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

IntroductionTuberculosis (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.MethodsWe 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.ResultsSensitivity 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.DiscussionAdditional 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]

Building capacity for advances in tuberculosis research; proceedings of the third RePORT international meeting

RePORT International is a global network of research sites in India, Brazil, Indonesia, South Africa, China, and the Philippines dedicated to collaborative tuberculosis research in the context of HIV. A standardized research protocol (the Common Protocol) guides the enrollment of participants with active pulmonary tuberculosis and contacts into observational cohorts. The establishment of harmonized clinical data and bio-repositories will allow cutting-edge, large-scale advances in the understanding of tuberculosis, including identification of novel biomarkers for progression to active tuberculosis and relapse after treatment. The RePORT International infrastructure aims to support research capacity development through enabling globally-diverse collaborations. To that end, representatives from the RePORT International network sites, funding agencies, and other stakeholders gathered together in Brazil in September 2017 to present updates on relevant research findings and discuss ideas for collaboration. Presenters emphasized research involving biomarker identification for incipient tuberculosis, host immunity and pharmacogenomics, co-morbidities such as HIV and type 2 diabetes mellitus, and tuberculosis transmission in vulnerable and high-risk populations. Currently, 962 active TB participants and 670 household contacts have contributed blood, sputum, urine and microbes to in-country biorepositories. Cross-consortium collaborations have begun sharing data and specimens to analyze molecular and cytokine predictive patterns

The characteristics of bacteremia among patients with acute febrile illness requiring hospitalization in Indonesia

Blood culturing remains the "gold standard"for bloodstream infection (BSI) diagnosis, but the method is inaccessible to many developing countries due to high costs and insufficient resources. To better understand the utility of blood cultures among patients in Indonesia, a country where blood cultures are not routinely performed, we evaluated data from a previous cohort study that included blood cultures for all participants. An acute febrile illness study was conducted from July 2013 to June 2016 at eight major hospitals in seven provincial capitals in Indonesia. All participants presented with a fever, and two-sided aerobic blood cultures were performed within 48 hours of hospital admission. Positive cultures were further assessed for antimicrobial resistance (AMR) patterns. Specimens from participants with negative culture results were screened by advanced molecular and serological methods for evidence of causal pathogens. Blood cultures were performed for 1,459 of 1,464 participants, and the 70.6 (1,030) participants that were negative by dengue NS1 antigen test were included in further analysis. Bacteremia was observed in 8.9 (92) participants, with the most frequent pathogens being Salmonella enterica serovar Typhi (41) and Paratyphi A (10), Escherichia coli (14), and Staphylococcus aureus (10). Two S. Paratyphi A cases had evidence of AMR, and several E. coli cases were multidrug resistant (42.9, 6/14) or monoresistant (14.3, 2/14). Culture contamination was observed in 3.6 (37) cases. Molecular and serological assays identified etiological agents in participants having negative cultures, with 23.1 to 90 of cases being missed by blood cultures. Blood cultures are a valuable diagnostic tool for hospitalized patients presenting with fever. In Indonesia, pre-screening patients for the most common viral infections, such as dengue, influenza, and chikungunya viruses, would maximize the benefit to the patient while also conserving resources. Blood cultures should also be supplemented with advanced laboratory tests when available. © 2022 This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication

The seroprevalence of anti-Histoplasma capsulatum IgG antibody among pulmonary tuberculosis patients in seven referral tuberculosis hospitals in Indonesia

BACKGROUND: Histoplasma 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.METHODOLOGY: This 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.RESULTS: 12.7% (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).CONCLUSIONS: Our 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.</p

The seroprevalence of anti-Histoplasma capsulatum IgG antibody among pulmonary tuberculosis patients in seven referral tuberculosis hospitals in Indonesia.

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

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

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

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

Anti-<i>H</i>. <i>capsulatum</i> IgG antibody results among DS-TB, DR-TB, and clinically-diagnosed pulmonary TB patients.

Anti-H. capsulatum IgG antibody results among DS-TB, DR-TB, and clinically-diagnosed pulmonary TB patients.</p