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. 2019 Jan 24;14(1):e0211355.
doi: 10.1371/journal.pone.0211355. eCollection 2019.

The impact of improved detection and treatment of isoniazid resistant tuberculosis on prevalence of multi-drug resistant tuberculosis: A modelling study

Kamila Romanowski  1 , Jonathon R Campbell  2 , Olivia Oxlade  2 , Federica Fregonese  2 , Dick Menzies  2   3 , James C Johnston  1   2   4
Affiliations

The impact of improved detection and treatment of isoniazid resistant tuberculosis on prevalence of multi-drug resistant tuberculosis: A modelling study

Kamila Romanowski et al. PLoS One. .

Abstract

Introduction: Isoniazid-resistant, rifampin susceptible tuberculosis (INHR-TB) is the most common form of drug resistant TB globally. Treatment of INHR-TB with standard first-line therapy is associated with high rates of multidrug resistant TB (MDR-TB). We modelled the potential impact of INHR-TB detection and appropriate treatment on MDR-TB prevalence.

Methods: A decision analysis model was developed to compare three different strategies for the detection of TB (AFB smear, Xpert MTB/RIF, and Line-Probe Assays (LPA)), combined with appropriate treatment. The population evaluated were patients with a globally representative prevalence of newly diagnosed, drug-susceptible (88.6%), isoniazid-resistant (7.3%), and multidrug resistant (4.1%) pulmonary TB. Our primary outcome was the proportion of patients with MDR-TB after initial attempt at diagnosis and treatment within a 2-year period. Secondary outcomes were the proportion of i) individuals with detected TB who acquired MDR-TB ii) individuals who died after initial attempt at diagnosis and treatment.

Results: After initial attempt at diagnosis and treatment, LPA combined with appropriate INHR-TB therapy resulted in a lower proportion of prevalent MDR-TB (1.61%; 95% Uncertainty Range (UR: 2.5th and 97.5th percentiles generated from 10 000 Monte Carlo simulation trials) 1.61-1.65), when compared to Xpert (1.84%; 95% UR 1.82-1.85) and AFB smear (3.21%; 95% UR 3.19-3.26). LPA also resulted in fewer cases of acquired MDR-TB in those with detected TB (0.35%; 95% UR 0.34-0.35), when compared to Xpert (0.67%; 95% UR 0.65-0.67) and AFB smear (0.68%; 95% UR 0.67-0.69). The majority of acquired MDR-TB arose from the treatment of INHR-TB in all strategies. Xpert-based strategies resulted in a lower proportion of death (2.89%; 95% UR 2.87-2.90) compared to LPA (2.93%; 95% UR 2.91-2.94) and AFB smear (3.21%; 95% UR 3.19-3.23).

Conclusion: Accurate diagnosis and tailored treatment of INHR-TB with LPA led to an almost 50% relative decrease in acquired MDR-TB when compared with an Xpert MTB/RIF strategy. Continued reliance on diagnostic and treatment protocols that ignore INHR-TB will likely result in further generation of MDR-TB.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Simplified schematic of model.
This diagram depicts a simplified representation of the decision analysis model. The square indicates a decision node and the circles indicate probability nodes. Three different diagnostic and treatment strategies were considered over a two-year period in the decision analysis model: (1) AFB smear with WHO standard first line therapy for all people diagnosed with TB (2 months isoniazid, rifampin, pyrazinamide, ethambutol, followed by 4 months isoniazid, rifampin (2HRZE/4HR)); (2) Xpert MTB/RIF with standardized WHO recommended MDR-TB therapy for those with detected MDR-TB, and 2HRZE/4HR for the remainder; (3) LPA with a daily regimen of 6 months of rifampin, ethambutol, and pyrazinamide with or without isoniazid (6(H)REZ) for detected INHR-TB, standardized WHO recommended MDR-TB therapy for those with detected MDR-TB, and 2HRZE/4HR for the remainder. TB (tuberculosis); INHR (isoniazid resistant); MDR (multi-drug resistant); LPA (Line Probe Assay).
Fig 2
Fig 2. Total proportion of patients with MDR-TB after initial attempt at diagnosis and treatment, based on varying population INHR-TB prevalence.
Fig 3
Fig 3. Proportion of patients with acquired MDR-TB after initial attempt at diagnosis and treatment, based on varying population INHR-TB prevalence.
Fig 4
Fig 4. Relationship between drug resistance prevalence and diagnostic test to minimize total MDR-TB.
See this image and copyright information in PMC

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