Spillover, hybridization, and persistence in schistosome transmission dynamics at the human-animal interface.

Zoonotic spillover and hybridization of parasites are major emerging public and veterinary health concerns at the interface of infectious disease biology, evolution, and control. Schistosomiasis is a neglected tropical disease of global importance caused by parasites of the Schistosoma genus, and the Schistosoma spp. system within Africa represents a key example of a system where spillover of animal parasites into human populations has enabled formation of hybrids. Combining model-based approaches and analyses of parasitological, molecular, and epidemiological data from northern Senegal, a region with a high prevalence of schistosome hybrids, we aimed to unravel the transmission dynamics of this complex multihost, multiparasite system. Using Bayesian methods and by estimating the basic reproduction number (R0 ), we evaluate the frequency of zoonotic spillover of Schistosoma bovis from livestock and the potential for onward transmission of hybrid S. bovis × S. haematobium offspring within human populations. We estimate R0 of hybrid schistosomes to be greater than the critical threshold of one (1.76; 95% CI 1.59 to 1.99), demonstrating the potential for hybridization to facilitate spread and establishment of schistosomiasis beyond its original geographical boundaries. We estimate R0 for S. bovis to be greater than one in cattle (1.43; 95% CI 1.24 to 1.85) but not in other ruminants, confirming cattle as the primary zoonotic reservoir. Through longitudinal simulations, we also show that where S. bovis and S. haematobium are coendemic (in livestock and humans respectively), the relative importance of zoonotic transmission is predicted to increase as the disease in humans nears elimination.

Inhibition of the Formation In Vitro of Putatively Carcinogenic Metabolites Derived from S. haematobium and O. viverrini by Combination of Drugs with Antioxidants.

Infections caused by Schistosoma haematobium and Opisthorchis viverrini are classified as carcinogenic. Although carcinogenesis might be a multifactorial process, it has been postulated that these helminth produce/excrete oxysterols and estrogen-like metabolites that might act as initiators of their infection-associated carcinogenesis. Current treatment and control of these infections rely on a single drug, praziquantel, that mainly targets the parasites and not the pathologies related to the infection including cancer. Thus, there is a need to search for novel therapeutic alternatives that might include combinations of drugs and drug repurposing. Based on these concepts, we propose a novel therapeutic strategy that combines drugs with molecule antioxidants. We evaluate the efficacy of a novel therapeutic strategy to prevent the formation of putative carcinogenic metabolites precursors and DNA adducts. Firstly, we used a methodology previously established to synthesize metabolites precursors and DNA adducts in the presence of CYP450. Then, we evaluated the inhibition of their formation induced by drugs and antioxidants alone or in combination. Drugs and resveratrol alone did not show a significant inhibitory effect while N-acetylcysteine inhibited the formation of most metabolite precursors and DNA adducts. Moreover, the combinations of classical drugs with antioxidants were more effective rather than compounds alone. This strategy might be a valuable tool to prevent the initiation of helminth infection-associated carcinogenesis.

Haemostatic changes in urogenital schistosomiasis haematobium: a case-control study in Gabonese schoolchildren.

In many tropical areas schistosomiasis is a major health problem causing hepatosplenic, intestinal or urogenital complaints. Hepatosplenic schistosomiasis mansoni is also characterized by blood coagulation abnormalities. Liver pathology plays a role in the development of haemostatic changes and the parasitic infection may directly affect coagulation. However, these contributing factors cannot be studied separately in hepatosplenic schistosomiasis infections. This pilot study provides insight in haemostatic changes in urinary schistosomiasis by studying coagulation parameters in schistosomiasis haematobium-infected Gabonese schoolchildren. Selection on urinary schistosomiasis patients without hepatosplenic complaints allows for the investigation of the direct effects of the parasite on haemostasis. Levels of von Willebrand Factor (VWF) antigen, active VWF and osteoprotegerin were elevated, indicating inflammation-mediated endothelial activation. In contrast to hepatosplenic schistosomiasis, thrombin-antithrombin complex and D-dimer levels were not affected. Despite its small sample size, this study clearly indicates that Schistosoma haematobium directly alters the activation status of the endothelium, without initiation of coagulation.

Pharmacokinetics of Praziquantel in Schistosoma mansoni- and Schistosoma haematobium-Infected School- and Preschool-Aged Children.

There is a growing consensus to include preschool-aged children in preventive chemotherapy programs with praziquantel to improve schistosomiasis control. However, pharmacokinetic data, crucial to establish a safe and effective dose for this age group, are sparse. The objective of this study was to establish and compare the pharmacokinetic parameters of praziquantel in preschool- and school-aged children with schistosomiasis. Two pharmacokinetic trials in school- and preschool-aged children infected with Schistosoma mansoni or S. haematobium were conducted in Côte d'Ivoire. Dried blood spot samples were taken from 492 children at 10 time points following a single oral dose of 20, 40, or 60 mg/kg of body weight of praziquantel and analyzed using liquid chromatography-mass spectrometry. Noncompartmental analysis (NCA) was performed to obtain the pharmacokinetic parameters of R-praziquantel (RPZQ), S-praziquantel (SPZQ), and R-trans-4-hydroxy-praziquantel. No significant differences in pharmacokinetic parameters between species-specific infections were observed. While pharmacokinetic parameters differed significantly between age groups for S. mansoni, this trend was not observed with S. haematobium Neither the area under the curve (AUC) nor the maximal blood concentration (Cmax) presented clear dose proportionality for R- and SPZQ. Logistic regression indicated a relationship between the RPZQ AUC and Cmax and the probability of cure. Praziquantel is subject to complex metabolic processes following erratic absorption. While the results of NCA are a very informative base for a better understanding of the drug, a more targeted approach in the form of population modeling is needed to quantify the factors influencing metabolic processes and draw conclusions.

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

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

Protocol and baseline data for a multi-year cohort study of the effects of different mass drug treatment approaches on functional morbidities from schistosomiasis in four African countries.

BACKGROUND: The Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) focus is on randomized trials of different approaches to mass drug administration (MDA) in endemic countries in Africa. Because their studies provided an opportunity to evaluate the effects of mass treatment on Schistosoma-associated morbidity, nested cohort studies were developed within SCORE's intervention trials to monitor changes in a suite of schistosomiasis disease outcomes. This paper describes the process SCORE used to select markers for prospective monitoring and the baseline prevalence of these morbidities in four parallel cohort studies. METHODS: In July 2009, SCORE hosted a discussion of the potential impact of MDA on morbidities due to Schistosoma infection that might be measured in the context of multi-year control. Candidate markers were reviewed and selected for study implementation. Baseline data were then collected from cohorts of children in four country studies: two in high endemic S. mansoni sites (Kenya and Tanzania), and two in high endemic S. haematobium sites (Niger and Mozambique), these cohorts to be followed prospectively over 5 years. RESULTS: At baseline, 62% of children in the S. mansoni sites had detectable eggs in their stool, and 10% had heavy infections (≥ 400 eggs/g feces). Heavy S. mansoni infections were found to be associated with increased baseline risk of anemia, although children with moderate or heavy intensity infections had lower risk of physical wasting. Prevalence of egg-positive infection in the combined S. haematobium cohorts was 27%, with 5% of individuals having heavy infection (≥50 eggs/10 mL urine). At baseline, light intensity S. haematobium infection was associated with anemia and with lower scores in the social domain of health-related quality-of-life (HRQoL) assessed by Pediatric Quality of Life Inventory. CONCLUSIONS: Our consensus on practical markers of Schistosoma-associated morbidity indicated that height, weight, hemoglobin, exercise tolerance, HRQoL, and ultrasound abnormalities could be used as reference points for gauging treatment impact. Data collected over five years of program implementation will provide guidance for future evaluation of morbidity control in areas endemic for schistosomiasis. TRIAL REGISTRATION: These cohort studies are registered and performed in conjunction with the International Standard Randomised Controlled Trial Registry trials ISRCTN16755535 , ISRCTN14117624 , ISRCTN95819193 , and ISRCTN32045736 .

Parasite-Associated Cancers (Blood Flukes/Liver Flukes).

Parasitic infection remains as a persistent public health problem and can be carcinogenic. Three helminth parasites, namely, Clonorchis sinensis (liver fluke) and Opisthorchis viverrini as well as Schistosoma haematobium (blood fluke), are classified as Group 1 carcinogens by the World Health Organization's International Agency for Research on Cancer (IARC Infection with liver flukes (Opisthorchis viverrini, Opisthorchis felineus and Clonorchis sinensis), World Health Organization, International Agency for Research on Cancer, 2011). Infection by these parasites is frequently asymptomatic and is thus rarely diagnosed at early exposure. Persistent infection can cause severe cancer complications. Until now, the cellular and molecular mechanisms linking fluke infections to cancer formation have yet to be defined, although many studies have focused on these mechanisms in recent years, and numerous findings were made in various aspects of parasite-associated cancers. Herein, we only introduce the fluke-induced cholangiocarcinoma (CCA) and bladder carcinoma and mainly focus on key findings in the last 5 years.

Estrogen Metabolism-Associated CYP2D6 and IL6-174G/C Polymorphisms in Schistosoma haematobium Infection.

Schistosoma haematobium is a human blood fluke causing a chronic infection called urogenital schistosomiasis. Squamous cell carcinoma of the urinary bladder (SCC) constitutes chronic sequelae of this infection, and S. haematobium infection is accounted as a risk factor for this type of cancer. This infection is considered a neglected tropical disease and is endemic in numerous countries in Africa and the Middle East. Schistosome eggs produce catechol-estrogens. These estrogenic molecules are metabolized to active quinones that induce modifications in DNA. The cytochrome P450 (CYP) enzymes are a superfamily of mono-oxygenases involved in estrogen biosynthesis and metabolism, the generation of DNA damaging procarcinogens, and the response to anti-estrogen therapies. IL6 Interleukin-6 (IL-6) is a pleiotropic cytokine expressed in various tissues. This cytokine is largely expressed in the female urogenital tract as well as reproductive organs. Very high or very low levels of IL-6 are associated with estrogen metabolism imbalance. In the present study, we investigated the polymorphic variants in the CYP2D6 gene and the C-174G promoter polymorphism of the IL-6 gene on S. haematobium-infected children patients from Guine Bissau. CYP2D6 inactivated alleles (28.5%) and IL6G-174C (13.3%) variants were frequent in S. haematobium-infected patients when compared to previously studied healthy populations (4.5% and 0.05%, respectively). Here we discuss our recent findings on these polymorphisms and whether they can be predictive markers of schistosome infection and/or represent potential biomarkers for urogenital schistosomiasis associated bladder cancer and infertility.

Development of Urinary Bladder Pre-Neoplasia by Schistosoma haematobium Eggs and Chemical Carcinogen in Mice.

Schistosoma haematobium is a biocarcinogen of human urinary bladder (UB). The present study investigated developing UB cancer mouse model by injecting S. haematobium eggs into the bladder wall and introduction of chemical carcinogens. Histopathological findings showed mild hyperplasia to epithelial vacuolar change, and high grade dysplasia. Squamous metaplasia was observed in the S. haematobium eggs+NDMA group at week 12 but not in other groups. Immunohistochemistry revealed significantly high expression of Ki-67 in urothelial epithelial cells of the S. haematobium eggs+BBN group at week 20. The qRT-PCR showed high expression of p53 gene in S. haematobium eggs group at week 4 and S. haematobium eggs+BBN group at week 20. E-cadherin and vimentin showed contrasting expression in S. haematobium eggs+BBN group. Such inverse expression of E-cadherin and vimentin may indicate epithelial mesenchymal transition in the UB tissue. In conclusion, S. haematobium eggs and nitrosamines may transform UB cells into squamous metaplasia and dysplasia in correlation with increased expression of Ki-67. Marked decrease in E-cadherin and increase in p53 and vimentin expressions may support the transformation. The present study introduces a promising modified animal model for UB cancer study using S. haematobium eggs.

Natural and human induced factors influencing the abundance of Schistosoma host snails in Zambia.

Schistosomiasis remains a global public health problem affecting about 240 million people. In Zambia, 2 million are infected while 3 million live with the risk of getting infected. Research and interventions relating to schistosomiasis are mainly linked to disease epidemiology. Malacological and ecological aspects of the disease are superficially understood. Developing effective control measures requires an understanding of interacting environmental and socioeconomic factors of host snails vis-a-vis schistosomiasis. Therefore, the present work involved collecting social and environmental data in a large field study in two zones in Zambia that are different in terms of temperature and rainfall amounts. Social data collected through questionnaires included demographic, educational and knowledge of schistosomiasis disease dynamics. Environmental data included physicochemical factors, aquatic plants and snails. Gender (P < 0.001) significantly influences livelihood strategies, while age (P = 0.069) and level of education (P = 0.086) have a moderate influence in zone I. In zone III, none of these factors (age, P = 0.378; gender, P = 0.311; education, P = 0.553) play a significant role. Environmental parameters explained 43 and 41 % variation in species composition for zones I and III, respectively. Most respondents' (52 %, 87 %) perception is that there are more cases of bilharzia in hot season than in other seasons (rainy season 23 %, 7 %; cold season 8 %, 0 % and year round 17 %, 6 %) for zone I and zone III, respectively.

Schistosoma haematobium egg-induced bladder urothelial abnormalities dependent on p53 are modulated by host sex.

INTRODUCTION AND OBJECTIVE: The bladder urothelium changes dramatically during Schistosoma haematobium infection (urogenital schistosomiasis). These alterations include hyperplasia, ulceration, dysplasia, squamous metaplasia and frank carcinogenesis. Defining the pathways underpinning these urothelial responses will contribute to a deeper understanding of how S. haematobium egg expulsion, hematuria, and bladder cancer develop in humans. The tumor suppressor gene p53 is of particular interest, given its role in many cancers, including bladder cancer generally and schistosomal bladder cancer specifically. METHODS: Transgenic mice featuring tamoxifen-inducible Cre recombinase activity in cells expressing the urothelial-specific gene uroplakin-3a (Upk3a-GCE mice) were crossed with either TdTomato-floxed-EGFP reporter or p53-floxed mice. Mice were administered tamoxifen or vehicle control to induce excision of floxed genes. TdTomato-EGFP reporter mice were sacrificed and their bladders harvested, sectioned, and imaged by fluorescence microscopy. p53-floxed mice underwent bladder wall injection with S. haematobium eggs or vehicle controls. Three months later, mice were sacrificed and their bladders subjected to histological analysis (H&E staining). RESULTS: We first confirmed the phenotypic fidelity of Upk3a-GCE mice by crossing them with TdTomato-floxed-EGFP reporter mice and administering tamoxifen to their progeny. As expected, these progeny switched from TdTomato to EGFP expression in their bladder urothelium. Having confirmed the phenotype of Upk3a-GCE mice, we next crossed them to p53-floxed mice. The resulting progeny were given tamoxifen or vehicle control to render them urothelial p53-haploinsufficient or -intact, respectively. Then, we injected S. haematobium eggs or control vehicle into the bladder walls of these mice. Male p53-intact, egg-injected mice exhibited similar histological changes as their p53-haploinsufficient counterparts, including urothelial hyperplasia and ulceration. In contrast, female p53-intact, egg-injected mice featured no urothelial ulceration, whereas their p53-haploinsufficient counterparts often had significant ulceration. CONCLUSIONS: Urothelial p53 signaling indeed seems to affect urothelial homeostasis during S. haematobium infection, albeit in a sex-specific manner. Ongoing work seeks to determine whether p53 mediates associated alterations in urothelial cell cycle status and frank carcinogenesis in the setting of urogenital schistosomiasis.

Rigidity and resistance of larval- and adult schistosomes-medium interface.

Schistosomiasis is second only to malaria in prevalence and severity, and is still a major health problem in many tropical countries worldwide with about 200-300 million cases and with more than 800 million people at risk of infection. Based on these data, the World Health Organization recommends fostering research efforts for understanding at any level the mechanisms of the infection and then decreasing the social and economical impact of schistosomiasis. A key role is played by the parasite apical lipid membrane, which is entirely impervious to the surrounding elements of the immune system. We have previously demonstrated that the interaction between schistosomes and surrounding medium is governed by a parasite surface membrane sphingomyelin-based hydrogen barrier. In the present article, the elastic contribution to the total motion as a function of the exchanged wave-vector Q and the mean square displacement values for Schistosoma mansoni larvae and worms and Schistosomahaematobium worms have been evaluated by quasi elastic neutron scattering (QENS). The results point out that S. mansoni larvae show a smaller mean square displacement in comparison to S. mansoni and S. haematobium worms. These values increased by repeating the measurements after one day. These differences, which are analogous to those observed for the diffusion coefficient we previously evaluated, are interpreted in terms of rigidity of the parasite-medium interaction. S. mansoni larvae are the most rigid systems, while S. haematobium worms are the most flexible. In addition, temperature and hypoxia induce a weakening of the schistosome-medium interaction. These evidences are related to the strength of the hydrogen-bonded interaction between parasites and environment that we previously determined. We have shown that S. mansoni worms are characterized by a weakened interaction in respect to the larvae, while the S. haematobium worms more weakly interact with the surrounding medium than S. mansoni. The present QENS analysis allowed us to characterize the rigidity of larval- and adult S. mansoni and S. haematobium-host interface and to relate it to the parasite resistance to the hostile elements of the surrounding medium and to the immune effectors attack.

A novel mouse model of Schistosoma haematobium egg-induced immunopathology.

Schistosoma haematobium is the etiologic agent for urogenital schistosomiasis, a major source of morbidity and mortality for more than 112 million people worldwide. Infection with S. haematobium results in a variety of immunopathologic sequelae caused by parasite oviposition within the urinary tract, which drives inflammation, hematuria, fibrosis, bladder dysfunction, and increased susceptibility to urothelial carcinoma. While humans readily develop urogenital schistosomiasis, the lack of an experimentally-tractable model has greatly impaired our understanding of the mechanisms that underlie this important disease. We have developed an improved mouse model of S. haematobium urinary tract infection that recapitulates several aspects of human urogenital schistosomiasis. Following microinjection of purified S. haematobium eggs into the bladder wall, mice consistently develop macrophage-rich granulomata that persist for at least 3 months and pass eggs in their urine. Importantly, egg-injected mice also develop urinary tract fibrosis, bladder dysfunction, and various urothelial changes morphologically reminiscent of human urogenital schistosomiasis. As expected, S. haematobium egg-induced immune responses in the immediate microenvironment, draining lymph nodes, and systemic circulation are associated with a Type 2-dominant inflammatory response, characterized by high levels of interleukin-4, eosinophils, and IgE. Taken together, our novel mouse model may help facilitate a better understanding of the unique pathophysiological mechanisms of epithelial dysfunction, tissue fibrosis, and oncogenesis associated with urogenital schistosomiasis.

Soluble CD23 levels are inversely associated with atopy and parasite-specific IgE levels but not with polyclonal IgE levels in people exposed to helminth infection.

BACKGROUND: Protective acquired immunity against helminths and allergic sensitisation are both characterised by high IgE antibody levels. Levels of IgE antibodies are naturally tightly regulated by several mechanisms including binding of the CD23 receptor. Following observations that helminth infections and allergic sensitisation may co-present, the current study aims to investigate the relationship between the soluble CD23 (sCD23) receptor, parasite-specific IgE responses and allergic sensitisation in people exposed to the helminth parasite Schistosoma haematobium. METHODS: A cohort of 434 participants was recruited in two villages with different levels of S. haematobium infection in Zimbabwe. Serum levels of the 25-kDa fragment of sCD23 were related to levels of schistosome infection intensity, allergen (house dust mite, HDM) and schistosome-specific IgE, total IgE and skin sensitisation to HDM. RESULTS: sCD23 levels rose significantly with schistosome infection intensity but declined significantly with schistosome-specific IgE levels. Furthermore, sCD23 levels were negatively associated with skin sensitisation and IgE reactivity against HDM, but showed no relationship with total IgE. CONCLUSION: The results are consistent with the suppression of parasite and allergen-specific IgE levels by sCD23. Further mechanistic studies will determine the relevance of this potential regulatory mechanism in the development of helminth-specific immune responses in atopic individuals.

Detectable urogenital schistosome DNA and cervical abnormalities 6 months after single-dose praziquantel in women with Schistosoma haematobium infection.

We explored response to single-dose praziquantel therapy in a cohort of 33 women with Schistosoma haematobium infection in rural Mwanza, Tanzania. Women with S. haematobium infection confirmed both by eggs in urine and by polymerase chain reaction (PCR) received single-dose praziquantel and treatment of concomitant sexually transmitted infections. Macroscopic cervical abnormalities were also quantified. After 6 months, microscopically detectable egg excretion was eliminated, but 8 of 33 women (24%) were persistently positive for S. haematobium by PCR, and 11 (33%) had cervical abnormalities potentially attributable to schistosomiasis. This suggests that praziquantel treatment more frequently than every 6 months may be necessary for complete elimination of the parasite and prevention of genital tissue pathology. This aggressive therapy may in turn play a key role decreasing HIV susceptibility in millions of people living in regions in which S. haematobium is endemic.

Snail intermediate host/Schistosoma haematobium relationships from three transmission sites in Benin (West Africa).

The relationships between three strains of Schistosoma haematobium (Doh, Sô-Tchanhoué and Toho-Todougba; from Benin, West Africa) and their snail hosts were assessed by measurement of several life-history traits, including the infection rate; pre-patent period; cercarial production of each parasite strain; and growth, fecundity and survival of the host snails. Adaptations to its local snail host was found for the Toho-Todougba strain and included a short pre-patent period, a long patent period and production of more cercariae in its local snail host. In contrast, the life-history traits of the Doh and Sô-Tchanhoué strains indicated non-local adaptations, as some sympatric host-parasite combinations were not compatible, the highest infection rates occurred in the allopatric snail Bulinus wrighti, and the duration of cercarial production was short because of the high level of mortality of the snails. Furthermore, snail reproduction ceased following infection by each of the three parasite strains, and the life-history traits were not influenced by the miracidial dose.

An outbreak of schistosomiasis in travellers returning from endemic areas: the importance of rigorous tracing in peer groups exposed to risk of infection.

BACKGROUND: Each year, schools across Scotland send their students on exchange programmes to Malawi. Between 2005 and 2009, 22.8% of Scotland's new cases of schistosomiasis were from freshwater exposure in Malawi, with 41.5% diagnosed in 15-24 year olds. In January 2011, a 17-year-old male presented to our urology department with visible haematuria following freshwater exposure during a school trip to Malawi. He was subsequently diagnosed with urinary schistosomiasis. METHODS: The potential involvement of other individuals from the trip prompted further public health enquiry. The school, public health department and education authorities were notified promptly and all individuals potentially exposed to Schistosoma haematobium were invited for screening. RESULTS: All 21 participants of the exchange programme underwent serological screening. Thirteen tested positive for Schistosoma infection. Only two individuals displayed symptoms of schistosomiasis; the other 11 were asymptomatic. CONCLUSIONS: Infection rates, even following a limited exposure to S. haematobium, are high. The majority of seropositive cases may never have symptoms. Therefore, a history of foreign travel to endemic schistosomiasis areas should be sought from any young person presenting with visible heamaturia and appropriate tests instigated. Schools should adopt policies forbidding activities involving freshwater exposure in Malawi. Effective public health measures must be set in place to trace and treat any other possible cases of exposure.

Parasitological and histopathological effects of immunosuppression in guinea-pigs (Cavia porcellus) experimentally infected with Schistosoma haematobium.

The parasitological and histopathological effects of immunosuppression in guinea-pigs (Cavia porcellus) experimentally infected with Schistosoma haematobium were studied. A total of 16 guinea-pigs were divided into four groups (four per group): non-immunosuppressed, non-infected group (NN); immunosuppressed, non-infected group (IN); immunosuppressed, infected group (II); non-immunosuppressed, infected group (NI). The IN and II groups were immunosuppressed with 5 mg/kg prednisolone while the II and NI animals were infected with 200-300 S. haematobium cercariae. Excretion of eggs in urine/faeces, worm burden and histopathology of some vital organs of the guinea-pigs were studied. Eggs of S. haematobium were observed in the urine of the NI and II groups from 9 weeks post-infection and in faeces from 10 and 13 weeks post-infection for the NI and II groups, respectively. However, II animals excreted more viable eggs in urine and faeces than those of the NI group. Worm recovery at 14 weeks post-infection showed that NI and II guinea-pigs had more female worms than male worms and a greater proportion of worm recovery for NI animals was of immature worms. Significant differences (P < 0.05) existed between female, male and immature worm burden of the two groups but not in their total worm burden (P>0.05). Histological changes, which were notably reactions to adult S. haematobium worms, were observed in the organs of the NI and II groups but these changes were seen more in the organs of the immunosuppressed, infected (II) than in the non-immunosuppressed, infected (NI) guinea-pigs. The results suggest that immunosuppression before infection increased worm survival and had a moderate effect on liver and bladder histology of S. haematobium infected guinea-pigs.

Host tissue proteomics reveal insights into the molecular basis of Schistosoma haematobium-induced bladder pathology.

Urogenital schistosomiasis remains a major public health concern worldwide. In response to egg deposition, the host bladder undergoes gross and molecular morphological changes relevant for disease manifestation. However, limited mechanistic studies to date imply that the molecular mechanisms underlying pathology are not well-defined. We leveraged a mouse model of urogenital schistosomiasis to perform for the first time, proteome profiling of the early molecular events that occur in the bladder after exposure to S. haematobium eggs, and to elucidate the protein pathways involved in urogenital schistosomiasis-induced pathology. Purified S. haematobium eggs or control vehicle were microinjected into the bladder walls of mice. Mice were sacrificed seven days post-injection and bladder proteins isolated and processed for proteome profiling using mass spectrometry. We demonstrate that biological processes including carcinogenesis, immune and inflammatory responses, increased protein translation or turnover, oxidative stress responses, reduced cell adhesion and epithelial barrier integrity, and increased glucose metabolism were significantly enriched in S. haematobium infection. S. haematobium egg deposition in the bladder results in significant changes in proteins and pathways that play a role in pathology. Our findings highlight the potential bladder protein indicators for host-parasite interplay and provide new insights into the complex dynamics of pathology and characteristic bladder tissue changes in urogenital schistosomiasis. The findings will be relevant for development of improved interventions for disease control.