RESUMO
The relative and synergistic contributions of genetics and environment to interindividual immune response variation remain unclear, despite implications in evolutionary biology and medicine. Here we quantify interactive effects of genotype and environment on immune traits by investigating C57BL/6, 129S1 and PWK/PhJ inbred mice, rewilded in an outdoor enclosure and infected with the parasite Trichuris muris. Whereas cellular composition was shaped by interactions between genotype and environment, cytokine response heterogeneity including IFNγ concentrations was primarily driven by genotype with consequence on worm burden. In addition, we show that other traits, such as expression of CD44, were explained mostly by genetics on T cells, whereas expression of CD44 on B cells was explained more by environment across all strains. Notably, genetic differences under laboratory conditions were decreased following rewilding. These results indicate that nonheritable influences interact with genetic factors to shape immune variation and parasite burden.
Assuntos
Interação Gene-Ambiente , Camundongos Endogâmicos C57BL , Tricuríase , Trichuris , Animais , Trichuris/imunologia , Tricuríase/imunologia , Tricuríase/parasitologia , Camundongos , Receptores de Hialuronatos/genética , Receptores de Hialuronatos/metabolismo , Linfócitos B/imunologia , Genótipo , Interferon gama/metabolismo , Linfócitos T/imunologia , Feminino , MasculinoRESUMO
BACKGROUND: Trichuris spp. (whipworms) are soil-transmitted helminths distributed worldwide, parasitizing several mammalian hosts such as ruminants, primates, and rodents. Trichuris spp. is one of the most common intestinal parasites affecting both humans and animals, and it can spread directly through the fecal-oral route, resulting in severe illness and financial loss. So, this work aims to detect the frequency of Trichuris spp. in camels in Beheira Governorate, Egypt, and to identify Trichuris spp. through morphometrical studies, molecular analysis, and phylogenetic analysis. RESULTS: A total of 35 dromedaries out of 127 investigated had Trichuris spp. infection, meaning that the overall prevalence was 27.56%. The age of the camel affected the infection rate, older animals (> 5 years) having a higher prevalence of infection (24%) than animals of ages (< 3 years) (20%) than animals of ages (3-5 years) (19.14%). According to season: Trichuris spp. showed a unique pattern in camels in different seasons: summer (31.25%) > autumn (28.13%) > spring (25.8%) > winter (25%) indicating year-round infection. T. globulosa was identified morphometrically from camels in Beheira Governorate, Egypt. The BLAST analysis revealed the presence of T. globulosa isolate from camels using the Genbank database depending on nuclear small subunit ribosomal RNA (18s) and cytochrome b (Cytb) genes. CONCLUSION: A high prevalence of T. globulosa was found in camels in Beheira Governorate, Egypt. This is the first report to confirm the identification of T. globulosa from camel based on morphometrical studies and molecular and phylogenetic analysis in Egypt. More thorough studies on the incidence, molecular, and genetic analysis of Trichuris spp. in Egypt are required in addition to camel control programs.
Assuntos
Camelus , Filogenia , Tricuríase , Trichuris , Animais , Camelus/parasitologia , Egito/epidemiologia , Tricuríase/veterinária , Tricuríase/epidemiologia , Tricuríase/parasitologia , Trichuris/genética , Trichuris/isolamento & purificação , Trichuris/classificação , Prevalência , Masculino , Feminino , Estações do AnoRESUMO
Polyphenols are phytochemicals commonly found in plant-based diets which have demonstrated immunomodulatory and anti-inflammatory properties. However, the interplay between polyphenols and pathogens at mucosal barrier surfaces has not yet been elucidated in detail. Here, we show that proanthocyanidin (PAC) polyphenols interact with gut parasites to influence immune function and gut microbial-derived metabolites in mice. PAC intake inhibited mastocytosis during infection with the small intestinal roundworm Heligmosomoides polygyrus, and altered the host tissue transcriptome at the site of infection with the large intestinal whipworm Trichuris muris, with a notable enhancement of type-1 inflammatory and interferon-driven gene pathways. In the absence of infection, PAC intake promoted the expansion of Turicibacter within the gut microbiota, increased fecal short chain fatty acids, and enriched phenolic metabolites such as phenyl-γ-valerolactones in the cecum. However, these putatively beneficial effects were reduced in PAC-fed mice infected with T. muris, suggesting concomitant parasite infection can attenuate gut microbial-mediated PAC catabolism. Collectively, our results suggest an inter-relationship between a phytonutrient and infection, whereby PAC may augment parasite-induced inflammation (most prominently with the cecum dwelling T. muris), and infection may abrogate the beneficial effects of health-promoting phytochemicals.
Assuntos
Microbioma Gastrointestinal , Nematospiroides dubius , Polifenóis , Proantocianidinas , Tricuríase , Trichuris , Animais , Camundongos , Polifenóis/farmacologia , Polifenóis/metabolismo , Trichuris/metabolismo , Tricuríase/parasitologia , Tricuríase/imunologia , Nematospiroides dubius/imunologia , Proantocianidinas/metabolismo , Proantocianidinas/farmacologia , Camundongos Endogâmicos C57BL , Infecções por Strongylida/imunologia , Infecções por Strongylida/parasitologia , Infecções por Strongylida/metabolismo , Feminino , Bactérias/classificação , Bactérias/metabolismo , Bactérias/genética , Bactérias/isolamento & purificação , Fezes/parasitologia , Fezes/microbiologiaRESUMO
BACKGROUND: Parasitic helminths influence the composition of the gut microbiome. However, the microbiomes of individuals living in helminth-endemic regions are understudied. The Orang Asli, an indigenous population in Malaysia with high burdens of the helminth Trichuris trichiura, display microbiotas enriched in Clostridiales, an order of spore-forming obligate anaerobes with immunogenic properties. We previously isolated novel Clostridiales that were enriched in these individuals and found that a subset promoted the Trichuris life cycle. In this study, we aimed to further characterize the functional properties of these bacteria. RESULTS: Clostridiales isolates were profiled for their ability to perform 57 enzymatic reactions and produce short-chain fatty acids (SCFAs) and hydrogen sulfide, revealing that these bacteria were capable of a range of activities associated with metabolism and host response. Consistent with this finding, monocolonization of mice with individual isolates identified bacteria that were potent inducers of regulatory T-cell (Treg) differentiation in the colon. Comparisons between variables revealed by these studies identified enzymatic properties correlated with Treg induction and Trichuris egg hatching. CONCLUSION: We identified Clostridiales species that are sufficient to induce high levels of Tregs. We also identified a set of metabolic activities linked with Treg differentiation and Trichuris egg hatching mediated by these newly isolated bacteria. Altogether, this study provides functional insights into the microbiotas of individuals residing in a helminth-endemic region. Video Abstract.
Assuntos
Diferenciação Celular , Clostridiales , Microbioma Gastrointestinal , Linfócitos T Reguladores , Trichuris , Animais , Linfócitos T Reguladores/imunologia , Camundongos , Malásia , Clostridiales/isolamento & purificação , Humanos , Ácidos Graxos Voláteis/metabolismo , Feminino , Tricuríase/parasitologia , Tricuríase/imunologia , Tricuríase/microbiologiaRESUMO
Laboratory model organisms have provided a window into how the immune system functions. An increasing body of evidence, however, suggests that the immune responses of naive laboratory animals may differ substantially to those of their wild counterparts. Past exposure, environmental challenges and physiological condition may all impact on immune responsiveness. Chronic infections of soil-transmitted helminths, which we define as establishment of adult, fecund worms, impose significant health burdens on humans, livestock and wildlife, with limited treatment success. In laboratory mice, Th1 versus Th2 immune polarisation is the major determinant of helminth infection outcome. Here we compared antigen-specific immune responses to the soil-transmitted whipworm Trichuris muris between controlled laboratory and wild free-ranging populations of house mice (Mus musculus domesticus). Wild mice harbouring chronic, low-level infections produced lower levels of cytokines in response to Trichuris antigen than laboratory-housed C57BL/6 mice. Wild mouse effector/memory CD4+ T cell phenotype reflected the antigen-specific cytokine response across the Th1/Th2 spectrum. Increasing egg shedding was associated with body condition loss. However, local Trichuris-specific Th1/Th2 balance was positively associated with worm burden only in older wild mice. Thus, although the fundamental relationships between the CD4+ T helper cell response and resistance to T. muris infection are similar in both laboratory and wild M. m. domesticus, there are quantitative differences and age-specific effects that are analogous to human immune responses. These context-dependent immune responses demonstrate the fundamental importance of understanding the differences between model and natural systems for translating mechanistic models to 'real world' immune function.
Assuntos
Imunidade Adaptativa , Camundongos Endogâmicos C57BL , Tricuríase , Trichuris , Animais , Trichuris/imunologia , Tricuríase/imunologia , Tricuríase/parasitologia , Camundongos , Imunidade Adaptativa/imunologia , Modelos Animais de Doenças , Feminino , Animais Selvagens/imunologia , Animais Selvagens/parasitologia , Células Th2/imunologia , Citocinas/imunologia , Citocinas/metabolismo , Antígenos de Helmintos/imunologia , MasculinoRESUMO
Trichuriasis is a neglected tropical disease widely distributed among tropical and sub-tropical areas and associated with poverty and lack of access to safe drinking water, sanitation and hygiene. Existing drugs have limited efficacy and face a constant risk of developing resistance, necessitating the search for alternative treatments. However, drug discovery efforts are sparse and little research has been performed on anthelminthic effects on embryonated eggs, the infectious life stage of Trichuris spp. We examined bacterial species dependent egg hatching of the murine model parasite Trichuris muris and identified Escherichia coli, Pseudomonas aeruginosa and Enterobacter hormaechei effective as hatching inducers, resulting in hatching yields of 50-70%. Streptococcus salivarius, reported to be associated with reduced drug efficacy of ivermectin-albendazole coadministration in Trichuris trichiura infected patients, did not promote egg hatching in vitro. We optimized hatching conditions using E. coli grown in luria broth or brain-heart infusion media to reach consistently high hatching yields to provide a sensitive, robust and simple egg-hatching assay. Oxantel pamoate demonstrated the strongest potency in preventing hatching, with an EC50 value of 2-4 µM after 24 h, while pyrantel pamoate, levamisole and tribendimidine exhibited only moderate to weak inhibitory effects. Conversely, all tested benzimidazoles and macrolide anthelminthics as well as emodepside failed to prevent hatching (EC50 > 100 µM). Our study demonstrates that egg-hatching assays complement larval and adult stage drug sensitivity assays, to expand knowledge about effects of current anthelminthics on Trichuris spp. Further, the developed T. muris egg-hatching assay provides a simple and cheap screening tool that could potentially lead to the discovery of novel anthelminthic compounds.
Assuntos
Anti-Helmínticos , Tricuríase , Humanos , Animais , Camundongos , Trichuris , Escherichia coli , Anti-Helmínticos/uso terapêutico , Albendazol/farmacologia , Tricuríase/tratamento farmacológico , Tricuríase/parasitologiaRESUMO
Trichuris trichiura and T. suis are gastrointestinal dwelling roundworms that infect humans and pigs, respectively. Heavy infections cause gastrointestinal symptoms and impaired growth and development. Vaccination has the potential to reduce the disease burden of whipworm infection; however, there are currently no commercially available vaccines against these parasites and very few against other gastrointestinal-dwelling nematodes of medical and agricultural importance. The naturally occurring mouse whipworm, T. muris, has been used for decades to model human trichuriasis, and the immunogenic potential of the excretory/secretory material (E/S, which can be collected following ex vivo culture of worms) has been studied in the context of vaccine candidate identification. Despite this, researchers are yet to progress an effective vaccine candidate to clinical trials. The T. muris, T. trichiura, and T. suis genomes each encode between 10 and 27 whey acidic protein (WAP) domain-containing proteins and 15 to 34 cysteine-rich secretory protein/antigen 5/pathogenesis related-1 (CAP) family members. WAP and CAP proteins have been postulated to play key roles in host-parasite interactions and may possess immunomodulatory functions. In addition, both protein families have been explored in the context of helminth vaccines. Here, we use phylogenetic and functional analysis to investigate the evolutionary relationship between WAP and CAP proteins encoded by T. muris, T. trichiura, and T. suis. We highlight several WAP and CAP proteins that warrant further study to understand their biological function and as possible vaccine candidates against T. trichiura and/or T. suis, based on the close evolutionary relationship with WAP or CAP proteins identified within T. muris E/S products.
Assuntos
Tricuríase , Vacinas , Humanos , Animais , Camundongos , Trichuris , Filogenia , Vacinação , Antígenos de Helmintos/genética , Tricuríase/parasitologiaRESUMO
Whipworm (Trichuris) is a genus of roundworms that causes gastrointestinal infections in humans and animals. Of particular interest are T. trichiura, the causative agent of human trichuriasis, a neglected tropical disease that affects 477 million people worldwide, and T. suis, the pig whipworm species, responsible for growth stunting and economic losses within the agricultural industry. The naturally occurring mouse whipworm, T. muris, has been used for decades as a model for trichuriasis, yielding knowledge on the biology of these parasites and the host response to infection. Ex vivo culture of T. muris (and to some extent, T. suis) has provided insight into the composition of the excretory/secretory (E/S) products released by worms, which include a myriad of proteins, RNAs, lipids, glycans, metabolites and extracellular vesicles. T. muris E/S has formed the basis of the search for whipworm vaccine candidates, while the immunomodulatory potential of T. suis and T. muris secretions has been investigated with the aim of improving our understanding of how these parasites modulate host immunity, as well as identifying immunomodulatory candidates with therapeutic potential in the context of inflammatory diseases. This article will review the various components found within Trichuris E/S, their potential as vaccine candidates and their immunomodulatory properties.
Assuntos
Tricuríase , Vacinas , Animais , Interações Hospedeiro-Parasita , Humanos , Lipídeos , Camundongos , Suínos , Tricuríase/parasitologia , TrichurisRESUMO
Regulation of macrophage (Mɸ) function can maintain tissue homeostasis and control inflammation. Parasitic worms (helminths) are potent modulators of host immune and inflammatory responses. They have evolved various strategies to promote immunosuppression, including redirecting phagocytic cells toward a regulatory phenotype. Although soluble products from the whipworm Trichuris suis (TSPs) have shown significant effects on Mɸ function, the mechanisms underlying these modulatory effects are still not well understood. In this study, we find that TSPs suppressed inflammatory cytokines (TNF and IL-6) in Mɸs stimulated with a broad panel of TLR agonists, whilst inducing IL-10. Moreover, M1 markers such as MHCII, CD86, iNOS, and TNF were downregulated in TSP-treated Mɸs, without polarizing them towards an M2-like phenotype. We showed that TSPs could establish a suppressed activation state of Mɸs lasting at least for 72 h, indicating an anti-inflammatory innate training. Moreover, we found that TSPs, via repression of intracellular TNF generation, decreased its secretion rather than interfering with the release of surface-bound TNF. Metabolic analysis showed that TSPs promote oxidative phosphorylation (OXPHOS) without affecting glycolytic rate. Collectively, these findings expand our knowledge on helminth-induced immune modulation and support future investigations into the anti-inflammatory properties of TSPs for therapeutic purposes.
Assuntos
Tricuríase , Trichuris , Animais , Anti-Inflamatórios/farmacologia , Células Cultivadas , Citocinas/metabolismo , Macrófagos/metabolismo , Tricuríase/metabolismo , Tricuríase/parasitologia , Trichuris/metabolismoRESUMO
Soil-transmitted helminths (STH) are the most prevalent pathogens among the group of neglected tropical diseases (NTDs). The Kato-Katz technique is the diagnosis method recommended by the World Health Organization (WHO) although it often presents a decreased sensitivity in low transmission settings and it is labour intensive. Visual reading of Kato-Katz preparations requires the samples to be analyzed in a short period of time since its preparation. Digitizing the samples could provide a solution which allows to store the samples in a digital database and perform remote analysis. Artificial intelligence (AI) methods based on digitized samples can support diagnosis by performing an objective and automatic quantification of disease infection. In this work, we propose an end-to-end pipeline for microscopy image digitization and automatic analysis of digitized images of STH. Our solution includes (a) a digitization system based on a mobile app that digitizes microscope samples using a 3D printed microscope adapter, (b) a telemedicine platform for remote analysis and labelling, and (c) novel deep learning algorithms for automatic assessment and quantification of parasitological infections by STH. The deep learning algorithm has been trained and tested on 51 slides of stool samples containing 949 Trichuris spp. eggs from 6 different subjects. The algorithm evaluation was performed using a cross-validation strategy, obtaining a mean precision of 98.44% and a mean recall of 80.94%. The results also proved the potential of generalization capability of the method at identifying different types of helminth eggs. Additionally, the AI-assisted quantification of STH based on digitized samples has been compared to the one performed using conventional microscopy, showing a good agreement between measurements. In conclusion, this work has presented a comprehensive pipeline using smartphone-assisted microscopy. It is integrated with a telemedicine platform for automatic image analysis and quantification of STH infection using AI models.
Assuntos
Aprendizado Profundo , Microscopia/métodos , Telemedicina/métodos , Tricuríase/diagnóstico , Trichuris/isolamento & purificação , Algoritmos , Animais , Humanos , Tricuríase/parasitologiaRESUMO
BACKGROUND: Despite several years of school-based MDA implementation, STH infections remain an important public health problem in Benin, with a country-wide prevalence of 20% in 2015. The DeWorm3 study is designed to assess the feasibility of using community-based MDA with albendazole to interrupt the transmission of STH, through a series of cluster-randomized trials in Benin, India and Malawi. We used the pre-treatment baseline survey data to describe and analyze the factors associated with STH infection in Comé, the study site of the DeWorm3 project in Benin. These data will improve understanding of the challenges that need to be addressed in order to eliminate STH as a public health problem in Benin. METHODS: Between March and April 2018, the prevalence of STH (hookworm spp., Ascaris and Trichuris trichiura) was assessed by Kato-Katz in stool samples collected from 6,153 residents in the community of Comé, Benin using a stratified random sampling procedure. A standardized survey questionnaire was used to collect information from individual households concerning factors potentially associated with the presence and intensity of STH infections in pre-school (PSAC, aged 1-4), school-aged children (SAC, aged 5-14) and adults (aged 15 and above). Multilevel mixed-effects models were used to assess associations between these factors and STH infection. RESULTS: The overall prevalence of STH infection was 5.3%; 3.2% hookworm spp., 2.1% Ascaris lumbricoides and 0.1% Trichuris. Hookworm spp. were more prevalent in adults than in SAC (4.4% versus 2.0%, respectively; p = 0.0001) and PSAC (4.4% versus 1.0%, respectively; p<0.0001), whilst Ascaris lumbricoides was more prevalent in SAC than in adults (3.0% versus 1.7%, respectively; p = 0.004). Being PSAC (adjusted Odds Ratio (aOR) = 0.2, p< 0.001; adjusted Infection Intensity Ratio (aIIR) = 0.1, p<0.001) or SAC (aOR = 0.5, p = 0.008; aIIR = 0.3, p = 0.01), being a female (aOR = 0.6, p = 0.004; aIIR = 0.3, p = 0.001), and having received deworming treatment the previous year (aOR = 0.4, p< 0.002; aIIR = 0.2, p<0.001) were associated with a lower prevalence and intensity of hookworm infection. Lower income (lowest quintile: aOR = 5.0, p<0.001, 2nd quintile aOR = 3.6, p = 0.001 and 3rd quintile aOR = 2.5, p = 0.02), being a farmer (aOR = 1.8, p = 0.02), medium population density (aOR = 2.6, p = 0.01), and open defecation (aOR = 0.5, p = 0.04) were associated with a higher prevalence of hookworm infection. Lower education-no education, primary or secondary school- (aIIR = 40.1, p = 0.01; aIIR = 30.9, p = 0.02; aIIR = 19.3, p = 0.04, respectively), farming (aIIR = 3.9, p = 0.002), natural flooring (aIIR = 0.2, p = 0.06), peri-urban settings (aIIR = 6.2, 95%CI 1.82-20.90, p = 0.003), and unimproved water source more than 30 minutes from the household (aIIR = 13.5, p = 0.02) were associated with a higher intensity of hookworm infection. Improved and unshared toilet was associated with lower intensity of hookworm infections (aIIR = 0.2, p = 0.01). SAC had a higher odds of Ascaris lumbricoides infection than adults (aOR = 2.0, p = 0.01) and females had a lower odds of infection (aOR = 0.5, p = 0.02). CONCLUSION: Hookworm spp. are the most prevalent STH in Comé, with a persistent reservoir in adults that is not addressed by current control measures based on school MDA. Expanding MDA to target adults and PSAC is necessary to substantially impact population prevalence, particularly for hookworm. TRIAL REGISTRATION: ClinicalTrials.gov NCT03014167.
Assuntos
Ascaríase/epidemiologia , Infecções por Uncinaria/epidemiologia , Saneamento , Solo/parasitologia , Tricuríase/epidemiologia , Adolescente , Ancylostomatoidea/isolamento & purificação , Animais , Ascaríase/parasitologia , Ascaríase/transmissão , Ascaris lumbricoides/isolamento & purificação , Benin/epidemiologia , Criança , Pré-Escolar , Características da Família , Fezes/parasitologia , Feminino , Infecções por Uncinaria/parasitologia , Infecções por Uncinaria/transmissão , Humanos , Modelos Logísticos , Masculino , Prevalência , Fatores de Risco , Instituições Acadêmicas , Tricuríase/parasitologia , Tricuríase/transmissão , Trichuris/isolamento & purificaçãoRESUMO
Four adult female worms of Trichuris were isolated from an individual of the wild blue sheep (Pseudois nayaur) inhabiting the Helan Mountains, China, during an epidemiological survey of this wild ruminant. Although there were some differences among the worms in posterior end (rectum) morphology and egg shape, little information regarding species status could be inferred from their morphology. Phylogenetic trees were constructed based on sequences of the ITS1 segment of ribosomal RNA (rRNA), and the sequences of the four Trichuris specimens from wild blue sheep were divided into two distinct lineages (Clade A and Clade B). The two specimens in Clade A were named Genotype I, and had the closest relationship with Trichuris skrjabini; the two specimens in Clade B were named Genotype II and had the closest genetic relationship with a previously described Trichuris sp. In the two Trichuris genotypes identified in the present study, the 18S fragments (261 to 262 bp) of the newly obtained sequences were found to be highly conserved, with merely one insert mutation of a single nucleotide present. The genetic distance based on ITS1 between members of Clade A, composed of two T. skrjabini individuals and two Genotype I individuals, ranged from 0 to 0.0034. These distances are within the intraspecies variation of Trichuris (0-0.0272), suggesting that the Genotype I individuals infesting the wild blue sheep were T. skrjabini. In Clade B, the newly obtained sequences clustered with Trichuris sp. specimens isolated from ruminants (sheep and black goat) with strong support, and the genetic distance ranged from 0.0068 to 0.017, which is also within the intraspecies variation of Trichuris (0-0.0272). However, the genetic distances between the Clade A and Clade B were 0.0442 to 0.0578, which are higher than the intraspecies distances in Trichuris but lower than the interspecies distances (0.102-0.5078). These results implied that Clade A and Clade B most likely represent two subpopulations of T. skrjabini; however, the possibility that Clade A is T. skrjabini and Clade B is a Candidatus Trichuris could not be excluded.
Assuntos
Ruminantes/parasitologia , Tricuríase/veterinária , Trichuris/isolamento & purificação , Animais , Animais Selvagens , Sequência de Bases , Teorema de Bayes , China/epidemiologia , Sequência Consenso , Feminino , Genótipo , Filogenia , Tricuríase/epidemiologia , Tricuríase/parasitologia , Trichuris/anatomia & histologia , Trichuris/classificaçãoRESUMO
Background: Tuberculosis (TB) is still a major challenge for humankind. Because regions with the highest incidence also have a high prevalence of helminthiasis and nutritional scarcity, we wanted to understand the impact of these on TB progression. Methods: We have developed an experimental murine model for active TB in C3HeB/FeJ, coinfected with Trichuris muris and Heligmosomoides polygyrus nematodes, and exposed to an environmental mycobacterium (M. manresensis) and intermittent fasting. Cause-effect relationships among these factors were explored with Partial Least Squares Path modelling (PLSPM). Results: Previous parasitization had a major anti-inflammatory effect and reduced systemic levels of ADA, haptoglobin, local pulmonary levels of IL-1ß, IL-6, TNF-α, CXCL-1, CXCL-5 and IL-10. Oral administration of heat-killed M. manresensis resulted in a similar outcome. Both interventions diminished pulmonary pathology and bacillary load, but intermittent food deprivation reduced this protective effect increasing stress and inflammation. The PLSPM revealed nematodes might have protective effects against TB progression. Conclusions: Significantly higher cortisol levels in food-deprivation groups showed it is a stressful condition, which might explain its deleterious effect. This highlights the impact of food security on TB eradication policies and the need to prioritize food supply over deworming activities.
Assuntos
Coinfecção , Privação de Alimentos , Helmintíase/parasitologia , Enteropatias Parasitárias/parasitologia , Pulmão/microbiologia , Mycobacterium tuberculosis/patogenicidade , Nematospiroides dubius/patogenicidade , Infecções por Strongylida/parasitologia , Tricuríase/parasitologia , Trichuris/patogenicidade , Tuberculose Pulmonar/microbiologia , Fenômenos Fisiológicos da Nutrição Animal , Animais , Citocinas/metabolismo , Modelos Animais de Doenças , Progressão da Doença , Feminino , Helmintíase/imunologia , Helmintíase/metabolismo , Interações Hospedeiro-Parasita , Mediadores da Inflamação/metabolismo , Enteropatias Parasitárias/imunologia , Enteropatias Parasitárias/metabolismo , Pulmão/imunologia , Pulmão/metabolismo , Masculino , Camundongos Endogâmicos C3H , Mycobacterium tuberculosis/imunologia , Nematospiroides dubius/imunologia , Estado Nutricional , Infecções por Strongylida/imunologia , Infecções por Strongylida/metabolismo , Tricuríase/imunologia , Tricuríase/metabolismo , Trichuris/imunologia , Tuberculose Pulmonar/imunologia , Tuberculose Pulmonar/metabolismoRESUMO
Since 2015, India has coordinated the largest school-based deworming program globally, targeting soil-transmitted helminths (STH) in ~250 million children aged 1 to 19 years twice yearly. Despite substantial progress in reduction of morbidity associated with STH, reinfection rates in endemic communities remain high. We conducted a community based parasitological survey in Tamil Nadu as part of the DeWorm3 Project-a cluster-randomised trial evaluating the feasibility of interrupting STH transmission at three geographically distinct sites in Africa and Asia-allowing the estimation of STH prevalence and analysis of associated factors. In India, following a comprehensive census, enumerating 140,932 individuals in 36,536 households along with geospatial mapping of households, an age-stratified sample of individuals was recruited into a longitudinal monitoring cohort (December 2017-February 2018) to be followed for five years. At enrolment, a total of 6089 consenting individuals across 40 study clusters provided a single adequate stool sample for analysis using the Kato-Katz method, as well as answering a questionnaire covering individual and household level factors. The unweighted STH prevalence was 17.0% (95% confidence interval [95%CI]: 16.0-17.9%), increasing to 21.4% when weighted by age and cluster size. Hookworm was the predominant species, with a weighted infection prevalence of 21.0%, the majority of which (92.9%) were light intensity infections. Factors associated with hookworm infection were modelled using mixed-effects multilevel logistic regression for presence of infection and mixed-effects negative binomial regression for intensity. The prevalence of both Ascaris lumbricoides and Trichuris trichiura infections were rare (<1%) and risk factors were therefore not assessed. Increasing age (multivariable odds ratio [mOR] 21.4, 95%CI: 12.3-37.2, p<0.001 for adult age-groups versus pre-school children) and higher vegetation were associated with an increased odds of hookworm infection, whereas recent deworming (mOR 0.3, 95%CI: 0.2-0.5, p<0.001) and belonging to households with higher socioeconomic status (mOR 0.3, 95%CI: 0.2-0.5, p<0.001) and higher education level of the household head (mOR 0.4, 95%CI: 0.3-0.6, p<0.001) were associated with lower odds of hookworm infection in the multilevel model. The same factors were associated with intensity of infection, with the use of improved sanitation facilities also correlated to lower infection intensities (multivariable infection intensity ratio [mIIR] 0.6, 95%CI: 0.4-0.9, p<0.016). Our findings suggest that a community-based approach is required to address the high hookworm burden in adults in this setting. Socioeconomic, education and sanitation improvements alongside mass drug administration would likely accelerate the drive to elimination in these communities. Trial Registration: NCT03014167.
Assuntos
Ascaríase/epidemiologia , Infecções por Uncinaria/epidemiologia , Saneamento , Solo/parasitologia , Banheiros , Tricuríase/epidemiologia , Adolescente , Adulto , Animais , Ascaríase/parasitologia , Ascaríase/transmissão , Ascaris lumbricoides/isolamento & purificação , Criança , Pré-Escolar , Características da Família , Fezes/parasitologia , Feminino , Helmintos/isolamento & purificação , Infecções por Uncinaria/parasitologia , Infecções por Uncinaria/transmissão , Humanos , Índia/epidemiologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Instituições Acadêmicas , Tricuríase/parasitologia , Tricuríase/transmissão , Trichuris/isolamento & purificação , Adulto JovemRESUMO
We conducted a controlled before-and-after trial to evaluate the impact of an onsite urban sanitation intervention on the prevalence of enteric infection, soil transmitted helminth re-infection, and diarrhea among children in Maputo, Mozambique. A non-governmental organization replaced existing poor-quality latrines with pour-flush toilets with septic tanks serving household clusters. We enrolled children aged 1-48 months at baseline and measured outcomes before and 12 and 24 months after the intervention, with concurrent measurement among children in a comparable control arm. Despite nearly exclusive use, we found no evidence that intervention affected the prevalence of any measured outcome after 12 or 24 months of exposure. Among children born into study sites after intervention, we observed a reduced prevalence of Trichuris and Shigella infection relative to the same age group at baseline (<2 years old). Protection from birth may be important to reduce exposure to and infection with enteric pathogens in this setting.
Assuntos
Infecções Bacterianas/prevenção & controle , Helmintíase/prevenção & controle , Engenharia Sanitária , Banheiros , Saúde da População Urbana , Infecções Bacterianas/diagnóstico , Infecções Bacterianas/epidemiologia , Infecções Bacterianas/microbiologia , Pré-Escolar , Diarreia/epidemiologia , Diarreia/microbiologia , Diarreia/prevenção & controle , Disenteria Bacilar/epidemiologia , Disenteria Bacilar/microbiologia , Disenteria Bacilar/prevenção & controle , Feminino , Helmintíase/diagnóstico , Helmintíase/epidemiologia , Helmintíase/parasitologia , Humanos , Lactente , Masculino , Moçambique/epidemiologia , Prevalência , Reinfecção , Características de Residência , Solo/parasitologia , Fatores de Tempo , Tricuríase/epidemiologia , Tricuríase/parasitologia , Tricuríase/prevenção & controleRESUMO
The price of certain antiparasitic drugs (e.g., albendazole and mebendazole) has dramatically increased since 2010. The effect of these rising prices on treatment costs and use of standard of care (SOC) drugs is unknown. To measure the impact of drug prices on overall outpatient cost and quality of care, we identified outpatient visits associated with ascariasis, hookworm, and trichuriasis infections from the 2010 to 2017 MarketScan Commercial Claims and Encounters and Multi-state Medicaid databases using Truven Health MarketScan Treatment Pathways. Evaluation was limited to members with continuous enrollment in non-capitated plans 30 days prior, and 90 days following, the first diagnosis. The utilization of SOC prescriptions was considered a marker for quality of care. The impact of drug price on the outpatient expenses was measured by comparing the changes in drug and nondrug outpatient payments per patient through Welch's two sample t-tests. The total outpatient payments per patient (drug and nondrug), for the three parasitic infections, increased between 2010 and 2017. The increase was driven primarily by prescription drug payments, which increased 20.6-137.0 times, as compared with nondrug outpatient payments, which increased 0.3-2.2 times. As prices of mebendazole and albendazole increased, a shift to alternative SOC and non-SOC drug utilization was observed. Using parasitic infection treatment as a model, increases in prescription drug prices can act as the primary driver of increasing outpatient care costs. Simultaneously, there was a shift to alternative SOC, but also to non-SOC drug treatment, suggesting a decrease in quality of care.
Assuntos
Albendazol/economia , Anti-Helmínticos/economia , Ascaríase/economia , Infecções por Uncinaria/economia , Ivermectina/economia , Mebendazol/economia , Tricuríase/economia , Albendazol/uso terapêutico , Animais , Anti-Helmínticos/uso terapêutico , Ascaríase/diagnóstico , Ascaríase/tratamento farmacológico , Ascaríase/parasitologia , Custos de Medicamentos/tendências , Gastos em Saúde/estatística & dados numéricos , Infecções por Uncinaria/diagnóstico , Infecções por Uncinaria/tratamento farmacológico , Infecções por Uncinaria/parasitologia , Humanos , Ivermectina/uso terapêutico , Mebendazol/uso terapêutico , Pacientes Ambulatoriais , Solo/parasitologia , Padrão de Cuidado/tendências , Tricuríase/diagnóstico , Tricuríase/tratamento farmacológico , Tricuríase/parasitologia , Estados UnidosRESUMO
In the absence of efficient alternative strategies, the control of parasitic nematodes, impacting human and animal health, mainly relies on the use of broad-spectrum anthelmintic compounds. Unfortunately, most of these drugs have a limited single-dose efficacy against infections caused by the whipworm, Trichuris. These infections are of both human and veterinary importance. However, in contrast to a wide range of parasitic nematode species, the narrow-spectrum anthelmintic oxantel has a high efficacy on Trichuris spp. Despite this knowledge, the molecular target(s) of oxantel within Trichuris is still unknown. In the distantly related pig roundworm, Ascaris suum, oxantel has a small, but significant effect on the recombinant homomeric Nicotine-sensitive ionotropic acetylcholine receptor (N-AChR) made up of five ACR-16 subunits. Therefore, we hypothesized that in whipworms, a putative homolog of an ACR-16 subunit, can form a functional oxantel-sensitive receptor. Using the pig whipworm T. suis as a model, we identified and cloned a novel ACR-16-like subunit and successfully expressed the corresponding homomeric channel in Xenopus laevis oocytes. Electrophysiological experiments revealed this receptor to have distinctive pharmacological properties with oxantel acting as a full agonist, hence we refer to the receptor as an O-AChR subtype. Pyrantel activated this novel O-AChR subtype moderately, whereas classic nicotinic agonists surprisingly resulted in only minor responses. We observed that the expression of the ACR-16-like subunit in the free-living nematode Caenorhabditis elegans conferred an increased sensitivity to oxantel of recombinant worms. We demonstrated that the novel Tsu-ACR-16-like receptor is indeed a target for oxantel, although other receptors may be involved. These finding brings new insight into the understanding of the high sensitivity of whipworms to oxantel, and highlights the importance of the discovery of additional distinct receptor subunit types within Trichuris that can be used as screening tools to evaluate the effect of new synthetic or natural anthelmintic compounds.
Assuntos
Antinematódeos/farmacologia , Proteínas de Helminto/antagonistas & inibidores , Pirantel/análogos & derivados , Receptores Colinérgicos/química , Tricuríase/tratamento farmacológico , Trichuris/efeitos dos fármacos , Animais , Caenorhabditis elegans/efeitos dos fármacos , Feminino , Proteínas de Helminto/classificação , Proteínas de Helminto/metabolismo , Masculino , Pirantel/farmacologia , Receptores Colinérgicos/classificação , Receptores Colinérgicos/metabolismo , Suínos , Tricuríase/metabolismo , Tricuríase/parasitologia , Xenopus laevis/metabolismoRESUMO
The study of ancient parasites, named paleoparasitology, traditionally focused on microscopic eggs disseminated in past environments and archaeological structures by humans and other animals infested by gastrointestinal parasites. Since the development of paleogenetics in the early 1980s, few paleoparasitological studies have been based on the ancient DNA (aDNA) of parasites, although such studies have clearly proven their utility and reliability. In this paper, we describe our integrative approach for the paleoparasitological study of an ancient population from Florence in Italy, dated to the 4th-5th c. CE. The first stage consisted in the study of sediment samples from the pelvic area of 18 individuals under light microscopy. This allowed us to detect Ascarid-type eggs belonging very probably to the human-infesting roundworm Ascaris lumbricoides. Ten subsamples were selected corresponding to five individuals, and we extracted their whole DNA following sediment aDNA protocols. A targeted approach allowed us to detect two nematodes and one trematode aDNA fragments, namely Ascaris sp., Trichuris trichiura, and Dicrocoelium dendriticum. Among the five individuals tested for microscopic eggs and aDNA, three of them showed the remains of eggs (only Ascarid-type), but all of them tested positive to the presence of at least one parasite aDNA. Microscopic diagnosis first guided our research for the selection of promising samples while the targeted aDNA approach significantly improved our knowledge in terms of parasitic diversity and frequency in this population subgroup. These results enabled us to discuss the possible impact of latent parasitism in this past population at the time of an epidemic, as suggested in Florence. In particular, the singular case of D. dendriticum detection is discussed in light of the present-day scarcity of genuine human infections. Nevertheless, actual infections are known in the paleoparasitological record, and food habits may have led to false parasitism in this historical context. aDNA leaching from overlying strata may also explain this detection. This study strongly pleads for a systematic integrative approach combining microscopy and aDNA in paleoparasitology.
Assuntos
Ascaríase/história , Ascaris/isolamento & purificação , Dicrocelíase/história , Dicrocoelium/isolamento & purificação , Enteropatias Parasitárias/história , Tricuríase/história , Trichuris/isolamento & purificação , Animais , Ascaríase/parasitologia , Cidades , Dicrocelíase/parasitologia , História Antiga , Humanos , Enteropatias Parasitárias/parasitologia , Itália , Tricuríase/parasitologiaRESUMO
Whipworms are responsible for up to 500 million cases of trichuriasis worldwide, with higher endemicity in tropical and sub-tropical countries. In non-endemic countries, trichuriasis can be accidentally diagnosed upon colonoscopy, often in the presence of negative microscopy. Here, we describe an incidental diagnosis of trichuriasis in an HIV patient residing in a non-endemic area (i.e., Turin, Italy), six months after his return from Antigua. The species-level diagnosis was made thanks to PCR-based molecular identification of Trichuris sp. following optical microscopy detection. Overall, this case highlights the importance of improving parasitic diseases diagnosis through cutting-edge clinical and laboratory diagnostic tools alongside advanced training of specialists in the area of parasitology.
Assuntos
Tricuríase/diagnóstico , Trichuris/isolamento & purificação , Animais , Antígua e Barbuda , Sequência de Bases , Citocromos b/análise , Endoscopia , Infecções por HIV , Proteínas de Helminto/análise , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Alinhamento de Sequência , Turismo , Tricuríase/parasitologia , Trichuris/genéticaRESUMO
BACKGROUND: Soil-transmitted helminths (STH), i.e., Ascaris lumbricoides, Trichuris trichiura and hookworms are among the most prevalent Neglected Tropical Diseases (NTDs) in Ethiopia. Although pre-school aged children pay a high morbidity toll associated with STH infections, evidence on prevalence, intensity and intervention status is lacking in Ethiopia. This study, therefore, aimed to address these gaps to inform decision made on STH. METHODS: We did a community-based cross-sectional study in five districts of Gamo Gofa zone, Southern Ethiopia; in January 2019. Data were collected using pre-tested questionnaire, and the Kato-Katz technique was used to diagnose parasites eggs in stool. Then, collected data were edited and entered into EpiData 4.4.2, and exported to SPSS software (IBM, version 25) for analysis. RESULTS: A total of 2462 PSAC participated in this study. Overall, the prevalence of STH was 23.5% (578/2462) (95% confidence interval (CI) = 21.8%-25.2%). As caris lumbricoides was the most prevalent (18.6%), followed by Trichuris trichiura (9.2%), and hookworms (3.1%). Of the total, 7.4% PSAC were infected with two STH species. Most of the positive cases with STH showed low infection intensities, while 15.1% ascariasis cases showed moderate infection intensities. The study found that 68.7% of PSAC were treated with albendazole. Also, household's level data showed that 39.4% used water from hand-dug well; 52.5% need to travel ≥30 minutes to collect water; 77.5% did not treat water, and 48.9% had no hand washing facility. In addition, almost 93% care givers achieved less than the mean knowledge and practice score (≤5) on STH prevention. CONCLUSIONS: This study showed that significant proportions of pre-school aged children are suffering from STH infections despite preventive chemotherapy exist at the study area. Also, gaps in the interventions against STH were highlighted. Thus, a call for action is demanding to eliminate STH among PSAC in Ethiopia by 2030.