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1.
Parasitol Res ; 119(11): 3691-3698, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33009945

RESUMO

Fascioliasis, a food- and water-borne trematodiasis, has been identified as a public health threat by the World Health Organization, with millions of people estimated to be infected or at risk of infection worldwide. We developed an immunochromatographic test (ICT) as a point-of-care (POC) tool for the rapid serodiagnosis of human fascioliasis caused by Fasciola gigantica and evaluated their diagnostic ability. Two tests were developed using antigens from adult F. gigantica excretory-secretory (ES) product and recombinant F. gigantica cathepsin L (rFgCL). Sera from 12 patients with parasitologically proven fascioliasis caused by F. gigantica, 18 with clinically suspected fascioliasis, 65 with other parasitic infections, and 30 healthy controls were used. Using a cutoff of > 0.5 for antibody detection, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the ES-based ICT method were 100%, 98.9% 96.8%, 100%, and 99.2%, respectively, and those of the rFgCL-based ICT method were 86.7%, 93.7%, 81.3%, 95.7%, and 92.0%, respectively. The concordance between the two methods was 91.2%. Tests using F. gigantica ES and rFgCL antigens can be employed quickly and easily as POC diagnostic tools. They can be used to support the clinical diagnosis of human fascioliasis gigantica and in large-scale surveys in endemic areas throughout tropical regions without necessitating additional facilities or ancillary supplies.


Assuntos
Antígenos de Helmintos/imunologia , Catepsina L/imunologia , Fasciola/isolamento & purificação , Fasciolíase/diagnóstico , Animais , Anticorpos Anti-Helmínticos/sangue , Catepsina F/sangue , Cromatografia de Afinidade , Fasciola/imunologia , Humanos , Testes Imediatos , Sensibilidade e Especificidade , Testes Sorológicos/métodos
2.
PLoS Negl Trop Dis ; 14(9): e0008632, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32976511

RESUMO

There is an urgent need for the development of new, improved vaccine adjuvants against T. spiralis infection. Polysaccharides are effective, safe, and biodegradable as adjuvant. In our study, we first observed the protective efficacy of lentinan as adjuvant against helminth T. spiralis infection. Recombinant T. spiralis Serpin (rTs-Serpin) immunoscreened from a cDNA library of T. spiralis, as a vaccine, protect host against Trichinella infection. The reduction rate of helminth burden of rTs-Serpin+lentinan-immunized mice was significantly increased compared with rTs-Serpin+FCA -immunized mice. rTs-Serpin+lentinan induced IgG1-dominant immune response and higher levels of IFN-γ and IL-4. rTs-Serpin+lentinan displayed a lower reduction rate of parasite burden in NLRP3-/- mice than that in WT mice and lower level of IgG1 than that in WT mice. The level of IL-4, but not IFN-γ, from NLRP3-/- mice immunized by rTs-Serpin+lentinan was significantly lower than that from WT mice, suggesting that NLRP3 is associated with rTs-Serpin+lentinan -triggering Th2 protective immunity against T. spiralis infection. In summary, we revealed that lentinan was a novel adjuvant against T. spiralis infection via NLRP3. NLRP3 therefore represents an important target for adjuvant discovery and the control of T. spiralis infection.


Assuntos
Adjuvantes Imunológicos , Lentinano/imunologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/imunologia , Trichinella spiralis/efeitos dos fármacos , Trichinella spiralis/imunologia , Triquinelose/imunologia , Vacinas/imunologia , Animais , Anticorpos Anti-Helmínticos , Antígenos de Helmintos/genética , Antígenos de Helmintos/imunologia , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Imunização , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Serpinas/genética , Serpinas/imunologia , Trichinella spiralis/genética , Triquinelose/prevenção & controle
3.
Exp Parasitol ; 218: 107999, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32956649

RESUMO

Angiostrongylus cantonensis is the main causative agent of eosinophilic meningoencephalitis (EoM) in humans. Molecular diagnostic methods are essential since the identification of larvae in cerebrospinal fluid (CSF) is extremely rare. To date, the detection of a 31 kDa antigen by Western blotting has been the primary immunodiagnostic method for EoM caused by A. cantonensis. However, cross-reactivity with other parasites has been observed. Therefore, we conducted a comparative analysis using sera from individuals with angiostrongyliasis. We also characterized proteins isolated from different cellular sources of A. cantonensis, Toxocara canis, Schistosoma mansoni, and Strongyloides stercoralis with mass spectrometry. A total of 115 cross-reactive proteins were identified. Three of these proteins, heat shock protein, an intermediate filament protein, and galectin 1, represent potential markers for cross-reactivity. In addition, synthetic peptides were generated from previously identified diagnostic targets and tested against sera from individuals infected with several other parasites. As a result, two other markers of cross-reactivity were identified: peptide #4 derived from the 14-3-3 protein and peptide #12 derived from the Lec-5 protein. In contrast, 34 proteins were exclusively present in the Angiostrongylus extracts and represent promising diagnostic molecules for specific identification of A. cantonensis infection. In particular, cytochrome oxidase subunit I is of great interest as a possible immunodiagnostic target for angiostrongyliasis.


Assuntos
Angiostrongylus cantonensis/imunologia , Antígenos de Helmintos/imunologia , Proteínas de Helminto/imunologia , Meningoencefalite/diagnóstico , Meningoencefalite/parasitologia , Infecções por Strongylida/diagnóstico , Sequência de Aminoácidos , Angiostrongylus cantonensis/química , Animais , Antígenos de Helmintos/sangue , Antígenos de Helmintos/química , Antígenos de Helmintos/isolamento & purificação , Western Blotting , Sequência Conservada , Reações Cruzadas , Eletroforese , Eletroforese em Gel Bidimensional , Proteínas de Helminto/química , Proteínas de Helminto/isolamento & purificação , Humanos , Imunoensaio , Testes Imunológicos , Espectrometria de Massas , Meningoencefalite/imunologia , Infecções por Strongylida/imunologia , Infecções por Strongylida/parasitologia
4.
PLoS Negl Trop Dis ; 14(9): e0008518, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32915790

RESUMO

To eliminate schistosomiasis, appropriate diagnostic tests are required to monitor its prevalence and transmission, especially in the settings with low endemicity resulting from the consecutive mass drug administration. Antibodies that react with either crude soluble schistosome egg antigens or soluble worm antigen preparations have been used to monitor infection in low-prevalence regions. However, these detection methods cannot discriminate current and past infections and are cross-reactive with other parasites because both antigens contain numerous proteins and glycans from schistosomes, and standard preparations need maintenance of the life cycle of the schistosome. To evaluate the potential utility of nine recombinant Schistosoma mansoni proteins as single defined antigens for serological diagnosis, we monitored the kinetics of antibodies to each antigen during S. mansoni infection in mice before and after the treatment with praziquantel. C57BL/6 mice were infected with 50 cercariae. The levels of immunoglobulin G (IgG) raised against five recombinant antigens (RP26, sm31, sm32, GST, and LAP1) significantly increased as early as 2-4 weeks after infection and rapidly declined by 2 weeks after the treatment, whereas those raised against crude S. mansoni egg antigens or other antigens remained elevated long after the treatment. The IgG1 raised against RP26, sm31, and serpin decreased after the treatment with praziquantel, whereas the IgE raised against serpin declined strikingly after the treatment. This study clarifies the dynamics of the serological responses to recombinant S. mansoni proteins during infection and after the treatment with praziquantel and identifies several candidate antigens with potential utility in the monitoring and surveillance of schistosomiasis toward the elimination of schistosomiasis.


Assuntos
Praziquantel/farmacologia , Schistosoma mansoni/imunologia , Esquistossomose mansoni/imunologia , Animais , Anti-Helmínticos/farmacologia , Anticorpos Anti-Helmínticos , Antígenos de Helmintos/imunologia , Feminino , Proteínas de Helminto/imunologia , Imunoglobulina G , Camundongos Endogâmicos C57BL , Proteínas Recombinantes/imunologia , Schistosoma mansoni/efeitos dos fármacos , Esquistossomose mansoni/diagnóstico , Esquistossomose mansoni/tratamento farmacológico , Serpinas
5.
PLoS Negl Trop Dis ; 14(7): e0008470, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32644998

RESUMO

BACKGROUND: Sm16, also known as SPO-1 and SmSLP, is a low molecular weight protein (~16kDa) secreted by the digenean trematode parasite Schistosoma mansoni, one of the main causative agents of human schistosomiasis. The molecule is secreted from the acetabular gland of the cercariae during skin invasion and is believed to perform an immune-suppressive function to protect the invading parasite from innate immune cell attack. METHODOLOGY/PRINCIPAL FINDINGS: We show that Sm16 homologues of the Schistosomatoidea family are phylogenetically related to the helminth defence molecule (HDM) family of immunomodulatory peptides first described in Fasciola hepatica. Interrogation of 69 helminths genomes demonstrates that HDMs are exclusive to trematode species. Structural analyses of Sm16 shows that it consists predominantly of an amphipathic alpha-helix, much like other HDMs. In S. mansoni, Sm16 is highly expressed in the cercariae and eggs but not in adult worms, suggesting that the molecule is of importance not only during skin invasion but also in the pro-inflammatory response to eggs in the liver tissues. Recombinant Sm16 and a synthetic form, Sm16 (34-117), bind to macrophages and are internalised into the endosomal/lysosomal system. Sm16 (34-117) elicited a weak pro-inflammatory response in macrophages in vitro but also suppressed the production of bacterial lipopolysaccharide (LPS)-induced inflammatory cytokines. Evaluation of the transcriptome of human macrophages treated with a synthetic Sm16 (34-117) demonstrates that the peptide exerts significant immunomodulatory effects alone, as well as in the presence of LPS. Pathways most significantly influenced by Sm16 (34-117) were those involving transcription factors peroxisome proliferator-activated receptor (PPAR) and liver X receptors/retinoid X receptor (LXR/RXR) which are intricately involved in regulating the cellular metabolism of macrophages (fatty acid, cholesterol and glucose homeostasis) and are central to inflammatory responses. CONCLUSIONS/SIGNIFICANCE: These results offer new insights into the structure and function of a well-known immunomodulatory molecule, Sm16, and places it within a wider family of trematode-specific small molecule HDM immune-modulators with immuno-biotherapeutic possibilities.


Assuntos
Antígenos de Helmintos/metabolismo , Proteínas de Helminto/metabolismo , Schistosoma mansoni/metabolismo , Animais , Anticorpos Anti-Helmínticos , Antígenos de Helmintos/genética , Antígenos de Helmintos/imunologia , Células da Medula Óssea , Linhagem Celular Tumoral , Regulação da Expressão Gênica , Proteínas de Helminto/genética , Humanos , Macrófagos/parasitologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Óvulo , Filogenia , Transporte Proteico
6.
Rev Bras Parasitol Vet ; 29(2): e023419, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32520090

RESUMO

In experimental autoimmune hepatitis (EAH) of Th1 profile, an extract of adult Ascaris suum worms (ASC) was previously found to deviate the immune response to a Th2/IL-10 pattern. Here, the effects of treatment with ASC on production of TGF-ß and the anti-Ascaris isotypes IgG1 and IgG2a in EAH were evaluated. EAH was induced in BALB/c mice, intravenously with concanavalin A. Two hours later, these animals received ASC (EAH+ASC group) or PBS vehicle (EAH group). IgG1 and IgG2a were evaluated 8 h, 24 h and 7 d after induction. TGF-ß was measured in a splenocyte culture at this last time. The isotype levels in the EAH group were low throughout the kinetics. In the EAH+ASC group, there was significant production of IgG1 at 24 h and 7 d, but of IgG2a only at 7 d. There was statistically greater production of TGF-ß in the EAH+ASC group. The higher levels of IgG1 and TGF-ß in this group suggest that an additional Th1 response control route exists in EAH, which needs to be investigated.


Assuntos
Ascaris suum/imunologia , Hepatite Autoimune/parasitologia , Imunoglobulina G/biossíntese , Fator de Crescimento Transformador beta/biossíntese , Animais , Anticorpos Anti-Helmínticos/imunologia , Antígenos de Helmintos/imunologia , Modelos Animais de Doenças , Hepatite Autoimune/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C
7.
PLoS Negl Trop Dis ; 14(6): e0008322, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32574160

RESUMO

BACKGROUND: The World Health Organization now recommends semiannual mass drug administration (MDA) of albendazole with integrated vector management as an option for eliminating lymphatic filariasis (LF) in areas of loiasis-endemic countries where it may not be safe to use diethylcarbamazine or ivermectin in MDA programs. However, the published evidence base to support this policy is thin, and uptake by national programs has been slow. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a community trial to assess the impact of semiannual MDA on lymphatic filariasis and soil-transmitted helminth infections (STH) in two villages in the Bandundu province of the Democratic Republic of the Congo with moderately high prevalences for LF and hookworm infections. MDA with albendazole was provided every six months from June 2014 to December 2017 with treatment coverages of the eligible population (all ≥ 2 year of age) that ranged between 56% and 88%. No adverse effects were reported during the trial. Evaluation at 48 months, (i.e. 6 months after the 8th round of MDA), showed that W. bancrofti microfilaremia (Mf) prevalence in the study communities had decreased between 2014 to 2018 from 12% to 0.9% (p<0.001). The prevalence of W. bancrofti antigenemia was also significantly reduced from 31.6% to 8.5% (p<0.001). MDA with albendazole also reduced hookworm, Ascaris lumbricoides and Trichuris trichiura infection prevalences in the community from 58.6% to 21.2% (p<0.001), from 14.0% to 1.6% and 4.1% to 2.9%, respectively. Hookworm and Ascaris infection intensities were reduced by 93% (p = 0.02) and 57% (p = 0.03), respectively. In contrast, Trichuris infection intensity was not significantly reduced by MDA (p = 0.61) over this time period. CONCLUSION/SIGNIFICANCE: These results provide strong evidence that semiannual MDA with albendazole alone is a safe and effective strategy for LF elimination in Central Africa. Community MDA also had a major impact on STH infections.


Assuntos
Albendazol/uso terapêutico , Anti-Helmínticos/uso terapêutico , Filariose Linfática/tratamento farmacológico , Helmintíase/tratamento farmacológico , Adolescente , Adulto , Animais , Antígenos de Helmintos/imunologia , Ascaríase/tratamento farmacológico , Ascaríase/epidemiologia , Ascaris lumbricoides/efeitos dos fármacos , Ascaris lumbricoides/isolamento & purificação , Criança , República Democrática do Congo/epidemiologia , Filariose Linfática/epidemiologia , Feminino , Helmintíase/epidemiologia , Helmintíase/parasitologia , Infecções por Uncinaria/tratamento farmacológico , Infecções por Uncinaria/epidemiologia , Humanos , Masculino , Solo/parasitologia , Tricuríase/epidemiologia , Trichuris/efeitos dos fármacos , Trichuris/isolamento & purificação , Wuchereria bancrofti/efeitos dos fármacos , Wuchereria bancrofti/isolamento & purificação , Adulto Jovem
8.
Parasitol Res ; 119(8): 2521-2529, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32591864

RESUMO

The enzyme-linked immunoelectrotransfer blot (EITB) assay to detect antibodies in serum is a complementary tool for the diagnosis of neurocysticercosis (NCC). Presence of at least one glycoprotein band corresponding to a Taenia solium (T. solium) antigen indicates a positive result; however, EITB assays have multiple glycoprotein bands, and previous work has suggested that band patterns may have additional diagnostic value. We included 58 participants with a definitive diagnosis of NCC who received care at the Instituto Nacional de Neurología y Neurocirugía in Mexico City. Three different EITB tests were applied to participants' serum samples (LDBio, France; US Centers for Disease Control and Prevention [CDC]; and Instituto de Diagnóstico y Referencia Epidemiológicos [InDRE]). There was substantial variability in specific glycoprotein band patterns among the three assays. However, in age- and sex-adjusted logistic regression models, the number of glycoprotein bands was positively associated with the presence of vesicular extraparenchymal cysts (InDRE adjusted odds ratio [aOR] 1.60 p < 0.001; CDC aOR 6.31 p < 0.001; LDBio aOR 2.45 p < 0.001) and negatively associated with the presence of calcified parenchymal cysts (InDRE aOR 0.63 p < 0.001; CDC aOR 0.25 p < 0.001; LDBio aOR 0.44 p < 0.001). In a sensitivity analysis also adjusting for cyst count, results were similar. In all three EITB serum antibody tests, the number of glycoprotein bands consistently predicted cyst stage and location, although magnitude of effect differed.


Assuntos
Ensaio de Imunoadsorção Enzimática/métodos , Glicoproteínas/análise , Proteínas de Helminto/análise , Neurocisticercose/diagnóstico , Taenia solium/isolamento & purificação , Animais , Anticorpos Anti-Helmínticos/análise , Antígenos de Helmintos/análise , Antígenos de Helmintos/imunologia , Feminino , França , Glicoproteínas/imunologia , Proteínas de Helminto/imunologia , Humanos , Masculino , México , Neurocisticercose/parasitologia , Razão de Chances , Sensibilidade e Especificidade , Taenia solium/crescimento & desenvolvimento , Taenia solium/imunologia
9.
Mol Immunol ; 124: 91-99, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32544656

RESUMO

The prevalence of allergic diseases in Brazil is one of the biggest in the world. Among these pathologies, we highlight asthma as one of the most importance. Asthma is characterized as a chronic inflammatory disease of airways, associated with hyperresponsiveness. Many environmental factors can trigger asthma symptoms, among them house dust mites can stimulate hypersensitivity type I reaction. The most common in house dust mite, in tropical countries, are Dermatophagoides pteronysinus and Blomia tropicalis. Several studies have shown that helminths, especially Schistosoma mansoni, lead to reduction of symptoms of atopy and allergic diseases. Therefore, the present study aims to evaluate the ability of recombinant S. mansoni proteins Sm200, and SmKI-1 to induce immunomodulation in vitro, using peripheral blood mononuclear cells (PBMCs) from atopic and non-atopic individuals, stimulated or not with B. tropicalis extract, and in vivo, in a murine model of allergy to the mite B. tropicalis. As results, we observed that the fragment called rSm200-3 and the protein rSmKI-1 stood out for their immunomodulatory potential, stimulating IL-10 production by human PBMCs in vitro. When these proteins were associated with B. tropicalis extract, it was observed the reduction of the production of the cytokine IL-5, with a statistically significant difference in non-atopic individual's cells. In vivo, both proteins presented similar results, with a reduction of IL-5 and IL-4 levels in lung homogenates and of serum IgE. SmKI-1 was also able to decrease the levels of EPO in lung homogenates and in BAL. These results showed that both proteins were able to downmodulate Th2 cells on human PBMCs, and in a murine model of allergy. However, SmKI-1 also reduced significantly the levels of EPO in BAL and lungs showing that this protein may be a good candidate to be used as a possible replacement or in conjunction with pharmacotherapy in individuals with unregulated immune response in asthma.


Assuntos
Antígenos de Helmintos/imunologia , Hipersensibilidade/imunologia , Pyroglyphidae/imunologia , Adulto , Animais , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Camundongos , Schistosoma mansoni/imunologia , Adulto Jovem
10.
Artigo em Inglês | MEDLINE | ID: mdl-32401955

RESUMO

In experimental infection with Strongyloides venezuelensis, the acute and recovery phases can be distinguished, unlike human infections caused by Strongyloides stercoralis. The objective of this study was to evaluate the production of anti-Strongyloides IgG antibodies and the recognition of immunogenic protein bands during the acute and the recovery phases in rats experimentally infected with S. venezuelensis. Rats were infected subcutaneously with 400 or 4,000 S. venezuelensis infective larvae. The acute phase was characterized by elimination of a large number of eggs in the faeces on days 6-14 post infection; the recovery phase was characterized by the resolution of the infection between days 30 and 35 post infection. Differences in IgG levels were observed in the acute and the recovery phases. Different antigenic fractions were recognized in both phases of infection. It is concluded that proteins within the 30-40 kDa range are immunoreactive markers for both the acute and the recovery phases in rats experimentally infected with S. venezuelensis, particularly using membrane antigen.


Assuntos
Anticorpos Anti-Helmínticos/imunologia , Antígenos de Helmintos/imunologia , Proteínas de Helminto/imunologia , Imunoglobulina G/imunologia , Estrongiloidíase/imunologia , Doença Aguda , Animais , Western Blotting , Reações Cruzadas , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Fezes/parasitologia , Masculino , Ratos Wistar , Fatores de Tempo
11.
Am J Trop Med Hyg ; 103(1_Suppl): 50-57, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32400344

RESUMO

The Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) was funded in 2008 to conduct research that would support country schistosomiasis control programs. As schistosomiasis prevalence decreases in many places and elimination is increasingly within reach, a sensitive and specific test to detect infection with Schistosoma mansoni and Schistosoma haematobium has become a pressing need. After obtaining broad input, SCORE supported Leiden University Medical Center (LUMC) to modify the serum-based antigen assay for use with urine, simplify the assay, and improve its sensitivity. The urine assay eventually contributed to several of the larger SCORE studies. For example, in Zanzibar, we demonstrated that urine filtration, the standard parasite egg detection diagnostic test for S. haematobium, greatly underestimated prevalence in low-prevalence settings. In Burundi and Rwanda, the circulating anodic antigen (CAA) assay provided critical information about the limitations of the stool-based Kato-Katz parasite egg-detection assay for S. mansoni in low-prevalence settings. Other SCORE-supported CAA work demonstrated that frozen, banked urine specimens yielded similar results to fresh ones; pooling of specimens may be a useful, cost-effective approach for surveillance in some settings; and the assay can be performed in local laboratories equipped with adequate centrifuge capacity. These improvements in the assay continue to be of use to researchers around the world. However, additional work will be needed if widespread dissemination of the CAA assay is to occur, for example, by building capacity in places besides LUMC and commercialization of the assay. Here, we review the evolution of the CAA assay format during the SCORE period with emphasis on urine-based applications.


Assuntos
Antígenos de Helmintos/imunologia , Glicoproteínas/imunologia , Proteínas de Helminto/imunologia , Schistosoma/imunologia , Esquistossomose/diagnóstico , Animais , Biomarcadores , Burundi/epidemiologia , Criança , Testes Diagnósticos de Rotina , Fezes/parasitologia , Feminino , Humanos , Testes Imunológicos , Masculino , Modelos Animais , Papio/parasitologia , Contagem de Ovos de Parasitas , Prevalência , Ruanda/epidemiologia , Santa Lúcia/epidemiologia , Schistosoma/isolamento & purificação , Schistosoma haematobium/imunologia , Schistosoma haematobium/isolamento & purificação , Schistosoma japonicum/imunologia , Schistosoma japonicum/isolamento & purificação , Schistosoma mansoni/imunologia , Schistosoma mansoni/isolamento & purificação , Esquistossomose/epidemiologia , Sensibilidade e Especificidade , Tanzânia/epidemiologia , Urina/parasitologia
12.
Am J Trop Med Hyg ; 103(1_Suppl): 125-134, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32400345

RESUMO

Herein, we summarize what we consider are major contributions resulting from the Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) program, including its key findings and key messages from those findings. Briefly, SCORE's key findings are as follows: i) biennial mass drug administration (MDA) with praziquantel can control schistosomiasis to moderate levels of prevalence; ii) MDA alone will not achieve elimination; iii) to attain and sustain control throughout endemic areas, persistent hotspots need to be identified following a minimal number of years of annual MDA and controlled through adaptive strategies; iv) annual MDA is more effective than biennial MDA in high-prevalence areas; v) the current World Health Organization thresholds for decision-making based on the prevalence of heavy infections should be redefined; and vi) point-of-care circulating cathodic antigen urine assays are useful for Schistosoma mansoni mapping in low-to-moderate prevalence areas. The data and specimens collected and curated through SCORE efforts will continue to be critical resource for future research. Besides providing useful information for program managers and revision of guidelines for schistosomiasis control and elimination, SCORE research and outcomes have identified additional questions that need to be answered as the schistosomiasis community continues to implement effective, evidence-based programs. An overarching contribution of SCORE has been increased cohesiveness within the schistosomiasis field-oriented community, thereby fostering new and productive collaborations. Based on SCORE's findings and experiences, we propose new approaches, thresholds, targets, and goals for control and elimination of schistosomiasis, and recommend research and evaluation activities to achieve these targets and goals.


Assuntos
Diretrizes para o Planejamento em Saúde , Schistosoma mansoni/efeitos dos fármacos , Esquistossomose/prevenção & controle , África/epidemiologia , Animais , Anti-Helmínticos/uso terapêutico , Antígenos de Helmintos/imunologia , Biomarcadores/sangue , Criança , Fezes/parasitologia , Glicoproteínas/imunologia , Proteínas de Helminto/imunologia , Humanos , Masculino , Administração Massiva de Medicamentos , Doenças Negligenciadas/tratamento farmacológico , Doenças Negligenciadas/epidemiologia , Doenças Negligenciadas/prevenção & controle , Contagem de Ovos de Parasitas , Praziquantel/uso terapêutico , Prevalência , Saúde Pública , Esquistossomose/diagnóstico , Esquistossomose/tratamento farmacológico , Esquistossomose/epidemiologia , Esquistossomose mansoni/diagnóstico , Esquistossomose mansoni/tratamento farmacológico , Esquistossomose mansoni/epidemiologia , Esquistossomose mansoni/prevenção & controle
13.
Am J Trop Med Hyg ; 103(1_Suppl): 42-49, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32400347

RESUMO

Efforts to control Schistosoma mansoni infection depend on the ability of programs to effectively detect and quantify infection levels and adjust programmatic approaches based on these levels and program goals. One of the three major objectives of the Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) has been to develop and/or evaluate tools that would assist Neglected Tropical Disease program managers in accomplishing this fundamental task. The advent of a widely available point-of-care (POC) assay to detect schistosome circulating cathodic antigen (CCA) in urine with a rapid diagnostic test (the POC-CCA) in 2008 led SCORE and others to conduct multiple evaluations of this assay, comparing it with the Kato-Katz (KK) stool microscopy assay-the standard used for more than 45 years. This article describes multiple SCORE-funded studies comparing the POC-CCA and KK assays, the pros and cons of these assays, the use of the POC-CCA assay for mapping of S. mansoni infections in areas across the spectrum of prevalence levels, and the validation and recognition that the POC-CCA, although not infallible, is a highly useful tool to detect low-intensity infections in low-to-moderate prevalence areas. Such an assay is critical, as control programs succeed in driving down prevalence and intensity and seek to either maintain control or move to elimination of transmission of S. mansoni.


Assuntos
Antígenos de Helmintos/imunologia , Glicoproteínas/imunologia , Proteínas de Helminto/imunologia , Schistosoma mansoni/imunologia , Esquistossomose mansoni/diagnóstico , Animais , Criança , Testes Diagnósticos de Rotina , Fezes/parasitologia , Feminino , Humanos , Testes Imunológicos , Masculino , Sistemas Automatizados de Assistência Junto ao Leito , Prevalência , Esquistossomose mansoni/epidemiologia , Sensibilidade e Especificidade , Urina/parasitologia
14.
PLoS Pathog ; 16(4): e1008465, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32271834

RESUMO

Roundworm parasite infections are a major cause of human and livestock disease worldwide and a threat to global food security. Disease control currently relies on anthelmintic drugs to which roundworms are becoming increasingly resistant. An alternative approach is control by vaccination and 'hidden antigens', components of the worm gut not encountered by the infected host, have been exploited to produce Barbervax, the first commercial vaccine for a gut dwelling nematode of any host. Here we present the structure of H-gal-GP, a hidden antigen from Haemonchus contortus, the Barber's Pole worm, and a major component of Barbervax. We demonstrate its novel architecture, subunit composition and topology, flexibility and heterogeneity using cryo-electron microscopy, mass spectrometry, and modelling. Importantly, we demonstrate that complexes with the same architecture are present in other Strongylid roundworm parasites including human hookworm. This suggests a common ancestry and the potential for development of a unified hidden antigen vaccine.


Assuntos
Endopeptidases/metabolismo , Endopeptidases/ultraestrutura , Haemonchus/imunologia , Proteínas de Helminto/metabolismo , Proteínas de Helminto/ultraestrutura , Glicoproteínas de Membrana/metabolismo , Glicoproteínas de Membrana/ultraestrutura , Animais , Anti-Helmínticos/farmacologia , Anticorpos Anti-Helmínticos , Antígenos de Helmintos/imunologia , Microscopia Crioeletrônica , Endopeptidases/imunologia , Haemonchus/patogenicidade , Proteínas de Helminto/imunologia , Glicoproteínas de Membrana/imunologia , Parasitos , Vacinação , Vacinas/imunologia
15.
PLoS Negl Trop Dis ; 14(4): e0008037, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32282815

RESUMO

BACKGROUND: The scientific community has recently summarized the desired characteristics for diagnostic tools across the different phases of a soil-transmitted helminth (STH) mass drug administration (MDA) program. Although serology meets some of the desired criteria, there is a scarcity of data on baseline serological profiles in human populations, both prior to and during MDA programs. METHODS: In this study, we compared the copromicroscopic and the serological infection profiles in 600 school-aged children (SAC) and 600 adults at the advent of the MDA program in Jimma Town, Ethiopia. The serological profiles were examined by two ELISAs that measure IgG4 responses to the Ascaris suum haemoglobin antigen (AsHb) and a somatic extract of lung stage larvae (AsLungL3). Three years into the MDA program, we sampled another group of 600 SAC from the same schools to assess the reduction in prevalence and intensity of Ascaris infections measured by copromicroscopy and serology. PRINCIPAL FINDINGS: Prior to the start of MDA, copromicroscopy revealed an Ascaris prevalence of 31.0% and a mean fecal egg count of 2,919 eggs per gram (EPG) in SAC. Following three years of biannual treatment, the prevalence reduced to 13.2% (57.8% reduction) and the mean fecal egg count to 1,513 EPG (48.1% reduction). This reduction was also reflected in the serological results. The seroprevalence reduced with 40.9% and 27.4% and the mean optical density ratio reduced with 44.2% and 38.2% as measured by the AsHb or AsLungL3 ELISA respectively. We also showed that, despite a decreasing coproprevalence, seroprevalence to Ascaris increased with age. CONCLUSIONS: This study is the first to provide IgG4 response profiles of an endemic population to two different A. suum antigens. The results suggest that exposure to the infectious stages of Ascaris reaches beyond SAC alone. Furthermore, it highlights the possible use of serological assays to monitor changes in STH exposure during MDA programs.


Assuntos
Ascaríase/diagnóstico , Ascaris suum/imunologia , Ascaris suum/isolamento & purificação , Monitoramento de Medicamentos/métodos , Administração Massiva de Medicamentos/métodos , Microscopia/métodos , Testes Sorológicos/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Anticorpos Anti-Helmínticos/sangue , Antígenos de Helmintos/imunologia , Ascaríase/tratamento farmacológico , Ascaríase/epidemiologia , Ascaríase/prevenção & controle , Criança , Pré-Escolar , Estudos Transversais , Ensaio de Imunoadsorção Enzimática/métodos , Etiópia/epidemiologia , Fezes/parasitologia , Feminino , Humanos , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , Prevalência , Resultado do Tratamento , Adulto Jovem
16.
PLoS Negl Trop Dis ; 14(4): e0008192, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32236093

RESUMO

Trichinella spiralis can modulate host immune responses to retain a suitable environment for its long-term survival. Incidentally, the parasite elicits regulatory effects through immunomodulatory molecule release, which can suppress host inflammation and may be used for the treatment of unrelated inflammatory diseases in someday. Here we identified and characterized a novel T. spiralis cystatin (TsCstN), which inhibits inflammation mediated by LPS-treated macrophages.Proteins contained in the excretory-secretory (ES) product of muscle-stage T. spiralis (ES-L1) were fractionated, and each was treated with mouse bone marrow-derived macrophages (mBMDMs) before LPS stimulation. The fractions that exhibited high immunomodulatory property by decreasing pro-inflammatory cytokines or increasing anti-inflammatory cytokines were identified by mass spectrometry. Incidentally, the conserved hypothetical protein (Tsp_04814) was selected for further characterization as it presented the most significant MS score. An annotation of Tsp_04814 using protein structural homology comparison suggested that it has high structural similarity to human cystatin E/M (TM score 0.690). The recombinant T. spiralis novel cystatin (rTsCstN) was expressed in Escherichia coli at a molecular weight of approximately 13 kDa. Mouse anti-rTsCstN polyclonal antibody (pAb) could detect native TsCstN in crude worm antigens (CWA) and ES-L1 and be predominantly localized in the stichosome and subcuticular cells. rTsCstN inhibited cysteine proteases in vitro, especially cathepsin L, at an optimal pH of 6. Besides, rTsCstN could be internalized into mBMDMs, which were mostly distributed in the cytoplasm and lysosome both before and after LPS stimulation. To evaluate the rTsCstN immunomodulatory properties on mBMDMs, rTsCstN was incubated with mBMDM before LPS stimulation; this demonstrated that rTsCstN suppressed pro-inflammatory cytokine production and MHC class II expression.T. spiralis L1-derived TsCstN was characterized as a novel cysteine protease inhibitor. The protein elicits an anti-inflammatory property by suppressing pro-inflammatory cytokines and interfering with the antigen presentation process through depletion of MHC class II expression.


Assuntos
Antígenos de Helmintos/imunologia , Cistatinas/imunologia , Citocinas/imunologia , Macrófagos/imunologia , Trichinella spiralis , Animais , Meios de Cultivo Condicionados/farmacologia , Cistatinas/genética , Inibidores de Cisteína Proteinase , Inflamação/induzido quimicamente , Inflamação/imunologia , Larva , Lipopolissacarídeos , Macrófagos/efeitos dos fármacos , Macrófagos/enzimologia , Espectrometria de Massas , Camundongos , Camundongos Endogâmicos BALB C
17.
PLoS Negl Trop Dis ; 14(4): e0008177, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32243436

RESUMO

Urticaria remains a major problem in terms of aetiology, investigation, and management, and although parasitic diseases are considered potential causes, the absence of a consistent link between parasitic infections and skin allergy symptoms leads to the need for a deeper study of parameters that support this association. The objectives of this study were to analyse a possible relationship between parasitism by Ascarididae (Toxocara canis and Anisakis simplex) and the clinical expression of urticaria and to identify possible parasitic molecular markers for improving the diagnosis of unknown urticaria aetiology. The prevalence of Toxocara and Anisakis infestations was evaluated by measuring the levels of specific IgG (sIgG) and IgE (sIgE) antibodies against crude extracts and isolated components from whole larvae of Anisakis simplex (Ani s 1, Ani s 3 and Ani s 7) and Toxocara canis (TES-120, TES-70, TES-32 and TES-26) using immunologic and molecular diagnostic methods. A cross-sectional study was performed in a group of 400 individuals. The study group consisted of 95 patients diagnosed with urticaria (55 with chronic urticaria and 40 with acute urticaria). A control group consisted of 305 subjects without urticaria (182 diagnosed with respiratory allergy and 123 without allergy). Statistically significant differences were demonstrated in the seroprevalence of specific IgG and IgE antibodies between the urticaria patients and the healthy general population when isolated ascarid antigens were evaluated. The prevalence of IgG antibodies against Ani s 1, IgE antibodies against TES-120 and IgE antibodies against TES-70 were significantly different between the control individuals (healthy general population) and patients with urticaria. Moreover, the urticaria patient group demonstrated a higher seroprevalence of antibodies (sIgE and sIgG) against Anisakis simplex larva whole extract than the control group but just with statistically diferences when sIgE was evaluated. The presence of IgE and/or IgG antibodies against Ani s 3 (tropomyosin) can help to discriminate between patients with and without urticaria. Both ascarids seem to be associated with urticaria, although in our region, Anisakis seems to have greater involvement than Toxocara in this relationship. Molecular diagnostics can be used to associate urticaria with parasite infestations. Tropomyosin and Ani s 1 were the most relevant markers to demonstrate the association between urticaria and the most relevant Ascarididae parasites in our region.


Assuntos
Anticorpos Anti-Helmínticos/imunologia , Antígenos de Helmintos/imunologia , Ascaridoidea/patogenicidade , Urticária/diagnóstico , Urticária/imunologia , Urticária/parasitologia , Adolescente , Adulto , Alérgenos/imunologia , Animais , Anisaquíase/imunologia , Anisakis/imunologia , Estudos Transversais , Feminino , Proteínas de Helminto/imunologia , Humanos , Imunoglobulina E/imunologia , Imunoglobulina G/imunologia , Larva/imunologia , Masculino , Pessoa de Meia-Idade , Estudos Soroepidemiológicos , Pele/imunologia , Toxocara canis/imunologia , Adulto Jovem
18.
Mol Immunol ; 121: 127-135, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32200170

RESUMO

Consumption of fermentable dietary fibres, such as inulin, or administration of helminth products (e.g. Trichuris suis ova) have independently been shown to alleviate inflammation in vivo. We recently found that dietary inulin and T. suis infection in pigs co-operatively suppressed type-1 inflammatory responses in the gut, suggesting the potential of dietary components to augment anti-inflammatory responses induced by certain helminths. Here, we explored whether T. suis antigens and inulin could directly suppress inflammatory responses in vitro in a cooperative manner. T. suis soluble products (TsSP) strongly suppressed lipopolysaccharide (LPS)-induced IL-6 and TNF-α secretion from murine macrophages and induced an anti-inflammatory phenotype as evidenced by transcriptomic and gene pathway analyses. Inulin regulated the expression of a small number of genes and transcriptional pathways in macrophages after exposure to LPS, but did not enhance the suppressive activity of TsSP, either directly or in co-culture experiments with intestinal epithelial cells. Culture of macrophages with short-chain fatty acids, the products of microbial fermentation of inulin, did however appear to enhance TsSP-mediated inhibition of TNF-α production. Our results confirm a direct role for helminth products in suppressing inflammatory responses in macrophages. In contrast, inulin had little capacity to directly modulate LPS-induced responses. Our results suggest distinct mode-of-actions of T. suis and inulin in regulating inflammatory responses, and that the role of inulin in modulating the response to helminth infection may be dependent on other factors such as production of metabolites by the gut microbiota.


Assuntos
Antígenos de Helmintos/farmacologia , Inflamação/terapia , Inulina/farmacologia , Macrófagos/efeitos dos fármacos , Trichuris/imunologia , Animais , Antígenos de Helmintos/imunologia , Antígenos de Helmintos/uso terapêutico , Células Cultivadas , Técnicas de Cocultura , Fibras na Dieta/farmacologia , Células Epiteliais , Ácidos Graxos Voláteis/farmacologia , Humanos , Inflamação/imunologia , Interleucina-6/imunologia , Interleucina-6/metabolismo , Mucosa Intestinal/citologia , Lipopolissacarídeos/imunologia , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos , Células RAW 264.7 , Fator de Necrose Tumoral alfa/imunologia , Fator de Necrose Tumoral alfa/metabolismo
19.
PLoS Negl Trop Dis ; 14(2): e0008057, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32053593

RESUMO

BACKGROUND: Ascaris lumbricoides is one of the three major soil-transmitted gastrointestinal helminths (STHs) that infect more than 440 million people in the world, ranking this neglected tropical disease among the most common afflictions of people living in poverty. Children infected with this roundworm suffer from malnutrition, growth stunting as well as cognitive and intellectual deficits. An effective vaccine is urgently needed to complement anthelmintic deworming as a better approach to control helminth infections. As37 is an immunodominant antigen of Ascaris suum, a pig roundworm closely related to the human A. lumbricoides parasite, recognized by protective immune sera from A. suum infected mice. In this study, the immunogenicity and vaccine efficacy of recombinant As37 were evaluated in a mouse model. METHODOLOGY/PRINCIPAL FINDINGS: As37 was cloned and expressed as a soluble recombinant protein (rAs37) in Escherichia coli. The expressed rAs37 was highly recognized by protective immune sera from A. suum egg-infected mice. Balb/c mice immunized with 25 µg rAs37 formulated with AddaVax™ adjuvant showed significant larval worm reduction after challenge with A. suum infective eggs when compared with a PBS (49.7%) or adjuvant control (48.7%). Protection was associated with mixed Th1/2-type immune responses characterized by high titers of serological IgG1 and IgG2a and stimulation of the production of cytokines IL-4, IL-5, IL-10 and IL-13. In this experiment, the AddaVax™ adjuvant induced better protection than the Th1-type adjuvant MPLA (38.9%) and the Th2-type adjuvant Alhydrogel (40.7%). Sequence analysis revealed that As37 is a member of the immunoglobulin superfamily (IgSF) and highly conserved in other human STHs. Anti-As37 antibodies strongly recognized homologs in hookworms (Necator americanus, Ancylostoma ceylanicum, A. caninum) and in the whipworm Trichuris muris, but there was no cross-reaction with human spleen tissue extracts. These results suggest that the nematode-conserved As37 could serve as a pan-helminth vaccine antigen to prevent all STH infections without cross-reaction with human IgSF molecules. CONCLUSIONS/SIGNIFICANCE: As37 is an A. suum expressed immunodominant antigen that elicited significant protective immunity in mice when formulated with AddaVax™. As37 is highly conserved in other STHs, but not in humans, suggesting it could be further developed as a pan-helminth vaccine against STH co-infections.


Assuntos
Ascaríase/imunologia , Ascaris suum/metabolismo , Proteínas de Helminto/imunologia , Sequência de Aminoácidos , Animais , Anticorpos Anti-Helmínticos/sangue , Antígenos de Helmintos/imunologia , Ascaris suum/genética , Ascaris suum/imunologia , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Filogenia , Solo/parasitologia
20.
Nat Med ; 26(3): 326-332, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32066978

RESUMO

Schistosomiasis treatment relies on the use of a single drug, praziquantel, which is insufficient to control transmission in highly endemic areas1. Novel medicines and vaccines are urgently needed2,3. An experimental human model for schistosomiasis could accelerate the development of these products. We performed a dose-escalating clinical safety trial in 17 volunteers with male Schistosoma mansoni cercariae, which do not produce eggs (clinicaltrials.gov NCT02755324), at the Leiden University Medical Center, the Netherlands. The primary endpoints were adverse events and infectivity. We found a dose-related increase in adverse events related to acute schistosomiasis syndrome, which occurred in 9 of 17 volunteers. Overall, 5 volunteers (all 3 of the high dose group and 2 of 11 of the medium dose group) reported severe adverse events. Worm-derived circulating anodic antigen, the biomarker of the primary infection endpoint, peaked in 82% of volunteers at 3-10 weeks following exposure. All volunteers showed IgM and IgG1 seroconversion and worm-specific cytokine production by CD4+ T cells. All volunteers were cured with praziquantel provided at 12 weeks after exposure. Infection with 20 Schistosoma mansoni cercariae led to severe adverse events in 18% of volunteers and high infection rates. This infection model paves the way for fast-track product development for treatment and prevention of schistosomiasis.


Assuntos
Antiparasitários/uso terapêutico , Modelos Biológicos , Schistosoma mansoni/fisiologia , Esquistossomose mansoni/tratamento farmacológico , Esquistossomose mansoni/imunologia , Vacinas/imunologia , Adolescente , Adulto , Animais , Antígenos de Helmintos/sangue , Antígenos de Helmintos/imunologia , Antiparasitários/farmacologia , Citocinas/sangue , Feminino , Humanos , Imunidade Humoral/efeitos dos fármacos , Imunoglobulina M/sangue , Masculino , Pessoa de Meia-Idade , Praziquantel/farmacologia , Praziquantel/uso terapêutico , Schistosoma mansoni/efeitos dos fármacos , Esquistossomose mansoni/sangue , Esquistossomose mansoni/microbiologia , Adulto Jovem
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