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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*
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 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
Nested PCR for the rapid detection of TB from pleural fluid at HUKM Malaysia

Salleh SA, Hussin S, Rahman MM

Pak J Biol Sci, 2008 Jul 01;11(13):1728-32.
PMID: 18819627

The aim of the present study is rapid detection of tuberculosis from pleural effusion of suspected patients. Molecular technique Nested Polymerase Chain Reaction (PCR) was used for the purpose. A total of 67 pleural fluid collected at Hospital University Kebangsaan Malaysia during May 2005 to October 2006 were sent to Microbiology Laboratory enrolled in the study. Detection rate of Mycobacterium tuberculosis in pleural effusion was 0% by acid-fast bacilli (AFB) staining and 1.5% by culture on Lowenstein-Jensen medium. Mycobacterium tuberculosis was detected by PCR in 9% of the cases. PCR of pleural fluid had 19% sensitivity and 96% specificity, compared to AFB staining (0% sensitivity and 100% specificity) and culture (4% sensitivity and 100% specificity). PCR also has 67% Positive Predictive Value (PPV) and 72% Negative Predictive Value (NPV) in detecting Mycobacterium tuberculosis. Culture ofpleural fluid has 100% PPV and 71% NPV while AFB staining has 0% PPV and 31% NPV. This preliminary study showed that PCR is a rapid method for detection of Mycobacterium tuberculosis in pleural fluid but its sensitivity is not up the marked.

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
Rapid detection of Mycobacterium tuberculosis in clinical samples by multiplex polymerase chain reaction (mPCR)

Tang TH, Ahmed SA, Musa M, Zainuddin ZF

World J Microbiol Biotechnol, 2013 Dec;29(12):2389-95.
PMID: 23807412 DOI: 10.1007/s11274-013-1407-0

Although the multi-copy and specific element IS6110 provides a good target for the detection of Mycobacterium tuberculosis complex by PCR techniques, the emergence of IS6110-negative strains suggested that false negative may occur if IS6110 alone is used as the target for detection. In this report, a multiplex polymerase chain reaction (mPCR) system was developed using primers derived from the insertion sequence IS6110 and an IS-like elements designated as B9 (GenBank accession no. U78639.1) to overcome the problem of detecting negative or low copy IS6110 containing strains of M. tuberculosis. The mPCR was evaluated using 346 clinical samples which included 283 sputum, 19 bronchial wash, 18 pleural fluid, 9 urine, 7 CSF, 6 pus, and 4 gastric lavage samples. Our results showed that the sensitivity (93.1 %) and specificity (89.6 %) of the mPCR system exceeds that of the conventional method of microscopy and culture. The mPCR assay provides an efficient strategy to detect and identify M. tuberculosis from clinical samples and enables prompt diagnosis when rapid identification of infecting mycobacteria is necessary.

Matched MeSH terms: Tuberculosis/diagnosis
Fulltext Prevalence of tuberculosis symptoms and latent tuberculous infection among prisoners in northeastern Malaysia

Margolis B, Al-Darraji HA, Wickersham JA, Kamarulzaman A, Altice FL

Int J Tuberc Lung Dis, 2013 Dec;17(12):1538-44.
PMID: 24200265 DOI: 10.5588/ijtld.13.0193

There are currently no routine screening procedures for active tuberculosis (TB) or latent tuberculous infection (LTBI) in Malaysian prisons.

Matched MeSH terms: Latent Tuberculosis/diagnosis
Detection and discrimination of Mycobacterium tuberculosis complex

Issa R, Mohd Hassan NA, Abdul H, Hashim SH, Seradja VH, Abdul Sani A

Diagn Microbiol Infect Dis, 2012 Jan;72(1):62-7.
PMID: 22078904 DOI: 10.1016/j.diagmicrobio.2011.09.021

A real-time quantitative polymerase chain reaction (qPCR) was developed for detection and discrimination of Mycobacterium tuberculosis (H37Rv and H37Ra) and M. bovis bacillus Calmette-Guérin (BCG) of the Mycobacterium tuberculosis complex (MTBC) from mycobacterial other than tuberculosis (MOTT). It was based on the melting curve (Tm) analysis of the gyrB gene using SYBR(®) Green I detection dye and the LightCycler 1.5 system. The optimal conditions for the assay were 0.25 μmol/L of primers with 3.1 mmol/L of MgCl(2) and 45 cycles of amplification. For M. tuberculosis (H37Rv and H37Ra) and M. bovis BCG of the MTBC, we detected the crossing points (Cp) at cycles of 16.96 ± 0.07, 18.02 ± 0.14, and 18.62 ± 0.09, respectively, while the Tm values were 90.19 ± 0.06 °C, 90.27 ± 0.09 °C, and 89.81 ± 0.04 °C, respectively. The assay was sensitive and rapid with a detection limit of 10 pg of the DNA template within 35 min. In this study, the Tm analysis of the qPCR assay was applied for the detection and discrimination of MTBC from MOTT.

Matched MeSH terms: Tuberculosis/diagnosis*
Fulltext Influence of co-morbidity in the interpretation of tuberculin skin reactivity in multi-ethnic adult patients with tuberculosis

Loh LC, Chan SK, Ch'ng KI, Tan LZ, Vijayasingham P, Thayaparan T

Med J Malaysia, 2005 Oct;60(4):426-31.
PMID: 16570703

In the Malaysian setting of multi-ethnicity and high BCG coverage, interpretation of Tuberculin Skin Testing (TST) may be difficult. Between January 2001 and December 2003, a retrospective study on all adult patients with documented TST results treated for tuberculosis (TB) in chest clinics of two government hospitals was conducted to determine the reliability of TST and factors affecting its interpretation. One hundred and three patients [mean age (SD): 43 (17); male: 67%] were eligible for data collection: 72% and 57% of patients had positive TST results based on cut-off points of 10mm and 15mm respectively. The only significant univariate association with TST results was the severity of co-morbidity. A patient with co-morbidity score of 3 defined as those with any cancer, end-stage renal or liver disease, or HIV disease, was more likely to have a negative TST results [10mm cut-off point: Odd Ratio (95% CI) 6.6 (1.82 to 24.35), p = 0.003; 15mm cut-off point: 4.8 (1.21 to 18.95), p = 0.012]. A TST reading of 10mm had a higher sensitivity than 15mm as the cut-off point in diagnosing TB infection. Considering all possible confounding factors like ethnicity, prior BCG vaccination and TB burden in the population, severity of co-morbidity remains strongly predictive of a negative TST. Caution should be exercised in interpreting TST in these patients.
Study site: Chest clinic, Hospital Seremban, Hospital Kuala Pilah, Negeri Sembilan, Malaysia

Matched MeSH terms: Tuberculosis/diagnosis*
Comparison of BACTEC MGIT 960 system and BACTEC 460 TB system for growth and detection of Mycobacteria from clinical specimens

Ganeswrie R, Chui CS, Balan S, Puthucheary SD

Malays J Pathol, 2004 Dec;26(2):99-103.
PMID: 16329561

This study was carried out to compare the performance of BACTEC MGIT 960 with the BACTEC 460 TB for growth and detection of Mycobacteria from human clinical specimens. The BACTEC MGIT 960 instrument is a fully automated system that utilizes MGIT tubes containing an oxygen sensor embedded in silicon at the bottom and filled with 7 mL of modified Middlebrook 7H9 broth. Identical samples were inoculated into the two automated systems and incubated for six weeks. Over a period of three months, 279 specimens were decontaminated and processed according to the standard CDC NALC/NaOH method, using the commercial MycoPrep kit. Forty-two specimens (15%) yielded Mycobacterium tuberculosis; 37 (88%) were detected by the fluorescent BACTEC MGIT 960 and 35 (83%) detected by the radiometric BACTEC 460 TB. Fifteen specimens (5%) yielded Mycobacterium Other Than Tuberculosis (MOTT); 10 (66%) were detected by BACTEC MGIT 960 and 11 (73%) detected by BACTEC 460 TB. The average time to detection and contamination rates and the average time to obtain results of antimicrobial susceptibility tests between the two systems were compared. The performance of the BACTEC MGIT 960 was comparable to the BACTEC 460 TB system which has been the "Gold Standard" for automated detection of TB. The former was more rapid, as sensitive and less labour intensive than the BACTEC 460. Our data demonstrates that the BACTEC MGIT 960 system is an accurate, automated and a non-radioactive alternative to the BACTEC 460 TB for the culture and susceptibility testing of M. tuberculosis.

Matched MeSH terms: Tuberculosis/diagnosis*
Tuberculosis in HIV/AIDS patients: a Malaysian experience

Nissapatorn V, Kuppusamy I, Sim BL, Quek KF, Khairul Anuar A

Southeast Asian J. Trop. Med. Public Health, 2005 Jul;36(4):946-53.
PMID: 16295550

This retrospective study was conducted at the National Tuberculosis Center (NTBC) where 252 HIV-positive patients coexisting with tuberculosis (TB/HIV) were examined. We found that patients with pulmonary (PTB) and extrapulmonary tuberculosis (EPT) had similar mean age. A higher sex ratio between male to female (10.7:1) was observed in patients with PTB. The other characteristics of patients with pulmonary and extrapulmonary tuberculosis were not statistically different from each other. Cough (88%) and hemoptysis were the most common presenting symptoms, significantly related to patients with PTB. Lymphadenopathy (33.5%) was the most common sign in patients with EPT. The majority of patients with pulmonary and extrapulmonary tuberculosis had CD4 cell counts of less than 200 cells/mm3 (range 0-1,179 with a median of 57 cells/mm3). Lung (89%) and miliary (55.6%) forms were the most frequent disease locations in patients with PTB and EPT, respectively. A higher percentage of patients with PTB (42%) were treated successfully with short-course (6 months) therapy, whereas in patients with EPT (43%) needed a longer period (9 months) for successful treatment. Of the patients who defaulted treatment, a higher proportion (87%) had PTB. No MDR-TB or relapse cases were found in this study.

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
Serum antigen 85 levels in adjunct testing for active mycobacterial infections in orangutans

Kilbourn AM, Godfrey HP, Cook RA, Calle PP, Bosi EJ, Bentley-Hibbert SI, et al.

J. Wildl. Dis., 2001 Jan;37(1):65-71.
PMID: 11272506

Diagnosis of active mycobacterial disease in orangutans (Pongo pygmaeus) has been impeded by high levels of non-specific intradermal skin test reactivity to mycobacterial antigens. This may be due in part to cross reactivity between antigens, tuberculin concentrations used or other species-specific factors. Antigen 85 (Ag85) complex proteins are major secretory products of actively growing mycobacteria, and measurement of serum Ag85 could provide a method for determining active mycobacterial infections that was not dependent on host immunity. Serum Ag85 was measured by dot-immunobinding assay using monoclonal anti-Ag85, purified Ag85 standard and enhanced chemiluminescence technology in coded serum samples from 14 captive orangutans from a zoo in Colorado, 15 semi-captive orangutans in Malaysia, and 19 free-ranging wild orangutans in Malaysia. Orangutans from Colorado (USA) were culture negative for Mycobacterium tuberculosis and M. avium, although all had laboratory suspicion or evidence of mycobacterial infection; median serum Ag85 was 10 microU/ml (range, <0.25-630 microU/ml). Of the semi-captive orangutans, six were skin test reactive and two were culture positive for M. avium on necropsy. Median serum Ag85 for this group was 1,880 microU/ml (0.75-7,000 microU/ml), significantly higher than that of Colorado zoo or free-ranging Malaysian orangutans. Median serum Ag85 in the latter group was 125 microU/ml (range, 0.75-2,500 microU/ml). These data suggest that suggest that additional studies using more specific reagents and more samples from animals of known status are appropriate.

Matched MeSH terms: Tuberculosis/diagnosis*
Hypercalcaemia in patients with newly diagnosed tuberculosis in Malaysia

Liam CK, Lim KH, Srinivas P, Poi PJ

Int J Tuberc Lung Dis, 1998 Oct;2(10):818-23.
PMID: 9783529

University Hospital, Kuala Lumpur, Malaysia.

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*
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*
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 Latent tuberculosis infection screening in foreign-born populations: a successful mobile clinic outreach model

Morano JP, Zelenev A, Walton MR, Bruce RD, Altice FL

Am J Public Health, 2014 Aug;104(8):1508-15.
PMID: 24922157 DOI: 10.2105/AJPH.2014.301897

OBJECTIVES: We evaluated the efficacy of a mobile medical clinic (MMC) screening program for detecting latent tuberculosis infection (LTBI) and active tuberculosis.
METHODS: A LTBI screening program in a MMC in New Haven, Connecticut, used medical surveys to examine risk factors and tuberculin skin test (TST) screening eligibility. We assessed clinically relevant correlates of total (prevalent; n = 4650) and newly diagnosed (incident; n = 4159) LTBI from 2003 to 2011.
RESULTS: Among 8322 individuals, 4159 (55.6%) met TST screening eligibility criteria, of which 1325 (31.9%) had TST assessed. Similar to LTBI prevalence (16.8%; 779 of 4650), newly diagnosed LTBI (25.6%; 339 of 1325) was independently correlated with being foreign-born (adjusted odds ratio [AOR] = 8.49; 95% confidence interval [CI] = 5.54, 13.02), Hispanic (AOR = 3.12; 95% CI = 1.88, 5.20), Black (AOR = 2.16; 95% CI = 1.31, 3.55), employed (AOR = 1.61; 95% CI = 1.14, 2.28), and of increased age (AOR = 1.04; 95% CI = 1.02, 1.05). Unstable housing (AOR = 4.95; 95% CI = 3.43, 7.14) and marijuana use (AOR = 1.57; 95% CI = 1.05, 2.37) were significantly correlated with incident LTBI, and being male, heroin use, interpersonal violence, employment, not having health insurance, and not completing high school were significantly correlated with prevalent LTBI.
CONCLUSIONS: Screening for TST in MMCs successfully identifies high-risk foreign-born, Hispanic, working, and uninsured populations and innovatively identifies LTBI in urban settings.
Study site: Mobile clinic, New Haven, Connecticut, United States

Matched MeSH terms: Latent Tuberculosis/diagnosis*
Fulltext Bilateral atypical optic neuritis associated with tuberculosis in an immunocompromised patient

Jaafar J, Hitam WH, Noor RA

Asian Pac J Trop Biomed, 2012 Jul;2(7):586-8.
PMID: 23569976 DOI: 10.1016/S2221-1691(12)60102-6

A 27 year-old lady, presented with sudden loss of vision in the right eye for a week. It was followed by poor vision in the left eye after 3 days. It involved the whole entire visual field and was associated with pain on eye movement. She was diagnosed to have miliary tuberculosis and retroviral disease 4 months ago. She was started on anti-TB since then but defaulted highly active anti-retroviral therapy (HAART). On examination, her visual acuity was no perception of light in the right eye and 6/120 (pinhole 3/60) in the left eye. Anterior segment in both eyes was unremarkable. Funduscopy showed bilateral optic disc swelling with presence of multiple foci of choroiditis in the peripheral retina. The vitreous and retinal vessels were normal. Chest radiography was normal. CT scan of orbit and brain revealed bilateral enhancement of the optic nerve sheath that suggest the diagnosis of bilateral atypical optic neuritis. This patient was managed with infectious disease team. She was started on HAART and anti-TB treatment was continued. She completed anti-TB treatment after 9 months without any serious side effects. During follow up the visual acuity in both eyes was not improved. However, funduscopy showed resolving of disc swelling and choroiditis following treatment.

Matched MeSH terms: Tuberculosis/diagnosis*

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