Comparative Yield of Different Diagnostic Tests for Tuberculosis among People Living with HIV in Western Kenya

Cavanaugh, Joseph S.; Modi, Surbhi; Musau, Susan; McCarthy, Kimberly D.; Alexander, Heather; Burmen, Barbara; Heilig, Charles M.; Shiraishi, Ray W.; Cain, Kevin P.

doi:10.1371/journal.pone.0152364

Cited by 12 publications

(16 citation statements)

References 27 publications

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“…NanoDisk-MS demonstrated similar sensitivity for both PTB cases (87.5%) and clinically challenging EPTB cases (85.7%) in the HIV-positive study population, where it equaled or significantly outperformed Xpert MTB/RIF in terms of sensitivity for detecting EPTB using highly invasive lymph node (84%), pleural fluid (17%), and cerebrospinal fluid (56%) samples in a metaanalysis (34), and significantly outperformed AFB smear (31%), mycobacteria growth indicator tube culture (69%), and Xpert MTB/RIF (66%) in another study (35). Moreover, our results were achieved irrespective of Mtb culture status, and although greater sensitivity was achieved in culture-positive samples, results from culture-negative samples markedly outperformed the WHO-defined 66% optimal sensitivity for new high-priority nonsputum diagnostic tests (13).…”

Section: Discussionmentioning

confidence: 98%

Quantification of circulating Mycobacterium tuberculosis antigen peptides allows rapid diagnosis of active disease and treatment monitoring

Liu

Zhao

Fan

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Tuberculosis (TB) is a major global health threat, resulting in an urgent unmet need for a rapid, non-sputum-based quantitative test to detect active Mycobacterium tuberculosis (Mtb) infections in clinically diverse populations and quickly assess Mtb treatment responses for emerging drug-resistant strains. We have identified Mtb-specific peptide fragments and developed a method to rapidly quantify their serum concentrations, using antibody-labeled and energy-focusing porous discoidal silicon nanoparticles (nanodisks) and high-throughput mass spectrometry (MS) to enhance sensitivity and specificity. NanoDisk-MS diagnosed active Mtb cases with high sensitivity and specificity in a case-control study with cohorts reflecting the complexity of clinical practice. Similar robust sensitivities were obtained for cases of culture-positive pulmonary TB (PTB; 91.3%) and extrapulmonary TB (EPTB; 92.3%), and the sensitivities obtained for culture-negative PTB (82.4%) and EPTB (75.0%) in HIV-positive patients significantly outperformed those reported for other available assays. NanoDisk-MS also exhibited high specificity (87.1-100%) in both healthy and high-risk groups. Absolute quantification of serum Mtb antigen concentration was informative in assessing responses to antimycobacterial treatment. Thus, a NanoDisk-MS assay approach could significantly improve the diagnosis and management of active TB cases, and perhaps other infectious diseases as well.D espite international efforts and initiatives, tuberculosis (TB) remains a major public health concern worldwide, associated with high morbidity and mortality (1, 2). Detecting active TB cases and monitoring their responses to therapy are fraught with challenges, relying predominantly on microbiologic techniques that use sputum samples, including acid-fast Bacillus (AFB) smear microscopy-widely used as an initial test for TB diagnosis (3, 4)-and Mycobacterium tuberculosis (Mtb) culture, both of which have only moderate sensitivity and specificity and a long turnaround time (5, 6). Moreover, sputum samples are difficult to obtain after symptom improvement, and often are not diagnostically useful for extrapulmonary TB (EPTB) cases. The PCR-based Xpert MTB/RIF sputum assay was introduced to improve the speed and specificity of TB diagnosis, but this assay has poor sensitivity under low bacterial loads and cannot distinguish live and nonviable Mtb contributions (7,8). A recent World Health Organization (WHO) policy update acknowledged the low quality of evidence supporting the use of Xpert MTB/RIF to diagnose EPTB (9). Diagnostic challenges can be further magnified in patients coinfected with HIV and TB (10). In addition, none of these techniques provides quantitative results that can be used to monitor treatment effects (11,12).Consequently, there is an urgent need, highlighted as a high priority in a recent WHO consensus report (13), for the development of rapid, quantitative, non-sputum-based biomarker tests that do not require bacterial isolation to detect active TB (13). Non-s...

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Section: Discussionmentioning

confidence: 98%

Quantification of circulating Mycobacterium tuberculosis antigen peptides allows rapid diagnosis of active disease and treatment monitoring

Liu

Zhao

Fan

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…Detailed study procedures have been described elsewhere [14]. Briefly, the sample frame included all public HIV care and treatment facilities (including associated PMTCT services) with at least 200 enrolled patients in the Siaya, Bondo, and Kisumu East Districts of the Nyanza Province.…”

Section: Methodsmentioning

confidence: 99%

Performance of Clinical Screening Algorithms for Tuberculosis Intensified Case Finding among People Living with HIV in Western Kenya

et al. 2016

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ObjectiveTo assess the performance of symptom-based screening for tuberculosis (TB), alone and with chest radiography among people living with HIV (PLHIV), including pregnant women, in Western Kenya.DesignProspective cohort studyMethodsPLHIV from 15 randomly-selected HIV clinics were screened with three clinical algorithms [World Health Organization (WHO), Ministry of Health (MOH), and “Improving Diagnosis of TB in HIV-infected persons” (ID-TB/HIV) study], underwent chest radiography (unless pregnant), and provided two or more sputum specimens for smear microscopy, liquid culture, and Xpert MTB/RIF. Performance of clinical screening was compared to laboratory results, controlling for the complex design of the survey.ResultsOverall, 738 (85.6%) of 862 PLHIV enrolled were included in the analysis. Estimated TB prevalence was 11.2% (95% CI, 9.9–12.7). Sensitivity of the three screening algorithms was similar [WHO, 74.1% (95% CI, 64.1–82.2); MOH, 77.5% (95% CI, 68.6–84.5); and ID-TB/HIV, 72.5% (95% CI, 60.9–81.7)]. Sensitivity of the WHO algorithm was significantly lower among HIV-infected pregnant women [28.2% (95% CI, 14.9–46.7)] compared to non-pregnant women [78.3% (95% CI, 67.3–86.4)] and men [77.2% (95% CI, 68.3–84.2)]. Chest radiography increased WHO algorithm sensitivity and negative predictive value to 90.9% (95% CI, 86.4–93.9) and 96.1% (95% CI, 94.4–97.3), respectively, among asymptomatic men and non-pregnant women.ConclusionsClinical screening missed approximately 25% of laboratory-confirmed TB cases among all PLHIV and more than 70% among HIV-infected pregnant women. National HIV programs should evaluate the feasibility of laboratory-based screening for TB, such as a single Xpert MTB/RIF test for all PLHIV, especially pregnant women, at enrollment in HIV services.

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“…These patients were more likely to have active TB infections, and so these results may differ from those obtained in routine clinical settings. Other limitations include the low HIV prevalence in the study population, as the assessments of false-negative rates for the different methods may not be representative of populations with high HIV rates [ 21 ], and the use of Xpert MTB/RIF on concentrated samples in this study, which has been previously associated with slightly lower sensitivity on smear-negative samples [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

Feasibility of the TBDx automated digital microscopy system for the diagnosis of pulmonary tuberculosis

et al. 2017

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BackgroundImproved and affordable diagnostic or triage tests are urgently needed at the microscopy centre level. Automated digital microscopy has the potential to overcome issues related to conventional microscopy, including training time requirement and inconsistencies in results interpretation.MethodsFor this blinded prospective study, sputum samples were collected from adults with presumptive pulmonary tuberculosis in Lima, Peru and Ho Chi Minh City, Vietnam. TBDx performance was evaluated as a stand-alone and as a triage test against conventional microscopy and Xpert, with culture as the reference standard. Xpert was used to confirm positive cases.FindingsA total of 613 subjects were enrolled between October 2014 and March 2015, with 539 included in the final analysis. The sensitivity of TBDx was 62·2% (95% CI 56·6–67·4) and specificity was 90·7% (95% CI 85·9–94·2) compared to culture. The algorithm assessing TBDx as a triage test achieved a specificity of 100% while maintaining sensitivity.InterpretationWhile the diagnostic performance of TBDx did not reach the levels obtained by experienced microscopists in reference laboratories, it is conceivable that it would exceed the performance of less experienced microscopists. In the absence of highly sensitive and specific molecular tests at the microscopy centre level, TBDx in a triage-testing algorithm would optimize specificity and limit overall cost without compromising the number of patients receiving up-front drug susceptibility testing for rifampicin. However, the algorithm would miss over one third of patients compared to Xpert alone.

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Comparative Yield of Different Diagnostic Tests for Tuberculosis among People Living with HIV in Western Kenya

Cited by 12 publications

References 27 publications

Quantification of circulating Mycobacterium tuberculosis antigen peptides allows rapid diagnosis of active disease and treatment monitoring

Quantification of circulating Mycobacterium tuberculosis antigen peptides allows rapid diagnosis of active disease and treatment monitoring

Performance of Clinical Screening Algorithms for Tuberculosis Intensified Case Finding among People Living with HIV in Western Kenya

Feasibility of the TBDx automated digital microscopy system for the diagnosis of pulmonary tuberculosis

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