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1.
Parasit Vectors ; 17(1): 340, 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39135121

RESUMO

BACKGROUND: The Gran Chaco ecoregion is a well-known hotspot of several neglected tropical diseases (NTDs) including Chagas disease, soil-transmitted helminthiasis and multiparasitic infections. Interspecific interactions between parasite species can modify host susceptibility, pathogenesis and transmissibility through immunomodulation. Our objective was to test the association between human co-infection with intestinal parasites and host parasitaemia, infectiousness to the vector and immunological profiles in Trypanosoma cruzi-seropositive individuals residing in an endemic region of the Argentine Chaco. METHODS: We conducted a cross-sectional serological survey for T. cruzi infection along with an intestinal parasite survey in two adjacent rural villages. Each participant was tested for T. cruzi and Strongyloides stercoralis infection by serodiagnosis, and by coprological tests for intestinal parasite detection. Trypanosoma cruzi bloodstream parasite load was determined by quantitative PCR (qPCR), host infectiousness by artificial xenodiagnosis and serum human cytokine levels by flow cytometry. RESULTS: The seroprevalence for T. cruzi was 16.1% and for S. stercoralis 11.5% (n = 87). We found 25.3% of patients with Enterobius vermicularis. The most frequent protozoan parasites were Blastocystis spp. (39.1%), Giardia lamblia (6.9%) and Cryptosporidium spp. (3.4%). Multiparasitism occurred in 36.8% of the examined patients. Co-infection ranged from 6.9% to 8.1% for T. cruzi-seropositive humans simultaneously infected with at least one protozoan or helminth species, respectively. The relative odds of being positive by qPCR or xenodiagnosis (i.e. infectious) of 28 T. cruzi-seropositive patients was eight times higher in people co-infected with at least one helminth species than in patients with no such co-infection. Trypanosoma cruzi parasite load and host infectiousness were positively associated with helminth co-infection in a multiple regression analysis. Interferon-gamma (IFN-γ) response, measured in relation to interleukin (IL)-4 among humans infected with T. cruzi only, was 1.5-fold higher than for T. cruzi-seropositive patients co-infected with helminths. The median concentration of IL-4 was significantly higher in T. cruzi-seropositive patients with a positive qPCR test than in qPCR-negative patients. CONCLUSIONS: Our results show a high level of multiparasitism and suggest that co-infection with intestinal helminths increased T. cruzi parasitaemia and upregulated the Th2-type response in the study patients.


Assuntos
Doença de Chagas , Coinfecção , Helmintíase , Enteropatias Parasitárias , Trypanosoma cruzi , Humanos , Trypanosoma cruzi/imunologia , Trypanosoma cruzi/genética , Trypanosoma cruzi/isolamento & purificação , Coinfecção/parasitologia , Coinfecção/epidemiologia , Coinfecção/imunologia , Doença de Chagas/epidemiologia , Doença de Chagas/complicações , Doença de Chagas/parasitologia , Doença de Chagas/sangue , Doença de Chagas/imunologia , Animais , Adulto , Estudos Transversais , Masculino , Feminino , Enteropatias Parasitárias/epidemiologia , Enteropatias Parasitárias/parasitologia , Enteropatias Parasitárias/complicações , Enteropatias Parasitárias/imunologia , Pessoa de Meia-Idade , Helmintíase/complicações , Helmintíase/parasitologia , Helmintíase/epidemiologia , Helmintíase/imunologia , Adulto Jovem , Adolescente , Argentina/epidemiologia , Estudos Soroepidemiológicos , Strongyloides stercoralis/imunologia , Strongyloides stercoralis/isolamento & purificação , Parasitemia/parasitologia , Parasitemia/epidemiologia , Células Th2/imunologia , Criança , Estrongiloidíase/epidemiologia , Estrongiloidíase/parasitologia , Estrongiloidíase/complicações , Estrongiloidíase/imunologia , Estrongiloidíase/sangue , Idoso , Citocinas/sangue , Anticorpos Antiprotozoários/sangue
2.
PLoS Negl Trop Dis ; 18(7): e0012319, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38968318

RESUMO

BACKGROUND: Strongyloidiasis is caused by a neglected nematode, manifesting as chronic intestinal infection with potentially severe manifestations. The disease is an emerging problem in non-endemic countries affecting travelers and migrants. Diagnosis of strongyloidiasis is hampered by the lack of standardization and absence of a gold standard. Since adequate direct methods to detect the motile larvae in stool samples are not widely available, other techniques such as serology have been developed. METHODS: We evaluated three commercial ELISA kits (DRG Instruments, IVD Research, and Bordier Affinity Products) to detect IgG antibodies against Strongyloides stercoralis assays utilizing serum samples from travelers with microscopically confirmed strongyloidiasis (n = 50) and other imported helminthic infections (n = 159) as well as healthy controls (n = 50). RESULTS: The DRG, IVD, and Bordier assays showed sensitivities of 58.0%, 64.0%, and 56.0%, respectively. Specificity values were 96.0%, 96.0%, and 92.0% in healthy controls, and 67.3%, 62.9%, and 76.7% in cases with other helminth infections, respectively. Cross-reactions were mostly observed in cases with other nematodes (37.5%, 42.5%, and 20.0%, respectively), but also in trematode (33.3%, 38.1%, and 19.0%, respectively) and in cestode infections (25.0%, 30.0%, and 32.5%, respectively). CONCLUSION: The study demonstrates the diagnostic limitations of serological assays to detect or exclude cases of strongyloidiasis in returning travelers, who frequently present with recent or acute infections.


Assuntos
Anticorpos Anti-Helmínticos , Ensaio de Imunoadsorção Enzimática , Imunoglobulina G , Sensibilidade e Especificidade , Testes Sorológicos , Strongyloides stercoralis , Estrongiloidíase , Estrongiloidíase/diagnóstico , Estrongiloidíase/imunologia , Humanos , Animais , Strongyloides stercoralis/imunologia , Strongyloides stercoralis/isolamento & purificação , Anticorpos Anti-Helmínticos/sangue , Ensaio de Imunoadsorção Enzimática/métodos , Imunoglobulina G/sangue , Testes Sorológicos/métodos , Masculino , Adulto , Feminino , Pessoa de Meia-Idade , Kit de Reagentes para Diagnóstico/normas , Reações Cruzadas
3.
PLoS Negl Trop Dis ; 18(7): e0012320, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39008519

RESUMO

BACKGROUND: The sensitivity of parasitological and molecular methods is unsatisfactory for the diagnosis of strongyloidiasis, and serological techniques are remaining as the most effective diagnostic approach. The present study aimed to design and produce a chimeric recombinant antigen from Strongyloides stercoralis immunoreactive antigen (SsIR) and Ss1a antigens, using immune-informatics approaches, and evaluated its diagnostic performance in an ELISA system for the diagnosis of human strongyloidiasis. METHODOLOGY/PRINCIPAL FINDINGS: The coding sequences for SsIR and Ss1a were selected from GenBank and were gene-optimized. Using bioinformatics analysis, the regions with the highest antigenicity that did not overlap with other parasite antigens were selected. The chimeric recombinant antigen SsIR- Ss1a, was constructed. The solubility and physicochemical properties of the designed construct were analyzed and its tertiary structures were built and evaluated. The construct was expressed into the pET-23a (+) expression vector and the optimized DNA sequences of SsIR-Ss1a (873 bp) were cloned into competent E. coli DH5α cells. Diagnostic performances of the produced recombinant antigen, along with a commercial kit were evaluated in an indirect ELISA system, using a panel of sera from strongyloidiasis patients and controls. The physicochemical and bioinformatics evaluations revealed that the designed chimeric construct is soluble, has a molecular with of 35 KDa, and is antigenic. Western blotting confirmed the immunoreactivity of the produced chimeric recombinant antigen with the sera of strongyloidiasis patients. The sensitivity and specificity of the indirect ELISA system, using the produced SsIR-Ss1a chimeric antigen, were found to be 93.94% (95% CI, 0.803 to 0.989) and 97.22% (95% CI, 0.921 to 0.992) respectively. CONCLUSIONS/SIGNIFICANCE: The preliminary findings of this study suggest that the produced SsIR-Ss1a chimeric antigen shows promise in the diagnosis of human strongyloidiasis. However, these results are based on a limited panel of samples, and further research with a larger sample size is necessary to confirm its accuracy. The construct has potential as an antigen in the ELISA system for the serological diagnosis of this neglected parasitic infection, but additional validation is required.


Assuntos
Antígenos de Helmintos , Ensaio de Imunoadsorção Enzimática , Sensibilidade e Especificidade , Testes Sorológicos , Strongyloides stercoralis , Estrongiloidíase , Humanos , Estrongiloidíase/diagnóstico , Estrongiloidíase/imunologia , Animais , Testes Sorológicos/métodos , Ensaio de Imunoadsorção Enzimática/métodos , Strongyloides stercoralis/imunologia , Strongyloides stercoralis/genética , Antígenos de Helmintos/genética , Antígenos de Helmintos/imunologia , Anticorpos Anti-Helmínticos/sangue , Proteínas Recombinantes de Fusão/imunologia , Proteínas Recombinantes de Fusão/genética , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Expressão Gênica
4.
Parasite Immunol ; 46(7): e13059, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39039790

RESUMO

Immunosuppressed patients, particularly transplant recipients, can develop severe strongyloidiasis. This study aimed to detect anti-Strongyloides IgG antibodies in a panel of sera from liver transplant patients. Two techniques were used: ELISA as the initial screening test and Western blotting as a confirmatory test. ELISA reactivity of 10.9% (32/294) was observed. The 40-30 kDa fraction was recognised in 93.7% (30/32) of the patients, resulting in a positivity rate of 10.2%. These data highlight the importance of serological screening for Strongyloides stercoralis infection in liver transplant recipients.


Assuntos
Anticorpos Anti-Helmínticos , Ensaio de Imunoadsorção Enzimática , Imunoglobulina G , Transplante de Fígado , Strongyloides stercoralis , Estrongiloidíase , Transplantados , Humanos , Estrongiloidíase/diagnóstico , Estrongiloidíase/imunologia , Estrongiloidíase/sangue , Anticorpos Anti-Helmínticos/sangue , Animais , Strongyloides stercoralis/imunologia , Imunoglobulina G/sangue , Western Blotting , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Feminino , Adulto , Doenças Negligenciadas/diagnóstico , Doenças Negligenciadas/epidemiologia , Doenças Negligenciadas/imunologia , Hospedeiro Imunocomprometido , Idoso
5.
J Infect Public Health ; 17(8): 102466, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38879920

RESUMO

COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can stimulate a systemic inflammatory response with severe lung involvement, multisystem dysfunction, and death in some cases. Immunosuppressive treatments have been proposed for management of COVID-19 patients, but these bring the risk of flare-up of pre-existing infections. Strongyloidiasis can become severe or fatal in immunocompromised individuals. This cross-sectional study determined the prevalence of anti-Strongyloides IgG antibody in sera collected from SARS-CoV-2 infected persons in a tertiary-care Thai hospital from January 2021 to January 2022. The survey was conducted using a rapid immunochromatographic test (ICT) kit based on a recombinant antigen of Strongyloides stercoralis known to be IgG-immunoreactive. High prevalence of anti-Strongyloides IgG antibody was found. Out of 297 SARS-CoV-2-infected patients 117 (39.4 %, 95 % CI 33.8-45.2 %) were positive for S. stercoralis according to the ICT kit. In areas where strongyloidiasis is endemic, we suggest using this point-of-care ICT kit for routine rapid screening in seriously ill COVID-19 patients who will be subjected to immunosuppressive treatment. Prompt anthelminthic treatment should be administered to prevent serious systemic strongyloidiasis in at-risk patients.


Assuntos
Anticorpos Anti-Helmínticos , COVID-19 , Imunoglobulina G , SARS-CoV-2 , Strongyloides stercoralis , Estrongiloidíase , Humanos , Tailândia/epidemiologia , Estudos Transversais , Estrongiloidíase/epidemiologia , Estrongiloidíase/diagnóstico , Estrongiloidíase/imunologia , COVID-19/epidemiologia , COVID-19/diagnóstico , COVID-19/imunologia , Masculino , Feminino , Strongyloides stercoralis/imunologia , Pessoa de Meia-Idade , Animais , Adulto , Imunoglobulina G/sangue , SARS-CoV-2/imunologia , Idoso , Anticorpos Anti-Helmínticos/sangue , Estudos Soroepidemiológicos , Prevalência , Adulto Jovem , Idoso de 80 Anos ou mais , População do Sudeste Asiático
7.
Am J Trop Med Hyg ; 106(2): 695-699, 2021 11 29.
Artigo em Inglês | MEDLINE | ID: mdl-34844210

RESUMO

Strongyloidiasis, a neglected tropical disease (NTD), which is caused by Strongyloides stercoralis, can be fatal in immunocompromised patients. In most chronic cases, infections most frequently are asymptomatic, and eosinophilia might be the only clinical characteristic of this disease. The use of corticosteroids in some diseases like chronic obstructive pulmonary disease (COPD) may lead to the development of the life-threatening S. stercoralis hyperinfection syndrome. In the present research, we presented five cases of strongyloidiasis with a history of COPD and receiving corticosteroids from Abadan County, southwestern Iran. By performing the direct smear stool examinations, two cases were identified and the other three cases were diagnosed using the agar plate culture method. Despite reporting eosinophilia in previous patients' hospitalizations, the fecal examination was not performed for parasitic infections. Moreover, pulmonary symptoms were similar, but gastrointestinal symptoms were varied, including nausea, vomiting, abdominal pain, epigastric pain, constipation, and diarrhea. All the included patients were treated with albendazole, which is the second-line drug for S. stercoralis, and relapse of infection was observed in two patients by passing few months from the treatment. The increased blood eosinophil count was shown to play important roles in both the management of COPD and diagnosis of helminthic infections. In COPD patients who are receiving steroids, screening and follow-up for strongyloidiasis should be considered as priorities. In addition, ivermectin, which is the first-line drug for strongyloidiasis, should be available in the region.


Assuntos
Albendazol/uso terapêutico , Anti-Helmínticos/uso terapêutico , Eosinofilia/parasitologia , Hospedeiro Imunocomprometido , Doença Pulmonar Obstrutiva Crônica/parasitologia , Strongyloides stercoralis/patogenicidade , Estrongiloidíase/parasitologia , Corticosteroides/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Animais , Eosinofilia/diagnóstico por imagem , Eosinofilia/tratamento farmacológico , Eosinofilia/imunologia , Feminino , Humanos , Irã (Geográfico) , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/diagnóstico por imagem , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/imunologia , Strongyloides stercoralis/efeitos dos fármacos , Strongyloides stercoralis/crescimento & desenvolvimento , Estrongiloidíase/diagnóstico por imagem , Estrongiloidíase/tratamento farmacológico , Estrongiloidíase/imunologia , Tomografia Computadorizada por Raios X
8.
Cell ; 184(23): 5715-5727.e12, 2021 11 11.
Artigo em Inglês | MEDLINE | ID: mdl-34717799

RESUMO

The enteric nervous system (ENS) controls several intestinal functions including motility and nutrient handling, which can be disrupted by infection-induced neuropathies or neuronal cell death. We investigated possible tolerance mechanisms preventing neuronal loss and disruption in gut motility after pathogen exposure. We found that following enteric infections, muscularis macrophages (MMs) acquire a tissue-protective phenotype that prevents neuronal loss, dysmotility, and maintains energy balance during subsequent challenge with unrelated pathogens. Bacteria-induced neuroprotection relied on activation of gut-projecting sympathetic neurons and signaling via ß2-adrenergic receptors (ß2AR) on MMs. In contrast, helminth-mediated neuroprotection was dependent on T cells and systemic production of interleukin (IL)-4 and IL-13 by eosinophils, which induced arginase-expressing MMs that prevented neuronal loss from an unrelated infection located in a different intestinal region. Collectively, these data suggest that distinct enteric pathogens trigger a state of disease or tissue tolerance that preserves ENS number and functionality.


Assuntos
Sistema Nervoso Entérico/microbiologia , Sistema Nervoso Entérico/parasitologia , Infecções/microbiologia , Infecções/parasitologia , Neurônios/patologia , Neuroproteção , Especificidade de Órgãos , Yersinia pseudotuberculosis/fisiologia , Animais , Eosinófilos/metabolismo , Células-Tronco Hematopoéticas/metabolismo , Imunidade , Infecções/imunologia , Interleucina-13/metabolismo , Interleucina-4/metabolismo , Macrófagos/metabolismo , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Strongyloides/fisiologia , Estrongiloidíase/genética , Estrongiloidíase/imunologia , Estrongiloidíase/parasitologia , Transcriptoma/genética , Infecções por Yersinia pseudotuberculosis/genética , Infecções por Yersinia pseudotuberculosis/imunologia , Infecções por Yersinia pseudotuberculosis/microbiologia
9.
Front Immunol ; 12: 715766, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34475874

RESUMO

Parasitic nematodes such as hookworms actively penetrate the skin of their hosts, encountering skin-resident innate immune cells that represent the host´s first line of defense. Here we use Strongyloides ratti as a model for an intestinal helminth parasite with tissue migrating stages. We show that interception and killing of migrating larvae in mice during a 1st infection occurred predominantly in skin and muscle tissue before larvae migrated via lung and head tissue to the intestine. Inhibition of larval migration was even more efficient in immune mice during a 2nd infection where larvae barely left the site of entry i.e. the foot. Using cell-deficient mice we show that interception in the tissue was predominantly mediated by neutrophils and eosinophils while basophils and mast cells were dispensable in vivo. Likewise, neutrophils and eosinophils inhibited S. ratti L3 motility in vitro in the context of ETosis. Thereby eosinophils were strictly dependent on the presence of anti-S. ratti antibodies while neutrophils inhibited L3 motility as such. Also, MPO and MMP-9 were released by neutrophils in response to L3 alone, but immune plasma further stimulated MPO release in an antibody-dependent manner. In summary, our findings highlight the central role of the skin as first line of defense against helminth parasites in both, innate and adaptive immunity.


Assuntos
Eosinófilos/imunologia , Armadilhas Extracelulares/imunologia , Interações Hospedeiro-Parasita/imunologia , Neutrófilos/imunologia , Strongyloides ratti/imunologia , Estrongiloidíase/imunologia , Estrongiloidíase/parasitologia , Animais , Degranulação Celular/imunologia , Citotoxicidade Imunológica , Modelos Animais de Doenças , Suscetibilidade a Doenças , Armadilhas Extracelulares/parasitologia , Imunidade Inata , Larva/imunologia , Camundongos , Estrongiloidíase/metabolismo
10.
Immunobiology ; 226(5): 152129, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34433129

RESUMO

Inflammatory bowel diseases (IBD) are chronic health problems of difficult management and treatment. Epidemiological studies indicate an inverse association between helminth infections and IBD, and experimental data confirm that helminth infections modulate the severity of experimental acute colitis in mice. However, the effects of helminth infections on chronic colitis, which is clinically more relevant, have been poorly explored. Herein, we investigated whether Strongyloides venezuelensis infection in BALB/c mice can ameliorate chronic colitis induced by the ingestion of water containing 2.5% Dextran Sodium Sulfate (DSS) over three seven-day treatment cycles, with an interval of fourteen days between cycles. Infected-only, DSS-exposed-only, and non-exposed/uninfected experimental groups served as controls for comparing the severity of colitis and intestinal inflammation among different groups. Our data showed that S. venezuelensis infection in mice with DSS-induced chronic colitis reduced clinical signs, attenuated colon shortening and inflammation, and prevented mucus ablation. The modulatory effect was accompanied by a low concentration of IFN-γ, high concentrations of TGF-ß, IL-22, and IL-33 in the colon, and a significant increase of the percentage of CD4+CD25+Foxp3+ Treg cells in the mesenteric lymph node (MLN). In conclusion, S. venezuelensis infection can reduce the severity of DSS-induced chronic colitis in mice possibly through the stimulation of Treg cells and modulatory cytokines, and induction of mucosal repair mechanisms.


Assuntos
Colite , Strongyloides , Estrongiloidíase , Animais , Doença Crônica , Colite/induzido quimicamente , Colite/imunologia , Colite/parasitologia , Colite/patologia , Colo/imunologia , Colo/patologia , Citocinas/imunologia , Sulfato de Dextrana , Ingestão de Alimentos , Feminino , Camundongos Endogâmicos BALB C , Estrongiloidíase/imunologia , Estrongiloidíase/patologia , Linfócitos T Reguladores/imunologia
11.
Am J Trop Med Hyg ; 105(5): 1214-1217, 2021 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-34460427

RESUMO

A lateral flow rapid test for strongyloidiasis will greatly facilitate the control and elimination of the disease. Previously SsRapid prototype rapid test showed high diagnostic specificity to detect Strongyloides infection, determined using non-Strongyloides sera negative by IgG-ELISAs. Since high specificity is crucial before a test is used for public health control activities, further validation of its specificity is needed. Also, it needs to be ascertained whether non-Strongyloides sera positive by IgG-ELISAs and SsRapid are truly positive for Strongyloides or are cases of cross-reactivity. We performed 84 rapid tests (two types of dipsticks and cassettes) using 34 serum samples. They were divided into four groups based on Strongyloides infection and coinfection with other parasites and the availability of recombinant proteins and rapid tests for the latter. Sera was adsorbed using polystyrene microspheres beads separately coated with four recombinant parasite proteins. The small sample size is a limitation of this study; however, the overall results showed that the sera adsorption procedure was successful, and the SsRapid test is specific.


Assuntos
Adsorção , Anticorpos Anti-Helmínticos/sangue , Anticorpos Anti-Helmínticos/imunologia , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Estrongiloidíase/sangue , Estrongiloidíase/imunologia , Animais , Humanos , Malásia , Sensibilidade e Especificidade , Testes Sorológicos , Strongyloides stercoralis/isolamento & purificação
12.
Parasit Vectors ; 14(1): 412, 2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34407876

RESUMO

BACKGROUND: The diagnosis of strongyloidiasis is challenging. Serological tests are acknowledged to have high sensitivity, but issues due to cross-reactions with other parasites, native parasite antigen supply and intrinsic test variability do occur. Assays based on recombinant antigens could represent an improvement. The aim of this study was to assess the sensitivity and specificity of two novel immunoglobulin (Ig)G and IgG4 enzyme-linked immunosorbent assays (ELISAs) based on the recombinant antigens NIE/SsIR for the diagnosis of strongyloidiasis. METHODS: This was a retrospective diagnostic accuracy study. We included serum samples collected from immigrants from strongyloidiasis endemic areas for whom there was a matched result for Strongyloides stercoralis on agar plate culture and/or PCR assay, or a positive microscopy for S. stercoralis larvae. For the included samples, results were also available from an in-house indirect fluorescent antibody test (IFAT) and a commercial (Bordier ELISA; Bordier Affinity Products SA) ELISA. We excluded: (i) samples with insufficient serum volume; (ii) samples from patients treated with ivermectin in the previous 6 months; and (iii) sera from patients for whom only routine coproparasitology was performed after formol-ether concentration, if negative for S. stercoralis larvae. The performance of the novel assays was assessed against: (i) a primary reference standard, with samples classified as negative/positive on the basis of the results of fecal tests; (ii) a composite reference standard (CRS), which also considered patients to be positive who had concordant positive results for the IFAT and Bordier ELISA or with a single "high titer" positive result for the IFAT or Bordier ELISA. Samples with a single positive test, either for the IFAT or Bordier ELISA, at low titer, were considered to be "indeterminate," and analyses were carried out with and without their inclusion. RESULTS: When assessed against the primary reference standard, the sensitivities of the IgG and IgG4 ELISAs were 92% (95% confidence interval [CI]: 88-97%) and 81% (95% CI: 74-87%), respectively, and the specificities were 91% (95% CI: 88-95%) and 94% (95% CI: 91-97%), respectively. When tested against the CRS, the IgG ELISA performed best, with 78% sensitivity (95% CI: 72-83%) and 98% specificity (95% CI: 96-100%), when a cut-off of 0.675 was applied and the indeterminate samples were excluded from the analysis. CONCLUSION: The NIE-SsIR IgG ELISA demonstrated better accuracy than the IgG4 assay and was deemed promising particularly for serosurveys in endemic areas.


Assuntos
Anticorpos Anti-Helmínticos/sangue , Antígenos de Helmintos/genética , Ensaio de Imunoadsorção Enzimática/métodos , Ensaio de Imunoadsorção Enzimática/normas , Imunoglobulina G/sangue , Strongyloides stercoralis/imunologia , Estrongiloidíase/diagnóstico , Animais , Antígenos de Helmintos/imunologia , Pré-Escolar , Reações Cruzadas , Humanos , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Padrões de Referência , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Estrongiloidíase/sangue , Estrongiloidíase/imunologia
13.
PLoS Negl Trop Dis ; 15(7): e0009559, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34314415

RESUMO

Viral and parasitic coinfections are known to lead to both enhanced disease progression and altered disease states. HTLV-1 and Strongyloides stercoralis are co-endemic throughout much of their worldwide ranges resulting in a significant incidence of coinfection. Independently, HTLV-1 induces a Th1 response and S. stercoralis infection induces a Th2 response. However, coinfection with the two pathogens has been associated with the development of S. stercoralis hyperinfection and an alteration of the Th1/Th2 balance. In this study, a model of HTLV-1 and S. stercoralis coinfection in CD34+ umbilical cord blood hematopoietic stem cell engrafted humanized mice was established. An increased level of mortality was observed in the HTLV-1 and coinfected animals when compared to the S. stercoralis infected group. The mortality was not correlated with proviral loads or total viral RNA. Analysis of cytokine profiles showed a distinct shift towards Th1 responses in HTLV-1 infected animals, a shift towards Th2 cytokines in S. stercoralis infected animals and elevated TNF-α responses in coinfected animals. HTLV-1 infected and coinfection groups showed a significant, yet non-clonal expansion of the CD4+CD25+ T-cell population. Numbers of worms in the coinfection group did not differ from those of the S. stercoralis infected group and no autoinfective larvae were found. However, infective larvae recovered from the coinfection group showed an enhancement in growth, as was seen in mice with S. stercoralis hyperinfection caused by treatment with steroids. Humanized mice coinfected with S. stercoralis and HTLV-1 demonstrate features associated with human infection with these pathogens and provide a unique opportunity to study the interaction between these two infections in vivo in the context of human immune cells.


Assuntos
Antígenos CD34/sangue , Citocinas/metabolismo , Infecções por HTLV-I/imunologia , Células-Tronco Hematopoéticas/metabolismo , Strongyloides stercoralis/crescimento & desenvolvimento , Estrongiloidíase/imunologia , Animais , Linhagem Celular , Coinfecção , Citocinas/genética , Sangue Fetal , Infecções por HTLV-I/complicações , Vírus Linfotrópico T Tipo 1 Humano , Larva/crescimento & desenvolvimento , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Estrongiloidíase/complicações
14.
PLoS Pathog ; 17(7): e1009709, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34237106

RESUMO

Helminths are distinct from microbial pathogens in both size and complexity, and are the likely evolutionary driving force for type 2 immunity. CD4+ helper T cells can both coordinate worm clearance and prevent immunopathology, but issues of T cell antigen specificity in the context of helminth-induced Th2 and T regulatory cell (Treg) responses have not been addressed. Herein, we generated a novel transgenic line of the gastrointestinal nematode Strongyloides ratti expressing the immunodominant CD4+ T cell epitope 2W1S as a fusion protein with green fluorescent protein (GFP) and FLAG peptide in order to track and study helminth-specific CD4+ T cells. C57BL/6 mice infected with this stable transgenic line (termed Hulk) underwent a dose-dependent expansion of activated CD44hiCD11ahi 2W1S-specific CD4+ T cells, preferentially in the lung parenchyma. Transcriptional profiling of 2W1S-specific CD4+ T cells isolated from mice infected with either Hulk or the enteric bacterial pathogen Salmonella expressing 2W1S revealed that pathogen context exerted a dominant influence over CD4+ T cell phenotype. Interestingly, Hulk-elicited 2W1S-specific CD4+ T cells exhibited both Th2 and Treg phenotypes and expressed high levels of the EGFR ligand amphiregulin, which differed greatly from the phenotype of 2W1S-specific CD4+ T cells elicited by 2W1S-expressing Salmonella. While immunization with 2W1S peptide did not enhance clearance of Hulk infection, immunization did increase total amphiregulin production as well as the number of amphiregulin-expressing CD3+ cells in the lung following Hulk infection. Altogether, this new model system elucidates effector as well as immunosuppressive and wound reparative roles of helminth-specific CD4+ T cells. This report establishes a new resource for studying the nature and function of helminth-specific T cells.


Assuntos
Epitopos de Linfócito T/genética , Estrongiloidíase/imunologia , Linfócitos T Reguladores/imunologia , Células Th2/imunologia , Animais , Animais Geneticamente Modificados , Antígenos de Helmintos , Linfócitos T CD4-Positivos/imunologia , Modelos Animais de Doenças , Epitopos de Linfócito T/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Strongyloides ratti/imunologia
15.
Am J Trop Med Hyg ; 105(3): 564-572, 2021 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-34181579

RESUMO

Reports on tropical infections among kidney transplant (KT) recipients have increased in recent years, mainly because of the growing number of KT programs located in tropical and subtropical areas, and greater mobility or migration between different areas of the world. Endemic in emerging and developing regions, like most countries in Latin America, tropical infections are an important cause of morbidity and mortality in this population. Tropical infections in KT recipients may exhibit different pathways for acquisition compared with those in nonrecipients, such as transmission through a graft and reactivation of a latent infection triggered by immunosuppression. Clinical presentation may differ compared with that in immunocompetent patients, and there are also particularities in diagnostic aspects, treatment, and prognosis. KT patients must be screened for latent infections and immunized properly. Last, drug-drug interactions between immunosuppressive agents and drugs used to treat tropical infections are an additional challenge in KT patients. In this review, we summarize the management of tropical infections in KT patients.


Assuntos
Infecções por Arbovirus/diagnóstico , Doença de Chagas/diagnóstico , Transplante de Rim , Leishmaniose/diagnóstico , Estrongiloidíase/diagnóstico , Tuberculose/diagnóstico , Infecções por Arbovirus/imunologia , Infecções por Arbovirus/terapia , Doença de Chagas/imunologia , Doença de Chagas/terapia , Febre de Chikungunya/diagnóstico , Febre de Chikungunya/imunologia , Febre de Chikungunya/terapia , Dengue/diagnóstico , Dengue/imunologia , Dengue/terapia , Rejeição de Enxerto/prevenção & controle , Humanos , Hospedeiro Imunocomprometido , Imunossupressores/uso terapêutico , América Latina , Leishmaniose/imunologia , Leishmaniose/terapia , Estrongiloidíase/imunologia , Estrongiloidíase/terapia , Tuberculose/imunologia , Tuberculose/terapia , Febre Amarela/diagnóstico , Febre Amarela/imunologia , Febre Amarela/terapia , Infecção por Zika virus/diagnóstico , Infecção por Zika virus/imunologia , Infecção por Zika virus/terapia
16.
Am J Trop Med Hyg ; 104(6): 2038-2041, 2021 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-33872212

RESUMO

Strongyloides stercoralis is a soil-transmitted nematode that can cause life-threatening conditions in immunocompromised persons. In the United States, strongyloidiasis should be considered mainly in immigrants, refugees, or travelers. The confirmatory laboratory diagnosis is usually performed by detecting larvae from the stool, duodenal material, and sputum. In persons who are immunocompromised with severe strongyloidiasis, adult worms and eggs can be detected from duodenal material. For serological diagnosis, most assays use crude antigens to detect anti-S. stercoralis IgG. Recently, recombinant proteins such as rSs-NIE-1 and rSs-IR have been used to detect IgG antibodies. We used rSs-NIE-1 and rSs-IR recombinant antigens to develop a biplex Western blot assay to detect the IgG4 antibody in individuals with strongyloidiasis. The sensitivities of rSs-NIE-1 and rSs-IR were 97.4% and 90.8%, respectively, whereas the specificities were 97.6% and 98%, respectively. In conclusion, the biplex rSs-NIE-1 and rSs-IR immunoblot performs well in detecting IgG4 antibody in S. stercoralis-infected persons.


Assuntos
Anticorpos Anti-Helmínticos/sangue , Antígenos de Helmintos/imunologia , Immunoblotting/métodos , Strongyloides stercoralis/imunologia , Estrongiloidíase/diagnóstico , Animais , Antígenos de Helmintos/genética , Fezes/parasitologia , Humanos , Immunoblotting/normas , Imunoglobulina G/sangue , Larva/imunologia , Proteínas Recombinantes/imunologia , Sensibilidade e Especificidade , Strongyloides stercoralis/química , Estrongiloidíase/imunologia
17.
Biochem Biophys Res Commun ; 555: 168-174, 2021 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-33819747

RESUMO

When animals are infected with helminthic parasites, resistant hosts mount type II helper T (Th2) immune responses to expel worms. Recent studies have clearly shown that epithelial cell-derived cytokines contribute to the induction of Th2 immune responses. Here we demonstrate the role of endogenous thymic stromal lymphopoietin (TSLP) for protection against Strongyloides venezuelensis (S. venezuelensis) infection, utilizing TSLP receptor-deficient Crlf2-/- mice. The number of eggs per gram of feces (EPG) and worm burden were significantly higher in Crlf2-/- mice than in wild type (WT) mice. S. venezuelensis infection induced Tslp mRNA expression in the skin, lung, and intestine and also facilitated the accumulation of mast cells in the intestine in a TSLP-dependent manner. Furthermore, CD4+ T cells from S. venezuelensis-infected Crlf2-/- mice showed diminished capacity to produce Th2 cytokines in the early stage of infection. Finally, CD4+ cell-depleted Crlf2-/- mice still showed higher EPG counts and worm burden than CD4+ cell-depleted WT mice, indicating that TSLP contributes to protecting mice against S. venezuelensis infection in both CD4+ T cell-dependent and -independent manners.


Assuntos
Linfócitos T CD4-Positivos/parasitologia , Citocinas/fisiologia , Estrongiloidíase/imunologia , Animais , Linfócitos T CD4-Positivos/imunologia , Resistência à Doença/fisiologia , Fezes/parasitologia , Interações Hospedeiro-Parasita , Imunoglobulina E/sangue , Imunoglobulinas/genética , Intestinos/parasitologia , Masculino , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Mutantes , Receptores de Citocinas/genética , Estrongiloidíase/parasitologia , Linfopoietina do Estroma do Timo
18.
Sci Rep ; 11(1): 1536, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-33452272

RESUMO

Helminths are large multicellular parasites that infect one quarter of the human population. To prolong their survival, helminths suppress the immune responses of their hosts. Strongyloides ratti delays its expulsion from the gut by induction of regulatory circuits in a mouse strain-specific manner: depletion of Foxp3+ regulatory T cells (Treg) improves the anti-S. ratti immunity in BALB/c but not in C57BL/6 mice. In the current study we compare the hierarchy of immunoregulatory pathways in BALB/c, C57BL/6 mice and their F1 progeny (BALB/c × C57BL/6). Using multicolor flow cytometry, we show that S. ratti induces a distinct pattern of inhibitory checkpoint receptors by Foxp3+ Treg and Foxp3- T cells. Intensity of expression was highest in C57BL/6 and lowest in BALB/c mice, while the F1 cross had an intermediate phenotype or resembled BALB/c mice. Treg subsets expanded during infection in all three mouse strains. Similar to BALB/c mice, depletion of Treg reduced intestinal parasite burden and increased mucosal mast cell activation in S. ratti-infected F1 mice. Our data indicate that Treg dominate the regulation of immune responses in BALB/c and F1 mice, while multiple regulatory layers exist in C57BL/6 mice that may compensate for the absence of Treg.


Assuntos
Estrongiloidíase/imunologia , Linfócitos T Reguladores/imunologia , Animais , Feminino , Citometria de Fluxo/métodos , Fatores de Transcrição Forkhead/imunologia , Fatores de Transcrição Forkhead/metabolismo , Imunidade , Masculino , Mastócitos/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Fenótipo , Strongyloides ratti/patogenicidade , Estrongiloidíase/parasitologia , Estrongiloidíase/veterinária , Linfócitos T Reguladores/metabolismo , Células Th2/imunologia
20.
Parasite Immunol ; 43(1): e12793, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32969488

RESUMO

AIMS: To describe an anti-Strongyloides IgA, IgG and IgG immune complex antibody response profile in patients with pulmonary tuberculosis. METHODS AND RESULTS: Saliva and serum samples were collected from 100 individuals: group I, 50 apparently healthy individuals; and group II, 50 pulmonary tuberculosis patients. The IgA, IgG and IgG immune complex detection were carried out via an ELISA immunoenzymatic test. Optical density medians in saliva samples of IgA antibody (median of 7.21) and IgG-IC (median of 4.95) were significantly higher in tuberculosis group compared to control individuals (median IgA of 3.93 and IgG-IC of 2.38). CONCLUSION: This study presents antibody data to the field of pulmonary tuberculosis and strongyloidiasis coinfection, including saliva samples, and especially IgG immune complex detection.


Assuntos
Anticorpos Antiprotozoários/sangue , Complexo Antígeno-Anticorpo/sangue , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Strongyloides/imunologia , Adulto , Animais , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Larva/imunologia , Masculino , Pessoa de Meia-Idade , Saliva/imunologia , Estrongiloidíase/imunologia , Estrongiloidíase/patologia , Tuberculose Pulmonar/patologia
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