The decline of measles antibody titers in previously vaccinated adults: a cross-sectional analysis.

The global reemergence of measles in 2018-2019 reinforces the relevance of high-coverage immunization to maintain the disease elimination. During an outbreak in the Sao Paulo State in 2019, several measles cases were reported in individuals who were adequately vaccinated according to the current immunization schedule recommends. This study aimed to assess measles IgG antibody seropositivity and titers in previously vaccinated adults. A cross-sectional study was conducted at CRIE-HC-FMUSP (Sao Paulo, Brazil) in 2019. It included healthy adults who had received two or more Measles-Mumps-Rubella vaccines (MMR) and excluded individuals with immunocompromising conditions. Measles IgG antibodies were measured and compared by ELISA (Euroimmun®) and chemiluminescence (LIASON®). The association of seropositivity and titers with variables of interest (age, sex, profession, previous measles, number of measles-containing vaccine doses, interval between MMR doses, and time elapsed since the last MMR dose) was analyzed. A total of 162 participants were evaluated, predominantly young (median age 30 years), women (69.8%) and healthcare professionals (61.7%). The median interval between MMR doses was 13.2 years, and the median time since the last dose was 10.4 years. The seropositivity rate was 32.7% by ELISA and 75.3% by CLIA, and a strong positive correlation was found between the tests. Multivariate analyses revealed that age and time since the last dose were independently associated with positivity. Despite being a single-center evaluation, our results suggest that measles seropositivity may be lower than expected in adequately immunized adults. Seropositivity was higher among older individuals and those with a shorter time since the last MMR vaccine dose.

The decline of measles antibody titers in previously vaccinated adults: a cross-sectional analysis

ABSTRACT The global reemergence of measles in 2018-2019 reinforces the relevance of high-coverage immunization to maintain the disease elimination. During an outbreak in the Sao Paulo State in 2019, several measles cases were reported in individuals who were adequately vaccinated according to the current immunization schedule recommends. This study aimed to assess measles IgG antibody seropositivity and titers in previously vaccinated adults. A cross-sectional study was conducted at CRIE-HC-FMUSP (Sao Paulo, Brazil) in 2019. It included healthy adults who had received two or more Measles-Mumps-Rubella vaccines (MMR) and excluded individuals with immunocompromising conditions. Measles IgG antibodies were measured and compared by ELISA (Euroimmun®) and chemiluminescence (LIASON®). The association of seropositivity and titers with variables of interest (age, sex, profession, previous measles, number of measles-containing vaccine doses, interval between MMR doses, and time elapsed since the last MMR dose) was analyzed. A total of 162 participants were evaluated, predominantly young (median age 30 years), women (69.8%) and healthcare professionals (61.7%). The median interval between MMR doses was 13.2 years, and the median time since the last dose was 10.4 years. The seropositivity rate was 32.7% by ELISA and 75.3% by CLIA, and a strong positive correlation was found between the tests. Multivariate analyses revealed that age and time since the last dose were independently associated with positivity. Despite being a single-center evaluation, our results suggest that measles seropositivity may be lower than expected in adequately immunized adults. Seropositivity was higher among older individuals and those with a shorter time since the last MMR vaccine dose.

Correlation between inflammatory mediators and biochemical markers in patients with active pulmonary tuberculosis / Correlação entre mediadores inflamatórios e marcadores bioquímicos em pacientes com tuberculose pulmonar ativa

Objective: Correlate inflammatory mediators and biochemical parameters in patients with active pulmonary tuberculosis (TB) treated at a public hospital in São Luís, MA. Methods: This is a case-control study of patients with a positive diagnosis of active pulmonary TB. Serum samples from patients and the control group were collected for the clinical trials, and epidemiological data were collected through medical records and interviews. The control group consisted of healthy volunteers with no previous contact with TB cases, matched by age and sex to the clinical group. To measure inflammatory cytokines, we used the Human IL-6 ELISA Set and Human IFN-γ ELISA Set kits. Oxidative stress was measured by quantification of thiobarbituric acid reactive substances (TBARS) and nitric oxide (NO). In biochemistry, the levels of uric acid, antistreptolysin "O" (AEO), alanine aminotransferase (ALT), amylase, aspartate aminotransferase (AST), calcium, total cholesterol, gamma-glutamyl transferase (Gamma GT), glucose, alkaline phosphatase, high-density lipoprotein (HDL), C-reactive protein (CRP) and triglycerides were measured. Results: The clinical group consisted of 53 patients. There was a substantial decrease in IFN-γ (p<0.0001) and a significant increase in IL-6 (p<0.0001). TBARS production increased significantly (p= 0.0414). There was no significant difference in NO production (p= 0.3194). In biochemistry, there was a significant increase in ALT (p= 0.0072), AST (p= 0.0016), Gamma GT (p= 0.0011), alkaline phosphatase (p<0.0001), CRP (p<0. .0001) and triglycerides (p= 0.0343), and a significant decrease in calcium (p<0.0001). A significant positive correlation was found between IL-6 and IFN-γ (p= 0.0448), as well as AST and ALT (p<0.0001); CRP and gamma GT (p<0.0001); Gamma GT and ALT (p= 0.0016); Gamma GT and AST (p=0.0004); triglycerides and cholesterol (p= 0.0002); alkaline phosphatase and gamma GT (p<0.0001); CRP and alkaline phosphatase (p<0.0001); triglycerides and calcium (p= 0.0121); cholesterol and calcium (p= 0.0261); glucose and cholesterol (p= 0.0373); and triglycerides and glucose (p= 0.0127) in biochemistry, with a significant negative correlation between glucose and uric acid (p= 0.0092); and CRP and HDL (p=0.0037). The correlation between inflammatory mediators and biochemical markers was positive between IL-6 and gamma GT (p= 0.0011); IL-6 and CRP (p<0.0001); IL-6 and alkaline phosphatase (p=0.0076); and NO and triglycerides (p= 0.0016), and significant negative correlation between IFN-γ and cholesterol (p= 0.0171) and TBARS and cholesterol (p= 0.0138). Conclusion: Immunosuppression of IFN-γ activity was observed. A correlation was found between IL-6 and inflammatory biochemical markers, indicating damage and injury caused by M. tuberculosis (AU).

Objetivo: Correlacionar mediadores inflamatórios e parâmetros bioquímicos em pacientes com tuberculose (TB) pulmonar ativa atendidos em um hospital público, em São Luís, MA. Métodos: Trata-se um caso-controle de pacientes com diagnóstico positivo para TB pulmonar ativa. Amostras de soro dos pacientes e grupo controle foram coletadas para os experimentos clínicos e os dados epidemiológicos foram coletados por meio de prontuários e entrevistas. O grupo controle foi formado por voluntários saudáveis sem contato prévio com casos de TB, pareados com idade e sexo ao grupo clínico. Para dosar citocinas inflamatórias, utilizaram-se os kits Human IL-6 ELISA Set e Human IFN-γ ELISA Set. Mediu-se o estresse oxidativo pela quantificação das espécies reativas do ácido tiobarbitúrico (TBARS) e óxido nítrico (ON). Na bioquímica, mediram-se os níveis de ácido úrico, anti-estreptolisina-O (AEO), alanina aminotransferase (ALT), amilase, aspartato aminotransferase (AST), cálcio, colesterol total, gama glutamil transferase (Gama GT), glicose, fosfatase alcalina, lipoproteína de alta densidade (HDL), proteína C reativa (PCR) e triglicerídeos. A análise estatística foi realizada pelo software Graph Pad Prism 8, com p<0,05 significativo. Re -sultados: O grupo clínico foi formado por 53 pacientes. Houve uma diminuição significativa de IFN-γ (p<0,0001), e aumento significativo de IL-6 (p<0,0001). A produção de TBARS aumentou significativamente (p= 0,0414). Não houve diferença significativa na produção de ON (p= 0,3194). Na bioquímica, houve aumento significativo em ALT (p= 0,0072), AST (p= 0,0016), gama GT (p= 0,0011), fosfatase alcalina (p<0,0001), PCR (p<0,0001) e triglice-rídeos (p= 0,0343), e diminuição significativa de cálcio (p<0,0001). Encontrou-se correlação positiva significativa entre IL-6 e IFN-γ (p= 0,0448), assim como AST e ALT (p<0,0001); PCR e gama GT (p<0,0001); gama GT e ALT (p= 0,0016); gama GT e AST (p= 0,0004); triglicerídeos e colesterol (p= 0,0002); fosfatase alcalina e gama GT (p<0,0001); PCR e fosfatase alcalina (p<0,0001); triglicerídeos e cálcio (p= 0,0121); colesterol e cálcio (p= 0,0261); glicose e colesterol (p= 0,0373); e triglicerídeos e glicose (p= 0,0127) na bioquímica, sendo negativa significativa entre glicose e ácido úrico (p= 0,0092); e PCR e HDL (p= 0,0037). A correlação entre marcadores infla-matório e bioquímicos foi positiva entre IL-6 e gama GT (p= 0,0011); IL-6 e PCR (p<0,0001); IL-6 e fosfatase alcalina (p= 0,0076); e ON e triglicerídeos (p= 0,0016), e negativa significativa entre IFN-γ e colesterol (p= 0,0171) e TBARS e colesterol (p= 0,0138). Conclusões: Observou-se imunossupressão da atividade de IFN-γ. Encontrou-se correlação entre IL-6 e marcadores bioquímicos inflamatórios, indicando dano e lesão causados por M. tuberculosis (AU).

Clinical Features, Biochemical Parameters, and Treatment Adherence of Individuals Who Started the Treatment for Active Pulmonary Tuberculosis during the Pandemic Period.

This descriptive prospective study investigated the clinical features and treatment adherence of individuals who started the treatment for Pulmonary tuberculosis (TB) during the COVID-19 pandemic in São Luís. Thirty-six TB patients and thirty-five age/sex-matched individuals were recruited between January 2021 and January 2022. The clinical features, sociodemographic information, and serum were obtained at the diagnosis time. Adherence to treatment and adverse reactions were investigated monthly. The most common symptoms in TB patients were cough (91.6%) and fever (83.3%). All TB patients had elevated pre-therapy levels of CRP and reduced HDL: 88.9% presented hypocalcemia and 47.2% showed elevated ALP and GGT. TB patients showed higher levels of ALT, AST, ALP, GGT, CRP, amylase, and triglycerides than the comparison group (p < 0.05), while the calcium levels were reduced (p < 0.0001). TB patients with anti-SARS-CoV-2-IgG antibodies (seroprevalence of 66.7%) presented higher values of amylase and lower CRP levels (p < 0.05). Most patients (~70%) reported at least one adverse drug reaction, mainly pruritus and nausea. The treatment abandonment rate was 19.2%. In conclusion, TB patients showed elevated pre-therapy levels of CRP, low levels of HDL, and hypocalcemia. Liver and pancreatic functions were also compromised in several patients before the therapy. The treatment non-adherence rate observed was similar to other studies performed before the pandemic period.

Short-Term Intake of Theobroma grandiflorum Juice Fermented with Lacticaseibacillus rhamnosus ATCC 9595 Amended the Outcome of Endotoxemia Induced by Lipopolysaccharide.

Endotoxemia is a condition caused by increasing levels of lipopolysaccharide (LPS) characterized by an impaired systemic response that causes multiple organ dysfunction. Lacticaseibacillus rhamnosus ATCC 9595 is a strain with probiotic potential which shows immunomodulatory properties. The incorporation of this bacterium in food rich in bioactive compounds, such as cupuaçu juice (Theobroma grandiflorum), could result in a product with interesting health properties. This work evaluated the effects of the oral administration of cupuaçu juice fermented with L. rhamnosus on the outcome of LPS-induced endotoxemia in mice. C57BL/6 mice (12/group) received oral doses (100 µL) of saline solution and unfermented or fermented cupuaçu juice (108 CFU/mL). After 5 days, the endotoxemia was induced by an intraperitoneal injection of LPS (10 mg/kg). The endotoxemia severity was evaluated daily using a score based on grooming behavior, mobility, presence of piloerection, and weeping eyes. After 6 h and 120 h, the mice (6/group) were euthanized for analysis of cell counts (in peritoneal lavage and serum) and organ weight. L. rhamnosus grew in cupuaçu juice and produced organic acids without the need for supplementation. The bacteria counts were stable in the juice during storage at 4 °C for 28 days. The fermentation with L. rhamnosus ATCC 9595 changed the metabolites profile of cupuaçu juice due to the biotransformation and enhancement of some compounds. In general, the administration of L. rhamnosus-fermented juice allowed a significant improvement in several characteristics of endotoxemic status (weight loss, hypothermia, severity index, cell migration). In addition, treatment with fermented juice significantly reduced the weight of the spleen, liver, intestine, and kidneys compared to the saline-treated endotoxemic group. Taken together, our data show that short-term intake therapy of cupuaçu juice fermented with L. rhamnosus ATCC 9595 can reduce systemic inflammation in an experimental model of LPS-induced endotoxemia in mice.

Adverse events following immunization of elderly with COVID-19 inactivated virus vaccine (CoronaVac) in Southeastern Brazil: an active surveillance study.

Healthcare workers, the elderly and other vulnerable populations were the first to receive COVID-19 vaccines in public health programs. There were few vaccine safety data available on the elderly. This observational study aimed to evaluate the inactivated vaccine (CoronaVac) safety in the elderly, at the beginning of the vaccination program, in Sao Paulo city, Brazil. The elderly people that received CoronaVac at the Reference Center for Special Immunobiologicals (CRIE) or at home, administered by the Interdisciplinary Home Care Team (NADI) of the Hospital das Clinicas were invited to participate in this phase 4 observational study. The vaccination schedule included two CoronaVac doses 28 days apart. The information on solicited and unsolicited adverse events following immunization were collected by phone calls on days 4 and 8 after each vaccine dose. We enrolled 158 adults aged 65 to 101 years (mean of 84.1 years); 63.9% were females and 95.6% had chronic conditions, 21.5% had moderate or severe impairment in daily living activities; 34.2% were pre-frail and 19.6% were frail. We were able to contact 95.6% and 91.6% of the vaccinated people, after the first and second doses, respectively; 31.8% and 23.4% of the contacted participants reported some adverse events (AE) following the first and second doses, respectively. Pain at the injection site, fatigue, myalgia and headaches were the most frequent solicited AE. Most AE were mild to moderate. There were eight severe adverse events, but none of them were considered related to the vaccine. The CoronaVac was safe and well tolerated by these adults of advanced age with frailty and comorbidities.

Adverse events following immunization of elderly with COVID-19 inactivated virus vaccine (CoronaVac) in Southeastern Brazil: an active surveillance study

ABSTRACT Healthcare workers, the elderly and other vulnerable populations were the first to receive COVID-19 vaccines in public health programs. There were few vaccine safety data available on the elderly. This observational study aimed to evaluate the inactivated vaccine (CoronaVac) safety in the elderly, at the beginning of the vaccination program, in Sao Paulo city, Brazil. The elderly people that received CoronaVac at the Reference Center for Special Immunobiologicals (CRIE) or at home, administered by the Interdisciplinary Home Care Team (NADI) of the Hospital das Clinicas were invited to participate in this phase 4 observational study. The vaccination schedule included two CoronaVac doses 28 days apart. The information on solicited and unsolicited adverse events following immunization were collected by phone calls on days 4 and 8 after each vaccine dose. We enrolled 158 adults aged 65 to 101 years (mean of 84.1 years); 63.9% were females and 95.6% had chronic conditions, 21.5% had moderate or severe impairment in daily living activities; 34.2% were pre-frail and 19.6% were frail. We were able to contact 95.6% and 91.6% of the vaccinated people, after the first and second doses, respectively; 31.8% and 23.4% of the contacted participants reported some adverse events (AE) following the first and second doses, respectively. Pain at the injection site, fatigue, myalgia and headaches were the most frequent solicited AE. Most AE were mild to moderate. There were eight severe adverse events, but none of them were considered related to the vaccine. The CoronaVac was safe and well tolerated by these adults of advanced age with frailty and comorbidities.