Perceived discrimination in health services and associated factors in Manaus Metropolitan Region, Brazil: a cross-sectional population-based study.

Objectives: Discrimination is the differentiated treatment of individuals due to prejudgments. Discriminatory practices in health care result in negative effects on patients' health. In Brazil, skin color represents the main form of racial discrimination, which may have an impact on the accessibility and quality of health care. The Brazilian Amazon lacks investigations on this topic at the population level. This study aims to estimate the prevalence of perceived discrimination in health services and associated factors in the Manaus Metropolitan Region, state of Amazonas, Brazil.Design: A population-based cross-sectional study was conducted with a probabilistic sample of adults interviewed in 2015. The associated factors were investigated by calculating the prevalence ratio (PR) using Poisson regression with robust variance.Results: A total of 4,001 participants were included. The overall prevalence of perceived discrimination was 12.9% (95% confidence interval [CI]: 11.8-13.9%). When compared to the reference categories, women (PR = 1.43; 95%CI: 1.20-1.70), individuals with brown skin color (Brazilian mixed race; PR = 1.33; 95%CI: 1.04-1.71), people who suffer from hypertension (PR = 1.27;95%CI: 1.03-1.57), and people who frequently used health services (p≤0.03) experienced more discrimination from health professionals.Conclusions: The prevalence of perceived discrimination in health services in Manaus Metropolitan Region is frequent and is associated with ethnic, social and health-related factors. Investments in inclusive public health policies and a better quality of health assistance are required to tackle this problem.

StreptInCor, a Group A Streptococcal Adsorbed Vaccine: Evaluation of Repeated Intramuscular Dose Toxicity Testing in Rats.

Streptococcus pyogenes infections continue to be a worldwide public health problem, causing various diseases in humans, with rheumatic fever and rheumatic heart disease being the most harmful manifestations. Impetigo and post-streptococcal glomerulonephritis are also important sequelae of skin infections. We have developed a candidate vaccine epitope (StreptInCor) that presents promising results in diverse animal models. To assess whether the StreptInCor alum-adsorbed vaccine could induce undesirable effects, a certified independent company conducted a repeated intramuscular dose toxicity evaluation in Wistar rats, a choice model for toxicity studies. We did not observe significant alterations in clinical, hematological, biochemical, anatomical, or histopathological parameters due to vaccine administration, even when the animals received the highest dose. In conclusion, repeated intramuscular doses did not show signs of macroscopic or other significant changes in the clinical or histopathological parameters, indicating that StreptInCor can be considered a safe candidate vaccine.

Prevalence of Self-Reported Chronic Diseases and Health Services Utilization by Ethnic Minorities in Manaus Metropolitan Region.

Objectives: To assess the prevalence of, and associated factors to, self-reported chronic diseases and health care utilization by ethnicity in the Manaus Metropolitan Region. Methods: We conducted a cross-sectional, population-based survey from May through August 2015. Using probabilistic sampling in three stages, we recruited adults aged ≥18 years. Ethnicity was self-identified as White, Black, Yellow, Brown (Brazilian mixed-race), and Indigenous. We calculated adjusted prevalence ratios (PR) and 95% CI of chronic diseases and health service utilization for each ethnic minority and compared the data using Poisson regression with data from White respondents. Results: In this study, we interviewed 4,001 people. Of these, 15.9% were White, 7.5% Black, 3.4% Yellow, 72.1% Brown, and 1.0% Indigenous. Indigenous respondents had the highest prevalence of self-reported hypertension (29.4%), diabetes (12.3%) and hypercholesterolemia (17.0%) among the ethnic respondent groups. Compared with the White population, Browns had less health insurance coverage (PR=.76; 95% CI: .62-.93) and reported hypertension (PR=.84; 95% CI: .72-0.98) and diabetes (PR=.69; 95% CI: .51-.94) less frequently. Yellows visited the doctor more frequently than Whites (PR=1.13; 95% CI: 1.04-1.22), with no significant difference in prevalence of diseases. Conclusions: Indigenous respondents had higher prevalence rates of the investigated diseases. Compared with Whites, Brown respondents had lower rates of self-reported arterial hypertension and diabetes, as well as lower rates of private health insurance coverage.

Long-term administration of IgG2a anti-NK1.1 monoclonal antibody ameliorates lupus-like disease in NZB/W mice in spite of an early worsening induced by an IgG2a-dependent BAFF/BLyS production.

The role of natural killer (NK) T cells in the development of lupus-like disease in mice is still controversial. We treated NZB/W mice with anti-NK1.1 monoclonal antibodies (mAbs) and our results revealed that administration of either an irrelevant immunoglobulin G2a (IgG2a) mAb or an IgG2a anti-NK1.1 mAb increased the production of anti-dsDNA antibodies in young NZB/W mice. However, the continuous administration of an anti-NK1.1 mAb protected aged NZB/W mice from glomerular injury, leading to prolonged survival and stabilization of the proteinuria. Conversely, the administration of the control IgG2a mAb led to an aggravation of the lupus-like disease. Augmented titres of anti-dsDNA in NZB/W mice, upon IgG2a administration, correlated with the production of BAFF/BLyS by dendritic, B and T cells. Treatment with an anti-NK1.1 mAb reduced the levels of interleukin-16, produced by T cells, in spleen cell culture supernatants from aged NZB/W. Adoptive transfer of NK T cells from aged to young NZB/W accelerated the production of anti-dsDNA in recipient NZB/W mice, suggesting that NK T cells from aged NZB/W are endowed with a B-cell helper activity. In vitro studies, using purified NK T cells from aged NZB/W, showed that these cells provided helper B-cell activity for the production of anti-dsDNA. We concluded that NK T cells are involved in the progression of lupus-like disease in mature NZB/W mice and that immunoglobulin of the IgG2a isotype has an enhancing effect on antibody synthesis due to the induction of BAFF/BLyS, and therefore have a deleterious effect in the NZB/W mouse physiology.

Natural killer T cells are required for the development of a superantigen-driven T helper type 2 immune response in mice.

We show, here, that one single injection or weekly injections of staphylococcal enterotoxin B (SEB), starting in 1-day-old newborn mice, induced a powerful immune response with a T helper type 2 (Th2) pattern, as judged by the isotype and cytokine profile, with the production of large amounts of SEB-specific immunoglobulin G1 (IgG1), detectable levels of SEB-specific IgE and increased production of interleukin-4 by spleen cells. These protocols also induced an increase in the levels of total IgE in the serum. Memory of SEB was transferred to secondary recipients by using total spleen cells from primed animals. The secondary humoral response in transferred mice was diminished if spleen cells from SEB-treated mice were previously depleted of CD3+ or Vbeta8+ T cells or NK1.1+ cells. In vivo depletion of NK1.1+ cells in adult mice resulted in a marked reduction in the SEB-specific antibody response in both the primary and secondary immune responses. Additionally, purified NK1.1+ T cells were able to perform SEB-specific helper B-cell actions in vitro and in vivo. These results suggest that NK1.1+ T cells are required for the full development of humoral immunological memory, whilst making neonatal tolerance to SEB unachievable.

Potentiation of immunological tolerance induction in adult mice by co-administration of pooled normal IgG and oral tolerogens: a potential therapeutic approach for autoimmune diseases.

Oral tolerance can be defined as the inability of an adult animal to produce specific antibodies or cellular immune responses upon conventional immunization, after oral antigenic administration. Recently, the oral administration of antigens has gained renewed interest because of the possibility of inducing tolerance in nonimmunized adult animals and, consequently, opening up the theoretical possibility of preventing or treating diseases caused by malfunction of the immune system. This strategy has been proven to be useful in the prevention of allergic and autoimmune diseases in rodents, as well as in the amelioration of certain autoimmune diseases in humans. Although there is experimental and clinical evidence for the usefulness of oral tolerance in medical practice, the mechanisms responsible for this phenomenon are still poorly understood, and the results obtained are not always satisfactory. Herein, we show that the thymus is required for the induction and maintenance of oral tolerance, providing evidence that it is not a pure form of clonal deletion-based peripheral tolerance. Oral tolerance could therefore depend on the formation and release to the periphery of regulatory T cells, such as gammadelta or alphabeta T cells, by the thymus. This finding may have profound implications for the treatment of autoimmune diseases, since most of them are associated with thymic hypofunction. On the other hand, due to so far unknown mechanisms, the intraperitoneal co-administration of normal IgG to mice orally treated with tolerogen leads to a sustained and intense immunological tolerance, both in euthymic and thymectomized mice, including those of the lupus erythematosus-prone NZB x NZW lineage. This approach for inducing and maintaining tolerance in thymus-deficient conditions is discussed and put forth herein as a new evidence-based proposition for the therapy of autoimmune diseases.