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1.
PLoS Negl Trop Dis ; 16(2): e0010176, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-35167594

RESUMEN

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


Asunto(s)
Interacciones Huésped-Parásitos/fisiología , Schistosoma haematobium/patogenicidad , Esquistosomiasis Urinaria/fisiopatología , Vejiga Urinaria/parasitología , Animales , Modelos Animales de Enfermedad , Femenino , Ratones Endogámicos BALB C , Óvulo , Proteoma , Vejiga Urinaria/metabolismo , Vejiga Urinaria/patología
2.
Proc Natl Acad Sci U S A ; 118(41)2021 10 12.
Artículo en Inglés | MEDLINE | ID: mdl-34615712

RESUMEN

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


Asunto(s)
Número Básico de Reproducción/estadística & datos numéricos , Ganado/parasitología , Schistosoma haematobium/patogenicidad , Esquistosomiasis Urinaria/transmisión , Esquistosomiasis Urinaria/veterinaria , Animales , Bovinos/parasitología , Cabras/parasitología , Humanos , Enfermedades Desatendidas/parasitología , Senegal/epidemiología , Ovinos/parasitología , Zoonosis/parasitología , Zoonosis/transmisión
3.
Am J Trop Med Hyg ; 103(1_Suppl): 30-35, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32400348

RESUMEN

The Schistosomiasis Consortium for Operational Research (SCORE) was funded in 2008 to improve the evidence base for control and elimination of schistosomiasis-better understanding of the systemic morbidities experienced by children in schistosomiasis-endemic areas and the response of these morbidities to treatment, being essential for updating WHO guidelines for mass drug administration (MDA) in endemic areas. This article summarizes the SCORE studies that aimed to gauge the impact of MDA-based treatment on schistosomiasis-related morbidities. Morbidity cohort studies were embedded in the SCORE's larger field studies of gaining control of schistosomiasis in Kenya and Tanzania. Following MDA, cohort children had less undernutrition, less portal vein dilation, and increased quality of life in Year 5 compared with baseline. We also conducted a pilot study of the Behavioral Assessment System for Children (BASC-2) in conjunction with the Kenya gaining control study, which demonstrated beneficial effects of treatment on classroom behavior. In addition, the SCORE's Rapid Answers Project performed systematic reviews of previously available data, providing two meta-analyses related to morbidity. The first documented children's infection-related deficits in school attendance and achievement and in formal tests of learning and memory. The second showed that greater reductions in egg output following drug treatment correlates significantly with reduced odds of most morbidities. Overall, these SCORE morbidity studies provided convincing evidence to support the use of MDA to improve the health of school-aged children in endemic areas. However, study findings also support the need to use enhanced metrics to fully assess and better control schistosomiasis-associated morbidity.


Asunto(s)
Schistosoma/patogenicidad , Esquistosomiasis Urinaria , Esquistosomiasis mansoni , Adolescente , Animales , Niño , Estudios de Cohortes , Femenino , Humanos , Kenia/epidemiología , Masculino , Administración Masiva de Medicamentos , Morbilidad , Recuento de Huevos de Parásitos , Praziquantel/uso terapéutico , Prevalencia , Schistosoma/efectos de los fármacos , Schistosoma haematobium/efectos de los fármacos , Schistosoma haematobium/patogenicidad , Schistosoma mansoni/efectos de los fármacos , Schistosoma mansoni/patogenicidad , Esquistosomiasis Urinaria/tratamiento farmacológico , Esquistosomiasis Urinaria/epidemiología , Esquistosomiasis mansoni/tratamiento farmacológico , Esquistosomiasis mansoni/epidemiología , Instituciones Académicas , Tanzanía/epidemiología
4.
Commun Biol ; 3(1): 155, 2020 04 02.
Artículo en Inglés | MEDLINE | ID: mdl-32242065

RESUMEN

Helminth parasites have been shown to have systemic effects in the host. Using shotgun metagenomic sequencing, we characterise the gut microbiome and resistome of 113 Zimbabwean preschool-aged children (1-5 years). We test the hypothesis that infection with the human helminth parasite, Schistosoma haematobium, is associated with changes in gut microbial and antimicrobial resistance gene abundance/diversity. Here, we show that bacteria phyla Bacteroidetes, Firmicutes, Proteobacteria, and fungi phyla Ascomycota, Microsporidia, Zoopagomycota dominate the microbiome. The abundance of Proteobacteria, Ascomycota, and Basidiomycota differ between schistosome-infected versus uninfected children. Specifically, infection is associated with increases in Pseudomonas, Stenotrophomonas, Derxia, Thalassospira, Aspergillus, Tricholoma, and Periglandula, with a decrease in Azospirillum. We find 262 AMR genes, from 12 functional drug classes, but no association with individual-specific data. To our knowledge, we describe a novel metagenomic dataset of Zimbabwean preschool-aged children, indicating an association between urogenital schistosome infection and changes in the gut microbiome.


Asunto(s)
Bacterias/crecimiento & desarrollo , Microbioma Gastrointestinal , Intestinos/microbiología , Schistosoma haematobium/patogenicidad , Esquistosomiasis Urinaria/microbiología , Esquistosomiasis Urinaria/parasitología , Factores de Edad , Animales , Bacterias/clasificación , Bacterias/genética , Estudios de Casos y Controles , Preescolar , Estudios Transversales , Femenino , Interacciones Huésped-Parásitos , Humanos , Lactante , Masculino , Metagenoma , Metagenómica , Esquistosomiasis Urinaria/diagnóstico , Zimbabwe
5.
Biomed Res Int ; 2019: 2972630, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31886198

RESUMEN

Urine reagent strip used in detecting microhaematuria has been recommended in pregnancy for diagnosis of urogenital schistosomiasis (UGS) during routine antenatal care (ANC). This study evaluated its sensitivity, specificity, and predictive values in the diagnosis of maternal UGS using filtration method as a reference test. We also assessed the variation in its performance in the diagnosis of UGS using multiple-sample collection. A total of 93 pregnant women reporting for first ANC clinic visit at any of the three functional health care centres (Munyenge Integrated Health Centre, Banga Annex Health Centre, and Trans African Health Centre) were enrolled and followed up for three consecutive monthly visits. Urine samples were observed microscopically for S. haematobium egg using urine filtration and screened for microhaematuria and proteinuria using urine reagent strips. Twenty-two (23.7%) out of the 93 women were diagnosed for UGS, all of whom showed S. haematobium egg excretion during all three visits. There was a significant difference (p < 0.001) between the prevalence of S. haematobium infection and the prevalence of microhaematuria. The intensity of infection was significantly higher in microhaematuria-positive women compared with microhaematuria-negative cases. Sensitivity of reagent strip ranged from 54.5 to 59.1%, while specificity was above 98.0% (range: 98.6-100%). The measure of agreement between urine filtration and reagent strip method was substantial (0.61-0.8) irrespective of different sampling periods. Urine reagent strip is a moderately sensitive method in the detection of UGS and will most likely identify women with high egg load burden. Proper diagnosis of schistosomiasis during pregnancy is recommended.


Asunto(s)
Diagnóstico Prenatal , Schistosoma haematobium/aislamiento & purificación , Esquistosomiasis Urinaria/diagnóstico , Adulto , Atención Ambulatoria , Instituciones de Atención Ambulatoria , Animales , Femenino , Hematuria/diagnóstico , Hematuria/epidemiología , Hematuria/parasitología , Humanos , Examen Físico , Embarazo , Proteinuria/diagnóstico , Proteinuria/epidemiología , Proteinuria/parasitología , Tiras Reactivas/uso terapéutico , Schistosoma haematobium/patogenicidad , Esquistosomiasis Urinaria/epidemiología , Esquistosomiasis Urinaria/parasitología
6.
Molecules ; 24(21)2019 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-31731402

RESUMEN

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


Asunto(s)
Antioxidantes/farmacología , Neoplasias/tratamiento farmacológico , Opistorquiasis/tratamiento farmacológico , Esquistosomiasis Urinaria/tratamiento farmacológico , Acetilcisteína/química , Animales , Carcinogénesis/efectos de los fármacos , Carcinogénesis/patología , Carcinógenos/química , Aductos de ADN/efectos de los fármacos , Combinación de Medicamentos , Humanos , Metaboloma/efectos de los fármacos , Metaboloma/genética , Neoplasias/metabolismo , Neoplasias/parasitología , Opistorquiasis/complicaciones , Opistorquiasis/metabolismo , Opistorquiasis/parasitología , Opisthorchis/efectos de los fármacos , Opisthorchis/patogenicidad , Praziquantel/farmacología , Resveratrol/farmacología , Schistosoma haematobium/efectos de los fármacos , Schistosoma haematobium/patogenicidad , Esquistosomiasis Urinaria/complicaciones , Esquistosomiasis Urinaria/metabolismo , Esquistosomiasis Urinaria/parasitología
7.
J Helminthol ; 94: e84, 2019 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-31500673

RESUMEN

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


Asunto(s)
Coagulación Sanguínea , Hemostáticos/análisis , Esquistosomiasis Urinaria/orina , Instituciones Académicas/estadística & datos numéricos , Infecciones Urinarias/parasitología , Adolescente , Animales , Estudios de Casos y Controles , Niño , Femenino , Gabón , Hemostasis , Humanos , Masculino , Proyectos Piloto , Schistosoma haematobium/patogenicidad , Esquistosomiasis Urinaria/sangre
8.
Nat Rev Dis Primers ; 4(1): 13, 2018 08 09.
Artículo en Inglés | MEDLINE | ID: mdl-30093684

RESUMEN

Schistosomiasis (bilharzia) is a neglected tropical disease caused by parasitic flatworms (blood flukes) of the genus Schistosoma, with considerable morbidity in parts of the Middle East, South America, Southeast Asia and, particularly, in sub-Saharan Africa. Infective larvae grow in an intermediate host (fresh-water snails) before penetrating the skin of the definitive human host. Mature adult worms reside in the mesenteric (Schistosoma mansoni and Schistosoma japonicum) or pelvic (Schistosoma haematobium) veins, where female worms lay eggs, which are secreted in stool or urine. Eggs trapped in the surrounding tissues and organs, such as the liver and bladder, cause inflammatory immune responses (including granulomas) that result in intestinal, hepato-splenic or urogenital disease. Diagnosis requires the detection of eggs in excreta or worm antigens in the serum, and sensitive, rapid, point-of-care tests for populations living in endemic areas are needed. The anti-schistosomal drug praziquantel is safe and efficacious against adult worms of all the six Schistosoma spp. infecting humans; however, it does not prevent reinfection and the emergence of drug resistance is a concern. Schistosomiasis elimination will require a multifaceted approach, including: treatment; snail control; information, education and communication; improved water, sanitation and hygiene; accurate diagnostics; and surveillance-response systems that are readily tailored to social-ecological settings.


Asunto(s)
Esquistosomiasis/complicaciones , Esquistosomiasis/diagnóstico , Animales , Antihelmínticos/uso terapéutico , Ensayo de Inmunoadsorción Enzimática/métodos , Humanos , Praziquantel/uso terapéutico , Schistosoma haematobium/microbiología , Schistosoma haematobium/patogenicidad , Schistosoma japonicum/microbiología , Schistosoma japonicum/patogenicidad , Schistosoma mansoni/microbiología , Schistosoma mansoni/patogenicidad , Esquistosomiasis/fisiopatología , Caracoles/microbiología , Caracoles/patogenicidad , Ultrasonografía/métodos , Zoonosis/etiología , Zoonosis/fisiopatología
9.
Artículo en Inglés | MEDLINE | ID: mdl-29866859

RESUMEN

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


Asunto(s)
Praziquantel/farmacocinética , Schistosoma haematobium/patogenicidad , Schistosoma mansoni/patogenicidad , Esquistosomiasis mansoni/sangre , Adolescente , Animales , Niño , Preescolar , Cromatografía Liquida , Humanos , Praziquantel/uso terapéutico , Esquistosomiasis mansoni/tratamiento farmacológico , Espectrometría de Masas en Tándem
10.
Am J Trop Med Hyg ; 99(1): 94-96, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-29714164
11.
Sultan Qaboos Univ Med J ; 18(3): e304-e310, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-30607270

RESUMEN

OBJECTIVES: This study aimed to assess the efficacy of praziquantel in reducing urinary schistosomiasis prevalence, parasite burden and morbidity rates among a previously reported sample of Schistosoma haematobium-infected children. In addition, predisposing factors for reinfection one year post-treatment were also determined. METHODS: This prospective follow-up study was conducted between March 2014 and February 2015 among 675 previously reported children with urinary schistosomiasis in the Murbai and Surbai communities of Ardo Kola, Taraba State, Nigeria. A single dose of 40 mg/kg of praziquantel was administered to each infected child, with a second dose administered one month later if necessary. The number of S. haematobium eggs in urine samples was calculated at baseline and post-treatment. RESULTS: At four weeks post-treatment, the overall cure rate was 98.1%. Among children with low and heavy parasite burdens at baseline, egg reduction rates (ERRs) were 100% and 96.5%, respectively. The vast majority of children with microhaematuria (98.7%) and proteinuria (98.6%) at baseline were cured at follow-up. Following a second dose, the ERR, overall and morbidity cure rates increased to 100%. At one year post-treatment, 272 infected children (40.3%) were re-assessed; of these, 51 children (18.8%) were reinfected. Close proximity to bodies of water (odds ratio [OR] = 1.23, 95% confidence interval [CI]: 0.998-1.530; P = 0.05) and fishing (OR = 2.23, 95% CI: 0.828-6.040; P = 0.01) were significant factors that predisposed children to reinfection. CONCLUSION: A moderate rate of reinfection was noted. Governmental and nongovernmental organisations in Nigeria should collaborate on mass treatment and health education campaigns to reduce the incidence of urinary schistosomiasis reinfections.


Asunto(s)
Praziquantel/análisis , Praziquantel/farmacología , Esquistosomiasis Urinaria/tratamiento farmacológico , Adolescente , Animales , Antihelmínticos/análisis , Antihelmínticos/farmacología , Antihelmínticos/uso terapéutico , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Nigeria , Pediatría/métodos , Pediatría/tendencias , Praziquantel/uso terapéutico , Estudios Prospectivos , Schistosoma haematobium/efectos de los fármacos , Schistosoma haematobium/patogenicidad , Esquistosomiasis Urinaria/orina , Resultado del Tratamiento
12.
Int J Mol Sci ; 18(12)2017 Nov 28.
Artículo en Inglés | MEDLINE | ID: mdl-29182577

RESUMEN

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


Asunto(s)
Citocromo P-450 CYP2D6/metabolismo , Estrógenos/metabolismo , Interleucina-6/metabolismo , Polimorfismo Genético/genética , Schistosoma haematobium/patogenicidad , Adolescente , Animales , Índice de Masa Corporal , Niño , Citocromo P-450 CYP2D6/genética , Femenino , Genotipo , Humanos , Interleucina-6/genética , Masculino , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/metabolismo
13.
Trans R Soc Trop Med Hyg ; 111(7): 316-324, 2017 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-29165707

RESUMEN

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<0.05). Levels at baseline were 8.31 times higher (p<0.01) in participants with bladder morbidity than in those without. There was no correlation with kidney morbidity and no significant effect of a repeated dose of PZQ 40 mg/kg. Baseline ECP and ECP after 9 weeks were associated with microhaematuria (geometric mean ratio at baseline 7.56 [95% confidence limit {CL} 2.34-24.45]; p<0.01) and macrohaematuria (geometric mean ratio at baseline 6.22 [95% CL 2.71-14.24]; p<0.001). Mean levels of ECP dropped significantly during the first follow-up period and far less so in the second follow-up period (mean ECP at baseline: 70.8 ng/mL; ECP at 24 h: 24.5 ng/mL; ECP at 9 weeks: 14.6 ng/mL). Conclusion: The urine ECP decrease happened immediately after treatment, reflecting the rapid action of PZQ on eggs in the bladder tissue. ECP in urine can be used as an indirect marker of the degree of local inflammatory reaction in the bladder and is not significantly affected by a repeated dose of PZQ.


Asunto(s)
Antihelmínticos/uso terapéutico , Proteína Catiónica del Eosinófilo/orina , Inflamación/orina , Praziquantel/uso terapéutico , Schistosoma haematobium/efectos de los fármacos , Esquistosomiasis Urinaria/tratamiento farmacológico , Vejiga Urinaria , Adolescente , Adulto , Animales , Antihelmínticos/administración & dosificación , Antihelmínticos/farmacología , Biomarcadores/orina , Niño , Preescolar , Estudios de Cohortes , Femenino , Hematuria , Humanos , Inflamación/etiología , Riñón , Masculino , Recuento de Huevos de Parásitos , Praziquantel/administración & dosificación , Praziquantel/farmacología , Schistosoma haematobium/crecimiento & desarrollo , Schistosoma haematobium/patogenicidad , Esquistosomiasis Urinaria/parasitología , Esquistosomiasis Urinaria/patología , Esquistosomiasis Urinaria/orina , Vejiga Urinaria/efectos de los fármacos , Vejiga Urinaria/parasitología , Vejiga Urinaria/patología , Adulto Joven
15.
Adv Exp Med Biol ; 1018: 193-205, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-29052139

RESUMEN

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


Asunto(s)
Carcinogénesis/genética , Fasciola hepatica/patogenicidad , Enfermedades Parasitarias/epidemiología , Neoplasias de la Vejiga Urinaria/epidemiología , Animales , Clonorchis sinensis/patogenicidad , Humanos , Opisthorchis/patogenicidad , Enfermedades Parasitarias/parasitología , Schistosoma haematobium/patogenicidad , Neoplasias de la Vejiga Urinaria/complicaciones , Neoplasias de la Vejiga Urinaria/parasitología
16.
BMC Infect Dis ; 17(1): 652, 2017 09 29.
Artículo en Inglés | MEDLINE | ID: mdl-28962552

RESUMEN

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


Asunto(s)
Antihelmínticos/uso terapéutico , Esquistosomiasis Urinaria/tratamiento farmacológico , Esquistosomiasis mansoni/tratamiento farmacológico , Anemia/tratamiento farmacológico , Anemia/etiología , Animales , Niño , Estudios de Cohortes , Heces/parasitología , Humanos , Kenia/epidemiología , Masculino , Morbilidad , Mozambique/epidemiología , Niger/epidemiología , Prevalencia , Calidad de Vida , Schistosoma haematobium/patogenicidad , Schistosoma mansoni/patogenicidad , Esquistosomiasis Urinaria/epidemiología , Esquistosomiasis mansoni/epidemiología , Tanzanía/epidemiología
17.
APMIS ; 125(12): 1056-1062, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-28960560

RESUMEN

Schistosoma haematobium, a parasitic flatworm that infects more than 100 million people, mostly in the developing world, is the causative agent of urogenital schistosomiasis, and is associated with a high incidence of squamous cell carcinoma (SCC) of the bladder. During infection, eggs are deposited in the bladder causing an intense inflammatory reaction. Angiogenesis is defined as the formation of new blood vessels from preexisting ones and is recognized as a key event in cell proliferation and carcinogenesis and spread of malignant lesions. A growing amount of evidence points to angiogenesis playing a key role in schistosomiasis-associated bladder cancer. Thus, identifying biomarkers of this process plays an important role in the study of cancer. Here, we review recent findings on the role of angiogenesis in bladder cancer and the growth factors that induce and assist in their development, particularly SCC of the bladder associated to urogenital schistosomiasis.


Asunto(s)
Carcinoma de Células Escamosas/etiología , Esquistosomiasis Urinaria/complicaciones , Neoplasias de la Vejiga Urinaria/etiología , Animales , Biomarcadores de Tumor/metabolismo , Carcinoma de Células Escamosas/irrigación sanguínea , Carcinoma de Células Escamosas/patología , Humanos , Linfangiogénesis , Neovascularización Patológica , Schistosoma haematobium/patogenicidad , Neoplasias de la Vejiga Urinaria/irrigación sanguínea , Neoplasias de la Vejiga Urinaria/patología , Factor A de Crecimiento Endotelial Vascular/metabolismo
18.
Infect Immun ; 85(12)2017 12.
Artículo en Inglés | MEDLINE | ID: mdl-28923894

RESUMEN

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


Asunto(s)
Proteínas del Helminto/metabolismo , Óvulo/metabolismo , Schistosoma haematobium/patogenicidad , Animales , Línea Celular Tumoral , Núcleo Celular/parasitología , Clonación Molecular , Proteínas de Unión al ADN , Proteínas del Huevo/genética , Proteínas del Huevo/metabolismo , Proteínas del Helminto/genética , Humanos , Inmunomodulación , Inflamación , Proteínas Recombinantes/genética , Esquistosomiasis Urinaria/parasitología , Vejiga Urinaria/citología , Vejiga Urinaria/efectos de los fármacos
20.
Infect Dis Poverty ; 6(1): 57, 2017 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-28457230

RESUMEN

BACKGROUND: Given that increase in temperature may alter host-parasite relationships, the anticipated rise in temperature due to global warming might change transmission patterns of certain diseases. However, the extent to which this will happen is not well understood. METHODS: Using a host-parasite system involving Bulinus globosus and Schistosoma haematobium, we assessed the effect of temperature on snail fecundity, growth, survival and parasite development under laboratory conditions. RESULTS: Our results show that temperature may have a non-linear effect on snail fecundity and snail growth. Snails maintained at 15.5 °C and 36.0 °C did not produce egg masses while those maintained at 25.8 °C laid 344 and 105 more egg masses than snails at 31.0 °C and 21.2 °C, respectively. Attainment of patency led to a reduction in egg mass production among the snails. However, the reduction in fecundity for snails maintained at 21.2 °C occurred before snails started shedding cercariae. Parasite development was accelerated at high temperatures with snails maintained at 31.0 °C reaching patency after three weeks. Furthermore, snail growth rate was highest at 25.8 °C while it was inhibited at 15.5 °C and reduced at 31.0 °C. Increase in temperature increased snail mortality rates. Snails maintained at 36.0 °C had the shortest survival time while those maintained at 15.5 °C had the longest survival time. CONCLUSIONS: We concluded that temperature influences fecunxdity, growth, survival and parasite development in the snail and thus dictates the time it takes the parasite to complete the life cycle. This has implications on transmission of schistosomiasis in the context of global warming.


Asunto(s)
Bulinus/fisiología , Bulinus/parasitología , Interacciones Huésped-Parásitos/fisiología , Schistosoma haematobium/patogenicidad , Esquistosomiasis Urinaria/fisiopatología , Esquistosomiasis Urinaria/parasitología , Animales , Fertilidad , Estadios del Ciclo de Vida , Carga de Parásitos , Temperatura
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