Expression of TIGIT, PD-1 and HLA-DR/CD38 markers on CD8-T cells of children and adolescents infected with HIV and uninfected controls.

Immune exhaustion and senescence are scarcely studied in HIV-pediatric patients. We studied the circulatory CD8 T cells activation/exhaustion and senescent phenotype of children and adolescents vertically infected with HIV or uninfected controls based on the expression of human leukocyte antigen (HLA-DR), CD38, T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT), programmed death 1 (PD-1) and CD57 by flow cytometry, during approximately one year. Eleven HIV-infected (HI) and nine HIV-uninfected (HU) children/adolescents who received two doses or one dose of meningococcal C conjugate vaccine (MenC), respectively, were involved in this study. Blood samples were collected before the immunization (T0), 1-2 months after the first dose (T1), and 1-2 months after the second dose (T2), which was administered approximately one year after the first one. HI patients not receiving combined antiretroviral therapy (cART) showed a higher frequency of CD8 T cells TIGIT+, PD-1+ or CD57+, as well as a higher frequency of CD8 T cells co-expressing CD38/HLA-DR/TIGIT or CD38/HLA-DR/PD-1 when compared to HI treated or HU individuals, at all times that they were assessed. CD8 T cells co-expressing CD38/DR/TIGIT were inversely correlated with the CD4/CD8 ratio but positively associated with viral load. The co-expression of CD38/DR/TIGIT or CD38/DR/PD-1 on CD8 T cells was also inversely associated with the CD4 T cells expressing co-stimulatory molecules CD127/CD28. The results showed a higher expression of exhaustion/senescence markers on CD8 T cells of untreated HI children/adolescents and its correlations with viral load.

Expression of TIGIT, PD-1 and HLA-DR/CD38 markers on CD8-T cells of children and adolescents infected with HIV and uninfected controls

ABSTRACT Immune exhaustion and senescence are scarcely studied in HIV-pediatric patients. We studied the circulatory CD8 T cells activation/exhaustion and senescent phenotype of children and adolescents vertically infected with HIV or uninfected controls based on the expression of human leukocyte antigen (HLA-DR), CD38, T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT), programmed death 1 (PD-1) and CD57 by flow cytometry, during approximately one year. Eleven HIV-infected (HI) and nine HIV-uninfected (HU) children/adolescents who received two doses or one dose of meningococcal C conjugate vaccine (MenC), respectively, were involved in this study. Blood samples were collected before the immunization (T0), 1-2 months after the first dose (T1), and 1-2 months after the second dose (T2), which was administered approximately one year after the first one. HI patients not receiving combined antiretroviral therapy (cART) showed a higher frequency of CD8 T cells TIGIT+, PD-1+ or CD57+, as well as a higher frequency of CD8 T cells co-expressing CD38/HLA-DR/TIGIT or CD38/HLA-DR/PD-1 when compared to HI treated or HU individuals, at all times that they were assessed. CD8 T cells co-expressing CD38/DR/TIGIT were inversely correlated with the CD4/CD8 ratio but positively associated with viral load. The co-expression of CD38/DR/TIGIT or CD38/DR/PD-1 on CD8 T cells was also inversely associated with the CD4 T cells expressing co-stimulatory molecules CD127/CD28. The results showed a higher expression of exhaustion/senescence markers on CD8 T cells of untreated HI children/adolescents and its correlations with viral load.

An emergency system for monitoring pulse oximetry, peak expiratory flow, and body temperature of patients with COVID-19 at home: Development and preliminary application.

BACKGROUND: COVID-19 is characterized by a rapid change in the patient's condition, with major changes occurring over a few days. We aimed to develop and evaluate an emergency system for monitoring patients with COVID-19, which may be useful in hospitals where more severe patients stay in their homes. METHODOLOGY/PRINCIPAL FINDINGS: The system consists of the home-based patient unit, which is set up around the patient and the hospital unit, which enables the medical staff to telemonitor the patient's condition and help to send medical recommendations. The home unit allows the data transmission from the patient to the hospital, which is performed using a cell phone application. The hospital unit includes a virtual instrument developed in LabVIEW® environment that can provide a real-time monitoring of the oxygen saturation (SpO2), beats per minute (BPM), body temperature (BT), and peak expiratory flow (PEF). Abnormal events may be fast and automatically identified. After the design details are described, the system is validated by a 30-day home monitoring study in 12 controls and 12 patients with COVID-19 presenting asymptomatic to mild disease. Patients presented reduced SpO2 (p<0.0001) and increased BPM values (p<0.0001). Three patients (25%) presented PEF values between 50 and 80% of the predicted. Three of the 12 monitored patients presented events of desaturation (SpO2<92%). The experimental results were in close agreement with the involved pathophysiology, providing clear evidence that the proposed system can be a useful tool for the remote monitoring of patients with COVID-19. CONCLUSIONS: An emergency system for home monitoring of patients with COVID-19 was developed in the current study. The proposed system allowed us to quickly respond to early abnormalities in these patients. This system may contribute to conserving hospital resources for those most in need while simultaneously enabling early recognition of patients under acute deterioration, requiring urgent assessment.

Detection of Neisseria meningitidis in asymptomatic carriers in a university hospital from Brazil.

Asymptomatic meningococcus carriers in hospitals is a risk factor for acquiring meningococcal disease. Meningococcal carrier (MC) frequency was investigated in oropharyngeal swab samples collected from 200 staff members at a teaching hospital from Brazil. MC prevalence was 9% (95% CI 5-13%). Risk factors associated with MC were: mean age of 26.5 years, male gender, bar attendance frequency and number of persons/house. Of 18 isolated meningococcal strains, 14 were non-group able (NG), 3 corresponded to serogroup B and 1 to serogroup 29E. The frequency of serotypes and serosubtypes was heterogenous, with a slight predominance of serotypes 4 and 7 and serosubtypes P1.7 and P1.5. Most strains (n=13) were susceptible to the antimicrobials tested. The ctrA gene (PCR) was identified in 9 (64.3%) of the 14 NG strains, suggesting virulence in most of the NG isolated strains. Therefore, a constant surveillance of these asymptomatic carriers is required.

Psychosocial factors and T lymphocyte counts in Brazilian peacekeepers.

OBJECTIVE: To investigate the associations between psychosocial factors and peripheral blood CD4 and CD8 T lymphocyte numbers in Brazilian peacekeepers. METHODS: Venous blood was collected from 759 peacekeepers who had just returned from a peace mission in Haiti. Among the 759 soldiers, 642 individuals completed the psychosocial measures. CD4 and CD8 T lymphocyte counts were measured by flow cytometry using a commercially available kit. Psychosocial factors, including military peace force stressors, clinical stress, anxiety and depression, were recorded. As a reference for T lymphocyte numbers, we measured T lymphocyte counts in 75 blood donors from the Instituto de Biologia do Exército, Rio de Janeiro. RESULTS: The median numbers of CD4 and CD8 T lymphocytes in the blood donors were 819 cells/µl and 496 cells/µl, respectively, with a CD4:CD8 ratio of 1.6. Significantly (p<0.05) lower CD4 T cell counts (759 cells/µl) were recorded for peacekeepers, with similar CD8 levels (548 cells/µl) and smaller CD4:CD8 ratios (1.3, p<0.001) compared to blood donors. These differences were due to a group of 14 military personnel with CD4 and CD8 medians of 308 and 266 cells/µl, respectively. Only one (7.1%) of these 14 individuals was diagnosed with clinical stress compared with 13.5% of the individuals with normal levels of CD4 T lymphocytes. One individual out of 628 (0.16%) had a Lipp's Stress Symptom Inventory score of 3, indicating near exhaustion. CONCLUSION: The prevalence of psychological disorders was low and there were no associations with CD4 or CD8 T cell numbers.

Diphtheria-neutralizing antibody levels in healthy adults from Rio de Janeiro, Brazil.

In Brazil, until 2004, the immunization policy against diphtheria involved childhood vaccination with no official routine booster dose administered after 15 years of age. This study assessed functional antibody levels against diphtheria among blood donors. A total of 140 blood samples were collected, and diphtheria antitoxin levels were evaluated by Vero cell neutralization test. The mean age of the population was 34 years old (range: 18-61 years); 37.8% females and 62.2% males. Overall, 30.7% (95%, CI: 23.4-38.7) individuals presented neutralizing antitoxin antibody titers < 0.01 IU/ml; 42.1% (95%, CI: 34.1-50.4) showed values between 0.01-0.09 IU/ml and, 27.1% (95%, CI: 20.2-34.9) had (3) 0.1 IU/ml. In the subgroup of individuals with history of diphtheria immunization during childhood (85%), a number of 28.5% showed unprotective levels of circulating neutralizing antibody (< 0.01 IU/ml). Despite the continuous progress of immunization programs directed to Brazilian population, currently healthy adults remain susceptible to diphtheria.

Diphtheria-neutralizing antibody levels in healthy adults from Rio de Janeiro, Brazil

In Brazil, until 2004, the immunization policy against diphtheria involved childhood vaccination with no official routine booster dose administered after 15 years of age. This study assessed functional antibody levels against diphtheria among blood donors. A total of 140 blood samples were collected, and diphtheria antitoxin levels were evaluated by Vero cell neutralization test. The mean age of the population was 34 years old (range: 18-61 years); 37.8 percent females and 62.2 percent males. Overall, 30.7 percent (95 percent, CI: 23.4-38.7) individuals presented neutralizing antitoxin antibody titers < 0.01 IU/ml; 42.1 percent (95 percent, CI: 34.1-50.4) showed values between 0.01-0.09 IU/ml and, 27.1 percent (95 percent, CI: 20.2-34.9) had ³ 0.1 IU/ml. In the subgroup of individuals with history of diphtheria immunization during childhood (85 percent), a number of 28.5 percent showed unprotective levels of circulating neutralizing antibody (< 0.01 IU/ml). Despite the continuous progress of immunization programs directed to Brazilian population, currently healthy adults remain susceptible to diphtheria.

Anticorpos batericidas contra Neisseria miningitidis B após vacinação ou infecção invasiva

A doença miningocócica representa um sério problema de saúde pública no Brasil. A única vacina (VA-MENGOC-BC r) comercialmente disponível contra N.meningitidis B foi produzida em Cuba sendo composta por proteínas da membrana externa de uma cepa B:4:P1.15. Porém, esta vacina apresentou uma eficácia limitada em prevenir a doença em crianças menores de 9 anos procedentes da Grande São Paulo ou municipio do Rio de Janeiro. A imunidade ao menigococo tem sido associada ao desenvolvimento de anticorpos capazes de ativarem o sistema complemento gerando lise bacteriana (anticorpos bactericidas). Um dos objetivos desta tese foi estudar a especificidade dos anticorpos bactericidas de crianças da Grande São Paulo imunizadas com a vacina Va-MENGOC BC r. Observou-se grupos de indivíduos com perfis de respostas distintos quando cepas mutantes sem as proteínas C1 e/ou C5, cepas de subtipos heterólogos e diferentes cepas B:4:P1.15 foram empregadas no ensaio bactericida. Vinte e seis porcento dos individuos estudados (n=77), soroconverteu em termos de anticorpos bactericidas contra a cepa N44/89(B:4:P1.15). Entre os soros positivos...

Induction of iron regulated proteins during normal growth of Neisseria meningitidis in a chemically defined medium

A expressao das proteinas reguladas pelo ferro (IRPs), in vitro, tem sido obtida pela adicao de quelantes de ferro ao meio de cultura, apos o crescimento bacteriano, na presenca de fonte de ferro organico. Neste estudo foram investigados aspectos da maxima expressao das IRPs de meningococo durante o crescimento normal, em condicoes de cultura definidas, utilizando-se o meio de Catlin e os caldos Mueller-Hinton e Tryptic Soja (TSB). Foram avaliadas as melhores condicoes para se obter vesiculas de membrana externa (OMVs) contendo IRPs para uso em vacina de meningococo B....

Imunidade conferida por vacinas anti-meningocócicas / Immunity confered by anti-meningococci vaccines

Em razäo da recente epidemia de doença meningocócica causada por N. meningitidis B na Grande Säo Paulo, Brasil, foi feita revisäo das epidemias dessa doença ocorridas no Brasil desde o início do século e uma análise das vacinas atuais contra N. meningitidis A, C, Y e W135. Também säo discutidos os mais recentes avanços no desenvolvimento e aplicaçäo de vacina contra N. meningitidis B, um desafio constante para os maiores centros de pesquisa de todo o mundo

Utilizaçäo do meio de cultura novobiocina-nitrato-sacarose (NNS) no diagnóstico presuntivo de staphylococcus saprophyticus / Use of NNS (Novobiocin-Nitrate-Sucrose) medium to differentiate staphylococcus saprophyticus from other coagulase-negative staphylococci

O meio de cultura NNS, constituído de púrpura de bromocresol, nitrato de potássio, sacarose e novobiocina, foi utilizado na diferenciaçäo de Staphylococcus saprophyticus isolados de urina. Na formulaçäo do meio NNS, a resistência à novobiocina, característica normalmente utilizada no diagnóstico presuntivo de Staphylococcus saprophyticus, foi associada a sua capacidade de utilizar a sacarose e à ausência da enzima nitrato-redutase, visando a diferenciaçäo deste microorganismo dos demais estafilococos coagulase negativa, inclusive os igualmente resistentes à novobiocina (STAPHYLOCOCCUS COHNII, STAPHYLOCOCCUS XYLOSUS E STAPHYLOCOCCUS SCIURI). Os Staphylococcus Cohnii näo utilizam a sacarose (88% das cepas), enquanto os Staphylococcus xylosus e Staphylococcus sciuri reduzem nitrato a nitrito em 100 e 80% das cepas, respectivamente. De 74 cepas de estafilococos coagulase negativa isoladas de urina, 49 (66,2%) cepas de Staphylococcus saprophyticus foram diferenciadas pelo meio NNs, tendo sido obtidos resultados de valor predicativo de resultado positivo de 100%, sensibilidade de 95,9%, especificidade de 100% e eficiência de 97,2%...