Abstract
Influence of host factors, including human immunodeficiency virus (HIV) co-infection, on the distribution and diagnostic potential of previously evaluated biomarkers of pulmonary tuberculosis (PTB), such as anti-antigen 60 (A60) immunoglobulin (Ig) G, anti-A60 IgA, and C-reactive protein (CRP), remain unclear. Anti-A60 IgG, anti-A60 IgA, and CRP in PTB and non-PTB patient sera (n = 404, including smear-positive/negative, culture-positive (SPCP/SNCP) and HIV+ve/−ve) were measured by enzyme-linked immunoassay and statistically analysed. In multinomial logistic regression, expectoration, chest pain, wasting, and culture count positively associated with CRP (p < 0.001), while smear count positively associated with anti-A60 IgG (p = 0.090). Expectoration and enlarged lymph nodes negatively associated with anti-A60 IgA (p = 0.018). Biomarker distribution and diagnostic potential varied significantly by symptoms and bacilli burden, and across different PTB subpopulations. CRP was correlated poorly with anti-A60 antibodies, while anti-A60 IgA and IgG were correlated in non-tuberculosis (TB) and SPCP patients (p < 0.001). When combined, anti-A60 IgG and CRP best discriminated SPCP/HIV−ve from non-TB (AUC: 0.838, 95% CI: 0.783–0.894), while anti-A60 IgA and CRP performed best in discriminating HIV+ve PTB from non-TB (AUC: 0.687, 95% CI: 0.598–0.777). Combined CRP and anti-A60 antibodies had significantly reduced accuracy in SNCP and SNCP/HIV+ve compared to SPCP/HIV−ve subpopulations. The complex relationships between host factors and biomarkers suggest their limited utility, especially in SNCP/HIV+ve subpopulations, highlighting the importance of examining host response and immune biomarkers across relevant patient subpopulations.
Highlights
Pulmonary tuberculosis (PTB) remains an important cause of morbidity and mortality, in low-middle income countries [1] and areas with high prevalence of human immunodeficiency virus (HIV) [2]
Subsequent multinomial logistic regression revealed that smear-positive culture-positive (SPCP) were more likely male (RR: 2.9, 95% CI: 1.3–6.5), had longer duration of coughing (RR: 3.0, 95% CI: 1.4–6.3), and were less likely to be older (RR: 0.2, 95% CI: 0.1–0.5) compared to non-TB
SPCP were more likely to have longer duration of coughing compared to smear-negative culture-positive (SNCP) (RR: 3.3 95% CI: 1.2–8.7)
Summary
Pulmonary tuberculosis (PTB) remains an important cause of morbidity and mortality, in low-middle income countries [1] and areas with high prevalence of human immunodeficiency virus (HIV) [2]. Case detection of active PTB relies on sputum-based diagnostics—either through detection of acid-fast bacilli (AFB) under smear microscopy or culture, or detection of Mycobacterium tuberculosis (MTB) nucleic acid—the use of which are generally confined to laboratories, and do not reach the majority of people at risk for PTB [4,5]. These challenges are compounded in subpopulations of PTB, such as HIV-positive patients, who have higher mortality due to difficulty and subsequent delay in diagnosis [6,7]. Research and product development of biomarker-based assays appear to have stalled [1,11], in part due to scientific challenges arising from heterogenous patient immune response and the complex spectrum of TB disease manifestation [12]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
