The Association Between Female Genital Schistosomiasis and Other Infections of the Lower Genital Tract in Adolescent Girls and Young Women: A Cross-Sectional Study in South Africa.

OBJECTIVES/PURPOSES OF THE STUDY: This study aimed to explore the relationship between female genital schistosomiasis (FGS), sexually transmitted infections, bacterial vaginosis, and yeast among young women living in Schistosoma haematobium-endemic areas. METHODS: In a cross-sectional study of young women, sexually active, aged 16 to 22 years in rural KwaZulu-Natal, South Africa, in 32 randomly selected rural schools in schistosomiasis-endemic areas, the authors performed gynecological and laboratory investigations, diagnosed FGS and other infections, and did face-to-face interviews. RESULTS: Female genital schistosomiasis was the second most prevalent current genital infection (23%), significantly more common in those who had urinary schistosomiasis (35%), compared with those without (19%, p < .001). In the FGS-positive group, 35% had human papillomavirus compared with 24% in the FGS-negative group (p = .010). In the FGS-positive group, 37% were seropositive for herpes simplex virus infection, compared with 30% in the FGS-negative group (p = .079). There were significantly fewer chlamydia infections among women with FGS (20%, p = .018) compared with those who did not have FGS (28%). CONCLUSIONS: Female genital schistosomiasis was the second most common genital infection after herpes simplex virus. Human papillomavirus infection was significantly associated with FGS, but Chlamydia was negatively associated with FGS. Women with FGS may have had more frequent contact with the health system for genital discharge. The results show the importance of the inclusion of FGS in the national management protocols for genital infections in areas endemic for S. haematobium and highlight a more comprehensive approach to diagnosis and genital disease management.

Environmental DNA for improved detection and environmental surveillance of schistosomiasis.

Schistosomiasis is a water-based, infectious disease with high morbidity and significant economic burdens affecting >250 million people globally. Disease control has, with notable success, for decades focused on drug treatment of infected human populations, but a recent paradigm shift now entails moving from control to elimination. To achieve this ambitious goal, more sensitive diagnostic tools are needed to monitor progress toward transmission interruption in the environment, especially in low-intensity infection areas. We report on the development of an environmental DNA (eDNA)-based tool to efficiently detect DNA traces of the parasite Schistosoma mansoni directly in the aquatic environment, where the nonhuman part of the parasite life cycle occurs. This is a report of the successful detection of S. mansoni in freshwater samples by using aquatic eDNA. True eDNA was detected in as few as 10 cercariae per liter of water in laboratory experiments. The field applicability of the method was tested at known transmission sites in Kenya, where comparison of schistosome detection by conventional snail surveys (snail collection and cercariae shedding) with eDNA (water samples) showed 71% agreement between the methods. The eDNA method furthermore detected schistosome presence at two additional sites where snail shedding failed, demonstrating a higher sensitivity of eDNA sampling. We conclude that eDNA provides a promising tool to substantially improve the environmental surveillance of S. mansoni Given the proper method and guideline development, eDNA could become an essential future component of the schistosomiasis control tool box needed to achieve the goal of elimination.

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

BACKGROUND: South 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. METHODS: In 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. RESULTS: 1. Early 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. 2. 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). 3. 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). 4. FGS: FGS prevalence (19.7%) was associated with previous anti-schistosomal treatment (AOR: 2.18, 95% CI: 1.57-3.05). CONCLUSION: There 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.

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.

Molecular diversity of avian schistosomes in Danish freshwater snails.

Avian schistosomes are widespread parasites of snails and waterfowl and may cause cercarial dermatitis (swimmer's itch) in humans, a disease that is frequently reported in European countries. These parasites are known to occur in Denmark, but here, we applied a new approach using molecular tools to identify the parasites at species level. In order to do that, 499 pulmonate freshwater snails (Radix sp., Lymnaea stagnalis, Stagnicola sp. and Planorbarius corneus) were sampled from 12 lakes, ponds, and marshes in the greater Copenhagen area. Avian schistosome cercariae were identified by microscopy and subjected to molecular investigation by sequencing and phylogenetic analysis of the 5.8S and ITS2 ribosomal DNA for species identification. Additionally, snail hosts belonging to the genus Radix were identified by sequencing and phylogenetic analysis of partial ITS2 ribosomal DNA. Three out of 499 snails shed different species of Trichobilharzia cercariae: Trichobilharzia szidati was isolated from L. stagnalis, Trichobilharzia franki from Radix auricularia and Trichobilharzia regenti from Radix peregra. In the light of the public health risk represented by bird schistosomes, these findings are of concern and, particularly, the presence of the potentially neuro-pathogenic species, T. regenti, in Danish freshwaters calls for attention.

Gynecological manifestations, histopathological findings, and schistosoma-specific polymerase chain reaction results among women with Schistosoma haematobium infection: a cross-sectional study in Madagascar.

BACKGROUND: The pathophysiology of female genital schistosomiasis (FGS) is only partially understood. This study aims to describe the histopathological findings, polymerase chain reaction (PCR) results, and gynecological manifestations of FGS in women with different intensities of Schistosoma haematobium infection. METHODS: Women aged 15-35 years living in an S. haematobium-endemic area in Madagascar underwent pelvic and colposcopic examinations. Small biopsy specimens were obtained from lesions and examined histopathologically. Schistosoma PCR was done on urine, biopsy, cervicovaginal lavage, and genital mucosal surface specimens. RESULTS: Sandy patches and rubbery papules were found in 41 of 118 women (35%). Rubbery papules reflected an intense cellular immune reaction dominated by eosinophils, epithelial erosion, and viable ova. There was a significant decrease in the prevalence of rubbery papules with age, even after adjustment for urinary ova excretion. The sandy patches with grains showed moderate cellular immune reaction and ova (viable and/or calcified). They were most prevalent in cases with low-intensity urinary S. haematobium infection. Forty-two percent of women with Schistosoma-negative urine specimens had at least 1 genital specimen test positive for Schistosoma by PCR. CONCLUSIONS: The results indicate a diversity of lesions caused by S. haematobium and a dynamic evolution of the genital lesions. Schistosoma PCR may give an indication of the diagnosis.

The impact of anthelmintic treatment intervention on malaria infection and anaemia in school and preschool children in Magu district, Tanzania: an open label randomised intervention trial.

BACKGROUND: Some studies have suggested that helminth infections increase the risk of malaria infection and are associated with increased number of malaria attacks and anaemia. Thus interventions to control helminth infections may have an impact on incidence of clinical malaria and anaemia. The current study assessed the impact of two anthelmintic treatment approaches on malaria infection and on anaemia in school and pre-school children in Magu district, Tanzania. METHODS: A total of 765 children were enrolled into a prospective randomized anthelmintic intervention trial following a baseline study of 1546 children. Enrolled children were randomized to receive either repeated treatment with praziquantel and albendazole four times a year (intervention group, 394 children) or single dose treatment with praziquantel and albendazole once a year (control group, 371 children). Follow up examinations were conducted at 12 and 24 months after baseline to assess the impact of the intervention. Stool and urine samples were collected and examined for schistosome and soil transmitted helminth infections. Blood samples were also collected and examined for malaria parasites and haemoglobin concentrations. Monitoring of clinical malaria attacks was performed at each school during the two years of the intervention. RESULTS: Out of 1546 children screened for P. falciparum, S. mansoni, S. haematobium, hookworm and T. Trichiura at baseline, 1079 (69.8%) were infected with at least one of the four parasites. There was no significant difference in malaria infection (prevalence, parasite density and frequency of malaria attacks) and in the prevalence of anaemia between the repeated and single dose anthelmintic treatment groups at 12 and 24 months follow up (p>0.05). However, overall, there was significant improvement in mean haemoglobin concentrations (p<0.001) from baseline levels of 122.0 g/L and 123.0 g/L to 136.0 g/L and 136.8 g/L for the repeated and single dose treatment groups, respectively, at 24 months follow-up which resulted in significant reduction in prevalence of anaemia. CONCLUSIONS: These results suggest that repeated anthelmintic treatment did not have an impact on malaria infection compared to single dose treatment. However, both treatment approaches had overall impact in terms of improvements of haemoglobin levels and hence reductions in prevalence of anaemia.

Human Schistosoma haematobium antifecundity immunity is dependent on transmission intensity and associated with immunoglobulin G1 to worm-derived antigens.

BACKGROUND: Immunity that reduces worm fecundity and, in turn, reduces morbidity is proposed for Schistosoma haematobium, a parasite of major public health importance. Mathematical models of epidemiological trends suggest that antifecundity immunity is dependent on antibody responses to adult-worm-derived antigen. METHODS: For a Malian cohort (age, 5-29 years) residing in high-transmission fishing villages or a moderate-transmission village, worm fecundity was assessed using the ratio of urinary egg excretion to levels of circulating anodic antigen, a Schistosoma-specific antigen that is steadily secreted by adult worms. Fecundity was modeled against host age, infection transmission intensity, and antibody responses specific to soluble worm antigen (SWA), tegument allergen-like 1, and 28-kDa glutathione-S-transferase. RESULTS: Worm fecundity declined steadily until a host age of 11 years. Among children, host age and transmission were negatively associated with worm fecundity. A significant interaction term between host age and transmission indicates that antifecundity immunity develops earlier in high-transmission areas. SWA immunoglobulin G1 (IgG1) levels explained the effect of transmission on antifecundity immunity. CONCLUSION: Antifecundity immunity, which is likely to be protective against severe morbidity, develops rapidly during childhood. Antifecundity immunity is associated with SWA-IgG1, with higher infection transmission increasing this response at an earlier age, leading to earlier development of antifecundity immunity.

A latent Markov modelling approach to the evaluation of circulating cathodic antigen strips for schistosomiasis diagnosis pre- and post-praziquantel treatment in Uganda.

Regular treatment with praziquantel (PZQ) is the strategy for human schistosomiasis control aiming to prevent morbidity in later life. With the recent resolution on schistosomiasis elimination by the 65th World Health Assembly, appropriate diagnostic tools to inform interventions are keys to their success. We present a discrete Markov chains modelling framework that deals with the longitudinal study design and the measurement error in the diagnostic methods under study. A longitudinal detailed dataset from Uganda, in which one or two doses of PZQ treatment were provided, was analyzed through Latent Markov Models (LMMs). The aim was to evaluate the diagnostic accuracy of Circulating Cathodic Antigen (CCA) and of double Kato-Katz (KK) faecal slides over three consecutive days for Schistosoma mansoni infection simultaneously by age group at baseline and at two follow-up times post treatment. Diagnostic test sensitivities and specificities and the true underlying infection prevalence over time as well as the probabilities of transitions between infected and uninfected states are provided. The estimated transition probability matrices provide parsimonious yet important insights into the re-infection and cure rates in the two age groups. We show that the CCA diagnostic performance remained constant after PZQ treatment and that this test was overall more sensitive but less specific than single-day double KK for the diagnosis of S. mansoni infection. The probability of clearing infection from baseline to 9 weeks was higher among those who received two PZQ doses compared to one PZQ dose for both age groups, with much higher re-infection rates among children compared to adolescents and adults. We recommend LMMs as a useful methodology for monitoring and evaluation and treatment decision research as well as CCA for mapping surveys of S. mansoni infection, although additional diagnostic tools should be incorporated in schistosomiasis elimination programs.

Urinary cytokines in Schistosoma haematobium-infected schoolchildren from Tana Delta District of Kenya.

BACKGROUND: Pathological changes due to infection with Schistosoma haematobium include cytokine-mediated urinary tract inflammation. The involved cytokines may be excreted in urine and their presence in urine may therefore reflect S. haematobium-related urinary tract pathology. The present study, for the first time, reports on the relationship between selected cytokines in urine and infection with S. haematobium in children from an area highly affected by this parasite. METHODS: Children aged 5-12 years from two primary schools in Tana Delta District of Kenya were examined for S. haematobium eggs using urine filtration technique, for haematuria using dipstix and for eosinophil cationic protein (ECP), IL-6, IFN- γ, TNF-α and IL-10 levels using ELISA, and for S. haematobium-related urinary tract pathology using ultrasonography. In addition, venous blood was examined for serum IL-6, IFN- γ, TNF-α and IL-10 levels using ELISA. RESULTS: There was no significant correlation between urinary and serum levels of IL-6, IFN- γ, TNF-α or IL-10. There was no significant difference in geometric mean intensity (GMI) in any of the serum cytokines, or in urinary TNF-α or IFN-γ, between children with light and heavy S. haematobium infections. However, children with heavy S. haematobium infections had significantly higher GMI of urinary IL-6 (p < 0.001) and lower GMI of urinary IL-10 (p = 0.002) than children with light infections. There was also a significant positive correlation between urinary IL-6 and urinary ECP (p < 0.001) and a significant negative correlation between urinary IL-10 and urinary ECP (p = 0.012). CONCLUSION: Urinary IL-6 was positively correlated to and IL-10 was negatively correlated to infection intensity and urinary tract inflammation in S. haematobium-infected children. Urinary IL-6 and IL-10 ELISA may be a useful non-invasive tool to complement the already available tools for studying S. haematobium-related urinary tract pathology in children.

Associations between maternal helminth and malaria infections in pregnancy and clinical malaria in the offspring: a birth cohort in entebbe, Uganda.

BACKGROUND: Helminth and malaria coinfections are common in the tropics. We investigated the hypothesis that prenatal exposure to these parasites might influence susceptibility to malaria in childhood. METHODS: In a birth cohort of 2345 mother-child pairs in Uganda, maternal helminth and malaria infection status was determined during pregnancy, and childhood malaria episodes were recorded from birth to age 5 years. We examined associations between maternal infections and malaria in the offspring. RESULTS: Common maternal infections were hookworm (45%), Mansonella perstans (21%), Schistosoma mansoni (18%), and Plasmodium falciparum (11%). At age 5 years, 69% of the children were still under follow-up. The incidence of malaria was 34 episodes per 100 child-years, and the mean prevalence of asymptomatic malaria at annual visits was 5.4%. Maternal hookworm and M. perstans infections were associated with an increased rate of childhood clinical malaria (adjusted hazard ratio [aHR], 1.24, 95% confidence interval [CI], 1.10-1.41; aHR, 1.20, 95% CI, 1.05-1.38, respectively). S. mansoni infection had no consistent association with childhood malaria. CONCLUSIONS: This is the first report of an association between helminth infections in pregnancy and malaria in the offspring and indicates that helminth infections in pregnancy may increase the burden of childhood malaria morbidity.

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

OBJECTIVE: 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. METHOD: 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. RESULTS: 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). CONCLUSION: 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.

Update on the Geographic Distribution of the Intermediate Host Snails of Schistosoma mansoni on St. Lucia: A Step Toward Confirming the Interruption of Transmission of Human Schistosomiasis.

To provide information to guide considerations of declaring interruption of transmission of human schistosomiasis due to Schistosoma mansoni on St. Lucia, we undertook an island-wide survey in June-July 2022 to determine the presence of Biomphalaria snails, the intermediate hosts of S. mansoni, and their infection status. Snail surveys were carried out at 58 habitats to determine presence of Biomphalaria snails followed by examination of the collected snails for evidence of infection with S. mansoni. Furthermore, water samples were collected at the snail habitats and screened for presence of S. mansoni DNA using an eDNA approach. We found B. glabrata present in one habitat (Cul de Sac) where it was abundant. Specimens provisionally identified as Biomphalaria kuhniana were recovered from 10 habitats. None of the Biomphalaria specimens recovered were positive for S. mansoni. None of the eDNA water samples screened were positive for S. mansoni. Experimental exposures of both field-derived and laboratory-reared St. Lucian B. glabrata and B. kuhniana to Puerto Rican and Kenyan-derived S. mansoni strains revealed B. glabrata to be susceptible to both and B. kuhniana proved refractory from histological and snail shedding results. We conclude, given the current rarity of B. glabrata on the island and lack of evidence for the presence of S. mansoni, that transmission is unlikely to be ongoing. Coupled with negative results from recent human serological surveys, and implementation of improved sanitation and provision of safe water supplies, St. Lucia should be considered a candidate for declaration of interruption of human schistosomiasis transmission.

Potential Hybridization of Fasciola hepatica and F. gigantica in Africa-A Scoping Review.

The occurrence of Fasciola gigantica and F. hepatica in Africa is well documented; however, unlike in Asia, there is a paucity of information on the existence of hybrids or parthenogenetic species on the continent. Nonetheless, these hybrid species may have beneficial characteristics, such as increased host range and pathogenicity. This study provides evidence of the potential existence of Fasciola hybrids in Africa. A literature search of articles published between 1980 and 2022 was conducted in PubMed, Google Scholar, and Science Direct using a combination of search terms and Boolean operators. Fasciola species were documented in 26 African countries with F. hepatica being restricted to 12 countries, whilst F. gigantica occurred in 24 countries, identified based on morphological features of adult Fasciola specimens or eggs and molecular techniques. The co-occurrence of both species was reported in 11 countries. However, the occurrence of potential Fasciola hybrids was only confirmed in Egypt and Chad but is suspected in South Africa and Zimbabwe. These were identified based on liver fluke morphometrics, assessment of the sperms in the seminal vesicle, and molecular techniques. The occurrence of intermediate host snails Galba truncatula and Radix natalensis was reported in Ethiopia, Egypt, South Africa, Tanzania, and Uganda, where F. hepatica and F. gigantica co-occurrences were reported. The invasive Pseudosuccinea columella snails naturally infected with F. gigantica were documented in South Africa and Egypt. In Zimbabwe, P. columella was infected with a presumed parthenogenetic Fasciola. This suggests that the invasive species might also be contributing to the overlapping distributions of the two Fasciola species since it can transmit both species. Notwithstanding the limited studies in Africa, the potential existence of Fasciola hybrids in Africa is real and might mimic scenarios in Asia, where parthenogenetic Fasciola exist in most Asian countries. In South Africa, aspermic F. hepatica and Fasciola sp. have been reported already, and Fasciola hybrids have been reported? in Chad and Egypt. Thus, the authors recommend future surveys using molecular markers recommended to identify Fasciola spp. and their snail intermediate hosts to demarcate areas of overlapping distribution where Fasciola hybrids and/or parthenogenetic Fasciola may occur. Further studies should also be conducted to determine the presence and role of P. columella in the transmission of Fasciola spp. in these geographical overlaps to help prevent parasite spillbacks.

Infection intensity-dependent accuracy of reagent strip for the diagnosis of Schistosoma haematobium and estimation of treatment prevalence thresholds.

BACKGROUND: Reagent strip to detect microhematuria as a proxy for Schistosoma haematobium infections has been considered an alternative to urine filtration for individual diagnosis and community-based estimates of treatment needs for preventive chemotherapy. However, the diagnostic accuracy of reagent strip needs further investigation, particularly at low infection intensity levels. METHODS: We used existing data from a study conducted in Tanzania that employed urine filtration and reagent strip testing for S. haematobium in two villages, including a baseline and six follow-up surveys after praziquantel treatment representing a wide range of infection prevalence. We developed a Bayesian model linking individual S. haematobium egg count data based on urine filtration to reagent strip binary test results available on multiple days and estimated the relation between infection intensity and sensitivity of reagent strip. Furthermore, we simulated data from 3,000 hypothetical populations with varying mean infection intensity to infer on the relation between prevalence observed by urine filtration and the interpretation of reagent strip readings. PRINCIPAL FINDINGS: Reagent strip showed excellent sensitivity even for single measurement reaching 100% at around 15 eggs of S. haematobium per 10 ml of urine when traces on reagent strip were considered positive. The corresponding specificity was 97%. When traces were considered negative, the diagnostic accuracy of the reagent strip was equivalent to urine filtration data obtained on a single day. A 10% and 50% urine filtration prevalence based on a single day sampling corresponds to 11.2% and 48.6% prevalence by reagent strip, respectively, when traces were considered negative, and 17.6% and 57.7%, respectively, when traces were considered positive. CONCLUSIONS/SIGNIFICANCE: Trace results should be included in reagent strip readings when high sensitivity is required, but excluded when high specificity is needed. The observed prevalence of reagent strip results, when traces are considered negative, is a good proxy for prevalence estimates of S. haematobium infection by urine filtration on a single day.

Effect of praziquantel treatment of Schistosoma mansoni during pregnancy on immune responses to schistosome antigens among the offspring: results of a randomised, placebo-controlled trial.

BACKGROUND: Offspring of women with schistosomiasis may exhibit immune responsiveness to schistosomes due to in utero sensitisation or trans-placental transfer of antibodies. Praziquantel treatment during pregnancy boosts maternal immune responses to schistosome antigens and reduces worm burden. Effects of praziquantel treatment during pregnancy on responses among offspring are unknown. METHODS: In a trial of anthelminthic treatment during pregnancy in Uganda (ISRCTN32849447; http://www.controlled-trials.com/ISRCTN32849447/elliott), offspring of women with Schistosoma mansoni were examined for cytokine and antibody responses to schistosome worm (SWA) and egg (SEA) antigen, in cord blood and at age one year. Relationships to maternal responses and pre-treatment infection intensities were examined, and responses were compared between the offspring of women who did, or did not receive praziquantel treatment during pregnancy. RESULTS: Of 388 S. mansoni-infected women studied, samples were obtained at age one year from 215 of their infants. Stool examination for S. mansoni eggs was negative for all infants. Cord and infant samples were characterised by very low cytokine production in response to schistosome antigens with the exception of cord IL-10 responses, which were substantial. Cord and infant cytokine responses showed no association with maternal responses. As expected, cord blood levels of immunoglobulin (Ig) G to SWA and SEA were high and correlated with maternal antibodies. However, by age one year IgG levels had waned and were hardly detectable. Praziquantel treatment during pregnancy showed no effect on cytokine responses or antibodies levels to SWA or SEA either in cord blood or at age one year, except for IgG1 to SWA, which was elevated in infants of treated mothers, reflecting maternal levels. There was some evidence that maternal infection intensity was positively associated with cord blood IL-5 and IL-13 responses to SWA, and IL-5 responses to SEA, and that this association was modified by treatment with praziquantel. CONCLUSIONS: Despite strong effects on maternal infection intensity and maternal immune responses, praziquantel treatment of infected women during pregnancy had no effect on anti-schistosome immune responses among offspring by age one year. Whether the treatment will impact upon the offspring's responses on exposure to primary schistosome infection remains to be elucidated. TRIAL REGISTRATION: ISRCTN: ISRCTN32849447.

Mapping Schistosoma haematobium for Novel Interventions against Female Genital Schistosomiasis and Associated HIV Risk in KwaZulu-Natal, South Africa.

Women with female genital schistosomiasis (FGS) have been found to have genital symptoms and a three-fold higher risk of HIV infection. Despite WHO recommendations, regular antischistosomal mass drug administration (MDA) has not yet been implemented in South Africa possibly because of the lack of updated epidemiological data. To provide data for future prevention efforts against FGS and HIV, this study explored Schistosoma haematobium prevalence in girls and young women and the effects of antischistosomal MDA, respectively. Urinary schistosomiasis and genital symptoms were investigated in 70 randomly selected secondary schools in three districts within KwaZulu-Natal and 18 primary schools. All study participants were treated for schistosomiasis, and schools with the highest urinary prevalence were followed up after 1 and 4 years of MDA. At baseline, urine analysis data showed that most schools were within the moderate-risk prevalence category where biennial antischistosomal MDA is recommended, as per WHO guidelines. Young women had high prevalence of genital symptoms (36%) after correcting for sexually transmitted infections. These symptoms may be caused by infection with schistosomes. However, FGS cannot be diagnosed by urine analysis alone. In KwaZulu-Natal rural schools, this study suggests that antischistosomal MDA with praziquantel could prevent genital symptoms in more than 200,000 young women. Furthermore, it is feasible that more than 5,000 HIV infections could be prevented in adolescent girls and young women by treatment and prevention of FGS.

Novel automated biomarker discovery work flow for urinary peptidomics.

BACKGROUND: Urine is potentially a rich source of peptide biomarkers, but reproducible, high-throughput peptidomic analysis is often hampered by the inherent variability in factors such as pH and salt concentration. Our goal was to develop a generally applicable, rapid, and robust method for screening large numbers of urine samples, resulting in a broad spectrum of native peptides, as a tool to be used for biomarker discovery. METHODS: Peptide samples were trapped, desalted, pH-normalized, and fractionated on a miniaturized automatic reverse-phase strong cation exchange (RP-SCX) cartridge system. We analyzed eluted peptides using MALDI-TOF, Fourier transform ion cyclotron resonance, and liquid chromatography-iontrap mass spectrometry. We determined qualitative and quantitative reproducibility of the system and robustness of the method using BSA digests and urine samples, and we used a selected set of urine samples from Schistosoma haematobium-infected individuals to evaluate clinical applicability. RESULTS: The automated RP-SCX sample cleanup and fractionation system exhibits a high qualitative and quantitative reproducibility, with both BSA standards and urine samples. Because of the relatively high cartridge binding capacity (1-2 mL urine), eluted peptides can be measured with high sensitivity using multiple mass spectrometric techniques. As proof of principle, hemoglobin-derived peptides were identified in urine samples from S. haematobium-infected individuals, even when the microhematuria test was negative. CONCLUSIONS: We present a practical, step-by-step method for screening and identification of urinary peptides. Alongside the analytical method evaluation on standard samples, we demonstrate its feasibility with actual clinical material.

Effect of praziquantel treatment of Schistosoma mansoni during pregnancy on intensity of infection and antibody responses to schistosome antigens: results of a randomised, placebo-controlled trial.

BACKGROUND: Praziquantel treatment of schistosomiasis during pregnancy was only recommended in 2002; hence the effects of treatment during pregnancy are not fully known. We have therefore evaluated the effects on infection intensity and the immunological effects of praziquantel treatment against Schistosoma mansoni during pregnancy, compared with treatment after delivery. METHODS: A nested cohort of 387 Schistosoma mansoni infected women was recruited within a larger trial of de-worming during pregnancy. Women were randomised to receive praziquantel or placebo during pregnancy. All women were treated after delivery. Infection intensity after treatment was assessed by a single Kato-Katz examination of stool samples with duplicate slides and categorised as undetected, light (1-99 eggs per gram (epg)), moderate (100-399 epg) or heavy (>or=400 epg). Antibodies against S. mansoni worm and egg antigens were measured by ELISA. Results were compared between women first treated during pregnancy and women first treated after delivery. RESULTS: At enrollment, 252 (65.1%) of the women had light infection (median (IQR) epg: 35 (11, 59)), 75 (19.3%) moderate (median (IQR) epg: 179(131, 227)) and 60 (15.5%) had heavy infection (median (IQR) epg: 749 (521, 1169)) with S. mansoni. At six weeks after praziquantel treatment during pregnancy S. mansoni infection was not detectable in 81.9% of the women and prevalence and intensity had decreased to 11.8% light, 4.7% moderate and 1.6% heavy a similar reduction when compared with those first treated after delivery (undetected (88.5%), light (10.6%), moderate (0.9%) and heavy (0%), p = 0.16). Parasite specific antibody levels were lower during pregnancy than after delivery. Praziquantel treatment during pregnancy boosted anti-worm IgG isotypes and to a lesser extent IgE, but these boosts were less pronounced than in women whose treatment was delayed until after delivery. Praziquantel had limited effects on antibodies against egg antigens. CONCLUSION: S mansoni antigen-specific antibody levels and praziquantel-induced boosts in antibody levels were broadly suppressed during pregnancy, but this was not associated with major reduction in the efficacy of praziquantel. Long-term implications of these findings in relation to resistance to re-infection remain to be explored.

Hepatosplenomegaly is associated with low regulatory and Th2 responses to schistosome antigens in childhood schistosomiasis and malaria coinfection.

Hepatosplenomegaly among Kenyan schoolchildren has been shown to be exacerbated where there is transmission of both Schistosoma mansoni and Plasmodium falciparum. This highly prevalent and chronic morbidity often occurs in the absence of ultrasound-detectable periportal fibrosis and may be due to immunological inflammation. For a cohort of school-age children, whole-blood cultures were stimulated with S. mansoni soluble egg antigen (SEA) or soluble worm antigen (SWA). Responses to SWA were found to be predominantly Th2 cytokines; however, they were not significantly associated with either hepatosplenomegaly or infection with S. mansoni or P. falciparum. In comparison, SEA-specific Th2 cytokine responses were low, and the levels were negatively correlated with S. mansoni infection intensities and were lower among children who were coinfected with P. falciparum. Tumor necrosis factor alpha levels in response to stimulation with SEA were high, and a negative association between presentation with hepatomegaly and the levels of the regulatory cytokines interleukin-6 and transforming growth factor beta(1) suggests that a possible mechanism for childhood hepatomegaly in areas where both malaria and schistosomiasis are endemic is poor regulation of an inflammatory response to schistosome eggs.