High-sensitivity C-reactive protein in HIV care: Tuberculosis diagnosis and short-term mortality in a cohort of Kenyan HIV patients in the DREAM programme

Abstract

Objective: Tuberculosis (TB) is the leading cause of death in HIV-positive people. In Kenya, 140 000 new TB cases occurred in 2019, and 13 000 HIV-positive patients died due to TB. The objective of this study was to investigate the role of high-sensitivity C-reactive protein (HS-CRP) in TB diagnosis and the prediction of mortality in HIV-positive patients. Methods: The IDEA-TB Study enrolled HIV-positive adult patients attending three DREAM centres in Kenya who were suspected of having TB. A lateral flow urine lipoarabinomannan assay (LF-LAM), serum HS-CRP, and GeneXpert MTB/RIF assay (Xpert MTB/RIF) were performed. Six-month survival was evaluated. Results: A total of 574 patients were enrolled. The median (interquartile range) age, body mass index, and CD4 count were 45 years (37-54 years), 20.5 kg/m 2 (18.5-23.69 kg/m 2 ), and 477 cells/mL (290-700 cells/ mL), respectively. TB was confirmed in 87 (15.2%) patients. Concordance between the Xpert MTB/RIF and LF-LAM tests was 87.1%. HS-CRP was higher in TB patients (35.39 mg/l vs 9.21 mg/l). Malnutrition and elevated HS-CRP were associated with TB: odds ratio (OR) 2.5 (95% confidence interval (CI) 1.14-5.72) and OR 6.6 (95% CI 3.87-11.52), respectively. Nine (1.6%) patients died during follow-up. No single factor was associated with mortality. Only the combination of malnutrition and elevated HS-CRP was highly predictive of death (odds ratio (OR) 9.8, 95% CI 1.88-50.95); the association was stronger in TB patients (33.3% vs 1.0%; OR 47.6, 95% CI 7.03-322.23). Conclusion: TB diagnosis in HIV-positive patients remains challenging. HS-CRP could play a role in predicting early mortality in symptomatic patients.

Screening performance of C-reactive protein for active pulmonary tuberculosis in HIV-positive patients: A systematic review with a meta-analysis

“…A sputum-smear negative and/or negative culture does not always exclude TB diagnosis and may lead to wrong TB management ( 7 – 9 ); this accelerated the use of Xpert Gene MTB/RIF automated rapid molecular assay, which is less sensitive than culture (92%), as a more sensitive method than sputum-smear microscopy for fast identification of PTB as well as rapid assessment of rifampicin susceptibility ( 6 , 10 , 11 ). However, available diagnostic tests and mycobacterial cultures are rather time-consuming compared to point-of-care tests and also require both logistical measures and experienced personnel in order to properly diagnose TB ( 12 , 13 ). Although GeneXpert MTB/RIF assay is preferred as a diagnostic tool in HIV-positive individuals due to higher sensitivity compared to smear microscopy and faster results compared to mycobacterial culture ( 14 ), it imposes various demands such as constant connection to electricity, proper temperature flow, and dedicated personnel to ensure installation functionality in comparison with rapid serological assays ( 13 , 15 ).…”

“…However, available diagnostic tests and mycobacterial cultures are rather time-consuming compared to point-of-care tests and also require both logistical measures and experienced personnel in order to properly diagnose TB ( 12 , 13 ). Although GeneXpert MTB/RIF assay is preferred as a diagnostic tool in HIV-positive individuals due to higher sensitivity compared to smear microscopy and faster results compared to mycobacterial culture ( 14 ), it imposes various demands such as constant connection to electricity, proper temperature flow, and dedicated personnel to ensure installation functionality in comparison with rapid serological assays ( 13 , 15 ). Even more, following WHO recommendations to maximize case findings, preclinical evaluation is also based on symptom screening (WHO 4-SS: the presence of at least one of the following in the last 30 days: cough, fever, night sweats, or weight loss), characterized by high sensitivity, but reduced specificity, hence low effectiveness in evaluating TB ( 8 , 11 , 16 ).…”

“…Cicacci et al. draw attention that screening HIV-positive patients through the WHO-4-SS method may lead to more than 22% of missed TB cases ( 13 ), as a significant proportion of M.tb. -infected individuals may be asymptomatic ( 17 ).…”

“…LF-LAM has multiple advantages: cost-effectiveness, involves a simple procedure, does not require special equipment, provides rapid results, and high specificity in HIV-infected patients ( 20 ). However, LF-LAM presents low sensitivity (56% in patients with CD4 count ≤ 100 cells/μl and 26% in patients with CD4 count > 100 cells/μl), and its specificity decreases proportionally with higher CD4 counts in severe HIV infection ( 13 , 20 ). Nevertheless, increased sensitivity values for a screening test would rule out TB in non-infected individuals and would also limit the use of more expensive confirmatory tests, as the ones mentioned above, in patients exposed to a higher risk of M.tb.…”

High sensitivity C-reactive protein level in various manifestations of tuberculosis in children

“…This observation was consistent with several previous studies in which serum hs-CRP levels were significantly increased in TB patients compared to healthy groups. 15,18,19 In addition, CRP levels are higher in pulmonary TB and disseminated TB patients. 7 In the extra-pulmonary TB group, the highest levels of hs-CRP were in abdominal TB [84.5 (range 0.6-321.5) mg/L], followed by arthritis TB [51.75 (range 20.5-83) mg/L].…”