Diagnosis and treatment of tuberculosis infection (TBI) are the core elements of tuberculosis elimination. Interferon gamma release assays have advantages over the tuberculin skin test, although their implementation in low-resource settings is challenging. The performance of a novel digital lateral flow assay QIAreach® QuantiFERON®-TB (QIAreach QFT) against the QuantiFERON®-TB Gold Plus (QFT-Plus) assay was evaluated in an intermediate incidence setting (Malaysia) according to the manufacturer's instructions. Individuals aged 4-82 years, who were candidates for TB infection screening for contact investigation were prospectively recruited. On 196 samples, the QIAreach-QFT showed a positive percent agreement (sensitivity) was 96.5% (CI 87.9-99.6%), a negative percent agreement (specificity) 94.2% (CI 88.4% to 97.6%) and an overall percentage of agreement was 94.9% (95% CI 90.6-97.6%) with a Cohen's κ of 0,88. Out of 196, 5.6% (11/196) samples gave an error result on QIAreach-QFT and 4.1% (8/196) samples gave indeterminate result on QFT-plus. The TTR for QIAreach QFT positive samples varied from 210-1200 seconds (20 min) and significantly correlated with IFN-γ level of QFT-Plus. QIAreach QFT could be considered an accurate and reliable point-of-need test to diagnose TB infection helping to achieve the WHO End TB programme goals even in decentralised settings where laboratory expertise and infrastructure may be limited.
Tuberculosis (TB) remains a very common disease in most of the low- and middle-income countries. As a result of high disease burden, TB control measures in these countries are usually concentrated on intensifying active disease case-finding and early treatment of infectious TB. On the contrary, in countries with low disease burden, the focus is on contact investigation to identify latently infected individuals and prophylactically treating them to prevent disease reactivation and transmission. These two strategies are deemed important for the effective TB control. Nonetheless, WHO cautions that targeted contact investigation and latent TB infection (LTBI) treatment should only be undertaken by countries that have the operational capacity/ resources and have achieved ≥ 85% treatment success rate of active TB. The screening of LTBI is further challenged by the lack of a “gold standard” test to identify and validate individuals with this condition. Tuberculin skin test (TST) is still the preferred investigation as it is cheap, widely available and validated in many trials. The sensitivity and specificity of the newer test—interferon gamma release assay (IGRA) for LTBI screening has been encouraging in low prevalence countries. However, the evidence supporting such usage remains uncertain in high burden settings. Diagnosis of LTBI should adhere to the strict criteria outlined in the guidelines to avoid misdiagnosing active TB as LTBI. The treatment of the latter involved only one or two anti-TB drugs. It has been demonstrated that in the properly conducted contact screening and LTBI treatment, chances of the emergence of multi-drug-resistant TB is very low.
To estimate the costs and benefits of screening for latent tuberculosis infection (LTBI) in a migrant population in Malaysia. An economic model was developed from a Malaysian healthcare perspective to compare QuantiFERON-TB Gold Plus (QuantiFERON) with the tuberculin skin test (TST). A decision tree was used to capture outcomes relating to LTBI screening followed by a Markov model that simulated the lifetime costs and benefits of the patient cohort. The Markov model did not capture the impact of secondary infections. The model included an R shiny interactive interface to allow adaptation to other scenarios and settings. QuantiFERON is both more effective and less costly than TST (dominant). Compared with QuantiFERON, the lifetime risk of developing active TB increases by approximately 40% for TST due to missed LTBI cases during screening (i.e. a higher number of false negative cases for TST). For a migrant population in Malaysia, QuantiFERON is cost-effective when compared with TST. Further research should consider targeted LTBI screening for migrants in Malaysia based on common risk factors.
Introduction: Biologic patients are at increased risk of tuberculosis (TB) infection, especially in TB prevalent areas like Sabah. We present three cases of rheumatology patients who developed tuberculosis infection while on bi-ologics. Case description: Case1: 47 year old lady with active rheumatoid arthritis despite being on four disease modifying antirheumatic drugs (DMARDS) was given subcutaneous Etanercept after prescreening with mantoux test and interferon gamma release assay (IGRA). Due to poor response, she was switched to Tofacitinib with a repeat pre-screening done except IGRA. Three months after biologics, she developed pulmonary tuberculosis and Tofacitinib was stopped. Case2: 50 year old male with seropositive rheumatoid arthritis and seroconverted hepatitis B. He was worked up for biologic treatment after failing multiple DMARDS; mantoux was 10mm, IGRA not done. He was start-ed on subcutaneous Etanercept for disabling arthritis while being treated for latent TB but developed TB Lymphadeni-tis on his third month of biologic therapy which was withheld thereafter. Case3:48 year old teacher with seropositive rheumatoid arthritis and old pulmonary TB, had intolerance to methotrexate, was initiated on three DMARDS but symptoms remained uncontrolled. Prescreening with IGRA was negative and Adalimumab commenced. Following two years of biologic, she developed reactivation of TB. Rituximab was commenced a year after for persistent active arthritis but withheld due to dermatitis. Conclusion: All patients had mantoux test done routinely but not IGRA due to its cost and limited availability. A follow up study to analyze the effectiveness of IGRA versus Mantoux in detecting latent TB in such patients would be beneficial.
A cross-sectional study was conducted from 10 January to 9 April 2012, to determine the seroprevalence of tuberculosis (TB) of all captive Asian elephants and their handlers in six locations in Peninsular Malaysia. In addition, trunk-wash samples were examined for tubercle bacillus by culture and polymerase chain reaction (PCR). For 63 elephants and 149 elephant handlers, TB seroprevalence was estimated at 20.4% and 24.8%, respectively. From 151 trunkwash samples, 24 acid-fast isolates were obtained, 23 of which were identified by hsp65-based sequencing as non-tuberculous mycobacteria. The Mycobacterium tuberculosis-specific PCR was positive in the trunk-wash samples from three elephants which were also seropositive. Conversely, the trunk wash from seven seropositive elephants were PCR negative. Hence, there was evidence of active and latent TB in the elephants and the high seroprevalence in the elephants and their handlers suggests frequent, close contact, two-way transmission between animals and humans within confined workplaces.