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Frontiers in Immunology 2021Schistosomes infect about 250 million people globally causing the devastating and persistent disease of schistosomiasis. These blood flukes have a complicated life cycle... (Review)
Review
Schistosomes infect about 250 million people globally causing the devastating and persistent disease of schistosomiasis. These blood flukes have a complicated life cycle involving alternating infection of freshwater snail intermediate and definitive mammalian hosts. To survive and flourish in these diverse environments, schistosomes transition through a number of distinct life-cycle stages as a result of which they change their body plan in order to quickly adapt to each new environment. Current research suggests that stem cells, present in adults and larvae, are key in aiding schistosomes to facilitate these changes. Given the recent advances in our understanding of schistosome stem cell biology, we review the key roles that two major classes of cells play in the different life cycle stages during intramolluscan and intramammalian development; these include the germinal cells of sporocysts involved in asexual reproduction in molluscan hosts and the neoblasts of adult worms involved in sexual reproduction in human and other mammalian hosts. These studies shed considerable new light in revealing the stem cell heterogeneity driving the propagation of the schistosome life cycle. We also consider the possibility and value of establishing stem cell lines in schistosomes to advance schistosomiasis research. The availability of such self-renewable resources will provide new platforms to study stem cell behavior and regulation, and to address fundamental aspects of schistosome biology, reproductive development and survival. In turn, such studies will create new avenues to unravel individual gene function and to optimize genome-editing processes in blood flukes, which may lead to the design of novel intervention strategies for schistosomiasis.
Topics: Animals; Biomedical Research; Schistosoma; Schistosomiasis; Stem Cells
PubMed: 33746946
DOI: 10.3389/fimmu.2021.599014 -
Parasitology Apr 2023Human schistosomiasis is caused by helminths of the genus . Macrophages play a crucial role in the immune regulation of this disease. These cells acquire different... (Review)
Review
Human schistosomiasis is caused by helminths of the genus . Macrophages play a crucial role in the immune regulation of this disease. These cells acquire different phenotypes depending on the type of stimulus they receive. M1 macrophages can be ‘classically activated’ and can display a proinflammatory phenotype. M2 or ‘alternatively activated’ macrophages are considered anti-inflammatory cells. Despite the relevance of macrophages in controlling infections, the role of the functional types of these cells in schistosomiasis is unclear. This review highlights different molecules and/or macrophage activation and polarization pathways during and infection. This review is based on original and review articles obtained through searches in major databases, including Scopus, Google Scholar, ACS, PubMed, Wiley, Scielo, Web of Science, LILACS and ScienceDirect. Our findings emphasize the importance of and antigens in macrophage polarization, as they exert immunomodulatory effects in different stages of the disease and are therefore important as therapeutic targets for schistosomiasis and in vaccine development. A combination of different antigens can provide greater protection, as it possibly stimulates an adequate immune response for an M1 or M2 profile and leads to host resistance; however, this warrants and studies.
Topics: Animals; Humans; Macrophage Activation; Schistosomiasis; Schistosomiasis japonica; Macrophages; Schistosoma mansoni
PubMed: 36601859
DOI: 10.1017/S0031182023000021 -
Malaria Journal Sep 2023Malaria and schistosomiasis persist as major public health challenge in sub-Saharan Africa. These infections have independently and also in polyparasitic infection been...
BACKGROUND
Malaria and schistosomiasis persist as major public health challenge in sub-Saharan Africa. These infections have independently and also in polyparasitic infection been implicated in anaemia and nutritional deficiencies. This study aimed at assessing asymptomatic malaria, intestinal Schistosoma infections and the risk of anaemia among school children in the Tono irrigation area in the Kassena Nankana East Municipal (KNEM) in the Upper East Region of Northern Ghana.
METHODS
A cross sectional survey of 326 school children was conducted in the KNEM. Kato Katz technique was used to detect Schistosoma eggs in stool. Finger-prick capillary blood sample was used for the estimation of haemoglobin (Hb) concentration and blood smear for malaria parasite detection by microscopy.
RESULTS
The average age and Hb concentration were 10.9 years (standard deviation, SD: ± 2.29) and 11.2 g/dl (SD: ± 1.39) respectively with 58.9% (n = 192) being females. The overall prevalence of infection with any of the parasites (single or coinfection) was 49.4% (n = 161, 95% confidence interval, CI [44.0-54.8]). The prevalence of malaria parasite species or Schistosoma mansoni was 32.0% (n = 104) and 25.2% (n = 82), respectively with 7.7% (n = 25) coinfection. The prevalence of anaemia in the cohort was 40.5% (95%CI [35.3-45.9]), of which 44.4% harboured at least one of the parasites. The prevalence of anaemia in malaria parasite spp or S. mansoni mono-infections was 41.8% and 38.6%, respectively and 64.0% in coinfections. There was no statistically significant difference in the odds of being anaemic in mono-infection with malaria (OR = 1.22, 95% CI 0.71-2.11, p = 0.47) or S. mansoni (OR = 1.07, 95% CI 0.58-1.99, p = 0.83) compared to those with no infection. However, the odds of being anaemic and coinfected with malaria parasite species and S. mansoni was 3.03 times higher compared to those with no infection (OR = 3.03, 95% CI 1.26-7.28, p = 0.013). Conclusion The data show a high burden of malaria, S. mansoni infection and anaemia among school children in the irrigation communities. The risk of anaemia was exacerbated by coinfections with malaria parasite(s) and S. mansoni. Targeted integrated interventions are recommended in this focal area of KNEM.
Topics: Child; Female; Animals; Humans; Male; Schistosoma mansoni; Coinfection; Plasmodium falciparum; Cross-Sectional Studies; Anemia
PubMed: 37710279
DOI: 10.1186/s12936-023-04709-w -
BioMed Research International 2023Schistosomiasis is causing high morbidity and significant mortality in endemic areas. Kato-Katz stool examination and urine filtration techniques are the conventional... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Schistosomiasis is causing high morbidity and significant mortality in endemic areas. Kato-Katz stool examination and urine filtration techniques are the conventional methods for the detection of intestinal and urinary schistosomiasis. The most appropriate diagnostic tools for the detection of schistosomiasis especially in low-prevalence settings should be used. Therefore, this study is aimed at investigating the diagnostic accuracy of and diagnostic tools in sub-Saharan Africa.
METHODS
Electronic databases such as PubMed, PubMed Central/Medline, HINARI, Scopus, EMBASE, Science Direct, Google Scholar, and Cochrane Library were reviewed. The pooled estimates and heterogeneity were determined using Midas in Stata 14.0. The diagnostic accuracy of index tests was compared using the hierarchical summary of the receiver operating characteristic (HSROC) curve in Stata 14.0.
RESULTS
Twenty-four studies consisting of 12,370 individuals were tested to evaluate the accuracy of antigen, antibody, and molecular test methods for the detection of and . The pooled estimate of sensitivity and specificity of CCA was 88% (95% CI: 83-92) and 72 (95% CI: 62-80), respectively, when it is compared with parasitological stool examination for detection. On the other hand, ELISA showed a pooled estimate of sensitivity and specificity of 95% (95% CI: 93-96) and 35% (95% CI: 21-52), respectively, for the examination of using stool examination as a reference test. With regard to , the pooled estimate of sensitivity and specificity of polymerase chain reaction was 97% (95% CI: 78-100) and 94% (95% CI: 74-99), respectively. Moreover, the sensitivity and specificity of urine CCA vary between 41-80% and 55-91%, respectively, compared to urine microscopy.
CONCLUSION
The effort of schistosomiasis elimination requires accurate case identification especially in low-intensity infections. This study showed that CCA had the highest sensitivity and moderate specificity for the diagnosis of . Similarly, the sensitivity of ELISA was excellent, but its specificity was low. The diagnostic accuracy of PCR for the detection of was excellent compared to urine microscopic examination.
Topics: Humans; Animals; Microscopy; Schistosoma mansoni; Urinalysis; Africa South of the Sahara; Diagnostic Tests, Routine
PubMed: 37621699
DOI: 10.1155/2023/3769931 -
Frontiers in Cellular and Infection... 2022Schistosomiasis remains to be a significant public health problem in tropical and subtropical regions. Despite remarkable progress that has been made in the control of... (Review)
Review
Schistosomiasis remains to be a significant public health problem in tropical and subtropical regions. Despite remarkable progress that has been made in the control of the disease over the past decades, its elimination remains a daunting challenge in many countries. This disease is an inflammatory response-driven, and the positive outcome after infection depends on the regulation of immune responses that efficiently clear worms and allow protective immunity to develop. The innate immune responses play a critical role in host defense against schistosome infection and pathogenesis. Initial pro-inflammatory responses are essential for clearing invading parasites by promoting appropriate cell-mediated and humoral immunity. However, elevated and prolonged inflammatory responses against the eggs trapped in the host tissues contribute to disease progression. A better understanding of the molecular mechanisms of innate immune responses is important for developing effective therapies and vaccines. Here, we update the recent advances in the definitive host innate immune response to schistosome infection, especially highlighting the critical roles of pattern recognition receptors and cytokines. The considerations for further research are also provided.
Topics: Animals; Immunity, Innate; Schistosoma; Receptors, Pattern Recognition; Schistosomiasis; Vaccines
PubMed: 36339337
DOI: 10.3389/fcimb.2022.1040270 -
Frontiers in Immunology 2020The deeply rooted, intricate relationship between the parasite and the human host has enabled the parasite to successfully survive within the host and surreptitiously... (Review)
Review
The deeply rooted, intricate relationship between the parasite and the human host has enabled the parasite to successfully survive within the host and surreptitiously evade the host's immune attacks. The parasite has developed a variety of strategies in its immunomodulatory armamentarium to promote infection without getting harmed or killed in the battlefield of immune responses. These include the production of immunomodulatory molecules, alteration of membranes, and the promotion of granuloma formation. Schistosomiasis thus serves as a paradigm for understanding the Th2 immune responses seen in various helminthiases. This review therefore aims to summarize the immunomodulatory mechanisms of the schistosome parasites to survive inside the host. Understanding these immunomodulatory strategies not only provides information on parasite-host interactions, but also forms the basis in the development of novel drugs and vaccines against the schistosome infection, as well as various types of autoimmune and inflammatory conditions.
Topics: Animals; Anthelmintics; Antigens, Helminth; Host-Parasite Interactions; Humans; Immunity, Innate; Immunomodulation; Schistosoma; Schistosomiasis; Th2 Cells
PubMed: 32582161
DOI: 10.3389/fimmu.2020.01018 -
Molecules (Basel, Switzerland) Sep 2023It is estimated that 250 million people worldwide are affected by schistosomiasis. Disease transmission is related to the poor sanitation and hygiene habits that affect... (Review)
Review
It is estimated that 250 million people worldwide are affected by schistosomiasis. Disease transmission is related to the poor sanitation and hygiene habits that affect residents of impoverished regions in tropical and subtropical countries. The main species responsible for causing disease in humans are , , and , each with different geographic distributions. Praziquantel is the drug predominantly used to treat this disease, which offers low effectiveness against immature and juvenile parasite forms. In addition, reports of drug resistance prompt the development of novel therapeutic approaches. Natural products represent an important source of new compounds, especially those obtained from plant sources. This review compiles data from several in vitro and in vivo studies evaluating various compounds and essential oils derived from plants with cercaricidal and molluscicidal activities against both juvenile and adult forms of the parasite. Finally, this review provides an important discussion on recent advances in molecular and computational tools deemed fundamental for more rapid and effective screening of new compounds, allowing for the optimization of time and resources.
Topics: Humans; Animals; Anthelmintics; Schistosoma haematobium; Biological Products; Schistosomiasis; Praziquantel; Schistosoma mansoni
PubMed: 37836650
DOI: 10.3390/molecules28196807 -
International Journal For Parasitology.... Aug 2021Human schistosomiasis is a debilitating, life-threatening disease affecting more than 229 million people in as many as 78 countries. There is only one drug of choice... (Review)
Review
Human schistosomiasis is a debilitating, life-threatening disease affecting more than 229 million people in as many as 78 countries. There is only one drug of choice effective against all three major species of Schistosoma, praziquantel (PZQ). However, as with many monotherapies, evidence for resistance is emerging in the field and can be selected for in the laboratory. Previously used therapies include oxamniquine (OXA), but shortcomings such as drug resistance and affordability resulted in discontinuation. Employing a genetic, biochemical and molecular approach, a sulfotransferase (SULT-OR) was identified as responsible for OXA drug resistance. By crystallizing SmSULT- OR with OXA, the mode of action of OXA was determined. This information allowed a rational approach to novel drug design. Our team approach with schistosome biologists, medicinal chemists, structural biologists and geneticists has enabled us to develop and test novel drug derivatives of OXA to treat this disease. Using an iterative process for drug development, we have successfully identified derivatives that are effective against all three species of the parasite. One derivative CIDD-0149830 kills 100% of all three human schistosome species within 5 days. The goal is to generate a second therapeutic with a different mode of action that can be used in conjunction with praziquantel to overcome the ever-growing threat of resistance and improve efficacy. The ability and need to design, screen, and develop future, affordable therapeutics to treat human schistosomiasis is critical for successful control program outcomes.
Topics: Animals; Drug Discovery; Humans; Oxamniquine; Praziquantel; Schistosoma mansoni; Schistosomiasis
PubMed: 34111649
DOI: 10.1016/j.ijpddr.2021.05.002 -
EBioMedicine Nov 2023A controlled human infection model for schistosomiasis (CHI-S) can speed up vaccine development and provides insight into early immune responses following schistosome...
BACKGROUND
A controlled human infection model for schistosomiasis (CHI-S) can speed up vaccine development and provides insight into early immune responses following schistosome exposure. Recently, we established CHI-S model using single-sex male-only Schistosoma mansoni (Sm) cercariae in Schistosoma-naïve individuals. Given important differences in antigenic profile and human immune responses to schistosomes of different sex, we pioneered a single-sex female-only CHI-S model for future use in vaccine development.
METHODS
We exposed 13 healthy, Schistosoma-naïve adult participants to 10 (n = 3) or 20 (n = 10) female cercariae and followed for 20 weeks, receiving treatment with praziquantel (PZQ) 60 mg/kg at week 8 and 12 after exposure.
FINDINGS
The majority (11/13) participants reported rash and/or itch at the site of exposure, 5/13 had transient symptoms of acute schistosomiasis. Exposure to 20 cercariae led to detectable infection, defined as serum circulating anodic antigen levels >1.0 pg/mL, in 6/10 participants. Despite two rounds of PZQ treatment, 4/13 participants showed signs of persistent infection. Additional one- or three-day PZQ treatment (1 × 60 mg/kg and 3 × 60 mg/kg) or artemether did not result in cure, but over time three participants self-cured. Antibody, cellular, and cytokine responses peaked at week 4 post infection, with a mixed Th1, Th2, and regulatory profile. Cellular responses were (most) discriminative for symptoms.
INTERPRETATION
Female-only infections exhibit similar clinical and immunological profiles as male-only infections but are more resistant to PZQ treatment. This limits future use of this model and may have important implications for disease control programs.
FUNDING
European Union's Horizon 2020 (grant no. 81564).
Topics: Adult; Animals; Humans; Male; Female; Schistosomiasis mansoni; Healthy Volunteers; Schistosoma mansoni; Praziquantel; Cytokines; Anthelmintics
PubMed: 37837930
DOI: 10.1016/j.ebiom.2023.104832 -
The American Journal of Tropical... Jul 2020An essential mission of the Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) was to help inform global health practices related to the control... (Review)
Review
An essential mission of the Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) was to help inform global health practices related to the control and elimination of schistosomiasis. To provide more accurate, evidence-based projections of the most likely impact of different control interventions, whether implemented alone or in combination, SCORE supported mathematical modeling teams to provide simulations of community-level infection outcomes in the setting of real or hypothetical programs implementing multiyear mass drug administration (MDA) for parasite control. These models were calibrated using SCORE experience with and gaining and sustaining control studies, and with data from comparable programs that used community-based or school-based praziquantel MDA in other parts of sub-Saharan Africa. From 2010 to 2019, models were developed and refined, first to project the likely SCORE control outcomes, and later to more accurately reflect impact of MDA across different transmission settings, including the role of snail ecology and the impact of seasonal rainfall on snail abundance. Starting in 2014, SCORE modeling projections were also compared with the models of colleagues in the Neglected Tropical Diseases Modelling Consortium. To explore further possible improvement to program-based control, later simulations examined the cost-effectiveness of combining MDA with environmental snail control, and the utility of early impact assessment to more quickly identify persistent hot spots of transmission. This article provides a nontechnical summary of the 11 SCORE-related modeling projects and provides links to the original open-access articles describing model development and projections relevant to schistosomiasis control policy.
Topics: Africa South of the Sahara; Animals; Anthelmintics; Child; Cost-Benefit Analysis; Disease Reservoirs; Humans; Mass Drug Administration; Models, Theoretical; Praziquantel; Schistosoma haematobium; Schistosoma mansoni; Schistosomiasis haematobia; Schistosomiasis mansoni; Snails
PubMed: 32400357
DOI: 10.4269/ajtmh.19-0852