Barriers and facilitators to programmatic mass drug administration in persistent schistosomiasis hotspot communities: An ethnographic study along Lake Albert, midwestern Uganda.

Background: The WHO Neglected Tropical Disease Roadmap for 2021-2030 includes the goal of eliminating schistosomiasis as a public health problem in all endemic countries. Despite heightened efforts since 2012, critical action is still required in addressing barriers to Mass Drug Administration, the primary control method. This includes improvement in adherence by the populations in persistent schistosomiasis hotspots.

Revisiting immunity vs. exposure in schistosomiasis: A mathematical modeling study of delayed concomitant immunity.

The relative contributions of exposure vs. acquired immunity to the epidemiology of human schistosomiasis has been long debated. While there is considerable evidence that humans acquire partial immunity to infection, age- and sex-related contact patterns with water bodies contaminated with infectious cercarial schistosome larvae also contribute to typical epidemiological profiles of infection.

Protective human IgE responses are promoted by comparable life-cycle dependent Tegument Allergen-Like expression in Schistosoma haematobium and Schistosoma mansoni infection.

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.

Exploring the Use of Antibiotics for Dental Patients in a Middle-Income Country: Interviews with Clinicians in Two Ghanaian Hospitals.

Background: Antimicrobial resistance is a global problem driven by the overuse of antibiotics. Dentists are responsible for about 10% of antibiotics usage across healthcare worldwide. Factors influencing dental antibiotic prescribing are numerous, with some differences in low- and middle-income countries compared with high-income countries.

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

Background: Evidence from recent studies in Schistosoma mansoni-endemic areas show an age-associated immunity that is positively correlated with IgE titres to Schistosoma mansoni-specific tegumental allergen-like protein 1 (SmTAL1). The structural homology between SmTAL1 and the S. haematobium-specific TAL1 (ShTAL1) has been verified, yet it remains unclear whether similar age- and immune-associated trends characterize ShTAL1.

Schistosoma mansoni Larval Extracellular Vesicle protein 1 (SmLEV1) is an immunogenic antigen found in EVs released from pre-acetabular glands of invading cercariae.

Extracellular Vesicles (EVs) are an integral component of cellular/organismal communication and have been found in the excreted/secreted (ES) products of both protozoan and metazoan parasites. Within the blood fluke schistosomes, EVs have been isolated from egg, schistosomula, and adult lifecycle stages. However, the role(s) that EVs have in shaping aspects of parasite biology and/or manipulating host interactions is poorly defined.

Schistosomiasis Morbidity Hotspots: Roles of the Human Host, the Parasite and Their Interface in the Development of Severe Morbidity.

Schistosomiasis is the second most important human parasitic disease in terms of socioeconomic impact, causing great morbidity and mortality, predominantly across the African continent. For intestinal schistosomiasis, severe morbidity manifests as periportal fibrosis (PPF) in which large tracts of macro-fibrosis of the liver, visible by ultrasound, can occlude the main portal vein leading to portal hypertension (PHT), sequelae such as ascites and collateral vasculature, and ultimately fatalities. For urogenital schistosomiasis, severe morbidity manifests as pathology throughout the urinary system and genitals, and is a definitive cause of squamous cell bladder carcinoma.

Screening of a Library of Recombinant Schistosoma mansoni Proteins With Sera From Murine and Human Controlled Infections Identifies Early Serological Markers.

Background: Schistosomiasis is a major global health problem caused by blood-dwelling parasitic worms, which is currently tackled primarily by mass administration of the drug praziquantel. Appropriate drug treatment strategies are informed by diagnostics that establish the prevalence and intensity of infection, which, in regions of low transmission, should be highly sensitive.

Methods: To identify sensitive new serological markers of Schistosoma mansoni infections, we have compiled a recombinant protein library of parasite cell-surface and secreted proteins expressed in mammalian cells.

Transcriptome of the parasitic flatworm Schistosoma mansoni during intra-mammalian development.

Schistosomes are parasitic blood flukes that survive for many years within the mammalian host vasculature. How the parasites establish a chronic infection in the hostile bloodstream environment, whilst evading the host immune response is poorly understood. The parasite develops morphologically and grows as it migrates to its preferred vascular niche, avoiding or repairing damage from the host immune system.

Community knowledge, perceptions and water contact practices associated with transmission of urinary schistosomiasis in an endemic region: a qualitative cross-sectional study.

Background: In an effort to complement the current chemotherapy based schistosomiasis control interventions in Shinyanga district, community knowledge, perceptions and water contact practices were qualitatively assessed using focus group discussions and semi structured interviews involving 271 participants in one S. haematobium prevalent community of Ikingwamanoti village, Shinyanga district, Northwestern, Tanzania.

Methods: In October, 2016 we conducted 29 parent semi structured interviews and 16 focus group discussions with a total of 168 parent informants.

Antibody responses to Schistosoma mansoni schistosomula antigens.

While antigens from Schistosoma schistosomula have been suggested as potential vaccine candidates, the association between antibody responses with schistosomula antigens and infection intensity at reinfection is not well known. Schistosoma mansoni-infected individuals were recruited from a schistosomiasis endemic area in Uganda (n = 372), treated with 40 mg/kg praziquantel (PZQ) and followed up at five weeks and at one year post-treatment. Pre-treatment and five weeks post-treatment immunoglobulin (Ig) E, IgG1 and IgG4 levels against recombinant schistosomula antigens rSmKK7, rSmLy6A, rSmLy6B and rSmTSP7 were measured using ELISA.

Schistosoma mansoni schistosomula antigens induce Th1/Pro-inflammatory cytokine responses.

Larvae of Schistosoma (schistosomula) are highly susceptible to host immune responses and are attractive prophylactic vaccine targets, although cellular immune responses against schistosomula antigens in endemic human populations are not well characterized. We collected blood and stool from 54 Schistosoma mansoni-infected Ugandans, isolated peripheral blood mononuclear cells and stimulated them for 24 hours with schistosome adult worm and soluble egg antigens (AWA and SEA), along with schistosomula recombinant proteins rSmKK7, Lymphocyte Antigen 6 isoforms (rSmLy6A and rSmLy6B), tetraspanin isoforms (rSmTSP6 and rSmTSP7). Cytokines, chemokines and growth factors were measured in the culture supernatants using a multiplex luminex assay, and infection intensity was determined before and at 1 year after praziquantel (PZQ) treatment using the Kato-Katz method.

Geographical and behavioral risks associated with Schistosoma haematobium infection in an area of complex transmission.

Background: Schistosoma haematobium infection in endemic areas varies depending on the nature and complexity of the transmission networks present. Studies of micro-geographical transmission of S. haematobium infection indicate that discrepancy in prevalence between households is associated with diverse water contact behaviors and transmission that is restricted to particular sites harboring snail intermediate hosts.

Organomegaly in Mali before and after praziquantel treatment. A possible association with .

Continuous exposure to schistosome-infested water results in acute and chronic morbidity in all ages. We analysed occurence of organomegaly via ultrasonography and investigated a possible additive effect of dual-dose drug administration in 401 infected individuals from a highly endemic area in Mali. Mean intensity of infection at baseline (22.

Inflammation dynamics after praziquantel treatment of Schistosoma haematobium reflected by urinary eosinophil cationic protein.

Background: This cohort study assessed urinary eosinophil cationic protein (ECP) as an indicator for urinary tract morbidity and inflammation indication related to single-dose or dual-dose praziquantel (PZQ) treatment.

Methods: Urinary ECP was measured at baseline, 24 h and 9 weeks after treatment (baseline 305, follow-up 204 participants, ages 2-40 years).

Results: ECP was significantly associated with the intensity of infection at baseline (p<0.

Rapid clearance of Schistosoma mansoni circulating cathodic antigen after treatment shown by urine strip tests in a Ugandan fishing community - Relevance for monitoring treatment efficacy and re-infection.

Unlabelled: Schistosomiasis control and elimination has priority in public health agendas in several sub-Saharan countries. However, achieving these goals remains a substantial challenge. In order to assess progress of interventions and treatment efficacy it is pertinent to have accurate, feasible and affordable diagnostic tools.

The Interdependence between Schistosome Transmission and Protective Immunity.

Mass drug administration (MDA) for control of schistosomiasis is likely to affect transmission dynamics through a combination of passive vaccination and reduction of local transmission intensity. This is indicated in phenomenological models of immunity and the impact of MDA, yet immunity parameters in these models are not validated by empirical data that reflects protective immunity to reinfection. There is significant empirical evidence supporting the role of IgE in acquired protective immunity.

Anemia and growth retardation associated with Schistosoma haematobium infection in Mali: a possible subtle impact of a neglected tropical disease.

Background: The aim of this cross-sectional study was to investigate a possible association of Schistosoma haematobium with child growth development and describe a plausible schistosomiasis-related anemia in children and adults in a highly schistosomiasis endemic area of Mali.

Methods: Urine, feces and blood samples from 399 participants of both sexes (2-40 years of age) were analyzed and supplemented by anthropometric measurements.

Results: S.

Co-infection with Schistosoma mansoni and Human Immunodeficiency Virus-1 (HIV-1) among residents of fishing villages of north-western Tanzania.

Background: Co-infection with S. mansoni and Human Immunodeficiency Virus-1 (HIV-1) has been described in sub-Saharan Africa. However, few community-based studies have been conducted to assess the association between the two diseases.

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

Background: Immunity that reduces worm fecundity and, in turn, reduces morbidity is proposed for Schistosoma haematobium, a parasite of major public health importance. Mathematical models of epidemiological trends suggest that antifecundity immunity is dependent on antibody responses to adult-worm-derived antigen.

Methods: For a Malian cohort (age, 5-29 years) residing in high-transmission fishing villages or a moderate-transmission village, worm fecundity was assessed using the ratio of urinary egg excretion to levels of circulating anodic antigen, a Schistosoma-specific antigen that is steadily secreted by adult worms.

Suppression of basophil histamine release and other IgE-dependent responses in childhood Schistosoma mansoni/hookworm coinfection.

Background: The poor correlation between allergen-specific immunoglobulin E (asIgE) and clinical signs of allergy in helminth infected populations suggests that helminth infections could protect against allergy by uncoupling asIgE from its effector mechanisms. We investigated this hypothesis in Ugandan schoolchildren coinfected with Schistosoma mansoni and hookworm.

Methods: Skin prick test (SPT) sensitivity to house dust mite allergen (HDM) and current wheeze were assessed pre-anthelmintic treatment.

Aflatoxin exposure is inversely associated with IGF1 and IGFBP3 levels in vitro and in Kenyan schoolchildren.

Scope: This study explores the relationship between aflatoxin and the insulin-like growth factor (IGF) axis and its potential effect on child growth.

Methods And Results: One hundred and ninety-nine Kenyan schoolchildren were studied for aflatoxin-albumin adduct (AF-alb), IGF1 and IGF-binding protein-3 (IGFBP3) levels using ELISA. AF-alb was inversely associated with IGF1 and IGFBP3 (p < 0.

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

Regular treatment with praziquantel (PZQ) is the strategy for human schistosomiasis control aiming to prevent morbidity in later life. With the recent resolution on schistosomiasis elimination by the 65th World Health Assembly, appropriate diagnostic tools to inform interventions are keys to their success. We present a discrete Markov chains modelling framework that deals with the longitudinal study design and the measurement error in the diagnostic methods under study.

Posttreatment changes in cytokines induced by Schistosoma mansoni egg and worm antigens: dissociation of immunity- and morbidity-associated type 2 responses.

Background: Human type 2 cytokine responsiveness to schistosome antigens increases after treatment; due either to removal of the immunosuppressive effects of active infection or immunological boosting by antigens released from dying parasites. We determined the responsiveness to Schistosoma mansoni over a 2-year period, when reinfection was restricted by interrupting transmission.

Methods: The proinflammatory and type 2 responses of Kenyan schoolchildren were measured before, and 1 year and 2 years posttreatment in whole blood cultures stimulated with soluble egg antigen (SEA) or soluble worm antigen (SWA).