Performance of Xpert MTB/RIF and sputum microscopy compared to sputum culture for diagnosis of tuberculosis in seven hospitals in Indonesia

Anis Karuniawati; Erlina Burhan; Eko Budi Koendhori; Desvita Sari; Budi Haryanto; Titik Nuryastuti; A A A Yuli Gayatri; Uleng Bahrun; R Lia Kusumawati; Retna Indah Sugiyono; Nugroho Harry Susanto; Aly Diana; Herman Kosasih; Adhella Menur Naysilla; Dewi Lokida; Aaron Neal; Sophia Siddiqui; Chuen-Yen Lau; Muhammad Karyana

doi:10.3389/fmed.2022.909198

Performance of Xpert MTB/RIF and sputum microscopy compared to sputum culture for diagnosis of tuberculosis in seven hospitals in Indonesia

Front Med (Lausanne). 2023 Jan 20:9:909198. doi: 10.3389/fmed.2022.909198. eCollection 2022.

Authors

Anis Karuniawati¹, Erlina Burhan², Eko Budi Koendhori³, Desvita Sari⁴, Budi Haryanto⁵, Titik Nuryastuti⁶, A A A Yuli Gayatri⁷, Uleng Bahrun⁸, R Lia Kusumawati⁹, Retna Indah Sugiyono¹⁰, Nugroho Harry Susanto¹⁰, Aly Diana^{10

11}, Herman Kosasih¹⁰, Adhella Menur Naysilla¹⁰, Dewi Lokida¹², Aaron Neal¹³, Sophia Siddiqui¹³, Chuen-Yen Lau¹⁴, Muhammad Karyana¹⁵

Affiliations

¹ Department of Microbiology, Faculty of Medicine, Universitas Indonesia, Dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia.
² Department of Pulmonary and Respiratory Medicine, Faculty of Medicine, Universitas Indonesia, Persahabatan Hospital, Jakarta, Indonesia.
³ Department of Medical Microbiology, Faculty of Medicine, Universitas Airlangga, Dr. Soetomo Hospital, Surabaya, Indonesia.
⁴ Department of Microbiology, Faculty of Medicine, Universitas Diponegoro, Dr. Kariadi Hospital, Semarang, Indonesia.
⁵ Microbiology Unit, Persahabatan Hospital, Jakarta, Indonesia.
⁶ Department of Microbiology, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia.
⁷ Department of Internal Medicine, Faculty of Medicine, Universitas Udayana, Prof. IGNG. Ngoerah General Hospital, Bali, Indonesia.
⁸ Department of Clinical Pathology, Faculty of Medicine, University of Hasanuddin, Dr. Wahidin Sudirohusodo Hospital, Makassar, Indonesia.
⁹ Department of Microbiology, Faculty of Medicine, Universitas Sumatera Utara, H. Adam Malik General Hospital, Medan, Indonesia.
¹⁰ Indonesia Research Partnership on Infectious Disease (INA-RESPOND), Jakarta, Indonesia.
¹¹ Department of Public Health, Faculty of Medicine, Universitas Padjadjaran, Sumedang, Indonesia.
¹² Department of Clinical Pathology, Tangerang District Hospital, Tangerang, Indonesia.
¹³ National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States.
¹⁴ HIV Dynamics and Replication Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States.
¹⁵ National Institute of Health Research and Development, Ministry of Health, Republic of Indonesia, Jakarta, Indonesia.

Abstract

Introduction: Tuberculosis (TB) is a major public health concern in Indonesia, where the incidence was 301 cases per 100,000 inhabitants in 2020 and the prevalence of multi-drug resistant (MDR) TB is increasing. Diagnostic testing approaches vary across Indonesia due to resource limitations. Acid-fast bacilli (AFB) smear is widely used, though Xpert MTB/RIF has been the preferred assay for detecting TB and rifampicin resistance since 2012 due to higher sensitivity and ability to rapidly identify rifampicin resistance. However, <1,000 Xpert instruments were available in Indonesia as of 2020 and the Xpert supply chain has suffered interruptions.

Methods: We compared the performance of Xpert MTB/RIF and AFB smear to facilitate optimization of TB case identification. We analyzed baseline data from a cohort study of adults with pulmonary TB conducted at seven hospitals across Indonesia. We evaluated sensitivity and specificity of AFB smear and Xpert MTB/RIF using Mycobacterium tuberculosis (Mtb) culture as the gold standard, factors associated with assay results, and consistency of Xpert MTB/RIF with drug susceptibility test (DST) in detecting rifampicin resistance.

Results: Sensitivity of AFB smear was significantly lower than Xpert MTB/RIF (86.2 vs. 97.4%, p-value <0.001), but specificity was significantly better (86.7 vs. 73.3%, p-value <0.001). Performance varied by hospital. Positivity rate for AFB smear and Mtb culture was higher in subjects with pulmonary cavities and in morning sputum samples. Consistency of Xpert MTB/RIF with DST was lower in those with rifampicin- sensitive TB by DST.

Discussion: Additional evaluation using sputa from primary and secondary Indonesian health centers will increase the generalizability of the assessment of AFB smear and Xpert MTB/RIF performance, and better inform health policy.

Clinical trial registration: [https://clinicaltrials.gov/], identifier [NCT027 58236].

Trial registration: ClinicalTrials.gov NCT00000027.

Keywords: DST; Xpert MTB/RIF; diagnosis; mycobacteria; rifampicin; sputum culture; sputum microscopy; tuberculosis.

Associated data

ClinicalTrials.gov/NCT00000027

Grants and funding

This work has been funded in whole or in part with MOH Indonesia; the Intramural Research Program, National Institutes of Health; National Cancer Institute, Center for Cancer Research, National Institutes of Health; and federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, under contract No. HHSN261201500003I.