Antischistosomal Treatment Research Articles

A soap to fight schistosomiasis: a field intervention worth considering?

An experiment was carried out in 1985-87 against schistosomiasis using products neutralizing the intermediate stages of schistosomes. In the laboratory, it had been shown that lauryl betaines, amphoteric substances, used for children's shampoos, quickly immobilized miracidiums and cercariae. Studies in Niger in field conditions with water laden with organic matter gave similar results. This surfactant can be incorporated into ordinary soaps at a dose of 5% without changing their characteristics. Betaine soaps were put on sale in ordinary commercial channels in Niger then in Côte d'Ivoire, in hyperendemic villages for Schistosoma haematobium. Betaines diffused without external intervention into the water used by populations for washing. The soaps were well accepted by these populations. However, after one year, the results in tested villages compared to control ones were unclear on the dynamics of urinary schistosomiasis in terms of prevalence and oviuria. Anti-schistosome treatment seems necessary at the start of the procedure. The use of soap by populations needed to be measured. In conclusion, this promising laboratory action deserves to be evaluated again in the field, in addition to health education and systematic treatment actions.

Predictors for participation in mass-treatment and female genital schistosomiasis re-investigation, and the effect of praziquantel treatment in South African adolescents.

Female Genital Schistosomiasis (FGS) causes intravaginal lesions and symptoms that could be mistaken for sexually transmitted diseases or cancer. In adults, FGS lesions [grainy sandy patches (GSP), homogenous yellow patches (HYP), abnormal blood vessels and rubbery papules] are refractory to treatment. The effect of treatment has never been explored in young women; it is unclear if gynaecological investigation will be possible in this young age group (16-23 years). We explored the predictors for accepting anti-schistosomal treatment and/or gynaecological reinvestigation in young women, and the effects of anti-schistosomal mass-treatment (praziquantel) on the clinical manifestations of FGS at an adolescent age. The study was conducted between 2011 and 2013 in randomly selected, rural, high schools in Ilembe, uThungulu and Ugu Districts, KwaZulu-Natal Province, East Coast of South Africa. At baseline, gynaecological investigations were conducted in female learners in grades 8 to 12, aged 16-23 years (n = 2293). Mass-treatment was offered in the low-transmission season between May and August (a few in September, n = 48), in accordance with WHO recommendations. Reinvestigation was offered after a median of 9 months (range 5-14 months). Univariate, multivariable and logistic regression analysis were used to measure the association between variables. Prevalence: Of the 2293 learners who came for baseline gynaecological investigations, 1045 (46%) had FGS lesions and/or schistosomiasis, 209/1045 (20%) had GSP; 208/1045 (20%) HYP; 772/1045 (74%) had abnormal blood vessels; and 404/1045 (39%) were urine positive. Overall participation rate for mass treatment and gynaecological investigation: Only 26% (587/2293) learners participated in the mass treatment and 17% (401/2293) participated in the follow up gynaecological reinvestigations. Loss to follow-up among those with FGS: More than 70% of learners with FGS lesions at baseline were lost to follow-up for gynaecological investigations: 156/209 (75%) GSP; 154/208 (74%) HYP; 539/722 (75%) abnormal blood vessels; 238/404 (59%) urine positive. The grade 12 pupil had left school and did not participate in the reinvestigations (n = 375; 16%). Follow-up findings: Amongst those with lesions who came for both treatment and reinvestigation, 12/19 still had GSP, 8/28 had HYP, and 54/90 had abnormal blood vessels. Only 3/55 remained positive for S. haematobium ova. Factors influencing treatment and follow-up gynaecological investigation: HIV, current water contact, water contact as a toddler and urinary schistosomiasis influenced participation in mass treatment. Grainy sandy patches, abnormal blood vessels, HYP, previous pregnancy, current water contact, water contact as a toddler and father present in the family were strongly associated with coming back for follow-up gynaecological investigation. Challenges in sample size for follow-up analysis of the effect of treatment: The low mass treatment uptake and loss to follow up among those who had baseline FGS reduced the chances of a larger sample size at follow up investigation. However, multivariable analysis showed that treatment had effect on the abnormal blood vessels (adjusted odds ratio = 2.1, 95% CI 1.1-3.9 and p = 0.018). Compliance to treatment and gynaecological reinvestigation was very low. There is need to embark on large scale awareness and advocacy in schools and communities before implementing mass-treatment and investigation studies. Despite challenges in sample size and significant loss to follow-up, limiting the ability to fully understand the treatment's effect, multivariable analysis demonstrated a significant treatment effect on abnormal blood vessels.

Colonic High-grade Tubular Adenoma Associated withSchistosoma sp.

Abstract Introduction/Objective Although not endemic in the United States, Schistosoma infection can be encountered in clinical samples from patients that have been in endemic regions and can present a challenge to the pathologist. Usually, intestinal schistosomiasis present with a granulomatous inflammatory reaction surrounding the eggs. Schistosome eggs can be found throughout the lamina propria, mucosa, and or submucosa of the intestinal wall. Methods/Case Report We present a 79-year-old Asian male, with history of chronic constipation. He was previously diagnosed with schistosomiasis 11 years ago. He received antischistosomal treatment, however, no further tests were done to confirm parasite eradication. Initial endoscopic examination of the colorectum demonstrated two polyps: the first was 2 cm in diameter, located 10 cm proximal from the anal verge, while the second was 2cm in diameter, located 20cm proximal to the anal verge. A biopsy of the first polyp showed a tubular adenoma while the second polyp was hyperplastic showing few calcified schistosome eggs in the submuscosa. Eight days later, a second endoscopy was performed to resect the entirety of the first polyp. Microscopy examination showed sessile tubular adenoma with high grade dysplasia. In addition, there was abundant calcified 50-75 micrometer ova of Schistosoma sp., occupying the submucosa beneath the adenoma without associated inflammation. Results (if a Case Study enter NA) NA. Conclusion To our knowledge, there are a few case reports describing colonic Schistosoma eggs without inflammation in the presence of tubular adenoma. Our case report adds to the sparse literature that can aid in identifying associations in the future.

A descriptive qualitative case study of the experiences, perceptions and attitudes of pregnant women on Unguja island, Zanzibar, towards antischistosomal treatment

Many countries exclude pregnant and lactating women from mass drug administration (MDA) programmes with praziquantel against schistosomiasis due to historic safety concerns over drug use during gestation and breast feeding. More than 10 years of empirical evidence from the field and a growing body of dedicated research has prompted the World Health Organisation and schistosomiasis control initiatives to advocate the inclusion of this vulnerable group into MDA. This qualitative descriptive case study explored, over a five-week period, the subjective experiences, perceptions, opinions, and attitudes of pregnant women attending government supported clinics on Unguja island, United Republic of Tanzania, towards praziquantel use during pregnancy in MDA programmes. The aim of the study was to identify and determine how to overcome potential barriers to effective use of MDA medications during pregnancy. Additionally, it was to determine trusted communication channels for future messaging and discover behavioural and community opportunities to increase participation of pregnant women in future MDA efforts. A 60 min, semi-structured qualitative interview was undertaken with 25 pregnant women recruited from 4 health centres on Unguja along with testing for Schistosoma haematobium infection. Using a modified-grounded theory approach, narrative data were transcribed, coded and analysed using a thematic analysis of the emergent themes. Women reported that they rely on traditional home remedies to stay healthy during pregnancy. Influenced by their mothers, husbands and neighbours, women predominately made medication choices during pregnancy and breastfeeding based on what they heard at home. Most women had been excluded from government MDA programmes in the past due to pregnancy. Women valued healthcare services for antenatal education and pregnancy advice. Women reported they would trust and follow direction from healthcare providers about taking praziquantel during pregnancy. Antenatal clinics offer an excellent opportunity to educate and expand praziquantel treatment to this cohort. Efforts should be augmented with training for providers and behavioural education for the community as a whole and family members of pregnant women.

Schistosome infection promotes osteoclast-mediated bone loss.

Infection with schistosome results in immunological changes that might influence the skeletal system by inducing immunological states affecting bone metabolism. We investigated the relationships between chronic schistosome infection and bone metabolism by using a mouse model of chronic schistosomiasis, affecting millions of humans worldwide. Results showed that schistosome infection resulted in aberrant osteoclast-mediated bone loss, which was accompanied with an increased level of receptor activator of nuclear factor-κB (NF-κB) Ligand (RANKL) and decreased level of osteoprotegerin (OPG). The blockade of RANKL by the anti-RANKL antibody could prevent bone loss in the context of schistosome infection. Meanwhile, both B cells and CD4+ T cells, particularly follicular helper T (Tfh) cell subset, were the important cellular sources of RANKL during schistosome infection. These results highlight the risk of bone loss in schistosome-infected patients and the potential benefit of coupling bone therapy with anti-schistosome treatment.

Single oral fixed-dose praziquantel-miltefosine nanocombination for effective control of experimental schistosomiasis mansoni

BackgroundThe control of schistosomiasis has been centered to date on a single drug, praziquantel, with shortcomings including treatment failure, reinfection, and emergence of drug resistance. Drug repurposing, combination therapy or nanotechnology were explored to improve antischistosomal treatment. The aim of the present study was to utilize a novel combination of the three strategies to improve the therapeutic profile of praziquantel. This was based on a fixed-dose nanocombination of praziquantel and miltefosine, an antischistosomal repurposing candidate, co-loaded at reduced doses into lipid nanocapsules, for single dose oral therapy.MethodsTwo nanocombinations were prepared to provide 250 mg praziquantel-20 mg miltefosine/kg (higher fixed-dose) or 125 mg praziquantel-10 mg miltefosine/kg (lower fixed-dose), respectively. Their antischistosomal efficacy in comparison with a non-treated control and their praziquantel or miltefosine singly loaded counterparts was assessed in murine schistosomiasis mansoni. A single oral dose of either formulation was administered on the initial day of infection, and on days 21 and 42 post-infection. Scanning electron microscopic, parasitological, and histopathological studies were used for assessment. Preclinical data were subjected to analysis of variance and Tukeyʼs post-hoc test for pairwise comparisons.ResultsLipid nanocapsules (~ 58 nm) showed high entrapment efficiency of both drugs (> 97%). Compared to singly loaded praziquantel-lipid nanocapsules, the higher nanocombination dose showed a significant increase in antischistosomal efficacy in terms of statistically significant decrease in mean worm burden, particularly against invasive and juvenile worms, and amelioration of hepatic granulomas (P ≤ 0.05). In addition, scanning electron microscopy examination showed extensive dorsal tegumental damage with noticeable deposition of nanostructures.ConclusionsThe therapeutic profile of praziquantel could be improved by a novel multiple approach integrating drug repurposing, combination therapy and nanotechnology. Multistage activity and amelioration of liver pathology could be achieved by a new praziquantel-miltefosine fixed-dose nanocombination providing 250 mg praziquantel-20 mg miltefosine/kg. To the best of our knowledge, this is the first report of a fixed-dose nano-based combinatorial therapy for schistosomiasis mansoni. Further studies are needed to document the nanocombination safety and explore its prophylactic activity and potential to hinder the onset of resistance to the drug components.

HCV and HEV: two players in an Egyptian village, a study of prevalence, incidence, and co-infection.

The highest recorded hepatitis C virus (HCV) prevalence worldwide is in Egypt. A high prevalence of hepatitis E virus (HEV) in chronic liver disease has been reported. The aim of this study was to study prevalence, incidence, and outcome of HCV infection in an Egyptian Nile Delta village and the relation between HEV infection and HCV-related chronic hepatic affection. This prospective cohort study included 2085 Nagreej village residents. Mass HCV screening was conducted and testing for HEV antibodies among HCV-infected patients performed. The annual incidence of HCV was recorded. Five hundred five (24.22%) of the tested villagers were positive for HCV RNA. Prevalence escalated with age and male sex. The main recorded risk factors were a history of surgery, dental procedures, hospitalization, blood transfusion, and antischistosomal treatment. HEV IgG antibody was positive in 71.4% of individuals with chronic HCV and 96.1% with advanced liver disease (cirrhosis ± hepatocellular carcinoma (HCC)). After 1 year, 29 of the 1390 HCV Ab negative villagers had a positive HCV PCR, placing an annual incidence of new HCV infections at 2.09%. The Egyptian HCV prevalence remains high with infection particularly among the elderly. The annual incidence in a small Nile Delta village is 2.086%. HCV-HEV co-infection may lead to a worse prognosis among Egyptians with chronic liver disease.Electronic supplementary materialThe online version of this article (10.1007/s11356-020-09591-6) contains supplementary material, which is available to authorized users.

Molecular basis for hycanthone drug action in schistosome parasites

Hycanthone (HYC) is a retired drug formerly used to treat schistosomiasis caused by infection from Schistosoma mansoni and S. haematobium. Resistance to HYC was first observed in S. mansoni laboratory strains and in patients in the 1970s and the use of this drug was subsequently discontinued with the substitution of praziquantel (PZQ) as the single antischistosomal drug in the worldwide formulary. In endemic regions, multiple organizations have partnered with the World Health Organization to deliver PZQ for morbidity control and prevention. While the monotherapy reduces the disease burden, additional drugs are needed to use in combination with PZQ to stay ahead of potential drug resistance. HYC will not be reintroduced into the schistosomiasis drug formulary as a combination drug because it was shown to have adverse properties including mutagenic, teratogenic and carcinogenic activities. Oxamniquine (OXA) was used to treat S. mansoni infection in Brazil during the brief period of HYC use, until the 1990s. Its antischistosomal efficacy has been shown to work through the same mechanism as HYC and it does not possess the undesirable properties linked to HYC. OXA demonstrates cross-resistance in Schistosoma strains with HYC resistance and both are prodrugs requiring metabolic activation in the worm to toxic sulfated forms. The target activating enzyme has been identified as a sulfotransferase enzyme and is currently used as the basis for a structure-guided drug design program. Here, we characterize the sulfotransferases from S. mansoni and S. haematobium in complexes with HYC to compare and contrast with OXA-bound sulfotransferase crystal structures. Although HYC is discontinued for antischistosomal treatment, it can serve as a resource for design of derivative compounds without contraindication.

Insufficiency of annual praziquantel treatment to control Schistosoma mansoni infections in adult women: Alongitudinal cohort study in rural Tanzania.

BackgroundCurrent World Health Organization (WHO) guidelines recommend annual mass drug administration using praziquantel in areas with high schistosome endemicity. Yet little is known about incidence and reinfection rates after treatment in women with frequent exposure to schistosomes. We sought to quantify response to anti-schistosome treatment and incident S. mansoni infections in a cohort of rural women living in a schistosome-endemic area of northwest Tanzania.Methods and principal findingsWe enrolled women with and without S. mansoni infection into a 12-month longitudinal cohort. Every 3 months, women were tested for schistosome infection using microscopic examinations for ova on filtered urine, Kato Katz slides, and serum Circulating Anodic Antigen (CAA). Those with schistosome infection received treatment with praziquantel 40 mg/kg according to the standard of care.We studied 35 women who were S. mansoni positive by stool microscopy and 46 women without schistosome infection who returned for at least one follow-up. Of the women who were initially infected, 14 (40%) were schistosome-positive at a follow-up visit. Four women developed incident infections, for a cumulative incidence of 8.7% and incidence rate of 0.99 per 100 person-months throughout the year among initially uninfected women. Only 3 women were egg-positive at any follow-up.Women with persistent, recurrent, or incident infection during the study period were significantly younger (p = 0.032) and had fewer children than women who remained uninfected or those who cleared the infection and did not experience recurrence (p = 0.003). Having fewer children remained significant after controlling for age (p = 0.023). There was no difference in initial intensity of infection by CAA or stool egg count, HIV status, or socioeconomic status. Although most water contact behaviors were comparable between the two groups, women with recurrent or incident schistosome infections were significantly more likely to have recently swum in the lake (p = 0.023).ConclusionsOur data suggests that annual praziquantel treatment reduces intensity of schistosome infections but is insufficient in providing stable parasite eradication in over a third of women in endemic communities. Furthermore, microscopy lacks adequate sensitivity to evaluate efficacy of treatment in this population. Our work demonstrates that further investigation into treatment efficacy and reinfection rates is warranted and suggests that increased frequency of praziquantel treatment is needed to improve cure rates in high-risk populations.

Reproductive health problems in rural South African young women: risk behaviour and risk factors

BackgroundSouth African young women continue to be vulnerable, with high prevalence of teenage pregnancy, HIV, sexually transmitted infections (STIs) and female genital schistosomiasis (FGS). This study seeks to examine the underlying factors that may be associated with these four adverse reproductive health outcomes.MethodsIn a cross-sectional study of 1413 sexually active of young women, we explored these four adverse reproductive health outcomes by considering socio-demographic factors, socio-economic factors, sexual risk behaviour, substance abuse and knowledge about reproductive health by using a questionnaire. Consenting participants were asked about previous pregnancies and were tested for HIV, STIs and FGS. Multivariable regression analyses were used to explore the factors associated with these four reproductive health outcomes.ResultsEarly pregnancy: Among the young women, 44.4% had already been pregnant at least once. Associated factors were hormonal contraceptives, (adjusted odds ratio (AOR): 17.94, 95% confidence interval (CI): 12.73–25.29), and sexual debut < 16 years (AOR: 3.83, 95% CI: 2.68–5.47). Living with both parents (AOR 0.37, 95% CI: 0.25–0.57) and having a steady partner (AOR: 0.43, 95% CI: 0.24–0.76) were identified as protective factors against pregnancy.HIV: HIV prevalence was 17.1%. The odds of having HIV were higher in intergenerational (AOR: 2.06, 95% CI: 1.05–4.06) and intragenerational relationships (AOR: 1.51 95% CI: 1.06–2.15), compared to age-homogenous relationships. Other associated factors were: condom use (AOR: 1.60, 95% CI: 1.16–2.20), number of times treated for an STI (AOR: 1.32, 95% CI: 1.02–1.71), and total number of partners (AOR: 1.14, 95% CI: 1.03–1.28).STIs: Participants who had at least one STI (40.5%) were associated with total partner number (AOR 1.17, 95% CI: 1.06–1.30), and testing HIV positive (AOR: 1.88, 95% CI 1.41–2.50).FGS: FGS prevalence (19.7%) was associated with previous anti-schistosomal treatment (AOR: 2.18, 95% CI: 1.57–3.05).ConclusionThere is a high prevalence of pregnancy, HIV, STIs and FGS among sexually active young women in rural KwaZulu-Natal. Multidisciplinary approaches are urgently needed for educational and health literacy programs prior to sexual debut, and health care facilities, which should be made accessible for young women.

Significance of selected biochemical markers in predicting the outcome of schistosomiasis

This study aimed to correlate the histopathological changes in mice liver with alterations either in liver tissue antioxidants enzymes (catalase and reduced glutathione (GSH)), oxidative stress marker (malondialdehyde (MDA)) or in serum liver function parameters (Alanine aminotransferase (ALT), aspartate aminotransferase (AST), total protein (T.P.) and albumin) to predict the outcome of schistosomiasis. Fourty male Swiss albino mice were used in this study and infected with Schistosoma mansoni for 2, 4, 6 and 8 weeks (8 mice for each group), while, the uninfected mice were used as negative control. Liver tissue antioxidants enzymes, oxidative stress marker and serum liver function parameters were determined in coincide with the liver tissue histopathological changes. All selected biochemical makers showed a strong significant positive correlation (p &lt; 0.05) with liver histopathology score except serum albumin and liver tissue catalase enzyme. The last two parameters exhibited negative correlation with liver histopathology score. These results revealed that the more increase in the level of AST, ALT, T.P. and globulin in serum or liver tissue MDA and GSH indicating severs histopathological changed into the affected liver and hopeless prognosis is expected. On contrary, the increase in albumin level in serum or catalase level in liver tissue of affected patient/animal demonstrating mild liver histopathological changes. Subsequently, good prognosis and response to anti-schistosomal treatment will be predictable. This study opens the way to predict the outcome of schistosomiasis through easy and rapid biochemical test. Therefore, other studies are required to apply such correlation with other biochemical parameters especially that synthesized into the liver.

Cross-sectional interview study of fertility, pregnancy, and urogenital schistosomiasis in coastal Kenya: Documented treatment in childhood is associated with reduced odds of subfertility among adult women.

BackgroundPrevious research has documented an increased risk of subfertility in areas of sub-Saharan Africa, as well as an ecological association between urogenital schistosomiasis prevalence and decreased fertility. This pilot project examined reproductive patterns and the potential effects of childhood urogenital Schistosoma haematobium infection and individual treatment experience on adult subfertility among women who were long-term residents in an S. haematobium-endemic region of coastal Kenya.Methodology/Principal findingsWe analyzed findings from 162 in-depth interviews with women of childbearing age in a rural, coastal community, linking them, if possible, to their individual treatment records from previous multi-year longitudinal studies of parasitic infections. Reproductive histories indicated a much local higher local rate of subfertility (44%) than worldwide averages (8–12%). Although, due to the very high regional prevalence of schistosomiasis, a clear relationship could not be demonstrated between a history of S. haematobium infection and adult subfertility, among a convenience sub-sample of 61 women who had received documented treatment during previous interventional trials, a significant association was found between age at first anti-schistosomal treatment and later fertility in adulthood, with those women treated before age 21 significantly less likely to have subfertility (P = 0.001).Conclusions/SignificanceThe high subfertility rate documented in this pilot study suggests the importance of programs to prevent and treat pelvic infections in their early stages to preclude reproductive tract damage. The available documented treatment data also suggest that early anti-schistosomal treatment may prevent the fertility-damaging effects of urogenital schistosomiasis, and lend support for programs that provide universal treatment of children in S. haematobium-endemic regions.

Immunohistochemical Investigations of Treatment with Ro 13-3978, Praziquantel, Oxamniquine, and Mefloquine in Schistosoma mansoni-Infected Mice.

To date, there is only one drug in use, praziquantel, to treat more than 250 million people afflicted with schistosomiasis, a debilitating parasitic disease. The aryl hydantoin Ro 13-3978 is a promising drug candidate with in vivo activity superior to that of praziquantel against both adult and juvenile Schistosoma mansoni organisms. Given the drug's contrasting low activity in vitro and the timing of its onset of action in vivo, it was postulated that immune-assisted parasite clearance could contribute to the drug's in vivo activity. We undertook histopathological studies to investigate this hypothesis. Infected mice were treated with an effective dose of Ro 13-3978 (100 mg/kg of body weight) and were dissected before and after the drug's in vivo onset of action. The veins and livers were excised, paraffin-embedded, and sectioned, and macrophages (IBA-1), neutrophils (Neutro), B cells (CD45R), and T cells (CD3) were stained by immunohistochemistry. For comparison, samples from infected untreated mice and mice treated with effective doses of praziquantel (400 mg/kg), oxamniquine (200 mg/kg), and mefloquine (200 mg/kg) were examined. At 24 h after treatment with Ro 13-3978, significant macrophage recruitment to the veins was observed, along with a modest increase in circulating B cells, and at 48 h, neutrophils and T cells are also present. Treatment with praziquantel and oxamniquine showed similar patterns of recruitment but with comparatively higher cellular levels, whereas mefloquine treatment resulted in minimal cell recruitment until 3 days posttreatment. Our study sheds light on the immediate immune responses to antischistosomal treatment in mice and provides further insight into immune effector mechanisms of schistosome clearance.

The burden, pattern and factors that contribute to periportal fibrosis in HIV-infected patients in an S. mansoni endemic rural Uganda.

Both Human Immunodeficiency Virus (HIV) and S.mansoni infections are common in Uganda and can cause liver disease. No study has determined co-infection significance in Uganda. We carried out a study on the burden, pattern and factors that contribute to peri-portal fibrosis (PPF) in HIV infected patients attending a Primary healthcare setting at Pakwach. We conducted a cross-sectional study in the HIV clinic at Pakwach health centre IV. Data on demographics, contact with the Nile, CD4+ cell count, ART and alcohol use were collected. Urinary Circulating Cathodic Antigen (CCA), was done for S. Mansoni detection. Liver scan was done for presence and pattern of PPF. HBsAg testing was performed on all participants. Data was analyzed using Stata Version 10. We enrolled 299 patients, median age 39 years (IQR 16), most were female, 210 (73%). Overall, 206 (68.9%) had PPF, majority 191 (92.7%) had pattern c, either alone (63 participants) or in combination with pattern d (128 participants). Age of 30-50 years was significantly associated with PPF (OR 2.28 p-value-0.003). We found high prevalence of S. mansoni and PPF in the HIV infected population and age was a significant factor for PPF. We recommend all HIV infected patients be examined routinely for S. mansoni infection for early anti-schistosomal treatment.

The Schistosomiasis Clinical Trials Landscape: A Systematic Review of Antischistosomal Treatment Efficacy Studies and a Case for Sharing Individual Participant-Level Data (IPD).

BackgroundSchistosomiasis control mainly relies on preventive chemotherapy with praziquantel (PZQ) distributed through mass drug administration. With a target of 260 million treatments yearly, reliably assessing and monitoring efficacy is all-important. Recommendations for treatment and control of schistosomiasis are supported by systematic reviews and meta-analyses of aggregated data, which however also point to limitations due to heterogeneity in trial design, analyses and reporting. Some such limitations could be corrected through access to individual participant-level data (IPD), which facilitates standardised analyses.MethodologyA systematic literature review was conducted to identify antischistosomal drug efficacy studies performed since 2000; including electronic searches of the Cochrane Infectious Diseases Group specialised register and the Cochrane Library, PubMed, CENTRAL and Embase; complemented with a manual search for articles listed in past reviews. Antischistosomal treatment studies with assessment of outcome within 60 days post-treatment were eligible. Meta-data, i.e. study-level characteristics (Schistosoma species, number of patients, drug administered, country, etc.) and efficacy parameters were extracted from published documents to evaluate the scope of an individual-level data sharing platform.Principal findingsOut of 914 documents screened, 90 studies from 26 countries were included, enrolling 20,517 participants infected with Schistosoma spp. and treated with different PZQ regimens or other drugs. Methodologies varied in terms of diagnostic approaches (number of samples and test repeats), time of outcome assessment, and outcome measure (cure rate or egg reduction rate, as an arithmetic or geometric mean), making direct comparison of published data difficult.ConclusionsThis review describes the landscape of schistosomiasis clinical research. The volume of data and the methodological and reporting heterogeneity identified all indicate that there is scope for an individual participant-level database, to allow for standardised analyses.

Epidemiology of Hepatitis C Virus Infection in Egypt

Hepatitis C virus constitutes an epidemic in Egypt having the highest prevalence in the world of 14.7%. The reasons behind this unique epidemic may be dated back to iatrogenic role of parenteral antischistosom al therapy campaigns to control endemic schistosomiasis. Other routes of infection are contributing to the ongoing HCV transmission. The prevalent genotype in Egypt is type 4 (73%), the origin, evolution, and dynamics are difficult to determine. Risk facto rs for acquiring HCV infection include: History of antischistosomal injection treatment before 1986, old age, male gender, and residence in rural areas. Other risk factors include; injection therapy, blood transfusion prior to 1994, exposure to various facility - based medical procedures, and occupational transmission among health care workers. In community settings, a set of risk factors, mostly related to prevailing social and cultural conditions, are responsible for maintaining the high rates of HCV tra nsmission. Chronic HCV is the main cause of liver cirrhosis and liver cancer in Egypt and, indeed, one of the top five leading causes of death. It kills an estimated 40,000 Egyptians a year. Mini - review Article

A comprehensive hepatitis C virus risk factors meta-analysis (1989-2013): do they differ in Egypt?

The prevention and control of HCV infection is complex and challenging in terms of describing risk factors and modes of transmission. This meta-analysis was conducted to summarize the best available data on HCV risk factors worldwide and in Egypt. Through exhaustive literature searches (1989-2013) of HCV risk factors, 357 original eligible articles were included in this study. The highest detected risk was intravenous drug users (IDUs) (OR = 9.6) followed by HIV infection (OR = 4.9), having an IDU partner (OR = 4.1), HBV infection (OR = 3.5), Caesarean section (CS) (OR = 3.35), blood transfusion (OR = 3.2) and having an HCV+ partner (OR = 3). Organ transplantation, hospital admission, haemodialysis and having a sexually transmitted infection carry 2.96, 2.4, 2.18 and 2 risks of having HCV respectively. Other significant risk factors included poor education, older age, sharing sharp or blunt objects, MSM, tattooing, hijama, body piercing, minor operations and medical procedures. Some risks showed a decrease over the previous decade, including blood transfusion, organ transplantation, IDUs, IDU partner and CS. Others showed rising risks, including having an HCV+ partner, MSM and suffering from STI. In Egypt, male gender, rural residence, acupuncture and receiving parenteral antischistosomal treatment were significant risks, while neither HIV nor HBV were found to carry a risk of HCV infection. Blood transfusion, organ transplantation, CS, IDUs, haemodialysis, minor operations and medical procedures are established risk factors. Attention and urgent intervention should be given to the sexual route of transmission, as well as that through minor operations and medical procedures.

Effect of female genital schistosomiasis and anti-schistosomal treatment on monocytes, CD4+ T-cells and CCR5 expression in the female genital tract.

Background Schistosoma haematobium is a waterborne parasite that may cause female genital schistosomiasis (FGS), characterized by genital mucosal lesions. There is clinical and epidemiological evidence for a relationship between FGS and HIV. We investigated the impact of FGS on HIV target cell density and expression of the HIV co-receptor CCR5 in blood and cervical cytobrush samples. Furthermore we evaluated the effect of anti-schistosomal treatment on these cell populations.DesignThe study followed a case-control design with post treatment follow-up, nested in an on-going field study on FGS.MethodsBlood and cervical cytobrush samples were collected from FGS negative and positive women for flow cytometry analyses. Urine samples were investigated for schistosome ova by microscopy and polymerase chain reaction (PCR).ResultsFGS was associated with a higher frequency of CD14+ cells (monocytes) in blood (11.5% in FGS+ vs. 2.2% in FGS-, p = 0.042). Frequencies of CD4+ cells expressing CCR5 were higher in blood samples from FGS+ than from FGS- women (4.7% vs. 1.5%, p = 0.018). The CD14+ cell population decreased significantly in both compartments after anti-schistosomal treatment (p = 0.043). Although the frequency of CD4+ cells did not change after treatment, frequencies of CCR5 expression by CD4+ cells decreased significantly in both compartments (from 3.4% to 0.5% in blood, p = 0.036; and from 42.4% to 5.6% in genital samples, p = 0.025).ConclusionsThe results support the hypothesis that FGS may increase the risk of HIV acquisition, not only through damage of the mucosal epithelial barrier, but also by affecting HIV target cell populations, and that anti-schistosomal treatment can modify this.

Oesophageal varices, schistosomiasis, and mortality among patients admitted with haematemesis in Mwanza, Tanzania: a prospective cohort study.

BackgroundUpper gastrointestinal bleeding (UGIB) is a common cause of hospital admissions worldwide. Aetiologies vary by sociodemographics and geography. Retrospective studies of endoscopies in much of Africa have documented oesophageal varices as a leading cause of UGIB. Prospective studies describing outcomes and associations with clinical factors are lacking.MethodsWe conducted a prospective cohort study at a referral hospital in Mwanza, Tanzania where schistosomiasis is endemic. Adults admitted with haematemesis underwent laboratory workup, schistosomiasis antigen testing and elective endoscopy, and were followed for two months for death or re-bleeding. We assessed predictors of endoscopic findings using logistic regression models, and determined prediction rules that maximised sensitivity and positive predictive value (PPV).ResultsOf 124 enrolled patients, 13 died within two months (10%); active schistosomiasis prevalence was 48%. 64/91(70%) patients had oesophageal varices. We found strong associations between varices and numerous demographic or clinical findings, permitting construction of simple, high-fidelity prediction rules for oesophageal varices applicable even in rural settings. Portal vein diameter ≥ 13 mm or water sourced from the lake yielded sensitivity, specificity, PPV and NPV > 90% for oesophageal varices; presence of splenomegaly or water sourced from the lake maintained sensitivity and PPV > 90%.ConclusionsOur results guide identification of patients, via ultrasound and clinical examination, likely to have varices for whom referral for endoscopy may be life-saving. Furthermore, they support empiric anti-schistosome treatment for patients with UGIB in schistosome-endemic regions. These interventions have potential to reduce UGIB-related morbidity and mortality in Africa.

Rapid diagnosis of schistosomiasis in Yemen using a simple questionnaire and urine reagent strips

Schistosomiasis ranks second to malaria in terms of socioeconomic and public health importance in Yemen. This study assessed the validity of a morbidity questionnaire and urine reagent strips as a rapid tool for screening schoolchildren for urinary schistosomiasis as compared with the presence of eggs in urine as the gold-standard parasitological diagnosis. The study examined urine samples and interviewed 696 children (mean age 12.5 years) attending a primary-preparatory school in south Yemen. Urinary schistosomiasis was confirmed in 126 (18.1%) children. Diagnostic performance was poor for 2 items in the morbidity questionnaire (self-reported history of previous infection and self-reported history of antischistosomal treatment). However, self-reported dysuria, self-reported haematuria in the questionnaire and microhaematuria by reagent strips (alone or with macrohaematuria) revealed good diagnostic performance. The results indicated that reagent strips are a valid method for detection of microhaematuria for identifying individuals and communities infected with Schistosoma haematobium.