A Score to Predict the Risk of Major Adverse Drug Reactions Among Multi-Drug Resistant Tuberculosis Patients in Southern Ethiopia, 2014–2019

Abstract

Background

Adverse events (AE) contribute to poor drug adherence and withdrawal, which contribute to a low treatment success rate. AE are commonly reported among multi-drug resistance tuberculosis (MDR-TB) patients in Ethiopia. However, predictors of AE among MDR-TB patients were limited in Ethiopia. Thus, the current study aimed to develop and validate a score to predict the risks of major AE among MDR-TB patients in Southern Ethiopia.

Methods

A retrospective follow-up study design was employed among MDR-TB patients from 2014–2019 in southern Ethiopia at selected hospitals. A least absolute shrinkage and selection operator algorithm was used to select the most potent predictors of the outcome. The adverse event risk score was built based on the multivariable logistic regression analysis. Discriminatory power and calibration were checked to evaluate the performance of the model. Bootstrapping method with 100 repetitions was used for internal model validation.

Results

History of baseline khat use, long-term drug regimen use, and having coexisting disorders (co-morbidity) were predictors of AEs. The score has a satisfactory discriminatory power (AUC = 0.77, 95% CI: 0.68, 0.82) and a modest calibration (Prob > chi² = 0.2043). It was found to have the same c-statistics after validation by bootstrapping method of 100 repetitions with replacement.

Conclusion

A history of baseline khat use, co-morbidity, and long-term drug regimen use are helpful to predict individual risk of major adverse events in MDR-TB patients with a satisfactory degree of accuracy (AUC = 0.77).

Keywords:

• prediction
• multi-drug resistant tuberculosis
• major adverse events
• Southern Ethiopia

Abbreviations

BMI, Body Mass Index; CI, Confidence Interval; CXR, Chest X-ray; CV, Cross validation; DR, Drug-Resistance; DST, Drug Susceptibility Test; LASSO, Least Absolute Shrinkage and Selection Operator; MDR, Multidrug-Resistant; AEs, Major Adverse Events; SRR, Rifampicin Resistance; SNNPR, Southern Nation, Nationalities, and People’s Region; TIC, Treatment Initiation Centers; TB, Tuberculosis; WHO, World Health Organization; XDR, Extensively Drug-Resistant.

Data Sharing Statement

The data will be available on a reasonable request from the corresponding author.

Ethical Approval and Consent to Participate

Ethical grant was obtained from the University of Gondar institutional review board (IRB) and permission was secured from SNNPR health departments. Informed consent was not taken directly from the study subjects since the data were collected retrospectively. Confidentiality of information was kept. The study was conducted in accordance with the Declaration of Helsinki.

Acknowledgments

We would like to forward our gratitude to the University of Gondar for providing small financial support for the data collection. Moreover, we also extend our thanks to the data collectors and supervisors.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

We authors declare that there is no conflict of interest.

Additional information

Funding

The study received only minimal support from Amhara region health bureau for the data collection. However, the funder has no role in conception, design, analysis, interpretation, and decision on the publication of the manuscript in international journals.