Publications by authors named "Kritski A"

Background: Tuberculosis vaccine trials using disease as the primary endpoint are large, time consuming, and expensive. An earlier immunological measure of the protection against disease would accelerate tuberculosis vaccine development. We aimed to assess whether the effectiveness of the Bacillus Calmette-Guérin (BCG) vaccine for prevention of Mycobacterium tuberculosis infection was consistent with that for prevention of tuberculosis disease.

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Background: Genetic polymorphisms have been associated with risk of antituberculosis treatment toxicity. We characterized associations with adverse events and treatment failure/recurrence among adults treated for tuberculosis in Brazil.

Methods: Participants were followed in Regional Prospective Observational Research in Tuberculosis (RePORT)-Brazil.

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Article Synopsis
  • Drug resistance in tuberculosis (TB) poses significant challenges, and the introduction of bedaquiline (BED) aims to improve treatment outcomes and reduce adverse events (AEs).
  • A retrospective study conducted at a Brazilian clinic analyzed 297 patients with rifampicin-resistant (RR) or multidrug-resistant (MDR) TB, comparing outcomes between Injectable Containing Regimens (ICR) and BED Containing Regimens (BCR).
  • The findings indicated that AEs were significantly more common in the ICR group, while BCR patients experienced better treatment outcomes and fewer AEs, suggesting BED is a more effective option for managing DR-TB.
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Background: Few studies in routine settings have confirmed the high accuracy of the Xpert MTB/RIF assay for detecting rifampicin resistance (RR) and the first-line probe assay (FL-LPA) for detecting both RR and isoniazid resistance (INHR).

Methods: The performance of Xpert MTB/RIF and MTBDRplus VER 2.0 LPA was evaluated in 180 Mycobacterium tuberculosis samples collected from January 2018 to December 2019 in Rio de Janeiro, Brazil.

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  • TB treatment response varies based on genetic ancestry, with a study in Brazil showing differing risks for adverse drug reactions (ADRs) linked to African and European ancestry.
  • Patients with a higher proportion of African ancestry had a lower risk of Grade 2+ ADRs, while those with higher European ancestry faced an increased risk; however, this trend changed for patients living with HIV.
  • The research involved 941 pulmonary TB patients, and no significant associations were found for Amerindian ancestry or other treatment outcomes in the cohort.
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  • The study established new therapeutic drug ranges (TDR) for standard anti-tuberculosis (TB) drugs aimed at minimizing toxicity while maximizing effectiveness in treating TB.
  • It analyzed data from 448 patients with drug-susceptible pulmonary TB, identifying drug concentrations that maintained a low probability of adverse drug reactions (ADR) and a high probability of treatment success.
  • Findings revealed that the TDR for isoniazid (INH) and rifampin (RIF) were different from current recommendations, suggesting higher upper limits for INH and lower for RIF, while the ranges for ethambutol (EMB) and pyrazinamide (PZA) were consistent with existing guidelines.
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Background: Adherence to anti-tuberculosis treatment (ATT) in Brazil remains a challenge in achieving the goals set by the World Health Organization (WHO). Patients who are lost to follow-up during treatment pose a significant public health problem. This study aimed to investigate the factors associated with unfavorable ATT outcomes among those undergoing retreatment in Brazil.

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This study aimed to reinforce the importance of the epidemiological surveillance of multidrug-resistant tuberculosis (MDR-TB) in Rio de Janeiro State (RJ). Here, we reviewed seven articles we published between 2018 and 2022. This study had two phases.

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Article Synopsis
  • * This study aimed to analyze genetic variations (SNPs) related to the enzyme in a specific population, revealing that most individuals had slow or intermediate acetylation phenotypes.
  • * Identifying these genetic profiles can lead to personalized treatment strategies that improve patient outcomes, reduce treatment costs, and prevent drug-resistant strains of tuberculosis.
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Background: Tuberculosis (TB) and depression are highly comorbid and linked to higher rates of death and disability. Several evidence-based treatments for depression have been successfully implemented in low- and middle-income countries, but more knowledge is needed on how to bring these innovations to scale within complex 'real world' public health systems.

Objective: To explore whether the principles of social network analysis could be used to enhance receptivity to integrating depression treatment into primary care for individuals with and without TB in Brazil.

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The provision of tuberculosis preventive treatment is one of the critical interventions to reduce tuberculosis incidence and ultimately eliminate the disease, yet we still miss appropriate tools for an impactful intervention and treatment coverage remains low. We used recent data, epidemiological estimates, and research findings to analyze the challenges of each step of the cascade of tuberculosis prevention that currently delay the strategy implementation. We addressed research gaps and implementation bottlenecks that withhold key actions in tuberculosis case finding, testing for tuberculosis infection, provision of preventive treatment with safer, shorter regimens and supporting people to complete their treatment.

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Article Synopsis
  • - The study focused on analyzing the genetic diversity of Mycobacterium tuberculosis (Mtb) isolates from drug-resistant tuberculosis patients in Brazil, finding a high prevalence of multidrug-resistant cases at 54.8% and pre-extensively drug-resistant cases at 9.2%.
  • - Researchers utilized whole-genome sequencing (WGS) to scrutinize 298 Mtb isolates, identifying the most common sub-lineage as 4.3 and uncovering 20 new mutations linked to drug resistance, with significant ongoing transmission among patients noted through genomic clustering.
  • - The in-house WGS pipeline outperformed online tools in predicting drug resistance, revealing key associations between certain genotypes and severe disease outcomes, which enhances the understanding of
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Diagnosis of M. tuberculosis (Mtb) infection in close contacts is critical for TB control. Smoking is a risk factor for Mtb infection and TB disease but its effect on longitudinal interferon-gamma release assay (IGRA) results remains unknown.

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Background: Approximately 5% of people infected with Mycobacterium tuberculosis progress to tuberculosis (TB) disease without preventive therapy. There is a need for a prognostic test to identify those at highest risk of incident TB so that therapy can be targeted. We evaluated host blood transcriptomic signatures for progression to TB disease.

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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.

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Background: The high burden of drug-resistant tuberculosis (TB) is a problem to achieve the goals of the End TB Strategy by 2035. Whether isoniazid monoresistance (Hr) affects anti-TB treatment (ATT) outcomes remains unknown in high-burden countries.

Methods: We evaluated determinants of ATT outcome among pulmonary TB cases reported to the National Notifiable Disease Information System (SINAN) between June 2015 and June 2019, according to drug sensitivity testing (DST) results.

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Background: The Xpert® MTB/RIF rapid molecular test provides a quantitative measure of Mycobacterium tuberculosis (Mtb) DNA in the form of cycle threshold (Ct) values. This information can be translated into mycobacterial load and used as a potential risk measure of bacterial spread for tuberculosis cases, which can impact infection control. However, the role of Ct values in assessing Mtb transmission to close contacts has not yet been demonstrated.

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Background: Multidrug-resistant tuberculosis (MDR-TB) is a serious global public health concern associated with social vulnerability. In Brazil, the Unified Health System (SUS, Portuguese) provides free diagnosis and treatment for MDR-TB; however, other expenses may still be incurred for patients and their families which, according to the World Health Organization (WHO), can be catastrophic when these costs surpass 20.0% of the annual household income.

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Background: Genetic polymorphisms have been associated with risk of anti-tuberculosis treatment toxicity. We characterized associations with adverse events and treatment failure/recurrence among adults treated for tuberculosis in Brazil.

Methods: Participants were followed in Regional Prospective Observational Research in Tuberculosis (RePORT)-Brazil.

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Background: We aimed to evaluate the costs of GenoType® MTBDRplus and MTBDRsl incurred during the diagnosis of first- and second-line drug-resistant tuberculosis (TB) in São Paulo, Brazil.

Methods: Mean and activity-based costs of GenoType® were calculated in a referral laboratory for TB in Brazil.

Results: The mean cost value and activity-based cost of GenoType® MTBDRplus were USD 19.

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Tuberculosis (TB) and depression is common and is associated with poor TB outcomes. The World Health Organization End TB Strategy explicitly calls for the integration of TB and mental health services. Interpersonal Counseling (IPC) is a brief evidence-based treatment for depression that can be delivered by non-mental health specialists with expert supervision.

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Article Synopsis
  • * Mycobacterium kansasii was the most common NTM identified, present in about 11.5% of analyzed patients.
  • * Of the patients who met the diagnostic criteria, nearly half received treatment, with a high cure rate of about 75.8% among those treated, with dyspnea and cough being the most common symptoms.
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Tuberculosis (TB) is one of the infectious diseases that currently causes the most deaths, with 6.4 million new cases recorded in 2021. Although it is a curable disease, drug-resistant strains emerge due to a lack of hygiene and low-quality or inappropriate medications, among other factors.

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