Genetic variation of FcγRIIa induces higher uptake of Leishmania infantum and modulates cytokine production by adherent mononuclear cells in vitro.

Introduction: Single nucleotide variations (SNVs) are specific genetic variations that commonly occur in a population and often do not manifest phenotypically. However, depending on their location and the type of nucleotide exchanged, an SNV can alter or inhibit the function of the gene in which it occurs. Immunoglobulin G (IgG) receptor genes have exhibited several polymorphisms, including rs1801274, which is found in the FcgRIIa gene. The replacement of A with T results in a Histidine (H) to Arginine (R) substitution, altering the affinity of the IgG receptor for IgG subtypes and C-reactive protein (CRP). In this study, we analyzed rs1801274 and its functional implications concerning L. Infantum uptake and cytokine production. Methods: We genotyped 201 individuals from an endemic area for visceral leishmaniasis to assess the presence of rs1801274 using Taqman probes for a candidate gene study. Additionally, we included seventy individuals from a non-endemic area for a functional study. Subsequently, we isolated and cultivated one-week adherent mononuclear cells (AMCs) derived from the peripheral blood of participants residing in the non-endemic region in the presence of L. infantum promastigotes, with and without antigen-specific IgG and/or CRP. We analyzed the rate of phagocytosis and the production of nitric oxide (NO), tumor necrosis factor (TNF)-a, interleukin (IL)-10, IL-12 p70, IL-1b, IL- 6, and IL-8 in the culture supernatants. Results and discussion: In participants from the endemic region, the A/G (H/R isoform) heterozygous genotype was significantly associated with susceptibility to the disease. Furthermore, SNVs induced a change in the phagocytosis rate in an opsonin-dependent manner. Opsonization with IgG increased the production of IL-10, TNF-a, and IL-6 in AMCs with the H/R isoform, followed by a decrease in NO production. The results presented here suggest that the rs1801274 polymorphism is linked to a higher susceptibility to visceral leishmaniasis.

New immunological aspects of peri-implantitis.

BACKGROUND: The authors compared the levels of HIF1-α, VEGF, TNF-α, and IL-10 in peri-implant crevicular fluid between patients with or without peri-implantitis. HIF-1α levels were significantly high in the peri-implantitis possibly due to hypoxia triggered by persistent inflammation. OBJECTIVE: This study aimed to compare the levels of HIF1-α, VEGF, TNF-α, and IL-10 in the peri-implant crevicular fluid of patients with and without peri-implantitis. METHODS: Forty patients, comprising 16 with and 24 without peri-implantitis were selected. RESULTS: Patients with peri-implantitis exhibited significantly higher HIF-1α levels than those without peri-implantitis (p=0.0005). TNF-α revealed significant positive correlations with IL-10 (p=0.0008) and VEGF (p=0.0246), whereas HIF-1α and IL-10 levels (p=0.0041) demonstrated a negative and significative correlation in the peri-implantitis group. CONCLUSION: This study, for the first time demonstrates the balance of HIF-1α, TNFα, IL-10, and VEGF in peri-implantitis. It shows an elevated HIF-1α levels in patients with peri-implantitis, which could have stemmed from persistent inflammation- triggered hypoxia. Furthermore, the positive correlation between TNF-α and VEGF suggests intensified proinflammatory activity in peri-implantitis. Nevertheless, further studies are essential to understand these immune dynamics in peri-implantitis. BACKGROUND: Higher levels of HIF-1α in patients with peri-implantitis occurred possibly due to persistent hypoxia triggered by inflammation. BACKGROUND: Tissue hypoxia in peri-implantitis induced increase in HIF-1α consequently increased VEGF and angiogenesis, contributing to the persistence of inflammation.

New immunological aspects of peri-implantitis

ABSTRACT Objective: This study aimed to compare the levels of HIF1-α, VEGF, TNF-α, and IL-10 in the peri-implant crevicular fluid of patients with and without peri-implantitis. Methods: Forty patients, comprising 16 with and 24 without peri-implantitis were selected. Results: Patients with peri-implantitis exhibited significantly higher HIF-1α levels than those without peri-implantitis (p=0.0005). TNF-α revealed significant positive correlations with IL-10 (p=0.0008) and VEGF (p=0.0246), whereas HIF-1α and IL-10 levels (p=0.0041) demonstrated a negative and significative correlation in the peri-implantitis group. Conclusion: This study, for the first time demonstrates the balance of HIF-1α, TNFα, IL-10, and VEGF in peri-implantitis. It shows an elevated HIF-1α levels in patients with peri-implantitis, which could have stemmed from persistent inflammation- triggered hypoxia. Furthermore, the positive correlation between TNF-α and VEGF suggests intensified proinflammatory activity in peri-implantitis. Nevertheless, further studies are essential to understand these immune dynamics in peri-implantitis.

Multidrug-resistant tuberculous orchiepididymitis: a brief case report.

Tuberculosis (TB) is one of the leading causes of death by infectious diseases worldwide. Multidrug-resistant tuberculosis is a growing problem, especially in countries with high TB prevalence. Although the lungs are the organs most frequently affected by this disease, Mycobacterium tuberculosis can harm any organ, including the urogenital tract, causing extrapulmonary tuberculosis, which leads to a challenging diagnosis and consequent treatment delays. In this article, we present a case of orchiepididymitis caused by multidrug-resistant TB (MDR-TB) with a significantly delayed diagnosis, the proposed treatment according to the resistance profile, and the clinical outcomes.

Identifying patients with multidrug-resistant tuberculosis who may benefit from shorter durations of treatment.

OBJECTIVE: Studying treatment duration for rifampicin-resistant and multidrug-resistant tuberculosis (MDR/RR-TB) using observational data is methodologically challenging. We aim to present a hypothesis generating approach to identify factors associated with shorter duration of treatment. STUDY DESIGN AND SETTING: We conducted an individual patient data meta-analysis among MDR/RR-TB patients restricted to only those with successful treatment outcomes. Using multivariable linear regression, we estimated associations and their 95% confidence intervals (CI) between the outcome of individual deviation in treatment duration (in months) from the mean duration of their treatment site and patient characteristics, drug resistance, and treatments used. RESULTS: Overall, 6702 patients with successful treatment outcomes from 84 treatment sites were included. We found that factors commonly associated with poor treatment outcomes were also associated with longer treatment durations, relative to the site mean duration. Use of bedaquiline was associated with a 0.51 (95% CI: 0.15, 0.87) month decrease in duration of treatment, which was consistent across subgroups, while MDR/RR-TB with fluoroquinolone resistance was associated with 0.78 (95% CI: 0.36, 1.21) months increase. CONCLUSION: We describe a method to assess associations between clinical factors and treatment duration in observational studies of MDR/RR-TB patients, that may help identify patients who can benefit from shorter treatment.

Comparative Analysis of TNF-alpha, TNF-R1, and TNF-R2 in Patients with Low-impact Fractures Due to Osteoporosis.

Objective To analyze the serum levels of TNF-alpha and its TNF-R1 and TNF-R2 receptors in the blood of patients with low-impact fractures due to osteoporosis, comparing between genders and with healthy patients. Methods The present study was conducted with a blood sample of 62 patients, divided into patients with osteoporosis and healthy patients. The results were obtained using the ELISA method. Cytokine concentrations were determined based on the absorbance values obtained. Results Serum TNF-alpha levels were undetectable in female patients, while in males they were found only in one patient, with no significant difference. Similar results were found in the analyses of TNF-R1 and TNF-R2 levels, a significant increase in levels of TNF-alpha receptors in the groups of patients with osteoporosis compared with the control group in both sexes. There was no significant difference between the sexes in the dosage of both receptors within the group with osteoporosis. There was also a positive and significant correlation in the levels of TNF-R1 and TNF-R2 only in women. Conclusion The significant increase in TNF-R1 and TNF-R2 levels in women with osteoporosis suggest that the release and expression of these receptors may be contributing differently to the development of osteoporosis in men and women.

Comparative Analysis of TNF-alpha, TNF-R1, and TNF-R2 in Patients with Low-impact Fractures Due to Osteoporosis / Análise comparativa de TNF-alfa, TNF-R1 e TNF-R2 em pacientes com fraturas de baixo impacto decorrentes de osteoporose

Abstract Objective To analyze the serum levels of TNF-alpha and its TNF-R1 and TNF-R2 receptors in the blood of patients with low-impact fractures due to osteoporosis, comparing between genders and with healthy patients. Methods The present study was conducted with a blood sample of 62 patients, divided into patients with osteoporosis and healthy patients. The results were obtained using the ELISA method. Cytokine concentrations were determined based on the absorbance values obtained. Results Serum TNF-alpha levels were undetectable in female patients, while in males they were found only in one patient, with no significant difference. Similar results were found in the analyses of TNF-R1 and TNF-R2 levels, a significant increase in levels of TNF-alpha receptors in the groups of patients with osteoporosis compared with the control groupinbothsexes.There wasnosignificant difference between the sexes in the dosage of both receptors within the group with osteoporosis. There was also a positive and significant correlation in the levels of TNF-R1 and TNF-R2 only in women. Conclusion The significant increase in TNF-R1 and TNF-R2 levels in women with osteoporosis suggest that the release and expression of these receptors may be contributing differently to the development of osteoporosis in men and women.

Resumo Objetivo Analisar os níveis séricos de TNF-alfa e de seus receptores TNF-R1 e TNF-R2 no sangue de pacientes com fraturas de baixo impacto, decorrentes de osteoporose, comparando entre os sexos e com pacientes saudáveis. Métodos Oestudofoi realizadocom amostradesanguede 62 pacientes,divididos em pacientes com osteoporose e pacientes saudáveis. Os resultados foram obtidos através do método de ELISA. As concentrações de citocinas foram determinadas com base nos valores de absorbância obtidos. Resultados Os níveis séricos de TNF-alfa foram indetectáveis nos pacientes do sexo feminino, enquanto no masculino encontrou-se somente em um paciente, não havendo diferença significativa. Encontrou-se resultados semelhantes nas análises dos níveis de TNF-R1 e TNF-R2, aumento significativo nos níveis dos receptores de TNF-alfa nos grupos de pacientes com osteoporose em comparação com o grupo controle, em ambos os sexos. Não houve diferença significativa entre os sexos na dosagem de ambos os receptores dentro do grupo com osteoporose. Houve ainda correlação positiva e significativa nos níveis de TNF-R1 e TNF-R2 apenas nas mulheres. Conclusão O aumento significativo nos níveis de TNF-R1 e TNF-R2 em mulheres com osteoporose sugerem que a liberação e expressão destes receptores pode estar contribuindo de maneira distinta no desenvolvimento da osteoporose em homens e mulheres.

Evaluation of Specific Cellular and Humoral Immune Response to Toxoplasma gondii in Patients with Autoimmune Rheumatic Diseases Immunomodulated Due to the Use of TNF Blockers.

(1) Background: TNF antagonists have been used to treat autoimmune diseases (AD). However, during the chronic phase of toxoplasmosis, TNF-α and TNFR play a significant role in maintaining disease resistance and latency. Several studies have demonstrated the risk of latent infections' reactivation in patients infected with toxoplasmosis. Our objective was to verify whether patients with autoimmune rheumatic diseases, who use TNF antagonists and/or synthetic drugs and had previous contact with Toxoplasma gondii (IgG+), present any indication of an increased risk of toxoplasmosis reactivation. (2) Methods: Blood samples were collected, and peripheral blood mononuclear cells (PBMCs) were evaluated after stimulation with antigens of Toxoplasma gondii, with anti-CD3/anti-CD28 or without stimulus, at 48 and 96 h. CD69+, CD28+, and PD-1 stains were evaluated, in addition to intracellular expression of IFN-γ, IL-17, and IL-10 by CD4+ and the presence of regulatory CD4+ T cells by labeling CD25+, FOXP3, and LAP. The cytokines IL-2, IL-4, IL-6, IL-10, IFN-γ, TNF-α, and IL-17 were measured in the culture supernatant after 96 h. Serology for IgG and IgG1 was evaluated. (3) Results: There were no differences in the levels of IgG and IgG1 between the groups, but the IgG1 avidity was reduced in the immunobiological group compared to the control group. All groups exhibited a significant correlation between IgG and IgG1 positivity. CD4+ T lymphocytes expressing PD-1 were increased in individuals suffering from autoimmune rheumatic diseases and using disease-modifying antirheumatic drugs. In addition, treatment with TNF blockers did not seem to influence the populations of regulatory T cells and did not interfere with the expression of the cytokines IFN-γ, IL-17, and IL-10 by CD4+ cells or the production of cytokines by PBMCs from patients with AD. (4) Conclusions: This study presents evidence that the use of TNF-α blockers did not promote an immunological imbalance to the extent of impairing the anti-Toxoplasma gondii immune response and predisposing to toxoplasmosis reactivation.

Role of Interferon-Gamma Release Assay for the Diagnosis and Clinical Follow up in Ocular Tuberculosis.

PURPOSE: To assess the performance of interferon-gamma release assay (IGRA) associated with tuberculosis skin test (TST) for ocular tuberculosis (OTB) diagnosis and therapeutic decision making. METHOD: One hundred and ninety-one patients with ocular inflammation were prospectively followed-up. Patients with clinical signs highly suspected of OTB, TST≥10 mm, and/or IGRA≥0.35 IU/mL received antitubercular therapy (ATT). Sensitivity (Se), specificity (Sp), and area under the curve (AUC) were assessed. RESULTS: Seventy-two (37.7%) patients received ATT for presumed OTB. Combining TST and IGRA had Se=89.6%, Sp=99.2%, and AUC (0.98) significantly higher compared to TST (0.85, Z=6.3, p<.001) or IGRA (0.95, Z=2.5, p=.01). Prior history of corticosteroids or immunosuppressant with concomitantly oral prednisone and baseline IGRA> 2.0 IU/mL was associated significantly with more recurrences in ATT patients (p=.01)      . CONCLUSION: Considering TST and IGRA together was more effective in assessing OTB diagnosis. The real value of the IGRA test to predict recurrences needs further studies.

Metagenomics analysis of the morphological aspects and bacterial composition of broiler feces.

In this descriptive study, we used metagenomics to analyze the relationship between the morphological aspects of chicken feces and its respective bacterial compositions. The microbiota composition was determined by sequencing the V4 region of the 16S rRNA genes collected from fresh broiler feces at 19 d old. In total, 48 samples were collected and divided into 8 groups of 6 samples each. The morphological changes studied were feed passage (FP) and reddish mucus (RM). Each was classified into 3 levels of intensity: 1 (slight), 2 (moderate), or 3 (intense). Thus, the 8 groups studied were feed passage (FP-1; FP-2; FP-3), reddish mucus (RM-1; RM-2; RM-3), normal ileal feces (NIF), and cecal discharge (CD). The alpha diversity (Shannon's index) revealed that the CD group showed greater diversity, and was significantly different from FP-2, FP-3, and RM-1. The beta diversity showed that the CD group samples were more homogeneous than the ileal feces groups. The relative abundance analysis revealed that Firmicutes and Proteobacteria were the most abundant phyla in the ileal feces groups. In CD, Firmicutes and Bacteroidetes were the most abundant. The relative abundance at the genus level revealed 136 different bacterial genera. In the ileal feces groups, the two most abundant genera were Lactobacillus and Escherichia/Shigella, except in the FP-1 and RM-2 groups, which had the opposite order. Unlike the others, the CD group had a higher abundance of Bacteroides and Faecalibacterium. When comparing the NIF group with the others, significant changes were found in the fecal microbiota, with nine genera for the FP groups, 19 for the RM groups, and 61 when compared to CD. The results of the present study suggest that evaluation of fecal morphology is a fundamental task that makes it possible to act quickly and assertively, as the morphological aspects of the feces may be related to the composition and structure of fecal microbiota.

Multidrug-resistant tuberculous orchiepididymitis: a brief case report

ABSTRACT Tuberculosis (TB) is one of the leading causes of death by infectious diseases worldwide. Multidrug-resistant tuberculosis is a growing problem, especially in countries with high TB prevalence. Although the lungs are the organs most frequently affected by this disease, Mycobacterium tuberculosis can harm any organ, including the urogenital tract, causing extrapulmonary tuberculosis, which leads to a challenging diagnosis and consequent treatment delays. In this article, we present a case of orchiepididymitis caused by multidrug-resistant TB (MDR-TB) with a significantly delayed diagnosis, the proposed treatment according to the resistance profile, and the clinical outcomes.

Association of gestational diabetes mellitus and negative modulation of the specific humoral and cellular immune response against Toxoplasma gondii.

In order to evaluate and compare the specific immune response of pregnant women (PW) chronically infected with Toxoplasma gondii, with and without gestational diabetes mellitus (GDM), and the humoral response of their respective newborns (NB), the study was carried out on 81 PW (34 GDM and 47 controls) from whose medical records the results of the oral glucose tolerance test (OGTT) were obtained, and blood samples were collected at the third trimester of pregnancy; also, on 45 NBs (20 GDM and 25 controls) from whom umbilical cord blood samples were obtained. Humoral immunity was analyzed by measuring anti-T. gondii total IgG, IgG subclasses and IgG avidity. To evaluate cellular immunity, peripheral blood mononuclear cells (PBMC) from 32 PW (16 GDM and 16 controls) were cultured, supernatant cytokines were determined, and flow cytometry was performed to analyze the expression at lymphocytes of surface molecules, cytokines and transcription factors. All PW and NBs were positive for total IgG, and the prevalent subclass was IgG1. There was a negative correlation between the OGTT glycemia of PW and the levels of total IgG, IgG1 and IgG avidity. The IgG avidity of the GDM group was significantly lower than the control group. Patients from the GDM group had a higher number of T lymphocytes expressing markers of cell activation and exhaustion (CD28 and PD-1). In the presence of T. gondii soluble antigen (STAg) the amount of CD4+ T cells producing IFN-γ, IL-10 and IL-17 was significantly lower in the GDM group, while there was no difference between groups in the number of CD4+ CD25HighFOXP3+LAP+ functional Treg cells. Additionally, under STAg stimulus, the secretion of IL-17, IL-4, TNF and IL-2 cytokines at PBMCs culture supernatant was lower in the GDM group. In conclusion, there was a correlation between the increase in blood glucose and the decrease in levels of anti-T. gondii antibodies, associated with the decreased IgG avidity in patients who develop GDM. Also, the GDM group had decreased immune responses in Th1, Th2 and Th17 profiles, suggesting an association between GDM and the negative modulation of the humoral and cellular immune responses against T. gondii.

Immunophenotypic Analysis of T Lymphocytes and Cytokine Production in Elderly Practicing Physical Activities and Its Relationship with Quality of Life and Depression.

Aging is a complex process often associated with a chronic inflammatory profile that alters several biological functions, including the immune system and cognitive and physical capacity. The practice of physical activity is increasingly gaining popularity as a method of preventing infections, depression, and other disorders that affect the quality of life of the elderly. Thus, this work analyzes the profile of cytokines and molecular markers expressed in immune cells of elderly people who practice physical activities or not, evaluating their impacts on the immune system and quality of life. For this, 48 individuals were recruited, and peripheral blood samples were collected for hemogram analysis, cytokine determination, and immunophenotyping. Elderly people were separated into two groups: practitioners with low-intensity physical activity and non-practitioners. Quality of life was assessed using the Whoqol-Old instrument, and depression was assessed using the Beck II Depression Inventory. When comparing the scores of the Whoqol-Old and Beck questionnaires, we observed a significant negative correlation between these two factors. The perception of a higher quality of life was present in the elderly who exercised and was related to greater autonomy and sensory abilities, whereas the presence of depression was lower. In the hemogram, we observed higher basophil and segmented counts in the sedentary elderly, whereas lymphocytes and monocytes had lower counts. Elderly practitioners of physical activities had higher levels of IFN-γ, IL-4, and IL-10; increased expression of CD69, PD1, and TIM-3 in CD4+ T lymphocytes and increased CD14+CD80+ and CD14+CD86+ monocytes. Elderly people with an increased perception of quality of life had higher levels of IFN-γ, higher expression of CD14+CD80+CD86+, and decreased levels of TRAIL. An increase in TRAIL was observed in individuals with depression, in addition to an increased expression of CD14+CD86+. These results show a clear correlation between the quality of life, level of depression, physical activity, and immune system function. Although some cytokines with a typical proinflammatory profile (IFN-γ) were observed, the results point to a protective state with benefits reflected in the general well-being of the elderly who exercise.

Association of recurrent upper respiratory tract infections with low production of oxygen intermediates in children

Abstract Objectives: Upper respiratory tract infections in children generally have significant morbidity and mortality. There is little data available about functional immaturity of the immune system and the child's susceptibility to infections at the beginning of their lives, thus, justifying a more specific immunological analysis. Method: Analysis of hemograms and innate and adaptive immune responses in 95 children between age 1 to 6 years with episodes of recurrent respiratory infections (test group n = 39) and without these episodes (control group n = 56) was carried out. The production of reactive oxygen intermediates by peripheral blood cells stimulated by phorbol myristate acetate was analyzed. Additionally, the number of B lymphocytes, auxiliary T lymphocytes, and cytotoxic cells was determined using flow cytometry. Results: Results from both groups did not show statistically significant differences in red blood cells, total leukocytes count, and the differential neutrophils, eosinophils, basophils, lymphocytes, and monocytes count. The analysis of the number of B lymphocytes, auxiliary T lymphocytes (LTCD4), and cytotoxic cells (LTCD8) also did not show any difference between both groups. However, the production of radical oxygen intermediates was significantly reduced in the test group as compared to the control group (p < 0.05). Conclusions: There was no difference in the analysis of hemograms, leukograms, or the number of lymphocytes, LTCD4, LTCD8, or LTCD19. The reduced production of oxygen intermediates in the affected group suggests that these children's microbicide capacity is compromised, which may be related to their recurrent respiratory infections.

Low Body Mass Index at Treatment Initiation and Rifampicin-Resistant Tuberculosis Treatment Outcomes: An Individual Participant Data Meta-Analysis.

BACKGROUND: The impact of low body mass index (BMI) at initiation of rifampicin-resistant tuberculosis (RR-TB) treatment on outcomes is uncertain. We evaluated the association between BMI at RR-TB treatment initiation and end-of-treatment outcomes. METHODS: We performed an individual participant data meta-analysis of adults aged ≥18 years with RR-TB whose BMI was documented at treatment initiation. We compared odds of any unfavorable treatment outcome, mortality, or failure/recurrence between patients who were underweight (BMI <18.5 kg/m2) and not underweight. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were estimated using logistic regression, with matching on demographic, clinical, and treatment-related factors. We evaluated effect modification by human immunodeficiency virus (HIV) status and other variables using likelihood ratio tests. We also estimated cumulative incidence of mortality during treatment stratified by HIV. RESULTS: Overall, 5148 patients were included; 1702 (33%) were underweight at treatment initiation. The median (interquartile range) age was 37 years (29 to 47), and 455 (9%) had HIV. Compared with nonunderweight patients, the aOR among underweight patients was 1.7 (95% CI, 1.4-1.9) for any unfavorable outcome, 3.1 (2.4-3.9) for death, and 1.6 (1.2-2.0) for failure/recurrence. Significant effect modification was found for World Health Organization region of treatment. Among HIV-negative patients, 24-month mortality was 14.8% (95% CI, 12.7%-17.3%) for underweight and 5.6% (4.5%-7.0%) for not underweight patients. Among patients with HIV, corresponding values were 33.0% (25.6%-42.6%) and 20.9% (14.1%-27.6%). CONCLUSIONS: Low BMI at treatment initiation for RR-TB is associated with increased odds of unfavorable treatment outcome, particularly mortality.

Campimetry and visual changes after RHZE treatment for tuberculosis.

BACKGROUND: Tuberculosis (TB) caused by Mycobacterium tuberculosis has a high prevalence in Brazil (Global tuberculosis report 2020. Geneva: World Health Organization; 2020). The ethambutol-induced optic neuropathy damage is partly reversible, making its early diagnosis essential to reduce permanent visual damage. PURPOSE: To observe alterations in the computerized campimetry, Ishihara test and visual acuity secondary to rifampicin, isoniazid, pyrimethamine, ethambutol (RHZE) treatment. METHODS: Patients undergoing treatment with RHZE at the tuberculosis service of the Federal University of São Paulo were recruited from March 2019 to December 2020. The best-corrected visual acuity (VA) measurements, Ishihara test and visual fields were performed at baseline, monthly, until 2 weeks after treatment. RESULTS: Twenty-five patients were included. The VA decreased significantly (P = 0.0129) post-treatment compared to month 1. The mean deviation (MD) did not decrease significantly (P > 0.05); the pattern standard deviation (PSD) decreased post-treatment compared to month 1 (P = 0.0371). Changes in the Ishihara test increased significantly (P < 0.0001) in the second month. CONCLUSION: The VA and PSD decreased significantly after RHZE treatment. Changes in the Ishihara test were observed in the second month. TRIAL REGISTRATION: The Research Ethics Committee of Federal University of São Paulo, Paulista School of Medicine approved the study in March 2019. CAAE 04297018.4.0000.5505.

Association of recurrent upper respiratory tract infections with low production of oxygen intermediates in children.

OBJECTIVES: Upper respiratory tract infections in children generally have significant morbidity and mortality. There is little data available about functional immaturity of the immune system and the child's susceptibility to infections at the beginning of their lives, thus, justifying a more specific immunological analysis. METHOD: Analysis of hemograms and innate and adaptive immune responses in 95 children between age 1 to 6 years with episodes of recurrent respiratory infections (test group n = 39) and without these episodes (control group n = 56) was carried out. The production of reactive oxygen intermediates by peripheral blood cells stimulated by phorbol myristate acetate was analyzed. Additionally, the number of B lymphocytes, auxiliary T lymphocytes, and cytotoxic cells was determined using flow cytometry. RESULTS: Results from both groups did not show statistically significant differences in red blood cells, total leukocytes count, and the differential neutrophils, eosinophils, basophils, lymphocytes, and monocytes count. The analysis of the number of B lymphocytes, auxiliary T lymphocytes (LTCD4), and cytotoxic cells (LTCD8) also did not show any difference between both groups. However, the production of radical oxygen intermediates was significantly reduced in the test group as compared to the control group (p < 0.05). CONCLUSIONS: There was no difference in the analysis of hemograms, leukograms, or the number of lymphocytes, LTCD4, LTCD8, or LTCD19. The reduced production of oxygen intermediates in the affected group suggests that these children's microbicide capacity is compromised, which may be related to their recurrent respiratory infections.

Clinical features and management of presumed ocular tuberculosis: A long-term follow-up cohort study in a tertiary referral center in Brazil.

PURPOSE: To evaluate the clinical features and management of presumed ocular tuberculosis (OTB). METHOD: A prospective 3-year follow-up study of patients with ocular inflammation that performed Interferon-gamma release assay (IGRA) and tuberculin skin test (TST) was conducted in a tertiary referral center in Brazil. Patients with clinical signs highly suspect of OTB with a positive TST and/or IGRA with other causes ruled out were prescribed anti-tuberculosis therapy (ATT) during 9 months. Clinical features and treatment outcomes were recorded. RESULTS: Seventy-two patients (mean age 48.3 ± 15.7 years) were included in the study, and most were female (65.3%, n = 47). Posterior uveitis (43.1%, n = 31) was the main clinical feature. Multifocal choroiditis (25%, n = 18) was the most common choroidal involvement. Concomitant oral prednisone (45.8%, n = 33) during ATT was associated with more recurrences (p = 0.04). A significant difference (p < 0.001) between initial and final best-corrected visual acuity after ATT conclusion was observed. Cure or remission was observed in 58 (85.3%) patients that completed follow-up (n = 68). CONCLUSION: In our cohort some variation in demographics and ocular phenotypes of presumed OTB was observed. The high rates of cure or remission of our patients strongly support the ATT in presumed OTB. Oral corticosteroids during ATT were associated with higher recurrences rates.