Therapeutic Potential of Natural Products in the Treatment of Schistosomiasis.

It is estimated that 250 million people worldwide are affected by schistosomiasis. Disease transmission is related to the poor sanitation and hygiene habits that affect residents of impoverished regions in tropical and subtropical countries. The main species responsible for causing disease in humans are Schistosoma Mansoni, S. japonicum, and S. haematobium, each with different geographic distributions. Praziquantel is the drug predominantly used to treat this disease, which offers low effectiveness against immature and juvenile parasite forms. In addition, reports of drug resistance prompt the development of novel therapeutic approaches. Natural products represent an important source of new compounds, especially those obtained from plant sources. This review compiles data from several in vitro and in vivo studies evaluating various compounds and essential oils derived from plants with cercaricidal and molluscicidal activities against both juvenile and adult forms of the parasite. Finally, this review provides an important discussion on recent advances in molecular and computational tools deemed fundamental for more rapid and effective screening of new compounds, allowing for the optimization of time and resources.

Human schistosomiasis in Nigeria: present status, diagnosis, chemotherapy, and herbal medicines.

Schistosomiasis is a neglected tropical disease caused by a parasitic, trematode blood fluke of the genus Schistosoma. With 20 million people infected, mostly due to Schistosoma haematobium, Nigeria has the highest burden of schistosomiasis in the world. We review the status of human schistosomiasis in Nigeria regarding its distribution, prevalence, diagnosis, prevention, orthodox and traditional treatments, as well as snail control strategies. Of the country's 36 states, the highest disease prevalence is found in Lagos State, but at a geo-political zonal level, the northwest is the most endemic. The predominantly used diagnostic techniques are based on microscopy. Other methods such as antibody-based serological assays and DNA detection methods are rarely employed. Possible biomarkers of disease have been identified in fecal and blood samples from patients. With respect to preventive chemotherapy, mass drug administration with praziquantel as well as individual studies with artemisinin or albendazole have been reported in 11 out of the 36 states with cure rates between 51.1 and 100%. Also, Nigerian medicinal plants have been traditionally used as anti-schistosomal agents or molluscicides, of which Tetrapleura tetraptera (Oshosho, aridan, Aidan fruit), Carica papaya (Gwanda, Ìbépe, Pawpaw), Borreria verticillata (Karya garma, Irawo-ile, African borreria), and Calliandra portoricensis (Tude, Oga, corpse awakener) are most common in the scientific literature. We conclude that the high endemicity of the disease in Nigeria is associated with the limited application of various diagnostic tools and preventive chemotherapy efforts as well as poor knowledge, attitudes, and practices (KAP). Nonetheless, the country could serve as a scientific base in the discovery of biomarkers, as well as novel plant-derived schistosomicides and molluscicides.

Prevalence and risk distribution of schistosomiasis among adults in Madagascar: a cross-sectional study.

BACKGROUND: The goal to eliminate the parasitic disease of poverty schistosomiasis as a public health problem is aligned with the 2030 United Nations agenda for sustainable development goals, including universal health coverage (UHC). Current control strategies focus on school-aged children, systematically neglecting adults. We aimed at providing evidence for the need of shifting the paradigm of schistosomiasis control programs from targeted to generalized approaches as key element for both the elimination of schistosomiasis as a public health problem and the promotion of UHC. METHODS: In a cross-sectional study performed between March 2020 and January 2021 at three primary health care centers in Andina, Tsiroanomandidy and Ankazomborona in Madagascar, we determined prevalence and risk factors for schistosomiasis by a semi-quantitative PCR assay from specimens collected from 1482 adult participants. Univariable and multivariable logistic regression were performed to evaluate odd ratios. RESULTS: The highest prevalence of S. mansoni, S. haematobium and co-infection of both species was 59.5%, 61.3% and 3.3%, in Andina and Ankazomborona respectively. Higher prevalence was observed among males (52.4%) and main contributors to the family income (68.1%). Not working as a farmer and higher age were found to be protective factors for infection. CONCLUSIONS: Our findings provide evidence that adults are a high-risk group for schistosomiasis. Our data suggests that, for ensuring basic health as a human right, current public health strategies for schistosomiasis prevention and control need to be re-addressed towards more context specific, holistic and integrated approaches.

In vivo efficiency of praziquantel treatment of single-sex Schistosoma japonicum aged three months old in mice.

Schistosomiasis is a major neglected tropical disease mainly caused by Schistosoma haematobium, S. japonicum and S. mansoni, and results in the greatest disease burden. Mass drug administration (MDA) with praziquantel (PZQ), a single drug only available for the disease, has played a vital role in schistosomiasis control. Therefore, any possibility of selection of the parasites for PZQ resistance or low sensitivity may hamper the 2030's target of global disease elimination. We had experimentally demonstrated the long-term survival and reproductive potential of single-sex (of either sex) S. japonicum infections in definitive hosts mice. What has not yet been adequately addressed is whether the long live single-sex schistosomes remain sensitive to PZQ, and what reproduction potential for those schistosomes surviving treatment may have. We therefore performed experimental mice studies to explore the treatment effectiveness of PZQ (at total doses of 200 or 400 mg/kg, corresponding to the sub-standard or standard treatment doses in humans) for single-sex S. japonicum aged three months old. The results showed that no treatment efficiency was observed on female schistosomes, whereas on male schistosomes only at PZQ 400 mg/kg a significant higher efficiency in reducing worm burdens was observed. Moreover, either schistosome males or females surviving PZQ treatment remained their reproduction potential as normal. The results indicate that long (i.e., three months) live single-sex S. japonicum can easily survive the current treatment strategy, and moreover, any schistosomes, if with PZQ resistance or low sensitivity, could be easily transmitted in nature. Therefore, in order to realize the target for the national and the global schistosomiasis elimination, there is undoubtedly a great need for refining PZQ administration and dosage, looking for alternative therapies, and/or developing vaccines against schistosome.

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

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

"We know about schistosomiasis but we know nothing about FGS": A qualitative assessment of knowledge gaps about female genital schistosomiasis among communities living in Schistosoma haematobium endemic districts of Zanzibar and Northwestern Tanzania.

BACKGROUND: Schistosoma haematobium causes urogenital schistosomiasis and is widely distributed in Tanzania. In girls and women, the parasite can cause Female Genital Schistosomiasis (FGS), a gynecological manifestation of schistosomiasis that is highly neglected and overlooked by public health professionals and policy makers. This study explored community members' knowledge, attitudes and perceptions (KAP) on and health seeking behavior for FGS. METHODS/PRINCIPAL FINDINGS: Using qualitative research methods-including 40 Focus Group Discussions (FGDs) and 37 Key Informant Interviews (KIIs)-we collected data from 414 participants (Males n = 204 [49.3%] and Females n = 210 [50.7%]). The study engaged 153 participants from Zanzibar and 261 participants from northwestern Tanzania and was conducted in twelve (12) purposively selected districts (7 districts in Zanzibar and 5 districts in northwestern Tanzania). Most participants were aware of urogenital schistosomiasis. Children were reported as the most affected group and blood in urine was noted as a common symptom especially in boys. Adults were also noted as a risk group due to their involvement in activities like paddy farming that expose them to infection. Most participants lacked knowledge of FGS and acknowledged having no knowledge that urogenital schistosomiasis can affect the female reproductive system. A number of misconceptions on the symptoms of FGS and how it is transmitted were noted. Adolescent girls and women presenting with FGS related symptoms were reported to be stigmatized, perceived as having a sexually transmitted infection (STI), and sometimes labeled as "prostitutes". Health seeking behavior for FGS included a combination of traditional medicine, self-treatment and modern medicine. CONCLUSION/SIGNIFICANCE: Community members living in two very different areas of Tanzania exhibited major, similar gaps in knowledge about FGS. Our data illustrate a critical need for the national control program to integrate public health education about FGS during the implementation of school- and community-based mass drug administration (MDA) programs and the improvement of water, sanitation and hygiene (WASH) facilities.

Antischistosomal Activity of Origanum majorana, Ziziphus spina-christi, and Salvia fruticosa Plant Extracts on Hamster Infected with Schistosoma haematobium.

World Health Organization (WHO) has approved only one treatment for schistosomiasis, praziquantel (PZQ), but some poor efficacy was noticed in patients during the early stage of infection. Therefore, researchers have intensified their efforts to research new alternative medicines to treat schistosomiasis. In the present study, in vitro as well as in vivo studies have been accomplished to evaluate the effect of Origanum majorana, Ziziphus spina-christi, and Salvia fruticosa extracts in a different concentration 500, 250, 125, 62.5, and 31.25 µg/ml on golden hamster infected by Egyptian strains of schistosome (Schistosoma haematobium). In vitro, the adult worms and schistosomula of S. haematobium were investigated in RPMI-1640 medium for 48 hrs. The results showed that the concentration 500, 250, and 125 µg/ml of Origanum majorana, and Ziziphus spina-christi caused dead of 100% of Egyptian Schistosoma strains of adult worm and schistosomula of S. haematobium within 6 to 12 hrs of incubation. On the other hand, the extract of Salvia fruticosa at concentrations 500, 250, and 125 µg/ml showed death 100% parasites after 12 to 24 hrs of incubation. Inclusion, Origanum majorana, and Ziziphus spina-christi showed effectiveness against Egyptian Schistosoma strains (S. haematobium), a slight decrease in Salvia fruticosa was observed. Therefore, these medical plant extracts may be used as a safe and effective treatment for schistosomiasis.

Evaluation of Urine Reagent Strip as a Tool for Routine Diagnosis of Maternal Urogenital Schistosomiasis at Antenatal Clinic Visit in Munyenge, South West Region, Cameroon.

Urine reagent strip used in detecting microhaematuria has been recommended in pregnancy for diagnosis of urogenital schistosomiasis (UGS) during routine antenatal care (ANC). This study evaluated its sensitivity, specificity, and predictive values in the diagnosis of maternal UGS using filtration method as a reference test. We also assessed the variation in its performance in the diagnosis of UGS using multiple-sample collection. A total of 93 pregnant women reporting for first ANC clinic visit at any of the three functional health care centres (Munyenge Integrated Health Centre, Banga Annex Health Centre, and Trans African Health Centre) were enrolled and followed up for three consecutive monthly visits. Urine samples were observed microscopically for S. haematobium egg using urine filtration and screened for microhaematuria and proteinuria using urine reagent strips. Twenty-two (23.7%) out of the 93 women were diagnosed for UGS, all of whom showed S. haematobium egg excretion during all three visits. There was a significant difference (p < 0.001) between the prevalence of S. haematobium infection and the prevalence of microhaematuria. The intensity of infection was significantly higher in microhaematuria-positive women compared with microhaematuria-negative cases. Sensitivity of reagent strip ranged from 54.5 to 59.1%, while specificity was above 98.0% (range: 98.6-100%). The measure of agreement between urine filtration and reagent strip method was substantial (0.61-0.8) irrespective of different sampling periods. Urine reagent strip is a moderately sensitive method in the detection of UGS and will most likely identify women with high egg load burden. Proper diagnosis of schistosomiasis during pregnancy is recommended.

Evaluation of integrated interventions layered on mass drug administration for urogenital schistosomiasis elimination: a cluster-randomised trial.

BACKGROUND: Elimination of schistosomiasis as a public health problem and interruption of transmission in selected areas are targets set by WHO for 2025. Our aim was to assess biannual mass drug administration (MDA) applied alone or with complementary snail control or behaviour change interventions for the reduction of Schistosoma haematobium prevalence and infection intensity in children from Zanzibar and to compare the effect between the clusters. METHODS: In a 5-year repeated cross-sectional cluster-randomised trial, 90 shehias (small administrative regions; clusters) in Zanzibar eligible owing to available natural open freshwater bodies and public primary schools were randomly allocated (ratio 1:1:1) to receive one of three interventions: biannual MDA with praziquantel alone (arm 1) or in combination with snail control (arm 2), or behaviour change activities (arm 3). Neither participants nor field or laboratory personnel were blinded to the intervention arms. From 2012 to 2017, annually, a single urine sample was collected from approximately 100 children aged 9-12 years in the main public primary school of each shehia. The primary outcome was S haematobium infection prevalence and intensity in 9-12-year-old children after 5 years of follow-up. This study is completed and was registered with the ISRCTN, number 48837681. FINDINGS: The trial was done from Nov 1, 2011, through to Dec 31, 2017 and recruitment took place from Nov 2, 2011, until May 17, 2017. At baseline we enrolled 8278 participants, of whom 2899 (35%) were randomly allocated to arm 1, 2741 (33%) to arm 2, and 2638 (32%) to arm 3. 120 (4·2%) of 2853 in arm 1, 209 (7·8%) of 2688 in arm 2, and 167 (6·4%) of 2613 in arm 3 had S haematobium infections at baseline. Heavy infections (≥50 eggs per 10 mL of urine) were found in 126 (1·6%) of 8073 children at baseline. At the 5-year endline survey, 46 (1·4%) of 3184 in arm 1, 56 (1·7%) of 3217 (odds ratio [OR] 1·2 [95% CI 0·6-2·7] vs arm 1) in arm 2, and 58 (1·9%) of 3080 (1·3 [0·6-2·9]) in arm 3 had S haematobium infections. Heavy infections were detected in 33 (0·3%) of 9462 children. INTERPRETATION: Biannual MDA substantially reduced the S haematobium prevalence and infection intensity but was insufficient to interrupt transmission. Although snail control or behaviour change activities did not significantly boost the effect of MDA in our study, they might enhance interruption of transmission when tailored to focal endemicity and applied for a longer period. It is now necessary to focus on reducing prevalence in remaining hotspot areas and to introduce new methods of surveillance and public health response so that the important gains can be maintained and advanced. FUNDING: University of Georgia Research Foundation Inc and Bill & Melinda Gates Foundation.

Supplementation with micronutrients and schistosomiasis: systematic review and meta-analysis.

Schistosomiasis is a parasitic disease caused by helminths of the genus Schistosoma with two presentations; one intestinal and another urinary; which depend on the specie of Schistosoma. One of the species that can produce intestinal schistosomiasis is Schistosoma mansoni, and the specie that produces urinary schistosomiasis is Schistosoma haematobium. Infection can be aggravated by a deficient nutritional status, which negatively impacts the immune system and increases susceptibility to infection. The main objective of this meta-analysis is to determine if a relationship exists between multimicronutrient supplementation and the reduction of infestation with Schistosoma mansoni and Schistosoma haematobium in children and adolescents. A search was conducted through a scientific literature database, and articles that complied with the pre-established requirements were retrieved. The Review Manager (Rev Man) 5.3 computer program was used for data processing and analysis was carried out with the objective of testing whether the addition of micronutrient supplementation to treatment with broad-spectrum antiparasitic anthelmintic medication has an impact on schistosomiasis infection. Of the 257 initial articles retrieved, eight were included both quantitatively and qualitatively in the meta-analysis. Supplementation reduces infestation with Schistosoma spp 1.33 times more than placebo. In individuals infested with Schistosoma, mansoni supplementation is 1.30 times more effective than placebo and for individuals infested with Schistosoma haematobium, supplementation is 1.62 times more effective than the placebo. The results show a clear relationship between supplementation and reduction of infestation. The supplementation with micronutrients decreases the presence of Schistosoma spp in children and adolescents.

Interrupting seasonal transmission of Schistosoma haematobium and control of soil-transmitted helminthiasis in northern and central Côte d'Ivoire: a SCORE study protocol.

BACKGROUND: To achieve a world free of schistosomiasis, the objective is to scale up control and elimination efforts in all endemic countries. Where interruption of transmission is considered feasible, countries are encouraged to implement a comprehensive intervention package, including preventive chemotherapy, information, education and communication (IEC), water, sanitation and hygiene (WASH), and snail control. In northern and central Côte d'Ivoire, transmission of Schistosoma haematobium is seasonal and elimination might be achieved. In a cluster-randomised trial, we will assess different treatment schemes to interrupt S. haematobium transmission and control soil-transmitted helminthiasis over a 3-year period. We will compare the impact of (i) arm A: annual mass drug administration (MDA) with praziquantel and albendazole before the peak schistosomiasis transmission season; (ii) arm B: annual MDA after the peak schistosomiasis transmission season; (iii) arm C: two yearly treatments before and after peak schistosomiasis transmission; and (iv) arm D: annual MDA before peak schistosomiasis transmission, coupled with chemical snail control using niclosamide. METHODS/DESIGN: The prevalence and intensity of S. haematobium and soil-transmitted helminth infections will be assessed using urine filtration and Kato-Katz thick smears, respectively, in six administrative regions in northern and central parts of Côte d'Ivoire. Once a year, urine and stool samples will be collected and examined from 50 children aged 5-8 years, 100 children aged 9-12 years and 50 adults aged 20-55 years in each of 60 selected villages. Changes in S. haematobium and soil-transmitted helminth prevalence and intensity will be assessed between years and stratified by intervention arm. In the 15 villages randomly assigned to intervention arm D, intermediate host snails will be collected three times per year, before niclosamide is applied to the selected freshwater bodies. The snail abundance and infection rates over time will allow drawing inference on the force of transmission. DISCUSSION: This cluster-randomised intervention trial will elucidate whether in an area with seasonal transmission, the four different treatment schemes can interrupt S. haematobium transmission and control soil-transmitted helminthiasis. Lessons learned will help to guide schistosomiasis control and elimination programmes elsewhere in Africa. TRIAL REGISTRATION: ISRCTN ISRCTN10926858 . Registered 21 December 2016. Retrospectively registered.

Rational selection of immunodominant and preserved epitope Sm043300e from Schistosoma mansoni and design of a chimeric molecule for biotechnological purposes.

Human schistosomiasis is a neglected tropical disease of great importance in public health. A large number of people are infected with schistosomiasis, making vaccine development and effective diagnosis important control strategies. A rational epitope prediction workflow using Schistosoma mansoni hypothetical proteins was previously presented by our group, and an improvement to that approach is presented here. Briefly, immunodominant epitopes from parasite membrane proteins were predicted by reverse vaccinology strategy with additional in silico analysis. Furthermore, epitope recognition was evaluated using sera of individuals infected with S. mansoni. The epitope that stood out in both in silico and in vitro assays was used to compose a rational chimeric molecule to improve immune response activation. Out of 2185 transmembrane proteins, four epitopes with high binding affinities for human and mouse MHCII molecules were selected through computational screening. These epitopes were synthesized to evaluate their ability to induce TCD4+ lymphocyte proliferation in mice. Sm204830e and Sm043300e induced significant TCD4+ proliferation. Both epitopes were submitted to enzyme-linked immunosorbent assay to evaluate their recognition by IgG antibodies from the sera of infected individuals, and epitope Sm043300 was significantly recognized in most sera samples. Epitope Sm043300 also showed good affinity for human MHCII molecules in molecular docking, and its sequence is curiously highly conserved in four S. mansoni proteins, all of which are described as G-protein-coupled receptors. In addition, we have demonstrated the feasibility of incorporating this epitope, which showed low similarity to human sequences, into a chimeric molecule. The stability of the molecule was evaluated by molecular modeling aimed at future molecule production for use in diagnosis and vaccination trials.

[Current status of schistosomiasis in Santchou health area, (Santchou Health District, Cameroon western region)]. / Situation actuelle de la schistosomiase dans l'aire de santé de Santchou, (District de santé de Santchou, Région de l'Ouest-Cameroun).

INTRODUCTION: Schistosomiasis, the second endemic parasitic infection in the world, is a parasitosis caused by trematodes from the genus Schistosoma. Our study aims to assess the prevalence of different species of schistosomes (Schistosoma mansoni, haematobium and intercalatum) among schoolchildren and to identify risk factors, clinical signs of schistosomiasis, and schistosomiasis intermediate host snails in stagnant water. METHODS: We conducted a cross sectional study over a three months period. The study consisted of sociodemographic and clinical data recording, collection of stool samples and urine, molluscan research and treatment of positive students for other helminths. Laboratory tests were performed at the Medical Research Institute and the study of Medicinal Plants in Yaounde where stool samples and urine were examined using KATO KATZ and centrifugation technique respectively, and shellfish species were determined by a malacologist. RESULTS: A total of 400 students aged between 8-16 years, 223 (55.7%) girls and 177 (44.3%) boys attending 4 elementary school were enrolled in the study. The social survey revealed that 154 students out of 400 (or 38.5%) were in contact with the river water at least once a week, 58% from around noon. All students had at least one symptom of schistosomiasis although nonspecific and dominated by abdominal pain in 72% of cases (n = 288 of 400). Biologically, no schistosomiasis eggs were detected. Cercaria releasing rate was negative in the 100 watery species found. CONCLUSION: The Santchou health area is not an active outbreak of schistosomiasis, but remains a risk area because of rice cultivation and stagnant water. The intensification of health education campaigns among the general population would delay the onset of this infection in the locality.

Acute anuria after a family vacation to Corsica/France.

A 12-year-old male patient suffered hematuria. Histopathology of a biopsy showed granulomata suspicious for schistosomiasis. The patient had never travelled outside Europe during his entire lifetime. He had taken frequent bathes in various rivers during his last family holidays 5 months earlier in Corsica. Microfiltration of urine revealed viable ova of Schistosoma haematobium with alterated size and shape. Ultrasonography showed a large focal echopoor mass attached to the bladder roof. Four days after antihelminthic therapy, the patient suffered inferior abdominal pain and acute anuria. Ultrasound revealed an approximately 5-cm mass in the bladder lumen suspicious for a large blood clot. After taking non-invasive measures such as drinking high amounts of fluid and treating the lower abdomen with a warm water bag and massage, the clot was excreted with urine and symptoms subsided. The further course was uneventful until 11 months later when hematuria recurred. This time, parasitological urine examination confirmed non-viable schistosome ova. Hematuria was likely due to erosion of the bladder mucosa by calcified non-viable ova.

Schistosoma haematobium and soil-transmitted Helminths in Tana Delta District of Kenya: infection and morbidity patterns in primary schoolchildren from two isolated villages.

BACKGROUND: Schistosomes and soil-transmitted helminths (STH) (hookworm, Trichuris trichiura and Ascaris lumbricoides) are widely distributed in developing countries where they infect over 230 million and 1.5 billion people, respectively. The parasites are frequently co-endemic and many individuals are co-infected with two or more of the species, but information on how the parasites interact in co-infected individuals is scarce. The present study assessed Schistosoma haematobium and STH infection and morbidity patterns among school children in a hyper-endemic focus in the Tana River delta of coastal Kenya. METHODS: Two hundred and sixty-two children aged 5-12 years from two primary schools were enrolled in the study. For each child, urine was examined for S. haematobium eggs and haematuria, stool was examined for STH eggs, peripheral blood was examined for eosinophilia and haemoglobin level, the urinary tract was ultrasound-examined for S. haematobium-related pathology, and the height and weight was measured and used to calculate the body mass index (BMI). RESULTS: Prevalences of S. haematobium, hookworm, T. trichiura and A. lumbricoides infection were 94, 81, 88 and 46 %, respectively. There was no significant association between S. haematobium and STH infection but intensity of hookworm infection significantly increased with that of T. trichiura. Lower BMI scores were associated with high intensity of S. haematobium (difference =-0.48, p > 0.05) and A. lumbricoides (difference =-0.67, p < 0.05). Haematuria (both macro and micro) was common and associated with S. haematobium infection, while anaemia was associated with high intensity of S. haematobium (OR = 2.08, p < 0.05) and high hookworm infections OR = 4.75; p < 0.001). The majority of children had eosinophilia, which was significantly associated with high intensity of hookworm infection (OR = 5.34, p < 0.05). Overall 38 % of the children had ultrasound-detectable urinary tract morbidity, which was associated with high intensity of S. haematobium infection (OR = 3.13, p < 0.05). CONCLUSION: Prevalences of S. haematobium and STH infections among the primary school children were high and the parasites were responsible for significant morbidity. A clear synergistic interaction was observed between hookworm and T. trichiura infections. Increased coverage in administration of praziquantel and albendazole in the area is recommended to control morbidity due to these infections.

Schistosomiasis in school-age children in Burkina Faso after a decade of preventive chemotherapy.

OBJECTIVE: To assess the impact of a decade of biennial mass administration of praziquantel on schistosomiasis in school-age children in Burkina Faso. METHODS: In 2013, in a national assessment based on 22 sentinel sites, 3514 school children aged 7-11 years were checked for Schistosoma haematobium and Schistosoma mansoni infection by the examination of urine and stool samples, respectively. We analysed the observed prevalence and intensity of infections and compared these with the relevant results of earlier surveys in Burkina Faso. FINDINGS: S. haematobium was detected in 287/3514 school children (adjusted prevalence: 8.76%, range across sentinel sites: 0.0-56.3%; median: 2.5%). The prevalence of S. haematobium infection was higher in the children from the Centre-Est, Est and Sahel regions than in those from Burkina Faso's other eight regions with sentinel sites (P < 0.001). The adjusted arithmetic mean intensity of S. haematobium infection, among all children, was 6.0 eggs per 10 ml urine. Less than 1% of the children in six regions had heavy S. haematobium infections - i.e. at least 50 eggs per 10 ml urine - but such infections were detected in 8.75% (28/320) and 11.56% (37/320) of the children from the Centre-Est and Sahel regions, respectively. Schistosoma mansoni was only detected in two regions and 43 children - i.e. 1 (0.31%) of the 320 from Centre-Sud and 42 (8.75%) of the 480 from Hauts Bassins. CONCLUSION: By mass use of preventive chemotherapy, Burkina Faso may have eliminated schistosomiasis as a public health problem in eight regions and controlled schistosome-related morbidity in another three regions.

[Removal of weremit from the abdomen. Interpretation and efficacy of an ancient Egyptian prescription by the newest scientific results]. / A weremit kiuzése a hasból. Óegyiptomi recept hatásosságának értelmezése az újabb kutatási eredmények alapján.

Significant percentage of today's knowledge of ancient Egyptian medicine has been acquired from papyri left behind from various periods of Egyptian history. The longest and the most comprehensive is the Ebers papyrus, kept at the University Museum of Leipzig, which was written more than one thousand years before Hippocrates (c. 460-377 BC). One of the riddles among the prescriptions of the Ebers papyrus Eb20 has been used in order to remove the so called "wemyt" weremit from the abdomen with the help of a drink, which consists of "jnnk", Conyza dioscoridis in milk or sweet beer. The authors assume that the disease could be an infection of Schistosoma haematobium and/or Schistosoma mansoni. Nowadays the tea of Conyza dioscoridis is widely used as an important part of traditional medicine against rheumatism, intestinal distention and cramps, as well as an antiperspirant, and with external use for wound healing. The authors' intent is to interpret the efficacy of the above-mentioned ancient prescription with the help of modern medical and pharmaceutical knowledge.

Study and implementation of urogenital schistosomiasis elimination in Zanzibar (Unguja and Pemba islands) using an integrated multidisciplinary approach.

BACKGROUND: Schistosomiasis is a parasitic infection that continues to be a major public health problem in many developing countries being responsible for an estimated burden of at least 1.4 million disability-adjusted life years (DALYs) in Africa alone. Importantly, morbidity due to schistosomiasis has been greatly reduced in some parts of the world, including Zanzibar. The Zanzibar government is now committed to eliminate urogenital schistosomiasis. Over the next 3-5 years, the whole at-risk population will be administered praziquantel (40 mg/kg) biannually. Additionally, snail control and behaviour change interventions will be implemented in selected communities and the outcomes and impact measured in a randomized intervention trial. METHODS/DESIGN: In this 5-year research study, on both Unguja and Pemba islands, urogenital schistosomiasis will be assessed in 45 communities with urine filtration and reagent strips in 4,500 schoolchildren aged 9-12 years annually, and in 4,500 first-year schoolchildren and 2,250 adults in years 1 and 5. Additionally, from first-year schoolchildren, a finger-prick blood sample will be collected and examined for Schistosoma haematobium infection biomarkers. Changes in prevalence and infection intensity will be assessed annually. Among the 45 communities, 15 were randomized for biannual snail control with niclosamide, in concordance with preventive chemotherapy campaigns. The reduction of Bulinus globosus snail populations and S. haematobium-infected snails will be investigated. In 15 other communities, interventions triggering behaviour change have been designed and will be implemented in collaboration with the community. A change in knowledge, attitudes and practices will be assessed annually through focus group discussions and in-depth interviews with schoolchildren, teachers, parents and community leaders. In all 45 communities, changes in the health system, water and sanitation infrastructure will be annually tracked by standardized questionnaire-interviews with community leaders. Additional issues potentially impacting on study outcomes and all incurring costs will be recordedand monitored longitudinally. DISCUSSION: Elimination of schistosomiasis has become a priority on the agenda of the Zanzibar government and the international community. Our study will contribute to identifying what, in addition to preventive chemotherapy, needs to be done to prevent, control, and ultimately eliminate schistosomiasis, and to draw lessons for current and future schistosomiasis elimination programmes in Africa and elsewhere. TRIAL REGISTRATION: ISRCTN48837681.

Development of an in vitro drug screening assay using Schistosoma haematobium schistosomula.

BACKGROUND: The development of novel antischistosomal drugs is crucial, as currently no vaccine and only a single drug is available for the treatment of schistosomiasis. Fast and accurate in vitro assays are urgently needed to identify new drug candidates and research efforts should include Schistosoma haematobium. The aim of the present study was to develop a S. haematobium drug sensitivity assay based on newly transformed schistosomula (NTS). METHODS: We first undertook comparative studies on the cercarial emergence rhythms of the intermediate host snails Biomphalaria glabrata (S. mansoni) and Bulinus truncatus (S. haematobium). Two transformation methods as well as three purification methods were studied on S. haematobium cercariae in order to produce a large number of viable and clean NTS. Known antischistosomal drugs were tested in the established NTS assay in vitro. Drug effects were evaluated either microscopically or fluorometrically, using a resazurin based viability marker. Microscopically obtained IC50 values were compared with results obtained for S. mansoni. RESULTS: A circadian rhythm existed in both snail species. Infected B. truncatus snails shed less cercariae than B. glabrata during the testing period. The highest transformation rate (69%) of S. haematobium cercariae into NTS was obtained with the vortex transformation (mechanical input) and the highest purification factor was observed using Percoll®. The fluorimetric readout based on resazurin was very precise in detecting dead or/and severely damaged schistosomula. CONCLUSIONS: With the use of viability markers such as resazurin, drug screening assays using S. haematobium NTS can be efficiently performed. However, drugs acting on the morphology and motility of S. haematobium NTS, such as metrifonate are missed. Drug sensitivity assays with NTS of both species, S. haematobium and S. mansoni, showed very similar results using known antischistosomal drugs. The S. mansoni NTS assay might be more suitable as primary screen in drug discovery efforts, which ultimately aim for a broad-spectrum antischistosomal drug as a larger number of S. mansoni NTS can be generated.

Efficacy and mechanism of action of arachidonic acid in the treatment of hamsters infected with Schistosoma mansoni or Schistosoma haematobium.

We have recently shown that in vitro and in vivo exposure of Schistosoma mansoni and Schistosoma haematobium to 5-10mM arachidonic acid (ARA) induces parasite surface membrane disintegration and eventual attrition. Here we report on the optimum ARA dose and post-infection treatment time for maximum schistosome demise in hamsters. A series of four experiments for each schistosome species indicated that oral administration of ARA after patency led to a highly significant (P<0.02 to <0.001) reduction in worm burden accompanied by a significant (P<0.05) decrease in worm egg load. ARA-mediated attrition in vivo appeared to be associated with high titres of serum antibodies to tegumental antigens. In support, serum antibodies from patently infected and ARA-treated hamsters readily bound to the surface membrane of ARA-exposed adult worms, as judged by indirect membrane immunofluorescence. More importantly, addition of serum antibodies and peripheral blood mononuclear cells significantly enhanced ARA-mediated adult worm attrition in vitro. These data together show that the schistosomicidal effect of ARA in laboratory animals is enhanced by immune effectors and is highly efficacious and entirely safe.