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Objectives In Brazil, annual tuberculin skin tests (TST) are recommended for people living with HIV (PLWH) with CD4>350, with tuberculosis preventive therapy (TPT) provided upon test conversion. We aimed to determine the yield of repeat TST for PLWH. Design Secondary analysis of the stepped-wedge, cluster-randomized THRio trial for isoniazid preventive therapy (IPT) to prevent tuberculosis (TB). Methods We analyzed data from newly registered PLWH with negative baseline TST results. We calculated the number of TST conversions after 1 and/or 2 years among patients eligible for follow-up TSTs; the proportion of converters initiating IPT; and incidence of TB/death. Results Among 1,770 PLWH with a negative baseline TST, 679 (38%) were female and median age was 36 years (IQR 29-43). Eighty-six (5%) developed TB or died within 1 year. Among 1,684 eligible for a follow-up 1-year TST, 582 (35%) were tested and 53 (9%) were positive. Forty-nine (92%) converters started IPT. Of 529 patients with a negative 1-year TST, 7 (1%) developed TB or died over the following year. Of 522 patients eligible for a 2-year TST, 158 (30%) were tested and 13 (8%) were positive. Ten (77%) converters started IPT. Of 1,102 patients who did not receive a 1-year TST, 33 (3%) developed TB or died. Of the 1,069 patients eligible for a 2-year TST, 259 (24%) were tested and 34 (13%) were positive. Thirty (88%) converters started IPT. Conclusions In this cohort of PLWH in Brazil, TST conversion was high among those re-tested, but only 48% received a follow-up TST within 2 years.

Background It is unknown whether dysglycemia is associated with Mycobacterium tuberculosis transmission. Methods We assessed epidemiological and clinical characteristics of patients with culture-confirmed pulmonary tuberculosis and their close contacts, enrolled in a multicenter prospective cohort in Brazil. Contacts were investigated at baseline and 6 months after enrollment. QuantiFERON positivity at baseline and conversion (from negative to positive at month 6) were compared between subgroups of contacts according to glycemic status of persons with tuberculosis (PWTB) as diabetes mellitus (DM) or prediabetes. Multivariable mixed-effects logistic regression models were performed to test independent associations with baseline QuantiFERON positive and QuantiFERON conversion. Results There were 592 PWTB (153 DM, 141 prediabetes, 211 normoglycemic) and 1784 contacts, of whom 658 were QuantiFERON-positive at baseline and 106 converters. Multivariable analyses demonstrated that tuberculosis-prediabetes cases, acid-fast bacilli-positive, pulmonary cavities, and living with someone who smoked were independently associated with QuantiFERON positive in contacts at baseline. DM, persistent cough, acid-fast bacilli-positive, and pulmonary cavities in tuberculosis source cases were associated with QuantiFERON conversion. Conclusions Contacts of persons with pulmonary tuberculosis and dysglycemia were at increased risk of being QuantiFERON positive at baseline or month 6. Increased focus on such close contacts could improve tuberculosis control.

O presente texto trata-se de uma entrevista com o poeta marginal Pedro Tostes, o qual escreve poesiasdesde muito cedo, quando se descobriu no vasto mundo da escrita poética. É produtor cultural, mesmo não se considerando empreendedor no mercado da literatura, vive de poesia de forma audaciosa, resistente e marginal. Desde 2003, começou uma jornada pelo Brasil para levar sua poesia a diferentes locais como: feiras, universidades, congressos, espaços culturais diversos, etc., vivendo mediante a compreensão de que esta ação seria uma forma de “popularizar” a literatura. O escritor já tem vários livros publicados, sendo o útimo deles "Na Casamata de Si" (Patuá, São Paulo, 2018).Acreditamos que Tostes seja um poeta visionário e que não tenha medo de se expor, principalmente, em seus diferentes modos de ver a vida/poesia. Concebemos a poesia como um modo de trilhar muitas experiências estéticas, e Tostes tem experimentado amplamente com/a linguagem. Sabemos que viver de poesia no Brasil é um grande desafio, especialmente por se tratar de um “país com vários problemas nos campos educacional e cultural” (para usarmos as palavras de Tostes, obtida nesta entrevista). E mesmo diante de tal situação, Tostes tem incentivado os jovens a lerem e a se deixarem afetar pela poesia. Tostes pode ser relacionado à poesia marginal no sentido mais utópico e implicado à força da poesia para abrir (des)caminhos na vida, a começar pela ideia de ocupar as periferias, com saraus eSlams.Em seu último trabalho, “Na Casa Mata de Si” (Patuá/SP, 2018), Tostes nos mostra o seu lado de poeta “guerrilheiro” e chama a atenção, por meio de seus versos, para a guerra do “presente”, uma guerra, aliás, tanto interna como externa a nós. Em entrevista realizada via e-mail, Tostes nos faz revelações da sua vida como escritor e de muitos dos seus (des)caminhos no mundo da poesia.

Background A major goal of tuberculosis (TB) epidemiological studies is to obtain results that can be generalized to the larger population with TB. The ability to extrapolate findings on the determinants of TB treatment outcomes is also important. Methods We compared baseline clinical and demographic characteristics and determinants of anti-TB treatment outcomes between persons enrolled in the Regional Prospective Observational Research in Tuberculosis (RePORT)-Brazil cohort between June 2015 and June 2019, and the registry of TB cases reported to the Brazilian National TB Program (Information System for Notifiable Diseases [SINAN]) during the same time period. Multivariable regression models adjusted for the study site were performed using second-generation p-values, a novel statistical approach. Associations with unfavorable treatment outcomes were tested for both RePORT-Brazil and SINAN cohorts. Findings A total of 1,060 culture-confirmed TB patients were enrolled in RePORT-Brazil and 455,873 TB cases were reported to SINAN. Second-generation p-value analyses revealed that the cohorts were strikingly similar with regard to sex, age, use of antiretroviral therapy and positive initial smear sputum microscopy. However, diabetes, HIV infection, and smoking were more frequently documented in RePORT-Brazil. Illicit drug use, the presence of diabetes, and history of prior TB were associated with unfavorable TB treatment outcomes; illicit drug use was associated with such outcomes in both cohorts. Conclusions There were important similarities in demographic characteristics and determinants of clinical outcomes between the RePORT-Brazil cohort and the Brazilian National registry of TB cases.

Background Successful tuberculosis (TB) treatment is necessary for disease control. The World Health Organization (WHO) has a target TB treatment success rate of ≥90%. We assessed whether the different types of unfavorable TB treatment outcome had different predictors. Methods Using data from Regional Prospective Observational Research for Tuberculosis-Brazil, we evaluated biological and behavioral factors associated with each component of unsuccessful TB outcomes, recently updated by WHO (death, loss to follow-up [LTFU], and treatment failure). We included culture-confirmed, drug-susceptible, pulmonary TB participants receiving standard treatment in 2015–2019. Multinomial logistic regression models with inverse probability weighting were used to evaluate the distinct determinants of each unsuccessful outcome. Results Of 915 participants included, 727 (79%) were successfully treated, 118 (13%) were LTFU, 44 (5%) had treatment failure, and 26 (3%) died. LTFU was associated with current drug-use (adjusted odds ratio [aOR] = 5.3; 95% confidence interval [CI], 3.0–9.4), current tobacco use (aOR = 2.9; 95% CI, 1.7–4.9), and being a person with HIV (PWH) (aOR = 2.0; 95% CI, 1.1–3.5). Treatment failure was associated with PWH (aOR = 2.7; 95% CI, 1.2–6.2) and having diabetes (aOR = 2.2; 95% CI, 1.1–4.4). Death was associated with anemia (aOR = 5.3; 95% CI, 1.4–19.7), diabetes (aOR = 3.1; 95% CI, 1.4–6.7), and PWH (aOR = 3.9; 95% CI, 1.3–11.4). Direct observed therapy was protective for treatment failure (aOR = 0.5; 95% CI, .3–.9) and death (aOR = 0.5; 95% CI, .2–1.0). Conclusions The treatment success rate was below the WHO target. Behavioral factors were most associated with LTFU, whereas clinical comorbidities were correlated with treatment failure and death. Because determinants of unsuccessful outcomes are distinct, different intervention strategies may be needed to improve TB outcomes.

The interferon gamma release assay (IGRA) has emerged as a useful tool for identifying latent tuberculosis infection (LTBI). This assay can be performed through testing platforms such as the QuantiFERON-TB Gold Plus (QFT-Plus) assay. This in vitro test has been incorporated into several guidelines worldwide and has recently been considered by the World Health Organization (WHO) for the diagnosis of LTBI. The possibility of systematically implementing IGRAs such as the QFT-Plus assay in centers that perform LTBI screening has been accelerated by the decreased availability of the tuberculin skin test (TST) in several countries. Nevertheless, the process to implement IGRA testing in routine clinical care has many gaps. The study utilized the expertise acquired by the laboratory teams of the Regional Prospective Observational Research in Tuberculosis (RePORT)-Brazil consortium during study protocol implementation of LTBI screening of tuberculosis (TB) close contacts. RePORT-Brazil includes clinical research sites from Brazilian cities and is the largest multicenter cohort of TB close contacts in the country to date. Operational and logistical challenges faced during IGRA implementation in all study laboratories are described, as well as the solutions that were developed and led to the successful establishment of IGRA testing in RePORT-Brazil. The descriptions of the problems identified and resolved in this study can assist laboratories implementing IGRAs, in addition to manufacturers of IGRAs providing effective technical support. This will facilitate the implementation of IGRA testing in countries with large TB burdens, such as Brazil. IMPORTANCE The IGRA has emerged as a useful tool for identifying persons with LTBI. Although the implementation of IGRAs is of utmost importance, to our knowledge there is scarce information on the identification of logistical and technical challenges for systematic screening for LTBI on a large scale. Thus, the descriptions of the problems identified and resolved in this study can assist laboratories implementing IGRAs, in addition to manufacturers of IGRAs providing effective technical support. This will facilitate the implementation of IGRA testing in countries with large TB burdens, such as Brazil.

BackgroundThere are scarce data on the prevalence and disease presentation of HIV in patients with tuberculosis (TB) and dysglycemia (diabetes [DM] and prediabetes [PDM]), especially in TB-endemic countries.MethodsWe assessed the baseline epidemiological and clinical characteristics of patients with culture-confirmed pulmonary TB, enrolled in a multicenter prospective cohort in Brazil (RePORT-Brazil) during 2015-2019. Dysglycemia was defined by elevated glycated hemoglobin and stratified as PDM or DM. Additionally, we used data from TB cases obtained through the Brazilian National Notifiable Diseases Information System (SINAN), during 2015-2019. In SINAN, diagnosis of diabetes was based on self-report. Logistic regression models were performed to test independent associations between HIV, dysglycemia status, and other baseline characteristics in both cohorts.ResultsIn the RePORT-Brazil cohort, the prevalence of DM and of PDM was 23.7% and 37.8%, respectively. Furthermore, the prevalence of HIV was 21.4% in the group of persons with TB-dysglycemia and 20.5% in that of patients with TBDM. In the SINAN cohort, the prevalence of DM was 9.2%, and among the TBDM group the prevalence of HIV was 4.1%. Logistic regressions demonstrated that aging was independently associated with PDM or DM in both the RePORT-Brazil and SINAN cohorts. In RePORT-Brazil, illicit drug use was associated with PDM, whereas a higher body mass index (BMI) was associated with DM occurrence. Of note, HIV was not associated with an increased risk of PDM or DM in patients with pulmonary TB in both cohorts. Moreover, in both cohorts, the TBDM-HIV group presented with a lower proportion of positive sputum smear and a higher frequency of tobacco and alcohol users.ConclusionThere is a high prevalence of dysglycemia in patients with pulmonary TB in Brazil, regardless of the HIV status. This reinforces the idea that DM should be systematically screened in persons with TB. Presence of HIV does not substantially impact clinical presentation in persons with TBDM, although it is associated with more frequent use of recreational drugs and smear negative sputum samples during TB screening.

Background It is unclear whether diabetes or prediabetes affects unfavorable treatment outcomes and death in people with tuberculosis (PWTB). Methods Culture-confirmed, drug-susceptible PWTB, enrolled in the Regional Prospective Observational Research in Tuberculosis (RePORT)–Brazil cohort between 2015 and 2019 (N = 643) were stratified based on glycemic status according to baseline glycated hemoglobin. Unfavorable tuberculosis (TB) outcome was defined as treatment failure or modification, recurrence, or death; favorable outcome was cure or treatment completion. We corroborated the findings using data from PWTB reported to the Brazilian National System of Diseases Notification (SINAN) during 2015–2019 (N = 20 989). Logistic regression models evaluated associations between glycemic status and outcomes. Results In both cohorts, in univariate analysis, unfavorable outcomes were more frequently associated with smoking, illicit drug use, and human immunodeficiency virus infection. Diabetes, but not prediabetes, was associated with unfavorable outcomes in the RePORT-Brazil (adjusted relative risk [aRR], 2.45; P < .001) and SINAN (aRR, 1.76; P < .001) cohorts. Furthermore, diabetes was associated with high risk of death (during TB treatment) in both RePORT-Brazil (aRR, 2.16; P = .040) and SINAN (aRR, 1.93; P = .001). Conclusions Diabetes was associated with an increased risk of unfavorable outcomes and mortality in Brazilian PWTB. Interventions to improve TB treatment outcomes in persons with diabetes are needed.

IntroductionFactors associated with losses in the latent tuberculosis infection (LTBI) cascade of care in contacts of patients with tuberculosis (TB) were investigated in a multicentre prospective cohort from highly endemic regions in Brazil.MethodsClose contacts of 1187 patients with culture-confirmed pulmonary TB were prospectively studied between 2015 and 2019, with follow-up of 6–24 months. Data on TB screening by clinical investigation, radiographic examination and interferon-gamma release assay (IGRA) were collected. Multivariable regressions were used to identify determinants of losses in the LTBI cascade.ResultsAmong 4145 TB contacts initially identified, 1901 were examined (54% loss). Among those examined, 933 were people living with HIV, ≤5 years old and/or had positive IGRA results, and therefore had a recommendation to start TB preventive treatment (TPT). Of those, 454 (23%) initiated treatment, and 247 (54% of those initiating; 26% of those in whom treatment was recommended) completed TPT. Multivariable regression analysis revealed that living with HIV, illiteracy and black/pardo (brown) race were independently associated with losses in the cascade.ConclusionThere were losses at all LTBI cascade stages, but particularly at the initial screening and examination steps. Close contacts of low socioeconomic status and living with HIV were at heightened risk of not completing the LTBI cascade of care in Brazil.

BackgroundInterferon-gamma release assay (IGRA) has emerged as a useful tool in identifying latent tuberculosis infection (LTBI). This assay can be performed through testing platforms, such as QuantiFERON-TB Gold Plus (QFT®-Plus). This in vitro test has been incorporated by several guidelines worldwide and has recently been considered for the diagnosis of LTBI by the World Health Organization (WHO). The possibility of systematically implementing IGRAs such as QFT®-Plus in centers that perform LTBI screening has been accelerated by the decreased availability of tuberculin skin testing (TST) in several countries. Nevertheless, the process to implement IGRA testing in routine clinical care has many gaps.MethodsThe study utilized the expertise acquired by the laboratory teams of the Regional Prospective Observational Research in Tuberculosis (RePORT)-Brazil consortium during study protocol implementation of LTBI screening of TB close contacts.ResultsRePORT-Brazil includes clinical research sites from Brazilian cities and is the largest multicenter cohort of TB close contacts to date in the country. Operational and logistical challenges faced during IGRA implementation in all four study laboratories are described, as well as the solutions that were developed and led to the successful establishment of IGRA testing in RePORT-Brazil.ConclusionsThe problems identified and resolved in this study can assist laboratories implementing IGRAs, in addition to manufacturers of IGRAs providing effective technical support. This will facilitate the implementation of IGRA testing in countries with a high TB burden, such as Brazil.ImportanceThe interferon-gamma release assay (IGRA) has emerged as a useful tool in identifying persons with latent tuberculosis infection (LTBI). Although the implementation of IGRAs is of utmost importance, to our knowledge, there is scarce information on identification of logistical and technical challenges of systematic screening of for LTBI on a large scale. Thus, the problems identified and resolved in this study can assist laboratories implementing IGRAs, in addition to manufacturers of IGRAs providing effective technical support. This will facilitate the implementation of IGRA testing in countries with a high TB burden, such as Brazil.

Background Brazil is one of the highest tuberculosis (TB) burden countries of the world. Cutaneous tuberculosis (CTB) is a rare form of extrapulmonary manifestation of tuberculosis. This study aimed to describe the clinico-evolutive, laboratory and therapeutic aspects of CTB cases among patients from a cohort with TB in Rio de Janeiro, Brazil. Methods Cases of diagnosed CTB with microbiologic confirmation or clinical response to anti-tuberculous treatment associated with positive smear or histopathological findings between the years 2000 and 2016 were selected. Results Seventy-five patients with CTB were included, most were women (58.7%) with a median age of 42 years. CTB diagnosis was based on culture in only 42.7% of the cases. Scrofuloderma represented 50.7% of the cases, followed by erythema induratum of Bazin (EIB) (18.7%), tuberculous gumma (13.3%), lupus vulgaris (8%), TB verrucosa cutis (4%), orificial TB (2.7%) and associated forms (2.7%). Other TB presentations were pulmonary (22.7%), mammary (6.6%) and osteoarticular (4%). All patients who completed the treatment (97.3%) had their lesions healed. Only two patients (2.6%) needed to change the therapy due to adverse reactions. Fifty percent of EIB patients presented recurrence. Conclusions These data highlight the diversity of CTB presentations and the importance of the skin to assist in early identification and treatment of TB. More studies are necessary to improve the knowledge on EIB for a better approach towards these patients, mainly in cases of recurrence.

BackgroundIt is unclear whether diabetes or prediabetes drives adverse treatment outcomes and death in people with tuberculosis (PWTB).MethodsCulture-confirmed PWTB, enrolled in the Regional Prospective Observational Research in Tuberculosis (RePORT)-Brazil cohort between 2015 and 2019 (n=756) were stratified based on glycemic status by baseline glycated hemoglobin levels. Unfavorable TB outcome was defined as treatment failure or modification, recurrence or death, whereas favorable outcome was cure or treatment completion. We validated the findings using data from PWTB reported to the Brazilian National System of Diseases Notification (SINAN) during 2015-2019 (n=20,989). Stepwise binary multivariable regression analysis models evaluated associations between glycemic status and unfavorable outcomes.ResultsIn both cohorts, in univariate analysis, unfavorable outcomes were more frequently associated with drug resistance and HIV infection. Diabetes was associated with unfavorable outcomes in the RePORT (aOR: 2.85, p=0.001) and in SINAN (aOR: 1.56, p=0.040) cohorts. Furthermore, diabetes was associated with higher risk of death in both, RePORT-Brazil (aOR:3.23, p=0.006) and in the SINAN (aOR:2.75, p= 0.047) cohorts.ConclusionDiabetes was associated with an increased risk of unfavorable outcomes and mortality in Brazilian PWTB. Interventions to improve tuberculosis treatment outcomes in persons with diabetes are needed.40-word summary of the article’s main pointIn a multicenter prospective cohort study from Brazil, diabetes was associated with an increased risk of unfavorable treatment outcomes, including mortality, in pulmonary tuberculosis patients. These observations were validated in the Brazilian National Disease Notification System during the same period.

BackgroundFactors associated with losses in the latent tuberculosis infection (LTBI) cascade of care in contacts of tuberculosis (TB) patients were investigated in a multicenter prospective cohort from highly endemic regions in Brazil.MethodsClose contacts of 1,187 culture-confirmed pulmonary TB patients were prospectively studied between 2015 and 2019, with follow-up between 6 and 24 months. Data on TB screening by clinical investigation, radiographic examination and interferon-gamma release assay (IGRA) were collected. Stepwise multivariable models were used to identify determinants of losses in the LTBI cascade.ResultsAmong 4,145 TB contacts initially identified, 1,901 were examined (54% loss). Within those individuals, 933 were people living with HIV, ≤5 years-old and/or had positive IGRA results, therefore having recommendation to start TB preventive treatment (TPT). Of those, 454 (23%) initiated treatment, and 247 (6% of all TB contacts) completed TPT. Multivariable regression analysis revealed that living with HIV, illiteracy, and black/pardo (brown) race were independently associated with losses in cascade.ConclusionThere were losses at all LTBI cascade stages, but particularly at the initial screening and examination steps. Close contacts who are socially vulnerable and living with HIV were at heightened risk of not completing the LTBI cascade of care in Brazil.40-word summary of the article’s main pointWe investigated factors associated with losses in the latent tuberculosis infection cascade of care in a large cohort of contacts in Brazil. Social vulnerability and HIV infection were the most relevant determinants of losses in the LTBI cascade of care.

Latent tuberculosis infection (LTBI) is characterised by the presence of immune responses to previously acquired Mycobacterium tuberculosis infection without clinical evidence of active tuberculosis (TB). Here we report evidence-based guidelines from the World Health Organization for a public health approach to the management of LTBI in high risk individuals in countries with high or middle upper income and TB incidence of, Guidelines on LTBI for low TB incidence countries – essential element of the @WHO #EndTB strategy and TB elimination http://ow.ly/RW8xn

In 2018, Brazilian guidelines changed to recommend tuberculosis (TB) preventive therapy for all people with HIV and a CD4 cell count 350 cells/μl or less, but only for those with a positive tuberculin skin test (TST) if CD4 cell count is than 350 cells/μl. We determined the potential effectiveness of CD4-based guidelines for TB testing and preventive therapy.Secondary analysis of the stepped-wedge, cluster-randomized THRio trial for isoniazid preventive therapy (IPT).We analyzed data from 4114 newly registered patients with HIV in 29 clinics followed until TB diagnosis, death, or administrative censoring. We compared incidence rates of TB and TB/death between CD4, TST, IPT, and antiretroviral therapy categories.Initial CD4 cell count was 350 cells/μl or less in 2138 (52%) and more than 350 cells/μl in 1976 (48%) patients. TST was performed for 2922 (71%), of whom 657 (16%) were TST-positive [278 (13%) CD4 ≤ 350 vs. 379 (19%) CD4 350]. A total of 619 (15%) received IPT and 2806 (68%) received antiretroviral therapy. For patients with CD4 cell count 350 cells/μl or less who did not receive IPT, the incidence rate of TB was 1.79/100 person-years (pys) and TB/death was 3.89/100 pys. For patients with CD4 cell count more than 350 who did not receive IPT, the incidence rates of TB and TB/death were 0.57/100 and 1.49/100 pys for TST-negatives, and 1.05/100 and 1.64/100 pys for TST-unknowns.TB incidence was high among all patients who did not receive IPT, including those with CD4 cell count more than 350 cells/μl and negative or unknown TST results. TB preventive therapy should be provided to all people living with HIV in medium burden settings, regardless of CD4 cell count and TST status.

Background: A major goal of tuberculosis (TB) epidemiologic studies is to obtain results that can be generalized to the larger population with TB. The ability to extrapolate findings on determinants of TB treatment outcomes is also important. Methods: We compared baseline clinical and demographic characteristics and determinants of anti-TB treatment outcomes between persons enrolled into the Regional Prospective Observational Research in Tuberculosis (RePORT)-Brazil cohort between June 2015 and June 2019, and the registry of TB cases reported to the Brazilian National TB Program (Information System for Notifiable Diseases [SINAN]) during the same time period. Multivariable regression models adjusted for study site were performed using second-generation p-values, a novel statistical approach. Associations with unfavorable treatment outcomes were tested for both RePORT-Brazil and SINAN cohorts. Findings: 1,060 culture-confirmed TB patients were enrolled in RePORT-Brazil and 455,873 TB cases were reported to SINAN. Second-generation p-value analyses revealed that the cohorts were strikingly similar with regard to sex, age, use of antiretroviral therapy and positive initial smear sputum microscopy. However, diabetes, HIV infection and smoking were more frequently documented in RePORT-Brazil. Illicit drug use, presence of diabetes and history of prior TB were associated with unfavorable TB treatment outcomes; illicit drug use was associated with such outcomes in both cohorts. Interpretations: There were important similarities in demographic characteristics and determinants of clinical outcomes between the RePORT-Brazil cohort and the Brazilian National registry of TB cases. Funding Statement: Fundacao Jose Silveira and Ministerio da Saude, Brazil and the National Institutes of Allergy and Infectious Diseases. Declaration of Interests: All authors: none reported. Ethics Approval Statement: All clinical investigations were conducted according to the principles of the Declaration of Helsinki. The RePORT-Brazil protocol, informed consent, and study documents were approved by the institutional review boards at each study site and at Vanderbilt University Medical Center. Participation in RePORT Brazil was voluntary, and written informed consent was obtained from all such participants. For the data extracted from SINAN, the anonymity of study subjects was preserved, and all data were de-identified.

Purpose of review: Tuberculosis (TB) remains the leading cause of death in people living with HIV (PLHIV) despite the achievements in antiretroviral therapy coverage. TB preventive therapy (TPT) has proved efficacy but has been neglected and poorly implemented. We reviewed recent publications and guidelines about TPT in PLHIV. Recent findings: High-quality studies showed that TPT has a durable effect, over 5 years, preventing TB and all-cause mortality. There is new evidence showing the noninferiority of shorter, rifamycin-based regimens of TPT increasing the options for treatment. Recent studies describing robust implementation in different settings showed promising results for feasibility, tolerance, retention, and cost-effectiveness. New WHO recommendations, unifying previous versions, have been released to guide countries implementation. Summary: New evidence support the scale up of TPT for PLHIV globally, further studies are needed to bring more evidence for specific populations, like pregnant women and for drug–drug interactions with antiretroviral agents.

BACKGROUND Cutaneous tuberculosis (CTB) is a rare extrapulmonary form of tuberculosis (TB). Despite the increase in the number of cases of TB and HIV, few cases of CTB have been reported. OBJECTIVE To describe CTB cases among patients with HIV infection from a cohort with tuberculosis. METHODS We describe a series of 15 CTB and HIV cases, based on secondary data from 2000 to 2016. Diagnosis was based on isolation of Mycobacterium tuberculosis in culture or clinical response to anti-tuberculous treatment associated with positive smear or histopathologic findings from affected skin or an adjacent lymph node. FINDINGS Scrofuloderma was present in 12 (80%) patients and solitary gumma in three (20%) patients. One case of scrofuloderma was associated with papulonecrotic tuberculid. Seven (46.6%) patients had pulmonary TB. Diagnosis was based on culture in nine patients (60%). The median CD4 cell count was 262 cells/µL. All patients were cured at the end of treatment (median time 6 months). Three patients presented with immune reconstitution inflammatory syndrome. CONCLUSIONS In this study, CTB associated with HIV infection presented as localised forms or in association with pulmonary TB. In patients with HIV who have subacute and chronic skin lesions, CTB should be considered in differential diagnosis, which may represent a good opportunity for early diagnosis of active TB.

Objective To estimate the incremental cost-effectiveness of tuberculosis (TB) screening and isoniazid preventive therapy (IPT) among human immunodeficiency virus (HIV) infected adults in Rio de Janeiro, Brazil. Design We used decision analysis, populated by data from a cluster-randomized trial, to project the costs (in 2010 USD) and effectiveness (in disability-adjusted life years [DALYs] averted) of training health care workers to implement the tuberculin skin test (TST), followed by IPT for TST-positive patients with no evidence of active TB. This intervention was compared to a baseline of usual care. We used time horizons of 1 year for the intervention and 20 years for disease outcomes, with all future DALYs and medical costs discounted at 3% per year. Results Providing this intervention to 100 people would avert 1.14 discounted DALYs (1.57 undiscounted DALYs). The median estimated incremental cost-effectiveness ratio was $2273 (IQR $1779-$3135) per DALY averted, less than Brazil's 2010 per capita gross domestic product (GDP) of $11,700. Results were most sensitive to the cost of providing the training. Conclusion Training health care workers to screen HIV-infected adults with TST and provide IPT to those with latent tuberculous infection can be considered cost-effective relative to the Brazilian GDP per capita.

Background Unsuccessful tuberculosis outcomes are frequent; bold policies are needed to end the tuberculosis (TB) epidemic to attain the third Sustainable Development Goal (SDG) by 2030. We examined the effect of the Family Health Strategy (FHS) and its interactions with the conditional cash transfer programme (CTP) on TB outcomes in Rio de Janeiro, Brazil. Methods We performed individual-based analyses of a database resulting from deterministic and probabilistic linkages of the TB information system, FHS registries and CTP payrolls. Patients ≥15 years old treated with the standard RHZE regimen were included. The rates of successful outcomes were analysed according to coverage by FHS. Effects from the CTP and its interactions with the FHS were examined among the poorest. Results FHS coverage increased the likelihood for successful outcomes by 14% (12-17%) among 13 482 new cases, and by 35% (25-47%) among 1880 retreatment cases. The CTP had an independent effect but no interaction with the FHS among the poorest. Conclusions This is the first individual-based study to show a relevant protection of poor urban communities regarding patient-important health outcomes by the Brazilian FHS and CTP. These findings support strategies of universal health coverage, primary care strengthening and social protection to achieve a major SDG.

Background: The timing of highly active antiretroviral therapy (HAART) after a tuberculosis diagnosis in HIV-infected patients can affect clinical outcomes and survival. We compared survival after tuberculosis diagnosis in HIV-infected adults who initiated HAART and tuberculosis therapy simultaneously to those who delayed the start of HAART for at least two months. Methods: The THRio cohort includes 17,983 patients receiving HIV care in 29 public clinics in Rio de Janeiro, Brazil. HAART-naïve patients at the time of a new TB diagnosis between September 2003 and June 2008 were included. Survival was measured in days from diagnosis of TB. We compared survival among patients who initiated HAART within 60 days of TB treatment (simultaneous – ST) to those who started HAART >60 days of TB treatment or never started (deferred – DT). Kaplan–Meier plots and Cox proportional hazards regression analyses were conducted. Results: Of 947 patients diagnosed with TB, 572 (60%) were HAART naïve at the time of TB diagnosis; 135 were excluded because of missing CD4 count results. Among the remaining 437 TB patients, 56 (13%) died during follow-up: 25 (10%) among ST patients and 31 (16%) in DT group (p = 0.08). ST patients had lower median CD4 counts at TB diagnosis than DT patients (106 vs. 278, p

Background: Determine TB-LAM Ag (LAM) is a point of care test developed to diagnose tuberculosis (TB). The aim of this study was to evaluate the diagnostic performance of LAM in people living with HIV using Brazilian public health network algorithm for TB diagnosis. Methods and findings A cross-sectional study design was used to enroll 199 adult patients in two sites in Rio de Janeiro and two in Sao Paulo. The study enrolled HIV-infected patients with CD4 counts ≤ 200 cells/mm3 (in the Alere PIMA CD4 assay at study screening), patients coughing for at least 2 weeks or presenting a chest radiography suggestive of TB. LAM, in conjunction with sputum smear microscopy or Xpert MTB/RIF (Xpert) as compared to Mycobacterium tuberculosis culture, which was used as a reference standard. TB prevalence was 24.6%. Overall accuracy of LAM was 79.9% (73.8%-84.9%), positive and negative predictive values were 62.2% (46.1%-75.9%) and 84% (77.5%-88.8%), respectively. The overall LAM sensitivity was 46.9% (33.7%-60.6%) and specificity was 90.7% (84.9%-94.4%). The best performance of LAM was observed among patients with CD4 counts ≤ 50 cells/mm3 (sensitivity = 70.4% and specificity = 85.9%). When 2 respiratory smears were used in conjunction with LAM, sensitivity increased 22%, as compared to just 2 smears. Furthermore, LAM when used in conjunction with two respiratory smears, was as sensitive as compared to a single one. However, no improvement in TB diagnosis occurred when LAM was used with Xpert as compared to Xpert alone. Among 14 LAM false positive tests, Non-Tuberculosis Mycobacteria were isolated in three cases. Conclusion: LAM is a point of care test that increased TB diagnosis in immunosuppressed HIV-infected patients when used in conjunction with smear microscopy, but not when used with Xpert in Brazilian public health network sites. Use of LAM test should be considered in settings where immunosuppressed HIV patients need rapid TB diagnosis.

OBJECTIVES To evaluate the population-based impact of a comprehensive intervention to strengthen tuberculosis (TB) control in Rocinha, the largest urban slum in Rio de Janeiro, Brazil. DESIGN In July 2003, 40 lay persons were hired and trained as community health workers to supervise treatment, implement educational activities and establish a supportive social network for anti-tuberculosis treatment. Between July 2005 and June 2008, a door-to-door active case finding campaign was conducted. Data were obtained from the Brazilian National Reporting System, which collects information from the TB notification form for every reported case. RESULTS Between January 2001 and December 2008, 2623 TB cases were reported, 852 before and 1771 after the start of the program. Following the intervention, treatment success rates increased (67.6% vs. 83.2%, P < 0.001) and default rates dropped (17.8% vs. 5.5%, P < 0.001). Compared to the pre-intervention period, the TB case rate declined by an average of 39 cases per 100,000 population per 6 months (P = 0.003) in the post-intervention period, although this may have been due to secular trends already in place at the start of the intervention. Case rates declined from 591/100,000 in 2001 to 496/100,000 in 2008. CONCLUSION With proper planning and effective community involvement, a successful intervention can lead to high cure rates and may contribute to a decrease in TB notification rates.