Impact of Migrant Populations on Tuberculosis Rates in Saudi Arabia: Assessing How Migration Patterns Affect TB Incidence and Control Measures: A Narrative Review

This research focuses on the effects of migration on the TB infection rate and its prevention in Saudi Arabia, which has a large number of expatriates from TB-affected countries. Despite, based on the current global statistics of TB occurrence, it is evident that the national incidence of TB has reduced from 10.55 per 100,000 in 2015 to 8.36 per 100,000 in 2019;despite this, there are still some difficulties because migrants bring new strains of Mycobacterium tuberculosis. Hindrances, including language barriers and perceived immigration status, hinder patients from seeking medical attention or doctors from diagnosing diseases. Each patient and each cultural group need special attention to public health, enhancing living circumstances, and health care support. Community participation, inclusion of TB control programs into functional healthcare facilities, and the functioning of TB programs need to be stressed to address TB issues. Considering the focus on social, economic, and cultural approaches, the country can make severe advancements in TB control and population protection. This holistic analysis is critical for a long-term effective strategy to combat TB in the Kingdom.

Clinical Evaluation of Two Interferon-Gamma Release Assays for Diagnostic Tests of Tuberculosis Infection in a Tertiary Hospital: Clinical Evaluation of Two IGRAs for TB Infection

Background: The aim of this study was to evaluate the usefulness of two interferon-gamma release assays (IGRAs) (QuantiFERON-TB Plus (QFT-plus) and T-SPOT.TB assay) for patients suspected of having tuberculosis (TB) infection as supportive methods for diagnosing TB. Patients and Methods: The subjects consisted of 45 patients who required clinical differentiation of TB disease from June 2019 to August 2023. The final clinical diagnoses were: 14 patients with active TB disease, 4 with latent TB infection (LTBI), 17 with old (cured) TB disease, and 10 with pulmonary nontuberculous mycobacterial (NTM) disease. We used the two IGRAs for these patients and evaluated the data according to the manufacturer’s guidelines for interpretation or FDA-approved cutoffs. Results: Among the total of 14 patients with active TB disease (mean age: 64 years old, male: 9, and female: 5), a positive response was noted in 10 patients (71%) on QFT-plus and 9 (64%) on T-SPOT.TB. Four patients with a negative response on QFT-plus and T-SPOT.TB were elderly or cancer patients with lymphocytopenia or hypoalbuminemia. All four patients with LTBI showed a positive response (100%) on both QFT-plus and T-SPOT.TB. Among the seventeen patients with old (cured) TB disease, a positive response was noted in 8 patients (47%) on QFT-plus and 9 (53%) on T-SPOT.TB. All patients with pulmonary NTM disease showed a negative response on both QFT-plus and T-SPOT.TB. Conclusions: A false-negative response on QFT-plus as well as T-SPOT.TB was recognized in elderly patients and patients with an immunosuppressed condition, and half of patients with old (cured) TB showed no negative conversion after the completion of treatment through this study. Although it was recently reported that the positive response rate on QFT-plus of patients with active TB disease was high, we consider it necessary to be careful in diagnosing TB infection using IGRAs for patients with severe underlying diseases in a tertiary hospital based on the results.

Factors of Adherence to Concurrent Tuberculosis Treatment and Antiretroviral Therapy among HIV-TB Co-Infected Individuals in the East Region, Cameroon in the COVID-19 Era: A Retrospective Cohort Study

Context/Objectives: Tuberculosis (TB) and HIV co-infection is a serious health problem in Cameroon. The problems associated with poor adherence to treatment are on the increase worldwide. This problem can be observed in all situations where patients are required to administer their own medication, whatever the type of illness. The general objective of this study was to assess the factors affecting adherence to treatment among HIV-TB co-infected patients in health facilities in the East Region in the COVID context. Method: A retrospective cohort study before and during COVID-19 was conducted in HIV care units in 13 health districts in the East Region of Cameroon. Data were collected using a questionnaire recorded in the Kobo Collect android application, analyzed using SPSS version 25 software and plotted using Excel. Results: The pre-COVID-19 cohort compared to the during-COVID-19 cohort had a 1.90 risk of not adhering to treatment (OR: 1.90, CI {1.90 - 3.37}) and the difference was statistically significant at the 5% level (p-value = 0.029). Frequency of adherence was 65.4% (140/214). Adherence before COVID-19 was 56.9% whereas during COVID-19, it was 74.3%. Conclusion: The implementation of targeted interventions in the COVID-19 context, using evidence-based data and integrating the individual needs of HIV-TB co-infected patients, improved adherence to concurrent anti-tuberculosis treatment and antiretroviral therapy during the COVID-19 Era.

From immunology to artificial intelligence: revolutionizing latent tuberculosis infection diagnosis with machine learning

Latent tuberculosis infection(LTBI)has become a major source of active tuberculosis(ATB).Although the tuberculin skin test and interferon-gamma release assay can be used to diagnose LTBI,these methods can only differentiate infected individuals from healthy ones but cannot discriminate between LTBI and ATB.Thus,the diagnosis of LTBI faces many challenges,such as the lack of effective biomarkers from Mycobacterium tuberculosis(MTB)for distinguishing LTBI,the low diagnostic efficacy of biomarkers derived from the human host,and the absence of a gold standard to differentiate between LTBI and ATB.Sputum culture,as the gold standard for diagnosing tuberculosis,is time-consuming and cannot distinguish between ATB and LTBI.In this article,we review the pathogenesis of MTB and the immune mechanisms of the host in LTBI,including the innate and adaptive immune responses,multiple immune evasion mechanisms of MTB,and epigenetic regulation.Based on this knowledge,we summarize the current status and challenges in diagnosing LTBI and present the application of machine learning(ML)in LTBI diagnosis,as well as the advantages and limitations of ML in this context.Finally,we discuss the future development directions of ML applied to LTBI diagnosis.

Stochastic modeling and analysis of hepatitis and tuberculosis co-infection dynamics

Several mathematical models have been developed to investigate the dynamics of tuberculosis(TB)and hepatitis B virus(HBV).Numerous current models for TB,HBV,and their co-dynamics fall short in capturing the important and practical aspect of unpredictability.It is crucial to take into account a stochastic co-infection HBV–TB epidemic model since different random elements have a substantial impact on the overall dynamics of these diseases.We provide a novel stochastic co-model for TB and HBV in this study,and we establish criteria on the uniqueness and existence of a nonnegative global solution.We also looked at the persistence of the infections as long its dynamics are governable by the proposed model.To verify the theoretical conclusions,numerical simulations are presented keeping in view the associated analytical results.The infections are found to finally die out and go extinct with certainty when L´evy intensities surpass the specified thresholds and the related stochastic thresholds fall below unity.The findings also demonstrate the impact of noise on the decline in the co-circulation of HBV and TB in a given population.Our results provide insights into effective intervention strategies,ultimately aiming to improve the management and control of TB and HBV co-infections.

Surgical Management of Mitral Valve Infective Endocarditis with Accidental Finding of Open Pulmonary Tuberculosis

Objective: This case report aimed to highlight intersections of TB and Cardiovasular diseases which carry high morbidity and mortality rates. Methods: We are reporting the surgical management of forty seven years female who had back ground history of IDDM (Insulin dependent diabetic Mellitus), ESRD (End stage renal disease) on HD (haemodialysis) also she had left subclavian artery stenosis, and paroxysmal atrial fibrillation. She was diagnosed with mitral valve infective endocarditis and found accidently to have an open pulmonary tuberculosis (TB) on the day before surgery. Results: She was started on first line anti-TB treatment. She was isolated in her private room and airborne precautions measures applied. The patient underwent a tissue Mitral Valve replacement and tricuspid valve repair annuloplasty. Special precautions were applied in Theatre and on cardiopulmonary bypass Machine guided by KAMC-J disinfection protocol. The patient made good recovery postoperatively. She was discharged well on day 7 post operatively. Conclusion: Intersections of TB and cardiovasular diseases carry high morbidity and mortality rates. Early diagnosis and early anti tuberculosis treatment can surely improve the patient prognosis. Our decontamination and disinfective procedures are recommended. Cases like this should be monitored long term for the development of further cardiovascular complication.

Prospective study of SEVA TB peroxidase assay for cocktail antigen and antibody in the diagnosis of Tuberculosis in suspected patients attending a tertiary care hospital located in rural area

Objective:To evaluate inhouse developed SEVA TB peroxidase enzyme immunoassay using cocktail of mycobacterial excretory-secretory antigens(ES-31,ES-43 & EST-6) for antibody detection and their affinity purified antibodies for antigen detection in tuberculosis suspected patients.Methods:Inhouse developed SEVA TB peroxidase enzyme immunoassay was evaluated prospectively in 73 suspected pulmonary and 46 extra-pulmonary tuberculosis patients during November 2008~March 2009 in a tertiary hospital located in rural area.Results:Assay on prospective analysis showed 100% correlation of pulmonary tuberculosis(PTB) and extrapulmonary tuberculosis(EPTB) acid fast bacilli positivity and antitubercular treatment in 11 cases.Thirty nine PTB and 12 EPTB cases showed negative for EUSA test and were also not given antitubercular therapy.However 30 PTB and 27 EPTB cases showing ELISA positivity were neither acid fast bacilli positive nor antitubercular therapy treated.These cases may possibly have dormant infection and need further diagnosis.In EPTB cases ELISA was observed to be more useful than AFB smear test.Conclusions:This inhouse developed user-friendly peroxidase ELISA can be used as an adjunct test of smear microscopy or culture techniques for routine screening of patients suspected of PTB or EPTB.

Diagnostic Evaluation of GeneXpert MTB/RIF Assay for the Detection of Rifampicin Resistant Mycobacterium tuberculosis among Pulmonary Tuberculosis Patients in Bangladesh

Background: The emergence of multidrug resistant tuberculosis (MDR-TB) and extensively drug- resistant tuberculosis (XDR-TB) has highlighted the need for early accurate detection and drug susceptibility. Objective: The purpose of the present study was to evaluate the accuracy of GeneX-pert MTB/RIF assay for the detection of Mycobacterium tuberculosis and rifampicin resistance. Methodology: This cross sectional study was done in the Department of Microbiology at Sir Salimullah Medical College, Dhaka and National Institute of Chest Disease & Hospital (NIDCH), Dhaka during the period of January 2014 to December 2014 for a period of 1 (one) year. Sputum samples from suspected MDR-TB patients were collected by purposive sampling technique from OPD of Sir Salimullah Medical College (SSMC) and NIDCH. Microscopy, liquid culture in liquid MGIT 960 media and GeneXpert MTB/RIF were done for MTB diagnosis and detection of rifampicin resistance. MGIT 960 media were also used for determination of drug resistance. Result: Liquid culture yielded higher growth (68%) from 100 samples while GeneXpert MTB assay showed similar result (67% positive and 33% negative). Drug susceptibility test in MGIT 960 media showed that out of 68 positive cases Rifampicin resistant cases were 15 (22.05%) whereas GeneXpert MTB assay detected 14 (20.89%) were Rifampicin resistant out of 67 MTB positive samples. When compared to liquid culture the calculated sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV) and accuracy of GeneXpert MTB were 98.52%, 100%, 96.96%, 100% and 99%. Conclusion: GeneXpert MTB/RIF assay is high detection rate of pulmonary tuberculosis and multidrug resistant tuberculosis.

EGFR Mutation and FHIT Methylation: Inverse Relationship in Patients with Lung Adenocarcinoma and Tuberculosis

Objective:To investigate the genetic correlations between epithelial growth factor receptor(EGFR)mutation and FHIT methylation in patients diagnosed with lung adenocarcinoma(AC)and pulmonary tuberculosis(TB).Methods:The presence of EGFR mutations and the methylation status of the FHIT gene in patients presenting with AC and TB were analyzed.The correlation between TB status and the observed genetic and epigenetic variations was also examined.Results:Among the 90 patients included in the study,38 exhibited EGFR mutations(14 among those with TB and 24 among those without TB),while 29 exhibited FHIT myelination(19 among those with TB and 10 among those without TB).Furthermore,the protein expression levels of EGFR and FHIT were significantly higher in patients diagnosed solely with AC compared to those presenting with both AC and TB.A robust inverse correlation was identified between TB status and the frequency of EGFR mutation(P<0.001).Moreover,significant associations were observed between TB status and FHIT methylation(P<0.01).Conclusion:The findings suggest a correlation between TB and the prevalence of EGFR mutation and FHIT methylation in the pathogenesis of AC.

Candidate Vaccines against Tuberculosis and the Future of Novel TB Vaccine Research

Introduction: Tuberculosis (TB) continues to be a global health challenge and currently only one licensed vaccine is available. For nearly 100 years, the Bacillus Calmette-Guérin (BCG) vaccine has been in use. While it provides protection against disseminated TB in infants, its protection against adult and adolescent pulmonary tuberculosis (PTB) is variable. This literature review will provide an overview of the clinical status of candidate TB vaccines and discuss the challenges and future development trends of novel TB vaccine research, in combination with a general overview of the Tuberculosis (TB) disease and Mycobacterium tuberculosis itself. Methods: Bibliographic searches were carried out on medical journal databases, publishers, and aggregators. The most used databases were PubMed, NCBI and MDPI. Publications in English on these and other databases relating to novel TB vaccines were included in this review. Results: Currently, there are 12 main vaccine candidates in various phases of clinical trials, they include four protein or adjuvant vaccines, three viral-vectored vaccines, three mycobacterial whole cells or extract vaccines, and one each of the recombinant life and the attenuated Mycobacterium tuberculosis vaccine. Currently, the most likely candidate vaccines are the M72 + AS01E and Vaccae vaccines. M72 + AS01E is a recombinant fusion protein vaccine candidate, clinical trials showed that administering two doses of M72/AS01E was successful in reducing the development of active TB disease with 50% efficacy. Studies have also proven the efficacy of Vaccae (which is currently in phase III clinical trials) as an adjunctive therapy, with it being curative in conjunction with current therapy. Conclusion: Given the morbidity and mortality suffered globally by M. tuberculosis, it is time to realize the seriousness of the situation and accelerate our commitment and investment to the eradication of this infectious disease. With the number of vaccine candidates currently in clinical trials having promising results, it is imperative to continue these studies and accelerate towards phase III licensure trials if we are to achieve the milestone of “End TB Strategy” by 2035. Today, we are witnessing immense progress in both preclinical and clinical TB vaccine research despite disappointing results from some of the clinical efficacy trials like that of MVA85A. We can revisit the design of vaccines and learn from them. It is important not only to recognize and give credit to those that have tested well in human trials, such as M72 + AS01E, but to expedite and improve its efficacy through funding of its research.

Evaluation of Tuberculosis Treatment Outcome of TB/HIV Co-Infection: A Four-Year Retrospective Cohort Study in HIV-Prevalent Setting of North Central Nigeria

Background: Despite the availability of highly effective treatment for decades, Tuberculosis (TB) remains a major health problem in Nigeria due to the increasing association between HIV and TB observed over the past three decades when HIV was discovered. However, the proportion of TB and or TB/HIV co-infected patients who have successful TB treatment outcome is not well known. This study determined the treatment outcome of TB/HIV co-infected patients with HIV negative patients in two states in Nigeria. Materials and Methods: A retrospective study of secondary data from eight Directly Observed Treatment Short (DOTS) course and Anti- Retroviral Therapy (ART) service providers in Benue and Federal Capital Territory (FCT), Nigeria, was carried out. The period under review covers January, 2010 to December, 2013. Results: Out of the total 5266 TB cases reviewed, the HIV prevalence rate was 52%. They were predominantly (53.3%) male with mean age of 34.4 years (SD = 15.1 years). More than two-third (72.5%) of HIV-negative patients had successful treatment compared to 1718 (62.7%) HIV-positive patients. Of the 2334 HIV co-infected patients, 19.5% defaulted, 11.5% had died, 5.6% were transferred out and 0.7% failed treatment compared to HIV-negative patients amongst whom 18.3% defaulted, 3.6% died, 3.9% were transferred out and 1.6% failed treatment (p Conclusion: The favourable treatment outcome of HIV-negative patients is more than that of HIV-positive patients and the most probable predictable factor responsible is the CD4 count of patient;indicating that TB/HIV co-infection has remained a major public health problem in Benue state and FCT. Hence there is the need for sustained strengthening and expansion of the national TB/HIV programmes.

Identification, Synthesis, Isolation and Spectral Characterization of Multidrug-Resistant Tuberculosis (MDR-TB) Related Substances

Several related substances were detected at trace level in (2R)-2,3-dihydro-2-methyl-6-nitro-2-[[4-[4-[4-(trifluoromethoxy)phenoxy]-1-piperidinyl] phenoxy] methyl]imidazo[2, 1-b]oxazole drug substance by a newly developed high-performance liquid chromatography method. All related substances were characterized rapidly but some impurities were found to be intermediates. Proposed structures were further confirmed by characterization using NMR, FT-IR, and HRMS techniques. Based on the spectroscopic data;unknown related sub-stances were characterized as 1-(Methylsulfonyl)-4-[4-(trifluoromethoxy) phenoxy]piperidine;4-{4-[4-(Tri-fluoromethoxy)-phenoxy]piperidin-1-yl}phenol and 4-{4-[4-(trifluoromethoxy)phenoxy]piperidin-1-yl}phenyl methane sulfonate;4-Bromophenyl methane sulfonate, Ethyl 3,6-dihydro-1(2H)-pyridine carboxylate, (2S)-3-(4-Bromophenoxy)-2-hydroxy-2-methylpropyl methane sulfonate, (2S)-3-(4-Bromophenoxy)-2-methylpropane-1,2-diyldimethane-sulfonate, (2S)-2-Methyl-3-(4-{4-[4-(trifluoromethoxy) phenoxy]-piperidin-1-yl} phenoxy)-propane-1,2-diyldimethane sulfonate, (S)-3-(4-Bromophenoxy)-2-methyl-propane-1,2-diol and corresponding Enantiomer, (2R)-2-[(4-Bromo-phenoxy)methyl]-2-methyloxirane and (2R)-2-[(4-bromophenoxy)methyl]-2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b][1,3]oxazole. A possible mechanism for the formation of these related substances is also proposed.

“Kill-TB” Drug Reminder Mobile Application for Tuberculosis Patients at Bengaluru, India: Effectiveness and Challenges

Background: Tuberculosis remains a major public health problem in India. Newer digital technologies for treatment adherence have been tested for diseases with chronic medication. A mobile application (Kill-TB) that provides reminder to TB patients through alarm was tested for its effectiveness and challenges under programmatic settings. Methods: A cohort of TB patients initiated on treatment with and without mobile application at Bangalore city during January-March 2019 was observed for missed doses during their treatment period. Results: A total of 694 patients (347 patients with and without mobile application) were enrolled for the study. Among the patients with and without mobile application 1) loss to follow-up was 2% and 8%, 2) non-adherence rate to TB treatment was 1.5 and 3.3 per 100 person-months, 3) treatment success rate was 89% and 81%. Conclusion: The TB drug reminder mobile application benefits the patient’s treatment adherence and paves way for improved treatment outcomes despite the challenges in implementation. The programme should leverage mobile technologies as an additional monitoring tool to achieve the target of End-TB by 2025.

Clinical Performances of Pure TB-Lamp Kit for <i>M. tuberculosis</i>Complex Detection in Sputum Samples

Tuberculosis represents a main concern for public health worldwide. In poor countries, the most prevalent method for bacteriological confirmation re- mains Smear Sputum Microscopy (SSM). This study objective was to assess clinical performances of Loop Mediated Isothermal Amplification for TB detection (Lamp-TB). Sputum of patients presenting symptoms consistent with tuberculosis were collected according to the National Tuberculosis Control Programme guidelines in Centre Antituberculeux de Yopougon. SSM after Ziehl-Neelsen staining and TB-Lamp were blindly performed with spot sputum specimen. Samples, transported at Institut Pasteur de Cote d’Ivoire were decontaminated according to N-acetyl-L-cystein (NALC) method. In Mycobacteria Growth Indicator Tube (MGIT), 500 μl of pellet were inoculated and incubated in MGIT 960 instrument. MPT64 antigen was detected on positive culture. Of 500 patients enrolled, 469 were included. Clinical isolates of M. tuberculosis Complex were detected for 157 (33.5%). Comparatively to culture, Sensitivity and Specificity of SSM were 86% (95% Confidence interval (CI): 81% - 91%) 96% (95%IC: 94% - 98%) respectively. TB-Lamp Sensitivity was 92% (95%CI: 88% - 96%), and Specificity 94% (95%CI: 91% - 97%). Positive Predictive Value of SSM and TB-Lamp was 91.8% and 88.8% respectively. Negative Predictive Value of TB-Lamp assay was 95.7% whereas this of SSM was 93.3%. Positive Likelihood Ratio was 15.3 for TB-Lamp and 21.5 for SSM 21.5 whereas negative Likelihood of TB-Lamp was lower than SSM. Active tuberculosis was detected in162/469 (34.5%) with TB-Lamp and 147 (31.3%) with SSM. TB-Lamp assay performances estimated from sputum samples may improve detection of active TB cases in routine.

Onsite Performance Verification of DETERMINE^(TM) TB LAM Ag:A Rapid Diagnostic Test for Tuberculosis Screening in Urine

According to WHO, the rates of smear-negative and extra-pulmonary pulmonary tuberculosis are increasing in high prevalence HIV epidemic areas. Delays in diagnosis of tuberculosis can lead to large excess of mortality. It is extremely important to provide a strong diagnosis tool of tuberculosis if we want to reduce mortality due particularly to TB co-infection in HIV infected people in low-income countries such as Togo. This study aims to assess the performance of Determine? TB LAM Antigen, a rapid diagnostic test (RDT) for tuberculosis. It was an evaluation study, conducted at the National Reference Laboratory for Mycobacteria located at the Sylvanus Olympio University Teaching Hospital in Lomé, Togo from 01 July to 15 November 2017. We performed the assessment onto 100 urine specimens collected from 100 subjects (HIV-infected or not). The test allows qualitative detection of the Lipo Arabinno Mannan (LAM) antigen of Mycobacteria in the urine. Bacilloscopy was chosen as gold standard. Overall, the test Determine? TB LAM presented a sensitivity of 31.25% and a specificity of 95%. In contrast, the sensitivity and specificity of the test were respectively 82.35% and 66.67% in the group of HIV-infected subjects. In HIV non-infected subjects, the sensitivity was 17.46% and the specificity was 100%. Determine? TB LAM Antigen test can help detect TB in HIV-infected people unable to expectorate in our settings.

结核特异性QFT⁃TB在结核患者不同类型标本中的检测价值

目的比较结核诊断实验室特异性细胞免疫IGRAs体外检测QuantiFERON-TB Gold(QFTTB)方法对肺结核、肺外结核和特殊人群样本的诊断效能,为临床诊疗提供依据。方法收集2023年1-7月实验室检查细菌学检测结核患者546例[痰涂片阳性(AFB+)146例,痰涂片阳性(AFB-)247例],分子生物学阳性结核患者117例(Xpert 69例,TB-DNA 48例),病理组织学阳性患者36例。肺外结核患者72例,特殊样本胸水276例,腹水25例。采用QFT-TB方法进行检测,利用χ^(2)检验进行组间比较,对比其阳性率和符合率的方法学评估。结果肺结核、肺外结核和结核密切接触者QFT-TB检测阳性率为83.69%、69.44%和32.41%。在AFB+、GeneXpert、TB-DNA和病理证实确诊为结核病患者QFT-TB方法的符合率为91.09%、88.40%、81.25%和72.22%。结核性胸膜炎患者胸水检测阳性率为60.50%、腹水阳性率为44.00%。结论QFT-TB检测在辅助诊断肺结核有较好价值,对于基于胸、腹水的检测用于肺外结核的诊断有一定的参考意义。

Investigation of tuberculosis clusters in Dehradun city of India

Objective:To investigate the presence of statistically significant geographical clusters of tuberculosis(TB) using Geographical Information System and spatial scan statistics in Dehradun, India.Methods:The spatial scan statistic implemented with a software program,SaTScan v6.1, was used to test the presence of statistically significant spatial clusters of TB and to identify their approximate locations(P【0.05 for primary clusters and P【0.1 for secondary clusters). Geographical Information System was used for geographical analysis.Results:Significant high rate spatial clusters were identified in seven wards of the Dehradun Municipal area. Conclusions:There is sufficient evidence about the existence of statistically significant TB clusters in seven wards of Dehradun,India.The purely spatial scan statistics methodology used in this study has a potential use in surveillance of TB for detecting the true clusters of the disease.

Association of TNF-α-238G/A and 308 G/A Gene Polymorphisms with Pulmonary Tuberculosis among Patients with Coal Worker’s Pneumoconiosis

Objectives Tumor necrosis factor-α （TNF-α） may play an important role in host＇s immune response to mycobacterium tuberculosis （M. tuberculosis） infection. This study was to investigate the association of TNF-α gene polymorphism with pulmonary tuberculosis （TB） among patients with coal worker＇s pneumoconiosis （CWP）. Methods A case-control study was conducted in 113 patients with confirmed CWP complicated with pulmonary TB and 113 non-TB controls with CWP. They were matched in gender, age, job, and stage of pneumoconiosis. All participants were interviewed with questionnaires and their blood specimens were collected for genetic determination with informed consent. The TNF-α gene polymorphism was determined with polymerase chain reaction of restriction fragment length polymorphism （PCR-RFLP）. Frequency of genotypes was assessed for Hardy-Weinberg equilibrium by chi-square test or Fisher＇s exact probability. Factors influencing the association of individual susceptibility with pulmonary TB were evaluated with logistic regression analysis. Gene-environment interaction was evaluated by a multiplieative model with combined OR. All data were analyzed using SAS version 8.2 software. Results No significant difference in frequency of the TNF-α-308 genotype was found between CWP complicated with pulmonary TB and non-TB controls （2,2=5.44, P=-0.07）. But difference in frequency of the TNF-α-308 A allele was identified between them （2,2-5.14, P=0.02）. No significant difference in frequencies of the TNF-α-238 genotype and allele （P=0.23 and P=0.09, respectively） was found between cases and controls either, with combined （GG and AA） OR of 3.96 （95% confidence interval of 1.30-12.09） at the -308 locus of the TNF-α gene, as compared to combination of the TNF-α-238 GG and TNF-α-308 GG genotypes. Multivariate-adjusted odds ratio of the TNF-α-238 GG and TNF-α-308 GA genotypes was 1.98 （95% CI of 1.06-3.71） for risk for pulmonary TB in patients with CWP. There was a synergic interaction between the TNF-a-308 GG genotype and body mass index （OR=4.92）, as well as an interaction between the TNF-α-308 GG genotype and history of BCG immunization or history of TB exposure. And, the interaction of the TNF-α-238 GG genotype and history of BCG immunization or TB exposure with risk for pulmonary TB in them was also indicated. Conclusions TNF-α-308 A allele is associated with an elevated risk for pulmonary TB, whereas TNF-α-238 A allele was otherwise.

Tuberculosis in pregnancy—Diagnostic dilemma

The worldwide incidence of tuberculosis (TB) is rising and is linked to immigration patterns and the rise in incidence of HIV. Extra-pulmonary disease, in particular, can lead to diagnostic dilemmas. Because the total number of cases of TB in pregnancy in developed countries is small and often concentrated in specific urban areas with large immigrant populations, clinicians may rarely encounter the problem. This paper provides actual clinical experience of one recent case.

Serum IL-1β and IL-18 correlate with ESR and CRP in multidrug-resistant tuberculosis patients

Dear Editor： The emergence of multidrug-resistant tuberculosis （MDR-TB） is bringing new challenges. MDR-TB is caused by Mycobacterium tuberculosis （M. tuberculosis） that is resistant to isoniazid and rifampicin, with or with- out resistance to other anti-tuberculosis drugs. Approximately 450,000 people developed MDR-TB worldwide in 2012 and an estimated 170,000 people died from the disease. Bacterial burden is not strictly corre- lated with disease progression, and several hallmarks of severe tuberculosis suggest that insufficiently controlled inflammation plays an important role in pathogenesis.