Oral prednisolone severely suppressed QFT-IT and TST performance, whereas the long-acting corticosteroids methotrexate, azathioprine, and 5-ASA did not have a similar detrimental effect. Patients should be screened for LTBI with QFT-IT or TST prior to initiation of prednisolone therapy and negative QFT-IT or TST results interpreted with caution in patients treated with any corticosteroid until further data are available.
Background
Antigen specific release of IP-10 is an established marker for infection with
M.tuberculosis
. Compared to IFN-γ, IP-10 is released in 100-fold higher concentrations enabling the development of novel assays for detection. Dried blood spots are a convenient sample for high throughput newborn screening.
Aim
To develop a robust and sensitive ELISA-based assay for IP-10 detection in plasma, dried blood spots (DBS) and dried plasma spots (DPS); to validate the ELISA in clinically relevant samples; and to assess the performance of the assay for detection of Cytomegalovirus (CMV) and
M.tuberculosis
specific immune responses.
Method
We raised mice and rat monoclonal antibodies against human IP-10 and developed an ELISA. The assay was validated and applied to the detection of CMV and
M.tuberculosis
specific responses in 18 patients with immune reactivity towards
M.tuberculosis
and 32 healthy controls of which 22 had immune reactivity towards CMV and none towards
M.tuberculosis
. We compared the performance of this new assay to IFN-γ.
Results
The ELISA was reliable for IP-10 detection in both plasma and filter paper samples. The linear range of the ELISA was 2.5–600 pg/ml. IFN-γ was not readily detectable in DPS samples. IP-10 was stabile in filter paper samples for at least 4 weeks at 37°C. The correlation between IP-10 detected in plasma, DPS and DBS samples was excellent (r
2
>0.97).
Conclusions
This newly developed assay is reliable for IP-10 quantification in plasma, DBS and DPS samples from antigen stimulated and non-stimulated whole blood. The filter paper assays enable easy sample acquisition and transport at ambient temperature e.g. via the postal system. The system can potentially simplify diagnostic assays for
M.tuberculosis
and CMV infection.
Mortality of HIV/tuberculosis (TB) patients in Eastern Europe is high. Little is known about their causes of death.This study aimed to assess and compare mortality rates and cause of death in HIV/TB patients across Eastern Europe and Western Europe and Argentina (WEA) in an international cohort study. Mortality rates and causes of death were analysed by time from TB diagnosis (,3 months, 3-12 months or .12 months) in 1078 consecutive HIV/TB patients. Factors associated with TB-related death were examined in multivariate Poisson regression analysis. 347 patients died during 2625 person-years of follow-up. Mortality in Eastern Europe was three-to ninefold higher than in WEA. TB was the main cause of death in Eastern Europe in 80%, 66% and 61% of patients who died ,3 months, 3-12 months or .12 months after TB diagnosis, compared to 50%, 0% and 15% in the same time periods in WEA (p,0.0001). In multivariate analysis, follow-up in WEA (incidence rate ratio (IRR) 0.12, 95% CI 0.04-0.35), standard TB-treatment (IRR 0.45, 95% CI 0.20-0.99) and antiretroviral therapy (IRR 0.32, 95% CI 0.14-0.77) were associated with reduced risk of TB-related death.Persistently higher mortality rates were observed in HIV/TB patients in Eastern Europe, and TB was the dominant cause of death at any time during follow-up. This has important implications for HIV/TB programmes aiming to optimise the management of HIV/TB patients and limit TB-associated mortality in this region. @ERSpublications High TB-related death rates in HIV patients in Eastern Europe require measures to improve their clinical management
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