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Background: The Geshiyaro project aims to assess the feasibility of interrupting transmission of soil-transmitted helminths (STH) and schistosome (SCH) infection in the Wolaita zone of southern Ethiopia through high coverage community-wide mass drug administration (MDA), in combination with improved water, sanitation, and hygiene services and behaviour change communication delivered through the existing health care infrastructure. To accurately measure treatment coverage a population census was conducted enrolling individuals with biometric fingerprinting and barcoded ID cards. This paper details the baseline census and parasitology surveys conducted before the start of any interventions. Methods: The census was conducted in five of the 15 Wolaita districts between October 2018 and December 2019, enrolling all consenting participants from every household. Simultaneously, a cross-sectional parasitology survey was conducted in 130 out of 361 randomly selected communities from all 15 districts, with 100 individuals across all age groups (infant to adult) per community providing stool and urine for analysis by duplicate Kato-Katz and a point-of-care circulating cathodic antigen (POC-CCA) to test for Schistosoma mansoni and STH, and microhaematuria and urine filtration for Schistosoma haematobium. Of the 130 communities, 30 were randomly selected for annual, longitudinal parasitological monitoring, with 150 randomly selected individuals from infant to adult providing two days of stool and urine samples for analysis by the same diagnostic tests per community. Results: In total 97,919 households participated in the baseline census enrolling 466,071 individuals, with parasitological data obtained from 10,785 people. At baseline, 15.5% were infected with at least one STH species, with Ascaris lumbricoides (9.5%), followed by hookworm (7.2%) and Trichuris trichiura (1.8%). Substantial heterogeneity in STH prevalence was observed between communities ranging from 0% to 61% where most infections were low intensity. Schistosoma mansoni infection was the dominant schistosome infection (0.85% by Kato-Katz and 13.3% by POC-CCA trace negative and 21.5% trace positive), with few Schistosoma haematobium infections identified (2.77% haematuria positive and 0.13% positive by urine filtration). Conclusions: While the national control program in Ethiopia has made good progress in reducing prevalence of STH and SCH in Wolaita since it was launched in 2015, there remain areas of persistent infection suggesting the existence of environmental or behavioural risk factors that contribute to ongoing transmission. This project aims to identify the most efficient intervention strategies to reduce community burden and reach interruption of transmission. Author summary: The standard method of control for intestinal worms, a common public health problem in sub-Saharan Africa, is distribution of deworming treatment on a mass scale. These infections are difficult to eliminate as re-infection is common due a combination of people not being treated and high exposure to the parasites through poor access to sanitation and clean water. The Geshiyaro project in Ethiopia has the ambitious goal of breaking the transmission cycle of such infections through treatment in combination with provision of water and sanitation services. The impact of these interventions is being measured using a unique approach, that is, using finger printing to evaluate prevalence of infection with compliance to treatment and access water or sanitation. [ABSTRACT FROM AUTHOR]

Schistosoma haematobium is the most prevalent of the human-infecting schistosome species, causing significant morbidity in endemically exposed populations. Despite this, it has been relatively understudied compared to its fellow species, S. mansoni. Here we provide the first comprehensive characterization of the S. haematobium Tegument Allergen-Like protein family, a key protein family directly linked to protective immunity in S. mansoni infection. Comparable with observations for S. mansoni, parasite phylogenetic analysis and relative gene expression combined with host serological analysis support a cross-reactive relationship between S. haematobium TAL proteins, exposed to the host immune system as adult worms die, and closely related proteins, exposed during penetration by the infecting cercarial and early schistosomulae stages. Specifically, our results strengthen the evidence for host immunity driven by cross-reactivity between family members TAL3 and TAL5, establishing it for the first time for S. haematobium infection. Furthermore, we build upon this relationship to include the involvement of an additional member of the TAL protein family, TAL11 for both schistosome species. Finally, we show a close association between experience of infection and intensity of transmission and the development of protective IgE responses to these antigens, thus improving our knowledge of the mechanisms by which protective host immune responses develop. This knowledge will be critical in understanding how control efforts such as mass drug administration campaigns influence the development of host immunity and subsequent patterns of infection and disease within endemic populations. Author summary: S. haematobium is the most prevalent of the human infecting schistosomes. Along with S. mansoni, it is responsible for the majority of schistosomiasis cases that are borne by the populations of sub-Saharan Africa, where the global burden of this infection is centered. Here, we provide insight into the IgE antibody response that protects against these infections. Through utilization of in silico analysis in combination with immuno-epidemiological studies, we explore the relationship between host immune protection and a parasite protein family named the Tegument Allergen-Like (TAL) proteins. Our results show that several members of the TAL protein family are important in host protection to both these major schistosome species. For the first time we demonstrate that a progressive cross-reactive TAL-IgE response occurs against S. haematobium, similar to that previous observed in S. mansoni infection. We additionally expand upon previous knowledge for S. mansoni, identifying further complexity in the cross-reactive relationship between TAL family members, providing evidence of a key role for family member TAL11 in induction of the protective host immune response. [ABSTRACT FROM AUTHOR]

Populations within schistosomiasis control areas, especially those in Africa, are recommended to receive regular mass drug administration (MDA) with praziquantel (PZQ) as the main strategy for controlling the disease. The impact of PZQ treatment on schistosome genetics remains poorly understood, and is limited by a lack of high-resolution genetic data on the population structure of parasites within these control areas. We generated whole-genome sequence data from 174 individual miracidia collected from both children and adults from fishing communities on islands in Lake Victoria in Uganda that had received either annual or quarterly MDA with PZQ over four years, including samples collected immediately before and four weeks after treatment. Genome variation within and between samples was characterised and we investigated genomic signatures of natural selection acting on these populations that could be due to PZQ treatment. The parasite population on these islands was more diverse than found in nearby villages on the lake shore. We saw little or no genetic differentiation between villages, or between the groups of villages with different treatment intensity, but slightly higher genetic diversity within the pre-treatment compared to post-treatment parasite populations. We identified classes of genes significantly enriched within regions of the genome with evidence of recent positive selection among post-treatment and intensively treated parasite populations. The differential selection observed in post-treatment and pre-treatment parasite populations could be linked to any reduced susceptibility of parasites to praziquantel treatment. Author summary: Schistosomiasis is caused by parasitic helminths of the genus Schistosoma. Schistosoma mansoni is the primary cause of intestinal schistosomiasis, a devastating and widespread parasitic infection that causes morbidity, death and socio-economic impact on endemic communities across the world and especially sub-Saharan Africa. Using whole-genome sequencing, we were able to elucidate the parasite population within Lake Victoria island fishing communities in Uganda which are among the major hotspots for schistosomiasis. We further assessed genetic markers that might be linked to recent observations concerning reduced susceptibility to praziquantel, the major drug used in the treatment of this disease. Whole-genome data on the population genetics of S. mansoni in an African setting will provide a strong basis for future functional genomics or transcriptomic studies that will be key to identifying drug targets, improving existing drugs or developing new therapeutic interventions. [ABSTRACT FROM AUTHOR]

Schistosomiasis, also known as bilharzia or snail fever, is a debilitating neglected tropical disease (NTD), caused by parasitic trematode flatworms of the genus Schistosoma, that has an annual mortality rate of 280,000 people in sub-Saharan Africa alone. Schistosomiasis is transmitted via contact with water bodies that are home to the intermediate host snail which shed the infective cercariae into the water. Schistosome lifecycles are complex, and while not all schistosome species cause human disease, endemic regions also typically feature animal-infecting schistosomes that can have broader economic and/or food security implications. Therefore, the development of species-specific Schistosoma detection technologies may help to inform evidence-based local environmental, food security and health systems policy making. Crucially, schistosomiasis disproportionally affects low- and middle-income (LMIC) countries and for that reason, environmental screening of water bodies for schistosomes may aid with the targeting of water, sanitation, and hygiene (WASH) interventions and preventive chemotherapy to regions at highest risk of schistosomiasis transmission, and to monitor the effectiveness of such interventions at reducing the risk over time. To this end, we developed a DNA-based biosensor termed Specific Nucleic AcId Ligation for the detection of Schistosomes or 'SNAILS'. Here we show that 'SNAILS' enables species-specific detection from genomic DNA (gDNA) samples that were collected from the field in endemic areas. Author summary: Schistosomiasis is a neglected tropical disease, caused by the parasitic trematodes of the genus Schistosoma. Schistosomiasis is endemic to regions within Africa, Asia and South America with at least 250 million people infected and a further 779 million at risk of infection. The lifecycle of schistosomes are complex and involve specific freshwater intermediate snail hosts which shed infective cercariae into the waterbodies they inhabit. Schistosomiasis is subsequently transmitted to humans or animals that contact cercariae contaminated water. In Africa, human disease is largely caused by Schistosoma mansoni and Schistosoma haematobium. However, endemic regions also typically feature animal-infecting schistosomes that can have broader economic and/or food security implications. Therefore, the development of species-specific Schistosoma detection technologies may help to inform local environmental, food security and health programmes. To this end, we re-purposed a nucleic acid detection technology to enable the detection of different schistosome species. Our DNA-biosensor, abbreviated as 'SNAILS', employs carefully designed probes that recognise species-specific DNA sequences, coupled with enzymatic amplification steps, and a fluorescent signal-dye to indicate a positive detection. 'SNAILS' successfully differentiates between S. mansoni and S. haematobium samples and could conceivably be employed within future global health programmes. [ABSTRACT FROM AUTHOR]

Background: Undernutrition and schistosomiasis are public health problems and often occur in low and middle-income countries. Protein undernutrition can alter the host-parasite environment system and aggravate the course of schistosomiasis. This study aimed to assess the impact of a low-protein diet on the efficacy of praziquantel. Methodology/Principal findings: Thirty-day-old mice were fed with a low-protein diet, and 40 days later, they were individually infected with fifty Schistosoma mansoni cercariae. A 28-day-treatment with praziquantel at 100 mg/kg for five consecutive days followed by distilled water begins on the 36th day post-infection. Mice were sacrificed on the 64th day post-infection. We determined the parasitological burden, liver and intestine histomorphometry, liver injury, and immunomodulation parameters. Praziquantel treatment of infected mice fed with a standard diet (IN-PZQ) resulted in a significant reduction of worm and egg burdens and a normalization of iron and calcium levels. The therapy also improved schistosomiasis-induced hepatopathy and oxidative stress. The anti-inflammatory and immunomodulatory activities of praziquantel were also significant in these mice. When infected mice receiving the low-protein diet were treated with praziquantel (ILP-PZQ), the body weight loss and hepatomegaly were not alleviated, and the worm and liver egg burdens were significantly higher than those of IN-PZQ mice (P < 0.001). The treatment did not reduce the increased activities of ALT and γ-GGT, the high malondialdehyde concentration, and the liver granuloma volume. The iron and calcium levels were not ameliorated and differed from those of IN-PZQ mice (P < 0.001 and P < 0.05). Moreover, in these mice, praziquantel treatment did not reverse the high level of IL-5 and the low mRNA expression of CCL3/MIP-1α and CXCL-10/IP-10 induced by S. mansoni infection. Conclusion/Significance: These results demonstrated that a low-protein diet reduced the schistosomicidal, antioxidant, anti-inflammatory, and immunomodulatory activities of praziquantel. Author summary: Almost 90% of people requiring schistosomiasis preventive chemotherapy in 2018 lived in sub-Saharan Africa. Besides, 205.3 million children under five years suffer and die of undernutrition in low- and middle-income countries. The physiopathology of schistosomiasis mansoni involves liver damage, oxidative stress, and perturbation of the immune response. These disturbances are intensified by undernutrition. Praziquantel is used to treat schistosomiasis, but its efficacy on the comorbidity of S. mansoni infection and undernutrition has not been investigated. We conducted this study to assess the effectiveness of praziquantel on S. mansoni infection in mice fed with a low-protein diet. We recorded growth retardation, hepatomegaly, and high worm and egg burdens in mice fed with a low-protein diet and treated with PZQ. Moreover, the treatment did not reverse the liver function injury, oxidative stress, high iron level, and low calcium level. The proinflammatory cytokine IL-5 was still high, and the gene expression of some macrophage-associated chemokines was reduced. Therefore, this study demonstrated that in a murine model of a low-protein diet, the efficacy of praziquantel on S. mansoni infection was reduced. It also underlines the importance of targeting protein deficiency and malnutrition in populations living in schistosomiasis endemic areas for efficient disease control. [ABSTRACT FROM AUTHOR]

Schistosomiasis is a potentially lethal parasitic disease that profoundly impacts systemic immune function in chronically infected hosts through mechanisms that remain unknown. Given the immunoregulatory dysregulation experienced in infected individuals, this study examined the impact of chronic schistosomiasis on the sustainability of vaccine-induced immunity in both children living in endemic areas and experimental infections in mice. Data show that chronic Schistosoma mansoni infection impaired the persistence of vaccine specific antibody responses in poliovirus-vaccinated humans and mice. Mechanistically, schistosomiasis primarily fostered plasmablast and plasma cell death in the bone marrow and removal of parasites following praziquantel treatment reversed the observed cell death and partially restored vaccine-induced memory responses associated with increased serum anti-polio antibody responses. Our findings strongly suggest a previously unrecognized mechanism to explain how chronic schistosomiasis interferes with an otherwise effective vaccine regimen and further advocates for therapeutic intervention strategies that reduce schistosomiasis burden in endemic areas prior to vaccination. Author summary: Schistosoma mansoni (S. mansoni), a schistosomiasis disease-causing parasite species, is most common in sub-Saharan Africa. Schistosoma mansoni can influence immune responses and trigger physiological imbalances in their human and animal hosts, which improve their survival and multiplication in the host. These influences can disrupt the host's ability to maintain long term protective immunity mounted by vaccines for infectious diseases. Here, we investigated the impact of S. mansoni infection on poliovirus vaccine immunity in school-aged children and mice. We found that the parasite reduced its host's ability to maintain protective blood antibodies produced by immune responses to poliovirus vaccines. We also found that S. mansoni infection reduces the maintenance of antibody-producing plasma cells in the bone marrow of vaccinated mice. Our data showed that treating S. mansoni infected children and mice with praziquantel mitigated the parasite's negative influences on vaccine immunity. These findings suggest that in regions where schistosomiasis is endemic, the Schistosoma spp. parasites may be notable causes of suboptimal viral vaccine immunity maintenance by children, leaving them vulnerable to vaccine-preventable diseases. [ABSTRACT FROM AUTHOR]

Background: Schistosomiasis, caused by Schistosoma mansoni, is of great significance to public health in sub–Saharan Africa. In the Democratic Republic of Congo (DRC), information on the burden of S. mansoni infection is scarce, which hinders the implementation of adequate control measures. We assessed the geographical distribution of S. mansoni infection across Ituri province in north-eastern DRC and determined the prevailing risk factors. Methods/Principal findings: Two province–wide, community–based studies were conducted. In 2016, a geographical distribution study was carried out in 46 randomly selected villages across Ituri. In 2017, an in–depth study was conducted in 12 purposively–selected villages, across the province. Households were randomly selected, and members were enrolled. In 2016, one stool sample was collected per participant, while in 2017, several samples were collected per participant. S. mansoni eggs were detected using the Kato–Katz technique. In 2017, a point–of–care circulating cathodic S. mansoni antigen (POC–CCA) urine test was the second used diagnostic approach. Household and individual questionnaires were used to collect data on demographic, socioeconomic, environmental, behavioural and knowledge risk factors. Of the 2,131 participants in 2016, 40.0% were positive of S. mansoni infection. Infection prevalence in the villages ranged from 0 to 90.2%. Of the 707 participants in 2017, 73.1% were tested positive for S. mansoni. Prevalence ranged from 52.8 to 95.0% across the health districts visited. Infection prevalence increased from north to south and from west to east. Exposure to the waters of Lake Albert and the villages' altitude above sea level were associated with the distribution. Infection prevalence and intensity peaked in the age groups between 10 and 29 years. Preschool children were highly infected (62.3%). Key risk factors were poor housing structure (odds ratio [OR] 2.1, 95% 95% confidence interval [CI] 1.02–4.35), close proximity to water bodies (OR 1.72, 95% CI 1.1–2.49), long-term residence in a community (OR 1.41, 95% CI 1.11–1.79), lack of latrine in the household (OR 2.00, 95% CI 1.11–3.60), and swimming (OR 2.53, 95% CI 1.20–5.32) and washing (OR 1.75, 95% CI 1.10–2.78) in local water bodies. Conclusions/Significance: Our results show that S. mansoni is highly endemic and a major health concern in Ituri province, DRC. Infection prevalence and intensity, and the prevailing socioeconomic, environmental, and behavioural risk factors in Ituri reflect intense exposure and alarming transmission rates. A robust plan of action is urgently needed in the province. Author summary: Intestinal schistosomiasis threatens many people in the tropical world, particularly those in Sub–Saharan Africa. Information on schistosomiasis in the Democratic Republic of Congo (DRC) is very scarce, which is a major barrier to planning and implementing efficient control programmes. We conducted two community–based studies with the objective of assessing the geographical distribution of S. mansoni infection across the Ituri province in north-eastern DRC and determining the prevailing risk factors. In 2016, a geographical distribution and in 2017, an in–depth studies were conducted in selected villages. Households were randomly selected and members, aged one year and older and present on the survey day, were enrolled. In 2016, one stool sample was examined per participant, whereas several stool samples were examined for each participant in 2017. S. mansoni eggs were detected using the Kato–Katz technique. A point–of–care circulating cathodic S. mansoni antigen (POC–CCA) urine test was also used in 2017. Household and individual questionnaires were used to collect demographic, socioeconomic, environmental, behavioural and knowledge data. In 2016, of the 2,131 participants, 40.0% of were infected with S. mansoni. Of the 707 participants in 2017, 73.1% were tested positive for S. mansoni. Infection prevalence increased from north to south and from west to east. Exposure to the Lake Albert and villages' altitude were main drivers of the distribution. Men and women had the same infection risk. Infection prevalence and intensity peaked in the age groups between 10 and 29 years. Preschool children were highly infected. Poor housing structure, proximity to water bodies, long–term residence in a community, lack of latrine in the household, and swimming and washing in local water bodies were the main risk factors. Our results confirm that S. mansoni is highly endemic in Ituri province, DRC. Both infection prevalence and intensity indicate intense exposure and alarming transmission. Control interventions are warranted and should pay attention to high–risk communities and population groups, including preschool children. [ABSTRACT FROM AUTHOR]

Background: Reducing morbidity is the main target of schistosomiasis control efforts, yet only rarely do control programmes assess morbidity linked to Schistosoma sp. infection. In the Democratic Republic of Congo (DRC), and particularly in north-eastern Ituri Province, little is known about morbidity associated with Schistosoma mansoni infection. For this reason, we aimed to assess intestinal and hepatosplenic morbidity associated with S. mansoni infection in Ituri Province. Methods/Principal findings: In 2017, we conducted a cross-sectional study in 13 villages in Ituri Province, DRC. S. mansoni infection was assessed with a Kato-Katz stool test (2 smears) and a point-of-care circulating cathodic antigen (POC-CCA) urine test. A questionnaire was used to obtain demographic data and information about experienced intestinal morbidity. Each participant underwent an abdominal ultrasonography examination to diagnose hepatosplenic morbidity. Of the 586 study participants, 76.6% tested positive for S. mansoni. Intestinal morbidity reported in the two preceding weeks was very frequent, and included abdominal pain (52.7%), diarrhoea (23.4%) and blood in the stool (21.5%). Hepatosplenic morbidity consisted of abnormal liver parenchyma patterns (42.8%), hepatomegaly (26.5%) and splenomegaly (25.3%). Liver pathology (adjusted odds ratio [aOR] 1.20, 95% confidence interval [CI] 1.06–1.37, p = 0.005) was positively and significantly associated with S. mansoni infection. Hepatomegaly (aOR 1.52, 95% CI 0.99–2.32, p = 0.053) and splenomegaly (aOR 1.12, 95% CI 0.73–1.72, p = 0.619) were positively but not significantly associated with S. mansoni infection at the individual level. At the village level, S. mansoni prevalence was positively associated with the prevalence of hepatomegaly and splenomegaly. High-intensity S. mansoni infections were associated with diarrhoea, blood in the stool, hepatomegaly, splenomegaly, and liver parenchyma (C, D, E and F pathology patterns). Four study participants were diagnosed with ascites and five reported hematemesis. Conclusions/Significance: Our study documents a high burden of intestinal and hepatosplenic morbidity associated with S. mansoni infection status in Ituri Province. The findings call for targeted interventions to address both S. mansoni infection and related morbidity. Author summary: Schistosomiasis caused by Schistosoma mansoni is of great public health importance in sub-Saharan Africa. The World Health Organization (WHO) recommends that control efforts aim to reduce morbidity through large-scale intervention programmes. However, intestinal and liver morbidity is rarely assessed in such control programmes. Hence, little is known about (i) the magnitude of the intestinal and liver morbidity burden in the community, or about (ii) the morbidity associated with S. mansoni infection, specifically. We conducted a cross-sectional study in which we assessed intestinal morbidity by questionnaire and liver morbidity by abdominal ultrasonography. Additionally, we determined the infection status of the study participants using standard diagnostic procedures (Kato-Katz technique and point-of-care cathodic circulating S. mansoni antigen [POC-CCA] urine test). Among the 586 study participants, aged six years and older, from 13 villages in Ituri Province, DRC, we observed a high degree of intestinal (23.4% with diarrhoea; 21.5% with blood in stool) and hepatosplenic morbidity (42.8% with abnormal liver C, D, E, and F patterns; 26.5% with an enlarged liver; 25.3% with an enlarged spleen). S. mansoni infection was associated with liver and spleen enlargement. Likewise, S. mansoni infection intensity was linked to diarrhoea, to liver and spleen enlargement and to pathological changes in the liver parenchyma. At village level, we observed that the prevalence of an enlarged liver and spleen among patients increased with the prevalence of S. mansoni infection. We conclude that the population of Ituri Province carries an alarming burden of intestinal, liver and spleen morbidity associated with S. mansoni infection. A comprehensive control programme to address this infection and disease burden is urgently required. [ABSTRACT FROM AUTHOR]

Background: Schistosomiasis remains a global-health problem with over 90% of its burden concentrated in Africa. Field studies reflect the complex ways in which socio-cultural and socio-economic variables, affect the distribution of Schistosoma infections across different populations. This review set out to systematically investigate and quantify the differences in Schistosoma infection burdens between males and females in Africa for two of the most prevalent Schistosoma species—Schistosoma mansoni and Schistosoma haematobium. Methodology: We searched (from inception to 11th March 2020) Embase, MEDLINE, PubMed, and Web of Science for relevant studies on schistosomiasis. We included studies that report S. mansoni and/or S. haematobium prevalence and/or intensity data distributed between males and females. We conducted meta-analyses on the male to female (M:F) prevalence of infection ratios. Subgroup analyses were performed according to study baseline prevalence, sample size and the lower and upper age limit of study participants. We also present a descriptive analysis of differential risk and intensity of infection across males and females. Evidence for differences in the prevalence of schistosomiasis infection between males and females is presented, stratified by Schistosoma species. Result: We identified 128 relevant studies, with over 200,000 participants across 23 countries. Of all the reported differences in the prevalence of infection between males and females, only 41% and 34% were statistically significant for S. mansoni and S. haematobium, respectively. Similar proportions of studies (27% and 34% for for S. haematobium and S. mansoni, respectively) of the reported differences in intensity of infection between males and females were statistically significant. The meta-analyses summarized a higher prevalence of infection in males; pooled random-effects weighted M:F prevalence of infection ratios were 1.20 (95% CI 1.11–1.29) for S. haematobium and 1.15 (95% CI 1.08–1.22) for S. mansoni. However, females are underrespresented in some of the studies. Additionally, there was significant heterogeneity across studies (Higgins I2 statistic (p-values < 0.001, I2values>95%)). Results of the subgroup analysis showed that the baseline prevalence influenced the M:F prevalence ratios for S. haematobium and S. mansoni, with higher M:F prevalence of infection ratios in settings with a lower baseline prevalence of infection. Across the studies, we identified four major risk factors associated with infection rates: occupational and recreational water contact, knowledge, socio-economic factors and demographic factors. The effect of these risk factors on the burden of infection in males and females varied across studies. Conclusions: We find evidence of differences in prevalence of infection between males and females which may reflect differences in gender norms and water contact activities, suggesting that policy changes at the regional level may help ameliorate gender-related disparities in schistosomiasis infection burden. Collecting, robustly analysing, and reporting, sex-disaggregated epidemiological data, is currently lacking, but would be highly informative for planning effective treatment programmes and establishing those most at risk of schistosomiasis infections. Author summary: Schistosomiasis is a parasitic waterborne disease affecting more than 240 million people worldwide every year, especially in sub-Saharan Africa. The difference in schistosoma infection prevalence, infection intensity and risk between males and females has rarely been quantified. In this study, we aim to qualitatively and quantitatively synthesise published studies that present sex-disaggregated epidemiological data and investigate gender differences (e.g. those driven by social and cultural norms) that predispose males or females to higher risk of infection. Based on the 123 studies included in our meta-analysis, we found a higher prevalence of Schistosoma (S. mansoni and S. haematobium) in males. [ABSTRACT FROM AUTHOR]

Background: Schistosomiasis is one of the widely distributed neglected tropical diseases. It is a serious public health problem in sub-Saharan Africa. The disease is highly prevalent and widely distributed in Ethiopia due to suitable environmental factors and human activities. The prevalence and infection intensity varied from locality to locality in the country. This study aimed to assess the prevalence and intensity of S. mansoni infection and associated risk factors among schoolchildren around Lake Tana. Methods: A school-based cross-sectional study was conducted among 710 schoolchildren from February to April 2021 in eight selected primary schools around Lake Tana. A questionnaire was used to collect data on socio-demographic information and potential risk factors of S. mansoni infection. After collecting socio-demographic information, students were requested to bring about 2grams of stool specimens for parasitological examination. The collected stool samples were processed using a single Kato-Katz and Ritchie's concentration techniques. The data were analyzed using SPSS software version 23 and factors with a p-value < 0.05 were considered as statistically significant. Results: The overall prevalence of S. mansoni was 34.9% (95% CI: 31.4–38.7) among schoolchildren in the study area. The eggs per gram (EPG) of stool ranged from 24 to 1659 with arithmetic and geometric mean values of 138.1 EPG and 85.1 EPG, respectively. The majority of S. mansoni infections (61.4%) were classified as low infection intensity. Among the different determinant factors being male (AOR = 1.74; 95%CI = 1.233–2.457; P-value = 0.002), bathing habits (AOR = 1.494; 95%CI = 1.013–2.199; P-value = 0.043) and students attending at Qunzela primary school (AOR = 10.545; 95%CI = 3.264–34.067; P-value = 0.001), Alabo primary school (AOR = 3.386; 95%CI = 1.084–10.572; P-value = 0.036) were significantly associated with S. mansoni infection. Conclusion: This study revealed that more than one-third of schoolchildren were infected by S. mansoni in the study area. The majority of the infections were classified as low infection intensity. Being male, bathing habits and schools in which students attended were independent explanatory factors for S. mansoni infection. Therefore, integrated control strategies are needed to improve the health conditions of schoolchildren in the study area. Author summary: We conducted a school-based cross-sectional study to assess the prevalence and intensity of Schistosoma mansoni infection and associated risk factors. Stool samples were collected from 681 schoolchildren and processed using Kato-Katz and Ritchie's concentration techniques. Among those students, 238 (34.9%) were infected with S. mansoni. Kato-Katz and Ritchie's concentration detect 220 (92.4%) and 165 (69.3%) of the total positive cases, respectively. Most of the S. mansoni infections were categorized as low infection intensity based on egg per gram of stool. Among the potential risk factors assessed; being male, bathing habits in open water and schools in which students attended were independent predictors for S. mansoni infection. [ABSTRACT FROM AUTHOR]

Background: The prevalence of Schistosoma mansoni infection is usually assessed by the Kato-Katz diagnostic technique. However, Kato-Katz thick smears have low sensitivity, especially for light infections. Egg count models fitted on individual level data can adjust for the infection intensity-dependent sensitivity and estimate the 'true' prevalence in a population. However, application of these models is complex and there is need for adjustments that can be done without modelling expertise. This study provides estimates of the 'true' S. mansoni prevalence from population summary measures of observed prevalence and infection intensity using extensive simulations parametrized with data from different settings in sub-Saharan Africa. Methodology: An individual-level egg count model was applied to Kato-Katz data to determine the S. mansoni infection intensity-dependent sensitivity for various sampling schemes. Observations in populations with varying forces of transmission were simulated, using standard assumptions about the distribution of worms and their mating behavior. Summary measures such as the geometric mean infection, arithmetic mean infection, and the observed prevalence of the simulations were calculated, and parametric statistical models fitted to the summary measures for each sampling scheme. For validation, the simulation-based estimates are compared with an observational dataset not used to inform the simulation. Principal findings: Overall, the sensitivity of Kato-Katz in a population varies according to the mean infection intensity. Using a parametric model, which takes into account different sampling schemes varying from single Kato-Katy to triplicate slides over three days, both geometric and arithmetic mean infection intensities improve estimation of sensitivity. The relation between observed and 'true' prevalence is remarkably linear and triplicate slides per day on three consecutive days ensure close to perfect sensitivity. Conclusions/Significance: Estimation of 'true' S. mansoni prevalence is improved when taking into account geometric or arithmetic mean infection intensity in a population. We supply parametric functions and corresponding estimates of their parameters to calculate the 'true' prevalence for sampling schemes up to 3 days with triplicate Kato-Katz thick smears per day that allow estimation of the 'true' prevalence. Author summary: The World Health Organization (WHO) recommends the Kato-Katz diagnostic method, i.e., counting eggs in a thick-smear of stool using light microscopy, for estimation of Schistosoma mansoni infection prevalence. While the diagnostic specificity of Kato-Katz very high, the sensitivity varies strongly with infection intensity and the number of samples collected and thick smears per sample tested. Therefore, the performance of Kato-Katz in a population depends on the distribution of infections in the population and individual-level data is needed to determine the 'true' prevalence of infection. However, modelling capacity to determine 'true' prevalence from individual-level data is often not available to programme managers. In this study, we therefore provide simple equations to estimate the 'true' prevalence and associated uncertainty from observed prevalence and arithmetic or geometric mean infection intensity for a variety of common sampling schemes. We find that by including information about the mean infection intensity in a population the estimation of 'true' prevalence can be improved compared to assuming a constant value for the diagnostic sensitivity and supply parameters and functions to calculate the 'true' prevalence of infection. [ABSTRACT FROM AUTHOR]

Currently there is only one method of treatment for human schistosomiasis, the drug praziquantel. Strong selective pressure has caused a serious concern for a rise in resistance to praziquantel leading to the necessity for additional pharmaceuticals, with a distinctly different mechanism of action, to be used in combination therapy with praziquantel. Previous treatment of Schistosoma mansoni included the use of oxamniquine (OXA), a prodrug that is enzymatically activated in S. mansoni but is ineffective against S. haematobium and S. japonicum. The oxamniquine activating enzyme was identified as a S. mansoni sulfotransferase (SmSULT-OR). Structural data have allowed for directed drug development in reengineering oxamniquine to be effective against S. haematobium and S. japonicum. Guided by data from X-ray crystallographic studies and Schistosoma worm killing assays on oxamniquine, our structure-based drug design approach produced a robust SAR program that tested over 300 derivatives and identified several new lead compounds with effective worm killing in vitro. Previous studies resulted in the discovery of compound CIDD-0066790, which demonstrated broad-species activity in killing of schistosome species. As these compounds are racemic mixtures, we tested and demonstrate that the R enantiomer CIDD-007229 kills S. mansoni, S. haematobium and S. japonicum better than the parent drug (CIDD-0066790). The search for derivatives that kill better than CIDD-0066790 has resulted in a derivative (CIDD- 149830) that kills 100% of S. mansoni, S. haematobium and S. japonicum adult worms within 7 days. We hypothesize that the difference in activation and thus killing by the derivatives is due to the ability of the derivative to fit in the binding pocket of each sulfotransferase (SmSULT-OR, ShSULT-OR, SjSULT-OR) and to be efficiently sulfated. The purpose of this research is to develop a second drug to be used in conjunction with praziquantel to treat the major human species of Schistosoma. Collectively, our findings show that CIDD-00149830 and CIDD-0072229 are promising novel drugs for the treatment of human schistosomiasis and strongly support further development and in vivo testing. Author summary: Schistosomiasis affects more than 229 million people in 78 countries of the world. The main treatment is Mass Drug Administration with praziquantel. With donations to the World Health Organization, approximately 250 million tablets of praziquantel are being administered in sub-Saharan Africa where about 90% of the cases of schistosomiasis occur. The concern with a monotherapy is the development of drug resistance. The need for new drugs with a different mode of action to be used in combination with praziquantel is great. In this regard, we have taken oxamniquine, a drug that was previously used to treat Schistosoma mansoni but was ineffective against S. haematobium and S. japonicum, and determined the enzyme responsible for activation of oxamniquine as a sulfotransferase. With this knowledge and the sulfotransferase crystal structure, we were able to determine the mode of action of the drug and develop an iterative approach of soaking oxamniquine derivatives into sulfotransferase crystals, determining structure function relationships, synthesizing new derivatives and testing them in an in vitro killing assay. The most effective derivatives are soaked into new crystals and the process repeated. We have identified two derivatives, CIDD-0072229 and CIDD-149830 that will kill S. haematobium and S. japonicum in addition to S. mansoni. CIDD-149830 will kill 100% of the worms of all three species within 7 days. [ABSTRACT FROM AUTHOR]

Background: Clinical observations and animal studies have suggested that Salmonella intestinal carriage is promoted by concurrent Schistosoma infection. The present study assessed association of Salmonella intestinal carriage and Schistosoma mansoni infection among individuals in a Schistosoma endemic area in sub-Saharan Africa. Methods: From November 2015 to March 2016, a cross-sectional community-wide study was conducted in Kifua II, a rural village in Kongo Central Province, Democratic Republic of Congo. Stool samples were collected and analyzed for Salmonella intestinal carriage (culture) and Schistosoma mansoni infection (Kato Katz microscopy with determination of egg load). Salmonella Typhimurium and Enteritidis isolates were assessed for genetic similarity with blood culture isolates obtained during the same period in a neighboring hospital using multi-locus variable-numbers tandem repeat analysis (MLVA). Results: A total of 1,108 participants were included (median age 15 years (IQR: 7–36), male-to-female ratio of 1:1.1). The overall prevalence of Schistosoma mansoni infection and non-typhoidal Salmonella carriage was 51.2% (95% CI: 48.2–54.1) and 3.4% (95% CI: 2.5–4.7) respectively, with 2.2% (95% CI: 1.5–3.2) of participants coinfected. The proportion of Salmonella carriage tended to be higher among Schistosoma mansoni infected participants compared to non-infected participants but this difference did not reach statistical significance (4.2% versus 2.6%, p = 0.132). However, the proportion of Salmonella carriage among participants with a heavy Schistosoma mansoni infection was significantly higher compared to those with a light and moderate infection (8.7% versus 3.2%, p = 0.012) and compared to Schistosoma mansoni negatives (8.7% versus 2.6%, p = 0.002). The 38 Salmonella isolates comprised five and four Enteritidis and Typhimurium serotypes respectively, the majority of them had MLVA types identical or similar to those observed among blood culture isolates. Conclusion: Salmonella intestinal carriage was associated with a heavy intensity of Schistosoma mansoni infection. Further studies are needed to address causation. Author summary: Salmonella intestinal carriage may be facilitated by infection with Schistosoma mansoni, which is a flatworm that lives in the small blood vessels of the human intestinal tract. This situation has been described in tropical low and middle income countries, where both pathogens are endemic. The present study aimed to assess the association of Salmonella intestinal carriage with Schistosoma mansoni infection in Kifua II village, located in the Kongo Central province of the Democratic republic of Congo. We collected stool samples from 1,108 inhabitants of the village and analysed them for Salmonella (culture) and Schistosoma mansoni eggs (microscopy). Our findings showed that 3.4% of the participants had Salmonella in their stool and 51.2% were infected with Schistosoma mansoni. There was no association between overall Schistosoma infection and Salmonella carriage but Salmonella carriage was significantly higher among participants with heavy Schistosoma infection compared to those with a light and moderate infection (8.7% versus 3.2%, p = 0.012) and compared to those without Schistosoma mansoni infection (8.7% versus 2.6%, p = 0.002). Further, we showed that some Salmonella isolates recovered from stool were very similar to isolates obtained from invasive infections (blood cultures from patients in a neighbouring hospital). [ABSTRACT FROM AUTHOR]

Background: Schistosoma mansoni is one of the most common helminth infections affecting a large population of people in sub-Saharan Africa. This helminth infection is known to cause immunomodulation which has affected the efficacy of a number of vaccines. This study examined whether a chronic schistosoma infection has an effect on the immunogenicity of HPV vaccine which is currently administered to girls and women aged 9 to 24. Little is known about the immune responses of the HPV vaccine in individuals with chronic schistosomiasis. Methods: This study was carried out at the Institute of Primate Research (IPR) and involved an Olive baboon model. The experimental animals were randomly placed into three groups (n = 3–4); Two groups were infected with S. mansoni cercaria, and allowed to reach chronic stage (week 12 onwards), at week 13 and 14 post-infection, one group was treated with 80mg/kg of praziquantel (PZQ). Sixty four weeks post schistosoma infection, all groups received 2 doses of the Cervarix HPV vaccine a month apart. Specific immune responses to the HPV and parasite specific antigens were evaluated. Results: Animals with chronic S. mansoni infection elicited significantly reduced levels of HPV specific IgG antibodies 8 weeks after vaccination compared the PZQ treated and uninfected groups. There was no significant difference in cellular proliferation nor IL-4 and IFN-γ production in all groups. Conclusion: Chronic S. mansoni infection results in reduction of protective HPV specific IgG antibodies in a Nonhuman Primate model, suggesting a compromised effect of the vaccine. Treatment of schistosomiasis infection with PZQ prior to HPV vaccination, however, reversed this effect supporting anti-helminthic treatment before vaccination. [ABSTRACT FROM AUTHOR]

Background: Schistosoma mansoni is the main species causing hepatic and intestinal schistosomiasis in Sub-Saharan Africa, and it is the only species in South America. Adult stages of the parasite reside in the mesenteric venous plexus of infected hosts, and eggs are shed in feces. Collecting patient stool samples for S. mansoni diagnostic purposes is difficult in large-scale field trials. Urine samples would be an alternative approach for molecular S. mansoni detection since they have several advantages over stool samples, including better handling, management and storage. Additionally, loop-mediated isothermal amplification (LAMP) technology is a powerful molecular diagnostic tool for infectious diseases, particularly under field conditions in developing countries. The present study aimed to assess the effectiveness of our previously developed LAMP assay (SmMIT-LAMP) for S. mansoni-specific detection in clinical urine samples. Methodology/Principal findings: The sensitivity of SmMIT-LAMP in urine was established in simulated fresh human urine samples artificially spiked with genomic DNA from S. mansoni. LAMP for 120 min instead of 60 min improved the sensitivity, reaching values of 0.01 fg/μL. A set of well-defined frozen stored human urine samples collected from Sub-Saharan immigrant patients was selected from a biobank to evaluate the diagnostic validity of SmMIT-LAMP. The set included urine samples from patients with microscopy-confirmed infections with S. mansoni, S. haematobium and other nonschistosome parasites, as well as urine samples from patients with microscopy-negative eosinophilia without a confirmed diagnosis. The SmMIT-LAMP was incubated for 60 and 120 min. A longer incubation time was shown to increase the LAMP-positive results in patient urine samples. We also tested urine samples from mice experimentally infected with S. mansoni, and LAMP-positive results were obtained from the third week after infection. A real-time LAMP assay was also performed with three individual urine samples. Conclusions/Significance: The SmMIT-LAMP could effectively detect S. mansoni DNA in mouse urine samples and produced promising results for human clinical samples. The detection of S. mansoni DNA in mouse urine samples from the third week after infection indicates that early diagnosis of active S. mansoni infection is possible using urine as a source of DNA. Further studies are still needed, but our method could be used as a promising molecular tool applicable to urine samples to diagnose human intestinal schistosomiasis caused by S. mansoni. [ABSTRACT FROM AUTHOR]

Background: Schistosomiasis is a neglected infection affecting millions of people, mostly living in sub-Saharan Africa. Morbidity and mortality due to chronic infection are relevant, although schistosomiasis is often clinically silent. Different diagnostic tests have been implemented in order to improve screening and diagnosis, that traditionally rely on parasitological tests with low sensitivity. Aim of this study was to evaluate the accuracy of different tests for the screening of schistosomiasis in African migrants, in a non endemic setting. Methodology/Principal findings: A retrospective study was conducted on 373 patients screened at the Centre for Tropical Diseases (CTD) in Negrar, Verona, Italy. Biological samples were tested with: stool/urine microscopy, Circulating Cathodic Antigen (CCA) dipstick test, ELISA, Western blot, immune-chromatographic test (ICT). Test accuracy and predictive values of the immunological tests were assessed primarily on the basis of the results of microscopy (primary reference standard): ICT and WB resulted the test with highest sensitivity (94% and 92%, respectively), with a high NPV (98%). CCA showed the highest specificity (93%), but low sensitivity (48%). The analysis was conducted also using a composite reference standard, CRS (patients classified as infected in case of positive microscopy and/or at least 2 concordant positive immunological tests) and Latent Class Analysis (LCA). The latter two models demonstrated excellent agreement (Cohen’s kappa: 0.92) for the classification of the results. In fact, they both confirmed ICT as the test with the highest sensitivity (96%) and NPV (97%), moreover PPV was reasonably good (78% and 72% according to CRS and LCA, respectively). ELISA resulted the most specific immunological test (over 99%). The ICT appears to be a suitable screening test, even when used alone. Conclusions: The rapid test ICT was the most sensitive test, with the potential of being used as a single screening test for African migrants. [ABSTRACT FROM AUTHOR]

The interaction between schistosomiasis and Salmonella is a particularly important issue in Africa, where dual infection by the parasite and the bacterium are likely common. In this review, the ways in which schistosomiasis affects human biology as it relates to Salmonella are described. Those who are infected by both organisms experience reduced immunological functioning, exhibit irreversible organ damage due to prolonged schistosomiasis infection, and become latent carriers of Salmonella enterica serotypes Typhi and Paratyphi and S. Typhimurium. The sequestration of the bacteria in the parasite leads to ineffective antibiotic treatment because the bacteria cannot be completely killed, and lingering infection may then lead to antimicrobial resistance. These manifestations are likely not just for those dually infected but also for those first infected with schistosomes and, later, Salmonella. More data are needed to better understand dual infection, particularly as it may impact treatment and prevention of schistosomiasis and Salmonella in sub-Saharan Africa. [ABSTRACT FROM AUTHOR]

Background: Schistosoma mansoni infection is proven to be a major health problem of preschool-age children in sub-Saharan Africa, yet this age category is not part of the schistosomiasis control program. The objective of this study was to compare the impact of single and double dose praziquantel (PZQ) treatment on cure rates (CRs), egg reduction rates (ERRs) and re-infection rates 8 months later, in children aged 1-5 years living along Lake Victoria, Uganda. Methodology/Principal Findings: Infected children (n= 1017) were randomized to receive either a single or double dose of PZQ. Initially all children were treated with a single standard oral dose 40 mg/kg body weight of PZQ. Two weeks later a second dose was administered to children in the double dose treatment arm. Side effects were monitored at 30 minutes to 24 hours after each treatment. Efficacy in terms of CRs and ERRs for the two treatments was assessed and compared 1 month after the second treatment. Re-infection with S. mansoni was assessed in the same children 8 months following the second treatment. CRs were non-significantly higher in children treated with two 40 mg/kg PZQ doses (85.5%; 290/339) compared to a single dose (83.2%; 297/357). ERRs were significantly higher in the double dose with 99.3 (95%CI: 99.2-99.5) compared with 98.9 (95%CI: 98.7-99.1) using a single dose, (P = 0.01). Side effects occurred more frequently during the first round of drug administration and were mild and short-lived; these included vomiting, abdominal pain and bloody diarrhea. Overall re-infection rate 8 months post treatment was 44.5%. Conclusions: PZQ is efficacious and relatively safe to use in preschool-age children but there is still an unmet need to improve its formulation to suit small children. Two PZQ doses lead to significant reduction in egg excretion compared to a single dose. Re-infection rates with S. mansoni 8 months post treatment is the same among children irrespective of the treatment regimen. Author Summary: Intestinal schistosomiasis is a parasitic water borne neglected tropical disease of considerable public health relevance in the tropics and subtropics. In Uganda, approximately 20 million people are at risk of being infected with S. mansoni, which causes intestinal schistosomiasis, and 4 million individuals are estimated to be infected. Currently, schistosomiasis control using PZQ chemotherapy is mainly focusing on school-age children (age 6–19 years) and to those adults considered to have the highest risk of infection. So far preschool-age children are not targeted in schistosomiasis preventive chemotherapy campaigns due to the limited documentation on the safety of PZQ in this age group. However, a number of studies have revealed that children less than 6 years of age get infected with S. mansoni usually through bathing, playing or swimming in schistosome-infested waters and are at higher risk of infection than previously thought. This study compared efficacy of PZQ treatment in terms of CRs and ERRs using a single and double dose among children aged 1–5 years, living along Lake Victoria in eastern Uganda. The effect of the two different regimes on S. mansoni re-infection 8 months post treatment was also assessed. [ABSTRACT FROM AUTHOR]

Background: Schistosomiasis is a serious health problem especially in developing countries and affects more than 243 million people. Only few anthelmintic drugs are available up to now. A major obstacle for drug treatment is the different developmental stages and the varying host compartments during worm development. Anthelmintic drugs have been tested mainly on adult schistosomes or freshly transformed cercariae. Knowledge concerning the larval stages is lacking. Methodology/Principal Findings: In this study, we used in vitro-grown schistosomula (aged between 2 to 14 days) to investigate drug effects of the three anthelmintics praziquantel, artemether, and oxamniquine. Further, we analyzed the antibody accessibility of two exemplary schistosome antigens SmCD59a and SmKK7, before and after drug treatment. Our results demonstrated that praziquantel applied at a concentration of 1 μM inhibited development of all life stages. Application of 10 μM praziquantel led to dramatic morphological changes of all schistosomula. Artemether at 1 and 10 μM had differential effects depending on whether it was applied to 2-day as compared to 7- and 14-day schistosomula. While 2-day schistosomula were not killed but inhibited from further development, severe morphological damage was seen in 7- and 14-day schistosomula. Oxamniquine (1 and 10 μM) led to severe morphological impairment in all life stages. Analyzing the accessibility of the antigens SmCD59a and SmKK7 before drug treatment showed no antibody binding on living intact schistosomula. However, when schistosomula were treated with anthelmintics, both antigens became exposed on the larvae. Oxamniquine turned out to be most effective in promoting antibody binding to all schistosomula stages. Conclusion: This study has revealed marked differences in anthelmintic drug effects against larvae. Drug treatment increases surface antigen presentation and renders larvae accessible to antibody attack. Author Summary: Schistosomiasis is one of the major parasitic diseases in developing countries and still causes 200,000 deaths per year. Mass drug administration programs with praziquantel, the drug of choice against schistosomiasis, are currently undertaken in Sub-Saharan Africa. Praziquantel, although efficient against adult worms, fails to cure early infection. The complex developmental stages of schistosomes and migration through varying host compartments with different local drug concentration are a challenge for drug treatment. After infecting their mammalian host, schistosomula traverse through skin and the vasculature of lung, liver and intestines. During their migration, they develop from larvae to paired adults in approximately 4 to 5 weeks. So far, drug effects have been analyzed on adult worms or freshly transformed schistosomula only. Information about the effects on the larval stages is lacking. We were able to transfer the larval development of the first three weeks into the culture dish. This tool can be used for the analysis of drug effects against schistosomula and for investigation of the accessibility, expression and localization of antigens. Rendering the parasite's larvae vulnerable to the host's immune system by increasing antigen presentation is an important aspect of drug activity. We demonstrate on in vitro-cultured Schistosoma mansoni larvae, that SmCD59a and SmKK7, as examples for hidden antigens, become accessible to antibodies following drug treatment. [ABSTRACT FROM AUTHOR]

Background: Sub-Saharan Africa harbors the majority of the global burden of malaria and schistosomiasis infections. The co-endemicity of these two tropical diseases has prompted investigation into the mechanisms of coinfection, particularly the competing immunological responses associated with each disease. Epidemiological studies have shown that infection with Schistosoma mansoni is associated with a greater malaria incidence among school-age children. Methodology: We developed a co-epidemic model of malaria and S. mansoni transmission dynamics which takes into account key epidemiological interaction between the two diseases in terms of elevated malaria incidence among individuals with S. mansoni high egg output. The model was parameterized for S. mansoni high-risk endemic communities, using epidemiological and clinical data of the interaction between S. mansoni and malaria among children in sub-Saharan Africa. We evaluated the potential impact of the S. mansoni–malaria interaction and mass treatment of schistosomiasis on malaria prevalence in co-endemic communities. Principal Findings: Our results suggest that in the absence of mass drug administration of praziquantel, the interaction between S. mansoni and malaria may reduce the effectiveness of malaria treatment for curtailing malaria transmission, in S. mansoni high-risk endemic communities. However, when malaria treatment is used in combination with praziquantel, mass praziquantel administration may increase the effectiveness of malaria control intervention strategy for reducing malaria prevalence in malaria- S. mansoni co-endemic communities. Conclusions/Significance: Schistosomiasis treatment and control programmes in regions where S. mansoni and malaria are highly prevalent may have indirect benefits on reducing malaria transmission as a result of disease interactions. In particular, mass praziquantel administration may not only have the direct benefit of reducing schistosomiasis infection, it may also reduce malaria transmission and disease burden. Author Summary: Malaria and Schistosoma mansoni are co-endemic in many regions of sub-Saharan Africa. Evidence from clinical and epidemiological studies support the hypothesis that concurrent infection with S. mansoni is associated with greater malaria incidence among school-age children. We use mathematical modeling to evaluate the epidemiological impact of S. mansoni infection on malaria transmission in sub-Saharan Africa. Using epidemiological data on the increased risk of malaria incidence in S. mansoni endemic communities from Senegal, we developed a co-epidemic model of malaria and S. mansoni transmission dynamics to address key epidemiological interactions between the two diseases. Parameterizing our model for S. mansoni high-risk endemic communities, we show that the interaction between S. mansoni and malaria may reduce the effectiveness of malaria treatment for curtailing malaria transmission. Moreover, we show that in addition to reducing schistosomiasis health burden, mass praziquantel administration will generate indirect benefit in terms of reducing malaria transmission and disease burden in S. mansoni–malaria co-endemic communities. Our findings indicate the possible benefit of scaling up schistosomiasis control efforts in sub-Saharan Africa, and especially in areas were S. mansoni and malaria are highly prevalent. [ABSTRACT FROM AUTHOR]

Background: Sub-Saharan Africa harbors the majority of the global burden of malaria and schistosomiasis infections. The co-endemicity of these two tropical diseases has prompted investigation into the mechanisms of coinfection, particularly the competing immunological responses associated with each disease. Epidemiological studies have shown that infection with Schistosoma mansoni is associated with a greater malaria incidence among school-age children. Methodology: We developed a co-epidemic model of malaria and S. mansoni transmission dynamics which takes into account key epidemiological interaction between the two diseases in terms of elevated malaria incidence among individuals with S. mansoni high egg output. The model was parameterized for S. mansoni high-risk endemic communities, using epidemiological and clinical data of the interaction between S. mansoni and malaria among children in sub-Saharan Africa. We evaluated the potential impact of the S. mansoni–malaria interaction and mass treatment of schistosomiasis on malaria prevalence in co-endemic communities. Principal Findings: Our results suggest that in the absence of mass drug administration of praziquantel, the interaction between S. mansoni and malaria may reduce the effectiveness of malaria treatment for curtailing malaria transmission, in S. mansoni high-risk endemic communities. However, when malaria treatment is used in combination with praziquantel, mass praziquantel administration may increase the effectiveness of malaria control intervention strategy for reducing malaria prevalence in malaria- S. mansoni co-endemic communities. Conclusions/Significance: Schistosomiasis treatment and control programmes in regions where S. mansoni and malaria are highly prevalent may have indirect benefits on reducing malaria transmission as a result of disease interactions. In particular, mass praziquantel administration may not only have the direct benefit of reducing schistosomiasis infection, it may also reduce malaria transmission and disease burden. [ABSTRACT FROM AUTHOR]

Background: Two Kato-Katz thick smears (Kato-Katzs) from a single stool are currently recommended for diagnosing Schistosoma mansoni infections to map areas for intervention. This 'gold standard' has low sensitivity at low infection intensities. The urine point-of-care circulating cathodic antigen test (POC-CCA) is potentially more sensitive but how accurately they detect S. mansoni after repeated praziquantel treatments, their suitability for measuring drug efficacy and their correlation with egg counts remain to be fully understood. We compared the accuracies of one to six Kato-Katzs and one POC-CCA for the diagnosis of S. mansoni in primary-school children who have received zero to ten praziquantel treatments. We determined the impact each diagnostic approach may have on monitoring and evaluation (M&E) and drug-efficacy findings. Method/Principle Findings: In a high S. mansoni endemic area of Uganda, three days of consecutive stool samples were collected from primary school-aged children (six - 12 years) at five time-points in year one: baseline, one-week-post-, four-weeks-post-, six-months-post-, and six-months-one-week-post-praziquantel and three time-points in years two and three: pre-, one-week-post- and four-weeks-post-praziquantel-treatment/retreatment (n = 1065). Two Kato-Katzs were performed on each stool. In parallel, one urine sample was collected and a single POC-CCA evaluated per child at each time-point in year one (n = 367). At baseline, diagnosis by two Kato-Katzs (sensitivity = 98.6%) or one POC-CCA (sensitivity = 91.7%, specificity = 75.0%) accurately predicted S. mansoni infections. However, one year later, a minimum of three Kato-Katzs, and two years later, five Kato-Katzs were required for accurate diagnosis (sensitivity >90%) and drug-efficacy evaluation. The POC-CCA was as sensitive as six Kato-Katzs four-weeks-post and six-months-post-treatment, if trace readings were classified as positive. Conclusions/Significance: Six Kato-Katzs (two/stool from three stools) and/or one POC-CCA are required for M&E or drug-efficacy studies. Although unable to measure egg reduction rates, one POC-CCA appears to be more sensitive than six Kato-Katzs at four-weeks-post-praziquantel (drug efficacy) and six-months-post-praziquantel (M&E). Author Summary: Schistosomiasis is a parasitic disease infecting over 200 million people. It remains a major public health concern despite treatment of over 120 million people in sub-Saharan Africa alone. Accurate diagnostic methods are essential for monitoring drug efficacy and long-term control program success. The World Health Organization recommends two Kato-Katz thick smears (Kato-Katzs) from a single stool for Schistosoma mansoni diagnosis to map prevalence and areas for control interventions. Although highly specific, Kato-Katzs are thought to be insensitive at low egg counts. The recently refined urine point-of-care circulating cathodic antigen test (POC-CCA) has been proposed as a diagnostic alternative for mapping areas for interventions, and potentially for assessing drug efficacy. Over three years we assessed the accuracy of six Kato-Katzs and a single POC-CCA in detecting infections in Ugandan primary-school children at 11 time points with repeated praziquantel treatments. Our results demonstrate that two Kato-Katzs accurately detect S. mansoni infection pre-treatment, but at least three days of two Kato-Katzs per stool or one POC-CCA are required for annual monitoring and treatment evaluation and/or drug-efficacy studies. One POC-CCA may be more sensitive in measuring S. mansoni prevalence than six Kato-Katzs, but its accuracies for rigorous intensity measures are still to be proven. [ABSTRACT FROM AUTHOR]

Background: An increasing risk of Schistosoma mansoni infection has been observed around Lake Victoria, western Kenya since the 1970s. Understanding local transmission dynamics of schistosomiasis is crucial in curtailing increased risk of infection. Methodology/Principal Findings: We carried out a cross sectional study on a population of 310 children from eight primary schools. Overall, a total of 238 (76.8%) children were infected with S. mansoni, while seven (2.3%) had S. haematobium. The prevalence of hookworm, Trichuris trichiura and Ascaris lumbricoides were 6.1%, 5.2% and 2.3%, respectively. Plasmodium falciparum was the only malaria parasite detected (12.0%). High local population density within a 1 km radius around houses was identified as a major independent risk factor of S. mansoni infection. A spatial cluster of high infection risk was detected around the Mbita causeway following adjustment for population density and other potential risk factors. Conclusions/Significance: Population density was shown to be a major factor fuelling schistosome infection while individual socio-economic factors appeared not to affect the infection risk. The high-risk cluster around the Mbita causeway may be explained by the construction of an artificial pathway that may cause increased numbers of S. mansoni host snails through obstruction of the waterway. This construction may have, therefore, a significant negative impact on the health of the local population, especially school-aged children who frequently come in contact with lake water. Author Summary: It is estimated that more than ten percent of the world's population is at risk of schistosome transmission, with over 90% of infections occurring in sub-Saharan Africa. In Kenya, schistosomiasis remains a major public health concern particularly around Lake Victoria. The objective of this study was to identify the risk factors associated with Schistosoma mansoni infection among schoolchildren on the shores and adjacent islands of Lake Victoria in Mbita district, western Kenya. High local population density was identified as an important risk factor for S. mansoni infection. Socio-economic factors were not found to be significantly associated with infection risk. Our study suggests that environmental changes related to causeway construction and the dense human population around Mbita town may result in favourable ecological conditions for S. mansoni transmission. [ABSTRACT FROM AUTHOR]

Protein kinases C (PKCs) and extracellular signal-regulated kinases (ERKs) are evolutionary conserved cell signalling enzymes that coordinate cell function. Here we have employed biochemical approaches using 'smart' antibodies and functional screening to unravel the importance of these enzymes to Schistosoma mansoni physiology. Various PKC and ERK isotypes were detected, and were differentially phosphorylated (activated) throughout the various S. mansoni life stages, suggesting isotype-specific roles and differences in signalling complexity during parasite development. Functional kinase mapping in adult worms revealed that activated PKC and ERK were particularly associated with the adult male tegument, musculature and oesophagus and occasionally with the oesophageal gland; other structures possessing detectable activated PKC and/or ERK included the Mehlis' gland, ootype, lumen of the vitellaria, seminal receptacle and excretory ducts. Pharmacological modulation of PKC and ERK activity in adult worms using GF109203X, U0126, or PMA, resulted in significant physiological disturbance commensurate with these proteins occupying a central position in signalling pathways associated with schistosome muscular activity, neuromuscular coordination, reproductive function, attachment and pairing. Increased activation of ERK and PKC was also detected in worms following praziquantel treatment, with increased signalling associated with the tegument and excretory system and activated ERK localizing to previously unseen structures, including the cephalic ganglia. These findings support roles for PKC and ERK in S. mansoni homeostasis, and identify these kinase groups as potential targets for chemotherapeutic treatments against human schistosomiasis, a neglected tropical disease of enormous public health significance. Author Summary: Parasitic blood flukes, also called schistosomes, cause human schistosomiasis, a neglected tropical disease and major public health problem in developing countries, especially sub-Saharan Africa. Sustainable control of schistosomiasis is difficult, mainly because the complex life cycle of the parasite involves a freshwater snail host, and the ability of the parasite to evade the immune response of the human host and to survive for many years. Little is yet known about the cellular mechanisms in schistosomes and how they regulate parasite homeostasis, development and behaviour. In this paper, the nature of intracellular signalling by protein kinases C (PKCs) and extracellular signal-regulated kinases (ERKs) in schistosomes is studied and these proteins are found to be vital for the coordination of processes fundamental to parasite survival, such as muscular activity and reproductive function. Our results contribute to an understanding of molecular events regulating schistosome function and identify PKCs and ERKs as possible targets for the development of new chemotherapeutic treatments against schistosomiasis. [ABSTRACT FROM AUTHOR]

Significant numbers of pre-school children are infected with Schistosoma mansoni in sub-Saharan Africa and are likely to play a role in parasite transmission. However, they are currently excluded from control programmes. Molecular phylogenetic studies have provided insights into the evolutionary origins and transmission dynamics of S. mansoni, but there has been no research into schistosome molecular epidemiology in pre-school children. Here, we investigated the genetic diversity and population structure of S. mansoni in pre-school children and mothers living in lakeshore communities in Uganda and monitored for changes over time after praziquantel treatment. Parasites were sampled from children (<6 years) and mothers enrolled in the longitudinal Schistosomiasis Mothers and Infants Study at baseline and at 6-, 12- and 18-month follow-up surveys. 1347 parasites from 35 mothers and 45 children were genotyped by direct sequencing of the cytochrome c oxidase (cox1) gene. The cox1 region was highly diverse with over 230 unique sequences identified. Parasite populations were genetically differentiated between lakes and non-synonymous mutations were more diverse at Lake Victoria than Lake Albert. Surprisingly, parasite populations sampled from children showed a similar genetic diversity to those sampled from mothers, pointing towards a non-linear relationship between duration of exposure and accumulation of parasite diversity. The genetic diversity six months after praziquantel treatment was similar to pre-treatment diversity. Our results confirm the substantial genetic diversity of S. mansoni in East Africa and provide significant insights into transmission dynamics within young children and mothers, important information for schistosomiasis control programmes. Author Summary: Many pre-school children in sub-Saharan Africa are infected with the parasite Schistosoma mansoni, which causes intestinal schistosomiasis. However, there has been no work published on the molecular epidemiology of Schistosoma in children under six or the role that these children play in parasite transmission. We analysed the genetic structure of parasite populations collected from mothers and young children living on the shores of Lakes Albert and Victoria in Uganda. Parasite populations were different at the two lakes indicating that there is little flow of parasite genes between the lakes. We were surprised to discover a large amount of genetic variation in parasites sampled from both children and mothers, suggesting that genetic variation is not directly related to duration of exposure to infested water. In addition, we found some evidence that young children are involved in S. mansoni transmission. The substantial genetic variation of S. mansoni in young children suggests that these parasites could be operating as a source of a variety of genetic traits, including drug susceptibility. Overall our findings offer significant insights into population genetics of S. mansoni in pre-school children and their mothers and provide important information for effective control of intestinal schistosomiasis. [ABSTRACT FROM AUTHOR]

Background: In sub-Saharan Africa the recommended strategy to control schistosomiasis is preventive chemotherapy. Emphasis is placed on school-aged children, but in high endemicity areas, preschool-aged children are also at risk, and hence might need treatment with praziquantel. Since a pediatric formulation (e.g., syrup) is not available outside of Egypt, crushed praziquantel tablets are used, but the efficacy and safety of this treatment regimen is insufficiently studied. Methodology: We assessed the efficacy and safety of crushed praziquantel tablets among preschool-aged children (<6 years) in the Azaguié district, south Côte d'Ivoire, where Schistosoma mansoni and S. haematobium coexist. Using a cross-sectional design, children provided two stool and two urine samples before and 3 weeks after treatment. Crushed praziquantel tablets, mixed with water, were administered at a dose of 40 mg/kg. Adverse events were assessed and graded 4 and 24 hours posttreatment by interviewing mothers/guardians. Principal Findings: Overall, 160 preschool-aged children had at least one stool and one urine sample examined with duplicate Kato-Katz thick smears and a point-of-care circulating cathodic antigen (POC-CCA) cassette for S. mansoni, and urine filtration for S. haematobium diagnosis before and 3 weeks after praziquantel administration. According to the Kato-Katz and urine filtration results, we found high efficacy against S. mansoni (cure rate (CR), 88.6%; egg reduction rate (ERR), 96.7%) and S. haematobium (CR, 88.9%; ERR, 98.0%). POC-CCA revealed considerably lower efficacy against S. mansoni (CR, 53.8%). Treatment was generally well tolerated, but moderately severe adverse events (i.e., body and face inflammation), were observed in four Schistosoma egg-negative children. Conclusions/Significance: Crushed praziquantel administered to preschool-aged children at a dose of 40 mg/kg is efficacious against S. mansoni and S. haematobium in a co-endemic setting of Côte d'Ivoire. Further research is required with highly sensitive diagnostic tools and safety must be investigated in more depth. Trial Registration: Controlled-Trials.com ISRCTN53172722 Author Summary: Schistosomiasis is a parasitic worm infection that plagues more than 200 million people in the developing world, particularly in sub-Saharan Africa. The current strategy to control schistosomiasis is to regularly administer the deworming drug praziquantel to school-aged children. Younger children before reaching school-age are not included in these deworming campaigns, because they are considered at low risk of schistosomiasis, and because the amount of available data to evaluate the safety of praziquantel in young children is insufficient. We conducted a study in two villages in southern Côte d'Ivoire and examined the stool and urine of more than 250 children (<6 years) for schistosome eggs and antigens. Children were treated with crushed praziquantel tablets (40 mg/kg) and the efficacy of this treatment was determined 3 weeks after treatment. The safety of the treatment was assessed by interviewing mothers of treated children for adverse events (e.g., abdominal pain, diarrhea, and headache). Complete data records were available for 160 children. Praziquantel cleared most of the infections. The treatment was generally well tolerated, but we observed four children who were not infected at the baseline survey who developed face and body inflammation that required close supervision by the study physician. [ABSTRACT FROM AUTHOR]

Background: Eggs deposited in the liver of the mammalian host by the blood fluke parasite, Schistosoma mansoni, normally drive a T-helper-2 (Th2)-mediated granulomatous response in immune-competent mice. By contrast, in mice deprived of T-cells and incapable of producing granulomata, egg-secreted proteins (ESP) induce acute hepatic injury and death. Previous work has shown that one such ESP, the T2 ribonuclease known as omega-1, is hepatotoxic in vivo in that specific antisera to omega-1 prevent hepatocyte damage. Methodology/Principal Findings: Using an in vitro culture system employing mouse primary hepatocytes and alanine transaminase (ALT) activity as a marker of heptocyte injury, we demonstrated that S. mansoni eggs, egg-secreted proteins (ESP), soluble-egg antigen (SEA), and omega-1 are directly hepatotoxic and in a dose-dependent manner. Depletion of omega-1 using a monoclonal antibody abolished the toxicity of pure omega-1 and diminished the toxicity in ESP and SEA by 47 and 33%, respectively. Anion exchange chromatography of ESP yielded one predominant hepatotoxic fraction. Proteomics of that fraction identified the presence of IPSE/alpha-1 (IL-4 inducing principle from S. mansoni eggs), a known activator of basophils and inducer of Th2-type responses. Pure recombinant IPSE/alpha-1 also displayed a dose-dependent hepatotoxicity in vitro. Monoclonal antibody depletion of IPSE/alpha-1 abolished the latter's toxicity and diminished the total toxicity of ESP and SEA by 32 and 35%, respectively. Combined depletion of omega-1 and IPSE/alpha-1 diminished hepatotoxicity of ESP and SEA by 60 and 58% respectively. Conclusions: We identified IPSE/alpha-1 as a novel hepatotoxin and conclude that both IPSE/alpha-1 and omega-1 account for the majority of the hepatotoxicity secreted by S. mansoni eggs. Author Summary: The flatworm disease, schistosomiasis, is a major public health problem in sub-Saharan Africa, South America and East Asia. A hallmark of infection with Schistosoma mansoni is the immune response to parasite eggs trapped in the liver and other organs. This response involves an infiltration of cells that surround the parasite egg forming a "granuloma." In mice deprived of T-cells, this granulomatous response is lacking, and toxic products released by eggs quickly cause liver damage and death. Thus the granulomata protect the host from toxic egg products. Only one hepatotoxic molecule, omega-1, has been described to date. We set out to identify other S. mansoni egg hepatotoxins using liver cells grown in culture. We first showed that live eggs, their secretions, and pure omega-1 are toxic. Using a physical separation technique to prepare fractions from whole egg secretions, we identified the presence of IPSE/alpha-1, a protein that is known to strongly influence the immune system. We showed that IPSE/alpha-1 is also hepatotoxic, and that toxicity of both omega-1 and IPSE/alpha-1 can be prevented by first mixing the proteins with specific neutralizing antibodies. Both proteins constitute the majority of hepatotoxicity released by eggs. [ABSTRACT FROM AUTHOR]

Background: In Uganda, control of intestinal schistosomiasis with preventive chemotherapy is typically focused towards treatment of school-aged children; the needs of younger children are presently being investigated as in lakeshore communities very young children can be infected. In the context of future epidemiological monitoring, we sought to compare the detection thresholds of available diagnostic tools for Schistosoma mansoni and estimate a likely age of first infection for these children. Methods and Findings: A total of 242 infants and preschool children (134 boys and 108 girls, mean age 2.9 years, minimum 5 months and maximum 5 years) were examined from Bugoigo, a well-known disease endemic village on Lake Albert. Schistosome antigens in urine, eggs in stool and host antibodies to eggs were inspected to reveal a general prevalence of 47.5% (CI95 41.1–54.0%), as ascertained by a positive criterion from at least one diagnostic method. Although children as young as 6 months old could be found infected, the average age of infected children was between 3¼–3¾ years, when diagnostic techniques became broadly congruent. Conclusion: Whilst different assays have particular (dis)advantages, direct detection of eggs in stool was least sensitive having a temporal lag behind antigen and antibody methods. Setting precisely a general age of first infection is problematic but if present Ugandan policies continue, a large proportion of infected children could wait up to 3–4 years before receiving first medication. To better tailor treatment needs for this younger ageclass, we suggest that the circulating cathodic antigen urine dipstick method to be used as an epidemiological indicator. Author Summary: In sub-Saharan Africa, intestinal schistosomiasis is a debilitating disease caused by a worm infection. To arrest disease progression, de-worming medications are given out, often en masse, to school-aged children. In Uganda, however, much younger children can be infected, and in lakeshore communities both infants and pre-school children can already show signs and symptoms of intestinal schistosomiasis. To change de-worming practices, further information on the occurrence of infections in these younger is needed for evidence-based decision making. Our study applied current methods of disease diagnosis to better define the 'age of first infection' and estimate general infection prevalence within a disease-endemic village. Up to 50% of young children were clearly shown to have schistosomiasis and could likely wait up to 3–4 years before obtaining first treatment if present de-worming policies are not changed. In the context of identifying future treatment needs, we propose that antigen detection methods are most suitable. [ABSTRACT FROM AUTHOR]

Background: To date schistosomiasis control programmes based on chemotherapy have largely aimed at controlling morbidity in treated individuals rather than at suppressing transmission. In this study, a mathematical modelling approach was used to estimate reductions in the rate of Schistosoma mansoni reinfection following annual mass drug administration (MDA) with praziquantel in Uganda over four years (2003–2006). In doing this we aim to elucidate the benefits of MDA in reducing community transmission. Methods: Age-structured models were fitted to a longitudinal cohort followed up across successive rounds of annual treatment for four years (Baseline: 2003, Treatment: 2004–2006; n = 1,764). Instead of modelling contamination, infection and immunity processes separately, these functions were combined in order to estimate a composite force of infection (FOI), i.e., the rate of parasite acquisition by hosts. Results: MDA achieved substantial and statistically significant reductions in the FOI following one round of treatment in areas of low baseline infection intensity, and following two rounds in areas with high and medium intensities. In all areas, the FOI remained suppressed following a third round of treatment. Conclusions/Significance: This study represents one of the first attempts to monitor reductions in the FOI within a large-scale MDA schistosomiasis morbidity control programme in sub-Saharan Africa. The results indicate that the Schistosomiasis Control Initiative, as a model for other MDA programmes, is likely exerting a significant ancillary impact on reducing transmission within the community, and may provide health benefits to those who do not receive treatment. The results obtained will have implications for evaluating the cost-effectiveness of schistosomiasis control programmes and the design of monitoring and evaluation approaches in general. Author Summary: Schistosomiasis is a parasitic disease of enormous public health importance, infecting over 200 million people worldwide, of which the large majority live in sub-Saharan Africa. Control programmes based on the mass treatment of individuals in infected areas with the drug praziquantel have been shown to be successful in reducing the parasite burden and likelihood of developing morbidity in those individuals who receive treatment. Using data from an ongoing intestinal schistosomiasis control programme in Uganda and through the application of a mathematical model, we show that an additional benefit of mass treatment is a decrease in parasite acquisition, via a reduction in the number of transmission stages in the environment. This leads to a lower rate of infection and reinfection of individuals in those areas. We show that this result is valid in areas of differing average infection intensity. The importance of this finding is that this will benefit untreated as well as treated individuals, and will allow a fuller estimation of the benefits of schistosomiasis control programmes. [ABSTRACT FROM AUTHOR]

Background: Deworming HIV-1 infected individuals may delay HIV-1 disease progression. It is important to determine the prevalence and correlates of HIV-1/helminth co-infection in helminth-endemic areas. Methods: HIV-1 infected individuals (CD4>250 cells/ul) were screened for helminth infection at ten sites in Kenya. Prevalence and correlates of helminth infection were determined. A subset of individuals with soil-transmitted helminth infection was re-evaluated 12 weeks following albendazole therapy. Results: Of 1,541 HIV-1 seropositive individuals screened, 298 (19.3%) had detectable helminth infections. Among individuals with helminth infection, hookworm species were the most prevalent (56.3%), followed by Ascaris lumbricoides (17.1%), Trichuris trichiura (8.7%), Schistosoma mansoni (7.1%), and Stongyloides stercoralis (1.3%). Infection with multiple species occurred in 9.4% of infections. After CD4 count was controlled for, rural residence (RR 1.40, 95% CI: 1.08–1.81), having no education (RR 1.57, 95% CI: 1.07–2.30), and higher CD4 count (RR 1.36, 95% CI: 1.07–1.73) remained independently associated with risk of helminth infection. Twelve weeks following treatment with albendazole, 32% of helminth-infected individuals had detectable helminths on examination. Residence, education, and CD4 count were not associated with persistent helminth infection. Conclusions: Among HIV-1 seropositive adults with CD4 counts above 250 cells/mm3 in Kenya, traditional risk factors for helminth infection, including rural residence and lack of education, were associated with co-infection, while lower CD4 counts were not. Trial Registration: ClinicalTrials.gov NCT00130910 Author Summary: Over one-third of people worldwide are currently infected with parasitic worms. The majority of these infections occur in sub-Saharan Africa, where over half of the population may be infected with at least one type of parasitic worm. HIV infection is also common in many of these countries, and there is significant geographic overlap in the presence of HIV and worm infection. Several studies have suggested that treatment of worm infections in people with HIV may delay the progression of HIV disease. Treatment has been shown to both decrease levels of the HIV virus in the blood of people with HIV and to increase the number of immune cells (CD4 cells) targeted by HIV. It is important to determine which populations of HIV-infected individuals are at greatest risk of worm infection in order to develop potential interventions for the treatment and prevention of worm infection in HIV-infected individuals. We report findings from a large study examining the prevalence and associated co-factors for worm infection among individuals at ten sites in Kenya. [ABSTRACT FROM AUTHOR]

The parasitic trematode Schistosoma mansoni is one of the major causative agents of human schistosomiasis, which afflicts 200 million people worldwide. Praziquantel remains the main drug used for schistosomiasis treatment, and reliance on the single therapy has been prompting the search for new therapeutic compounds against this disease. Our group has demonstrated that heme crystallization into hemozoin (Hz) within the S. mansoni gut is a major heme detoxification route with lipid droplets involved in this process and acting as a potential chemotherapeutical target. In the present work, we investigated the effects of three antimalarial compounds, quinine (QN), quinidine (QND) and quinacrine (QCR) in a murine schistosomiasis model by using a combination of biochemical, cell biology and molecular biology approaches. Methodology/Principal Findings: Treatment of S. mansoni-infected female Swiss mice with daily intraperitoneal injections of QN, and QND (75 mg/kg/day) from the 11th to 17th day after infection caused significant decreases in worm burden (39%-61%) and egg production (42%-98%). Hz formation was significantly inhibited (40%-65%) in female worms recovered from QN- and QND-treated mice and correlated with reduction in the female worm burden. We also observed that QN treatment promoted remarkable ultrastructural changes in male and female worms, particularly in the gut epithelium and reduced the granulomatous reaction to parasite eggs trapped in the liver. Microarray gene expression analysis indicated that QN treatment increased the expression of transcripts related to musculature, protein synthesis and repair mechanisms. Conclusions: The overall significant reduction in several disease burden parameters by the antimalarial quinoline methanols indicates that interference with Hz formation in S. mansoni represents an important mechanism of schistosomicidal action of these compounds and points out the heme crystallization process as a valid chemotherapeutic target to treat schistosomiasis. [ABSTRACT FROM AUTHOR]