Agallu Metti and Shimala in Schistosoma mansoni endemic areas of the Abbey and Didessa valleys in Western Ethiopia. Using the list of households obtained from the Kebele administration, a systematic sampling technique was used to select households in each village.ResultsEven though the area is under the Ethiopian national Mass Drug Administration campaign, the present study reports prevalence above 50%. Although the majority of the infections were moderate, we found that 13% had heavy infection, above 400 eggs per gram of stool, which is at the same level as before the treatment campaign 30 years ago. The infection was significantly higher among those below 12 years of age, among non-attending school-age children and daily laborers.ConclusionSchistosoma mansoni infection is still a public health problem in the study areas, despite control efforts already 30 years ago and present mass treatment in the last years. We suggest making the mass treatment campaign just early after the rainy season, when the snails are washed away. This should be supplemented with provisions of clean water, sanitation, and hygiene (WASH) and reduction of water contact and possible snail control efforts’ to prevent reinfection.

Phenotypic Characterization of CD4+ T Lymphocytes in Periportal Fibrosis Secondary to Schistosomiasis.

Schistosomiasis is a parasitic disease that affects about 166 million people around the world. It is estimated that 5%–10% of individuals with schistosomiasis develop severe forms of the disease, which are characterized by pulmonary hypertension, ascites, periportal fibrosis, and other significant complications. The chronic phase of the disease is associated with a Th2 type immune response, but evidence also suggests there are roles for Th1 and Th17 in the development of severe disease. The aim of this study was to evaluate the CD4+ T lymphocyte profile of patients with different degrees of periportal fibrosis secondary to schistosomiasis. These individuals had been treated for schistosomiasis, but since they live in a S. mansoni endemic area, they are at risk of reinfection. They were evaluated in relation to the degree of periportal fibrosis and classified into three groups: without fibrosis or with incipient fibrosis (WF/IFNE), n=12, possible periportal fibrosis/periportal fibrosis, n=13, and advanced periportal fibrosis/advanced periportal fibrosis with portal hypertension, n=4. We observed in the group without fibrosis a balance between the low expression of Th2 cytokines and high expression of T reg cells. As has already been described in the literature, we found an increase of the Th2 cytokines IL-4, IL-5, and IL-13 in the group with periportal fibrosis. In addition, this group showed higher expression of IL-17 and IL-10 but lower IL-10/IL-13 ratio than patients in the WF/IFNE group. Cells from individuals who present any level of fibrosis expressed more TGF-β compared to the WF/IFNE group and a positive correlation with left lobe enlargement and portal vein wall thickness. There was a negative correlation between IL-17 and the thickness of the portal vein wall, but more studies are necessary in order to explore the possible protective role of this cytokine. Despite the fibrosis group having presented a higher expression of pro-fibrotic molecules compared to WF/IFNE patients, it seems there is a regulation through IL-10 and T reg cells that is able to maintain the low morbidity of this group.

Characteristics of persistent hotspots of Schistosoma mansoni in western C\xf4te d\u2019Ivoire

BackgroundPreventive chemotherapy with praziquantel is the cornerstone of schistosomiasis control. However, in some social-ecological settings, the prevalence and/or intensity of Schistosoma infection does not lower meaningfully despite multiple rounds of preventive chemotherapy, a phenomenon termed persistent hotspot (PHS). We assessed the characteristics of PHS in a Schistosoma mansoni-endemic area of Côte d’Ivoire.MethodsIn October 2016, a cross-sectional survey was conducted in 14 schools in the western part of Côte d’Ivoire, one year after multiple rounds of preventive chemotherapy. In each school, 50 children aged 9–12 years provided two stool samples and one urine sample. Stool samples were subjected to triplicate Kato-Katz thick smears for S. mansoni diagnosis. Urine samples were examined by a filtration method for S. haematobium eggs. PHS was defined as failure to achieve a reduction in the prevalence of S. mansoni infection of at least 35% and/or a reduction of infection intensity of at least 50%. Six schools underwent more detailed investigations, including a questionnaire survey for demographic characteristics and a malacological survey.ResultsIn the six schools subjected to detailed investigations, the overall prevalence of S. mansoni and S. haematobium was 9.5% and 2.6%, respectively. Four schools were classified as PHS. The S. mansoni prevalence in the four PHS was 10.9% compared to 6.6% in the remaining two schools. The S. mansoni infection intensity, expressed as arithmetic mean eggs per gram of stool (EPG) among infected children, was 123.8 EPG in PHS and 18.7 EPG in the other two schools. Children bathing in open freshwater bodies were at higher odds of S. mansoni infection (odds ratio: 4.5, 95% confidence interval: 1.6–12.6). A total of 76 human-water contact sites (53 in PHS and 23 in the other schools) were examined and 688 snails were collected, including potential intermediate host snails of Schistosoma (Biomphalaria pfeifferi, Bulinus forskalii, Bu. globosus and Bu. truncatus).ConclusionChildren in PHS schools bathed more frequently in open freshwater bodies, and hence, they are more exposed to Schistosoma transmission. Our findings call for an integrated control approach, complementing preventive chemotherapy with other interventions, particularly in PHS settings.

Plasma Endotoxin Levels Are Not Increased in Schistosoma mansoni–Infected Women without Signs or Symptoms of Hepatosplenic Disease

Elevated circulating endotoxin levels in the plasma of patients with advanced hepatosplenic schistosomiasis caused by Schistosoma mansoni have been reported, possibly caused by parasite egg-induced intestinal mucosal breaches facilitating bacterial access to the bloodstream. Neither endotoxin levels in people with S. mansoni but without hepatosplenic disease nor the impact of treatment on endotoxin levels have been described. We used a methodically optimized Limulus amebocyte lysate assay to measure plasma endotoxin in community-dwelling women from an S. mansoni-endemic area without clinical hepatosplenic disease. We found no difference in baseline mean plasma endotoxin levels between those with (n = 22) and without (n = 31) infection (1.001 versus 0.949 EU/mL, P = 0.61). Endotoxin levels did not change in schistosome-infected women after successful treatment (1.001 versus 1.093 EU/mL, P = 0.45) and were not correlated with circulating anodic antigen or stool egg burden. Our findings do not support the hypothesis that translocating eggs in S. mansoni infection introduce bacterial sources of endotoxin to the circulation.

Effects of Water Source, Sanitation and Hygiene on the Prevalence of Schistosoma mansoni among School Age Children in Jawe District, Northwest Ethiopia

Intestinal schistosomiasis is a disease caused by infection with one of the blood flukes called Schistosoma mansoni. The distribution of Schistosoma mansoni infection is high in Sub-Saharan Africa due to water source, sanitation and hygiene problems. This study aimed to determine the effect of water source, sanitation and hygiene on the prevalence of schistosomiasis among school-age children in Northwest Ethiopia. A cross-sectional study was conducted from Apr 2016 to Aug 2016. Children were selected by systematic random sampling and Formol Ether Concentration Technique (FECT) was used to identify Schistosoma mansoni infection. Statistical analysis was done using descriptive statistics and strength of association of schistosomiasis with determinant factors was calculated by bivariate analysis. Among 333 children, 7% were infected with Schistosoma mansoni. Using surface water for drinking, poor hand wash habit and latrine utilization were significantly associated (P<0.05) with Schistosoma mansoni infection. Absence of safe water for bathing, washing and swimming, poor sanitation and hygiene practices were major risk factors for schistosomiasis. Therefore, health education should be given on the transmission of S. mansoni infection, pure water, sanitation and hygiene in S. mansoni endemic areas.

Can Early Diagnosis of Varices, Regular Praziquantel, and Reduction of Hepatitis Coinfection Reduce Mortality among Patients Attended for Periportal Fibrosis in Northwestern Tanzania? A Case-Control Study.

Background Schistosoma mansoni is highly endemic in the Lake Zone part of Tanzania and most people are chronically infected. Periportal fibrosis (PPF) is the commonest complication of chronic S. mansoni infection documented in up to 42% of studied participants in the community-based studies. These patients are at high risk of mortality since most of them are diagnosed late with bleeding varices. At Bugando, Schistosoma-related varices contributed to 70% of patients admitted due to vomiting blood with a two months' mortality of over 10%. Earlier studies had reported higher mortality of up to 29% among patients with PPF even with the best in-hospital care. Understanding factors that increased the risk of mortality is important clinically in devising ways that can improve the outcome of this subgroup of patients. Methods A retrospective analysis of patients with PPF from 2015 through 2018 was done. Their sociodemographic, clinical, laboratory, ultrasonographic, endoscopic, and survival status data were collected for analysis. STATA 13 was used for analysis, the prevalence of varices, active schistosomiasis, and hepatitis B coinfection was determined. Cumulative mortality as a major outcome was also determined, and factors associated with increased risk of mortality were assessed by a logistic regression model. Results In total, 250 participants were included in this analysis. Majority, 222 (88.8%; 95% CI: 84.2-92.4) had active S. mansoni infection, and 40 (16.0%; 95% CI: 11.6-21.1) had S. mansoni-HBV coinfection. Cumulatively, 39 (15.6%; 95% CI: 11.3-20.7) patients died, with most deaths, 31 (79.5%; 95% CI: 63.5-90.7) occurring within two years following the diagnosis of PPF (chi2 = 6.3; p = 0.012). The odds of mortality were independently associated with fishing (OR: 10.8; 95% CI: 2.2-52; p = 0.003), upper gastro intestinal bleeding (OR: 2.4; 95% CI: 1.1-5.4; p = 0.037), HBV coinfection (OR: 3.3; 95% CI: 1.2-91; p = 0.019), and ascites (OR: 3.3; 95% CI: 1.3-8.2; p = 0.010). Conclusions In this, S. mansoni endemic area, varices, actives schistosomiasis, hepatitis B coinfection, and mortality are highly common. Screening for varices and initiation of prophylaxis, administration of praziquantel, and screening for hepatitis B should be part and parcel of care of these patients. The first two years of diagnosis, patients are at high risk of mortality; risk factors in this study should assist planning a closer follow-up of patients at risk of mortality to improve their long-term outcome.

An ultrasound-based referential of body height-adjusted normal liver organometry in school children from Bokito in rural Cameroon

The grading system for ultrasonographic assessment of Schistosoma mansoni morbidity is crucial for evaluation of control programs. This requires prior definition of normal liver organometric ranges in the population from the endemic area. A cross-sectional study was conducted in a S. mansoni endemic area in rural Cameroon. 1002 Participants were screened and 234 of them, free from all common liver-affecting diseases in the area (schistosomiasis, malaria, hepatitis B and C) and with no ultrasonographic signs of liver disease were selected and their liver parameters measured by ultrasonography. All statistics were considered significant for p-values < 0.05. Normal dimensions of livers lobe sizes, portal vein wall thickness and portal vein diameters are reported. The liver organometric data are presented for the entire study population as a whole and separately for males and females as prediction plots, with observed values and fitted regression line with 95% confidence. Reference ranges for liver parameters (size, portal vein thickness and diameter) adjusted for body height established in the current study are novel for Cameroon. The prediction plots generated should improve the accuracy of the assessment of liver morbidity by ultrasonography in the region.

Detection of Schistosoma DNA in genital specimens and urine: A comparison between five female African study populations originating from S. haematobium and/or S. mansoni endemic areas

Female Genital Schistosomiasis (FGS) is a neglected disease affecting millions, however challenging to diagnose. This explorative descriptive study compares Schistosoma real-time PCR analysis of cervico-vaginal lavages (CVL) with corresponding urine and stool samples of 933 women from five different previously described study populations. Sampling included 310 women from an S. mansoni endemic region in Mwanza, Tanzania and 112 women from a nearby S. haematobium endemic region. Findings were compared with samples collected from S. haematobium endemic regions in South Africa from 394 women and from 117 women from Madagascar of which 79 were urine pre-selected microscopy positive cases from highly-endemic communities and 38 were urine microscopy negatives from a low-endemic community. As anticipated, urine and stool microscopy and gynecological investigations varied substantially between study populations; however, the same Schistosoma real-time PCR was performed in one reference laboratory. Schistosoma DNA was detected in 13% (120/933) of the CVL, ranging from 3% in the S. mansoni Tanzanian endemic region to 61% in the pre-selected Malagasy urine microscopy positive cases. Detectable Schistosoma DNA in CVL was associated with Schistosoma DNA in urine but not with microscopic detection of eggs in urine or by cytological examination. This study confirmed real-time PCR for the detection of Schistosoma DNA in gynecological samples to be a valuable diagnostic tool to study the distribution of FGS within schistosomiasis endemic areas.

An innovative and user-friendly scoring system for standardised quantitative interpretation of the urine-based point-of-care strip test (POC-CCA) for the diagnosis of intestinal schistosomiasis: a proof-of-concept study

The point-of-care strip assay for the detection of the schistosome Circulating Cathodic Antigen (POC-CCA) in urine has shown to be a user-friendly and sensitive alternative to stool microscopy for the diagnosis of Schistosoma mansoni infections. However, visual scoring of the test is by definition observer dependent and leads to discussion about the qualitative interpretation, in particular in low intensity infections when test lines tend to be weak. In order to standardise visual scoring, an innovative approach for semi-quantitative interpretation of the POC-CCA cassettes, called G-scores, was developed and evaluated. Urines (n = 110) from a S. mansoni endemic area were used to evaluate this new approach. Test lines of the POC-CCA were visually compared against the G-scores, i.e. a series of artificial cassettes containing inkjet-printed strips of different intensities in order to grade the POC-CCA test line on a scale of 1 to 10. A significant positive correlation (Spearman 0.660, p < 0.001) was observed between G-scores and eggs per gram of faeces. This proof-of-concept study demonstrates the usefulness of the G-scores for standardising the visual scoring of the POC-CCA urine strip assay. Several research groups have already indicated an interest in the G-scores for their field work. Further distribution of the cassettes, in particular when provided in combination with reference standards, will assist the wider schistosomiasis community in dealing with issues like batch-to-batch differences and interpretation of trace readings.

PO 8409 SERUM HYALURONIC ACID: A POTENTIAL DIAGNOSTIC MARKER FOR SCHISTOSOMAL PERIPORTAL FIBROSIS IN SCHISTOSOMA MANSONI-ENDEMIC AREAS

BackgroundSchistosoma mansoni-induced infection is one of the most prevalent infections worldwide with serious public health and economic impact. Morbidity and mortality associated with S. mansoni is mainly the result of periportal fibrosis (PPF) which can be diagnosed using ultrasonography. As ultrasound equipment is not readily available in S. mansoni-endemic areas, serum markers like hyaluronic acid (HA) have been used as an alternative means of diagnosing PPF.MethodsA cross-sectional study was conducted with the aim of determining the importance of serum HA as a marker for schistosomal PPF in in 55 patients found in S. mansoni-endemic areas in northeastern Ethiopia and 20 non-endemic controls. PPF was determined using portable ultrasound equipment and graded according to the ‘Niamey protocol’. Serum HA concentration was determined using commercially available ELISA kit.ResultsThe mean concentration of HA in the sera of the cases was significantly higher than the controls (p&lt;0.001). The concentration of HA also increased significantly as the pattern of PPF became severe while serum HA concentration positively correlated with PPF scores (ρ=0.6438, p&lt;0.001). HA concentration of 27.9 µg/liter of serum differentiated moderate cases of PPF from advanced cases with a sensitivity, specificity, positive predictive value and negative predictive value of 85.71%, 75.61%, 60.5%, 93.9%, respectively (p&lt;0.001). In conclusion, serum HA concentrations could be used as a potential marker for schistosomal PPF and to assess its severity in patients found in S. mansoni-endemic areas.ConclusionBased on our results, serum HA concentrations could be used as an alternative, non-invasive potential marker for schistosomal PPF and to assess its severity in patients found in S. mansoni-endemic areas.

Capacity gaps in health facilities for case management of intestinal schistosomiasis and soil-transmitted helminthiasis in Burundi

BackgroundSchistosomiasis and soil-transmitted helminthiasis (STH) are endemic diseases in Burundi. STH control is integrated into health facilities (HF) across the country, but schistosomiasis control is not. The present study aimed to assess the capacity of HF for integrating intestinal schistosomiasis case management into their routine activities. In addition, the current capacity for HF-based STH case management was evaluated.MethodsA random cluster survey was carried out in July 2014, in 65 HF located in Schistosoma mansoni and STH endemic areas. Data were collected by semi-quantitative questionnaires. Staff with different functions at the HF were interviewed (managers, care providers, heads of laboratory and pharmacy and data clerks). Data pertaining to knowledge of intestinal schistosomiasis and STH symptoms, human and material resources and availability and costs of diagnostic tests and treatment were collected.FindingsLess than half of the 65 care providers mentioned one or more major symptoms of intestinal schistosomiasis (abdominal pain 43.1%, bloody diarrhoea 13.9% and bloody stool 7.7%). Few staff members (15.7%) received higher education, and less than 10% were trained in-job on intestinal schistosomiasis case management. Clinical guidelines and laboratory protocols for intestinal schistosomiasis diagnosis and treatment were available in one third of the HF. Diagnosis was performed by direct smear only. Praziquantel was not available in any of the HF. The results for STH were similar, except that major symptoms were more known and cited (abdominal pain 69.2% and diarrhoea 60%). Clinical guidelines were available in 61.5% of HF, and albendazole or mebendazole was available in all HF.ConclusionsThe current capacity of HF for intestinal schistosomiasis and STH detection and management is inadequate. Treatment was not available for schistosomiasis. These issues need to be addressed to create an enabling environment for successful integration of intestinal schistosomiasis and STH case management into HF routine activities in Burundi for better control of these diseases.