High seroprevalence of antibodies against arboviruses in postpartum women in Salvador, Brazil.

Objectives: Arboviruses represent a major challenge to public health in Brazil. Dengue (DENV) virus has been endemic for decades, and the introduction of Zika (2015) and Chikungunya (2014) viruses (CHIKV) has imposed a significant burden on the country. The present study aimed to investigate the seroprevalence of Zika virus (ZIKV), DENV and CHIKV in women in Salvador, Bahia-Brazil. Methods: Cross-sectional study involving postpartum women admitted to a maternity hospital in Salvador, Brazil. Anti-ZIKV, anti-DENV and anti-CHIKV immunoglobulin G was measured by enzyme-linked immunosorbent assay. Results: A total of 302 women were enrolled with a median age: 26 years, interquartile range (21-33). Most self-declared as mixed-race or black skin color (92.4%). The seroprevalence was 57% for ZIKV); 91.4% for DENV, and 7.6% for CHIKV. Most participants denied awareness of previous arboviral infection, although 67 (22.3%) reported a previous history of ZIKV infection, 34 (11.1%) DENV infection and 9 (3%) CHIKV infection. Conclusion: Our data indicate a high prevalence of past ZIKV and DENV infections in the population studied. Most of the participants remain susceptible to future CHIKV infection, highlighting the need for preventive and educational interventions. Our results suggest the need for continuous epidemiological surveillance of arboviral diseases, particularly among women residing in at-risk regions.

Multi-omic longitudinal study reveals immune correlates of clinical course among hospitalized COVID-19 patients.

The IMPACC cohort, composed of >1,000 hospitalized COVID-19 participants, contains five illness trajectory groups (TGs) during acute infection (first 28 days), ranging from milder (TG1-3) to more severe disease course (TG4) and death (TG5). Here, we report deep immunophenotyping, profiling of >15,000 longitudinal blood and nasal samples from 540 participants of the IMPACC cohort, using 14 distinct assays. These unbiased analyses identify cellular and molecular signatures present within 72 h of hospital admission that distinguish moderate from severe and fatal COVID-19 disease. Importantly, cellular and molecular states also distinguish participants with more severe disease that recover or stabilize within 28 days from those that progress to fatal outcomes (TG4 vs. TG5). Furthermore, our longitudinal design reveals that these biologic states display distinct temporal patterns associated with clinical outcomes. Characterizing host immune responses in relation to heterogeneity in disease course may inform clinical prognosis and opportunities for intervention.

Antibodies to repeat-containing antigens in Plasmodium falciparum are exposure-dependent and short-lived in children in natural malaria infections.

Protection against Plasmodium falciparum, which is primarily antibody-mediated, requires recurrent exposure to develop. The study of both naturally acquired limited immunity and vaccine induced protection against malaria remains critical for ongoing eradication efforts. Towards this goal, we deployed a customized P. falciparum PhIP-seq T7 phage display library containing 238,068 tiled 62-amino acid peptides, covering all known coding regions, including antigenic variants, to systematically profile antibody targets in 198 Ugandan children and adults from high and moderate transmission settings. Repeat elements - short amino acid sequences repeated within a protein - were significantly enriched in antibody targets. While breadth of responses to repeat-containing peptides was twofold higher in children living in the high versus moderate exposure setting, no such differences were observed for peptides without repeats, suggesting that antibody responses to repeat-containing regions may be more exposure dependent and/or less durable in children than responses to regions without repeats. Additionally, short motifs associated with seroreactivity were extensively shared among hundreds of antigens, potentially representing cross-reactive epitopes. PfEMP1 shared motifs with the greatest number of other antigens, partly driven by the diversity of PfEMP1 sequences. These data suggest that the large number of repeat elements and potential cross-reactive epitopes found within antigenic regions of P. falciparum could contribute to the inefficient nature of malaria immunity.

Evaluation of transplacental transfer of mRNA vaccine products and functional antibodies during pregnancy and infancy.

Studies are needed to evaluate the safety and effectiveness of mRNA SARS-CoV-2 vaccination during pregnancy, and the levels of protection provided to their newborns through placental transfer of antibodies. Here, we evaluate the transplacental transfer of mRNA vaccine products and functional anti-SARS-CoV-2 antibodies during pregnancy and early infancy in a cohort of 20 individuals vaccinated during late pregnancy. We find no evidence of mRNA vaccine products in maternal blood, placenta tissue, or cord blood at delivery. However, we find time-dependent efficient transfer of IgG and neutralizing antibodies to the neonate that persists during early infancy. Additionally, using phage immunoprecipitation sequencing, we find a vaccine-specific signature of SARS-CoV-2 Spike protein epitope binding that is transplacentally transferred during pregnancy. Timing of vaccination during pregnancy is critical to ensure transplacental transfer of protective antibodies during early infancy.

Multiple sclerosis therapies differentially affect SARS-CoV-2 vaccine-induced antibody and T cell immunity and function.

BACKGROUNDVaccine-elicited adaptive immunity is a prerequisite for control of SARS-CoV-2 infection. Multiple sclerosis (MS) disease-modifying therapies (DMTs) differentially target humoral and cellular immunity. A comprehensive comparison of the effects of MS DMTs on SARS-CoV-2 vaccine-specific immunity is needed, including quantitative and functional B and T cell responses.METHODSSpike-specific Ab and T cell responses were measured before and following SARS-CoV-2 vaccination in a cohort of 80 study participants, including healthy controls and patients with MS in 6 DMT groups: untreated and treated with glatiramer acetate (GA), dimethyl fumarate (DMF), natalizumab (NTZ), sphingosine-1-phosphate (S1P) receptor modulators, and anti-CD20 mAbs. Anti-spike-Ab responses were assessed by Luminex assay, VirScan, and pseudovirus neutralization. Spike-specific CD4+ and CD8+ T cell responses were characterized by activation-induced marker and cytokine expression and tetramer.RESULTSAnti-spike IgG levels were similar between healthy control participants and patients with untreated MS and those receiving GA, DMF, or NTZ but were reduced in anti-CD20 mAb- and S1P-treated patients. Anti-spike seropositivity in anti-CD20 mAb-treated patients was correlated with CD19+ B cell levels and inversely correlated with cumulative treatment duration. Spike epitope reactivity and pseudovirus neutralization were reduced in anti-CD20 mAb- and S1P-treated patients. Spike-specific CD4+ and CD8+ T cell reactivity remained robust across all groups, except in S1P-treated patients, in whom postvaccine CD4+ T cell responses were attenuated.CONCLUSIONThese findings from a large cohort of patients with MS exposed to a wide spectrum of MS immunotherapies have important implications for treatment-specific COVID-19 clinical guidelines.FUNDINGNIH grants 1K08NS107619, K08NS096117, R01AI159260, R01NS092835, R01AI131624, and R21NS108159; NMSS grants TA-1903-33713 and RG1701-26628; Westridge Foundation; Chan Zuckerberg Biohub; Maisin Foundation.

Evaluation of transplacental transfer of mRNA vaccine products and functional antibodies during pregnancy and early infancy.

Studies are needed to evaluate the safety and effectiveness of mRNA SARS-CoV-2 vaccination during pregnancy, and the levels of protection provided to their newborns through placental transfer of antibodies. We evaluated the transplacental transfer of mRNA vaccine products and functional anti-SARS-CoV-2 antibodies during pregnancy and early infancy in a cohort of 20 individuals vaccinated during pregnancy. We found no evidence of mRNA vaccine products in maternal blood, placenta tissue, or cord blood at delivery. However, we found time-dependent efficient transfer of IgG and neutralizing antibodies to the neonate that persisted during early infancy. Additionally, using phage immunoprecipitation sequencing, we found a vaccine-specific signature of SARS-CoV-2 Spike protein epitope binding that is transplacentally transferred during pregnancy. In conclusion, products of mRNA vaccines are not transferred to the fetus during pregnancy, however timing of vaccination during pregnancy is critical to ensure transplacental transfer of protective antibodies during early infancy.

Evaluation of transplacental transfer of mRNA vaccine products and functional antibodies during pregnancy and early infancy.

Studies are needed to evaluate the safety and effectiveness of mRNA SARS-CoV-2 vaccination during pregnancy, and the levels of protection provided to their newborns through placental transfer of antibodies. We evaluated the transplacental transfer of mRNA vaccine products and functional anti-SARS-CoV-2 antibodies during pregnancy and early infancy in a cohort of 20 individuals vaccinated during pregnancy. We found no evidence of mRNA vaccine products in maternal blood, placenta tissue, or cord blood at delivery. However, we found time-dependent efficient transfer of IgG and neutralizing antibodies to the neonate that persisted during early infancy. Additionally, using phage immunoprecipitation sequencing, we found a vaccine-specific signature of SARS-CoV-2 Spike protein epitope binding that is transplacentally transferred during pregnancy. In conclusion, products of mRNA vaccines are not transferred to the fetus during pregnancy, however timing of vaccination during pregnancy is critical to ensure transplacental transfer of protective antibodies during early infancy.

Impact of multiple sclerosis disease-modifying therapies on SARS-CoV-2 vaccine-induced antibody and T cell immunity.

Vaccine-elicited adaptive immunity is an essential prerequisite for effective prevention and control of coronavirus 19 (COVID-19). Treatment of multiple sclerosis (MS) involves a diverse array of disease-modifying therapies (DMTs) that target antibody and cell-mediated immunity, yet a comprehensive understanding of how MS DMTs impact SARS-CoV-2 vaccine responses is lacking. We completed a detailed analysis of SARS-CoV-2 vaccine-elicited spike antigen-specific IgG and T cell responses in a cohort of healthy controls and MS participants in six different treatment categories. Two specific DMT types, sphingosine-1-phosphate (S1P) receptor modulators and anti-CD20 monoclonal antibodies (mAb), resulted in significantly reduced spike-specific IgG responses. Longer duration of anti-CD20 mAb treatment prior to SARS-CoV-2 vaccination were associated with absent antibody responses. Except for reduced CD4+ T cell responses in S1P-treated patients, spike-specific CD4+ and CD8+ T cell reactivity remained robust across all MS treatment types. These findings have important implications for clinical practice guidelines and vaccination recommendations in MS patients and other immunosuppressed populations.

Phage display demonstrates durable differences in serological profile by route of inoculation in primary infections of non-human primates with Dengue Virus 1.

Natural dengue virus (DENV) infections occur by mosquito bite but how the inoculation route affects the humoral immune response is unknown. We serologically profiled 20 non-human primates (NHP) from a prior study of DENV1 infection where animals were inoculated by mosquito (N = 10) or subcutaneous injection (N = 10). Using a comprehensive, densely tiled and highly redundant pan-flavivirus programmable phage library containing 91,562 overlapping 62 amino acid peptides, we produced a high-resolution map of linear peptide sequences enriched during DENV seroconversion. Profiles in mosquito-inoculated and subcutaneously-inoculated animals were similar up to 90 days after primary infection, but diverged at 1 year with differences in sero-reactivity in the Envelope (E; residues 215-406; p < 0.08), and Nonstructural-3 (NS3; residues 549-615; p < 0.05) proteins in mosquito-inoculated versus subcutaneously-inoculated animals. Within the E protein, residues 339-384 in domain III accounted for > 99% of the observed sero-reactivity difference. Antibody breadth did not vary by mode of inoculation. The differential reactivity to E domain III seen by phage display validated orthogonally by ELISA, but did not correlate with late neutralization titers. Serological profiling of humoral immune responses to DENV infection in NHP by programmable phage display demonstrated durable differences in sero-reactivity by route of inoculation.

ReScan, a Multiplex Diagnostic Pipeline, Pans Human Sera for SARS-CoV-2 Antigens.

Comprehensive understanding of the serological response to SARS-CoV-2 infection is important for both pathophysiologic insight and diagnostic development. Here, we generate a pan-human coronavirus programmable phage display assay to perform proteome-wide profiling of coronavirus antigens enriched by 98 COVID-19 patient sera. Next, we use ReScan, a method to efficiently sequester phage expressing the most immunogenic peptides and print them onto paper-based microarrays using acoustic liquid handling, which isolates and identifies nine candidate antigens, eight of which are derived from the two proteins used for SARS-CoV-2 serologic assays: spike and nucleocapsid proteins. After deployment in a high-throughput assay amenable to clinical lab settings, these antigens show improved specificity over a whole protein panel. This proof-of-concept study demonstrates that ReScan will have broad applicability for other emerging infectious diseases or autoimmune diseases that lack a valid biomarker, enabling a seamless pipeline from antigen discovery to diagnostic using one recombinant protein source.

Evaluation of multi-antigen serological screening for active tuberculosis among people living with HIV.

Better triage tests for screening tuberculosis (TB) disease are needed for people living with HIV (PLHIV). We performed the first evaluation of a previously-validated 8-antigen serological panel to screen PLHIV for pulmonary TB in Kampala, Uganda. We selected a random 1:1 sample with and without TB (defined by sputum culture) from a cohort of PLHIV initiating antiretroviral therapy. We used a multiplex microbead immunoassay and an ensemble machine learning classifier to determine the area under the receiver operating characteristic curve (AUC) for Ag85A, Ag85B, Ag85C, Rv0934-P38, Rv3881, Rv3841-BfrB, Rv3873, and Rv2878c. We then assessed the performance with the addition of four TB-specific antigens ESAT-6, CFP-10, Rv1980-MPT64, and Rv2031-HSPX, and every antigen combination. Of 262 participants (median CD4 cell-count 152 cells/µL [IQR 65-279]), 138 (53%) had culture-confirmed TB. The 8-antigen panel had an AUC of 0.53 (95% CI 0.40-0.66), and the additional 4 antigens did not improve performance (AUC 0.51, 95% CI 0.39-0.64). When sensitivity was restricted to ≥90% for the 8- and 12-antigen panel, specificity was 2.2% (95% CI 0-17.7%) and 8.1% (95% CI 0-23.9%), respectively. A three-antigen combination (Rv0934-P38, Ag85A, and Rv2031-HSPX) outperformed both panels, with an AUC of 0.60 (95% CI 0.48-0.73), 90% sensitivity (95% CI 78.2-96.7%) and 29.7% specificity (95% CI 15.9-47%). The multi-antigen panels did not achieve the target accuracy for a TB triage test among PLHIV. We identified a new combination that improved performance for TB screening in an HIV-positive sample compared to an existing serological panel in Uganda, and suggests an approach to identify novel antigen combinations specifically for screening TB in PLHIV.

A Novel, 5-Transcript, Whole-blood Gene-expression Signature for Tuberculosis Screening Among People Living With Human Immunodeficiency Virus.

BACKGROUND: Gene-expression profiles have been reported to distinguish between patients with and without active tuberculosis (TB), but no prior study has been conducted in the context of TB screening. METHODS: We included all the patients (n = 40) with culture-confirmed TB and time-matched controls (n = 80) enrolled between July 2013 and April 2015 in a TB screening study among people living with human immunodeficiency virus (PLHIV) in Kampala, Uganda. We randomly split the patients into training (n = 80) and test (n = 40) datasets. We used the training dataset to derive candidate signatures that consisted of 1 to 5 differentially-expressed transcripts (P ≤ .10) and compared the performance of our candidate signatures with 4 published TB gene-expression signatures, both on the independent test dataset and in 2 external datasets. RESULTS: We identified a novel, 5-transcript signature that met the accuracy thresholds recommended for a TB screening test. On the independent test dataset, our signature had an area under the curve (AUC) of 0.87 (95% confidence interval [CI] 0.72-0.98), with sensitivity of 94% and specificity of 75%. None of the 4 published TB signatures achieved desired accuracy thresholds. Our novel signature performed well in external datasets from both high (AUC 0.81, 95% CI 0.74-0.88) and low (0.81, 95% CI 0.77-0.85) TB burden settings. CONCLUSIONS: We identified the first gene-expression signature for TB screening. Our signature has the potential to be translated into a point-of-care test to facilitate systematic TB screening among PLHIV and other high-risk populations.

A multivariate analysis of CalEnviroScreen: comparing environmental and socioeconomic stressors versus chronic disease.

BACKGROUND: The health-risk assessment paradigm is shifting from single stressor evaluation towards cumulative assessments of multiple stressors. Recent efforts to develop broad-scale public health hazard datasets provide an opportunity to develop and evaluate multiple exposure hazards in combination. METHODS: We performed a multivariate study of the spatial relationship between 12 indicators of environmental hazard, 5 indicators of socioeconomic hardship, and 3 health outcomes. Indicators were obtained from CalEnviroScreen (version 3.0), a publicly available environmental justice screening tool developed by the State of California Environmental Protection Agency. The indicators were compared to the total rate of hospitalization for 14 ICD-9 disease categories (a measure of disease burden) at the zip code tabulation area population level. We performed principal component analysis to visualize and reduce the CalEnviroScreen data and spatial autoregression to evaluate associations with disease burden. RESULTS: CalEnviroScreen was strongly associated with the first principal component (PC) from a principal component analysis (PCA) of all 20 variables (Spearman ρ = 0.95). In a PCA of the 12 environmental variables, two PC axes explained 43% of variance, with the first axis indicating industrial activity and air pollution, and the second associated with ground-level ozone, drinking water contamination and PM2.5. Mass of pesticides used in agriculture was poorly or negatively correlated with all other environmental indicators, and with the CalEnviroScreen calculation method, suggesting a limited ability of the method to capture agricultural exposures. In a PCA of the 5 socioeconomic variables, the first PC explained 66% of variance, representing overall socioeconomic hardship. In simultaneous autoregressive models, the first environmental and socioeconomic PCs were both significantly associated with the disease burden measure, but more model variation was explained by the socioeconomic PCs. CONCLUSIONS: This study supports the use of CalEnviroScreen for its intended purpose of screening California regions for areas with high environmental exposure and population vulnerability. Study results further suggest a hypothesis that, compared to environmental pollutant exposure, socioeconomic status has greater impact on overall burden of disease.

Prevalence and risk factors for latent tuberculosis infection among primary health care workers in Brazil.

Health care workers (HCW) are at increased risk of latent tuberculosis infection (LTBI) from occupational exposure to Mycobacterium tuberculosis. The objective was to determine the prevalence of and risk factors for LTBI among primary HCW in five Brazilian cities. We conducted a cross-sectional study, from 2011 to 2013, among primary HCW, using a structured questionnaire and an evaluated for LTBI using the Quantiferon-TB Gold in-tube test. The magnitude of the associations was assessed using hierarchical logistic regression models. Among 708 HCW, the LTBI prevalence was 27% (n = 196; 95%CI: 24%-31%). We found that the following factors were positively associated with LTBI in primary HCW: age > 50 years (OR = 2.94; 95%CI: 1.44-5.99), absence of a BCG scar (OR = 2.10; 95%CI: 1.28-3.43), self-reported ex-smoker status (OR = 1.80; 95%CI: 1.04-3.11), being a nurse (OR = 2.97; 95%CI: 1.13-7.83), being a nurse technician (OR = 3.10; 95%CI: 1.26-7.60), being a community health agent (OR = 2.60; 95%CI: 1.06-6.40), and irregular use of N95 masks (OR = 2.51; 95%CI: 1.11-5.98). In contrast, HCWs who do not work in health care facilities with a TB control program were less likely to have LTBI (OR = 0.66; 95%CI: 0.45-0.97). This study demonstrated a substantial occupational risk of LTBI among primary HCW in Brazil. The Brazilian TB control program, as well as local programs, need to target these high-risk HCW with education, as well as with better personal protective equipment to prevent acquisition of new TB infection.

Clinical and epidemiological characteristics associated with unfavorable tuberculosis treatment outcomes in TB-HIV co-infected patients in Brazil: a hierarchical polytomous analysis

Abstract Background: TB patients co-infected with HIV have worse treatment outcomes than non-coinfected patients. How clinical characteristics of TB and socioeconomic characteristics influence these outcomes is poorly understood. Here, we use polytomous regression analysis to identify clinical and epidemiological characteristics associated with unfavorable treatment outcomes among TB-HIV co-infected patients in Brazil. Methods: TB-HIV cases reported in the Brazilian information system (SINAN) between January 1, 2001 and December 31, 2011 were identified and categorized by TB treatment outcome (cure, default, death, and development of MDR TB). We modeled treatment outcome as a function of clinical characteristics of TB and patient socioeconomic characteristics by polytomous regression analysis. For each treatment outcome, we used cure as the reference outcome. Results: Between 2001 and 2011, 990,017 cases of TB were reported in SINAN, of which 93,147 (9.4%) were HIV co-infected. Patients aged 15–19 (OR = 2.86; 95% CI: 2.09–3.91) and 20–39 years old (OR = 2.30; 95% CI: 1.81–2.92) were more likely to default on TB treatment than those aged 0–14 years old. In contrast, patients aged ≥60 years were more likely to die from TB (OR = 2.22; 95% CI: 1.43–3.44) or other causes (OR = 2.86; 95% CI: 2.14–3.83). Black patients were more likely to default on TB treatment (OR = 1.33; 95% CI: 1.22–1.44) and die from TB (OR = 1.50; 95% CI: 1.29–1.74). Finally, alcoholism was associated with all unfavorable outcomes: default (OR = 1.94; 95% CI: 1.73–2.17), death due to TB (OR = 1.46; 95% CI: 1.25–1.71), death due to other causes (OR = 1.38; 95% CI: 1.21–1.57) and MDR-TB (OR = 2.29; 95% CI: 1.46–3.58). Conclusions: Socio-economic vulnerability has a significant effect on treatment outcomes among TB-HIV co-infected patients in Brazil. Enhancing social support, incorporation of alcohol abuse screening and counseling into current TB surveillance programs and targeting interventions to specific age groups are interventions that could improve treatment outcomes.

Differences in the Prevalence of Non-Communicable Disease between Slum Dwellers and the General Population in a Large Urban Area in Brazil.

Residents of urban slums are at greater risk for disease than their non-slum dwelling urban counterparts. We sought to contrast the prevalences of selected non-communicable diseases (NCDs) between Brazilian adults living in a slum and the general population of the same city, by comparing the age and sex-standardized prevalences of selected NCDs from a 2010 survey in Pau da Lima, Salvador Brazil, with a 2010 national population-based telephone survey. NCD prevalences in both populations were similar for hypertension (23.6% (95% CI 20.9⁻26.4) and 22.9% (21.2⁻24.6), respectively) and for dyslipidemia (22.7% (19.8⁻25.5) and 21.5% (19.7⁻23.4)). Slum residents had higher prevalences of diabetes mellitus (10.1% (7.9⁻12.3)) and of overweight/obesity (46.5% (43.1⁻49.9)), compared to 5.2% (4.2⁻6.1) and 40.6% (38.5⁻42.8) of the general population in Salvador. Fourteen percent (14.5% (12.1⁻17.0)) of slum residents smoked cigarettes compared to 8.3% (7.1⁻9.5) of the general population in Salvador. The national telephone survey underestimated the prevalence of diabetes mellitus, overweight/obesity, and smoking in the slum population, likely in part due to differential sampling inside and outside of slums. Further research and targeted policies are needed to mitigate these inequalities, which could have significant economic and social impacts on slum residents and their communities.

Clinical and epidemiological characteristics associated with unfavorable tuberculosis treatment outcomes in TB-HIV co-infected patients in Brazil: a hierarchical polytomous analysis.

BACKGROUND: TB patients co-infected with HIV have worse treatment outcomes than non-coinfected patients. How clinical characteristics of TB and socioeconomic characteristics influence these outcomes is poorly understood. Here, we use polytomous regression analysis to identify clinical and epidemiological characteristics associated with unfavorable treatment outcomes among TB-HIV co-infected patients in Brazil. METHODS: TB-HIV cases reported in the Brazilian information system (SINAN) between January 1, 2001 and December 31, 2011 were identified and categorized by TB treatment outcome (cure, default, death, and development of MDR TB). We modeled treatment outcome as a function of clinical characteristics of TB and patient socioeconomic characteristics by polytomous regression analysis. For each treatment outcome, we used cure as the reference outcome. RESULTS: Between 2001 and 2011, 990,017 cases of TB were reported in SINAN, of which 93,147 (9.4%) were HIV co-infected. Patients aged 15-19 (OR=2.86; 95% CI: 2.09-3.91) and 20-39 years old (OR=2.30; 95% CI: 1.81-2.92) were more likely to default on TB treatment than those aged 0-14 years old. In contrast, patients aged ≥60 years were more likely to die from TB (OR=2.22; 95% CI: 1.43-3.44) or other causes (OR=2.86; 95% CI: 2.14-3.83). Black patients were more likely to default on TB treatment (OR=1.33; 95% CI: 1.22-1.44) and die from TB (OR=1.50; 95% CI: 1.29-1.74). Finally, alcoholism was associated with all unfavorable outcomes: default (OR=1.94; 95% CI: 1.73-2.17), death due to TB (OR=1.46; 95% CI: 1.25-1.71), death due to other causes (OR=1.38; 95% CI: 1.21-1.57) and MDR-TB (OR=2.29; 95% CI: 1.46-3.58). CONCLUSIONS: Socio-economic vulnerability has a significant effect on treatment outcomes among TB-HIV co-infected patients in Brazil. Enhancing social support, incorporation of alcohol abuse screening and counseling into current TB surveillance programs and targeting interventions to specific age groups are interventions that could improve treatment outcomes.

Prevalence and risk factors for latent tuberculosis infection among primary health care workers in Brazil / Prevalência de infecção latente da tuberculose e fatores de risco entre profissionais de saúde na atenção primária no Brasil / Prevalencia de infección latente de la tuberculosis y factores de riesgo entre profesionales de salud en la atención primaria en Brasil

Health care workers (HCW) are at increased risk of latent tuberculosis infection (LTBI) from occupational exposure to Mycobacterium tuberculosis. The objective was to determine the prevalence of and risk factors for LTBI among primary HCW in five Brazilian cities. We conducted a cross-sectional study, from 2011 to 2013, among primary HCW, using a structured questionnaire and an evaluated for LTBI using the Quantiferon-TB Gold in-tube test. The magnitude of the associations was assessed using hierarchical logistic regression models. Among 708 HCW, the LTBI prevalence was 27% (n = 196; 95%CI: 24%-31%). We found that the following factors were positively associated with LTBI in primary HCW: age > 50 years (OR = 2.94; 95%CI: 1.44-5.99), absence of a BCG scar (OR = 2.10; 95%CI: 1.28-3.43), self-reported ex-smoker status (OR = 1.80; 95%CI: 1.04-3.11), being a nurse (OR = 2.97; 95%CI: 1.13-7.83), being a nurse technician (OR = 3.10; 95%CI: 1.26-7.60), being a community health agent (OR = 2.60; 95%CI: 1.06-6.40), and irregular use of N95 masks (OR = 2.51; 95%CI: 1.11-5.98). In contrast, HCWs who do not work in health care facilities with a TB control program were less likely to have LTBI (OR = 0.66; 95%CI: 0.45-0.97). This study demonstrated a substantial occupational risk of LTBI among primary HCW in Brazil. The Brazilian TB control program, as well as local programs, need to target these high-risk HCW with education, as well as with better personal protective equipment to prevent acquisition of new TB infection.

Os profissionais de saúde apresentam risco aumentado de infecção latente da tuberculose (ILTB) em função da exposição ocupacional ao Mycobacterium tuberculosis. O estudo teve como objetivo estimar a prevalência da ILTB e fatores de risco entre profissionais de saúde na atenção primária em cinco cidades brasileiras. Realizamos um estudo transversal entre 2011 e 2013 entre profissionais de saúde na atenção primária, usando um questionário estruturado, e avaliamos a ILTB com o teste Quantiferon-TB Gold In-Tube. A magnitude das associações foi avaliada com o uso de modelos de regressão logística hierárquica. Entre 708 profissionais de saúde, a prevalência de ILTB era 27% (n = 196; IC95%: 24%-31%). Os seguintes fatores mostraram associação positiva com ILTB entre profissionais de saúde na atenção primária: idade > 50 anos (OR = 2,94; IC95%: 1,44-5,99), ausência de cicatriz de BCG (OR = 2,10; IC95%: 1,28-3,43), ex-tabagista (OR = 1,80; IC95%: 1,04-3,11), profissão enfermeiro (OR = 2,97; IC95%: 1,13-7,83), profissão técnico de enfermagem (OR = 3,10; IC95%: 1,26-7,60), profissão agente comunitário de saúde (OR = 2,60; IC95%: 1,06-6,40) e uso irregular de máscaras N95 (OR = 2,51; IC95%: 1,11-5,98). Enquanto isso, os profissionais de saúde que não trabalham em serviços de saúde que dispõem de programa de controle da TB tem menor probabilidade de apresentar ILTB (OR = 0,66; IC95%: 0,45-0,97). O estudo demonstrou risco ocupacional substancial de ILTB entre profissionais de saúde na atenção primária no Brasil. O programa brasileiro de controle da tuberculose, assim como os programas locais, devem focar esses profissionais de saúde, de risco elevado, através de atividades educativas, assim como, equipamento de proteção individual melhor para prevenir a aquisição de novos casos de infecção pela tuberculose.

Los profesionales de salud presentan un riesgo aumentado de infección latente de la tuberculosis (ILTB), en función de la exposición ocupacional al Mycobacterium tuberculosis. El objetivo del estudio fue estimar la prevalencia de la ILTB y sus factores de riesgo entre profesionales de salud en la atención primaria en cinco ciudades brasileñas. Realizamos un estudio transversal entre 2011 y 2013 entre profesionales de salud en la atención primaria, usando un cuestionario estructurado, y evaluamos la ILTB con el test Quantiferon-TB Gold In-Tube. La magnitud de las asociaciones fue evaluada con el uso de modelos de regresión logística jerárquica. Entre 708 profesionales de salud, la prevalencia de ILTB era 27% (n = 196; IC95%: 24%-31%). Los siguientes factores mostraron una asociación positiva con ILTB entre profesionales de salud en la atención primaria: edad > 50 años (OR = 2,94; IC95%: 1,44-5,99), ausencia de cicatriz de BCG (OR = 2,10; IC95%: 1,28-3,43), ex-fumador (OR = 1,80; IC95%: 1,04-3,11), profesión enfermero (OR = 2,97; IC95%: 1,13-7,83), profesión técnico de enfermería (OR = 3,10; IC95%: 1,26-7,60), profesión agente comunitario de salud (OR = 2,60; IC95%: 1,06-6,40) y uso irregular de máscaras N95 (OR = 2,51; IC95%: 1,11-5,98). Por otra parte, los profesionales de salud que no trabajan en servicios de salud que disponen de programa de control de la TB tienen una menor probabilidad de presentar ILTB (OR = 0,66; IC95%: 0,45-0,97). El estudio demostró riesgo ocupacional substancial de ILTB entre profesionales de salud en la atención primaria en Brasil. El programa brasileño de control de la tuberculosis, así como los programas locales, deben centrarse en esos profesionales de salud, de riesgo elevado, a través de actividades educativas, así como un mejor equipamiento de protección individual para prevenir el surgimiento de nuevos casos de infección por tuberculosis.

Understanding the barriers to successful adoption and use of a mobile health information system in a community health center in São Paulo, Brazil: a cohort study.

BACKGROUND: Mobile technology to support community health has surged in popularity, yet few studies have systematically examined usability of mobile platforms for this setting. METHODS: We conducted a mixed-methods study of 14 community healthcare workers at a public healthcare clinic in São Paulo, Brazil. We held focus groups with community healthcare workers to elicit their ideas about a mobile health application and used this input to build a prototype app. A pre-use test survey was administered to all participants, who subsequently use-tested the app on three different devices (iPhone, iPad mini, iPad Air). Usability was assessed by objectively scored data entry errors and through a post-use focus group held to gather open-ended feedback on end-user satisfaction. RESULTS: All of the participants were women, ranging from 18-64 years old. A large percentage (85.7%) of participants had at least a high school education. Internet (92.8%), computer (85.7%) and cell phone (71.4%) use rates were high. Data entry error rates were also high, particularly in free text fields, ranging from 92.3 to 100%. Error rates were comparable across device type. In a post-use focus group, participants reported that they found the app easy to use and felt that its design was consistent with their vision. The participants raised several concerns, including that they did not find filling out the forms in the app to be a useful task. They also were concerned about an app potentially creating more work for them and personal security issues related to carrying a mobile device in low-income areas. CONCLUSION: In a cohort of formally educated community healthcare workers with high levels of personal computer and cell phone use, we identified no technological barriers to adapting their existing work to a mobile device based system. Transferring current data entry work into a mobile platform, however, uncovered underlying dissatisfaction with some data entry tasks. This dissatisfaction may be a more significant barrier than the data entry errors our testing revealed. Our results highlight the fact that without a deep understanding of local process to optimize usability, technology-based solutions in health may fail. Developing such an understanding must be a central component in the design of any mHealth solution in global health.

Interferon-ß therapy against EAE is effective only when development of the disease depends on the NLRP3 inflammasome.

Interferon-ß (IFN-ß) is widely used to treat multiple sclerosis (MS), and its efficacy was demonstrated in the setting of experimental autoimmune encephalomyelitis (EAE), an animal model of MS; however, IFN-ß is not effective in treating all cases of MS. Here, we demonstrate that signaling by IFNAR (the shared receptor for IFN-α and IFN-ß) on macrophages inhibits activation of Rac1 and the generation of reactive oxygen species (ROS) through suppressor of cytokine signaling 1 (SOCS1). The inhibition of Rac1 activation and ROS generation suppressed the activity of the Nod-like receptor (NLR) family, pyrin domain-containing 3 (NLRP3) inflammasome, which resulted in attenuated EAE pathogenicity. We further found that two subsets of EAE could be defined on the basis of their dependency on the NLRP3 inflammasome and that IFN-ß was not an effective therapy when EAE was induced in an NLRP3 inflammasome-independent fashion. Thus, our study demonstrates a previously uncharacterized signaling pathway that is involved in the suppression of EAE by IFN-ß and characterizes NLRP3-independent EAE, which cannot be treated with IFN-ß.