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Public Health Impact of the Genexpert MTB/RIF Implementation in Tuberculosis Control in Brazil: A Nationwide Intervention Time-Series Analysis

30 Pages Posted: 4 Dec 2023

See all articles by Klauss Villalva-Serra

Klauss Villalva-Serra

Oswaldo Cruz Foundation (FIOCRUZ) - Gonçalo Moniz Institute (IGM)

Beatriz Barreto Duarte

Oswaldo Cruz Foundation (FIOCRUZ) - Laboratório de Inflamação e Biomarcadores

João P. Miguez-Pinto

UNIFACS- Universidade Salvador

Artur T. L. Queiroz

Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative

Moreno M. S. Rodrigues

Oswaldo Cruz Foundation (FIOCRUZ) - Laboratório de Análise e Visualização de Dados

Peter F. Rebeiro

Vanderbilt University - Division of Infectious Diseases

Gustavo Amorim

Vanderbilt University

Marcelo Cordeiro-Santos

Universidade do Estado do Amazonas - Programa de Pós-Graduação em Medicina Tropical

Timothy R. Sterling

Vanderbilt University - Division of Infectious Diseases

Mariana Araújo-Pereira

Oswaldo Cruz Foundation (FIOCRUZ) - Laboratório de Inflamação e Biomarcadores; Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative

Bruno B. Andrade

Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative; Oswaldo Cruz Foundation (FIOCRUZ) - Laboratório de Inflamação e Biomarcadores

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Abstract

Background: Adequate laboratory diagnostic testing is essential for management of drug-resistant tuberculosis (DR-TB). Since 2014, Brazil has gradually implemented the GeneXpert MTB/RIF (GeneXpert) test to enhance early tuberculosis (TB) and DR-TB detection. Nonetheless, the nationwide public health impact of this implementation remains underexplored.

Methods: 1,088,544 cases from Brazil's National TB Registry (2011-2022) were evaluated to assesses the influence of the GeneXpert adoption on TB notification, including DR-TB and drug-susceptible TB (DS-TB) screening. Intervention time-series analysis gauged the impact of GeneXpert implementation on case detection, while Granger Causality assessed its predictive power on future disease trends. Dynamic regression modelling determined if incorporating GeneXpert testing as an external regressor enhanced forecasting accuracy for Brazil’s future TB trends. Geographical distribution in testing and notification rates were also examined.

Findings: GeneXpert implementation resulted in a 9·7% increase in TB notification and substantial improvements in DR-TB (63·6%) and DS-TB (92·1%) detection compared to counterfactual measures. Cross-correlation and Granger Causality validated the time-dependent relationship and predictive power of GeneXpert testing on DR-TB control. Dynamic regression analysis showed GeneXpert’s utility in enhancing forecasts of disease burden, projecting a possible scenario of increase in TB and DR-TB cases over the next 6 years. However, regional disparities were evident, with the Southeast and South regions reporting higher testing coverage.

Interpretation: Our study underscores the critical role of the GeneXpert adoption in boosting TB and DR-TB detection in Brazil, beneficiating disease management and offering insights for effective public health measures worldwide. Improvements in prediction accuracy caused by integrating GeneXpert data into dynamic regression models highlight the importance of using external predictors in epidemiological forecasting. By acknowledging the GeneXpert’s role in both disease management and improving predictions, we advocate for its expanded use and further research into advanced molecular diagnostics for effective TB and DR-TB control worldwide.

Funding: Oswaldo Cruz Foundation Intramural Research Program

Declaration of Interest: None to declare.

Ethical Approval: These data were pre-processed by the Brazilian MoH to check for duplicates, completeness, and consistency, following the guidelines of Resolution Number 466/12 on Research Ethics by the National Health Council, Brazil.

Keywords: GeneXpert MTB/RIF, intervention time-series, drug-resistant tuberculosis, laboratory diagnostics, public health measures

Suggested Citation

Villalva-Serra, Klauss and Barreto Duarte, Beatriz and Miguez-Pinto, João P. and Queiroz, Artur T. L. and Rodrigues, Moreno M. S. and Rebeiro, Peter F. and Amorim, Gustavo and Cordeiro-Santos, Marcelo and Sterling, Timothy R. and Araújo-Pereira, Mariana and Andrade, Bruno B., Public Health Impact of the Genexpert MTB/RIF Implementation in Tuberculosis Control in Brazil: A Nationwide Intervention Time-Series Analysis. Available at SSRN: https://ssrn.com/abstract=4650302 or http://dx.doi.org/10.2139/ssrn.4650302

Klauss Villalva-Serra

Oswaldo Cruz Foundation (FIOCRUZ) - Gonçalo Moniz Institute (IGM) ( email )

Beatriz Barreto Duarte

Oswaldo Cruz Foundation (FIOCRUZ) - Laboratório de Inflamação e Biomarcadores ( email )

Salvador
Brazil

João P. Miguez-Pinto

UNIFACS- Universidade Salvador ( email )

Artur T. L. Queiroz

Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative ( email )

Salvador
Brazil

Moreno M. S. Rodrigues

Oswaldo Cruz Foundation (FIOCRUZ) - Laboratório de Análise e Visualização de Dados ( email )

Rio de Janeiro
Brazil

Peter F. Rebeiro

Vanderbilt University - Division of Infectious Diseases ( email )

United States

Gustavo Amorim

Vanderbilt University ( email )

Marcelo Cordeiro-Santos

Universidade do Estado do Amazonas - Programa de Pós-Graduação em Medicina Tropical ( email )

Avenida Djalma Batista, 3578
Manaus, 69050-010
Brazil

Timothy R. Sterling

Vanderbilt University - Division of Infectious Diseases ( email )

United States

Mariana Araújo-Pereira

Oswaldo Cruz Foundation (FIOCRUZ) - Laboratório de Inflamação e Biomarcadores ( email )

Salvador
Brazil

Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative ( email )

Bruno B. Andrade (Contact Author)

Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative ( email )

Oswaldo Cruz Foundation (FIOCRUZ) - Laboratório de Inflamação e Biomarcadores ( email )

Salvador
Brazil

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