Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.679
Filtrar
2.
Cell Host Microbe ; 30(2): 154-162.e5, 2022 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-35120605

RESUMO

Characterizing SARS-CoV-2 evolution in specific geographies may help predict properties of the variants that come from these regions. We mapped neutralization of a SARS-CoV-2 strain that evolved over 6 months from ancestral virus in a person with advanced HIV disease in South Africa; this person was infected prior to emergence of the Beta and Delta variants. We longitudinally tracked the evolved virus and tested it against self-plasma and convalescent plasma from ancestral, Beta, and Delta infections. Early virus was similar to ancestral, but it evolved a multitude of mutations found in Omicron and other variants. It showed substantial but incomplete Pfizer BNT162b2 escape, weak neutralization by self-plasma, and despite pre-dating Delta, it also showed extensive escape of Delta infection-elicited neutralization. This example is consistent with the notion that SARS-CoV-2 evolving in individual immune-compromised hosts, including those with advanced HIV disease, may gain immune escape of vaccines and enhanced escape of Delta immunity, and this has implications for vaccine breakthrough and reinfections.


Assuntos
Anticorpos Neutralizantes/sangue , Infecções por HIV/patologia , Evasão da Resposta Imune/imunologia , Imunogenicidade da Vacina/imunologia , SARS-CoV-2/imunologia , Adulto , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , COVID-19/imunologia , Vacinas contra COVID-19/imunologia , Linhagem Celular , Chlorocebus aethiops , Feminino , HIV-1/imunologia , Humanos , Hospedeiro Imunocomprometido/imunologia , Testes de Neutralização , SARS-CoV-2/isolamento & purificação , África do Sul , Vacinação , Células Vero
3.
Mol Med ; 28(1): 20, 2022 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-35135470

RESUMO

Adaptive immune responses have been studied extensively in the course of mRNA vaccination against COVID-19. Considerably fewer studies have assessed the effects on innate immune cells. Here, we characterized NK cells in healthy individuals and immunocompromised patients in the course of an anti-SARS-CoV-2 BNT162b2 mRNA prospective, open-label clinical vaccine trial. See trial registration description in notes. Results revealed preserved NK cell numbers, frequencies, subsets, phenotypes, and function as assessed through consecutive peripheral blood samplings at 0, 10, 21, and 35 days following vaccination. A positive correlation was observed between the frequency of NKG2C+ NK cells at baseline (Day 0) and anti-SARS-CoV-2 Ab titers following BNT162b2 mRNA vaccination at Day 35. The present results provide basic insights in regards to NK cells in the context of mRNA vaccination, and have relevance for future mRNA-based vaccinations against COVID-19, other viral infections, and cancer.Trial registration: The current study is based on clinical material from the COVAXID open-label, non-randomized prospective clinical trial registered at EudraCT and clinicaltrials.gov (no. 2021-000175-37). Description: https://clinicaltrials.gov/ct2/show/NCT04780659?term=2021-000175-37&draw=2&rank=1 .


Assuntos
/imunologia , Vacinas contra COVID-19/imunologia , COVID-19/imunologia , Hospedeiro Imunocomprometido/imunologia , Células Matadoras Naturais/imunologia , SARS-CoV-2/imunologia , Adolescente , Adulto , Anticorpos Antivirais/imunologia , COVID-19/epidemiologia , COVID-19/virologia , Vacinas contra COVID-19/administração & dosagem , Feminino , Citometria de Fluxo , Humanos , Células Matadoras Naturais/metabolismo , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Subfamília C de Receptores Semelhantes a Lectina de Células NK/imunologia , Subfamília C de Receptores Semelhantes a Lectina de Células NK/metabolismo , Avaliação de Resultados em Cuidados de Saúde/métodos , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Pandemias/prevenção & controle , SARS-CoV-2/fisiologia , Vacinação/métodos , Vacinação/estatística & dados numéricos , Adulto Jovem
4.
Life Sci Alliance ; 5(6)2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35169017

RESUMO

SARS-CoV-2 vaccination has proven effective in inducing an immune response in healthy individuals and is progressively us allowing to overcome the pandemic. Recent evidence has shown that response to vaccination in some vulnerable patients may be diminished, and it has been proposed a booster dose. We tested the kinetic of development of serum antibodies to the SARS-CoV-2 Spike protein, their neutralizing capacity, the CD4 and CD8 IFN-γ T-cell response in 328 subjects, including 131 immunocompromised individuals (cancer, rheumatologic, and hemodialysis patients), 160 health-care workers (HCW) and 37 subjects older than 75 yr, after vaccination with two or three doses of mRNA vaccines. We stratified the patients according to the type of treatment. We found that immunocompromised patients, depending on the type of treatment, poorly respond to SARS-CoV-2 mRNA vaccines. However, an additional booster dose of vaccine induced a good immune response in almost all of the patients except those receiving anti-CD20 antibody. Similarly to HCW, previously infected and vaccinated immunocompromised individuals demonstrate a stronger SARS-CoV-2-specific immune response than those who are vaccinated without prior infection.


Assuntos
Vacinas contra COVID-19/imunologia , Hospedeiro Imunocomprometido/imunologia , Linfócitos T/imunologia , /imunologia , Idoso , Anticorpos Neutralizantes/imunologia , Linfócitos B/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , COVID-19/imunologia , Humanos , Imunização Secundária , Pessoa de Meia-Idade , Neoplasias/imunologia , Diálise Renal
5.
J Immunol ; 208(3): 660-671, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-35022276

RESUMO

Invasive candidiasis has high mortality rates in immunocompromised patients, causing serious health problems. In mouse models, innate immunity protects the host by rapidly mobilizing a variety of resistance and tolerance mechanisms to systemic Candida albicans infection. We have previously demonstrated that exogenous IL-33 regulates multiple steps of innate immunity involving resistance and tolerance processes. In this study, we systematically analyzed the in vivo functions of endogenous IL-33 using Il33 -/- mice and in vitro immune cell culture. Tubular epithelial cells mainly secreted IL-33 in response to systemic C. albicans infection. Il33 -/- mice showed increased mortality and morbidity, which were due to impaired fungal clearance. IL-33 initiated an innate defense mechanism by costimulating dendritic cells to produce IL-23 after systemic C. albicans infection, which in turn promoted the phagocytosis of neutrophils through secretion of GM-CSF by NK cells. The susceptibility of Il33 -/- mice was also associated with increased levels of IL-10, and neutralization of IL-10 resulted in enhanced fungal clearance in Il33 -/- mice. However, depletion of IL-10 overrode the effect of IL-33 on fungal clearance. In Il10 -/- mouse kidneys, MHC class II+F4/80+ macrophages were massively differentiated after C. albicans infection, and these cells were superior to MHC class II-F4/80+ macrophages that were preferentially differentiated in wild-type mouse kidneys in killing of extracellular hyphal C. albicans Taken together, our results identify IL-33 as critical early regulator controlling a serial downstream signaling events of innate defense to C. albicans infection.


Assuntos
Candida albicans/imunologia , Candidíase/imunologia , Imunidade Inata/imunologia , Interleucina-10/metabolismo , Subunidade p19 da Interleucina-23/metabolismo , Interleucina-33/imunologia , Animais , Candidíase/microbiologia , Células Dendríticas/imunologia , Modelos Animais de Doenças , Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Antígenos de Histocompatibilidade Classe II/imunologia , Hospedeiro Imunocomprometido/imunologia , Interleucina-10/genética , Interleucina-33/genética , Células Matadoras Naturais/imunologia , Macrófagos/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neutrófilos/imunologia , Fagocitose/imunologia , Transdução de Sinais/imunologia
6.
PLoS Med ; 19(1): e1003917, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-35089920

RESUMO

Ivan Gentile and Nicola Schiano Moriello discuss the potential of monoclonal antibody prophylaxis against COVID-19 infection in immunocompromised patients.


Assuntos
Anticorpos Monoclonais/administração & dosagem , COVID-19/imunologia , COVID-19/prevenção & controle , Hospedeiro Imunocomprometido/imunologia , Profilaxia Pré-Exposição/métodos , Vacinação/métodos , Anticorpos Antivirais/administração & dosagem , Humanos , Vacinação/tendências
7.
Clin Transl Med ; 12(1): e581, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-35075795

RESUMO

Tumor-associated macrophages (TAMs) support tumor progression within the tumor microenvironment (TME). Many questions remain as to the origin, development, and function of TAMs within the prostate TME. Evaluation of TAMs in prostate cancer (PCa) patients identified the immunosuppressive TAM marker CD163 in adjacent normal epithelium as an independent predictor of metastases or PCa death. Flow cytometry analyses identified prostate TAMs as frequently expressing both proinflammatory M1 (CCR7+) and immunosuppressive M2 (CD163+) markers. In vitro, we demonstrate PCa cells similarly subvert human M1 macrophages toward a mixed M1/M2 macrophage phenotype favoring tumor growth. Further the cytokine milieu-induced transition between immunosuppressive M2 to proinflammatory M1 (M2→M1) macrophages is abrogated by the presence of PCa cells. RNA sequencing suggests alterations in chemokine expression in prostate TAMs due to the presence of PCa cells. Together, our results suggest that prostate TAMs originate from inflammatory infiltrating macrophages, which are then reprogrammed mainly by PCa cells, but also the cytokine milieu. A better understanding of this subversion of macrophages within the prostate may lead to novel treatment strategies.


Assuntos
Hospedeiro Imunocomprometido/imunologia , Macrófagos/citologia , Próstata/citologia , Adulto , Idoso , Humanos , Macrófagos/imunologia , Macrófagos/metabolismo , Masculino , Pessoa de Meia-Idade , Fenótipo , Próstata/microbiologia , Quebeque
8.
J Hepatol ; 76(1): 148-159, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34689996

RESUMO

BACKGROUND & AIMS: Regulatory T cell (Treg) depletion increases antitumor immunity. However, severe autoimmunity can occur following systemic loss of Tregs, which could be avoided by selectively depleting intratumoral Tregs. Herein, we aimed to investigate the role of tumor-infiltrating CCR4+ Tregs in hepatocellular carcinoma (HCC) and to provide a potential target strategy for immunotherapy. METHODS: CCR4+ Tregs were analyzed by flow cytometry in murine models and clinical samples. The function of tumor-infiltrating and induced CCR4+ Tregs was interrogated by genetic and epigenetic approaches. To block CCR4+ Treg chemotaxis, we developed an N-terminus recombinant protein of CCR4 (N-CCR4-Fc) as a neutralizing pseudo-receptor that effectively bound to its ligand CCL22. The efficacy of CCR4 antagonism as an immunotherapeutic agent was evaluated by tumor weights, growth kinetics and survival curves. RESULTS: CCR4+ Tregs were the predominant type of Tregs recruited to hepatitis B-associated HCC (HBV+ HCC), correlating with sorafenib resistance and HBV load titers. Compared with CCR4- Tregs, CCR4+ Tregs exhibited increased IL-10 and IL-35 expression, and enhanced functionality in suppressing CD8+ T cells. CCR4+ Tregs also displayed PD-1+TCF1+ stem-like properties. ATAC-seq data revealed substantial chromatin remodeling between tumor-infiltrating Tregs (TIL-Tregs) and induced Tregs, suggesting that long-term chromatin reprogramming accounted for the acquisition of enhanced immunosuppressive stem-like specificity by CCR4+ TIL-Tregs. Treatment with a CCR4 antagonist or N-CCR4-Fc blocked intratumoral Treg accumulation, overcame sorafenib resistance, and sensitized tumors to PD-1 checkpoint blockade. CONCLUSIONS: Intratumoral stem-like CCR4+ Tregs orchestrated immunosuppressive resource cells in the tumor microenvironment. CCR4 could be targeted to enhance antitumor immunity by specifically blocking infiltration of Tregs into the tumor microenvironment and inhibiting maintenance of the TIL-Treg pool. LAY SUMMARY: Targeting regulatory T cells is a promising approach in cancer immunotherapy; however, severe autoimmunity can occur following systemic regulatory T cell loss. This could be avoided by selectively depleting intratumoral regulatory T cells. Herein, targeting intratumoral stem-like CCR4+ regulatory T cells helped to overcome sorafenib resistance and sensitize tumors to immune checkpoint blockade in mouse models of liver cancer. This approach could have wide clinical applicability.


Assuntos
Carcinoma Hepatocelular/etiologia , Hepatite B/complicações , Hospedeiro Imunocomprometido/efeitos dos fármacos , Receptores CCR4/metabolismo , Linfócitos T Reguladores/metabolismo , Animais , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/imunologia , China , Modelos Animais de Doenças , Hepatite B/imunologia , Vírus da Hepatite B/efeitos dos fármacos , Vírus da Hepatite B/patogenicidade , Hospedeiro Imunocomprometido/genética , Hospedeiro Imunocomprometido/imunologia , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/imunologia , Camundongos , Receptores CCR4/imunologia , Linfócitos T Reguladores/imunologia
10.
Cell Immunol ; 371: 104455, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34864514

RESUMO

Cytomegalovirus (CMV) viral load after liver transplantation (LT) is controlled by cell mediated immune responses (CMI). Quantification of CMV-specific T-cells may identify patients who control CMV spontaneously and avoid expensive and potentially toxic antiviral therapies. Prospective post-LT clinical, virological and immunological monitoring was carried out up to 1-year post-LT in a cohort of adult recipients. The CMV-specific T-cell response was characterized using flow cytometry intracellular cytokine staining in 49 LT recipients-R (79.6% R+, 20.4% R-). CMV infection occurred in 24 patients (18 D+/R+ and 6 D+/R-). Only patients with undetectable polyfunctional CMV-specific CD4+ T-cells developed CMV infection. Predictive models showed that polyfunctional CMV-specific CD4+ T-cells pre-existing before LT are protective for CMV reactivation posttransplantation. Quantitation of CD4+ T-cell responses to CMV may be a useful marker for spontaneous control of viral replication to tailor antiviral prophylaxis after LT.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Citomegalovirus/imunologia , Imunidade Celular/imunologia , Transplante de Fígado/efeitos adversos , Infecções por Citomegalovirus/imunologia , Feminino , Humanos , Hospedeiro Imunocomprometido/imunologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Carga Viral , Ativação Viral/imunologia , Replicação Viral/imunologia
11.
Scand J Immunol ; 95(2): e13118, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34768311

RESUMO

Children with rheumatic disease and compromised immune system have an increased risk of infection. Streptococcus pneumoniae is a frequent pathogen, and immunization is recommended. In this study, we investigated whether immunocompromised children with rheumatic disease do respond to pneumococcal immunization with 13-valent pneumococcal conjugate vaccine followed by 23-valent pneumococcal polysaccharide vaccine. The study was conducted at two tertiary referral hospitals in Denmark from 2015 to 2018. Patients with rheumatic disease and compromised immune system aged 2-19 years were eligible. Patients were vaccinated with 13-valent pneumococcal conjugate vaccine followed by 23-valent pneumococcal polysaccharide vaccine. A blood sample was collected before vaccination and after each vaccination. IgG antibodies were quantified for twelve serotypes. Seroprotection for each serotype was defined as IgG ≥0.35 µg/mL. A total of 27 patients were enrolled. After the conjugate vaccine, an increase in antibody titres compared with pre-vaccination was found for all serotypes and 9/12 were significant. After the polysaccharide vaccine, the antibody titres for all serotypes but one was seen to increase but none reached significance. The proportion of patients protected before immunization ranged from 20.8% to 100% for the individual serotypes. Odds ratio for achieving seroprotection after the conjugate vaccine was >1 for 10/12 serotypes but only significant for three serotypes. After the polysaccharide vaccine, the odds ratio was >1 for 9/12 serotypes but none reached significance. In conclusion, children with rheumatic disease and compromised immune system respond to pneumococcal immunization with 13-valent pneumococcal conjugate vaccine and maintain antibody levels upon subsequent immunization with 23-valent pneumococcal polysaccharide vaccine.


Assuntos
Anticorpos Antibacterianos/sangue , Hospedeiro Imunocomprometido/imunologia , Vacinas Pneumocócicas/imunologia , Doenças Reumáticas/imunologia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Imunização Secundária , Imunoglobulina G/sangue , Masculino , Infecções Pneumocócicas/imunologia , Infecções Pneumocócicas/prevenção & controle , Streptococcus pneumoniae/imunologia , Vacinação , Adulto Jovem
14.
J Med Virol ; 94(1): 417-423, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34581458

RESUMO

A 36-year-old male with diffuse large B-cell lymphoma on maintenance rituximab therapy presented to the emergency department with high fever and fatigue. A chest X-ray showed a lobar infiltrate, 40 days before admission the patient suffered from a mild coronavirus disease 2019 (COVID-19) infection and fully recovered. PCR nasopharyngeal swab was negative for COVID-19. Comprehensive biochemical, radiological, and pathological evaluation including 18-fluorodeoxyglucose positron emission tomography with computed tomography and transbronchial lung biopsy found no pathogen or lymphoma recurrence. Treatment for pneumonia with antibiotic and antifungal agents was nonbeneficial. A diagnosis of secondary organizing pneumonia (OP) was made after pneumonia migration and a rapid response to corticosteroids. OP secondary to a viral respiratory infection has been well described. Raising awareness for post-COVID-19 OP has therapeutic and prognostic importance because those patients benefit from steroid therapy. We believe the condition described here is underdiagnosed and undertreated by doctors worldwide. Because of the ongoing global pandemic we are now encountering a new kind of patient, patients that have recovered from COVID-19. We hope that this case may contribute to gaining more knowledge about this growing patient population.


Assuntos
Corticosteroides/uso terapêutico , COVID-19/terapia , Pneumonia em Organização Criptogênica/diagnóstico , Pneumonia em Organização Criptogênica/tratamento farmacológico , Adulto , Antineoplásicos Imunológicos/uso terapêutico , Pneumonia em Organização Criptogênica/patologia , Humanos , Hospedeiro Imunocomprometido/imunologia , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Masculino , Nasofaringe/virologia , Tomografia por Emissão de Pósitrons , Rituximab/uso terapêutico , SARS-CoV-2
15.
Oncol Rep ; 47(1)2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34779494

RESUMO

The incidence of cancer, which is the second leading cause of mortality globally, continues to increase, although continued efforts are being made to identify effective treatments with fewer side­effects. Previous studies have reported that chronic microinflammation, which occurs in diseases, including diabetes, along with weakened immune systems, may ultimately lead to cancer development. Chemotherapy, radiotherapy and surgery are the mainstream approaches to treatment; however, they all lead to immune system weakness, which in turn increases the metastatic spread. The aim of the present review was to provide evidence of a biological response modifier ß­glucan [ß­glucan vaccine adjuvant approach to treating cancer via immune enhancement (B­VACCIEN)] and its beneficial effects, including vaccine­adjuvant potential, balancing metabolic parameters (including blood glucose and lipid levels), increasing peripheral blood cell cytotoxicity against cancer and alleviating chemotherapy side effects in animal models. This suggests its value as a potential strategy to provide long­term prophylaxis in immunocompromised individuals or genetically prone to cancer.


Assuntos
/administração & dosagem , Hospedeiro Imunocomprometido/imunologia , Neoplasias/imunologia , Neoplasias/prevenção & controle , beta-Glucanas/imunologia , Animais , Humanos
16.
EBioMedicine ; 74: 103705, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34861491

RESUMO

BACKGROUND: Patients with immunocompromised disorders have mainly been excluded from clinical trials of vaccination against COVID-19. Thus, the aim of this prospective clinical trial was to investigate safety and efficacy of BNT162b2 mRNA vaccination in five selected groups of immunocompromised patients and healthy controls. METHODS: 539 study subjects (449 patients and 90 controls) were included. The patients had either primary (n=90), or secondary immunodeficiency disorders due to human immunodeficiency virus infection (n=90), allogeneic hematopoietic stem cell transplantation/CAR T cell therapy (n=90), solid organ transplantation (SOT) (n=89), or chronic lymphocytic leukemia (CLL) (n=90). The primary endpoint was seroconversion rate two weeks after the second dose. The secondary endpoints were safety and documented SARS-CoV-2 infection. FINDINGS: Adverse events were generally mild, but one case of fatal suspected unexpected serious adverse reaction occurred. 72.2% of the immunocompromised patients seroconverted compared to 100% of the controls (p=0.004). Lowest seroconversion rates were found in the SOT (43.4%) and CLL (63.3%) patient groups with observed negative impact of treatment with mycophenolate mofetil and ibrutinib, respectively. INTERPRETATION: The results showed that the mRNA BNT162b2 vaccine was safe in immunocompromised patients. Rate of seroconversion was substantially lower than in healthy controls, with a wide range of rates and antibody titres among predefined patient groups and subgroups. This clinical trial highlights the need for additional vaccine doses in certain immunocompromised patient groups to improve immunity. FUNDING: Knut and Alice Wallenberg Foundation, the Swedish Research Council, Nordstjernan AB, Region Stockholm, Karolinska Institutet, and organizations for PID/CLL-patients in Sweden.


Assuntos
/efeitos adversos , Hospedeiro Imunocomprometido/imunologia , Imunogenicidade da Vacina/imunologia , SARS-CoV-2/imunologia , Adenina/efeitos adversos , Adenina/análogos & derivados , Adenina/uso terapêutico , Anticorpos Antivirais/sangue , COVID-19/prevenção & controle , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Imunoterapia Adotiva , Leucemia Linfocítica Crônica de Células B , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/efeitos adversos , Ácido Micofenólico/uso terapêutico , Transplante de Órgãos , Piperidinas/efeitos adversos , Piperidinas/uso terapêutico , Doenças da Imunodeficiência Primária/imunologia , Estudos Prospectivos , Soroconversão , Glicoproteína da Espícula de Coronavírus/imunologia , Vacinação/efeitos adversos
17.
PLoS One ; 16(12): e0256947, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34855762

RESUMO

BACKGROUND: Toxoplasmosis is caused by an obligate intracellular tissue protozoan parasite, Toxoplasma gondii that infect humans and other warm-blooded animals. Transmission to humans is by eating raw or inadequately cooked infected meat or through ingestion of oocysts that cats have passed in faeces. Studies have shown life-threatening and substantial neurologic damage in immunocompromised patients; however, 80% of humans remain asymptomatic. The aim of this study was to determine the seroprevalence of Toxoplasma gondii infection in HIV positive patients and the risk factors associated with the infection, and to investigate the correlation between CD4+ T-cell count and toxoplasma specific antibodies as possible predictors of each other amongst HIV patients in the Bamenda Health District of the North West Region of Cameroon. METHODS: A cross-sectional study was conducted, in which 325 HIV patients were recruited for administration of questionnaire, serological diagnosis of T. gondii and measurement of CD4+ T-cell count. Bivariate and multivariate logistic regression was used to identify risk factors associated with T. gondii infection while the linear regression was used to investigate the relationship between CD4+ T-cell count and antibody levels against T. gondii. RESULTS: The findings showed that, majority (45.8%) of HIV patients suffered from chronic (IgG antibody) infection, and 6.5% from acute (IgM and IgM/IgG antibody) toxoplasma infection. The overall sero-prevalence of T. gondii infection amongst HIV patients was 50.5%. On the whole, 43 men (45.7%) and 127 women (55%) presented with anti- T. gondii antibodies; however, there was no significant difference amongst males and females who were positive to T. gondii infection (p = 0.131). Marital status (p = 0.0003), contact with garden soil (p = 0.0062), and garden ownership (p = 0.009), were factors that showed significant association with T. gondii infection. There was no significant difference (p = 0.909) between the mean CD4+ T-cell count of HIV patients negative for toxoplasma infection (502.7 cells/mL), chronically infected with T. gondii (517.7 cells/mL) and acutely infected with T. gondii (513.1 cells/mL). CD4+ T-cell count was neither a predictor of IgM antibody titer (r = 0.193, p = 0.401), nor IgG antibody titer (r = 0.149, p = 0.519) amongst HIV patients acutely infected with T. gondii. CONCLUSION: The findings from this study underscore the need to implement preventive and control measures to fight against T. gondii infection amongst HIV patients in the Bamenda Health District.


Assuntos
Anticorpos Antiprotozoários/imunologia , Linfócitos T CD4-Positivos/imunologia , Infecções por HIV/epidemiologia , Hospedeiro Imunocomprometido/imunologia , Toxoplasmose/epidemiologia , Adulto , Linfócitos T CD4-Positivos/citologia , Camarões/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Prevalência , Fatores de Risco , Estudos Soroepidemiológicos
18.
Pediatrics ; 148(6)2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34851422

RESUMO

Tuberculosis (TB) remains an important problem among children in the United States and throughout the world. There is no diagnostic reference standard for latent tuberculosis infection (also referred to as tuberculosis infection [TBI]). The tuberculin skin test (TST) has many limitations, including difficulty in administration and interpretation, the need for a return visit by the patient, and false-positive results caused by cross-reaction with Mycobacterium bovis-bacille Calmette-Guerin vaccines and many nontuberculous mycobacteria. Interferon-gamma release assays (IGRAs) are blood tests that use antigens specific for M tuberculosis; as a result, IGRAs yield fewer false-positive results than the TST. Both IGRAs and the TST have reduced sensitivity in immunocompromised children, including children with severe TB disease. Both methods have high positive predictive value when applied to children with risk factors for TBI, especially recent contact with a person who has TB disease. The advantages of using IGRAs and diminished experience with the placement and interpretation of the TST favor expanded use of IGRAs in children in the United States. There are now several effective and safe regimens for the treatment of TBI in children. For improved adherence to therapy, the 3 rifamycin-based regimens are preferred because of their short duration. Daily isoniazid can be used if there is intolerance or drug interactions with rifamycins. A TB specialist should be involved when there are questions regarding testing interpretation, selection of an appropriate treatment regimen, or management of adverse effects.


Assuntos
Antituberculosos/uso terapêutico , Testes de Liberação de Interferon-gama/métodos , Tuberculose Latente/diagnóstico , Tuberculose Latente/tratamento farmacológico , Teste Tuberculínico/métodos , Adolescente , Fatores Etários , Antituberculosos/efeitos adversos , Vacina BCG/imunologia , Criança , Pré-Escolar , Reações Cruzadas , Reações Falso-Positivas , Humanos , Hospedeiro Imunocomprometido/imunologia , Lactente , Isoniazida/uso terapêutico , Mycobacterium bovis/imunologia , Mycobacterium tuberculosis/imunologia , Micobactérias não Tuberculosas/imunologia , Rifampina/análogos & derivados , Rifampina/uso terapêutico , Sensibilidade e Especificidade
19.
Blood Cancer J ; 11(12): 202, 2021 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-34907159

RESUMO

There is evidence of reduced SARS-CoV-2 vaccine effectiveness in patients with hematological malignancies. We hypothesized that tumor and treatment-related immunosuppression can be depicted in peripheral blood, and that immune profiling prior to vaccination can help predict immunogenicity. We performed a comprehensive immunological characterization of 83 hematological patients before vaccination and measured IgM, IgG, and IgA antibody response to four viral antigens at day +7 after second-dose COVID-19 vaccination using multidimensional and computational flow cytometry. Health care practitioners of similar age were the control group (n = 102). Forty-four out of 59 immune cell types were significantly altered in patients; those with monoclonal gammopathies showed greater immunosuppression than patients with B-cell disorders and Hodgkin lymphoma. Immune dysregulation emerged before treatment, peaked while on-therapy, and did not return to normalcy after stopping treatment. We identified an immunotype that was significantly associated with poor antibody response and uncovered that the frequency of neutrophils, classical monocytes, CD4, and CD8 effector memory CD127low T cells, as well as naive CD21+ and IgM+D+ memory B cells, were independently associated with immunogenicity. Thus, we provide novel immune biomarkers to predict COVID-19 vaccine effectiveness in hematological patients, which are complementary to treatment-related factors and may help tailoring possible vaccine boosters.


Assuntos
Biomarcadores/sangue , Vacinas contra COVID-19 , COVID-19/imunologia , Neoplasias Hematológicas/complicações , Hospedeiro Imunocomprometido/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/prevenção & controle , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , SARS-CoV-2
20.
Nutrients ; 13(12)2021 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-34959964

RESUMO

BACKGROUND: In people living with HIV, combination antiretroviral therapy (cART) reduces the risk of death, but the persistent immune-deficient state predisposes them to pneumococcal infections. Current guidelines encourage administering pneumococcal vaccine Prevenar 13 to patients living with HIV. Since probiotic supplementation could act as adjuvants and improve vaccine immunogenicity by modulating gut microbiota, the present study aimed to assess whether the effect of a formulation containing a combination of specific probiotics (Vivomixx®) could improve the immune response to 13-valent pneumococcal conjugate vaccine (PCV13) in adult people living with HIV. METHODS: Thirty patients who were clinically stable and virologically suppressed, without opportunistic infections during this time and no ART changes in the 12 months before the study started were enrolled. Patients were divided into two groups: (1) received a placebo dose and (2) received Vivomixx® (1800 billion CFU) for four weeks before and after the vaccination with a single dose of PCV13. RESULTS: Vivomixx® supplementation induced a better response to PCV13 immunization, as shown by greater change in anti-Pn CPS13 IgG and increase in salivary IgA, IL-10 and IL-8. CONCLUSIONS: Additional investigations will help to clearly and fully elucidate the optimal strains, doses, and timing of administration of probiotics to improve protection upon vaccination in immunocompromised individuals and the elderly.


Assuntos
Suplementos Nutricionais , Infecções por HIV/imunologia , Imunidade/imunologia , Vacinas Pneumocócicas/imunologia , Probióticos/administração & dosagem , Adulto , Idoso , Terapia Antirretroviral de Alta Atividade , Infecções por HIV/tratamento farmacológico , Humanos , Hospedeiro Imunocomprometido/imunologia , Imunoglobulina A , Imunoglobulina G , Interleucina-10 , Interleucina-8 , Masculino , Pessoa de Meia-Idade
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...