Clinical utility of C-reactive protein-based triage for presumptive pulmonary tuberculosis in South African adults

Calderwood, Claire; Reeve, Byron W P; Mann, Tiffeney; Palmer, Zaida; Nyawo, Georgina; Mishra, Hridesh; Abubakar, Ibrahim; Noursadeghi, Mahdad; Theron, Grant; Rk, Gupta

doi:10.1016/j.jinf.2022.10.041

Cited by 20 publications

(21 citation statements)

References 20 publications

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“…9 However, our results are similar to a more recent study with similar demographics for PWH as our study (high median CD4 count and high proportion of PWH on ART) which also found no difference in CRP sensitivity by HIV status. 10 Combined, these studies suggest that HIV infection may have less of an impact on CRP performance when there are less differences in TB risk between people with and without HIV ( i.e., due to less immunosuppression among PWH) and may explain why HIV infection with CD4 count >200 was not associated with CRP accuracy in our ROC regression. As median pre-ART CD4 count and ART coverage increases, fewer settings are likely to report differences in CRP sensitivity by HIV status but differences in specificity may persist due to the increased susceptibility to other non-TB diseases associated with HIV infection ( e.g., bacterial pneumonia), regardless of CD4 count.…”

Section: Discussionmentioning

confidence: 75%

“…To-date, prior studies evaluating CRP TB triage testing have been limited to case-control studies and one prospective study. 9,10 We found that while CRP did not meet the minimum WHO targets for sensitivity or specificity overall, CRP demonstrated substantial geographic variability such that sensitivity exceeded 91% in reference to MRS in Africa but was much lower (64-82%) in Asia, where specificity was highest. These geographic differences in CRP sensitivity, which have also been reported by prior studies, correlated with observed geographic differences in mycobacterial load.…”

Section: Discussionmentioning

confidence: 85%

“…8 Similar results were found in a multi-country study analyzing CRP from banked plasma, but a more recent study from South Africa reported similar accuracy by HIV status. 9,10…”

Section: Introductionmentioning

confidence: 99%

“…8 Similar results were found in a multi-country study analyzing CRP from banked plasma, but a more recent study from South Africa reported similar accuracy by HIV status. 9,10 To better characterize the utility of CRP as a TB triage test, we performed a prospective, multi-country study among outpatient adults with presumptive TB in five high TB burden settings in Uganda, South Africa, the Philippines, Vietnam, and India.…”

Section: Introductionmentioning

confidence: 99%

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C-reactive protein-based tuberculosis triage testing: a multi-country diagnostic accuracy study

Derendinger,

Mochizuki,

Marcelo

et al. 2024

Preprint

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Rationale: C-reactive protein (CRP)-based tuberculosis (TB) screening is recommended for people with HIV (PWH). However, its performance among people without HIV and in diverse settings is unknown. Objectives: In a multi-country study, we aimed to determine whether CRP meets the minimum accuracy targets (sensitivity ≥90%, specificity ≥70%) for an effective TB triage test. Methods/Measurements: Consecutive outpatient adults with cough ≥2 weeks from five TB endemic countries in Africa and Asia had baseline blood collected for point-of-care CRP testing and HIV and diabetes screening. Sputum samples were collected for Xpert MTB/RIF Ultra (Xpert) testing and culture. CRP sensitivity and specificity (5 mg/L cut-point) was determined in reference to sputum test results and compared by country, sex, and HIV and diabetes status. Variables affecting CRP performance were identified using a multivariate receiver operating characteristic (ROC) regression model. Results: Among 2904 participants, of whom 613 (21%) had microbiologically-confirmed TB, CRP sensitivity was 84% (95% CI: 81-87%) and specificity was 61% (95% CI: 59-63%). CRP accuracy varied geographically, with higher sensitivity in African countries (≥91%) than Asian countries (64-82%). Sensitivity was higher among men than women (87% vs. 79%, difference +8%, 95% CI: 1-15%) and specificity was higher among people without HIV than PWH (64% vs. 45%, difference +19%, 95% CI: 13-25%). ROC regression identified country and measures of TB disease severity as predictors of CRP performance. Conclusions: Overall, CRP did not achieve the minimum accuracy targets and its performance varied by setting and in some sub-groups, likely reflecting population differences in mycobacterial load.

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Section: Discussionmentioning

confidence: 75%

Section: Discussionmentioning

confidence: 85%

“…8 Similar results were found in a multi-country study analyzing CRP from banked plasma, but a more recent study from South Africa reported similar accuracy by HIV status. 9,10…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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C-reactive protein-based tuberculosis triage testing: a multi-country diagnostic accuracy study

Derendinger,

Mochizuki,

Marcelo

et al. 2024

Preprint

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“…Passive case finding involves patients recognising and seeking care for their symptoms (often defined in research studies as a positive W4SS). After discussion with policy makers and domain experts, we supplemented the active case-finding IPD identified through systematic review with two further studies (three cohorts) from passive case-finding settings [ 15 , 25 ], comprising outpatient PLHIV receiving and not receiving ART. The purpose of this protocol change was to assess the effect of case-finding status on model performance, because case-finding status was deemed to be of significant interest to policy makers.…”

Section: Methodsmentioning

confidence: 99%

Clinical utility of WHO-recommended screening tools and development and validation of novel clinical prediction models for pulmonary tuberculosis screening among outpatients living with HIV: an individual participant data meta-analysis

Dhana¹,

Rk²,

Hamada³

et al. 2023

Eur Respir Rev

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Background:The World Health Organization (WHO) recommends that outpatient people living with HIV (PLHIV) undergo tuberculosis screening with the WHO four-symptom screen (W4SS) or C-reactive protein (CRP) (5 mg·L−1cut-off) followed by confirmatory testing if screen positive. We conducted an individual participant data meta-analysis to determine the performance of WHO-recommended screening tools and two newly developed clinical prediction models (CPMs).Methods:Following a systematic review, we identified studies that recruited adult outpatient PLHIV irrespective of tuberculosis signs and symptoms or with a positive W4SS, evaluated CRP and collected sputum for culture. We used logistic regression to develop an extended CPM (which included CRP and other predictors) and a CRP-only CPM. We used internal–external cross-validation to evaluate performance.Results:We pooled data from eight cohorts (n=4315 participants). The extended CPM had excellent discrimination (C-statistic 0.81); the CRP-only CPM had similar discrimination. The C-statistics for WHO-recommended tools were lower. Both CPMs had equivalent or higher net benefit compared with the WHO-recommended tools. Compared with both CPMs, CRP (5 mg·L−1cut-off) had equivalent net benefit across a clinically useful range of threshold probabilities, while the W4SS had a lower net benefit. The W4SS would capture 91% of tuberculosis cases and require confirmatory testing for 78% of participants. CRP (5 mg·L−1cut-off), the extended CPM (4.2% threshold) and the CRP-only CPM (3.6% threshold) would capture similar percentages of cases but reduce confirmatory tests required by 24, 27 and 36%, respectively.Conclusions:CRP sets the standard for tuberculosis screening among outpatient PLHIV. The choice between using CRP at 5 mg·L−1cut-off or in a CPM depends on available resources.

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Application of targeted next generation sequencing technology in the diagnosis of Mycobacterium Tuberculosis and first line drugs resistance directly from cell-free DNA of bronchoalveolar lavage fluid

Liang²,

Xiao

et al. 2023

Journal of Infection

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Clinical utility of C-reactive protein-based triage for presumptive pulmonary tuberculosis in South African adults

Cited by 20 publications

References 20 publications

C-reactive protein-based tuberculosis triage testing: a multi-country diagnostic accuracy study

C-reactive protein-based tuberculosis triage testing: a multi-country diagnostic accuracy study

Clinical utility of WHO-recommended screening tools and development and validation of novel clinical prediction models for pulmonary tuberculosis screening among outpatients living with HIV: an individual participant data meta-analysis

Application of targeted next generation sequencing technology in the diagnosis of Mycobacterium Tuberculosis and first line drugs resistance directly from cell-free DNA of bronchoalveolar lavage fluid

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