Search

Background. Pentavalent antimony (Sb(v)) is the mainstay therapy for mucosal leishmaniasis (ML), but it is toxic, and relapses are common. Immunotherapy using a mixture of killed parasites, with or without bacille Calmette-Guerin, is an alternative but is used sporadically because of inconsistent results. Methods. We developed a defined immunotherapeutic antigen preparation for use in an observational, open-label trial to treat 6 patients with ML with a history of Sb(v) therapy failure. All patients were treated with the antigens thiol-specific antioxidant, Leishmania major stress inducible protein 1, Leishmania elongation initiation factor, and Leishmania heat shock protein 83, plus granulocyte-macrophage colony-stimulating factor. Patients underwent clinical and pathological evaluations before the initiation of immunotherapy and at 3, 6, 9, 12, 18, 24, and 60 months after. Results. One month after the third injection, 1 patient showed complete clinical remission (CC) and remained disease free for the duration of the study. At the 9-month follow-up examination, 5 patients showed CC, and all patients were asymptomatic at a subsequent 5-year follow-up examination. Conclusions. These data support the concept that vaccine therapy with a defined antigen combination, used with standard chemotherapy, is a safe and effective approach to treat drug-refractory ML. Copyright © 2006 Infectious Diseases Society of America [ABSTRACT FROM AUTHOR]

In the past few decades, several emerging/re-emerging mosquito-borne flaviviruses have resulted in disease outbreaks of public health concern in the tropics and subtropics. Due to cross-reactivities of antibodies recognizing the envelope protein of different flaviviruses, serosurveillance remains a challenge. Previously we reported that anti-premembrane (prM) antibody can discriminate between three flavivirus infections by Western blot analysis. In this study, we aimed to develop a serological assay that can discriminate infection or exposure with flaviviruses from four serocomplexes, including dengue (DENV), Zika (ZIKV), West Nile (WNV) and yellow fever (YFV) viruses, and explore its application for serosurveillance in flavivirus-endemic countries. We employed Western blot analysis including antigens of six flaviviruses (DENV1, 2 and 4, WNV, ZIKV and YFV) from four serocomplexes. We tested serum samples from YF-17D vaccinees, and from DENV, ZIKV and WNV panels that had been confirmed by RT-PCR or by neutralization assays. The overall sensitivity/specificity of anti-prM antibodies for DENV, ZIKV, WNV, and YFV infections/exposure were 91.7%/96.4%, 91.7%/99.2%, 88.9%/98.3%, and 91.3%/92.5%, respectively. When testing 48 samples from Brazil, we identified multiple flavivirus infections/exposure including DENV and ZIKV, DENV and YFV, and DENV, ZIKV and YFV. When testing 50 samples from the Philippines, we detected DENV, ZIKV, and DENV and ZIKV infections with a ZIKV seroprevalence rate of 10%, which was consistent with reports of low-level circulation of ZIKV in Asia. Together, these findings suggest that anti-prM antibody is a flavivirus serocomplex-specific marker and can be employed to delineate four flavivirus infections/exposure in regions where multiple flaviviruses co-circulate.

Purpose: Body composition analysis using computed tomography (CT) is proposed as a predictor of cancer mortality. An association between subcutaneous adipose tissue radiodensity (SATr) and cancer-specific mortality was established, while gender effects and equipment bias were estimated., Methods: 7,475 CT studies were selected from 17 cohorts containing CT images of untreated cancer patients who underwent follow-up for a period of 2.1-118.8 months. SATr measures were collected from published data (n = 6,718) or calculated according to CT images using a deep-learning network (n = 757). The association between SATr and mortality was ascertained for each cohort and gender using the p-value from either logistic regression or ROC analysis. The Kruskal-Wallis test was used to analyze differences between gender distributions, and automatic segmentation was evaluated using the Dice score and five-point Likert quality scale. Gender effect, scanner bias and changes in the Hounsfield unit (HU) to detect hazards were also estimated., Results: Higher SATr was associated with mortality in eight cancer types (p < 0.05). Automatic segmentation produced a score of 0.949 while the quality scale measurement was good to excellent. The extent of gender effect was 5.2 HU while the scanner bias was 10.3 HU. The minimum proposed HU change to detect a patient at risk of death was between 5.6 and 8.3 HU., Conclusions: CT imaging provides valuable assessments of body composition as part of the staging process for several cancer types, saving both time and cost. Gender specific scales and scanner bias adjustments should be carried out to successfully implement SATr measures in clinical practice., Competing Interests: Declaration of competing interest Marcos A. D. Machado and Vinicius O. Menezes have a consulting agreement with Nuclearis corporation, and receive royalties for artificial intelligence product innovations. Bruno L. H. Anjos is employed by Nuclearis corporation and report no competing interest with this study., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Currently, integrase inhibitors (INIs)-based ART regimens are the preferred initial therapy for AIDS patients. There is scarce information on the use of dolutegravir (DTG) among late-presenter people living with HIV (PLHIV)., Objectives: To compare the effect of DTG- or efavirenz (EFV)-based regimens on the outcomes of patients with advanced AIDS., Methods: We compared two cohorts of consecutive symptomatic AIDS patients (WHO stage 4, CD4 count<50 cells/mL) starting therapy with DTG-based (2018-2021, prospective cohort) or EFV-based regimens (2013-2016, retrospective cohort) from five Brazilian cities. The main endpoints were early (all-cause) mortality, viral suppression at 24 and 48 weeks, changes in CD4 count, and changes in initial therapy (for any reason)., Results: We included all eligible patients in a consecutive way (in both groups) until we reached 92 individuals per arm. The median baseline CD4 count (20 vs. 21 cells/mL) and the median HIV plasma viral load (5.5 copies/mL log 10 ) were identical across the groups. Viral suppression rates were higher in the DTG group than in the EFV group at 24 (67.4% vs. 42.4%,) and 48 weeks (65.2% vs. 45.7%, p  < 0.001 for both comparisons). More patients in the DTG group presented with CD4 > 200 cells/mL compared to the EFV group at 48 weeks (45% vs. 29%, p  = 0.03). Treatment changes (ITT, M = F) were significantly more frequent in the EFV group (1% vs. 17%, p  < 0.0001). The relative mortality rate was 25% lower in the DTG group, but without statistical significance., Conclusion: We detected a higher rate of virological suppression and greater treatment durability in patients with advanced AIDS treated with DTG than in those treated with EFV., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Brites, Lacerda, Sprinz, Bay, Pinto, Azevedo, Luz, Lins-Kusterer and Netto.)

Men who have sex with men (MSM) and transgender women (TGW) are highly vulnerable to anal sexually transmitted infections (STIs). Objectives -to evaluate the prevalence of anal STIs among MSM and TGW attending a referral clinic for anal cancer prevention. Methods -MSM and TGW attending a medical visit for high-resolution anoscopy in Salvador, Brazil, from February 2021 to June 2022 were screened for HPV, gonorrhea, and chlamydial infection by PCR of anal swab and by serum VDRL titration for syphilis screening. They also responded to a questionnaire on sociodemographic characteristics and sexual behavior. Results -we evaluated 141 participants: 117 (82.9%) MSM, 9 (6.4%) bisexual men (BSM), and 15 (10.6%) TGW. Most (111/141, 78.7%) were older than 30 years, 89 (63.1%) had over 12 years of education, and 124 (87.9%) had a family income of up to five minimum wages. At least one STI was detected in 112 (79.4%) of the participants (86.7% among TGW). HIV infection was detected in 102 (72.3%) participants; HIV frequency was higher in BSM (7/9, 88.9%) and in MSM (89/116, 76.1%) than in TGW (5/15, 33.3%). A lower income ( p = 0.004) was predictive of anal STIs, while syphilis was significantly more frequent among participants with HIV (29.1% vs. 5,3%, for HIV positive and negative, respectively, p = 0.002). Presenting at least one active STI was also associated with having had group sex in the last year ( p = 0.03) and with use of sexualized drugs ( p = 0.02). Conclusions -MSM and TGW present a high vulnerability to anal STIs. Number of sexual partners, use of sexualized drugs, and lower income are predictive of a higher risk of acquiring an STI in such populations.

Raltegravir and other third-line drugs have shown promise in improving outcomes in treatment-experienced patients. However, the efficacy and tolerability of these agents vary. This study assessed real-life virologic success, long-term survival, and adverse events in patients receiving raltegravir or other third-line drugs as salvage regimens. This retrospective cohort study included adults who experienced treatment failure (human immunodeficiency syndrome-1 RNA plasma viral load >1000 copies/mL) and subsequently initiated raltegravir or other third-line drugs (darunavir/ritonavir, maraviroc, or etravirine). Propensity score matching methods were employed to account for differences at the time of switching from failing antiretroviral therapy regimens. The matched subset was analyzed using the Kaplan-Meier method and Generalized Wilcoxon tests to evaluate the probability of achieving virologic suppression (plasma viral load <50 copies/mL). Mortality rates, toxicity, treatment interruption, virologic failure, and loss to follow-up were determined using Poisson regression. One hundred and sixty-eight patients initiating salvage regimens were included, with 123 receiving raltegravir and 45 other third-line drugs. Propensity score matching resulted in a subset of 90 patients, 45 in each group. During the follow-up period, there were no significant differences observed between the groups in terms of virologic suppression (77.8% vs 82.2%, P = .73), mortality rates (4.04 vs 6.18 persons per 100 person-years [p-y]; P = .67), drug toxicity (0.00 vs 2.06 persons per 100 p-y; P = .49), treatment interruption (8.07 vs 0.00 persons per 100 p-y; P = .06), virologic failure (2.02 vs 4.12 persons per 100 p-y; P = .61), and loss of follow-up (6.05 vs 4.12 persons per 100 p-y; P = .70). Our findings indicate comparable survival and virological success rates between raltegravir and other drugs used in salvage regimens. Similar rates of drug toxicity, treatment interruption, virologic failure, and loss of follow-up were also observed. These results suggest that raltegravir may be a viable option for salvage therapy, demonstrating outcomes comparable to other third-line drugs in real life., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: COVID-19 can trigger different clinical presentations in distinct population groups, some of which are considered at higher risk of SARS-CoV-2 infection. Little is known about the susceptibility of certain populations to the infection., Objectives: We aimed to determine the prevalence of COVID-19 among People Living With HIV/AIDS (PLWH) attending a tertiary public hospital in Salvador, Brazil, patients with active pulmonary tuberculosis and Hospital's Healthcare Workers (HCW), and to compare their SARS-CoV-2 antibody levels., Methods: In this observational study we included 2294 participants from June 9, 2020 to August 10, 2021. IgG SARS-CoV-2 antibodies from all participants (275 PLWH, 42 with active tuberculosis and 1977 healthcare workers) were measured. Prevalence of COVID-19 and antibodies indexes were compared across groups., Results: We detected a higher prevalence of COVID-19 in patients with active tuberculosis (42.9%) than in PLWH (22.5%) or HCW (11.7%). Previously vaccinated participants with a COVID-19 history had median higher IgG antibody indexes (8.2; IQR: 5.5‒10) than those vaccinated who did not have COVID-19 until the time of this study (4.1; IQR: 1.6‒6.2, p < 0.001)., Conclusion: Prevalence of previous SARS-CoV-2 infection was higher among tuberculosis patients than that found in HCW and PLWH, but antibodies levels were similar across groups., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2023 Sociedade Brasileira de Infectologia. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Excessive weight gain is a current concern among People Living with HIV (PLHIV) starting ART., Objectives: To evaluate the weight gain after 48-weeks of ART in naive patients, according with baseline CD4 count., Methods: PLHIV starting 3TC + TDF + DTG with at least 48-weeks of follow up in two AIDS referral centers were stratified by baseline CD4 count (lower or higher than 200 cells/mm 3 ). Data on CD4 count, HIV viral load, weight/Body Mass Index (BMI), lipids and glucose levels were collected at baseline, 24 and 48 weeks of treatment. For analysis purpose, patients were categorized according to their BMI progression., Results: A total of 270 patients were included in the study. Mean CD4 count were 78.3 ± 61.7 and 536.7 ± 273 cells/mm 3 for low and high CD4 count groups, respectively (p < 0.001). Baseline BMI was significantly lower in low CD4 group (21.7 vs. 23.6 Kg/m 2 , p < 0.001). Patients in low CD4 group gained more weight than those in high CD4 group (11.2 ± 8.5 kg vs. 2.2 ± 4.2 Kg, p = 0.004). Overall weight gain was higher in women, regardless group (13.1 ± 7.9 Kg vs. 1.4 ± 3.6 Kg for women and men, respectively, p < 0.001). The proportion of overweight/obesity significantly increased in low CD4 group. Viral suppression rate was high for both groups. At week 48 the overall proportion of overweight/obesity was like that reported for the Brazilian population., Conclusions: Weight gain in the present study indicates a "return to health" phenomenon. Excessive weight gain was more frequent in women., Competing Interests: Conflicts of interest CB has served as speaker, advisory board participant, and/or research grants recipient from GSK, Merck, Gilead, and Pfizer. EMN and EC has no conflict to declare., (Copyright © 2023 Sociedade Brasileira de Infectologia. Published by Elsevier España, S.L.U. All rights reserved.)

Background and Aims: Faecal incontinence is an important complaint reported by patients with Crohn's disease [CD] and it is associated with several disease-related mechanisms, including anorectal functional disorders. This study aimed to assess the anorectal function and clinical characteristics to identify parameters associated with faecal incontinence in CD patients., Methods: This is a cross-sectional study of 104 patients with CD, aged 18 years or older, from a referral centre between August 2019 and May 2021. Patients responded to a specific questionnaire, and underwent medical record review, proctological examination and anorectal functional assessment with anorectal manometry., Results: Of the 104 patients, 49% were incontinent. Patients with incontinence had a lower mean resting pressure [43.5 vs 53.1 mmHg; p = 0.038], lower mean squeeze pressure [62.1 vs 94.1 mmHg; p = 0.036] and lower maximum rectal capacity [140 vs 180 mL; p < 0.001]. Faecal incontinence was also associated with disease activity [p < 0.001], loose stools [p = 0.02], perianal disease [p = 0.006], previous anoperineal surgery [p = 0.048] and number of anorectal surgeries [p = 0.036]., Conclusions: This is the largest reported study describing manometric findings of Crohn's disease patients with and without faecal incontinence. Our results identified an association between faecal incontinence and functional disorders, in addition to clinical features in these patients. Functional assessment with anorectal manometry may help choose the best treatment for faecal incontinence in patients with CD., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

We aimed to determine the prevalence of anxiety and to identify associated factors among multi-professional residents in Brazil during the early days of the COVID-19 pandemic. A cross-sectional study included a sample of 752 multi-professional residents selected by snowball technique. Symptoms of anxiety were measured by the Beck anxiety inventory scale (≥ 16 cut-off). We used WHOQOL-BREF to access the health-related quality of life and the Maslach Burnout Inventory to measure the burnout syndrome. PR and respective 95% confidence intervals (CI) were calculated using the Poisson regression model. The prevalence of anxiety was 41.2% (310/752). Some variables were strongly associated with anxiety: afraid of getting COVID-19; extra work demand during COVID-19 pandemic; sweating/wheezing/increased heart rate during work; feeling safe when using personal protective equipment at work, and psychological support from residence preceptors. Residents with symptoms of anxiety showed high emotional exhaustion at work (36.6 ± 9.6 vs. 24.7 ± 10.7, P = 0.001) and depersonalization (8.9 ± 6.0 vs. 5.6 ± 4.9, P = 0.001). Correlations coefficients between emotional exhaustion versus Physical WHOQOL-BREF and between emotional exhaustion versus Psychological WHOQOL-BREF were significantly lower among residents without anxiety (P = 0.027 and P = 0,03, respectively). The prevalence of anxiety was high and strongly associated with several variables, particularly with being afraid of getting COVID-19, the perception of workload, somatization (sweating, wheezing and increased heart rate during work), feeling unsafe when using personal protective equipment, and lack of psychological support from residence preceptors. Anxiety was associated with increased emotional exhaustion and depersonalization and low health-related quality of life during the COVID-19 pandemic in Brazil. Low WHOQOL-BREF environment domain, and high emotional exhaustion MBI domain increased the chances of presenting symptoms of anxiety., Competing Interests: Conflict of InterestAuthors declare no conflict of interests., (© The International Society for Quality-of-Life Studies (ISQOLS) and Springer Nature B.V. 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Purpose: To evaluate the classification performance of structured report features, radiomics, and machine learning (ML) models to differentiate between Coronavirus Disease 2019 (COVID-19) and other types of pneumonia using chest computed tomography (CT) scans., Methods: Sixty-four COVID-19 subjects and 64 subjects with non-COVID-19 pneumonia were selected. The data was split into two independent cohorts: one for the structured report, radiomic feature selection and model building ( n  = 73), and another for model validation ( n  = 55). Physicians performed readings with and without machine learning support. The model's sensitivity and specificity were calculated, and inter-rater reliability was assessed using Cohen's Kappa agreement coefficient., Results: Physicians performed with mean sensitivity and specificity of 83.4 and 64.3%, respectively. When assisted with machine learning, the mean sensitivity and specificity increased to 87.1 and 91.1%, respectively. In addition, machine learning improved the inter-rater reliability from moderate to substantial., Conclusion: Integrating structured reports and radiomics promises assisted classification of COVID-19 in CT chest scans., Competing Interests: Conflict of interestMarcos A. D. Machado receives royalties from Radtec Serviços em Física Médica for artificial intelligence product innovations., (© Taiwanese Society of Biomedical Engineering 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Objective: Determine the variables associated with hospitalisations in patients with Crohn's disease and those associated with surgery, intestinal resection, hospital readmission, need for multiple operations and immunobiological agent use., Design: A cross-sectional study was conducted from 2019 to 2021, using two centres for inflammatory bowel diseases in the Brazilian Public Health System., Results: This study included 220 patients. Only perianal disease was associated with hospitalisation (31.6% vs 13.0%, p=0.012). Stricturing or penetrating behaviour (35.8% vs 12.6%, p&lt;0.001) and perianal disease (45.9% vs 9.9%, p&lt;0.001) were associated with surgery. Ileal or ileocolonic location (80.0% vs 46.5%, p=0.044) and stricturing or penetrating behaviour (68.0% vs 11.2%, p&lt;0.001) were associated with intestinal resection. Steroids use at first Crohn's disease occurrence and postoperative complications were associated with hospital readmission and need for multiple operations, respectively. Age below 40 years at diagnosis (81.3% vs 62.0%, p=0.004), upper gastrointestinal tract involvement (21.8% vs 10.3%, p=0.040) and perianal disease (35.9% vs 16.3%, p&lt;0.001) were associated with immunobiological agent use., Conclusion: Perianal disease and stricturing or penetrating behaviour were associated with more than one significant outcome. Other variables related to Crohn's disease progression were age below 40 years at diagnosis, an ileal or ileocolonic disease localisation, an upper gastrointestinal tract involvement, the use of steroids at the first Crohn's disease occurrence and history of postoperative complications. These findings are similar to those in the countries with a high prevalence of Crohn's disease., Competing Interests: Competing interests: CdSBS is researcher for Roche and Bristol; received support to participate in meetings for Janssen and Pfizer. MPM is speaker for Janssen and Takeda; researcher for Bristol, EMS and Roche; received support to participate in meetings for Janssen and Takeda. CdOA is researcher for Roche and Bristol; received support to participate in meetings for Pfizer and Ferring. JAM is speaker for Takeda, Janssen and UCB; researcher for Sanofi; received support to participate in meetings for Abbvie, Pfizer, Janssen and Takeda. LMGdC is speaker for Janssen; received support to participate in meetings for Janssen. GOS is speaker for Abbvie, Janssen, Takeda and Pfizer; researcher for Janssen, Lilly, Roche and Takeda; received support to participate in meetings for Janssen and Takeda. There is no conflict of interest associated with the others authors who contributed to this manuscript., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Although blood transfusion is an important therapeutic resource, transfusion-transmitted infections (TTIs) are still a cause for concern. Measures to mitigate this risk involve improvement of donor screening criteria and improvements in laboratory tests, especially the use of nucleic acid test (NAT). In this retrospective study we evaluated HIV, HTLV, HCV and HBV infection rates in blood donors of the Hematology and Hemotherapy Foundation of Bahia (Hemoba), Brazil, through serological and NAT results and the characteristics of donors. From February/2008 to December/2017, 777,446 blood donations were made. Most donors were male, aged 25-44 years, black and mixed race, and single or divorced. The density-type incidence (DTI; per 100,000) for each virus was 91.1 for HBV; 66.5 for HCV; 54.3 for HIV; and 33.9 for HTLV, with a decreasing trend observed over the period studied, except in the last biennium. NAT detected only 1 donor in immunological window for HIV (0.46/100,000 donations) and 3 donors in immunological window for HBV (1.8/100,000 donations). Serological positivity for all viruses studied was higher in the metropolitan region of Salvador, the state capital. Conclusion: DTI rates show a decreasing trend over the years studied, with a predominance of HBV infection. NAT allowed the detection of donors in immunological window periods, having an important role in improving transfusion safety.

Background: BCG vaccines are given to more than 100 million children every year, but there is considerable debate regarding the effectiveness of BCG vaccination in preventing tuberculosis and death, particularly among older children and adults. We therefore aimed to investigate the age-specific impact of infant BCG vaccination on tuberculosis (pulmonary and extrapulmonary) development and mortality., Methods: In this systematic review and individual participant data meta-analysis, we searched MEDLINE, Web of Science, BIOSIS, and Embase without language restrictions for case-contact cohort studies of tuberculosis contacts published between Jan 1, 1998, and April 7, 2018. Search terms included "mycobacterium tuberculosis", "TB", "tuberculosis", and "contact". We excluded cohort studies that did not provide information on BCG vaccination or were done in countries that did not recommend BCG vaccination at birth. Individual-level participant data for a prespecified list of variables, including the characteristics of the exposed participant (contact), the index case, and the environment, were requested from authors of all eligible studies. Our primary outcome was a composite of prevalent (diagnosed at or within 90 days of baseline) and incident (diagnosed more than 90 days after baseline) tuberculosis in contacts exposed to tuberculosis. Secondary outcomes were pulmonary tuberculosis, extrapulmonary tuberculosis, and mortality. We derived adjusted odds ratios (aORs) using mixed-effects, binary, multivariable logistic regression analyses with study-level random effects, adjusting for the variable of interest, baseline age, sex, previous tuberculosis, and whether data were collected prospectively or retrospectively. We stratified our results by contact age and Mycobacterium tuberculosis infection status. This study is registered with PROSPERO, CRD42020180512., Findings: We identified 14 927 original records from our database searches. We included participant-level data from 26 cohort studies done in 17 countries in our meta-analysis. Among 68 552 participants, 1782 (2·6%) developed tuberculosis (1309 [2·6%] of 49 686 BCG-vaccinated participants vs 473 [2·5%] of 18 866 unvaccinated participants). The overall effectiveness of BCG vaccination against all tuberculosis was 18% (aOR 0·82, 95% CI 0·74-0·91). When stratified by age, BCG vaccination only significantly protected against all tuberculosis in children younger than 5 years (aOR 0·63, 95% CI 0·49-0·81). Among contacts with a positive tuberculin skin test or IFNγ release assay, BCG vaccination significantly protected against tuberculosis among all participants (aOR 0·81, 95% CI 0·69-0·96), participants younger than 5 years (0·68, 0·47-0·97), and participants aged 5-9 years (0·62, 0·38-0·99). There was no protective effect among those with negative tests, unless they were younger than 5 years (0·54, 0·32-0·90). 14 cohorts reported on whether tuberculosis was pulmonary or extrapulmonary (n=57 421). BCG vaccination significantly protected against pulmonary tuberculosis among all participants (916 [2·2%] in 41 119 vaccinated participants vs 334 [2·1%] in 16 161 unvaccinated participants; aOR 0·81, 0·70-0·94) but not against extrapulmonary tuberculosis (106 [0·3%] in 40 318 vaccinated participants vs 38 [0·2%] in 15 865 unvaccinated participants; 0·96, 0·65-1·41). In the four studies with mortality data, BCG vaccination was significantly protective against death (0·25, 0·13-0·49)., Interpretation: Our results suggest that BCG vaccination at birth is effective at preventing tuberculosis in young children but is ineffective in adolescents and adults. Immunoprotection therefore needs to be boosted in older populations., Funding: National Institutes of Health., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Purpose: There is a paucity of data on the spectrum and prevalence of pathogenic variants among women of African ancestry in the Northeast region of Brazil., Methods: We performed BROCA panel sequencing to identify inherited loss-of-function variants in breast cancer susceptibility genes among 292 Brazilian women referred to a single institution cancer risk assessment program., Results: The study included a convenient cohort of 173 women with invasive breast cancer (cases) and 119 women who were cancer-free at the time of ascertainment. The majority of the women self-reported as African-descended (67% for cases and 90.8% for unaffected volunteers). Thirty-seven pathogenic variants were found in 36 (20.8%) patients. While the spectrum of pathogenic variants was heterogeneous, the majority (70.3%) of the pathogenic variants were detected in high-risk genes BRCA1, BRCA2, PALB2, and TP53. Pathogenic variants were also found in the ATM, BARD1, BRIP1, FAM175A, FANCM, NBN, and SLX4 genes in 6.4% of the affected women. Four recurrent pathogenic variants were detected in 11 patients of African ancestry. Only one unaffected woman had a pathogenic variant in the RAD51C gene. Different risk assessment models examined performed well in predicting risk of carrying germline loss-of-function variants in BRCA1 and/or BRCA2 in breast cancer cases., Conclusion: The high prevalence and heterogenous spectrum of pathogenic variants identified among self-reported African descendants in Northeast Brazil is consistent with studies in other African ancestry populations with a high burden of aggressive young onset breast cancer. It underscores the need to integrate comprehensive cancer risk assessment and genomic testing in the management of newly diagnosed Black women with breast cancer across the African Diaspora, enabling improved cancer control in admixed underserved and understudied populations., (© 2022. The Author(s).)

Carnivores such as cats and minks are highly susceptible to SARS-CoV-2. Brazil is a global COVID-19 hot spot and several cases of human-to-cat transmission have been documented. We investigated the spread of SARS-CoV-2 by testing 547 domestic cats sampled between July-November 2020 from seven states in southern, southeastern, and northeastern Brazil. Moreover, we investigated whether immune responses elicited by enzootic coronaviruses affect SARS-CoV-2 infection in cats. We found infection with significantly higher neutralizing antibody titers against the Gamma variant of concern, endemic in Brazil during 2020, than against an early SARS-CoV-2 B.1 isolate (p<0.0001), validating the use of Gamma for further testing. The overall SARS-CoV-2 seroprevalence in Brazilian cats during late 2020 validated by plaque reduction neutralization test (PRNT 90 ) was 7.3% (95% CI, 5.3-9.8). There was no significant difference in SARS-CoV-2 seroprevalence in cats between Brazilian states, suggesting homogeneous infection levels ranging from 4.6% (95% CI, 2.2-8.4) to 11.4% (95% CI, 6.7-17.4; p=0.4438). Seroprevalence of the prototypic cat coronavirus Feline coronavirus (FCoV) in a PRNT 90 was high at 33.3% (95% CI, 24.9-42.5) and seroprevalence of Bovine coronavirus (BCoV) was low at 1.7% (95% CI, 0.2-5.9) in a PRNT 90 . Neutralizing antibody titers were significantly lower for FCoV than for SARS-CoV-2 (p=0.0001), consistent with relatively more recent infection of cats with SARS-CoV-2. Neither the magnitude of SARS-CoV-2 antibody titers (p=0.6390), nor SARS-CoV-2 infection status were affected by FCoV serostatus (p=0.8863). Our data suggest that pre-existing immunity against enzootic coronaviruses neither prevents, nor enhances SARS-CoV-2 infection in cats. High SARS-CoV-2 seroprevalence already during the first year of the pandemic substantiates frequent infection of domestic cats and raises concerns on potential SARS-CoV-2 mutations escaping human immunity upon spillback., Competing Interests: Authors OC and LR were employed by company Tecsa Laboratorios. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Oliveira-Filho, de Carvalho, Carneiro, Fernandes, Vaz, Pedroso, Gonzalez-Auza, Urbieta, Kühne, Mayoral, Jo, Moreira-Soto, Reusken, Drosten, Brites, Osterrieder, Netto, Ristow, Maia, Vogel, Almeida, Franke and Drexler.)

Purpose: Methodologies for optimization of SPECT image acquisition can be challenging due to imaging throughput, physiological bias, and patient comfort constraints. We evaluated a vendor-independent method for simulating lower count image acquisitions., Methods: We developed an algorithm that recombines the ECG-gated raw data into reduced counting acquisitions. We then tested the algorithm to simulate reduction of counting statistics from phantom SPECT image acquisition, which was synchronized with an ECG simulator. The datasets were reconstructed with a resolution recovery algorithm and the summed stress score (SSS) was assessed by three readers (two experts and one automatic)., Results: The algorithm generated varying counting levels, simulating multiple examinations at the same time. The error between the expected and the simulated countings ranged from approximately 5% to 10% for the ungated simulations and 0% for the gated simulations., Conclusions: The vendor-independent algorithm successfully generated lower counting statistics datasets from single-gated SPECT raw data. This method can be readily implemented for optimal SPECT research aiming to lower the injected activity and/ or to shorten the acquisition time., (© 2021 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, LLC on behalf of The American Association of Physicists in Medicine.)

Decades after its discovery in East Africa, Zika virus (ZIKV) emerged in Brazil in 2013 and infected millions of people during intense urban transmission. Whether vertebrates other than humans are involved in ZIKV transmission cycles remained unclear. Here, we investigate the role of different animals as ZIKV reservoirs by testing 1723 sera of pets, peri-domestic animals and African non-human primates (NHP) sampled during 2013-2018 in Brazil and 2006-2016 in Côte d'Ivoire. Exhaustive neutralization testing substantiated co-circulation of multiple flaviviruses and failed to confirm ZIKV infection in pets or peri-domestic animals in Côte d'Ivoire ( n =259) and Brazil ( n =1416). In contrast, ZIKV seroprevalence was 22.2% (2/9, 95% CI, 2.8-60.1) in West African chimpanzees ( Pan troglodytes verus ) and 11.1% (1/9, 95% CI, 0.3-48.3) in king colobus ( Colobus polycomos ). Our results indicate that while NHP may represent ZIKV reservoirs in Africa, pets or peri-domestic animals likely do not play a role in ZIKV transmission cycles.

Background: COVID-19 pandemic caused increased workload and stress for health professionals involved in the care of such patients. We aimed to describe the health-related quality of life, and burnout in frontline physicians diagnosed with anxiety during the COVID-19 pandemic., Methods: This was a cross-sectional study conducted during the first-wave phase of COVID-19, from September to October 2020. Questionnaires were sent electronically to 450 physicians from State of Bahia, assessing symptoms of anxiety, health-related quality of life (HRQOL) and burnout syndrome. For the categorical variables, the Pearson's chi-square test was used and difference between means was compare using the Mann-Whitney test. was Groups with and without anxiety symptoms were compared using prevalence ratios (PR). Pearson's correlation measured the correlation between WHOQOL-BREF and MBI (Maslach Burnout Inventory) domains. The Fisher r-to-z transformation was used to assess the significance of the difference between two correlation coefficients. The significance level was <0.05., Results: Out of the 450 physicians, 223 (49,6%) completely answered the questionnaire and 38 (17%) showed symptoms of anxiety. Physicians with anxiety had higher scores in emotional exhaustion (EE) (38.31 ± 8.59 vs 25.31±0.87; p = 0.0001) and depersonalization (DP) (9.0 ± 5.6 vs 5.9 ± 5.3; p = 0.001) domains, and lower scores in personal accomplishment (PA) (32.1 ± 8.2 vs 36.3 ± 7.6; p = 0.004), than those without anxiety. All correlations between WHOQOL-BREF domains and MBI in physicians without anxiety were significant (p = 0.01)., Conclusion: Physicians with anxiety showed more emotional exhaustion, less personal accomplishment, and lower quality of life. All domains of WHOQOL BREF were correlated with all MBI domains among physicians without anxiety. Differences in correlation according to anxiety were remarkable in psychological HOQOL BREF domain and emotional exhaustion and depersonalization MBI domains. The effect of anxiety leading to poorer levels of perceived health needs to be further investigated., Competing Interests: Conflicts of interest The authors declare no conflict of interest., (Copyright © 2021 Sociedade Brasileira de Infectologia. Published by Elsevier España, S.L.U. All rights reserved.)

Among 713 equids sampled in northeastern Brazil during 2013-2018, West Nile virus seroprevalence was 4.5% (95% CI 3.1%-6.3%). Mathematical modeling substantiated higher seroprevalence adjacent to an avian migratory route and in areas characterized by forest loss, implying increased risk for zoonotic infections in disturbed areas.

Background: Over-the-counter use of ivermectin amongst other drugs as SARS-CoV-2 treatment has been increasingly common, despite the lack of evidence on its clinical efficacy., Objective: To evaluate the effect of ivermectin use on production of antibodies against SARS-CoV-2 in health care workers (HCW) diagnosed with COVID-19 and of Th1/Th2 cytokines by stimulated peripheral blood mononuclear cells of the same cohort (PBMCs)., Methods: This cross-sectional study evaluated seroconversion and neutralizing antibodies production in HCW at Complexo Hospitalar Universitário Professor Edgard Santos (Salvador, Brazil), diagnosed with COVID-19 from May to July, 2020, as well as in vitro production of antibody against SARS-CoV-2 and Th1/Th2 cytokines. Analyses were performed between December 2020 and February 2021. Participants were stratified according to the use of ivermectin (≤ 1 dose vs. multiple doses) for treatment of COVID-19., Results: 45 HCW were included (62% women). Mean age was 39 years, and disease severity was similar across groups. Neutralizing antibodies were detected less frequently in multiple doses (70%) vs. ≤ 1 dose (97%) groups, p = 0.02). PBMCs of patients in multiple doses group also were less likely to produce antibodies against SARS-CoV-2 following in vitro stimulation with purified spike protein in comparison with patients in ≤ 1 dose group (p < 0.001). PBMC´s production of Th1/Th2 cytokines levels was similar across groups. Abdominal pain (15% vs 46%, p = 0.04), diarrhea (21% vs. 55%, p = 0.05) and taste perversion (0% vs. 18%, p = 0.05) were more frequently reported by participants that used multiple doses of ivermectin., Conclusions: Although there was no evidence for differential disease severity upon ivermectin use for treatment of COVID-19 it was associated with more gastro-intestinal side-effects and impairment of anti-SARS-CoV2 antibodies production, in a dose dependent manner. This potentially impacts the effectiveness of immune response and the risk of reinfection and warrants additional studies for clarifying the mechanisms and consequences of such immunomodulatory effects., Competing Interests: Conflicts of interest Authors declare no conflict of interest related to this work., (Copyright © 2021 Sociedade Brasileira de Infectologia. Published by Elsevier España, S.L.U. All rights reserved.)

The outbreak of the new coronavirus (SARS-CoV-2) causing the coronavirus disease (COVID-19) has spread globally. As of June 18, 2020, a high maternal mortality rate due to SARS-CoV-2 infections was identified in Brazil, representing most of the world cases at that time. An observational, cross-sectional study was performed with pregnant women admitted in two maternity hospitals located in Salvador/Bahia and their newborns, from May 24 th up to July 17 th of 2020. Among 329 pregnant women enrolled at hospital admission, a high prevalence (n=28; 8.5%) of pregnant women with COVID-19 was observed, as well as a high proportion of asymptomatic cases (n=19; 67.9%). Two newborns had detectable SARS-CoV-2 but evolved without abnormalities. This data highlight the importance of identifying pregnant women with COVID-19 for proper isolation measures to prevent in-hospital transmission., Competing Interests: Conflicts of Interest All authors declare that they have no conflict interests., (Copyright © 2021 Sociedade Brasileira de Infectologia. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Streptococcus pneumoniae is the most frequent bacterial causative agent of pneumonia. Due to its significant contribution to the morbidity and mortality profile and the country's economy, the 10-valent pneumococcal vaccine (PCV10) was introduced in Brazil in 2010. Brazil is divided into five administrative regions which differ in social-economic indices among each other. Estimates of PCV10 impact on hospitalization rates due to pneumonia stratified by distinct Brazilian regions are limited. We assessed this issue., Methods: This is a population-based ecological investigation. Data about hospitalizations due to pneumonia, asthma or urinary tract infection (UTI) among patients aged under 20 years in the pre-exposure (2003-2009) and in the post-exposure (2011-2017) periods were retrieved from the National Health System - Hospital Information System (SIH-SUS) database. The total resident population by age group in each year was retrieved from the Brazilian Institute for Geography and Statistics database. Hospitalization rates were estimated for each Brazilian region and the rates obtained in the pre-exposure and in the post-exposure periods were compared by Prais-Winsten regression. The Human Development Index (HDI) evolved differently in the distinct regions during the study period., Results: Overall, hospitalization rates due to pneumonia declined by 34.5%. Similar trends were observed for hospitalization rates due to asthma and UTI. The same pattern was observed in each Brazilian region. However, the North region was the only one that presented an exponential incidence decline pattern, which could be explained by PCV10 implementation (declined by 10.8% in the quadratic regression, p < 0.01). Only in the North region, significant decline was observed among patients aged 0-4 years (-12.5%; p = 0.01), 5-9 years (-38.5%; p < 0.01) or 10-14 years (-10.7%; p = 0.03)., Conclusion: Significant variation in the downward trend of hospitalization rate was only found in the North region, which evolved from very low HDI in 2003; medium HDI in 2010 to high HDI in 2017., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

In the pandemic, rapid and accurate detection of SARS-CoV-2 is crucial in controlling the outbreak. Recent studies have shown a high detection rate using saliva/oral fluids as specimens for laboratory detection of the virus. We intended to evaluate the test performance of the Xpert Xpress SARS-CoV-2 cartridge assay in comparison to a conventional qRT-PCR testing, using saliva as biological specimen. Forty saliva samples from symptomatic participants were collected. Conventional qRT-PCR was performed for amplification of E and RdRp genes and the Xpert Xpress SARS-CoV-2 assay amplified E and N2 genes. In the conventional assay, the median cycle threshold value of the E gene was 34.9, and of the RdRp gene was 38.3. In the Xpert Xpress assay, the median cycle threshold value of the E gene was 29.7, and of the N2 gene was 31.6. These results can allow a broaden use of molecular tests for management of COVID-19 pandemic, especially in resources-limited settings., (Copyright © 2021 Sociedade Brasileira de Infectologia. Published by Elsevier España, S.L.U. All rights reserved.)

Current diagnostic tests for tuberculosis (TB) are not able to predict reactivation disease progression from latent TB infection (LTBI). The main barrier to predicting reactivation disease is the lack of our understanding of host biomarkers associated with progression from latent infection to active disease. Here, we applied an immune-based gene expression profile by NanoString platform to identify whole blood markers that can distinguish active TB from other lung diseases (OPD), and that could be further evaluated as a reactivation TB predictor. Among 23 candidate genes that differentiated patients with active TB from those with OPD, nine genes (CD274, CEACAM1, CR1, FCGR1A/B, IFITM1, IRAK3, LILRA6, MAPK14, PDCD1LG2) demonstrated sensitivity and specificity of 100%. Seven genes (C1QB, C2, CCR2, CCRL2, LILRB4, MAPK14, MSR1) distinguished TB from LTBI with sensitivity and specificity between 82 and 100%. This study identified single gene candidates that distinguished TB from OPD and LTBI with high sensitivity and specificity (both > 82%), which may be further evaluated as diagnostic for disease and as predictive markers for reactivation TB.

The evaluation of quality of life could be a useful indicator of depression in HIV patients. We compared the performance of three health-related quality of life (HRQoL) instruments for detecting depression. This nested case-control study included 200 HIV patients attended at an AIDS referral center. Depression was measured by Beck Depression Inventory (BDI). We accessed HRQoL by SF-36v2, HAT-QoL, and WHOQOL-HIV Bref. The depression diagnostic accuracy was evaluated by receiver operating characteristic (ROC) curve analysis. SF-36v2 presented negative correlation with BDI score (- 0.72 to - 0.40), and HAT-QoL (- 0.66 to 0.05) and WHOQoL-HIV Bref (- 0.67 to 0.32) domains presented negative and positive correlations. Mental Health (r = - .71) and Mental Component Summary (r = - .72) showed high negative correlation with BDI. SF-36v2 showed excellent measure by the ROC curve analysis in four factors, and high correlation in Mental Health and MCS. Sf-36 may represent a useful tool for screening of depressive symptoms in HIV patients.

Zika virus (ZIKV) is a positive-stranded RNA virus within the Flaviviridae family. After decades of circulation in Asia, ZIKV was introduced to Brazil in 2014-2015, associated with a rise in congenital malformations. Unlike the genetically related dengue virus (DENV), ZIKV constitutes only one serotype. Although assumed that ZIKV infection may engender lifelong immunity, the long-term kinetics of ZIKV antibody responses are unclear. We assessed long-term kinetics of ZIKV NS1-IgG response in 144 individuals from 3 different subpopulations: HIV patients, tuberculosis patients and healthy individuals first tested in 2016 and retested 1.5-2 years after the 2015-2016 ZIKV epidemic in Salvador de Bahia, Brazil, using a widely distributed NS1-based commercial ELISA. The seropositivity in 2016 reached 59.0% (85/144, 95% confidence interval (CI) 50.7-66.7%), and decreased to 38.6% (56/144, CI 31.3-47.0%) 1.5-2 years later. In addition, the median ZIKV NS1-ELISA reactivity for individuals that remained positive in both timepoints significantly decreased from a ratio of 4.4 (95% CI 3.8-5.0) to 1.6 (95% CI 1.6-1.9) over the 2-year interval (Z: - 6.1; p < 0.001) irrespective of the subpopulation analyzed. Initial 2016 DENV antibody response was non-significant between groups, suggesting comparable DENV background. The high 20.6% seroreversion suggest that widely used serologic tests may fail to account a considerable proportion of past ZIKV infections in flavivirus endemic countries. In addition, ZIKV immunity might be shorter-lived than previously thought, which may contribute to local ZIKV resurgence once individual immune responses wane sufficiently to reduce community protective immunity in addition to birth and migration.

Background: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the cause of Coronavirus Disease 2019 (COVID-19). Although Real Time Reverse Transcription Polymerase Chain Reaction (qRT-PCR) of respiratory specimens is the gold standard test for detection of SARS-CoV-2 infection, collecting nasopharyngeal swabs causes discomfort to patients and may represent considerable risk for healthcare workers. The use of saliva as a diagnostic sample has several advantages., Objectives: The aim of this study was to validate the use of saliva as a biological sample for diagnosis of COVID-19., Methods: This study was conducted at Infectious Diseases Research Laboratory (LAPI), in Salvador, Brazil. Participants presenting with signs/symptoms suggesting SARS-CoV-2 infection underwent a nasopharyngeal swab (NPS) and/or oropharyngeal swab (OPS), and saliva collection. Saliva samples were diluted in PBS, followed by RNA isolation and RT-Real Time PCR for SARS-CoV-2. Results of conventional vs saliva samples testing were compared. Statistical analyses were performed using Statistical Package for the Social Sciences software (SPSS) version 18.0., Results: One hundred fifty-five participants were recruited and samples pairs of NPS/OPS and saliva were collected. The sensitivity and specificity of RT-PCR using saliva samples were 94.4% (95% CI 86.4-97.8) and 97.62% (95% CI 91.7-99.3), respectively. There was an overall high agreement (96.1%) between the two tests., Conclusions: Use of self-collected saliva samples is an easy, convenient, and low-cost alternative to conventional NP swab-based molecular tests. These results may allow a broader use of molecular tests for management of COVID19 pandemic, especially in resources-limited settings., (Copyright © 2020 Sociedade Brasileira de Infectologia. Published by Elsevier España, S.L.U. All rights reserved.)

An orthobunyavirus termed Fort Sherman virus (FSV) was isolated in 1985 from a febrile US soldier in Panama, yet potential animal reservoirs remained unknown. We investigated sera from 192 clinically healthy peri-domestic animals sampled in northeastern Brazil during 2014-2018 by broadly reactive RT-PCR for orthobunyavirus RNA, including 50 cattle, 57 sheep, 35 goats and 50 horses. One horse sampled in 2018 was positive (0.5%; 95% CI, 0.01-3.2) at 6.2 × 10 3 viral RNA copies/mL. Genomic comparisons following virus isolation in Vero cells and deep sequencing revealed high identity of translated amino acid sequences between the new orthobunyavirus and the Panamanian FSV prototype (genes: L, 98.8%; M, 83.5%; S, 100%), suggesting these viruses are conspecific. Database comparisons revealed even higher genomic identity between the Brazilian FSV and taxonomically unassigned Argentinian mosquito- and horse-derived viruses sampled in 1965, 1982 and 2013 with only 1.1% maximum translated amino acid distances across viral genes, suggesting the Argentinian viruses were also distinct FSV strains. The Panamanian FSV strain was an M gene reassortant relative to all Southern American FSV strains, clustering phylogenetically with Cache Valley virus (CVV). Mean dN/dS ratios among FSV genes ranged from 0.03 to 0.07, compatible with strong purifying selection. FSV-specific neutralizing antibodies occurred at relatively high end-point titres in the range of 1:300 in 22.0% of horses (11 out of 50 animals), 8.0% of cattle (4/50 animals), 7.0% of sheep (4/57 animals) and 2.9% of goats (1/35 animals). High specificity of serologic testing was suggested by significantly higher overall FSV-specific compared to CVV- and Bunyamwera virus-specific end-point titres (p = .009), corroborating a broad vertebrate host range within peri-domestic animals. Growth kinetics using mosquito-, midge- and sandfly-derived cell lines suggested Aedes mosquitos as potential vectors. Our findings highlight the occurrence of FSV across a geographic range exceeding 7,000 km, surprising genomic conservation across a time span exceeding 50 years, M gene-based reassortment events, and the existence of multiple animal hosts of FSV., (© 2020 The Authors. Transboundary and Emerging Diseases published by Blackwell Verlag GmbH.)

Background: Coinfection with human T-cell lymphotrophic virus type 1 (HTLV-1) is associated with shorter survival for adults and children infected with human immunodeficiency virus (HIV), although the reasons remain a matter of debate. We evaluated the factors associated with survival time in a large cohort of HIV/HTLV-1-coinfected and HIV-monoinfected individuals on combination antiretroviral therapy (cART)., Methods: In a nested, retrospective case-control study (1:1), we reviewed medical records of people with HIV infection on cART in a referral AIDS center in Salvador, Brazil. We matched 149 patients coinfected with HTLV-1 (cases) by age at HIV diagnosis and sex, to an equal number of HTLV-uninfected persons (controls). Death rates, survival time, baseline and current CD4 cell count, last HIV-1 RNA plasma viral load (pVL), and causes of death were compared between groups., Results: The overall mortality rate was 2.1 person-years (76 deaths, 53 among coinfected patients). Survival time for cases (16.7 ± 0.7 years) was significantly shorter than for controls (18.1 ± 0.4 years; P = .001). Among patients with pVL >50 copies/mL, coinfected patients had a shorter survival time (8.4 ± 0.8 years) than monoinfected ones (12.9 ± 1.4 years; P = .02), regardless of pVL magnitude. However, survival time did not differ for HIV-monoinfected (19.0 ± 0.4 years) or coinfected patients (20.2 ± 0.6 years) presenting with pVL <50 copies/mL (P = .5). Deceased coinfected patients had higher initial CD4 count (417 ± 219 cells) than monoinfected ones with the same outcome (177 ± 160 cells; P = .004), while survivors had similar CD4 cell count at baseline, regardless of HTLV status., Conclusions: Successful cART is able to normalize survival for coinfected patients and should be introduced for all coinfected patients, regardless of CD4 cell count.HIV/human T-cell lymphotrophic virus type 1 coinfection is believed to decrease survival of coinfected patients. In this case-control study, we demonstrate that successful combination antiretroviral therapy (last HIV viral load <50 copies/mL) is able to improve survival of coinfected patients to levels observed for those monoinfected., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: The present study evaluated factors associated with losses in the latent tuberculosis infection (LTBI) cascade of care in contacts of tuberculosis (TB) patients, in a referral center from a highly endemic region in Brazil., Methods: Contacts of 1672 TB patients were retrospectively studied between 2009 and 2014. Data on TB screening by clinical investigation, radiographic examination and tuberculin skin test (TST) were extracted from medical records. Losses in the cascade of care and TB incidence within 2-year follow-up were calculated., Results: From a total of 1180 TB contacts initially identified, only 495 were examined (58% loss), and 20 were diagnosed with active TB at this stage. Furthermore, 435 persons returned for TST result interpretation and 351 (∼81%) were TST positive. Among those with positive TST, 249 (73%) were treated with isoniazid for 6 months whereas 51 abandoned therapy early. Three individuals who did not receive LTBI treatment, one with incomplete treatment and another who completed treatment developed active TB. A logistic regression analysis revealed that increases in age were associated with losses in the LTBI cascade independent of other clinical and epidemiological characteristics., Conclusions: Major losses occur at initial stages and older patients are at higher risk of not completing the LTBI cascade of care., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Since 2013, the arthropod-borne Chikungunya virus (CHIKV) has cocirculated with the autochthonous Mayaro virus (MAYV) in Latin America. Both belong to the same alphavirus serocomplex, termed the Semliki Forest serocomplex. The extent of antibody cross-reactivity due to the antigenic relatedness of CHIKV and MAYV in commonly used serologic tests remains unclear. By testing 64 CHIKV- and 37 MAYV-specific sera from cohort studies conducted in Peru and Brazil, we demonstrate about 50% false-positive test results using commercially available enzyme-linked immunosorbent assays (ELISAs) based on structural antigens. In contrast, combining ELISAs for CHIKV and MAYV significantly increased positive predictive values (PPV) among all cohorts from 35.3% to 88.2% for IgM and from 61.3% to 96.8% for IgG ( P  < 0.0001). Testing of longitudinally collected CHIKV-specific patient sera indicated that ELISA specificity is highest for IgM testing at 5 to 9 days post-onset of symptoms (dpo) and for IgG testing at 10 to 14 dpo. IgG cross-reactivity in ELISA was asymmetric, occurring in 57.9% of MAYV-specific sera compared to 29.5% of CHIKV-specific sera. Parallel plaque reduction neutralization testing (PRNT) for CHIKV and MAYV increased the PPV from 80.0% to 100% ( P  = 0.0053). However, labor-intense procedures and delayed seroconversion limit PRNT for patient diagnostics. In sum, individual testing for CHIKV or MAYV only is prone to misclassifications that dramatically impact patient diagnostics and sero-epidemiologic investigation. Parallel ELISAs for both CHIKV and MAYV provide an easy and efficient solution to differentiate CHIKV from MAYV infections. This approach may provide a template globally for settings in which alphavirus coemergence imposes similar problems. IMPORTANCE Geographically overlapping transmission of Chikungunya virus (CHIKV) and Mayaro virus (MAYV) in Latin America challenges serologic diagnostics and epidemiologic surveillance, as antibodies against the antigenically related viruses can be cross-reactive, potentially causing false-positive test results. We examined whether widely used ELISAs and plaque reduction neutralization testing allow specific antibody detection in the scenario of CHIKV and MAYV coemergence. For this purpose, we used 37 patient-derived MAYV-specific sera from Peru and 64 patient-derived CHIKV-specific sera from Brazil, including longitudinally collected samples. Extensive testing of those samples revealed strong antibody cross-reactivity in ELISAs, particularly for IgM, which is commonly used for patient diagnostics. Cross-neutralization was also observed, albeit at lower frequencies. Parallel testing for both viruses and comparison of ELISA reactivities and neutralizing antibody titers significantly increased diagnostic specificity. Our data provide a convenient and practicable solution to ensure robust differentiation of CHIKV- and MAYV-specific antibodies., (Copyright © 2020 Fischer et al.)

Objective: To produce pooled estimates of the global results of tuberculosis (TB) treatment and analyze the predictive factors of successful TB treatment., Methods: Studies published between 2014 and 2019 that reported the results of the treatment of pulmonary TB and the factors that influenced these results. The quality of the studies was evaluated according to the Newcastle-Ottawa quality assessment scale. A random effects model was used to calculate the pooled odds ratio (OR) and 95% confidence interval (CI). This review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) in February 2019 under number CRD42019121512., Results: A total of 151 studies met the criteria for inclusion in this review. The success rate for the treatment of drug-sensitive TB in adults was 80.1% (95% CI: 78.4-81.7). America had the lowest treatment success rate, 75.9% (95% CI: 73.8-77.9), and Oceania had the highest, 83.9% (95% CI: 75.2-91.0). In children, the success rate was 84.8% (95% CI: 77.7-90.7); in patients coinfected with HIV, it was 71.0% (95% CI: 63.7-77.8), in patients with multidrug-resistant TB, it was 58.4% (95% CI: 51.4-64.6), in patients with and extensively drug-resistant TB it was 27.1% (12.7-44.5). Patients with negative sputum smears two months after treatment were almost three times more likely to be successfully treated (OR 2.7; 1.5-4.8), whereas patients younger than 65 years (OR 2.0; 1.7-2.4), nondrinkers (OR 2.0; 1.6-2.4) and HIV-negative patients (OR 1.9; 1.6-2.5 3) were two times more likely to be successfully treated., Conclusion: The success of TB treatment at the global level was good, but was still below the defined threshold of 85%. Factors such as age, sex, alcohol consumption, smoking, lack of sputum conversion at two months of treatment and HIV affected the success of TB treatment., Competing Interests: The authors have declared that no competing interests exist.

Background: The Ministry of Health in Brazil included ethambutol in the intensive phase of sensible tuberculosis (TB) treatment in March 2010, due to the increasing drug resistance, and implemented the fixed dose combination in the TB treatment guidelines., Methods: A retrospective cohort study was performed to determine the impact of change from three to four drugs schemes on the TB cure and frequency of adverse drug reactions (ADRs) in TB patients. To answer this question, we used data from 730 randomly selected patients who received anti-TB treatment between January 2007 and December 2014 in a reference center from Salvador, Brazil., Findings: TB patients who received the RHEZ regimen (n = 365) developed ADRs more frequently than those treated with the RHZ (n = 365) (86 [23.6%] vs. 55 [15.1%]; p = 0.01). This difference in ADR incidence was even higher in patients above 30 years-old (64 [74.4%] vs. 36 [65.5%]; p = 0.01). The overall number of ADR episodes was greater in patients from the RHEZ group than in the group that received RHZ (170 [61.4%] vs. 107 [38.6%]; p = 0.03). Multivariable logistic regression analysis adjusted for age, alcohol use and diabetes demonstrated that patients receiving the RHEZ regimen had increased odds of developing ADRs than those undertaking the RHZ scheme (odds ratio [OR]: 1.61, 95% confidence interval [CI]: 1.10-2.35; p = 0.015). The overall cure rate was similar between the distinct treatment groups., Conclusion: The patients treated with the four-drug regimen exhibited increased risk of ADRs compared to those who received the three-drug regimen, and especially in patients older than 30 years of age., Competing Interests: The authors have declared that no competing interests exist.

Background: The European Commission (EC) Horizon 2020 (H2020)-funded ZIKAlliance Consortium designed a multicentre study including pregnant women (PW), children (CH) and natural history (NH) cohorts. Clinical sites were selected over a wide geographic range within Latin America and the Caribbean, taking into account the dynamic course of the ZIKV epidemic., Methods: Recruitment to the PW cohort will take place in antenatal care clinics. PW will be enrolled regardless of symptoms and followed over the course of pregnancy, approximately every 4 weeks. PW will be revisited at delivery (or after miscarriage/abortion) to assess birth outcomes, including microcephaly and other congenital abnormalities according to the evolving definition of congenital Zika syndrome (CZS). After birth, children will be followed for 2 years in the CH cohort. Follow-up visits are scheduled at ages 1-3, 4-6, 12, and 24 months to assess neurocognitive and developmental milestones. In addition, a NH cohort for the characterization of symptomatic rash/fever illness was designed, including follow-up to capture persisting health problems. Blood, urine, and other biological materials will be collected, and tested for ZIKV and other relevant arboviral diseases (dengue, chikungunya, yellow fever) using RT-PCR or serological methods. A virtual, decentralized biobank will be created. Reciprocal clinical monitoring has been established between partner sites. Substudies of ZIKV seroprevalence, transmission clustering, disabilities and health economics, viral kinetics, the potential role of antibody enhancement, and co-infections will be linked to the cohort studies., Discussion: Results of these large cohort studies will provide better risk estimates for birth defects and other developmental abnormalities associated with ZIKV infection including possible co-factors for the variability of risk estimates between other countries and regions. Additional outcomes include incidence and transmission estimates of ZIKV during and after pregnancy, characterization of short and long-term clinical course following infection and viral kinetics of ZIKV. STUDY REGISTRATIONS: clinicaltrials.gov NCT03188731 (PW cohort), June 15, 2017; clinicaltrials.gov NCT03393286 (CH cohort), January 8, 2018; clinicaltrials.gov NCT03204409 (NH cohort), July 2, 2017.

Background: The 36-Item Short Form Health Survey questionnaire (SF-36) is a widely used instrument for evaluating health-related quality-of-life (HRQoL). The psychometric validation of the SF-36 version 2.0 (SF-36v2) in HIV-infected patients had not yet conducted in Brazil., Aim: To test data quality, reliability and validity of the SF-36v2 as a measure of HRQoL among Brazilian individuals living with HIV., Methods: A cross-sectional study included 393 HIV-infected patients in whom HRQoL was assessed by using the SF-36v2 questionnaire. Demographic characteristics, socioeconomic status and clinical data were also collected. The SF-36 version 1 translated into Brazilian-Portuguese was adapted and introduced version 2 improvements according to the instrument developers. SPSS version 21 was used for data analyses. Confirmatory factor analysis (CFA) and structural equation modelling were performed using AMOS SPSS version 18. T-test for independent samples was used to compare differences between mean levels of HRQoL components in different groups. Linear multiple regression techniques were used to analyze the relationship between Physical Component Summary (PCS), Mental Component Summary (MCS) and independent variables., Results: We performed the CFA and tested the hypothetical measurement model. We included five parameters to improve the adherence of data to the model. All indicators met the requirement suggested by specialized literature (χ2 (gl): 980.7 (527); CFI: 0.949; GFI: 0.873; TLI: 0.943; RMSEA: 0.047; 90% IC: 0.042-0.051). Multiple regression analyses revealed that depression (p=0.001), family income (p=0.007), sex (p=0.001) and age (p<0.021) were associated with MCS. Comorbidities (p=0.001), health self-perception (p=0.001), age (p=0.001), and sex (p=0.025) were associated with PCS., Conclusions: A consistent validation of the SF-36v2 in Brazilian HIV patients were shown. Further studies with SF-36v2 psychometric analyses would be required in other populations to establish Brazilian normative data., (Copyright © 2019 Sociedade Brasileira de Infectologia. Published by Elsevier España, S.L.U. All rights reserved.)

The Zika virus outbreak in Latin America resulted in congenital malformations, called congenital Zika syndrome (CZS). For unknown reasons, CZS incidence was highest in northeastern Brazil; one potential explanation is that dengue virus (DENV)-mediated immune enhancement may promote CZS development. In contrast, our analyses of historical DENV genomic data refuted the hypothesis that unique genome signatures for northeastern Brazil explain the uneven dispersion of CZS cases. To confirm our findings, we performed serotype-specific DENV neutralization tests in a case-control framework in northeastern Brazil among 29 Zika virus-seropositive mothers of neonates with CZS and 108 Zika virus-seropositive control mothers. Neutralization titers did not differ significantly between groups. In contrast, DENV seroprevalence and median number of neutralized serotypes were significantly lower among the mothers of neonates with CZS. Supported by model analyses, our results suggest that multitypic DENV infection may protect from, rather than enhance, development of CZS.

Introduction: Approximately 60% of emerging pathogens originate from wild animals, with mammals being the main hosts. Among Didelphis, which are restricted to the Americas, the species Didelphis aurita and Didelphis albiventris are particularly widely distributed throughout Brazil, where they act as hosts for several pathogens transmissible to humans. The reduction of their natural habitat has resulted in the adaptation of these species to human environments. Animals hunting, due to food necessity or cultural habit, may increase pathogen exposure with a potential to zoonotic disease transmission., Methodology: From November to December 2016, we administered semi-structured questionnaires in a rural community in northeastern Brazil to assess knowledge, practices and perceptions regarding human-didelphis interactions and possible exposure to zoonoses., Results: There were 213 respondents. Based on photographs of D. albiventris and D. aurita, 91.2% and 78% respondents, respectively, identified the animal by the popular name "sariguê", 61% (130/213) believed the animal could convey any disease, 4.7% stated they did not, and 34% did not know. Opossum meat consumption was reported by 20.2% (43/213), of which 58.1% admitted disease transmission possibility. Only 15.9% of respondents had a secondary or higher education level. The distribution of these frequencies is discussed according to the respondents educational level., Conclusions: The results reveal the need to carry out health educational activities, including better community knowledge regarding the possible exposure to pathogens due to marsupial consumption., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2019 Ianei de Oliveira Carneiro, Norlan de Jesus Santos, Namá Santos Silva, Pedro Cerqueira Lima, Roberto Meyer, Eduardo Martins Netto, Carlos Roberto Franke.)

Background: Oral health care may improve the health-related quality of life (HRQoL) of HIV/AIDS patients. We aimed to evaluate oral health and HRQoL of HIV/AIDS patients using antiretroviral therapy., Methods: A cross-sectional study included 120 HIV-infected patients, aged ≥18 years, from February, 2016 to September, 2017. The 36-Item Short Form Health Survey (SF-36) was used to evaluate the HRQoL. We assessed dental caries status using the Decayed, Missing and Filled Teeth (DMFT) index. Information about demographic, socioeconomic status, depression, and other comorbidities were collected. All patients with depression had a medical diagnosis. Comorbidities were defined as medical diagnoses of arterial hypertension, type-2 diabetes, tuberculosis, syphilis, cardiopathy, chronic renal failure, lymphoma, HCV infection, HBV infection and fatty liver disease. Independent t-tests were used to compare differences between mean levels of HRQoL, age, and DMFT and its components according to groups of sex, comorbidities and depression. Simple linear regression was used to analyze the relationship between the Mental Component Summary (MCS) and DMFT, and a multiple regression equation investigated depression, age, MCS, and comorbidities as predictors of DMFT., Results: The mean DMFT index was 12.4 ± 8.2. A linear regression equation estimated a significant (p = 0.022) decrease of 0.25 unit (%) in MCS for each unit increase in DMFT. Among depressed patients, a significant (p = 0.008) decrease of 0.67% in MCS for each unity increase in DMFT was estimated. Depressed patients showed worse oral health indicators (DFMT index; p ≤ 0.001; and mean Missing Teeth; p ≤ 0.052) and lower HRQoL domains than non-depressed patients. DMFT remained associated with depression (P < 0.005) after controlling for age, MCS, and comorbidities., Conclusions: We found association between poorer oral health (higher DMFT index) and lower Mental Health Component Summary in HIV-infected patients with depression. Patients with depression deserve especial attention to their HRQoL and oral care.