Showing papers on "Schistosoma haematobium published in 2015"

Spatial distribution of schistosomiasis and treatment needs in sub-Saharan Africa: a systematic review and geostatistical analysis

Abstract: Summary Background Schistosomiasis affects more than 200 million individuals, mostly in sub-Saharan Africa, but empirical estimates of the disease burden in this region are unavailable. We used geostatistical modelling to produce high-resolution risk estimates of infection with Schistosoma spp and of the number of doses of praziquantel treatment needed to prevent morbidity at different administrative levels in 44 countries. Methods We did a systematic review to identify surveys including schistosomiasis prevalence data in sub-Saharan Africa via PubMed, ISI Web of Science, and African Journals Online, from inception to May 2, 2014, with no restriction of language, survey date, or study design. We used Bayesian geostatistical meta-analysis and rigorous variable selection to predict infection risk over a grid of 1 155 818 pixels at 5 × 5 km, on the basis of environmental and socioeconomic predictors and to calculate the number of doses of praziquantel needed for prevention of morbidity. Findings The literature search identified Schistosoma haematobium and Schistosoma mansoni surveys done in, respectively, 9318 and 9140 unique locations. Infection risk decreased from 2000 onwards, yet estimates suggest that 163 million (95% Bayesian credible interval [CrI] 155 million to 172 million; 18·5%, 17·6–19·5) of the sub-Saharan African population was infected in 2012. Mozambique had the highest prevalence of schistosomiasis in school-aged children (52·8%, 95% CrI 48·7–57·8). Low-risk countries (prevalence among school-aged children lower than 10%) included Burundi, Equatorial Guinea, Eritrea, and Rwanda. The numbers of doses of praziquantel needed per year were estimated to be 123 million (95% CrI 121 million to 125 million) for school-aged children and 247 million (239 million to 256 million) for the entire population. Interpretation Our results will inform policy makers about the number of treatments needed at different levels and will guide the spatial targeting of schistosomiasis control interventions. Funding European Research Council, China Scholarship Council, UBS Optimus Foundation, and Swiss National Science Foundation.

Epidemiology of Bladder Cancer

Abstract: Bladder cancer incidence is higher in old men, shows geographic variation, and is mostly an environmental disease. Cigarette smoking, occupational exposures, water arsenic, Schistosoma haematobium infestation, and some medications are the best established risk factors. Low-penetrance genetic factors also contribute to its origin, some through interaction with environmental factors. Bladder cancer has high prevalence and a low mortality, being largely a chronic disease. Data on environmental and genetic factors involved in the disease outcome are inconclusive.

Isothermal Recombinase Polymerase amplification (RPA) of Schistosoma haematobium DNA and oligochromatographic lateral flow detection

Abstract: Accurate diagnosis of urogenital schistosomiasis is vital for surveillance/control programs. Amplification of schistosome DNA in urine by PCR is sensitive and specific but requires infrastructure, financial resources and skilled personnel, often not available in endemic areas. Recombinase Polymerase Amplification (RPA) is an isothermal DNA amplification/detection technology that is simple, rapid, portable and needs few resources. Here a Schistosoma haematobium RPA assay was developed and adapted so that DNA amplicons could be detected using oligochromatographic Lateral Flow (LF) strips. The assay successfully amplified S. haematobium DNA at 30–45 °C in 10 mins and was sensitive to a lower limit of 100 fg of DNA. The assay was also successful with the addition of crude urine, up to 5 % of the total reaction volume. Cross amplification occurred with other schistosome species but not with other common urine microorganisms. The LF-RPA assay developed here can amplify and detect low levels of S. haematobium DNA. Reactions are rapid, require low temperatures and positive reactions are interpreted using lateral flow strips, reducing the need for infrastructure and resources. This together with an ability to withstand inhibitors within urine makes RPA a promising technology for further development as a molecular diagnostic tool for urogenital schistosomiasis.

Sensitivity and Specificity of a Urine Circulating Anodic Antigen Test for the Diagnosis of Schistosoma haematobium in Low Endemic Settings.

Abstract: Elimination of schistosomiasis as a public health problem and interruption of transmission in selected areas are key goals of the World Health Organization for 2025. Conventional parasitological methods are insensitive for the detection of light-intensity infections. Techniques with high sensitivity and specificity are required for an accurate diagnosis in low-transmission settings and verification of elimination. We determined the accuracy of a urine-based up-converting phosphor-lateral flow circulating anodic antigen (UCP-LF CAA) assay for Schistosoma haematobium diagnosis in low-prevalence settings in Zanzibar, Tanzania.; A total of 1,740 urine samples were collected in 2013 from children on Pemba Island, from schools where the S. haematobium prevalence was >2%, 2-5%, and 5-10%, based on a single urine filtration. On the day of collection, all samples were tested for microhematuria with reagent strips and for the presence of S. haematobium eggs with microscopy. Eight months later, 1.5 ml of urine from each of 1,200 samples stored at -20°C were analyzed by UCP-LF CAA assay, while urine filtration slides were subjected to quality control (QCUF). In the absence of a true 'gold' standard, the diagnostic performance was calculated using latent class analyses (LCA).; The 'empirical' S. haematobium prevalence revealed by UCP-LF CAA, QCUF, and reagent strips was 14%, 5%, and 4%, respectively. LCA revealed a sensitivity of the UCP-LF CAA, QCUF, and reagent strips of 97% (95% confidence interval (CI): 91-100%), 86% (95% CI: 72-99%), and 67% (95% CI: 52-81%), respectively. Test specificities were consistently above 90%. The UCP-LF CAA assay shows high sensitivity for the diagnosis of S. haematobium in low-endemicity settings. Empirically, it detects a considerably higher number of infections than microscopy. Hence, the UCP-LF CAA employed in combination with QCUF, is a promising tool for monitoring and surveillance of urogenital schistosomiasis in low-transmission settings targeted for elimination.

Systematic Review and Meta-analysis of the Impact of Chemical-Based Mollusciciding for Control of Schistosoma mansoni and S. haematobium Transmission

Abstract: Background Programs for schistosomiasis control are advancing worldwide, with many benefits noted in terms of disease reduction. Yet risk of reinfection and recurrent disease remain, even in areas with high treatment coverage. In the search for means to better prevent new Schistosoma infections, attention has returned to an older strategy for transmission control, i.e., chemical mollusciciding, to suppress intermediate host snail species responsible for S. mansoni and S. haematobium transmission. The objective of this systematic review and meta-analysis was to summarize prior experience in molluscicide-based control of Bulinus and Biomphalaria spp. snails, and estimate its impact on local human Schistosoma infection. Methodology/Principal Findings The review was registered at inception with PROSPERO (CRD42013006869). Studies were identified by online database searches and hand searches of private archives. Eligible studies included published or unpublished mollusciciding field trials performed before January 2014 involving host snails for S. mansoni or S. haematobium, with a primary focus on the use of niclosamide. Among 63 included papers, there was large variability in terms of molluscicide dosing, and treatment intervals varied from 3–52 weeks depending on location, water source, and type of application. Among 35 studies reporting on prevalence, random effects meta-analysis indicated that, on average, odds of infection were reduced 77% (OR 0.23, CI95% 0.17, 0.31) during the course of mollusciciding, with increased impact if combined with drug therapy, and progressively greater impact over time. In 17 studies reporting local incidence, risk of new infection was reduced 64% (RR 0.36 CI95% 0.25, 0.5), but additional drug treatment did not appear to influence incidence effects. Conclusion/Significance While there are hurdles to implementing molluscicide control, its impact on local transmission is typically strong, albeit incomplete. Based on past experience, regular focal mollusciciding is likely to contribute significantly to the move toward elimination of schistosomiasis in high risk areas.

Schistosomiasis reaches Europe

Abstract: An outbreak of urogenital schistosomiasis has been detected in Europe, with patients affected in France,1,2 Germany,1,2 and Italy. The infection originated in Corsica, in a river north of Porto-Vecchio, a popular tourist destination (figure). The introduction of schistosomiasis is believed to be associated with infected people arriving from a region endemic for the exclusively African parasite, Schistosoma haematobium and disseminating parasite eggs through their urine into snail breeding sites along the river.

Differences in the Faecal Microbiome in Schistosoma haematobium Infected Children vs. Uninfected Children

Abstract: Background: Several infectious diseases and therapeutic interventions cause gut microbe dysbiosis and associated pathology. We characterised the gut microbiome of children exposed to the helminth Schistosoma haematobium pre- and post-treatment with the drug praziquantel (PZQ), with the aim to compare the gut microbiome structure (abundance and diversity) in schistosome infected vs. uninfected children. Methods: Stool DNA from 139 children aged six months to 13 years old; with S. haematobium infection prevalence of 27.34% was extracted at baseline. 12 weeks following antihelminthic treatment with praziqunatel, stool DNA was collected from 62 of the 139 children. The 16S rRNA genes were sequenced from the baseline and post-treatment samples and the sequence data, clustered into operational taxonomic units (OTUs). The OTU data were analysed using multivariate analyses and paired T- test. Results: Pre-treatment, the most abundant phyla were Bacteroidetes, followed by Firmicutes and Proteobacteria respectively. The relative abundance of taxa among bacterial classes showed limited variation by age group or sex and the bacterial communities had similar overall compositions. Although there were no overall differences in the microbiome structure across the whole age range, the abundance of 21 OTUs varied significantly with age (FDR<0.05). Some OTUs including Veillonella, Streptococcus, Bacteroides and Helicobacter were more abundant in children ≤ 1 year old compared to older children. Furthermore, the gut microbiome differed in schistosome infected vs. uninfected children with 27 OTU occurring in infected but not uninfected children, for 5 of these all Prevotella, the difference was statistically significant (p <0.05) with FDR <0.05. PZQ treatment did not alter the microbiome structure in infected or uninfected children from that observed at baseline. Conclusions: There are significant differences in the gut microbiome structure of infected vs. uninfected children and the differences were refractory to PZQ treatment.

Introgressive hybridizations of Schistosoma haematobium by Schistosoma bovis at the origin of the first case report of schistosomiasis in Corsica (France, Europe)

Abstract: This study concerns the first urinary schistosomiasis case observed in Corsica (France, Europe) occurring in a 12-year-old German boy. The aim was to identify the relationship between this Schistosoma haematobium infection and other schistosomes of the Schistosoma group with terminal-spined ova. Morphological and molecular analyses were conducted on the ova. The results showed that the schistosome responsible for the emergence of schistosomiasis in Corsica was due to S. haematobium introgressed by genes from S. bovis.

Diagnosis of Schistosoma haematobium infection with a mobile phone-mounted foldscope and a reversed-lens CellScope in Ghana

Abstract: We evaluated two novel, portable microscopes and locally acquired, single-ply, paper towels as filter paper for the diagnosis of Schistosoma haematobium infection. The mobile phone-mounted Foldscope and reversed-lens CellScope had sensitivities of 55.9% and 67.6%, and specificities of 93.3% and 100.0%, respectively, compared with conventional light microscopy for diagnosing S. haematobium infection. With conventional light microscopy, urine filtration using single-ply paper towels as filter paper showed a sensitivity of 67.6% and specificity of 80.0% compared with centrifugation for the diagnosis of S. haematobium infection. With future improvements to diagnostic sensitivity, newer generation handheld and mobile phone microscopes may be valuable tools for global health applications.

Is PCR the Next Reference Standard for the Diagnosis of Schistosoma in Stool? A Comparison with Microscopy in Senegal and Kenya.

Abstract: Background The current reference test for the detection of S. mansoni in endemic areas is stool microscopy based on one or more Kato-Katz stool smears. However, stool microscopy has several shortcomings that greatly affect the efficacy of current schistosomiasis control programs. A highly specific multiplex real-time polymerase chain reaction (PCR) targeting the Schistosoma internal transcriber-spacer-2 sequence (ITS2) was developed by our group a few years ago, but so far this PCR has been applied mostly on urine samples. Here, we performed more in-depth evaluation of the ITS2 PCR as an alternative method to standard microscopy for the detection and quantification of Schistosoma spp. in stool samples.

Prevalence of urinary schistosomiasis and associated risk factors among Abobo Primary School children in Gambella Regional State, southwestern Ethiopia: a cross sectional study

Abstract: In Ethiopia, urinary schistosomiasis caused by Schistosoma haematobium has been known to be endemic in several lowland areas of the country where it causes considerable public health problems, mainly among school-age children. However, information on recent magnitude and risk factors of the disease is lacking, particularly for Gambella area. Therefore, this study aimed to assess the prevalence of urinary schistosomiasis and associated risk factors among Abobo Primary School children in Gambella, southwestern Ethiopia. A cross-sectional study involving 304 school children was conducted in Abobo Primary School, Gambella Regional State, southwestern Ethiopia, from February to June 2014. Ten ml of urine sample was collected from each study participant and processed for microscopic examination by the urine filtration method; egg load for positive individuals was determined per 10 ml of urine. Data on socio-demographic characteristics and risk factors were collected using an interview-based questionnaire. The data were entered into and analyzed with SPSS version 20. Logistic regression and odds ratio were used to measure association and strength between variables, respectively. P-value < 0.05 at 95% CI was considered as statistically significant. The prevalence of urinary schistosomiasis was 35.9% (109/ 304) with a mean egg intensity of 8.76 per 10 ml of urine. Being male [AOR (95%CI) = 2.15(1.31, 3.52)], having father as a farmer [AOR (95%CI) = 1.96(1.19, 3.22)] and children living apart from parents [AOR (95% CI): 3.09 (1.14, 8.4)] were significantly associated with urinary schistosomiasis. The present study area in Gambella Regional State, southwestern Ethiopia, represents moderate-risk community for urinary schistosomiasis. Sex, father’s occupation and living apart from parents were found to be associated with infection. Treatment of all school-age children and fishermen is required once every 2 years until the prevalence of infection falls below the level of public health importance. It is also recommended to complement praziquantel treatment with supplementary measures such as provision of sanitation facilities and health education.

Modelling control of Schistosoma haematobium infection: predictions of the long-term impact of mass drug administration in Africa.

Abstract: Effective control of schistosomiasis remains a challenging problem for endemic areas of the world. Given knowledge of the biology of transmission and past experience with mass drug administration (MDA) programs, it is important to critically evaluate the likelihood that MDA programs will achieve substantial reductions in Schistosoma prevalence. In implementing the World Health Organization Roadmap for Neglected Tropical Diseases it would useful for policymaking to model projections of the status of Schistosoma control in MDA-treated areas in the next 5–10 years. Calibrated mathematical models were used to project the effects of different frequency and coverage of MDA for schistosomiasis haematobia control in present-day endemic communities, taking into account uncertainties of parasite biology and input data. The modeling approach in this analysis was the Stratified Worm Burden model developed in our earlier works, calibrated using data from longitudinal S. haematobium control trials in Kenya. Model-based simulations of MDA control in typical low-risk and higher-risk communities indicated that infection prevalence can be substantially reduced within 10 years only when there is a high degree of community participation (>70 %) with at least annual MDA. Significant risk for re-emergence of infection remains if MDA is suspended. In a stable (stationary) ecosystem, Schistosoma reproduction and transmission are sufficiently robust that the process of human infection continues, even under pressure from aggressive MDA. MDA alone is unlikely to interrupt transmission, and once mass treatment is suspended, the prevalence of human infection is likely to rebound to pre-control levels over a period of 25–30 years. MDA success in achieving very low levels of infection prevalence is highly dependent on treatment coverage and frequency within the local human population, and requires that both adults and children be included in drug delivery coverage. Ultimately, supplemental snail control and significant improvements in sanitation will be required to achieve full control of schistosomiasis by elimination of ongoing Schistosoma transmission.

Gynecological Manifestations, Histopathological Findings, and Schistosoma-Specific Polymerase Chain Reaction Results Among Women With Schistosoma haematobium Infection: A Cross-sectional Study in Madagascar

Abstract: Schistosoma haematobium may cause pathology in the urinary and genital tracts. In the urinary tract, morbidity is correlated with intensity of infection, as indicated by the number of eggs excreted in the urine [1]. Up to 75% of women excreting S. haematobium ova in the urine may have ova in the lower genital tract. However, female genital schistosomiasis (FGS) may also occur in the absence of urinary egg excretion [2, 3]. FGS is rarely seen without use of a colposcope and is often overlooked even by those who have this tool. In remote areas, where most patients live, the cost of the equipment, the logistical difficulties associated with light sources, electricity, and clean instruments, as well as the invasive nature of the biopsy and gynecological examination, may result in failure to diagnose FGS. Furthermore, identification of lesions requires several weeks of training and inspection of the entire intravaginal surfaces, including the fornices and the anterior and posterior vaginal walls [3]. The clinical pathology of FGS was described in 1949, but there is still a lack of diagnostic standards, partly because of the ethical limitations in obtaining specimens appropriate for analysis [3, 4]. Therefore, the pathophysiology of FGS is only partially understood [3, 5–7]. Furthermore, neither gynecology nor infectious diseases textbooks contain information about the macroscopic manifestations of the disease. This study aims to describe the clinical manifestations and histopathological characteristics of genital mucosal schistosomiasis lesions and to study these findings in relation to Schistosoma DNA in genital tissue. The diagnostic potential of specimens collected from the surfaces of the vagina and the cervix were evaluated in women with high- and low-intensity S. haematobium infection and in those without urinary S. haematobium egg excretion.

Of Monkeys and Men: Immunomic Profiling of Sera from Humans and Non-Human Primates Resistant to Schistosomiasis Reveals Novel Potential Vaccine Candidates

Abstract: Schistosoma haematobium affects more than 100 million people throughout Africa and is the causative agent of urogenital schistosomiasis. The parasite is strongly associated with urothelial cancer in infected individuals and as such is designated a group I carcinogen by the International Agency for Research on Cancer. Using a protein microarray containing schistosome proteins, we sought to identify antigens that were the targets of protective IgG1 immune responses in S. haematobium-exposed individuals that acquire drug-induced resistance (DIR) to schistosomiasis after praziquantel treatment. Numerous antigens with known vaccine potential were identified, including calpain (Smp80), tetraspanins, glutathione-S-transferases, and glucose transporters (SGTP1), as well as previously uncharacterized proteins. Reactive IgG1 responses were not elevated in exposed individuals who did not acquire DIR. To complement our human subjects study, we screened for antigen targets of rhesus macaques rendered resistant to S. japonicum by experimental infection followed by self-cure, and discovered a number of new and known vaccine targets, including major targets recognized by our human subjects. This study has further validated the immunomics-based approach to schistosomiasis vaccine antigen discovery and identified numerous novel potential vaccine antigens.

The Rapid-Heat LAMPellet Method: A Potential Diagnostic Method for Human Urogenital Schistosomiasis.

Abstract: Background Urogenital schistosomiasis due to Schistosoma haematobium is a serious underestimated public health problem affecting 112 million people - particularly in sub-Saharan Africa. Microscopic examination of urine samples to detect parasite eggs still remains as definitive diagnosis. This work was focussed on developing a novel loop-mediated isothermal amplification (LAMP) assay for detection of S. haematobium DNA in human urine samples as a high-throughput, simple, accurate and affordable diagnostic tool to use in diagnosis of urogenital schistosomiasis. Methodology/Principal Findings A LAMP assay targeting a species specific sequence of S. haematobium ribosomal intergenic spacer was designed. The effectiveness of our LAMP was assessed in a number of patients´ urine samples with microscopy confirmed S. haematobium infection. For potentially large-scale application in field conditions, different DNA extraction methods, including a commercial kit, a modified NaOH extraction method and a rapid heating method were tested using small volumes of urine fractions (whole urine, supernatants and pellets). The heating of pellets from clinical samples was the most efficient method to obtain good-quality DNA detectable by LAMP. The detection limit of our LAMP was 1 fg/µL of S. haematobium DNA in urine samples. When testing all patients´ urine samples included in our study, diagnostic parameters for sensitivity and specificity were calculated for LAMP assay, 100% sensitivity (95% CI: 81.32%-100%) and 86.67% specificity (95% CI: 75.40%-94.05%), and also for microscopy detection of eggs in urine samples, 69.23% sensitivity (95% CI: 48.21% -85.63%) and 100% specificity (95% CI: 93.08%-100%). Conclusions/Significance We have developed and evaluated, for the first time, a LAMP assay for detection of S. haematobium DNA in heated pellets from patients´ urine samples using no complicated requirement procedure for DNA extraction. The procedure has been named the Rapid-Heat LAMPellet method and has the potential to be developed further as a field diagnostic tool for use in urogenital schistosomiasis-endemic areas.

Research and control of advanced schistosomiasis japonica in China

Abstract: Among the three main schistosomes (Schistosoma japonicum, Schistosoma mansoni, and Schistosoma haematobium) known to infect humans, S. japonicum causes the most serious pathological lesions. In China, only schistosomiasis japonica is transmitted. From the 1950s, massive epidemiological investigations and active control measures for schistosomiasis japonica have been carried out. At the early stage of schistosomiasis control program, there were about 12 million schistosomiasis patients, and about 5% of schistosomiasis patients belong to advanced patients, which was 600,000. After more than a half century of active schistosomiasis control work, the schistosomiasis situation has been reduced markedly. The nearest epidemiological investigation showed that, by the end of 2012, there were still 240,000 schistosomiasis patients with the descent rate of 98% and 30,000 advanced patients with the descent rate of 95%. This paper reviews the rich experiences of advanced schistosomiasis research and control in China, including that the epidemiology researches confirm there is a family aggregation of advanced schistosomiasis and advanced schistosomiasis patients have no significance to the schistosomiasis transmission in transmission-interrupted areas but still are an infection source in endemic areas; pathogenic mechanism researches verify that genetic factors and immunoregulation play important roles in the disease developing process; ultrasound image examinations are used not only in the diagnosis and differential diagnosis of advanced schistosomiasis but also in the guidance of treatment and evaluation of therapeutic effects and, furthermore, in the risk predictions of portal hypertension and upper gastrointestinal hemorrhage; clinical practices demonstrate that praziquantel can be used in most of advanced schistosomiasis patients, and the therapy not only can interrupt the schistosomiasis transmission somewhat but also is favorable for liver fibrosis improvement; the ascetic fluid concentration afflux is used in the therapy for obstinate ascites, and endoscopic varices ligation is used in the treatment of upper gastrointestinal bleeding, and both have good effects; hundreds and thousands of severe splenomegaly advanced schistosomiasis patients received splenectomy, and the long-term survival rate is more than 90%, most of them are basically cured from the disease and their labor force recovers, some dwarf patients begin growing and developing again, and some sterile women became fertile; the researches of traditional Chinese medicine in the treatment of liver fibrosis have made progress, such as Cordyceps sinensis showing some anti-fibrosis effect in the animal experiments and primary clinical trials; the animal experiments and epidemiological investigations indicate that schistosome infection is one of the carcinogenesis risk factors, especially for liver cancer. In conclusion, these experiences and lessons are plentiful and worth sharing with the peers of other endemic countries for reference.

Schistosomiasis presenting in travellers: a 15 year observational study at the Hospital for Tropical Diseases, London.

Abstract: BACKGROUND: Schistosomiasis in returning travellers is one of the most common imported tropical infections with potentially serious complications, which are preventable if diagnosed early. METHODS: A review was undertaken of consecutive cases of schistosomiasis presenting at the Hospital for Tropical Diseases, London, UK from 1997 to 2012. RESULTS: All 1020 schistosomiasis cases were from Africa and Schistosoma haematobium was the predominant species in those with microscopy confirmed schistosomiasis (74.2%, 204/252). The number of cases of imported schistosomiasis is decreasing steadily as a proportion of travellers seen. The majority of cases were in travellers originating from non-endemic settings (81.8%, 707/864). The most common symptom was of genitourinary complaints (22.6%, 230/1020), predominantly haematuria (17.8%, 181/1020); 36.1% (368) of cases were asymptomatic. Overall 42% had eosinophilia, and 62% of ova positive S. haematobium cases had haematuria on urine dip. Thus, no single screening tool was sufficient to identify or rule out schistosomiasis when used alone. Serology testing was a more sensitive tool in travellers than in other patients (p=0.007). CONCLUSIONS: The prevalence of schistosomiasis in presenting travellers is decreasing. The predominant presenting species has shifted from S. mansoni to S. haematobium. No single test can reliably diagnose schistosomiasis, with eosinophilia and urine dip having low sensitivity. Clinicians need to continue to undertake a wide spectrum of diagnostic tests to ensure cases of schistosomiasis are not missed.

All that is blood is not schistosomiasis: experiences with reagent strip testing for urogenital schistosomiasis with special consideration to very-low prevalence settings

Abstract: Reagent strip testing for microhaematuria has long been used for community diagnosis of Schistosoma haematobium. Sensitivities and specificities are reasonable, and hence, microhaematuria can serve as a proxy for S. haematobium infection. However, assessment of test performance in the context of the underlying S. haematobium prevalence is rare and test parameters other than sensitivity and specificity have been neglected. Data about the association between microhaematuria and urine filtration results from three studies were compared and put into context with findings from a recent Cochrane review. Data were stratified by S. haematobium prevalence to identify prevalence-related differences in test performance. Kappa agreement and regression models were employed to compare data for different S. haematobium prevalence categories. We found a “background” prevalence of microhaematuria (13 %, on average) which does not seem to be associated with schistosomiasis in most settings, irrespective of the prevalence of S. haematobium. This background level of microhaematuria might be due to cases missed with urine filtration, or alternative causes apart from S. haematobium. Especially in very-low prevalence settings, positive results for microhaematuria likely give an inaccurate picture of the extent of S. haematobium, whereas negative results are a sound indicator for the absence of infection. Reagent strip testing for microhaematuria remains a good proxy for urogenital schistosomiasis, but implications of test results and scope of application differ depending on the setting in which reagent strips are employed. In very-low prevalence settings, microhaematuria is an unstable proxy for urogenital schistosomiasis and treatment decision should not be based on reagent strip test results alone. Our findings underscore the need for highly accurate diagnostic tools for settings targeted for elimination of urogenital schistosomiasis.

Defining the Schistosoma haematobium kinome enables the prediction of essential kinases as anti-schistosome drug targets.

Abstract: The blood fluke Schistosoma haematobium causes urogenital schistosomiasis, a neglected tropical disease (NTD) that affects more than 110 million people. Treating this disease by targeted or mass administration with a single chemical, praziquantel, carries the risk that drug resistance will develop in this pathogen. Therefore, there is an imperative to search for new drug targets in S. haematobium and other schistosomes. In this regard, protein kinases have potential, given their essential roles in biological processes and as targets for drugs already approved by the US Food and Drug Administration (FDA) for use in humans. In this context, we defined here the kinome of S. haematobium using a refined bioinformatic pipeline. We classified, curated and annotated predicted kinases, and assessed the developmental transcription profiles of kinase genes. Then, we prioritised a panel of kinases as potential drug targets and inferred chemicals that bind to them using an integrated bioinformatic pipeline. Most kinases of S. haematobium are very similar to those of its congener, S. mansoni, offering the prospect of designing chemicals that kill both species. Overall, this study provides a global insight into the kinome of S. haematobium and should assist the repurposing or discovery of drugs against schistosomiasis.

A review of the control of schistosomiasis in South Africa

Abstract: Schistosomiasis is the second most important tropical disease in the world in terms of public health impact. In South Africa, more than 4 million people are estimated to be infected with schistosomiasis. School-age children usually have the highest prevalence and intensity of infection. Schistosoma haematobium may result in female genital schistosomiasis which presents as inflammation and ulceration of the genital mucosa and pathological blood vessels. These effects may increase the susceptibility of women with female genital schistosomiasis to HIV. Praziquantel is the drug used to treat schistosomiasis and it is best to treat people during the early stages of infection, before female genital schistosomiasis presents as lesions and sandy patches, as there currently is no treatment for these symptoms. Schistosomiasis is not regarded as a serious public health issue in South Africa despite evidence revealing the seriousness of the disease. In areas endemic for schistosomiasis, the World Health Organization recommends regular mass treatment of all school-age children. In 2001, South Africa became a signatory to the World Health Assembly resolution 54.19 which urged all member states to achieve the minimum goal of 75% treatment coverage in school-age children at risk by 2010. This goal was not achieved in South Africa, despite efforts made by the Department of Health, such as the first statutory school-based geohelminth control programme in the province of KwaZulu-Natal. However, this programme has not been continued. Therefore, there is still much work to be done in order to control and decrease the prevalence of schistosomiasis in endemic areas.

Reduction of urogenital schistosomiasis with an integrated control project in Sudan.

Abstract: Purpose Schistosomiasis remains a major public health concern in Sudan, particularly Schistosoma haematobium infection. This study presents the disease-reduction outcomes of an integrated control program for schistosomiasis in Al Jabalain locality of White Nile State, Sudan from 2009 through 2011. Methods The total population of the project sites was 482,902, and the major target group for intervention among them was 78,615 primary school students. For the cross-sectional study of the prevalence, urine and stool specimens were examined using the urine sedimentation method and the Kato cellophane thick smear method, respectively. To assess the impacts of health education for students and a drinking water supply facility at Al Hidaib village, questionnaire survey was done. Results The overall prevalence for S. haematobium and S. mansoni at baseline was 28.5% and 0.4%, respectively. At follow-up survey after 6–9 months post-treatment, the prevalence of S. haematobium infection was reduced to 13.5% (95% CI = 0.331–0.462). A higher reduction in prevalence was observed among girls, those with moderately infected status (around 20%), and residents in rural areas, than among boys, those with high prevalence (>40%), and residents in urban areas. After health education, increased awareness about schistosomiasis was checked by questionnaire survey. Also, a drinking water facility was constructed at Al Hidaib village, where infection rate was reduced more compared to that in a neighboring village within the same unit. However, we found no significant change in the prevalence of S. mansoni infection between baseline and follow-up survey (95% CI = 0.933–6.891). Conclusions At the end of the project, the prevalence of S. haematobium infection was reduced by more than 50% in comparison with the baseline rate. Approximately 200,000 subjects had received either praziquantel therapy, health education, or supply of clean water. To consolidate the achievements of this project, the integrated intervention should be adapted continuously.

Schistosomiasis Screening of Travelers from Italy with Possible Exposure in Corsica, France.

Abstract: To the Editor: Since 2014, many cases of urogenital schistosomiasis acquired in Corsica, France, have been described (1–4). The infections, which all occurred in persons who had bathed in the Cavu River in 2011 or 2013, represent the first cases of autochthonous Schistosoma haematobium infection acquired in Europe since the last reported case in Portugal in 1965 (5). In June 2014, France established a screening program for persons reporting exposure to the Cavu River during 2011–2013. By March 2015, a national surveillance journal had reported 110 autochthonous urogenital schistosomiasis cases in residents of France (6). We describe the diagnostic work-up for and clinical management of persons from Italy who reported bathing in the Cavu River at least once during 2011–2014. All of the patients had requested screening after learning of the risk for acquiring schistosomiasis after freshwater exposure in Corsica. Exclusion criteria for the study included residence in or travel to a country where schistosomiasis is endemic. At least 3 months after their last exposure to the Cavu River, each participant had a filtered terminal urine sample and a serum sample tested for schistosomiasis. Different commercial tests were used, depending on local availability: 3 different ELISAs and an indirect immunofluorescent antibody test (IIFAT). All serum samples were tested in parallel in a laboratory in Florence, Italy, by using 2 Western blots (WBs): a Schistosoma WB IgG kit containing antigens from adult S. mansoni worms and a second kit containing S. mansoni and S. haematobium antigens from a crude adult extract (LDBio Diagnostics, Lyon, France). Confirmed urogenital schistosomiasis was defined by confirmation of S. haematobium eggs in urine by microscopy, positive WB result, or both. Probable urogenital schistosomiasis was defined by positive serologic test results. Possible urogenital schistosomiasis was defined by signs or symptoms suggestive of schistosomiasis (i.e., urogenital symptoms), eosinophilia (>0.4 × 109 cells/L of blood), or both (7). All participants who met the case definition received 1 oral dose of praziquantel (40 mg/kg). Forty-three persons were consecutively enrolled during January 2014–January 2015; of these, 15 (34%) had confirmed (6 patients), probable (2 patients), or possible (7 patients) urogenital schistosomiasis (Table). Of these 15 patients, 7 (47%) reported repeat visits to Cavu River over a period of at least 2 years. The mean eosinophil count was 295 (range 40–1,540) cells/μL of blood; 6 (40%) patients had eosinophilia. Genitourinary symptoms were reported by 7 (47%) patients, and blood was detected by dipstick in the urine of 1 patient. Schistosoma eggs were not found in any urine samples. Table Demographic, epidemiologic, clinical, and laboratory data for 15 patients with urogenital schistosomiasis acquired after bathing in the Cavu River, Corsica, France* Schistosomiasis screening has been suggested for persons with exposure to the Cavu River (6); however, clinical history and clinical evaluation alone and eosinophilia, have low sensitivity for the diagnosis of urogenital schistosomiasis (7,8). Asymptomatic infection has been reported in 25%–36% of persons with travel-associated schistosomiasis, and eosinophilia was present in 50% of the patients (7,8). In screenings in France, only 27% of schistosomiasis-positive patients reported genitourinary symptoms (6). For the diagnosis of urogenital schistosomiasis, serologic testing is more sensitive than detection of eggs in urine, particularly in mild infections (7–9). Many asymptomatic family members of the index case-patients who acquired infection in Corsica tested positive only by serologic testing (1–4). However, commercial serologic tests for schistosomiasis have low sensitivity (9). Kinkel et al. (9) showed that sensitivity of an IIFAT and 3 ELISAs for S. haematobium ranged from 21.4% to 71.4%. In the Corsica outbreak, serologic testing may be even less sensitive because of the hybrid nature of the schistosoma (S. haematobium/S. bovis) (6). In our study, only 2 patients had positive ELISA results. Combinations of >2 serologic tests can markedly increase testing sensitivity to almost 78.6% (9). Sulahian et al. (10) found that a WB containing S. mansoni antigens had 89.5% sensitivity and 100% specificity for S. mansoni. In our study, no patients with urogenital schistosomiasis tested positive by WB containing S. mansoni antigens, but 6 patients tested positive by WB containing S. haematobium antigens. In mild infections, the absence of schistosoma antibodies cannot exclude a diagnosis of urogenital schistosomiasis (7). Therefore, we provided treatment to patients with possible urogenital schistosomiasis; our decision to treat these patients considered the tolerability of praziquantel and the possible severe genitourinary complications of untreated infections (e.g., bladder carcinoma, infertility). Our findings suggest that a sensitive screening strategy for urogenital schistosomiasis consists of a patient’s travel history (exposure in multiple years), clinical history (any new genitourinary complaints after freshwater exposure), eosinophil count, and serologic testing. Because of the failure of commercial ELISA and IIFAT methods, we emphasize that a WB containing S. haematobium antigen should also be used for screening. Of note, a confirmed urogenital schistosomiasis case acquired after a single exposure in 2014 was never reported (1–4,6). The risk for delayed diagnosis of this insidious, neglected disease, which has recently reappeared in Europe, must be reduced. To accomplish this, information regarding the risk for schistosomiasis after freshwater exposure in Corsica must be disseminated to physicians worldwide.

Toward measuring Schistosoma response to praziquantel treatment with appropriate descriptors of egg excretion

Abstract: The control of schistosomiasis emphasizes preventive chemotherapy with praziquantel, which aims at decreasing infection intensity and thus morbidity in individuals, as well as transmission in communities. Standardizing methods to assess treatment efficacy is important to compare trial outcomes across settings, and to monitor program effectiveness consistently. We compared customary methods and looked at possible complementary approaches in order to derive suggestions for standardizing outcome measures.; We analyzed data from 24 studies conducted at African, Asian, and Latin American sites, enrolling overall 4,740 individuals infected with Schistosoma mansoni, S. haematobium, or S. japonicum, and treated with praziquantel at doses of 40-80 mg/kg. We found that group-based arithmetic and geometric means can be used interchangeably to express egg reduction rates (ERR) only if treatment efficacy is high (<95%). For lower levels of efficacy, ERR estimates are higher with geometric than arithmetic means. Using the distribution of individual responses in egg excretion, 6.3%, 1.7% and 4.3% of the subjects treated for S. haematobium, S. japonicum and S. mansoni infection, respectively, had no reduction in their egg counts (ERR = 0). The 5th, 10th, and 25th centiles of the subjects treated for S. haematobium had individual ERRs of 0%, 49.3%, and 96.5%; the corresponding values for S. japonicum were 75%, 99%, and 99%; and for S. mansoni 18.2%, 65.3%, and 99.8%. Using a single rather than quadruplicate Kato-Katz thick smear excluded 19% of S. mansoni-infected individuals. Whilst the effect on estimating ERR was negligible by individual studies, ERR estimates by arithmetic means were 8% lower with a single measurement.; Arithmetic mean calculations of Schistosoma ERR are more sensitive and therefore more appropriate to monitor drug performance than geometric means. However, neither are satisfactory to identify poor responders. Group-based response estimated by arithmetmean and the distribution of individual ERRs are correlated, but the latter appears to be more apt to detect the presence and to quantitate the magnitude of suboptimal responses to praziquantel.

Kidney disease among children in sub-Saharan Africa: systematic review

Abstract: The global burden of kidney disease is increasing, and several etiologies first begin in childhood. Risk factors for pediatric kidney disease are common in Africa, but data regarding its prevalence are lacking. We completed a systematic review of community-based studies describing the prevalence of proteinuria, hematuria, abnormal imaging, or kidney dysfunction among children in sub-Saharan Africa (SSA). Medline and Embase were searched. Five hundred twenty-three references were reviewed. Thirty-two references from nine countries in SSA were included in the qualitative synthesis. The degree of kidney damage and abnormal imaging varied widely: proteinuria 32.5% (2.2-56.0%), hematuria 31.1% (0.6-67.0%), hydronephrosis 11.3% (0.0-38.0%), hydroureter 7.5% (0.0-26.4%), and major kidney abnormalities 0.1% (0.0-0.8%). Serum creatinine was reported in four studies with insufficient detail to identify the prevalence renal dysfunction. A majority of the studies were performed in Schistosoma haematobium endemic areas. A lower prevalence of kidney disease was observed in the few studies from nonendemic areas. Published data on pediatric kidney disease in SSA are highly variable and dependent on S. haematobium prevalence. More community-based studies are needed to describe the burden of pediatric kidney disease, particularly in regions where S. haematobium infection is nonendemic.

The WHO ultrasonography protocol for assessing morbidity due to Schistosoma haematobium. Acceptance and evolution over 14 years. Systematic review.

Abstract: In 2000, the World Health Organization (WHO) published an ultrasound field protocol for assessing morbidity due to schistosomiasis. The present study aims to review the acceptance of the WHO protocol for Schistosoma haematobium. A PubMed literature research using the keywords "ultrasound OR ultrasonography (US) AND schistosomiasis," "US AND S. haematobium," "US AND urinary schistosomiasis" from 2001 through 2014 was performed. Thirty-eight eligible publications reporting on 17,861 patients from 13 endemic and 2 non-endemic countries were analysed. Of these, 33 referred to field studies on 17,317 patients. The Niamey protocol was applied to 15,367/17,317 (88.74%) patients in 23/33 (69.70%) of field studies (all studies: 15,649/17,861 [87.61%] patients (25/38 [68.42%] studies). The acceptance of the protocol by single country in field studies varied from 0 to 100%. It varied over time between 55.56% (5/9) in the period from 2001 to 2004, to 87.50% (7/8) from 2005 to 2008, to 62.50% (5/8) from 2009 to 2011 and 75.00% (6/8) from 2012 through 2014 (all studies: 50% [5/10], 88.89% [8/9], 62.50% [5/8], 63.64% [7/11], respectively). The Niamey protocol was applied also in 2/5 hospital studies in 282/544 (51.84%) patients.The usefulness of the WHO protocol for S. haematobium infections is confirmed by its worldwide acceptance. Some simplifications might facilitate its use also for focused ultrasound examinations performed by less skilled examiners. Organ abnormalities due to schistosomiasis detectable by ultrasonography not yet covered by the WHO protocol should be added to the additional investigations section.

Age-Stratified Profiles of Serum IL-6, IL-10, and TNF-α Cytokines Among Kenyan Children with Schistosoma haematobium, Plasmodium falciparum, and Other Chronic Parasitic Co-Infections.

Abstract: In a study of children having polyparasitic infections in a Schistosoma haematobium-endemic area, we examined the hypothesis that S. haematobium-positive children, compared with S. haematobium-negative children (anti-soluble worm antigen preparation [SWAP] negative and egg negative) have increased systemic production of pro-inflammatory cytokines (interleukin [IL]-6, tumor necrosis factor [TNF]-α) and decreased down-regulatory IL-10. A total of 804 children, 2-19 years of age, were surveyed between July and December 2009 and tested for S. haematobium, Plasmodium falciparum, filariasis, and soil-transmitted helminth infections. Plasma levels of IL-6, TNF-α, and IL-10 were compared for S. haematobium-positive and S. haematobium-negative children, adjusting for malaria, filaria, and hookworm co-infections, and for nutritional status, age group, sex, and geographic location. IL-10 was significantly elevated among children infected with S. haematobium, showing bimodal peaks in 7-8 and 13-14 years age groups. IL-10 was also higher among children who were acutely malnourished, whereas IL-10 levels were lower in the presence of S. haematobium-filaria co-infection. After adjustment for co-factors, IL-6 was significantly elevated among children of 5-6 years and among those with P. falciparum infection. Lower levels of IL-6 were found in malaria-hookworm co-infection. High levels of TNF-α were found in children aged 11-12 years regardless of infection status. In addition, village of residence was a strong predictor of IL-6 and IL-10 plasma levels. In adolescent children infected with S. haematobium, there is an associated elevation in circulating IL-10 that may reduce the risk of later morbidity. Although we did not find a direct link between S. haematobium infection and circulating pro-inflammatory IL-6 and TNF-α levels, future T-cell stimulation studies may provide more conclusive linkages between infection and cytokine responses in settings that are endemic for multiple parasites and multiple co-infections.

Induction of Protective Immune Responses Against Schistosomiasis haematobium in Hamsters and Mice Using Cysteine Peptidase-Based Vaccine

Abstract: One of the major lessons we learned from the radiation-attenuated cercariae (RA) vaccine studies is that protective immunity against schistosomiasis is dependent on the induction of T helper (Th)1/Th2-related immune responses. Since most schistosome larval and adult-worm-derived molecules used for vaccination uniformly induce a polarized Th1 response, it was essential to include a type 2 immune responses-inducing molecule, such as cysteine peptidases, in the vaccine formula. Here we demonstrate that a single subcutaneous injection of Syrian hamsters with 200 microg active papain 1 h before percutaneous exposure to 150 cercariae of Schistosoma haematobium led to highly significant (P 50% in worm burden and worm egg counts in intestine. Immunization of hamsters with 20 microg recombinant glyceraldehyde 3-phosphate dehydrogenase (rSG3PDH) and 20 ug 2-cys peroxiredoxin-derived peptide in a multiple antigen peptide construct (PRX MAP) together with papain (20 microg/hamster) as adjuvant led to considerable (64%) protection against challenge S. haematobium infection, similar to the levels reported with irradiated cercariae. Cysteine peptidases-based vaccination was also effective in protecting outbred mice against a percutaneous challenge infection with S. haematobium cercariae. In two experiments, a mixture of Schistosoma mansoni cathepsin B1 (SmCB1) and Fasciola hepatica cathepsin L1 (FhCL1) led to highly significant (P < 0.005) reduction of 70% in challenge S. haematobium worm burden and 60% reduction in liver egg counts. Mice vaccinated with SmCB1/FhCL1/ rSG3PDH mixture and challenged with S. haematobium cercariae three weeks after the second immunization displayed highly significant (P < 0.005) reduction of 72% in challenge worm burden and no eggs in liver of 8-10 mice/group, as compared to unimmunized mice, associated with production of a mixture of type 1 and type 2-related cytokines and antibody responses.

Development of a Biosensor-Based Rapid Urine Test for Detection of Urogenital Schistosomiasis.

Abstract: Schistosomiasis affects up to 300 million people in regions of South America, Southeast Asia, the Middle East, Mediterranean Europe, and sub-Saharan Africa. Chronic consequences of schistosomiasis include anemia, physical and cognitive retardation in children, and organ failure. With predilection for the genitourinary tract, Schistosoma haematobium increases the risk of bladder cancer and HIV infection in women. Microscopic identification and enumeration of parasite eggs in urine (S. haematobium) or stool (Schistosoma mansoni and Schistosoma japonicum) has remained the standard for schistosomiasis diagnosis [1]. Limitations of microscopy include the need for skilled personnel in the field with microscopy equipment and its time-consuming nature. Particularly in infrastructure-limited regions, point-of-care (POC) molecular diagnostics hold the potential to transform the management of infectious diseases such as schistosomiasis that carry significant long-term morbidity if left undiagnosed. POC diagnosis could allow selective drug administration to individuals with confirmed infection rather than entire schools or communities, and an integrated diagnosis–single dose therapy approach could reduce costs of drug administration campaigns and minimize treatment-associated adverse effects. Electrochemical biosensors are well suited for molecular diagnostics because of their high sensitivity, low cost, ease of integration into POC devices, and portability of the reader instrumentation [2]. We have developed a strategy for rapid (one hour) molecular diagnosis of bacterial urinary tract infections using electrochemical biosensors [3,4]. Urinary cells are lysed and directly applied to an array of sensors functionalized with oligonucleotide probes targeting the 16S ribosomal RNA (rRNA) of common uropathogens [3,4]. Formation of the sequence-specific hybridization complex between the pathogen rRNA and the labeled capture and detector probe pairs is detected by an enzyme tag that mediates an amperometric signal output (Fig 1). Fig 1 Biosensor-based molecular detection of urinary pathogen. In this work, we demonstrate the use of our biosensor-based platform for detection of S. haematobium in urine. We developed capture and detector probes targeting S. haematobium rRNA and integrated them into our established molecular diagnostics strategy. After determining an efficient egg lysis strategy, we demonstrated direct electrochemical detection of S. haematobium eggs spiked in human urine.

Mapping of Schistosomiasis and Soil-Transmitted Helminths in Namibia: The First Large-Scale Protocol to Formally Include Rapid Diagnostic Tests.

Abstract: Background Namibia is now ready to begin mass drug administration of praziquantel and albendazole against schistosomiasis and soil-transmitted helminths, respectively. Although historical data identifies areas of transmission of these neglected tropical diseases (NTDs), there is a need to update epidemiological data. For this reason, Namibia adopted a new protocol for mapping of schistosomiasis and geohelminths, formally integrating rapid diagnostic tests (RDTs) for infections and morbidity. In this article, we explain the protocol in detail, and introduce the concept of ‘mapping resolution’, as well as present results and treatment recommendations for northern Namibia. Methods/Findings/Interpretation This new protocol allowed a large sample to be surveyed (N = 17 896 children from 299 schools) at relatively low cost (7 USD per person mapped) and very quickly (28 working days). All children were analysed by RDTs, but only a sub-sample was also diagnosed by light microscopy. Overall prevalence of schistosomiasis in the surveyed areas was 9.0%, highly associated with poorer access to potable water (OR = 1.5, P<0.001) and defective (OR = 1.2, P<0.001) or absent sanitation infrastructure (OR = 2.0, P<0.001). Overall prevalence of geohelminths, more particularly hookworm infection, was 12.2%, highly associated with presence of faecal occult blood (OR = 1.9, P<0.001). Prevalence maps were produced and hot spots identified to better guide the national programme in drug administration, as well as targeted improvements in water, sanitation and hygiene. The RDTs employed (circulating cathodic antigen and microhaematuria for Schistosoma mansoni and S. haematobium, respectively) performed well, with sensitivities above 80% and specificities above 95%. Conclusion/Significance This protocol is cost-effective and sensitive to budget limitations and the potential economic and logistical strains placed on the national Ministries of Health. Here we present a high resolution map of disease prevalence levels, and treatment regimens are recommended.