Showing papers on "Schistosoma haematobium published in 2017"

Schistosomiasis is more prevalent than previously thought: what does it mean for public health goals, policies, strategies, guidelines and intervention programs?

Abstract: Mapping and diagnosis of infections by the three major schistosome species (Schistosoma haematobium, S. mansoni and S. japonicum) has been done with assays that are known to be specific but increasingly insensitive as prevalence declines or in areas with already low prevalence of infection. This becomes a true challenge to achieving the goal of elimination of schistosomiasis because the multiplicative portion of the life-cycle of schistosomes, in the snail vector, favors continued transmission as long as even a few people maintain low numbers of worms that pass eggs in their excreta. New mapping tools based on detection of worm antigens (circulating cathodic antigen – CCA; circulating anodic antigen – CAA) in urine of those infected are highly sensitive and the CAA assay is reported to be highly specific. Using these tools in areas of low prevalence of all three of these species of schistosomes has demonstrated that more people harbor adult worms than are regularly excreting eggs at a level detectable by the usual stool assay (Kato-Katz) or by urine filtration. In very low prevalence areas this is sometimes 6- to10-fold more. Faced with what appears to be a sizable population of “egg-negative/worm-positive schistosomiasis” especially in areas of very low prevalence, national NTD programs are confounded about what guidelines and strategies they should enact if they are to proceed toward a goal of elimination. There is a critical need for continued evaluation of the assays involved and to understand the contribution of this “egg-negative/worm-positive schistosomiasis” condition to both individual morbidity and community transmission. There is also a critical need for new guidelines based on the use of these more sensitive assays for those national NTD programs that wish to move forward to strategies designed for elimination.

Point-of-care mobile digital microscopy and deep learning for the detection of soil-transmitted helminths and Schistosoma haematobium.

Abstract: Background: Microscopy remains the gold standard in the diagnosis of neglected tropical diseases. As resource limited, rural areas often lack laboratory equipment and trained personnel, new diagnostic techniques are needed. Low-cost, point-of-care imaging devices show potential in the diagnosis of these diseases. Novel, digital image analysis algorithms can be utilized to automate sample analysis.Objective: Evaluation of the imaging performance of a miniature digital microscopy scanner for the diagnosis of soil-transmitted helminths and Schistosoma haematobium, and training of a deep learning-based image analysis algorithm for automated detection of soil-transmitted helminths in the captured images.Methods: A total of 13 iodine-stained stool samples containing Ascaris lumbricoides, Trichuris trichiura and hookworm eggs and 4 urine samples containing Schistosoma haematobium were digitized using a reference whole slide-scanner and the mobile microscopy scanner. Parasites in the images were identifie...

Schistosomiasis in European Travelers and Migrants: Analysis of 14 Years TropNet Surveillance Data.

Abstract: Schistosomiasis remains one of the most prevalent parasitic diseases worldwide and the infection is frequently found in travelers and migrants. The European Network for Tropical Medicine and Travel Health conducted a sentinel surveillance study on imported schistosomiasis between 1997 and 2010. This report summarizes epidemiological and clinical data from 1,465 cases of imported schistosomiasis. Direct pathogen detection and serology were the main diagnostic tools applied. Of these, 486 (33%) cases were identified among European travelers, 231 (16%) among long-term expatriates, and 748 (51%) among non-European immigrants. Overall, only 18.6% of travelers had received pretravel advice; 95% of infections were acquired in the African region. On species level, Schistosoma mansoni was identified in 570 (39%) and Schistosoma haematobium in 318 (22%) cases; 57.5% of patients were symptomatic. Acute symptoms were reported in 27% of patients leading to earlier presentation within 3 months. Praziquantel was used in all patients to treat schistosomiasis. Many infections were detected in asymptomatic patients. In 47.4% of asymptomatic patients infection was detected by microscopy and in 39% by serology or antigen testing. Schistosomiasis remains a frequent infection in travelers and migrants to Europe. Travelers should be made aware of the risk of schistosomiasis infection when traveling to sub-Saharan Africa. Posttravel consultations particularly for returning expatriates are useful given the high potential for detecting asymptomatic infections.

The microbiome in urogenital schistosomiasis and induced bladder pathologies.

Abstract: Background Human schistosomiasis is a highly prevalent neglected tropical disease (NTD) caused by Schistosoma species. Research on the molecular mechanisms influencing the outcomes of bladder infection by Schistosoma haematobium is urgently needed to develop new diagnostics, therapeutics and infection prevention strategies. The objective of the research study was to determine the microbiome features and changes in urine during urogenital schistosomiasis and induced bladder pathologies. Methodology Seventy participants from Eggua, southwestern Nigeria provided morning urine samples and were screened for urogenital schistosomiasis infection and bladder pathologies in a cross-sectional study. Highthroughput NGS sequencing was carried out, targeting the 16S V3 region. Filtered reads were processed and analyzed in a bioinformatics pipeline. Principal findings The study participants (36 males and 34 females, between ages 15 and 65) were categorized into four groups according to status of schistosomiasis infection and bladder pathology. Data analytics of the next-generation sequencing reads revealed that Proteobacteria and Firmicutes dominated and had influence on microbiome structure of both non-infected persons and persons with urogenital schistosomiasis. Furthermore, gender and age influenced taxa abundance independent of infection or bladder pathology. Several taxa distinguished urogenital schistosomiasis induced bladder pathologies from urogenital schistosomiasis infection alone and from healthy persons, including known immune-stimulatory taxa such as Fusobacterium, Sphingobacterium and Enterococcus. Some of these significant taxa, especially Sphingobacterium were projected as markers of infection, while several genera including potentially beneficial taxa such as Trabulsiella and Weissella, were markers of the non-infected. Finally, expected changes in protein functional categories were observed to relate to cellular maintenance and lipid metabolism. Conclusion The urinary microbiome is a factor to be considered in developing biomarkers, diagnostic tools, and new treatment for urogenital schistosomiasis and induced bladder pathologies.

In vitro and in vivo activity of R- and S- praziquantel enantiomers and the main human metabolite trans-4-hydroxy-praziquantel against Schistosoma haematobium.

Abstract: Praziquantel (PZQ) is the mainstay of schistosomiasis control and has been successfully used for decades. However, its mechanism of action is not fully understood. While the majority of studies have been conducted on Schistosoma mansoni, it is not known which enantiomer, R- or S-praziquantel (R-/S-PZQ), is responsible for the activity on Schistosoma haematobium. In vitro and in vivo studies were conducted to evaluate the activity of R- and S-PZQ, racemic PZQ and the main human metabolite, namely trans-4-OH-PZQ, on S. haematobium. IC50 values on adult S. haematobium were determined in vitro. Dose-response relationship studies were performed in golden Syrian hamsters, harbouring a chronic S. haematobium infection. R-PZQ displayed the highest activity against adult worms in vitro, revealing an IC50 of 0.007 μg/ml at 4 h and 0.01 μg/ml at 72 h. In contrast, S-PZQ was 501× less active (eudysmic ratio at 4 h), with an IC50 of 3.51 and 3.40 μg/ml (4 and 72 h, respectively). Racemic PZQ and trans-4-OH-PZQ resulted in an IC50 of 0.03 μg/ml and 1.47 μg/ml both at 4 and 72 h, respectively. In vivo, R-PZQ was the most potent drug with worm burden reductions (WBRs) of 98.5, 75.6 and 73.3% at 125.0, 62.5 and 31.0 mg/kg, respectively. A single oral dose of 250.0 mg/kg PZQ resulted in a WBR of 99.3%. S-PZQ was highly active in vivo at 250.0 and 500.0 mg/kg with WBRs of 83.0 and 94.1%, respectively. The lowest tested dose of S-PZQ, 125.0 mg/kg, showed moderate activity (WBR of 46.7%). The calculated ED50 for R- and S-PZQ were 24.7 and 127.6 mg/kg, respectively, with a corresponding eudysmic ratio of 5.17. Our data support the theory of R-PZQ driving the antischistosomal activity. Interestingly, also S-PZQ proved to possess a significant activity towards S. haematobium, particularly in vivo.

The hidden epidemic of schistosomiasis in recent African immigrants and asylum seekers to Italy

Abstract: The prevalence of schistosomiasis among recent refugees from sub-Saharan Africa in Italy is unknown This is a retrospective review of African immigrants screened at Centre for Tropical Diseases of Negrar from March 2014 to February 2016 Of the 373 immigrants tested, 34% were positive at least at one schistosomiasis test The proportion of positive ELISA serology was 103/373 (276%) At microscopy, infected subjects were 65/373 (174%), (51% Schistosoma haematobium, 38% Schistosoma mansoni, 11% both) CCA antigen for S mansoni was positive in 47/373 individuals (126%) We found a particularly high positivity rate in subjects from Mali (721%) and Ivory Coast (48%) This “hidden epidemic” of schistosomiasis cannot be longer neglected, considering the risk of severe complications, and the effective and inexpensive treatment available

Efficacy of praziquantel on Schistosoma haematobium and re-infection rates among school-going children in the Ndumo area of uMkhanyakude district, KwaZulu-Natal, South Africa.

Abstract: Despite its low cure rates and possible resistance, praziquantel (PZQ) is the only drug available for schistosomiasis treatment. Hence, monitoring its efficacy is crucial. This study assessed the efficacy of PZQ, determined re-infection and incidence rates of Schistosoma haematobium infection among school-going children in the Ndumo area, KwaZulu-Natal. A cohort of 320 school-going children (10 – 15 years) in 10 primary schools was screened for S. haematobium infection using the filtration technique. Infected children were treated at different times and hence were divided into two sub-cohorts; A1 and A2. Non-infected children constituted the sub-cohort B. Children who continued excreting viable eggs 4 weeks post-treatment received a second dose of PZQ. Re-infection rates were determined in sub-cohort A1 and A2 at 28 and 20 weeks post-treatment, respectively. Cure rates (CR) and egg reduction rates (ERR) were calculated. Incidence rate was assessed 28 weeks post baseline survey using children that were negative for schistosome eggs at that survey. Analysis of data was done using the Chi square and the Wilcoxon rank test. A 95% confidence interval with a P-value < 0.05 determined significance. At baseline, 120 (37.5%) of the 320 study participants were found infected with Schistosoma haematobium. Heavy infections accounted for 36.7%. The calculated cure rates were 88.07% and 82.92% for females and males, respectively. Egg Reduction Rates of 80% and 64% for females and males were observed 4 weeks after the initial treatment. After the second treatment, CR was 100% in females and 50% in males with an ERR of 100% in females and 70% in males. At 20 and 28 weeks post treatment, reinfection rates of 8.03% and 8.00% were observed, respectively, giving an overall rate of 8.1%. An incidence rate of 4.1% was observed 28 weeks after the baseline screening. The study indicated high CR while the ERR was low suggesting a reduced PZQ efficacy. The efficacy improved among females after the second dose. Re-infection rates at 20 and 28 weeks post-treatment were low. The study also indicated a low incidence rate for the 28 weeks period.

Prevalence and seasonal transmission of Schistosoma haematobium infection among school-aged children in Kaedi town, southern Mauritania

Abstract: Mauritania is at the fringe of transmission of human schistosomiasis, which mainly occurs in the southern and southeastern parts of the country. This study aimed to assess the influence of rainfall seasonality on the prevalence of Schistosoma haematobium infection among school-aged children in Kaedi, southern Mauritania. Cross-sectional surveys (i.e. parasitological, malacological and observations on water-related human activities) were carried out in Kaedi between September 2014 and May 2015, during both the wet and dry seasons. A total of 2162 children aged 5–15 years provided a single urine sample that was subjected to S. haematobium diagnosis. Snails were sampled and checked for cercarial shedding. Water contact patterns of the local population were recorded by direct observation. The prevalence of S. haematobium was 4.0% (86/2162, 95% confidence interval (CI): 3.2–4.9%) with a geometric mean egg count per 10 ml of urine of 3.7 (95% CI: 2.8–4.3). Being male (adjusted odds ratio (aOR) 1.78, 95% CI: 1.13–2.80), being at primary school (aOR 1.73, 95% CI: 1.04–2.87) and dry season (aOR 0.56, 95% CI: 0.35–0.89) were significantly associated with S. haematobium. Among 284 potential intermediate host snail specimens collected over the rainy and dry seasons, three species were identified: Bulinus senegalensis (n = 13) and B. forskalii (n = 161) in the rainy season, and B. truncatus (n = 157) in the wet season. No snail was shedding cercariae. On average, seven human water contacts were recorded per hour per observer over a 28-day observation period. Twelve types of water contact activities were identified among which, swimming/bathing was predominant (n = 3788, 36.9%), followed by washing clothes (n = 2016, 19.7%) and washing dishes (n = 1322, 12.9%). Females (n = 5270, 51.4%) were slightly more in contact with water than males (n = 4983, 48.6%). The average time spent in the water per person per day was 14.2 min (95% CI: 13.8–14.6 min). The frequency and duration of water contact followed a seasonal pattern. Our findings demonstrate a low prevalence and intensity of S. haematobium among school-aged children in Kaedi. Appropriate integrated control measures, including health education among at-risk communities and snail control may help to interrupt transmission of S. haematobium in Kaedi.

H-IPSE Is a Pathogen-Secreted Host Nucleus-Infiltrating Protein (Infiltrin) Expressed Exclusively by the Schistosoma haematobium Egg Stage.

Abstract: Urogenital schistosomiasis, caused by the parasitic trematode Schistosoma haematobium, affects over 112 million people worldwide. As with Schistosoma mansoni infections, the pathology of urogenital schistosomiasis is related mainly to the egg stage, which induces granulomatous inflammation of affected tissues. Schistosoma eggs and their secretions have been studied extensively for the related organism S. mansoni, which is more amenable to laboratory studies. Indeed, we have shown that IPSE/alpha-1 (here M-IPSE), a major protein secreted from S. mansoni eggs, can infiltrate host cells. Although the function of M-IPSE is unknown, its ability to translocate to the nuclei of host cells and bind DNA suggests a possible role in immune modulation of host cell tissues. Whether IPSE homologs are expressed in other schistosome species has not been investigated. Here, we describe the cloning of two paralog genes, H03-IPSE and H06-IPSE, which are orthologs of M-IPSE, from egg cDNA of S. haematobium. Using PCR and immunodetection, we confirmed that the expression of these genes is restricted to the egg stage and female adult worms, while the H-IPSE protein is detectable only in mature eggs and not adults. We show that both H03-IPSE and H06-IPSE proteins can infiltrate HTB-9 bladder cells when added exogenously to culture medium. Monopartite C-terminal nuclear localization sequence (NLS) motifs conserved in H03-IPSE, SKRRRKY, and H06-IPSE SKRGRKY, are responsible for targeting the proteins to the nucleus of HTB-9 cells, as demonstrated by site-directed mutagenesis and green fluorescent protein (GFP) tagging. Thus, S. haematobium eggs express IPSE homologs that appear to perform similar functions in infiltrating host cells.

Schistosomiasis risk factors based on the infection status among school-going children in the Ndumo area, uMkhanyakude district, South Africa

Abstract: Background: Schistosomiasis remains a public health burden in South Africa, particularly in KwaZulu-Natal. The study aimed to identify the risk factors for transmission of Schistosoma haematobium among school-going children in the Ndumo area of uMkhanyakude district, KwaZulu-Natal.Methods: A cross-sectional study involving 320 school-going children, aged 10–15 years, was conducted in 10 local primary schools in the Ndumo area, from May to June 2015. Data were collected using a structured questionnaire based on socio-demographic information, sanitation and water access, recreational, occupational activities, and knowledge about bilharzia. A filtration technique was used to detect S. haematobium eggs in 10 ml of urine. A Chi square test, bivariate and logistic regressions were performed to assess the association between variables. Odds ratios were used to determine the strength between significant predictors with 95% confidence interval and p value < 0.05.Results: From the 320 participants, 120 (37.5%) were...

Halting Schistosoma haematobium - associated bladder cancer.

Abstract: Background At present schistosomiasis is endemic in 78 countries affecting more than 260 million people. Schistosomiasis haematobia alone affects more than 112 millions. Material and methods We performed a computerized search of Pubmed database with keywords: bladder cancer cost and schistosomiasis mass treatment. Results Bladder cancer is an important sequelae of this infection. In low-resource countries, where this disease is endemic, individuals inflicted with bladder cancer have very limited access to treatment and death is most probably certain. Conclusion Mass treatment with praziquantel is an easy, safe and inexpensive treatment that could save the lives of thousands and reduce the morbidity of millions.

Increasing prevalence of genitourinary schistosomiasis in Europe in the Migrant Era: Neglected no more?

Abstract: 1 Department of Health Sciences (DISSAL), Infectious Disease Section, IRCCS AOU San Martino-IST, Genoa, Italy, 2 Department of Health Sciences (DISSAL), Radiology Section, University of Genoa, Genoa, Italy, 3 Department of Surgical Science (DISC), Luciano Giuliani Department of Urology, University of Genoa, IRCCS AOU San Martino-IST, Genoa, Italy, 4 Department of Surgery (DISC), Pathology Section, University of Genoa, Genoa, Italy, 5 Department of Health Sciences (DISSAL), Radiology Section, University of Genoa, Emergency Radiology, IRCCS AOU San Martino-IST, Genoa, Italy

Ferrocenyl, Ruthenocenyl, and Benzyl Oxamniquine Derivatives with Cross-Species Activity against Schistosoma mansoni and Schistosoma haematobium

Abstract: Schistosomiasis is a parasitic disease that affects more than 250 million people annually, mostly children in poor, tropical, rural areas. Only one treatment (praziquantel) is available, putting control efforts at risk should resistance occur. In pursuit of treatment alternatives, we derivatized an old antischistosomal agent, oxamniquine (OXA). Four organometallic derivatives of OXA were synthesized and tested against Schistosoma mansoni in vitro and in vivo. Of these, a ferrocenyl derivative, 1, killed larval and adult worms 24 h postexposure in vitro, in contrast to OXA, which lacks in vitro activity against adult worms. A dose of 200 mg/kg of 1 completely eliminated the worm burden in mice. Subsequently, a ruthenocenyl (5) and a benzyl derivative (6) of OXA were synthesized to probe the importance of the ferrocenyl group in 1. Compounds 1, 5, and 6 were lethal to both S. mansoni and S. haematobium adults in vitro. In vivo, at 100 mg/kg, all three compounds revealed S. mansoni worm burden reductions of 76 to 93%, commensurate with OXA. Our findings present three compounds with activity against S. mansoni in vitro, comparable activity in vivo, and high activity against S. haematobium in vitro. These compounds may possess a different binding mode or mode of action compared to OXA and present excellent starting points for further SAR studies.

Coinfection with Schistosoma haematobium and Plasmodium falciparum and Anaemia Severity among Pregnant Women in Munyenge, Mount Cameroon Area: A Cross-Sectional Study.

Abstract: Background. Malaria and urogenital schistosomiasis are coendemic in Mount Cameroon Area. This study investigated the prevalence of S. haematobium, P. falciparum, and coinfections and their effect on anaemia in pregnancy. Methods. Pregnant women reporting for antenatal care (ANC) clinic visit in Munyenge were enrolled. S. haematobium and P. falciparum infections were determined by urine filtration and microscopy, respectively. Haemoglobin (Hb) levels were measured using haemoglobinometer. Of 250 women, 46.8%, 39.2%, and 15.2% had S. haematobium, P. falciparum, and coinfections, respectively. Schistosomes infection was higher in younger women (≤25 years) and those who bathe in and had domestic contact with stream compared with older age (>25 years) women and those who had only domestic contact with stream. Lower infection rate was associated with less water contact (≤2 times/day) compared with more water contact (>2 times/day). Compared with no sulphadoxine-pyrimethamine (SP) usage, malaria parasitaemia was less among women who used SP. Stream usage increased risk of coinfection while less water contact and SP usage decreased its risk. All coinfected cases were anaemic and coinfection accounted for 93.8% of severe anaemia. Conclusion. Coinfection contributes to anaemia severity. Less water contact and SP usage will reduce coinfection in pregnancy in Munyenge.

Dynamics of freshwater snails and Schistosoma infection prevalence in schoolchildren during the construction and operation of a multipurpose dam in central Côte d'Ivoire.

Abstract: The construction and operation of small multipurpose dams in Africa have a history of altering the transmission of water-based diseases, including schistosomiasis. The current study was designed to investigate the abundance and dynamics of schistosomiasis intermediate host snails and Schistosoma infections in humans during the construction and the first years of operation of a small multipurpose dam in Cote d’Ivoire. The study was carried out in Raffierkro and four neighbouring villages in central Cote d’Ivoire between 2007 and 2012. Snails were collected by two experienced investigators using scoops and forceps for 15 min at each site. Snails were identified at genera and, whenever possible, species level, and subjected to testing for cercarial shedding. Schoolchildren aged 6–15 years were examined once every year for Schistosoma haematobium and S. mansoni infection, using urine filtration and duplication Kato-Katz thick smears, respectively. Additionally, 551 adults were examined for Schistosoma infection before (June 2007) and 359 individuals 2 years after dam construction (June 2009). Overall, 1 700 snails belonging to nine different genera were collected from 19 sampling sites. Bulinus (potential intermediate host snails of S. haematobium) and Pila were the most common genera, whereas Biomphalaria (potential intermediate host snail of S. mansoni), Lymnaea, Physa and Melanoides were found in two villages. During the first-year sampling period, 65 snails were collected, of which 13 (20%) were schistosomiasis intermediate hosts. In subsequent years, out of 1 635 snails collected, 1 079 (66%) were identified as potential intermediate host for schistosomiasis, but none were shedding cercariae. The prevalence of S. mansoni among adults in the study area was low (0.4% in 2007 and 0.3% in 2009), whereas the prevalence of S. haematobium declined from 13.9% to 2.9% in this two-year period. The low prevalence of schistosomiasis in humans and the absence of infected intermediate host snails during the construction and early phase of operation of a small multipurpose dam suggest that there was no or only very little local transmission. However, the considerable increase in the number of intermediate host snails and their dispersion in irrigation canals call for rigorous surveillance, so that adequate public health measures can be taken in case of early signs of an outbreak.

Schistosomiasis and Human Immunodeficiency Virus in Men in Tanzania.

Abstract: Schistosomiasis is a parasitic worm infection that affects over 260 million individuals worldwide. Women with schistosome infections have been demonstrated to have a 4-fold increase in the odds of human immunodeficiency virus (HIV) infection compared with women without schistosome infections. A relationship between schistosome and HIV infections has not been clearly defined in men. Among 674 men aged 18-50 years living in rural Tanzania, we identified 429 (63.6%) who had a schistosome infection as defined by serum positivity for schistosome circulating anodic antigen, visualization of parasite eggs in urine or stool, or both. HIV infection was identified in 38 (5.6%). The odds of HIV infection was 1.3 [95% confidence interval = 0.6-2.5] (P = 0.53) among men with any schistosome infection (Schistosoma haematobium or Schistosoma mansoni), and it was 1.4 [0.6-3.3] (P = 0.43) among men with S. haematobium infection. Men with S. haematobium infection were significantly more likely to report the symptom of hemospermia than men without S. haematobium infection. We conclude that schistosome infections appear to have little to no association with HIV infection in men.

Ultrasonographic evaluation of urinary tract morbidity in school-aged and preschool-aged children infected with Schistosoma haematobium and its evolution after praziquantel treatment : a randomized controlled trial

Abstract: Background Schistosoma haematobium infections are responsible for significant urinary tract (UT) complications. Schistosomiasis control programs aim to reduce morbidity, yet the extent of morbidity in preschool-aged children and the impact of treatment on morbidity reduction are not well studied. Methodology Our study was embedded in a randomized, placebo-controlled, single-blind trial in Cote d’Ivoire, which evaluated the efficacy and safety of three doses (20, 40 and 60 mg/kg) of praziquantel in school-aged (SAC) and preschool-aged (PSAC) children infected with S. haematobium. Enrolled children were invited to participate in an ultrasound examination prior and six months after treatment. At these time points 3 urine samples were collected for parasitological and clinical examinations. Principal findings 162 PSAC and 141 SAC participated in the ultrasound examination at baseline, of which 128 PSAC and 122 SAC were present at follow-up. At baseline 43% (70/162) of PSAC had UT morbidity, mostly at bladder level and 7% had hydronephrosis. 67% (94/141) of SAC revealed mainly moderate UT pathology, 4% presented pseudopolyps on the bladder wall, and 6% had pyelectasis. At follow up, 45% of PSAC and 58% of SAC were S. haematobium positive, mostly harboring light infection intensities (41% and 51%, respectively). Microhematuria was present in 33% of PSAC and 42% of SAC and leukocyturia in 53% and 40% of PSAC and SAC, respectively. 50% (64/128) of PSAC and 58% (71/122) of SAC presented urinary tract morbidity, which was mainly mild. A significant correlation (p<0.05) was observed between praziquantel treatment and reversal of S. haematobium induced morbidity. Progression of UT pathology decreased with increasing praziquantel dosages. A worsening of morbidity was observed among children in the placebo group. Conclusion/Significance Bladder morbidity is widespread among PSAC. Praziquantel treatment is significantly associated with the reversal of S. haematobium induced morbidity, which underscores the importance of preventive chemotherapy programs. These programs should be expanded to PSAC to prevent or decrease the prevalence of morbidity in young children. This trial is registered as an International Standard Randomized Controlled Trial, number ISRCTN15280205.

Cross-species prophylactic efficacy of Sm-p80-based vaccine and intracellular localization of Sm-p80/Sm-p80 ortholog proteins during development in Schistosoma mansoni, Schistosoma japonicum, and Schistosoma haematobium.

Abstract: Schistosomiasis remains a major global health problem. Despite large-scale schistosomiasis control efforts, clear limitations such as possible emergence of drug resistance and reinfection rates highlight the need for an effective schistosomiasis vaccine. Schistosoma mansoni large subunit of calpain (Sm-p80)-based vaccine formulations have shown remarkable efficacy in protecting against S. mansoni challenge infections in mice and baboons. In this study, we evaluated the cross-species protective efficacy of Sm-p80 vaccine against S. japonicum and S. haematobium challenge infections in rodent models. We also elucidated the expression of Sm-p80 and Sm-p80 ortholog proteins in different developmental stages of S. mansoni, S. haematobium, and S. japonicum. Immunization with Sm-p80 vaccine reduced worm burden by 46.75% against S. japonicum challenge infection in mice. DNA prime/protein boost (1 + 1 dose administered on a single day) resulted in 26.95% reduction in worm burden in S. haematobium-hamster infection/challenge model. A balanced Th1 (IFN-γ, TNF-α, IL-2, and IL-12) and Th2 (IL-4, IgG1) type of responses were observed following vaccination in both S. japonicum and S. haematobium challenge trials and these are associated with the prophylactic efficacy of Sm-p80 vaccine. Immunohistochemistry demonstrated that Sm-p80/Sm-p80 ortholog proteins are expressed in different life cycle stages of the three major human species of schistosomes studied. The data presented in this study reinforce the potential of Sm-p80-based vaccine for both hepatic/intestinal and urogenital schistosomiasis occurring in different geographical areas of the world. Differential expression of Sm-p80/Sm-p80 protein orthologs in different life cycle makes this vaccine potentially useful in targeting different levels of infection, disease, and transmission.

Assessing the benefits of five years of different approaches to treatment of urogenital schistosomiasis: A SCORE project in Northern Mozambique.

Abstract: Background In Mozambique, schistosomiasis is highly endemic across the whole country. The Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) coordinates a five-year study that has been implemented in various African countries, including Mozambique. The overall goal of SCORE was to better understand how to best apply preventive chemotherapy with praziquantel (PZQ) for schistosomiasis control by evaluating the impact of alternative treatment approaches. Methods This was a cluster-randomised trial that compared the impact of different treatment strategies in study areas with prevalence among school children of ≥21% S. haematobium infection by urine dipstick. Each village was randomly allocated to one of six possible combinations of community-wide treatment (CWT), school-based treatment (SBT), and/or drug holidays over a period of four years, followed by final data collection in the fifth year. The most intense intervention arm involved four years of CWT, while the least intensive arm involved two years of SBT followed by two consecutive years of PZQ holiday. Each study arm included 25 villages randomly assigned to one of the six treatment arms. The primary outcome of interest was change in prevalence and intensity of S. haematobium among 100 children aged 9-to-12-years that were sampled each year in every village. In addition to children aged 9-to-12 years, 100 children aged 5–8 years in their first-year of school and 50 adults (aged 20–55 years) were tested in the first and final fifth year of the study. Prevalence and intensity of S. haematobium infection was evaluated by two filtrations, each of 10mL, from a single urine specimen. Principal findings In total, data was collected from 81,167 individuals across 149 villages in ten districts of Cabo Delgado province, Northern Mozambique. Overall PZQ treatment resulted in a significant reduction in the prevalence of S. haematobium infection from Year 1 to Year 5, where the average prevalence went from 60.5% to 38.8%, across all age groups and treatment arms. The proportion of those heavily infected also reduced from 17.6% to 11.9% over five years. There was a significantly higher likelihood of males being infected than females at baseline, but no significant difference between the sexes in their response to treatment. The only significant response based on a study arm was seen in both the 9-to-12-year-old and first-year cross sections, where two consecutive treatment holidays resulted in a significantly higher final prevalence of S. haematobium than no treatment holidays. When the arms were grouped together, four rounds of treatment (regardless of whether it was CWT or SBT), however, did result in a significantly greater reduction in S. haematobium prevalence than two rounds of treatment (i.e. with two intermittent or consecutive holiday years) over a five-year period. Conclusions Although PC was successful in reducing the burden of active infection, even among those heavily infected, annual CWT did not have a significantly greater impact on disease prevalence or intensity than less intense treatment arms. This may be due to extremely high starting prevalence and intensity in the study area, with frequent exposure to reinfection, or related to challenges in achieving high treatment coverage More frequent treatment had a greater impact on prevalence and intensity of infection when arms were grouped by number of treatments, however, cost efficiency was greater in arms only receiving two treatments. Finally, a significant reduction in prevalence of S. haematobium was seen in adults even in the SBT arms implying the rate of transmission in the community had been decreased, even where only school children have been treated, which has significant logistical and cost-saving implications for a national control programme in justifying CWT.

Field evaluation of a schistosome circulating cathodic antigen rapid test kit at point-of-care for mapping of schistosomiasis endemic districts in The Gambia.

Abstract: Background Studies in Sub Saharan Africa have shown that the Circulating Cathodic Antigen point-of-care-test (POC-CCA) is more accurate in the detections of S. mansoni than the microscopic Kato-Katz technique but less is known about the accuracy of this rapid test in detecting S. haematobium infections. This study was intended to evaluate the field accuracy of POC-CCA as a rapid test kit for schistosomiasis mapping in The Gambia. Methods This prospective study was conducted in 4 regions in the country. Ten schools were randomly selected from each region, and a total of 2018 participants whose ages range from 7 to 14 years were enrolled in the study. Stool and urine samples were collected from each participant from May to June 2015, and tested for S. haematobium and S. mansoni infections in field and laboratory settings. The tests conducted included POC-CCA, double Kato-Katz slides, urine filtration and dipstick for hematuria. Results Of the 1954 participants that had complete data, the mean age of participants was 9.9 years. The prevalence of children infected with S. haematobium, using urine filtration technique was 10.1% (95% CI: 8.87–11.55). Central River Region had the highest level of urinary schistosomiasis with a prevalence of 28.0% (24.13–32.12).The lowest urinary schistosomiasis prevalence of 0.6% (0.12–1.86) was found in Lower River Region and North Bank Region had no cases of schistosomiasis detected. Only 5 participants were infected with S. mansoni. Using urine filtration as reference standard for the detection of S. haematobium, the sensitivity and specificity of POC-CCA was 47.7% and 75.8%. Whilst sensitivity and specificity of POC-CCA for detecting S. mansoni were 60.0% and 71.2% using double Kato-Katz as reference standard. Conclusion This study showed lower sensitivity of POC-CCA in detecting S. haematobium. Therefore POC-CCA is less useful for rapid diagnosis of urinary schistosomiasis.

Spatial distribution and risk factors of Schistosoma haematobium and hookworm infections among schoolchildren in Kwale, Kenya

Abstract: Background Large-scale schistosomiasis control programs are implemented in regions with diverse social and economic environments. A key epidemiological feature of schistosomiasis is its small-scale heterogeneity. Locally profiling disease dynamics including risk factors associated with its transmission is essential for designing appropriate control programs. To determine spatial distribution of schistosomiasis and its drivers, we examined schoolchildren in Kwale, Kenya. Methodology/Principal findings We conducted a cross-sectional study of 368 schoolchildren from six primary schools. Soil-transmitted helminths and Schistosoma mansoni eggs in stool were evaluated by the Kato-Katz method. We measured the intensity of Schistosoma haematobium infection by urine filtration. The geometrical mean intensity of S. haematobium was 3.1 eggs/10 ml urine (school range, 1.4–9.2). The hookworm geometric mean intensity was 3.2 eggs/g feces (school range, 0–17.4). Heterogeneity in the intensity of S. haematobium and hookworm infections was evident in the study area. To identify factors associated with the intensity of helminth infections, we utilized negative binomial generalized linear mixed models. The intensity of S. haematobium infection was associated with religion and socioeconomic status (SES), while that of hookworm infection was related to SES, sex, distance to river and history of anthelmintic treatment. Conclusions/Significance Both S. haematobium and hookworm infections showed micro-geographical heterogeneities in this Kwale community. To confirm and explain our observation of high S. haematobium risk among Muslims, further extensive investigations are necessary. The observed small scale clustering of the S. haematobium and hookworm infections might imply less uniform strategies even at finer scale for efficient utilization of limited resources.

Angiogenesis in Schistosoma haematobium-associated urinary bladder cancer.

Abstract: Schistosoma haematobium, a parasitic flatworm that infects more than 100 million people, mostly in the developing world, is the causative agent of urogenital schistosomiasis, and is associated with a high incidence of squamous cell carcinoma (SCC) of the bladder. During infection, eggs are deposited in the bladder causing an intense inflammatory reaction. Angiogenesis is defined as the formation of new blood vessels from preexisting ones and is recognized as a key event in cell proliferation and carcinogenesis and spread of malignant lesions. A growing amount of evidence points to angiogenesis playing a key role in schistosomiasis-associated bladder cancer. Thus, identifying biomarkers of this process plays an important role in the study of cancer. Here, we review recent findings on the role of angiogenesis in bladder cancer and the growth factors that induce and assist in their development, particularly SCC of the bladder associated to urogenital schistosomiasis.

Epidemiological, clinical, diagnostic and economic features of an immigrant population of chronic schistosomiasis sufferers with long-term residence in a non-endemic country (North Metropolitan area of Barcelona, 2002-2016).

Abstract: Background Schistosomiasis, one of the neglected tropical diseases (NTD) listed by the WHO, is an acute and chronic parasitic disease caused by blood flukes (trematode worms) of the genus Schistosoma. Complications of long-term infestation include liver cirrhosis, bladder tumors and kidney failure. The objective of this study was to carry out a clinical and epidemiological characterization of a schistosomiasis-diagnosed immigrant population with long-term residencein the EU as well as to evaluate the diagnostic methods available to date. Methods and results A total of 61 individuals with Schistosoma infection who received medical attention between June 2002 and June 2016 at the North Metropolitan International Health Unit in Barcelona (Catalonia, Spain), were included in the study. All patients were sub-Saharan African immigrants. The majority were male (91.8%) with a median age of 34 years. Symptoms attributable to infection such as haematuria, abdominal pain and dysuria were recorded in up to 90% of patients. The percentage of eosinophils decreased amongst older patients (p = 0.002) and those with symptoms associated with urinary tract infections (p = 0.017). Serology was used for diagnosis in 80.3% of the cases, with microscopic examination showing the remaining 9.8% positive for parasite eggs. Direct microbiological diagnosis was more useful in patients with less than 5 years of residence in the EU (p = 0.05). Chronic complications were present in 22 (36%) of the patients, with renal failure affecting 20 (33%). Of these 20, 6(10%) developed terminal renal failure and required hemodialysis, while 3 (5%) received a renal transplantation. Conclusion Morbidity associated with chronic long-term schistosomiasis is frequent among African immigrants in non-endemic countries. Better diagnostic tools and appropriate early treatment would prevent the development of visceral damage. Thorough screening in selected patients would also be useful to avoid chronic complications.

Female genital schistosomiasis (FGS) in Ogun State, Nigeria: a pilot survey on genital symptoms and clinical findings

Abstract: The Nigerian national control programme (NCP) for schistosomiasis does not have a specific action plan for female genital schistosomiasis (FGS), mainly due to gaps in epidemiological and clinical surveillance. To address this, we conducted a pilot investigation for FGS in girls (>5 and ≤15 years) and adult women (≥16 years) in four rural communities near Abeokuta, Ogun State. Urine samples were collected from 317 participants [children (n = 187), adults (n = 130)] and examined for ova of S chistosoma haematobium by microscopy. A total of 149 participants (47·0%) had egg-patent urogenital schistosomiasis [children (64·7%), adults (21·6%)], reported blood in urine was common (44·5%) as well as sign-post symptoms of FGS. To verify FGS directly, 20 adult women each underwent a gynaecological investigation by colposcopy with observed lesions classified according to the WHO FGS pocket atlas. Fourteen (70·0%) women presented with FGS as grainy-sandy patches (n = 10), homogenous yellow sandy patches (n = 6), nabothian cysts and rubbery papules (n = 1). Our study confirms FGS in Ogun State and calls for further appraisals of this disease in other areas where urogenital schistosomiasis is endemic. The Nigerian NCP should be encouraged to develop an appropriate response to FGS not only to detect it, but also to prevent it.

Quantitative label-free proteomic analysis of human urine to identify novel candidate protein biomarkers for schistosomiasis.

Abstract: Background Schistosomiasis is a chronic neglected tropical disease that is characterized by continued inflammatory challenges to the exposed population and it has been established as a possible risk factor in the aetiology of bladder cancer. Improved diagnosis of schistosomiasis and its associated pathology is possible through mass spectrometry to identify biomarkers among the infected population, which will influence early detection of the disease and its subtle morbidity. Methodology A high-throughput proteomic approach was used to analyse human urine samples for 49 volunteers from Eggua, a schistosomiasis endemic community in South-West, Nigeria. The individuals were previously screened for Schistosoma haematobium and structural bladder pathologies via microscopy and ultrasonography respectively. Samples were categorised into schistosomiasis, schistosomiasis with bladder pathology, bladder pathology, and a normal healthy control group. These samples were analysed to identify potential protein biomarkers. Results A total of 1306 proteins and 9701 unique peptides were observed in this study (FDR = 0.01). Fifty-four human proteins were found to be potential biomarkers for schistosomiasis and bladder pathologies due to schistosomiasis by label-free quantitative comparison between groups. Thirty-six (36) parasite-derived potential biomarkers were also identified, which include some existing putative schistosomiasis biomarkers that have been previously reported. Some of these proteins include Elongation factor 1 alpha, phosphopyruvate hydratase, histone H4 and heat shock proteins (HSP 60, HSP 70). Conclusion These findings provide an in-depth analysis of potential schistosoma and human host protein biomarkers for diagnosis of chronic schistosomiasis caused by Schistosoma haematobium and its pathogenesis.

Detecting hybridization in African schistosome species: does egg morphology complement molecular species identification?

Abstract: Hybrid parasites may have an increased transmission potential and higher virulence compared to their parental species. Consequently, hybrid detection is critical for disease control. Previous crossing experiments showed that hybrid schistosome eggs have distinct morphotypes. We therefore compared the performance of egg morphology with molecular markers with regard to detecting hybridization in schistosomes. We studied the morphology of 303 terminal-spined eggs, originating from 19 individuals inhabiting a hybrid zone with natural crosses between the human parasite Schistosoma haematobium and the livestock parasite Schistosoma bovis in Senegal. The egg sizes showed a high variability and ranged between 92·4 and 176·4 µm in length and between 35·7 and 93·0 µm in width. No distinct morphotypes were found and all eggs resembled, to varying extent, the typical S. haematobium egg type. However, molecular analyses on the same eggs clearly showed the presence of two distinct partial mitochondrial cox1 profiles, namely S. bovis and S. haematobium, and only a single nuclear ITS rDNA profile (S. haematobium). Therefore, in these particular crosses, egg morphology appears not a good indicator of hybrid ancestry. We conclude by discussing strengths and limitations of molecular methods to detect hybrids in the context of high-throughput screening of field samples.