Evaluation of Xpert MTB-RIF guided diagnosis and treatment of rifampicin-resistant tuberculosis in Indonesia: A retrospective cohort study

Arto Yuwono Soeroto, Bony Wiem Lestari, Prayudi Santoso, Lidya Chaidir, Basti Andriyoko, Bachti Alisjahbana, Reinout van Crevel, Philip C Hill, Arto Yuwono Soeroto, Bony Wiem Lestari, Prayudi Santoso, Lidya Chaidir, Basti Andriyoko, Bachti Alisjahbana, Reinout van Crevel, Philip C Hill

Abstract

Background: Rifampicin-resistant tuberculosis (RR-TB) is largely underdetected in Indonesia. Xpert MTB/RIF (Xpert) has recently been introduced, prioritizing patients at risk of RR-TB, followed by phenotypic drug-susceptibility (DST) if rifampicin resistance is detected.

Objective: This study investigated Xpert-based management of presumptive RR-TB cases under routine practice in West Java, Indonesia.

Methods: We examined all records of patients tested with Xpert in the referral hospital for West Java in 2015-2016. We measured loss across a limited cascade of care, time to Xpert diagnosis and the commencement of initial second-line treatment, and identified factors associated with diagnostic and treatment delay. Additionally, we analyzed the appropriateness of treatment according to DST results.

Results: Of 3415 patients with presumptive RR-TB, 3215 (94%) were tested by Xpert, of whom 339 (10.5%) were diagnosed as RR-TB. 288 (85%) of 339 RR-TB patients started initial second-line TB treatment, with 48 (14%) patients being lost between diagnosis and pre-treatment assessment. Second-line treatment was commenced at a median of 41 days (IQR 29-70) after RR-TB diagnosis. Delays in both diagnosis and treatment initiation were observed in 104 (52%) of 201 RR-TB patients with identifiable referral date. Rural residence was associated with delay to diagnosis (adjusted OR 2.7; 95%CI 1.5-5.2) and treatment initiation (adjusted OR 2.0; 1.2-3.4). Of 162 patients with available DST result, 107 (66%) had multidrug-resistant tuberculosis (MDR-TB) and 32 (20%) had either pre-extensively drug resistant (pre-XDR) or extensively drug resistant tuberculosis (XDR-TB). We estimated that with the current algorithm 41% of pre-XDR or XDR-TB patients are diagnosed, and 33% of them started on an appropriate treatment regimen.

Conclusions: Many patients with Xpert-diagnosed RR-TB either do not start MDR-TB treatment or encountered diagnostic and treatment delays under programmatic conditions in Indonesia, and most pre-XDR and XDR-TB cases remain undiagnosed. Further expansion and ongoing quality improvement of RR-TB services are urgently needed.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1. Time to diagnosis and treatment…
Fig 1. Time to diagnosis and treatment of presumptive rifampicin-resistant TB using Xpert.
Time between microscopic TB diagnosis and patient presentation for Xpert examination (a), Xpert result (b), time between Xpert result and patients visit for pre-treatment assessment (c), initiation of second line treatment (d), total time between microscopic TB diagnosis and diagnosis of RR-TB (e), and total time between RR-TB diagnosis and start of second line treatment (f). Total time between microscopic TB diagnosis and start of MDR-TB treatment (g).
Fig 2. Flow chart of study participants.
Fig 2. Flow chart of study participants.
MDR-TB: Multidrug-resistant TB, PMDT: Programmatic Management of Drug-resistant TB, NTM: Non-tuberculous Mycobacteria, DST: phenotypic Drug Susceptibility Testing. *pre-XDR (n = 27) and XDR (n = 3). ** Appropriate treatment was defined as compatibility between DST result and the choice of drug-resistant treatment regimen. ***Patients with DST result not suggesting MDR continued their 2nd line treatment according to Indonesian PMDT guideline. aThe 200 patients were not tested due to possible reasons, which were: 1) patients didn’t present to the laboratory for Xpert testing; 2) patients weren’t able to expectorate sputum.
Fig 3. Cascade of care and time…
Fig 3. Cascade of care and time to diagnosis and treatment of Xpert rifampicin-resistant TB patients.
Values in the bars indicate number (percentages). *12 of 118 with a failed result were imputed as Xpert positive and assigned the censored time of 180 days. **Pre-treatment examination included blood & urine test, HIV test, chest X-ray, audiometry and psychiatric assessment. ***Data were only available for 201 patients. Median (IQR) times between: microscopic TB diagnosis and patient presentation for Xpert examination (a), Xpert examination and Xpert result (b), Xpert result and visit for pre-treatment assessment (c), pre-treatment assessment and initiation of second line treatment (d), microscopic TB diagnosis and diagnosis of RR-TB (e), Xpert result and initiation of second line treatment (f), microscopic TB diagnosis and initiation of second-line treatment (g).
Fig 4. Kaplan Meier curves for time…
Fig 4. Kaplan Meier curves for time between specific cascade of care steps.
These figures show Kaplan-Meier time-to-event graphs for specific cascade of care steps between registration and Xpert result (n = 351) (A), Xpert result and pre-treatment examination (n = 339) (B), and pre-treatment examination and MDR-TB treatment initiation (n = 291) (C).

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