Abstract
BackgroundTuberculosis is one of the leading causes of morbidity and mortality in developing countries. Analysis of the host immune response may help with generating point-of-care tests for personalised monitoring. Thus, the aim of this study was to assess the relationship between immune activation markers: C-reactive protein (CRP), Beta2 microglobulin (B2M) and Neopterin, disease severity prior to treatment and response to therapy in adult pulmonary TB patients.MethodsHIV negative adult pulmonary TB index cases (n = 91) were recruited from the TB clinic at MRC, The Gambia. Plasma samples were collected at enrolment and at 2 and 6 months following TB treatment initiation. An enzyme linked immunosorbent assay (ELISA) was performed for evaluation of CRP, B2M and Neopterin levels and correlated with clinical and microbiological parameters including strain of infection. Disease severity was determined using Chest X-ray (CXR), Body Mass Index (BMI) and sputum smear grade.ResultsPlasma levels of all three markers were highly elevated in patients at recruitment and declined significantly during TB therapy. No correlation with disease severity was seen at recruitment. CRP showed the most significant decrease by 2 months of treatment (p < 0.0001) whereas levels of B2M and Neopterin showed little change by 2 months but a significant decrease by 6 months of treatment (p = 0.0002 and p < 0.0001 respectively). At recruitment, B2M levels were significantly higher in subjects infected with Mycobacterium africanum (Maf) compared with those infected with Mycobacterium tuberculosis sensu stricto (Mtb) (p = 0.0075). In addition, while CRP and Neopterin showed a highly significant decline post-treatment regardless of strain (p < 0.0001 for all), B2M showed differential decline depending on strain (p = 0.0153 for Mtb and p = 0.0048 for Maf) and levels were still significantly higher at 6 months in Maf compared to Mtb infected subjects (p = 0.0051).ConclusionOur findings suggest that activation markers, particularly CRP, may have a role in identifying good response to TB therapy regardless of the strain of infection and could be further developed as point-of-care tests. In addition, B2M levels may allow differentiation between Mtb and Maf-infected subjects.
Highlights
Tuberculosis is one of the leading causes of morbidity and mortality in developing countries
Despite many advances in treatment and campaigns such as Directly Observed Treatment Short course (DOTS) by the World Health Organisation (WHO), difficulty in diagnosis, non-adherence to treatment, emergence of multi-drug resistance (MDR) strains and TB/human immunodeficiency virus (HIV) co-infection have all fuelled the spread of the disease [2]
Body Mass Index (BMI) at recruitment was (median (IQR)) 18.6 kg/m2 (17.3–19.3) and this significantly increased by 6 months of treatment (19.6 kg/m2 (1.6–22.1; p = 0.0374; Table 1)
Summary
Tuberculosis is one of the leading causes of morbidity and mortality in developing countries. Tuberculosis (TB) is one of the leading global causes of morbidity and mortality, in Sub-Saharan Africa with 1.5 million deaths per year [1]. Though the disease produced by both strains looks similar [4], they have significant differences in their genomes in the Region of Difference 1 (RD1) containing crucial T cell epitopes. In this regard, Maf infected subjects were observed to be less responsive to both ESAT6 and TST compared to Mtb infected counterparts [5] and are more likely to have severe cavitation on chest x-ray [5]. Due to the intensive nature of anti-TB therapy and these differences in therapy response depending on the strain of infection [7, 8], a point-of-care test that allows personalised monitoring of treatment response would be beneficial
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