Effects of Introducing Xpert MTB/RIF on Diagnosis and Treatment of Drug-Resistant Tuberculosis Patients in Indonesia: A Pre-Post Intervention Study

<div><p>Background</p><p>In March 2012, the Xpert MTB/RIF assay (Xpert) was introduced in three provincial public hospitals in Indonesia as a novel diagnostic to detect tuberculosis and rifampicin resistance among high risk individuals.</p><p>Objective</p><p>This study assessed the effects of using Xpert in place of conventional solid and liquid culture and drug-susceptibility testing on case detection rates, treatment initiation rates, and health system delays among drug-resistant tuberculosis (TB) patients.</p><p>Methods</p><p>Cohort data on registration, test results and treatment initiation were collected from routine presumptive patient registers one year before and one year after Xpert was introduced. Proportions of case detection and treatment initiation were compared using the Pearson Chi square test and median time delays using the Mood’s Median test.</p><p>Results</p><p>A total of 975 individuals at risk of drug-resistant TB were registered in the pre-intervention year and 1,442 in the post-intervention year. After Xpert introduction, TB positivity rate increased by 15%, while rifampicin resistance rate reduced by 23% among TB positive cases and by 9% among all tested. Second-line TB treatment initiation rate among rifampicin resistant patients increased by 19%. Time from client registration to diagnosis was reduced by 74 days to a median of a single day (IQR 0–4) and time from diagnosis to treatment start was reduced by 27 days to a median of 15 days (IQR 7–51). All findings were significant with p<0.001.</p><p>Conclusion</p><p>Compared to solid and liquid culture and drug-susceptibility testing, Xpert detected more TB and less rifampicin resistance, increased second-line treatment initiation rates and shortened time to diagnosis and treatment. This test holds promise to improve rapid case finding and management of drug-resistant TB patients in Indonesia.</p></div

Culture and drug-susceptibility testing results following Xpert MTB/RIF testing within the same individuals at risk of multidrug-resistant TB in three provincial hospitals in Java, Indonesia.

<p><i>Abbreviations</i>: <i>DST</i>, <i>drug-susceptibility testing; TB</i>, <i>tuberculosis; RIF</i>, <i>rifampicin; NTM</i>, <i>non-tuberculosis mycobacteria</i>.</p><p>Culture and drug-susceptibility testing results following Xpert MTB/RIF testing within the same individuals at risk of multidrug-resistant TB in three provincial hospitals in Java, Indonesia.</p

Diagnosis and treatment of individuals at risk of multidrug-resistant pulmonary TB at three provincial hospitals in Java, Indonesia.

<p>The flowchart shows the number of tested, detected and treated individuals in two cohort years. From March 2011 to Feb 2012 (Year 1), individuals were tested with conventional culture and drug-susceptibility testing. From March 2012 to February 2013 (Year 2), individuals were tested with culture and drug-susceptibility testing or Xpert MTB/RIF. <i>Abbreviations</i>: <i>TB</i>, <i>tuberculosis; DST</i>, <i>drug-susceptibility testing; RIF</i>, <i>rifampicin; MDR-TB</i>, <i>multidrug-resistant TB; N</i>, <i>number</i>.</p

Time to diagnosis and treatment of rifampicin-resistant TB patients in three provincial hospitals in Java, Indonesia.

<p>These figures show Kaplan Meier time-to-event graphs of health system delays (a), diagnostic delays (b) and treatment delays (c) for rifampicin resistance TB patients detected with culture drug-susceptibility testing from March 2011 to February 2012 and Xpert MTB/RIF from March 2012 to February 2013. <i>Abbreviations</i>: <i>TB</i>, <i>tuberculosis; DST</i>, <i>drug-susceptibility testing; RIF</i>, <i>rifampicin</i>.</p

Follow-on culture results among individuals from various risk groups that tested Xpert MTB/RIF TB positive in three provincial hospitals in Java, Indonesia.

<p><i>Abbreviations</i>: <i>Xpert</i>, <i>Xpert MTB/RIF assay; TB</i>, <i>tuberculosis; NTM</i>, <i>non-tuberculosis mycobacteria; HIV</i>, <i>human immunodeficiency virus</i>.</p><p>Follow-on culture results among individuals from various risk groups that tested Xpert MTB/RIF TB positive in three provincial hospitals in Java, Indonesia.</p

Bivariate and multivariate logistic regression analyses of factors associated with the anti-<i>H</i>. <i>capsulatum</i> IgG antibody positive result.

Bivariate and multivariate logistic regression analyses of factors associated with the anti-H. capsulatum IgG antibody positive result.</p

The distribution of anti-<i>H</i>. <i>capsulatum</i> IgG antibody-positive serum specimens from pulmonary TB patients at seven TB referral hospitals in Indonesia.

The original map was obtained from an openly available source https://www.naturalearthdata.com/. The figure was developed with QGIS 3.32.1 and https://biorender.com/.</p

Anonymized dataset of 306 study participants.

BackgroundHistoplasma capsulatum exposure is rarely suspected in Indonesia. Pulmonary histoplasmosis can occur simultaneously with pulmonary tuberculosis (TB) or as an alternative diagnosis in clinically-diagnosed TB patients with no microbiological evidence of TB. This study aimed to determine the seroprevalence of anti-H. capsulatum IgG antibody among pulmonary TB patients.MethodologyThis was a sub-study of 306 participants from a prospective cohort pulmonary TB study conducted at seven TB referral hospitals in Indonesia. The study population was presumptive pulmonary TB adult patients who underwent microbiological TB examinations and were categorized as drug-sensitive (DS), drug-resistant (DR), and clinically-diagnosed TB. Anti-H. capsulatum IgG antibody levels at baseline were measured using MVista Histoplasma Ab enzyme immunoassays. Data were summarized using descriptive statistics. Bivariate and multivariate logistic regression analysis were performed to assess factors associated with anti-H. capsulatum IgG antibody positive result.Results12.7% (39/306) of pulmonary TB patients were positive for anti-H. capsulatum IgG antibodies (DR-TB patients (15.9%, 18/114), DS-TB (13.0%, 15/115), and clinically-diagnosed TB (7.8%, 6/77)). The median unit value of anti-H. capsulatum IgG antibody for all positive samples was 15.7 (IQR 10.2–28.9) EU. This median unit value was higher in clinically-diagnosed TB patients compared to DS-TB or DR-TB patients (38.1 (IQR 25.6–46.6) EU, 19.7 (IQR 12.3–28.9) EU, and 10.9 (IQR 9.2–15.4), respectively). There were 10 patients (3.3%) with anti-H. capsulatum IgG antibody levels above 30 EU. Factors associated with the anti-H. capsulatum IgG antibody positive result were malignancies (OR 4.88, 95% CI 1.09–21.69, p = 0.037) and cavitary lesions (OR 2.27, 95% CI 1.09–4.70, p = 0.028).ConclusionsOur results provide evidence of exposure to H. capsulatum among pulmonary TB patients in Indonesia. Further studies are needed to provide a comprehensive picture of this fungal disease in other populations and regions to enhance awareness among clinicians and public health officials.</div

Characteristics of participants based on anti-<i>H</i>. <i>capsulatum</i> IgG antibody results.

Characteristics of participants based on anti-H. capsulatum IgG antibody results.</p

Characteristics of the anti-<i>H</i>. <i>capsulatum</i> IgG antibody-positive pulmonary TB patients.

Characteristics of the anti-H. capsulatum IgG antibody-positive pulmonary TB patients.</p