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Abstract A multi-disciplinary approach of volcano-stratigraphy, petrology and geochemistry has shed light on the pre-eruptive processes, the eruptive triggering, behaviour and the architecture of the magma plumbing system during the explosive cycle of Petrazza at ca. 77–75 ka (PaleoStromboli I eruptive epoch, Stromboli). This was the largest magnitude eruptive cycle in Stromboli and one of the largest of the entire Aeolian archipelago, able to produce Vulcanian to sub-Plinian/Plinian phases with distal deposits found in the tephrostratigraphic record of the Tyrrhenian sea and surroundings. Our study highlighted that, differently from the present-day activity, the large magnitude Petrazza eruptive cycle could be attributed to phases of closed-system conditions, as also testified by the in equilibrium presence of amphibole, indicative of a “steady-state” magmatic status of the system. The explosive activity is then attributed to strong depressurization underwent by the plumbing system due to the cyclic closure/opening of the shallow conduit, possibly also in association with lateral collapse events. As shown by textural and compositional studies on plagioclase crystals, this decompression was also able to recall amphibole bearing mafic magma from the deep portion of the plumbing system (5–15 km of depth).

A multi-disciplinary approach of volcano-stratigraphy, petrology and geochemistry has shed light on the pre-eruptive processes, the eruptive triggering, behaviour and the architecture of the magma plumbing system during the explosive cycle of Petrazza at ca. 77-75 ka (PaleoStromboli I eruptive epoch, Stromboli). This was the largest magnitude eruptive cycle in Stromboli and one of the largest of the entire Aeolian archipelago, able to produce Vulcanian to sub-Plinian/Plinian phases with distal deposits found in the tephrostratigraphic record of the Tyrrhenian sea and surroundings. Our study highlighted that, differently from the present-day activity, the large magnitude Petrazza eruptive cycle could be attributed to phases of closed-system conditions, as also testified by the in equilibrium presence of amphibole, indicative of a "steady-state" magmatic status of the system. The explosive activity is then attributed to strong depressurization underwent by the plumbing system due to the cyclic closure/opening of the shallow conduit, possibly also in association with lateral collapse events. As shown by textural and compositional studies on plagioclase crystals, this decompression was also able to recall amphibole bearing mafic magma from the deep portion of the plumbing system (5-15 km of depth)., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Tuberculosis (TB) treatment is highly effective, but response to therapy can vary by geography, race, and ethnicity. We assessed for differences in TB treatment response in a representative and heterogeneous Brazilian population. We estimated genetic ancestry proportion according to major ancestry groups (African, European, and Amerindian ancestry) in the Regional Prospective Observational Research in Tuberculosis (RePORT)-Brazil cohort. RePORT-Brazil is an observational prospective cohort study of individuals with newly-diagnosed, culture-confirmed, pulmonary TB. TB treatment outcomes that were attributed to TB treatment included Grade 2 or higher adverse drug reaction (ADR), Grade 3 or higher ADR, hepatic ADR, and failure/recurrence. Ancestry proportion was the main predictor in logistic regression for each outcome, with adjustments for candidate confounders. There were 941 pulmonary TB patients included in this study. We observed a decreased risk of Grade 2+ ADR when African ancestry proportion increased by 10% (Odds Ratio [OR] 0.41, 95% Confidence Interval [CI] 0.20 -0.85) and an increased risk for Grade 2+ ADR with increasing European ancestry (OR 2.84, 95% CI 1.47 - 5.48). We then performed the same analysis adding HIV status as an interaction term. The decreased risk for Grade 2+ ADR seen for African ancestry proportion did not hold for persons living with HIV; we observed increased risk for Grade 2+ ADR with increasing African ancestry proportion. There were no associations with Amerindian ancestry or for other treatment outcomes. In this Brazilian TB cohort, toxicity risk was associated with African and European ancestry, divergent, and affected by HIV. #RePORT-Brazil Consortium members include: Aline Benjamin and Flavia M. Sant'Anna Instituto Nacional de Infectologia Evandro Chagas, Fiocruz, Rio de Janeiro, Brazil Jamile Garcia de Oliveira and João Marine Clínica de Saúde Rinaldo Delmare, Rio de Janeiro, Brazil Adriana Rezende and Anna Cristina Carvalho Secretaria de Saúde de Duque de Caxias, Rio de Janeiro, Brazil Michael Rocha and Betânia Nogueira Instituto Brasileiro para Investigação da Tuberculose, Fundação José Silveira, Salvador, Brazil Alexandra Brito and Renata Spener Fundação Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Brazil Megan Turner Vanderbilt University Medical Center, Nashville, USA.

Background: Tuberculosis (TB) treatment-related adverse drug reactions (TB-ADRs) can negatively affect adherence and treatment success rates., Methods: We developed prediction models for TB-ADRs, considering participants with drug-susceptible pulmonary TB who initiated standard TB therapy. TB-ADRs were determined by the physician attending the participant, assessing causality to TB drugs, the affected organ system, and grade. Potential baseline predictors of TB-ADR included concomitant medication (CM) use, human immunodeficiency virus (HIV) status, glycated hemoglobin (HbA1c), age, body mass index (BMI), sex, substance use, and TB drug metabolism variables (NAT2 acetylator profiles). The models were developed through bootstrapped backward selection. Cox regression was used to evaluate TB-ADR risk., Results: There were 156 TB-ADRs among 102 of the 945 (11%) participants included. Most TB-ADRs were hepatic (n = 82 [53%]), of moderate severity (grade 2; n = 121 [78%]), and occurred in NAT2 slow acetylators (n = 62 [61%]). The main prediction model included CM use, HbA1c, alcohol use, HIV seropositivity, BMI, and age, with robust performance (c-statistic = 0.79 [95% confidence interval {CI}, .74-.83) and fit (optimism-corrected slope and intercept of -0.09 and 0.94, respectively). An alternative model replacing BMI with NAT2 had similar performance. HIV seropositivity (hazard ratio [HR], 2.68 [95% CI, 1.75-4.09]) and CM use (HR, 5.26 [95% CI, 2.63-10.52]) increased TB-ADR risk., Conclusions: The models, with clinical variables and with NAT2, were highly predictive of TB-ADRs., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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., Competing Interests: Potential conflicts of interest. The authors do not have an association that might pose a conflict of interest. V. C. R. reports grants or contracts outside of the submitted work from TB Alliance for Drug Development (NC-008), Impacto da COVID-19 Nas Manifestações Clínicas, Diagnóstico, Desfecho Do Tratamento e Resposta Imune para Tuberculose Pulmonar (440933/2020-0 to CNPq account (not to self), Associative BRICS Research in COVID-19 and Tuberculosis (ABRICOT) (G-202105-67821 to Fiotec), RePORT International Data Harmonization (R-202108-68053 to Fiotec), Transcriptional Signature of TB in advanced HIV (DAA3-18-64313 to Fiotec), Predictors of Resistance Emergence Evaluation in Multidrug-resistant Tuberculosis patients on Treatment – PREEMPT (R01AI134430), Caribbean, Central, and South America network for HIV Epidemiology (CCASAnet) (U01AI069923 to Fiotec), and immunogenetic predictors of active and incipient TB in HIV-negative and -positive close TB contacts (R01AI147765 to Fiotec); consulting fees paid to self from ONU-OMS Country review for HIV response Myanmar; payment or honoraria paid to self from GLAXOSMITHKLINE BRASIL LTDA, Qiagen (Infecto Rio Conference), and virology education (Infecto Rio Conference); payment directly to the conference for registration for ViiV 18 European AIDS conference; and payment directly to self from NIH Data Safety Monitoring Board., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)