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1.
Nature ; 619(7971): 782-787, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37438520

RESUMO

Many communities in low- and middle-income countries globally lack sustainable, cost-effective and mutually beneficial solutions for infectious disease, food, water and poverty challenges, despite their inherent interdependence1-7. Here we provide support for the hypothesis that agricultural development and fertilizer use in West Africa increase the burden of the parasitic disease schistosomiasis by fuelling the growth of submerged aquatic vegetation that chokes out water access points and serves as habitat for freshwater snails that transmit Schistosoma parasites to more than 200 million people globally8-10. In a cluster randomized controlled trial (ClinicalTrials.gov: NCT03187366) in which we removed invasive submerged vegetation from water points at 8 of 16 villages (that is, clusters), control sites had 1.46 times higher intestinal Schistosoma infection rates in schoolchildren and lower open water access than removal sites. Vegetation removal did not have any detectable long-term adverse effects on local water quality or freshwater biodiversity. In feeding trials, the removed vegetation was as effective as traditional livestock feed but 41 to 179 times cheaper and converting the vegetation to compost provided private crop production and total (public health plus crop production benefits) benefit-to-cost ratios as high as 4.0 and 8.8, respectively. Thus, the approach yielded an economic incentive-with important public health co-benefits-to maintain cleared waterways and return nutrients captured in aquatic plants back to agriculture with promise of breaking poverty-disease traps. To facilitate targeting and scaling of the intervention, we lay the foundation for using remote sensing technology to detect snail habitats. By offering a rare, profitable, win-win approach to addressing food and water access, poverty alleviation, infectious disease control and environmental sustainability, we hope to inspire the interdisciplinary search for planetary health solutions11 to the many and formidable, co-dependent global grand challenges of the twenty-first century.


Assuntos
Agricultura , Ecossistema , Saúde da População Rural , Esquistossomose , Caramujos , Animais , Criança , Humanos , Esquistossomose/epidemiologia , Esquistossomose/prevenção & controle , Esquistossomose/transmissão , Caramujos/parasitologia , África Ocidental , Fertilizantes , Espécies Introduzidas , Intestinos/parasitologia , Água Doce , Plantas/metabolismo , Biodiversidade , Ração Animal , Qualidade da Água , Produção Agrícola/métodos , Saúde Pública , Pobreza/prevenção & controle , Organismos Aquáticos/metabolismo , Tecnologia de Sensoriamento Remoto
2.
Proc Natl Acad Sci U S A ; 121(2): e2315463120, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38181058

RESUMO

Schistosomiasis is a neglected tropical disease affecting over 150 million people. Hotspots of Schistosoma transmission-communities where infection prevalence does not decline adequately with mass drug administration-present a key challenge in eliminating schistosomiasis. Current approaches to identify hotspots require evaluation 2-5 y after a baseline survey and subsequent mass drug administration. Here, we develop statistical models to predict hotspots at baseline prior to treatment comparing three common hotspot definitions, using epidemiologic, survey-based, and remote sensing data. In a reanalysis of randomized trials in 589 communities in five endemic countries, a regression model predicts whether Schistosoma mansoni infection prevalence will exceed the WHO threshold of 10% in year 5 ("prevalence hotspot") with 86% sensitivity, 74% specificity, and 93% negative predictive value (NPV; assuming 30% hotspot prevalence), and a regression model for Schistosoma haematobium achieves 90% sensitivity, 90% specificity, and 96% NPV. A random forest model predicts whether S. mansoni moderate and heavy infection prevalence will exceed a public health goal of 1% in year 5 ("intensity hotspot") with 92% sensitivity, 79% specificity, and 96% NPV, and a boosted trees model for S. haematobium achieves 77% sensitivity, 95% specificity, and 91% NPV. Baseline prevalence is a top predictor in all models. Prediction is less accurate in countries not represented in training data and for a third hotspot definition based on relative prevalence reduction over time ("persistent hotspot"). These models may be a tool to prioritize high-risk communities for more frequent surveillance or intervention against schistosomiasis, but prediction of hotspots remains a challenge.


Assuntos
Esquistossomose mansoni , Esquistossomose , Humanos , Animais , Administração Massiva de Medicamentos , Esquistossomose/tratamento farmacológico , Esquistossomose/epidemiologia , Esquistossomose mansoni/tratamento farmacológico , Esquistossomose mansoni/epidemiologia , Schistosoma haematobium , Modelos Estatísticos
3.
PLoS Pathog ; 20(1): e1011949, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38285715

RESUMO

Schistosomes are flatworm parasites that undergo a complex life cycle involving two hosts. The regulation of the parasite's developmental processes relies on both coding RNAs and non-coding RNAs. However, the roles of non-coding RNAs, including long non-coding RNAs (lncRNAs) in schistosomes remain largely unexplored. Here we conduct advanced RNA sequencing on male and female S. japonicum during their pairing and reproductive development, resulting in the identification of nearly 8,000 lncRNAs. This extensive dataset enables us to construct a comprehensive co-expression network of lncRNAs and mRNAs, shedding light on their interactions during the crucial reproductive stages within the mammalian host. Importantly, we have also revealed a specific lncRNA, LNC3385, which appears to play a critical role in the survival and reproduction of the parasite. These findings not only enhance our understanding of the dynamic nature of lncRNAs during the reproductive phase of schistosomes but also highlight LNC3385 as a potential therapeutic target for combating schistosomiasis.


Assuntos
Parasitos , RNA Longo não Codificante , Schistosoma japonicum , Esquistossomose , Animais , Masculino , Feminino , Schistosoma japonicum/genética , RNA Longo não Codificante/genética , RNA Antissenso/genética , Esquistossomose/parasitologia , Parasitos/genética , Mamíferos
4.
J Immunol ; 212(4): 607-616, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38169327

RESUMO

Helminth infections are common in animals. However, the impact of a helminth infection on the function of hematopoietic stem cells (HSCs) and other hematopoietic cells has not been comprehensively defined. In this article, we describe the hematopoietic response to infection of mice with Schistosoma mansoni, a parasitic flatworm that causes schistosomiasis. We analyzed the frequency or number of hematopoietic cell types in the bone marrow, spleen, liver, thymus, and blood and observed multiple hematopoietic changes caused by infection. Schistosome infection impaired bone marrow HSC function after serial transplantation. Functional HSCs were present in the infected liver. Infection blocked bone marrow erythropoiesis and augmented spleen erythropoiesis, observations consistent with the anemia and splenomegaly prevalent in schistosomiasis patients. This work defines the hematopoietic response to schistosomiasis, a debilitating disease afflicting more than 200 million people, and identifies impairments in HSC function and erythropoiesis.


Assuntos
Medula Óssea , Esquistossomose , Humanos , Camundongos , Animais , Células-Tronco Hematopoéticas/metabolismo , Hematopoese/fisiologia , Eritropoese , Baço , Esquistossomose/complicações
5.
Clin Microbiol Rev ; 37(1): e0009823, 2024 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-38319102

RESUMO

Schistosomiasis is a neglected tropical disease caused by the helminth Schistosoma spp. and has the second highest global impact of all parasites. Schistosoma are transmitted through contact with contaminated fresh water predominantly in Africa, Asia, the Middle East, and South America. Due to the widespread prevalence of Schistosoma, co-infection with other infectious agents is common but often poorly described. Herein, we review recent literature describing the impact of Schistosoma co-infection between species and Schistosoma co-infection with blood-borne protozoa, soil-transmitted helminths, various intestinal protozoa, Mycobacterium, Salmonella, various urinary tract infection-causing agents, and viral pathogens. In each case, disease severity and, of particular interest, the immune landscape, are altered as a consequence of co-infection. Understanding the impact of schistosomiasis co-infections will be important when considering treatment strategies and vaccine development moving forward.


Assuntos
Coinfecção , Helmintíase , Esquistossomose , Humanos , Coinfecção/epidemiologia , Coinfecção/parasitologia , Esquistossomose/complicações , Esquistossomose/epidemiologia , Esquistossomose/parasitologia , África , Solo/parasitologia , Prevalência , Helmintíase/complicações , Helmintíase/epidemiologia , Helmintíase/parasitologia
6.
PLoS Pathog ; 19(7): e1011498, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37498810

RESUMO

Schistosomiasis, a severe parasitic disease, is primarily caused by Schistosoma mansoni, Schistosoma japonicum, or Schistosoma haematobium. Currently, praziquantel is the only recommended drug for human schistosome infection. However, the lack of efficacy of praziquantel against juvenile worms and concerns about the emergence of drug resistance are driving forces behind the research for an alternative medication. Schistosomes are obligatory parasites that survive on nutrients obtained from their host. The ability of nutrient uptake depends on their physiological structure. In short, the formation and maintenance of the structure and nutrient supply are mutually reinforcing and interdependent. In this review, we focus on the structural features of the tegument, esophagus, and intestine of schistosomes and their roles in nutrient acquisition. Moreover, we introduce the significance and modes of glucose, lipids, proteins, and amino acids intake in schistosomes. We linked the schistosome structure and nutrient supply, introduced the currently emerging targets, and analyzed the current bottlenecks in the research and development of drugs and vaccines, in the hope of providing new strategies for the prevention and control of schistosomiasis.


Assuntos
Schistosoma japonicum , Esquistossomose , Animais , Humanos , Praziquantel/uso terapêutico , Esquistossomose/parasitologia , Schistosoma haematobium , Schistosoma mansoni , Ingestão de Alimentos
7.
PLoS Pathog ; 19(3): e1011242, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36930687

RESUMO

Schistosomiasis is a zoonotic parasitic disease. Schistosoma japonicum eggs deposited in the liver tissue induce egg granuloma formation and liver fibrosis, seriously threatening human health. Natural killer (NK) cells kill activated hepatic stellate cells (HSCs) or induce HSC apoptosis and inhibit the progression of liver fibrosis. However, the function of NK cells in liver fibrosis caused by S. japonicum infection is significantly inhibited. The mechanism of this inhibition remains unclear. Twenty mice were percutaneously infected with S. japonicum cercariae. Before infection and 2, 4, 6, and 8 weeks after infection, five mice were euthanized and dissected at each time point. Hepatic NK cells were isolated and transcriptome sequenced. The sequencing results showed that Tigit expression was high at 4-6 weeks post infection. This phenomenon was verified by reverse transcription quantitative PCR (RT-qPCR) and flow cytometry. NK cells derived from Tigit-/- and wild-type (WT) mice were co-cultured with HSCs. It was found that Tigit-/- NK cells induced apoptosis in a higher proportion of HSCs than WT NK cells. Schistosomiasis infection models of Tigit-/- and WT mice were established. The proportion and killing activity of hepatic NK cells were significantly higher in Tigit-/- mice than in WT mice. The degree of liver fibrosis in Tigit-/- mice was significantly lower than that in WT mice. NK cells were isolated from Tigit-/- and WT mice and injected via the tail vein into WT mice infected with S. japonicum. The degree of liver fibrosis in mice that received NK cell infusion reduced significantly, but there was no significant difference between mice that received NK cells from Tigit-/- and WT mice, respectively. Our findings indicate that Tigit knockout enhanced the function of NK cells and reduced the degree of liver fibrosis in schistosomiasis, thus providing a novel strategy for treating hepatic fibrosis induced by schistosomiasis.


Assuntos
Receptores Imunológicos , Schistosoma japonicum , Esquistossomose Japônica , Esquistossomose , Animais , Camundongos , Células Matadoras Naturais/metabolismo , Fígado/patologia , Cirrose Hepática/metabolismo , Receptores Imunológicos/genética , Receptores Imunológicos/metabolismo , Esquistossomose/patologia
8.
PLoS Pathog ; 19(7): e1011018, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37428793

RESUMO

Human schistosomiasis is a neglected tropical disease caused by Schistosoma mansoni, S. haematobium, and S. japonicum. Praziquantel (PZQ) is the method of choice for treatment. Due to constant selection pressure, there is an urgent need for new therapies for schistosomiasis. Previous treatment of S. mansoni included the use of oxamniquine (OXA), a drug that is activated by a schistosome sulfotransferase (SULT). Guided by data from X-ray crystallography and Schistosoma killing assays more than 350 OXA derivatives were designed, synthesized, and tested. We were able to identify CIDD-0150610 and CIDD-0150303 as potent derivatives in vitro that kill (100%) of all three Schistosoma species at a final concentration of 71.5 µM. We evaluated the efficacy of the best OXA derivates in an in vivo model after treatment with a single dose of 100 mg/kg by oral gavage. The highest rate of worm burden reduction was achieved by CIDD -150303 (81.8%) against S. mansoni, CIDD-0149830 (80.2%) against S. haematobium and CIDD-066790 (86.7%) against S. japonicum. We have also evaluated the ability of the derivatives to kill immature stages since PZQ does not kill immature schistosomes. CIDD-0150303 demonstrated (100%) killing for all life stages at a final concentration of 143 µM in vitro and effective reduction in worm burden in vivo against S. mansoni. To understand how OXA derivatives fit in the SULT binding pocket, X-ray crystal structures of CIDD-0150303 and CIDD-0150610 demonstrate that the SULT active site will accommodate further modifications to our most active compounds as we fine tune them to increase favorable pharmacokinetic properties. Treatment with a single dose of 100 mg/kg by oral gavage with co-dose of PZQ + CIDD-0150303 reduced the worm burden of PZQ resistant parasites in an animal model by 90.8%. Therefore, we conclude that CIDD-0150303, CIDD-0149830 and CIDD-066790 are novel drugs that overcome some of PZQ limitations, and CIDD-0150303 can be used with PZQ in combination therapy.


Assuntos
Anti-Helmínticos , Esquistossomose mansoni , Esquistossomose , Animais , Humanos , Praziquantel/farmacologia , Praziquantel/química , Oxamniquine/farmacologia , Esquistossomose/tratamento farmacológico , Esquistossomose/parasitologia , Schistosoma mansoni , Terapia Combinada , Doenças Negligenciadas/tratamento farmacológico , Esquistossomose mansoni/tratamento farmacológico , Esquistossomose mansoni/parasitologia
9.
Trends Immunol ; 43(8): 657-673, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35835714

RESUMO

Schistosomiasis is the second most debilitating neglected tropical disease globally after malaria, with no available therapy to control disease-driven immunopathology. Although schistosomiasis induces a markedly heterogenous immune response, type 2 immunity is the dominating immune response following oviposition. While type 2 immunity has a crucial role in granuloma formation and host survival during the acute stage of disease, its chronic activation can result in tissue scarring, fibrosis, and organ impairment. Here, we discuss recent advances in schistosomiasis, demonstrating how different immune and non-immune cells and signaling pathways are involved in the induction, maintenance, and regulation of type 2 immunity. A better understanding of these immune responses during schistosomiasis is essential to inform the potential development of candidate therapeutic strategies that fine-tune type 2 immunity to ideally modulate schistosomiasis immunopathology.


Assuntos
Esquistossomose , Feminino , Fibrose , Humanos , Esquistossomose/metabolismo , Esquistossomose/patologia
10.
J Immunol ; 210(1): 82-95, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36445332

RESUMO

Schistosomiasis remains an important public health concern. The eggs deposited in livers invoke a Th2-dominant response, which mediates the fibrotic granulomatous response. However, the mechanisms involved in this immunopathological process are still not perfectly clear. Here, we report a single-cell transcriptional landscape of longitudinally collected BALB/c mouse splenocytes at different time points after Schistosoma japonicum infection. We found that exhausted CD4+ T cells were enriched after infection, changing from coproducing multiple cytokines to predominantly producing the Th2 cytokine IL-4. Regulatory B cells had high expression of Fcrl5, Ptpn22, and Lgals1, potentially regulating exhausted CD4+ T cells via direct PD-1-PD-L2 and PD-1-PD-L1 interactions. Within the myeloid compartment, the number of precursor and immature neutrophils sharply increased after infection. Moreover, dendritic cells, macrophages, and basophils showed inhibitory interactions with exhausted CD4+ T cells. Besides, in mouse livers, we found that exhausted CD4+ T cells were distributed around egg granuloma, promoting collagen expression in primary mouse hepatic stellate cells via IL-4 secretion, resulting in liver fibrosis. Our study provides comprehensive characterization of the composition and cellular states of immune cells with disease progression, which will facilitate better understanding of the mechanism underlying liver fibrotic granulomatous response in schistosomiasis.


Assuntos
Schistosoma japonicum , Esquistossomose Japônica , Esquistossomose , Camundongos , Animais , Esquistossomose Japônica/metabolismo , Esquistossomose Japônica/patologia , Linfócitos T CD4-Positivos , Interleucina-4 , Receptor de Morte Celular Programada 1 , Exaustão das Células T , Cirrose Hepática/patologia , Fígado , Fibrose , Citocinas
11.
Clin Infect Dis ; 78(Supplement_2): S153-S159, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38662699

RESUMO

BACKGROUND: Control of schistosomiasis (SCH) relies on the regular distribution of preventive chemotherapy (PC) over many years. For the sake of sustainable SCH control, a decision must be made at some stage to scale down or stop PC. These "stopping decisions" are based on population surveys that assess whether infection levels are sufficiently low. However, the limited sensitivity of the currently used diagnostic (Kato-Katz [KK]) to detect low-intensity infections is a concern. Therefore, the use of new, more sensitive, molecular diagnostics has been proposed. METHODS: Through statistical analysis of Schistosoma mansoni egg counts collected from Burundi and a simulation study using an established transmission model for schistosomiasis, we investigated the extent to which more sensitive diagnostics can improve decision making regarding stopping or continuing PC for the control of S. mansoni. RESULTS: We found that KK-based strategies perform reasonably well for determining when to stop PC at a local scale. Use of more sensitive diagnostics leads to a marginally improved health impact (person-years lived with heavy infection) and comes at a cost of continuing PC for longer (up to around 3 years), unless the decision threshold for stopping PC is adapted upward. However, if this threshold is set too high, PC may be stopped prematurely, resulting in a rebound of infection levels and disease burden (+45% person-years of heavy infection). CONCLUSIONS: We conclude that the potential value of more sensitive diagnostics lies more in the reduction of survey-related costs than in the direct health impact of improved parasite control.


Assuntos
Análise Custo-Benefício , Contagem de Ovos de Parasitas , Schistosoma mansoni , Esquistossomose mansoni , Humanos , Animais , Schistosoma mansoni/isolamento & purificação , Esquistossomose mansoni/diagnóstico , Esquistossomose mansoni/prevenção & controle , Esquistossomose mansoni/tratamento farmacológico , Esquistossomose mansoni/epidemiologia , Anti-Helmínticos/uso terapêutico , Anti-Helmínticos/economia , Feminino , Masculino , Esquistossomose/diagnóstico , Esquistossomose/prevenção & controle , Esquistossomose/tratamento farmacológico , Esquistossomose/epidemiologia , Adulto , Adolescente , Criança , Quimioprevenção/economia , Quimioprevenção/métodos , Adulto Jovem , Sensibilidade e Especificidade
12.
Emerg Infect Dis ; 30(6): 1236-1239, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38782022

RESUMO

A fecal survey in Tamil Nadu, India, revealed 2 persons passed schistosome eggs, later identified as Schistosoma incognitum, a parasite of pigs, dogs, and rats. We investigated those cases and reviewed autochthonous schistosomiasis cases from India and Nepal. Whether the 2 new cases represent true infection or spurious passage is undetermined.


Assuntos
Fezes , Schistosoma , Esquistossomose , Animais , Índia/epidemiologia , Humanos , Schistosoma/isolamento & purificação , Esquistossomose/epidemiologia , Esquistossomose/parasitologia , Fezes/parasitologia , Masculino , Feminino , Cães , Adulto , Suínos , Ratos/parasitologia , Nepal/epidemiologia , Pessoa de Meia-Idade , Ásia Meridional
13.
J Transl Med ; 22(1): 81, 2024 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-38245788

RESUMO

BACKGROUND: The long-term impact of COVID-19-associated public health interventions on zoonotic and vector-borne infectious diseases (ZVBs) remains uncertain. This study sought to examine the changes in ZVBs in China during the COVID-19 pandemic and predict their future trends. METHODS: Monthly incidents of seven ZVBs (Hemorrhagic fever with renal syndrome [HFRS], Rabies, Dengue fever [DF], Human brucellosis [HB], Leptospirosis, Malaria, and Schistosomiasis) were gathered from January 2004 to July 2023. An autoregressive fractionally integrated moving average (ARFIMA) by incorporating the COVID-19-associated public health intervention variables was developed to evaluate the long-term effectiveness of interventions and forecast ZVBs epidemics from August 2023 to December 2025. RESULTS: Over the study period, there were 1,599,647 ZVBs incidents. HFRS and rabies exhibited declining trends, HB showed an upward trajectory, while the others remained relatively stable. The ARFIMA, incorporating a pulse pattern, estimated the average monthly number of changes of - 83 (95% confidence interval [CI] - 353-189) cases, - 3 (95% CI - 33-29) cases, - 468 (95% CI - 1531-597) cases, 2191 (95% CI 1056-3326) cases, 7 (95% CI - 24-38) cases, - 84 (95% CI - 222-55) cases, and - 214 (95% CI - 1036-608) cases for HFRS, rabies, DF, HB, leptospirosis, malaria, and schistosomiasis, respectively, although these changes were not statistically significant besides HB. ARFIMA predicted a decrease in HB cases between August 2023 and December 2025, while indicating a relative plateau for the others. CONCLUSIONS: China's dynamic zero COVID-19 strategy may have exerted a lasting influence on HFRS, rabies, DF, malaria, and schistosomiasis, beyond immediate consequences, but not affect HB and leptospirosis. ARFIMA emerges as a potent tool for intervention analysis, providing valuable insights into the sustained effectiveness of interventions. Consequently, the application of ARFIMA contributes to informed decision-making, the design of effective interventions, and advancements across various fields.


Assuntos
COVID-19 , Febre Hemorrágica com Síndrome Renal , Leptospirose , Malária , Raiva , Esquistossomose , Doenças Transmitidas por Vetores , Humanos , Estações do Ano , Febre Hemorrágica com Síndrome Renal/epidemiologia , Saúde Pública , Análise de Séries Temporais Interrompida , Pandemias , Raiva/epidemiologia , Raiva/prevenção & controle , Incidência , COVID-19/epidemiologia , Doenças Transmitidas por Vetores/epidemiologia , China/epidemiologia , Leptospirose/epidemiologia , Esquistossomose/epidemiologia
14.
Br Med Bull ; 149(1): 45-59, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38220571

RESUMO

BACKGROUND: Female genital schistosomiasis (FGS) is a chronic gynaecological disease affecting girls and women in sub-Saharan Africa (SSA), caused by the parasite Schistosoma (S.) haematobium. FGS is associated with sexual dysfunction, reproductive tract morbidity and increased prevalence of HIV and cervical precancer lesions. SOURCE OF DATA: Key peer-reviewed published literature. AREAS OF AGREEMENT: FGS screening and diagnosis require costly equipment and specialized training, seldom available in resource-limited settings. FGS surveillance is not included in wider schistosomiasis control strategies. The interplay of FGS with other SRH infections is not fully understood. Integration of FGS within sexual and reproductive health (SRH) control programmes needs to be explored. AREAS OF CONTROVERSY: There are no standardized methods for individual or population-based FGS screening and diagnosis, hindering accurate disease burden estimates and targeted resource allocation. Treatment recommendations rely on public health guidelines, without rigorous clinical evidence on efficacy. GROWING POINTS: Integrating FGS screening with SRH programmes offers an opportunity to reach at-risk women with limited access to healthcare services. Home-based self-sampling coupled with handheld colposcopes operated by primary healthcare workers show promise for FGS diagnosis and surveillance at scale. AREAS TIMELY FOR DEVELOPING RESEARCH: There is growing interest in decentralizing strategies for FGS screening and diagnosis. The accurate predictions on the 'cost-effectiveness' of these approaches will determine their affordability and feasibility within the overburdened health systems in SSA. Clinical trials are needed to optimize FGS treatment. Longitudinal studies can expand on the epidemiological knowledge on co-morbidities and integration within other SRH interventions.


Assuntos
Doenças dos Genitais Femininos , Esquistossomose , Feminino , Humanos , Esquistossomose/tratamento farmacológico , Genitália Feminina/parasitologia , Doenças dos Genitais Femininos/diagnóstico , Doenças dos Genitais Femininos/epidemiologia , Doenças dos Genitais Femininos/parasitologia , Manejo de Espécimes , Prevalência
15.
PLoS Pathog ; 18(8): e1010706, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35939508

RESUMO

Hybridization between different species of parasites is increasingly being recognised as a major public and veterinary health concern at the interface of infectious diseases biology, evolution, epidemiology and ultimately control. Recent research has revealed that viable hybrids and introgressed lineages between Schistosoma spp. are prevalent across Africa and beyond, including those with zoonotic potential. However, it remains unclear whether these hybrid lineages represent recent hybridization events, suggesting hybridization is ongoing, and/or whether they represent introgressed lineages derived from ancient hybridization events. In human schistosomiasis, investigation is hampered by the inaccessibility of adult-stage worms due to their intravascular location, an issue which can be circumvented by post-mortem of livestock at abattoirs for Schistosoma spp. of known zoonotic potential. To characterise the composition of naturally-occurring schistosome hybrids, we performed whole-genome sequencing of 21 natural livestock infective schistosome isolates. To facilitate this, we also assembled a de novo chromosomal-scale draft assembly of Schistosoma curassoni. Genomic analyses identified isolates of S. bovis, S. curassoni and hybrids between the two species, all of which were early generation hybrids with multiple generations found within the same host. These results show that hybridization is an ongoing process within natural populations with the potential to further challenge elimination efforts against schistosomiasis.


Assuntos
Schistosoma , Esquistossomose , Animais , Genoma , Genômica , Humanos , Hibridização Genética , Gado/parasitologia , Schistosoma/genética , Esquistossomose/epidemiologia , Esquistossomose/genética , Esquistossomose/veterinária
16.
PLoS Pathog ; 18(3): e1010309, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35316298

RESUMO

The eggs of the parasitic blood fluke, Schistosoma, are the main drivers of the chronic pathologies associated with schistosomiasis, a disease of poverty afflicting approximately 220 million people worldwide. Eggs laid by Schistosoma mansoni in the bloodstream of the host are encapsulated by vascular endothelial cells (VECs), the first step in the migration of the egg from the blood stream into the lumen of the gut and eventual exit from the body. The biomechanics associated with encapsulation and extravasation of the egg are poorly understood. We demonstrate that S. mansoni eggs induce VECs to form two types of membrane extensions during encapsulation; filopodia that probe eggshell surfaces and intercellular nanotubes that presumably facilitate VEC communication. Encapsulation efficiency, the number of filopodia and intercellular nanotubes, and the length of these structures depend on the egg's vitality and, to a lesser degree, its maturation state. During encapsulation, live eggs induce VEC contractility and membranous structures formation in a Rho/ROCK pathway-dependent manner. Using elastic hydrogels embedded with fluorescent microbeads as substrates to culture VECs, live eggs induce VECs to exert significantly greater contractile forces during encapsulation than dead eggs, which leads to 3D deformations on both the VEC monolayer and the flexible substrate underneath. These significant mechanical deformations cause the VEC monolayer tension to fluctuate with the eventual rupture of VEC junctions, thus facilitating egg transit out of the blood vessel. Overall, our data on the mechanical interplay between host VECs and the schistosome egg improve our understanding of how this parasite manipulates its immediate environment to maintain disease transmission.


Assuntos
Esquistossomose mansoni , Esquistossomose , Animais , Células Endoteliais , Humanos , Óvulo , Schistosoma mansoni , Esquistossomose mansoni/parasitologia
17.
PLoS Pathog ; 18(2): e1010327, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35157732

RESUMO

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.


Assuntos
Esquistossomose mansoni , Esquistossomose , Vacinas , Animais , Medula Óssea , Morte Celular , Camundongos , Plasmócitos , Schistosoma mansoni , Vacinas/uso terapêutico
18.
PLoS Pathog ; 18(2): e1010233, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35108342

RESUMO

Schistosomiasis, which is caused by infection with Schistosoma spp., is characterized by granuloma and fibrosis in response to egg deposition. Pattern recognition receptors are important to sense invading Schistosoma, triggering an innate immune response, and subsequently shaping adaptive immunity. Cyclic GMP-AMP synthase (cGAS) was identified as a major cytosolic DNA sensor, which catalyzes the formation of cyclic GMP-AMP (cGAMP), a critical second messenger for the activation of the adaptor protein stimulator of interferon genes (STING). The engagement of STING by cGAMP leads to the activation of TANK-binding kinase 1 (TBK1), interferon regulatory factor 3 (IRF3), and the subsequent type I interferon (IFN) response. cGAS is suggested to regulate infectious diseases, autoimmune diseases, and cancer. However, the function of cGAS in helminth infection is unclear. In this study, we found that Cgas deficiency enhanced the survival of mice infected with S. japonicum markedly, without affecting the egg load in the liver. Consistently, Cgas deletion alleviated liver pathological impairment, reduced egg granuloma formation, and decreased fibrosis severity. In contrast, Sting deletion reduced the formation of egg granulomas markedly, but not liver fibrosis. Notably, Cgas or Sting deficiency reduced the production of IFNß drastically in mice infected with S. japonicum. Intriguingly, intravenous administration of recombinant IFNß exacerbated liver damage and promoted egg granuloma formation, without affecting liver fibrosis. Clodronate liposome-mediated depletion of macrophages indicated that macrophages are the major type of cells contributing to the induction of the type I IFN response during schistosome infection. Moreover, cGAS is important for type I IFN production and phosphorylation of TBK1 and IRF3 in response to stimulation with S. japonicum egg- or adult worm-derived DNA in macrophages. Our results clarified the immunomodulatory effect of cGAS in the regulation of liver granuloma formation during S. japonicum infection, involving sensing schistosome-derived DNA and producing type I IFN. Additionally, we showed that cGAS regulates liver fibrosis in a STING-type I-IFN-independent manner.


Assuntos
Interferon Tipo I/imunologia , Proteínas de Membrana/imunologia , Nucleotidiltransferases/imunologia , Esquistossomose Japônica/imunologia , Esquistossomose/imunologia , Esquistossomose/parasitologia , Animais , Feminino , Imunidade , Fator Regulador 3 de Interferon/metabolismo , Interferon Tipo I/metabolismo , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Nucleotidiltransferases/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais
19.
Bull World Health Organ ; 102(4): 265-275, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38562204

RESUMO

Objective: To determine if the prevalence of schistosomiasis in children aged 9-12 years is associated with the prevalence in 5-8-year-olds and adults after preventive chemotherapy in schools or the community. Methods: We combined data from four community-randomized, preventive chemotherapy trials in treatment-naïve populations in Côte d'Ivoire, Kenya and the United Republic of Tanzania during 2010-2016 according to the number of praziquantel treatments and the delivery method. Schistosoma mansoni infection was sought on two slides prepared from each participant's first stool using the Kato-Katz technique. We assessed associations between S. mansoni prevalence in 9-12-year-olds and 5-8-year-olds and adults in the community before and after treatment using Bayesian regression models. Findings: Stool samples from 47 985 5-8-year-olds, 81 077 9-12-year-olds and 20 492 adults were analysed. We found associations between the prevalence in 9-12-year-olds and that in 5-8-year-olds and adults after preventive treatment, even when only school-age children were treated. When the prevalence in 9-12-year-olds was under 10%, the prevalence in 5-8-year-olds was consistently under 10%. When the prevalence in 9-12-year-olds was under 50%, the prevalence in adults after two or four rounds of preventive chemotherapy was 10%-15% lower than before chemotherapy. Post-chemotherapy age-group associations were consistent with pre-chemotherapy associations in this analysis and previous studies. Conclusion: The prevalence of S. mansoni infection in 9-12-year-olds was associated with the prevalence in other age groups and could be used to guide community treatment decisions.


Assuntos
Esquistossomose , Criança , Adulto , Humanos , Côte d'Ivoire/epidemiologia , Prevalência , Teorema de Bayes , Quênia/epidemiologia , Tanzânia/epidemiologia , Esquistossomose/tratamento farmacológico , Esquistossomose/epidemiologia , Fezes
20.
BMC Cancer ; 24(1): 66, 2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38216912

RESUMO

BACKGROUND: The single-visit strategy, also known as the "screen-and-treat" approach, is widely used to screen for cervical cancer in low- and middle-income countries. The screen-and-treat approach leads to unnecessary or inadequate treatment. Thus, a study was conducted to determine the histopathological patterns of aceto-white lesions on visual inspection with acetic acid (VIA) in patients who underwent a Loop Electrosurgical Excision Procedure (LEEP) at Bugando Medical Centre between January 2016 and December 2020. METHOD: A 5-year retrospective cross-sectional case record review was conducted on 329 women who had LEEP at Bugando Medical Centre following a positive VIA cervical screening test. A standard data abstraction form was used to collect patient information. Missing client information records and LEEP without histopathological results were exclusion criteria. For statistical analysis, STATA version 15 was used; in descriptive statistics, frequency, mean, and standard deviation were used. The Chi2 and Fisher's exact tests were used to investigate the relationship between patient characteristics and histopathological patterns, and a P-value of 0.05 was considered statistically significant in multinomial models. RESULTS: This study looked at 329 patients who had LEEP following a VIA positive but were not eligible for cryotherapy. Our study participants had a mean age of 40 ± 8.2 SD. There were 203 (61.7%) patients with benign lesions, including 4 with schistosomiasis and 2 with cervical tuberculosis. The precancerous lesions were discovered in 100 cases (30.4%), and 26 (7.9%) already had invasive cervical cancer. Out of 100 patients with precancerous lesions, 58 (17.6%) and 42 (12.8%) have high- and low-grade squamous intraepithelial (HSIL and LSIL) lesions, respectively. The presence of a precancerous lesion was found to be associated with age 31-40 years (P-value 0.042) and HIV positivity (P-value 0.004). CONCLUSION: Most patients in this study had benign cervical lesions, which do not require LEEP treatment. Nonetheless, a considerable percentage of invasive cervical malignancies and rare benign diseases such as schistosomiasis and cervical tuberculosis were identified. A screen-and-treat approach within well-equipped tertiary hospitals like Bugando Medical Centre should explore alternative options instead of relying solely on straight LEEP.


Assuntos
Lesões Pré-Cancerosas , Esquistossomose , Tuberculose , Neoplasias do Colo do Útero , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/cirurgia , Detecção Precoce de Câncer/métodos , Ácido Acético , Estudos Retrospectivos , Estudos Transversais , Eletrocirurgia/métodos , Tanzânia , Lesões Pré-Cancerosas/cirurgia , Esquistossomose/cirurgia
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