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Fulltext The COVID-19/Tuberculosis Syndemic and Potential Antibody Therapy for TB Based on the Lessons Learnt From the Pandemic

Dass SA, Balakrishnan V, Arifin N, Lim CSY, Nordin F, Tye GJ

Front Immunol, 2022;13:833715.
PMID: 35242137 DOI: 10.3389/fimmu.2022.833715

2020 will be marked in history for the dreadful implications of the COVID-19 pandemic that shook the world globally. The pandemic has reshaped the normality of life and affected mankind in the aspects of mental and physical health, financial, economy, growth, and development. The focus shift to COVID-19 has indirectly impacted an existing air-borne disease, Tuberculosis. In addition to the decrease in TB diagnosis, the emergence of the TB/COVID-19 syndemic and its serious implications (possible reactivation of latent TB post-COVID-19, aggravation of an existing active TB condition, or escalation of the severity of a COVID-19 during TB-COVID-19 coinfection), serve as primary reasons to equally prioritize TB. On a different note, the valuable lessons learnt for the COVID-19 pandemic provide useful knowledge for enhancing TB diagnostics and therapeutics. In this review, the crucial need to focus on TB amid the COVID-19 pandemic has been discussed. Besides, a general comparison between COVID-19 and TB in the aspects of pathogenesis, diagnostics, symptoms, and treatment options with importance given to antibody therapy were presented. Lastly, the lessons learnt from the COVID-19 pandemic and how it is applicable to enhance the antibody-based immunotherapy for TB have been presented.

Matched MeSH terms: Tuberculosis/diagnosis
Human tuberculosis and Mycobacterium tuberculosis complex: A review on genetic diversity, pathogenesis and omics approaches in host biomarkers discovery

Kanabalan RD, Lee LJ, Lee TY, Chong PP, Hassan L, Ismail R, et al.

Microbiol Res, 2021 May;246:126674.
PMID: 33549960 DOI: 10.1016/j.micres.2020.126674

Mycobacterium tuberculosis complex (MTBC) refers to a group of mycobacteria encompassing nine members of closely related species that causes tuberculosis in animals and humans. Among the nine members, Mycobacterium tuberculosis (M. tuberculosis) remains the main causative agent for human tuberculosis that results in high mortality and morbidity globally. In general, MTBC species are low in diversity but exhibit distinctive biological differences and phenotypes among different MTBC lineages. MTBC species are likely to have evolved from a common ancestor through insertions/deletions processes resulting in species speciation with different degrees of pathogenicity. The pathogenesis of human tuberculosis is complex and remains poorly understood. It involves multi-interactions or evolutionary co-options between host factors and bacterial determinants for survival of the MTBC. Granuloma formation as a protection or survival mechanism in hosts by MTBC remains controversial. Additionally, MTBC species are capable of modulating host immune response and have adopted several mechanisms to evade from host immune attack in order to survive in humans. On the other hand, current diagnostic tools for human tuberculosis are inadequate and have several shortcomings. Numerous studies have suggested the potential of host biomarkers in early diagnosis of tuberculosis, in disease differentiation and in treatment monitoring. "Multi-omics" approaches provide holistic views to dissect the association of MTBC species with humans and offer great advantages in host biomarkers discovery. Thus, in this review, we seek to understand how the genetic variations in MTBC lead to species speciation with different pathogenicity. Furthermore, we also discuss how the host and bacterial players contribute to the pathogenesis of human tuberculosis. Lastly, we provide an overview of the journey of "omics" approaches in host biomarkers discovery in human tuberculosis and provide some interesting insights on the challenges and directions of "omics" approaches in host biomarkers innovation and clinical implementation.

Matched MeSH terms: Tuberculosis/diagnosis*
Development of an immunochromatographic lateral flow dipstick for the detection of Mycobacterium tuberculosis 16 kDa antigen (Mtb-strip)

Mohd Amiruddin MN, Ang GY, Yu CY, Falero-Diaz G, Otero O, Reyes F, et al.

J Microbiol Methods, 2020 09;176:106003.
PMID: 32702386 DOI: 10.1016/j.mimet.2020.106003

Mycobacterium tuberculosis (Mtb) is a pathogenic bacterium that causes tuberculosis (TB). This contagious disease remains a severe health problem in the world. The disease is transmitted via inhalation of airborne droplets carrying Mtb from TB patients. Early detection of the disease is vital to prevent transmission of the infection to people in close contact with the patients. To date, there is a need of a simple, rapid, sensitive and specific diagnostic test for TB. Previous studies showed the potential of Mtb 16 kDa antigen (Ag16) in TB diagnosis. In this study, lateral flow immunoassay, also called simple strip immunoassay or immunochromatographic test (ICT) for detection of Ag16 was developed (Mtb-strip) and assessed as a potential rapid TB diagnosis method. A monoclonal antibody against Ag16 was optimized as the capturing and detection antibody on the Mtb-strip. Parameters affecting the performance of the Mtb-strip were also optimized before a complete prototype was developed. Analytical sensitivity showed that Mtb-strip was capable to detect as low as 125 ng of purified Ag16. The analytical sensitivity of Mtb-strip suggests its potential usefulness in different clinical applications.

Matched MeSH terms: Tuberculosis/diagnosis*
Fulltext Epidemiology of tuberculosis in Sabah, Malaysia, 2012-2018

Goroh MMD, Rajahram GS, Avoi R, Van Den Boogaard CHA, William T, Ralph AP, et al.

Infect Dis Poverty, 2020 Aug 26;9(1):119.
PMID: 32843089 DOI: 10.1186/s40249-020-00739-7

BACKGROUND: Tuberculosis (TB) is of high public health importance in Malaysia. Sabah State, located on the island of Borneo, has previously reported a particularly high burden of disease and faces unique contextual challenges compared with peninsular Malaysia. The aim of this study is to describe the epidemiology of TB in Sabah to identify risk groups and hotspots of TB transmission.
METHODS: We conducted a retrospective review of TB cases notified in Sabah, Malaysia, between 2012 and 2018. Using data from the state's 'myTB' notification database, we calculated the case notification rate and described trends in the epidemiology, diagnostic practices and treatment outcomes of TB in Sabah within this period. The Chi-squared test was used for determining the difference between two proportions.
RESULTS: Between 2012 and 2018 there were 33 193 cases of TB reported in Sabah (128 cases per 100 000 population). We identified several geographic hotspots, including districts with > 200 cases per 100 000 population per year. TB rates increased with age and were highest in older males. Children

Matched MeSH terms: Tuberculosis/diagnosis
TCR-like domain antibody against Mycobacterium tuberculosis (Mtb) heat shock protein antigen presented by HLA-A*11 and HLA-A*24

Dass SA, Norazmi MN, Acosta A, Sarmiento ME, Tye GJ

Int J Biol Macromol, 2020 Jul 15;155:305-314.
PMID: 32240734 DOI: 10.1016/j.ijbiomac.2020.03.229

T cell receptor (TCR)-like antibodies, obtained with the use of phage display technology, sandwich the best of the both arms of the adaptive immune system. In this study, in vitro selections against the latency associated Mycobacterium tuberculosis (Mtb) heat shock protein 16 kDa antigen (16 kDa) presented by HLA-A*011 and HLA-A*24 were carried out with the use of a human domain phage antibody library. TCR-like domain antibodies (A11Ab and A24Ab) were successfully generated recognizing 16 kDa epitopes presented by HLA-A*011 and HLA-A*24 molecules respectively. Both antibodies were found to be functional in soluble form and exhibited strong binding capacity against its targets. The results obtained support the future evaluation of these ligands for the development of diagnostic and therapeutic tools for tuberculosis infection.

Matched MeSH terms: Tuberculosis/diagnosis*
Post mortem computed tomography (PMCT) guided lung biopsy: A preliminary case report

Abdul Hadi D, Mansharan Kaur CS, Effat O, Siew SF

Trop Biomed, 2019 Dec 01;36(4):850-854.
PMID: 33597457

Tuberculosis (TB) is a highly infectious disease on the rise caused by the organism Mycobacterium tuberculosis and health care workers working in emergency departments, medical wards and autopsy rooms are in danger of contacting this disease. We present a case of a 42 year old man found dead under a pedestrian bridge with no medical history available. Post mortem computed tomography showed multiple cavities involving upper lobes of both lungs and areas of consolidation in both lung fields raising the suspicion of pulmonary tuberculosis. This was followed by a computed tomography guided lung biopsy and a limited conventional autopsy done in situ in a special high risk autopsy suite with appropriate ventilation. This case highlights the importance of cross sectional imaging which can be coupled with image guided biopsy in cases of infectious disease to reduce the risk of transmission to health care workers.

Matched MeSH terms: Tuberculosis/diagnosis*
Fulltext Diagnosis and management of latent tuberculosis infection in Asia: Review of current status and challenges

Paton NI, Borand L, Benedicto J, Kyi MM, Mahmud AM, Norazmi MN, et al.

Int J Infect Dis, 2019 Oct;87:21-29.
PMID: 31301458 DOI: 10.1016/j.ijid.2019.07.004

Asia has the highest burden of tuberculosis (TB) and latent TB infection (LTBI) in the world. Optimizing the diagnosis and treatment of LTBI is one of the key strategies for achieving the WHO 'End TB' targets. We report the discussions from the Asia Latent TubERculosis (ALTER) expert panel meeting held in 2018 in Singapore. In this meeting, a group of 13 TB experts from Bangladesh, Cambodia, Hong Kong, India, Indonesia, Malaysia, Myanmar, the Philippines, Singapore, Taiwan, Thailand and Vietnam convened to review the literature, discuss the barriers and propose strategies to improve the management of LTBI in Asia. Strategies for the optimization of risk group prioritization, diagnosis, treatment, and research of LTBI are reported. The perspectives presented herein, may help national programs and professional societies of the respective countries enhance the adoption of the WHO guidelines, scale-up the implementation of national guidelines based on the regional needs, and provide optimal guidance to clinicians for the programmatic management of LTBI.

Matched MeSH terms: Latent Tuberculosis/diagnosis*
DNA markers for tuberculosis diagnosis

Chin KL, Sarmiento ME, Norazmi MN, Acosta A

Tuberculosis (Edinb), 2018 12;113:139-152.
PMID: 30514496 DOI: 10.1016/j.tube.2018.09.008

Tuberculosis (TB), caused by Mycobacterium tuberculosis complex (MTBC), is an infectious disease with more than 10.4 million cases and 1.7 million deaths reported worldwide in 2016. The classical methods for detection and differentiation of mycobacteria are: acid-fast microscopy (Ziehl-Neelsen staining), culture, and biochemical methods. However, the microbial phenotypic characterization is time-consuming and laborious. Thus, fast, easy, and sensitive nucleic acid amplification tests (NAATs) have been developed based on specific DNA markers, which are commercially available for TB diagnosis. Despite these developments, the disease remains uncontrollable. The identification and differentiation among MTBC members with the use of NAATs remains challenging due, among other factors, to the high degree of homology within the members and mutations, which hinders the identification of specific target sequences in the genome with potential impact in the diagnosis and treatment outcomes. In silico methods provide predictive identification of many new target genes/fragments/regions that can specifically be used to identify species/strains, which have not been fully explored. This review focused on DNA markers useful for MTBC detection, species identification and antibiotic resistance determination. The use of DNA targets with new technological approaches will help to develop NAATs applicable to all levels of the health system, mainly in low resource areas, which urgently need customized methods to their specific conditions.

Matched MeSH terms: Tuberculosis/diagnosis*
Fulltext Sandwich Electrochemical Immunosensor for Early Detection of Tuberculosis Based on Graphene/Polyaniline-Modified Screen-Printed Gold Electrode

Mohd Azmi UZ, Yusof NA, Kusnin N, Abdullah J, Suraiya S, Ong PS, et al.

Sensors (Basel), 2018 Nov 14;18(11).
PMID: 30441776 DOI: 10.3390/s18113926

A rapid and sensitive sandwich electrochemical immunosensor was developed based on the fabrication of the graphene/polyaniline (GP/PANI) nanocomposite onto screen-printed gold electrode (SPGE) for detection of tuberculosis biomarker 10-kDa culture filtrate protein (CFP10). The prepared GP/PANI nanocomposite was characterized using Fourier transform infrared spectroscopy (FTIR) and field emission scanning electron microscopy (FESEM). The chemical bonding and morphology of GP/PANI-modified SPGE were studied by Raman spectroscopy and FESEM coupled with energy dispersive X-ray spectroscopy, respectively. From both studies, it clearly showed that GP/PANI was successfully coated onto SPGE through drop cast technique. Cyclic voltammetry was used to study the electrochemical properties of the modified electrode. The effective surface area for GP/PANI-modified SPGE was enhanced about five times compared with bare SPGE. Differential pulse voltammetry was used to detect the CFP10 antigen. The GP/PANI-modified SPGE that was fortified with sandwich type immunosensor exhibited a wide linear range (20⁻100 ng/mL) with a low detection limit of 15 ng/mL. This proposed electrochemical immunosensor is sensitive, low sample volume, rapid and disposable, which is suitable for tuberculosis detection in real samples.

Matched MeSH terms: Tuberculosis/diagnosis*
Fulltext Immuno Nanosensor for the Ultrasensitive Naked Eye Detection of Tuberculosis

Mohd Bakhori N, Yusof NA, Abdullah J, Wasoh H, Md Noor SS, Ahmad Raston NH, et al.

Sensors (Basel), 2018 Jun 14;18(6).
PMID: 29899214 DOI: 10.3390/s18061932

In the present study, a beneficial approach for the ultrasensitive and affordable naked eye detection and diagnosis of tuberculosis (TB) by utilizing plasmonic enzyme-linked immunosorbent assay (ELISA) via antibody-antigen interaction was studied. Here, the biocatalytic cycle of the intracellular enzymes links to the formation and successive growth of the gold nanoparticles (GNPs) for ultrasensitive detection. The formation of different colored solutions by the plasmonic nanoparticles in the presence of enzyme labels links directly to the existence or non-existence of the TB analytes in the sample solutions. For disease detection, the adapted protocol is based mainly on the conventional ELISA procedure that involves catalase-labeled antibodies, i.e., the enzymes consume hydrogen peroxide and further produce GNPs with the addition of gold (III) chloride. The amount of hydrogen peroxide remaining in the solution determines whether the GNPs solution is to be formed in the color blue or the color red, as it serves as a confirmation for the naked eye detection of TB analytes. However, the conventional ELISA method only shows tonal colors that need a high concentration of analyte to achieve high confidence levels for naked eye detection. Also, in this research, we proposed the incorporation of protein biomarker, Mycobacterium tuberculosis ESAT-6-like protein esxB (CFP-10), as a means of TB detection using plasmonic ELISA. With the use of this technique, the CFP-10 detection limit can be lowered to 0.01 µg/mL by the naked eye. Further, our developed technique was successfully tested and confirmed with sputum samples from patients diagnosed with positive TB, thereby providing enough evidence for the utilization of our technique in the early diagnosis of TB disease.

Matched MeSH terms: Tuberculosis/diagnosis*
Asian Organization for Crohn's and Colitis and Asia Pacific Association of Gastroenterology consensus on tuberculosis infection in patients with inflammatory bowel disease receiving anti-tumor necrosis factor treatment. Part 2: Management

Park DI, Hisamatsu T, Chen M, Ng SC, Ooi CJ, Wei SC, et al.

J Gastroenterol Hepatol, 2018 Jan;33(1):30-36.
PMID: 29024102 DOI: 10.1111/jgh.14018

Because anti-tumor necrosis factor (anti-TNF) therapy has become increasingly popular in many Asian countries, the risk of developing active tuberculosis (TB) among anti-TNF users may raise serious health problems in this region. Thus, the Asian Organization for Crohn's and Colitis and the Asia Pacific Association of Gastroenterology have developed a set of consensus statements about risk assessment, detection and prevention of latent TB infection, and management of active TB infection in patients with inflammatory bowel disease (IBD) receiving anti-TNF treatment. Twenty-three consensus statements were initially drafted and then discussed by the committee members. The quality of evidence and the strength of recommendations were assessed by using the Grading of Recommendations Assessment, Development, and Evaluation methodology. Web-based consensus voting was performed by 211 IBD specialists from nine Asian countries concerning each statement. A consensus statement was accepted if at least 75% of the participants agreed. Part 2 of the statements comprised three parts: (3) management of latent TB in preparation for anti-TNF therapy, (4) monitoring during anti-TNF therapy, and (5) management of an active TB infection after anti-TNF therapy. These consensus statements will help clinicians optimize patient outcomes by reducing the morbidity and mortality related to TB infections in patients with IBD receiving anti-TNF treatment.

Matched MeSH terms: Tuberculosis/diagnosis
Asian Organization for Crohn's and Colitis and Asian Pacific Association of Gastroenterology consensus on tuberculosis infection in patients with inflammatory bowel disease receiving anti-tumor necrosis factor treatment. Part 1: Risk assessment

Park DI, Hisamatsu T, Chen M, Ng SC, Ooi CJ, Wei SC, et al.

J Gastroenterol Hepatol, 2018 Jan;33(1):20-29.
PMID: 29023903 DOI: 10.1111/jgh.14019

Because anti-tumor necrosis factor (anti-TNF) therapy has become increasingly popular in many Asian countries, the risk of developing active tuberculosis (TB) among anti-TNF users may raise serious health problems in this region. Thus, the Asian Organization for Crohn's and Colitis and the Asian Pacific Association of Gastroenterology have developed a set of consensus statements about risk assessment, detection, and prevention of latent TB infection and management of active TB infection in patients with inflammatory bowel disease (IBD) receiving anti-TNF treatment. Twenty-three consensus statements were initially drafted and then discussed by the committee members. The quality of evidence and the strength of recommendations were assessed by using the Grading of Recommendations Assessment, Development, and Evaluation methodology. Web-based consensus voting was performed by 211 IBD specialists from nine Asian countries concerning each statement. A consensus statement was accepted if at least 75% of the participants agreed. Part 1 of the statements comprised two parts: (i) risk of TB infection during anti-TNF therapy and (ii) screening for TB infection prior to commencing anti-TNF therapy. These consensus statements will help clinicians optimize patient outcomes by reducing the morbidity and mortality related to TB infections in patients with IBD receiving anti-TNF treatment.

Matched MeSH terms: Tuberculosis/diagnosis
RNomic identification and evaluation of npcTB_6715, a non-protein-coding RNA gene as a potential biomarker for the detection of Mycobacterium tuberculosis

Kanniappan P, Ahmed SA, Rajasekaram G, Marimuthu C, Ch'ng ES, Lee LP, et al.

J Cell Mol Med, 2017 10;21(10):2276-2283.
PMID: 28756649 DOI: 10.1111/jcmm.13148

Technological advances in RNA biology greatly improved transcriptome profiling during the last two decades. Besides the discovery of many small RNAs (sRNA) that are involved in the physiological and pathophysiological regulation of various cellular circuits, it becomes evident that the corresponding RNA genes might also serve as potential biomarkers to monitor the progression of disease and treatment. sRNA gene candidate npcTB_6715 was previously identified via experimental RNomic (unpublished data), and we report its application as potential biomarker for the detection of Mycobacterium tuberculosis (MTB) in patient samples. For proof of principle, we developed a multiplex PCR assay and report its validation with 500 clinical cultures, positive for Mycobacteria. The analysis revealed 98.9% sensitivity, 96.1% specificity, positive and negative predictive values of 98.6% and 96.8%, respectively. These results underscore the diagnostic value of the sRNA gene as diagnostic marker for the specific detection of MTB in clinical samples. Its successful application and the general ease of PCR-based detection compared to standard bacterial culture techniques might be the first step towards 'point-of-care' diagnostics of Mycobacteria. To the best of our knowledge, this is the first time for the design of diagnostic applications based on sRNA genes, in Mycobacteria.

Matched MeSH terms: Tuberculosis/diagnosis
Diagnostic accuracy of the Xpert® MTB/RIF cycle threshold level to predict smear positivity: a meta-analysis

Lange B, Khan P, Kalmambetova G, Al-Darraji HA, Alland D, Antonenka U, et al.

Int J Tuberc Lung Dis, 2017 05 01;21(5):493-502.
PMID: 28399963 DOI: 10.5588/ijtld.16.0702

SETTING: Xpert® MTB/RIF is the most widely used molecular assay for rapid diagnosis of tuberculosis (TB). The number of polymerase chain reaction cycles after which detectable product is generated (cycle threshold value, CT) correlates with the bacillary burden.OBJECTIVE To investigate the association between Xpert CT values and smear status through a systematic review and individual-level data meta-analysis.
DESIGN: Studies on the association between CT values and smear status were included in a descriptive systematic review. Authors of studies including smear, culture and Xpert results were asked for individual-level data, and receiver operating characteristic curves were calculated.
RESULTS: Of 918 citations, 10 were included in the descriptive systematic review. Fifteen data sets from studies potentially relevant for individual-level data meta-analysis provided individual-level data (7511 samples from 4447 patients); 1212 patients had positive Xpert results for at least one respiratory sample (1859 samples overall). ROC analysis revealed an area under the curve (AUC) of 0.85 (95%CI 0.82-0.87). Cut-off CT values of 27.7 and 31.8 yielded sensitivities of 85% (95%CI 83-87) and 95% (95%CI 94-96) and specificities of 67% (95%CI 66-77) and 35% (95%CI 30-41) for smear-positive samples.
CONCLUSION: Xpert CT values and smear status were strongly associated. However, diagnostic accuracy at set cut-off CT values of 27.7 or 31.8 would not replace smear microscopy. How CT values compare with smear microscopy in predicting infectiousness remains to be seen.

Matched MeSH terms: Tuberculosis/diagnosis*
Fulltext Role of Interferons in the Development of Diagnostics, Vaccines, and Therapy for Tuberculosis

Chin KL, Anis FZ, Sarmiento ME, Norazmi MN, Acosta A

J Immunol Res, 2017;2017:5212910.
PMID: 28713838 DOI: 10.1155/2017/5212910

Tuberculosis (TB) is an airborne infection caused by Mycobacterium tuberculosis (Mtb). About one-third of the world's population is latently infected with TB and 5-15% of them will develop active TB in their lifetime. It is estimated that each case of active TB may cause 10-20 new infections. Host immune response to Mtb is influenced by interferon- (IFN-) signaling pathways, particularly by type I and type II interferons (IFNs). The latter that consists of IFN-γ has been associated with the promotion of Th1 immune response which is associated with protection against TB. Although this aspect remains controversial at present due to the lack of established correlates of protection, currently, there are different prophylactic, diagnostic, and immunotherapeutic approaches in which IFNs play an important role. This review summarizes the main aspects related with the biology of IFNs, mainly associated with TB, as well as presents the main applications of these cytokines related to prophylaxis, diagnosis, and immunotherapy of TB.

Matched MeSH terms: Tuberculosis/diagnosis
Fulltext Effects of repeated comparative intradermal tuberculin testing on test results: a longitudinal study in TB-free red deer

Che-Amat A, Risalde MÁ, González-Barrio D, Ortíz JA, Gortázar C

BMC Vet Res, 2016 Sep 05;12(1):184.
PMID: 27596591 DOI: 10.1186/s12917-016-0825-2

Diagnosing tuberculosis (TB) in farmed red deer (Cervus elaphus) is challenging and might require combining cellular and humoral diagnostic tests. Repeated skin-testing with mycobacterial purified protein derivatives (PPDs) might sensitize or desensitize the subjects to both kinds of diagnostic tools. We evaluated the effect of repeated (every 6 months) comparative tuberculin skin testing on skin test and ELISA responsiveness in farmed red deer hinds from a TB-free herd. Eighteen 8-month old hinds were inoculated with bovine and avian PPDs and the mitogen phytohaemagglutinin (PHA), as positive control and concurrently tested by ELISA for antibodies against avian (avian PPD, aPPD and protoplasmatic antigen 3, PPA3) and bovine antigens (bPPD and MPB70). Blood serum was also sampled three weeks after each skin testing round and tested for antibodies against aPPD and bPPD, in order to detect eventual antibody level boosts. Testing took place every six months from winter 2012 until winter 2015.

Matched MeSH terms: Tuberculosis/diagnosis
RAIRS2 a new expert system for diagnosing tuberculosis with real-world tournament selection mechanism inside artificial immune recognition system

Saybani MR, Shamshirband S, Golzari S, Wah TY, Saeed A, Mat Kiah ML, et al.

Med Biol Eng Comput, 2016 Mar;54(2-3):385-99.
PMID: 26081904 DOI: 10.1007/s11517-015-1323-6

Tuberculosis is a major global health problem that has been ranked as the second leading cause of death from an infectious disease worldwide, after the human immunodeficiency virus. Diagnosis based on cultured specimens is the reference standard; however, results take weeks to obtain. Slow and insensitive diagnostic methods hampered the global control of tuberculosis, and scientists are looking for early detection strategies, which remain the foundation of tuberculosis control. Consequently, there is a need to develop an expert system that helps medical professionals to accurately diagnose the disease. The objective of this study is to diagnose tuberculosis using a machine learning method. Artificial immune recognition system (AIRS) has been used successfully for diagnosing various diseases. However, little effort has been undertaken to improve its classification accuracy. In order to increase the classification accuracy, this study introduces a new hybrid system that incorporates real tournament selection mechanism into the AIRS. This mechanism is used to control the population size of the model and to overcome the existing selection pressure. Patient epacris reports obtained from the Pasteur laboratory in northern Iran were used as the benchmark data set. The sample consisted of 175 records, from which 114 (65 %) were positive for TB, and the remaining 61 (35 %) were negative. The classification performance was measured through tenfold cross-validation, root-mean-square error, sensitivity, and specificity. With an accuracy of 100 %, RMSE of 0, sensitivity of 100 %, and specificity of 100 %, the proposed method was able to successfully classify tuberculosis cases. In addition, the proposed method is comparable with top classifiers used in this research.

Matched MeSH terms: Tuberculosis/diagnosis*
Congenital Tuberculosis Complicated by Hemophagocytic Lymphohistiocytosis

Osowicki J, Wang S, McKenzie C, Marshall C, Gard J, Ke Juin W, et al.

Pediatr Infect Dis J, 2016 Jan;35(1):108-10.
PMID: 26398869 DOI: 10.1097/INF.0000000000000932

We present the case of a male infant with congenital tuberculosis in a nonendemic setting complicated by hemophagocytic lymphohistiocytosis, who was treated successfully with antituberculous therapy and corticosteroids. We review the pediatric literature concerning the unusual association of these 2 rare conditions.

Matched MeSH terms: Tuberculosis/diagnosis
Fulltext One-Year Tuberculosis Risk in Rheumatoid Arthritis Patients Starting Their First Tumor Necrosis Factor Inhibitor Therapy from 2008 to 2012 in Taiwan: A Nationwide Population-Based Cohort Study

Lim CH, Lin CH, Chen DY, Chen YM, Chao WC, Liao TL, et al.

PLoS One, 2016;11(11):e0166339.
PMID: 27832150 DOI: 10.1371/journal.pone.0166339

OBJECTIVE: To investigate the risk of tuberculosis (TB) among rheumatoid arthritis (RA) patients within 1 year after initiation of tumor necrosis factor inhibitor (TNFi) therapy from 2008 to 2012.
METHODS: We used the 2003-2013 Taiwanese National Health Insurance Research Database to identify RA patients who started any RA-related medical therapy from 2008 to 2012. Those who initiated etanercept or adalimumab therapy during 2008-2012 were selected as the TNFi group and those who never received biologic disease-modifying anti-rheumatic drug therapy were identified as the comparison group after excluding the patients who had a history of TB or human immunodeficiency virus infection/acquired immune deficiency syndrome. We used propensity score matching (1:6) for age, sex, and the year of the drug index date to re-select the TNFi group and the non-TNFi controls. After adjusting for potential confounders, hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to examine the 1-year TB risk in the TNFi group compared with the non-TNFi controls. Subgroup analyses according to the year of treatment initiation and specific TNFi therapy were conducted to assess the trend of 1-year TB risk in TNFi users from 2008 to 2012.
RESULTS: This study identified 5,349 TNFi-treated RA patients and 32,064 matched non-TNFi-treated controls. The 1-year incidence rates of TB were 1,513 per 105 years among the TNFi group and 235 per 105 years among the non-TNFi controls (incidence rate ratio, 6.44; 95% CI, 4.69-8.33). After adjusting for age, gender, disease duration, comoridities, history of TB, and concomitant medications, TNFi users had an increased 1-year TB risk (HR, 7.19; 95% CI, 4.18-12.34) compared with the non-TNFi-treated controls. The 1-year TB risk in TNFi users increased from 2008 to 2011 and deceased in 2012 when the Food and Drug Administration in Taiwan announced the Risk Management Plan for patients scheduled to receive TNFi therapy.
CONCLUSION: This study showed that the 1-year TB risk in RA patients starting TNFi therapy was significantly higher than that in non-TNFi controls in Taiwan from 2008 to 2012.

Matched MeSH terms: Tuberculosis/diagnosis
Testing Eurasian wild boar piglets for serum antibodies against Mycobacterium bovis

Che' Amat A, González-Barrio D, Ortiz JA, Díez-Delgado I, Boadella M, Barasona JA, et al.

Prev Vet Med, 2015 Sep 1;121(1-2):93-8.
PMID: 26051843 DOI: 10.1016/j.prevetmed.2015.05.011

Animal tuberculosis (TB) caused by infection with Mycobacterium bovis and closely related members of the M. tuberculosis complex (MTC), is often reported in the Eurasian wild boar (Sus scrofa). Tests detecting antibodies against MTC antigens are valuable tools for TB monitoring and control in suids. However, only limited knowledge exists on serology test performance in 2-6 month-old piglets. In this age-class, recent infections might cause lower antibody levels and lower test sensitivity. We examined 126 wild boar piglets from a TB-endemic site using 6 antibody detection tests in order to assess test performance. Bacterial culture (n=53) yielded a M. bovis infection prevalence of 33.9%, while serum antibody prevalence estimated by different tests ranged from 19% to 38%, reaching sensitivities between 15.4% and 46.2% for plate ELISAs and between 61.5% and 69.2% for rapid immunochromatographic tests based on dual path platform (DPP) technology. The Cohen kappa coefficient of agreement between DPP WTB (Wildlife TB) assay and culture results was moderate (0.45) and all other serological tests used had poor to fair agreements. This survey revealed the ability of several tests for detecting serum antibodies against the MTC antigens in 2-6 month-old naturally infected wild boar piglets. The best performance was demonstrated for DPP tests. The results confirmed our initial hypothesis of a lower sensitivity of serology for detecting M. bovis-infected piglets, as compared to older wild boar. Certain tests, notably the rapid animal-side tests, can contribute to TB control strategies by enabling the setup of test and cull schemes or improving pre-movement testing. However, sub-optimal test performance in piglets as compared to that in older wild boar should be taken into account.

Matched MeSH terms: Tuberculosis/diagnosis

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