Towards a point-of-care test for active tuberculosis: obstacles and opportunities

McNerney, Ruth; Daley, Peter

doi:10.1038/nrmicro2521

Cited by 181 publications

(182 citation statements)

References 73 publications

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“…Tuberculosis (TB), an important infectious disease caused by the bacterium M. tuberculosis, is responsible for considerable morbidity and mortality worldwide (61). Currently available tests for the rapid detection of M. tuberculosis are inadequate, and there is an urgent need for improvements in TB diagnosis and for new methods to determine the efficacy of treatment, particularly in developing countries (62)(63)(64). The strategy of developing tests based on TB-associated VOC biomarkers offers substantial advantages over other approaches in that such tests are simple, noninvasive, and suitable for adaptation in the form of POC testing devices (e.g., e-noses).…”

Section: Respiratory Infectionsmentioning

confidence: 99%

Clinical Application of Volatile Organic Compound Analysis for Detecting Infectious Diseases

2013

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SUMMARY This review article introduces the significance of testing of volatile organic compounds (VOCs) in clinical samples and summarizes important features of some of the technologies. Compared to other human diseases such as cancer, studies on VOC analysis in cases of infectious diseases are limited. Here, we have described results of studies which have used some of the appropriate technologies to evaluate VOC biomarkers and biomarker profiles associated with infections. The publications reviewed include important infections of the respiratory tract, gastrointestinal tract, urinary tract, and nasal cavity. The results highlight the use of VOC biomarker profiles resulting from certain infectious diseases in discriminating between infected and healthy subjects. Infection-related VOC profiles measured in exhaled breath as well as from headspaces of feces or urine samples are a source of information with respect to disease detection. The volatiles emitted in clinical matrices may on the one hand represent metabolites of the infecting pathogen or on the other hand reflect pathogen-induced host responses or, indeed, a combination of both. Because exhaled-breath samples are easy to collect and online instruments are commercially available, VOC analysis in exhaled breath appears to be a promising tool for noninvasive detection and monitoring of infectious diseases.

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Section: Respiratory Infectionsmentioning

confidence: 99%

Clinical Application of Volatile Organic Compound Analysis for Detecting Infectious Diseases

2013

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“…However, the assay required long sample preparation time. Until recently, according to McNerney and Daley [23], there were no tests that can compare to sputum smear microscopy and, in addition to long analysis time of each smear, such tests required a microscopy abilities and a skilled technician. However, many advances in analytical techniques were made and the Cepheid GeneXpert MTB test now allows detection of M.tuberculosis directly from sputum sample within 3-4 hours.…”

Section: Introductionmentioning

confidence: 99%

“…In addition, the ag85 complex can be detected in HIV-positive patients with high specificity [30][31][32]. The detection of bacterial and viral proteins is more reliable compared to the detection of antibodies and can be directly correlated to the number of reproducing bacteria and viruses [23]. For example, a single HIV virus has 2,000 copies of p24 protein (or, 1 pg of p24 corresponds to 10,000 HIV virus particles) [33].…”

Section: Introductionmentioning

confidence: 99%

Centrifugal Microfluidic Platform for Rapid, Multiplexed Detection of TB and HIV Biomarkers in Whole Blood Samples

Litvinov¹,

St²,

Gj³

et al. 2017

J Bioengineer & Biomedical Sci

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Infection with Mycobacterium Tuberculosis represents a significant threat to people with immune disorders, such as HIV-positive individuals, and can result in significant health complications or death if not diagnosed and treated early. We present a centrifugal microfluidic platform for multiplexed detection of tuberculosis and HIV biomarkers in human whole blood with minimal sample preparation and a sample-to-answer time of 30 minutes. This multiplexed assay was developed for the detection of two M.tuberculosis secreted proteins, whose secretion represents an active and ongoing infection, as well as detection of HIV p24 protein and human anti-p24 antibodies. The limit of detection for this multiplex assay is in the pg/mL range for both HIV and M.tuberculosis proteins, making this assay potentially useful in the clinical diagnosis of both HIV and Tuberculosis proteins indicative of active infection. Antigen detection for the HIV assay sensitivity was 89%, the specificity 85%. Serological detection had 100% sensitivity and specificity for the limited sample pool. The centrifugal microfluidic platform presented here offers the potential for a portable, fast and inexpensive multiplexed diagnostic device that can be used in resource-limited settings for diagnosis of TB and HIV.

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“…In one common scheme of this technique, the antigen is initially introduced onto the device by adding a sample from a clinical specimen, such as urine or serum. Free antigen, if present, binds to an antibody/microsphere (bead) complex, providing a visually detectable color change (44). Dipsticks require little and sometimes no sample processing.…”

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confidence: 99%

Systematic Review and Meta-Analysis of Antigen Detection Tests for the Diagnosis of Tuberculosis

Flores

Steingart

Dendukuri

et al. 2011

Clin Vaccine Immunol

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Tests that detect Mycobacterium tuberculosis antigens in clinical specimens could provide rapid direct evidence of active disease. We performed a systematic review to assess the diagnostic accuracy of antigen detection tests for active tuberculosis (TB) according to standard methods and summarized test performance using bivariate random effects meta-analysis. Overall, study quality was a concern. For pulmonary TB (47 studies, 5,036 participants), sensitivity estimates ranged from 2% to 100% and specificity from 33% to 100%. Lipoarabinomannan (LAM) was the antigen most frequently targeted (23 studies, 49%). The pooled sensitivity of urine LAM was higher in HIV-infected than HIV-uninfected individuals (47%; 95% confidence interval [CI], 26 to 68% versus 14%; 95% CI, 4 to 38%); pooled specificity estimates were similar: 96%; 95% CI, 81 to 100% and 97%; 95% CI, 86 to 100%, respectively. For extrapulmonary TB (21 studies, 1,616 participants), sensitivity estimates ranged from 0% to 100% and specificity estimates from 62% to 100%. Five studies targeting LAM, ESAT-6, Ag85 complex, and the 65-kDa antigen in cerebrospinal fluid, when pooled, yielded the highest sensitivity (87%; 95% CI, 61 to 98%), but low specificity (84%; 95% CI, 60 to 95%). Because of the limited number of studies targeting any specific antigen other than LAM, we could not draw firm conclusions about the overall clinical usefulness of these tests. Further studies are warranted to determine the value of LAM detection for TB meningitis in high-HIV-prevalence settings. Considering that antigen detection tests could be translated into rapid point-of-care tests, research to improve their performance is urgently needed.The World Health Organization (WHO) estimates that in 2009, 9.4 million new cases of tuberculosis (TB) occurred and 1.7 million people died of the disease (89). The vast majority of these patients live in low-and middle-income countries (LMIC) where TB diagnosis depends primarily on smear microscopy. Microscopy has low sensitivity and does not detect smear-negative TB (77), which may account for 24% to 61% of all pulmonary cases in HIV-infected individuals (27). Improved diagnostic tests, such as mycobacterial culture and nucleic acid amplification (NAA) tests, are available in highincome countries but are often too expensive and complex for routine use by TB control programs in resource-constrained settings in which TB is endemic. Lack of access to diagnostic services in resource-limited settings presents an additional barrier to using these tests. The Xpert MTB/RIF (Cepheid, Inc., Sunnyvale, CA), recently endorsed by the WHO, is rapid and highly sensitive for detection of TB and drug resistance; however, this new technology is costly, preventing its use in many areas where the epidemic is most severe (10). Accurate, rapid, inexpensive, and simple diagnostic tests are urgently needed for TB care and control.There have been considerable efforts over the past 50 years to devise a rapid TB test based on antibody detection. However, substantial ...

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Towards a point-of-care test for active tuberculosis: obstacles and opportunities

Cited by 181 publications

References 73 publications

Clinical Application of Volatile Organic Compound Analysis for Detecting Infectious Diseases

Clinical Application of Volatile Organic Compound Analysis for Detecting Infectious Diseases

Centrifugal Microfluidic Platform for Rapid, Multiplexed Detection of TB and HIV Biomarkers in Whole Blood Samples

Systematic Review and Meta-Analysis of Antigen Detection Tests for the Diagnosis of Tuberculosis

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