scholarly journals Genetic Diversity of IFγ, IL1β, TLR2, and TLR8 Loci in Pulmonary Tuberculosis in Kazakhstan

Author(s):  
Dauren Yerezhepov ◽  
Axat Zhabagin ◽  
Ayken Askapuli ◽  
Saule Rakhimova ◽  
Zhannur Nurkina ◽  
...  

Introduction. Tuberculosis (TB) is caused by bacterium Mycobacterium tuberculosis (MTB), and according to the WHO, up to 30% of world population is infected with latent TB. Pathogenesis of TB is multifactorial, and its development depends on environmental, social, microbial, and genetic factors of both the bacterium and the host. The number of TB cases in Kazakhstan has decreased in the past decade, but multidrug-resistant (MDR) TB cases are dramatically increasing. Polymorphisms in genes responsible for immune response have been associated with TB susceptibility. The objective of this study was to investigate the risk of developing pulmonary TB (PTB) associated with polymorphisms in several inflammatory pathway genes among Kazakhstani population.Methods. 703 participants from 3 regions of Kazakhstan were recruited for a case-control study. 251 participants had pulmonary TB (PTB), and 452 were healthy controls (HC). Males and females represented 42.39% and 57.61%, respectively. Of all participants, 67.4% were Kazakhs, 22.8% Russians, 3.4% Ukrainians, and 6.4% were of other origins. Clinical and epidemiological data were collected from medical records, interviews, and questionnaires. DNA samples were genotyped using TaqMan assay on 4 polymorphisms: IFNγ (rs2430561) and IL1β (rs16944), TLR2 (rs5743708) and TLR8 (rs3764880). Statistical data was analyzed using SPSS 19.Results. Genotyping by IFγ, IL1β, TLR2 showed no significant association with PTB susceptibility (p > 0.05). TLR8 genotype A/G was significantly higher in females (F/M – 41.5%/1.3%) and G/G in males (M/F – 49%/20.7%) (χ2=161.43, p < 0.001). A significantly increased risk of PTB development was observed for TLR A/G with an adjusted OR of 1.48 (95%, CI: 0.96 - 2.28), and a protective feature was revealed for TLR8 G/G genotype (OR: 0.81, 95%, CI: 0.56 - 1.16, p = 0.024). Additional grouping by gender revealed that TLR8 G/G contributes as protective genotype (OR: 1.83, 95%, CI: 1.18 - 2.83, p = 0.036) in males of the control group.Conclusion. Results indicate that heterozygous genotype A/G of TLR8 increases the risk of PTB development, while G/G genotype may serve as protection mechanism. A/A genotype is strongly associated with susceptibility to PTB. To clarify the role of other polymorphisms in susceptibility to PTB in Kazakhstani population, further investigations are needed. 

2021 ◽  
Vol 3 (2) ◽  
Author(s):  
Mareta Dea Rosaline ◽  
Santi Herlina

Tuberculosis control in Indonesia is still not optimal. The problem of MDR TB (Multidrug-Resistant Tuberculosis) is an obstacle to controlling TB in Indonesia. MDR TB is caused by no response from TB germs to treatment isoniazid and rifampicin, anti-tuberculosis drugs. TB incidence rate in Serang district ranks second in Banten Province after Tangerang. The number of pulmonary TB cases is due to the lack of public knowledge and awareness about pulmonary TB disease. To reduce the adverse effects of MDR TB requires the involvement of cadres or family members who controlling drug ingestion (PMO). The form of activities carried out through the formation of cadres to care for TB through the KAMI-PMO TB (Education and Assistance for TB Medication Supervisors) in Desa Baros, Kabupaten Serang. The purpose is to increase the commitment, ability, and knowledge of cadres as coordinator of PMO (Drug Swallow Supervisor) to control MDR TB. The method of implementing activities is counseling, demonstrations, and assistance to cadres. The media used were PPT, WE-PMO TB Booklet, and educational videos. The result of the training was an increase in the ability of cadres in providing PMO counseling by 87%. The Paired T-Test analysis results showed a p-value of 0.000, which means that the training conducted affected cadres' knowledge of PMO TB. In conclusion, education and assistance to cadres have a good influence in increasing knowledge and abilities. The expected result is TB care cadres can provide aid and become the coordinator of TB PMO (Drug Ingestion Supervisor).  ABSTRAK:Pengendalian Tuberculosi di Indonesia masih belum optimal.Permasalahan MDR TB (Multidrug Resistant Tuberculosis) merupakan hambatan pengendalian TB di Indonesia. MDR TB disebabkan tidak ada respon kuman TB terhadap pengobatan isoniazid dan rifampizin yang merupakan obat anti tuberculosis. Angka kejadian TB di kabupaten Serang menempati urutan kedua di Provinsi Banten setelah Tangerang, dan banyaknya kasus TB Paru dikarenakan pengetahuan dan kesadaran masyarakat tentang penyakit TB Paru masih kurang. Untuk mengurangi dampak buruk MDR TB dibutuhkan keterlibatan peran serta kader peduli TB atau anggota keluarga yang berperan dalam pengawasan menelan obat (PMO). Bentuk kegiatan yang dilakukan sebagai bentuk pemberdayaan masyarakat melalui pembentukan kader peduli TB  melalui KAMI-PMO TB (Edukasi dan Pendampinga Pengawas Menelan Obat TB) di Desa Baros Kabupaten Serang. Tujuan dari pengabdian masyarakat adalah meningkatkan komitmen, kemampuan dan pengetahuan kader sebagai koordinator PMO (Pengawas Menelan Obat) dalam upaya pengendalian MDR TB. Metode pelaksanaan kegiatan adalah penyuluhan, demontrasi, dan pendampingan kader. Media yang digunakan yaitu PPT, Booklet KAMI-PMO TB , dan video edukasi. Hasil dari kegiatan adalah meningkatnya kemampuan kader dalam memberikan penyuluhan PMO cukup tinggi sebesar 87%. Hasil analisis uji Paired T- Test didapatkan nilai p value 0,000 yang artinya ada pengaruh pelatihan yang dilakukan terhadap pengetahuan kader tentang PMO TB. Kesimpulannya edukasi dan pendampingan kepada kader memiliki pengaruh yang baik  dalam meningkatkan pengetahuan dan kemampuan, sehingga hasil yang diharapkan kader peduli TB dapat melakukan pendampingan pada pasien TB dan menjadi koordinator PMO (Pengawas Menelan Obat) TB dalam upaya pengendalian MDR TB


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Peng Wen ◽  
Min Wei ◽  
Chao Han ◽  
Yu He ◽  
Mao-Shui Wang

AbstractTuberculous empyema (TE) is associated with high mortality and morbidity. In the retrospective cohort study, we aimed to find risk factors for TE among pleural tuberculosis (TB) patients. Between July 2011 and September 2015, all culture-confirmed pleural TB patients (474 cases) were enrolled in our study. Empyema was defined as grossly purulent pleural fluid. Demographic and epidemiological data were collected for further analysis. Multivariate logistic regression analysis was used to evaluate risk factors of TE in pleural TB, age–adjusted odds ratio (OR) and 95% confidence interval (CI) were calculated to show the risk. The mean age was 35.7 ± 18.1 years old, males comprised 79.1% of the participants (375 cases). Forty-seven patients (9.9%) were multidrug-resistant TB (MDR-TB), 29 (6.1%) had retreatment TB, 26 (5.5%) had diabetes mellitus. The percentage of empyema patients was 8.9% (42 cases). Multivariate analysis revealed that male (adjusted OR = 4.431, 95% CI: 1.411, 13.919), pleural adenosine deaminase (ADA, >88 U/L) (adjusted OR = 3.367, 95% CI: 1.533, 7.395) and white blood cell (WBC, >9.52 109/L) (adjusted OR = 5.763, 95% CI: 2.473, 13.431) were significant risk factors for empyema in pleural TB, while pulmonary TB (adjusted OR = 0.155, 95% CI: 0.072, 0.336) was the protective factor for the patients. TE remains a serious threat to public health in China. Male sex is a significant risk factor for TE while the presence of pulmonary TB is protective, and high levels of pleural ADA and WBC count could aid in early diagnosis of TE. This finding would help towards reducing the mortality and morbidity associated with TE.


2021 ◽  
Author(s):  
Qi Jiang ◽  
Hai-can Liu ◽  
Qing-yun Liu ◽  
Jody E. Phelan ◽  
Li Shi ◽  
...  

ABSTRACTObjectiveTibet has the highest prevalence of both tuberculosis disease and multidrug-resistant tuberculosis (MDR-TB) in China. The circulated Mycobacterium tuberculosis strains from Tibet were sequenced to investigate the underlying drivers for the high burden of MDR-TB.MethodsUsing whole-genome sequencing data of 576 M. tuberculosis strains isolated from consecutive patients in Tibet, we mapped resistance-conferring mutations onto phylogenetic trees to determine their evolution and spread. The impact of drug resistance on bacterial population growth was assessed with a Bayesian (Skyline Plot) analysis. Multivariable logistic regression was used to identify risk factors for the development of rifampicin resistance.ResultsOf the 576 isolates, 284 (49.3%), 280 (48.6%), and 236 (41.0%) were, respectively, genetically resistant to isoniazid, rifampicin, or both (MDR-TB). Among the isoniazid- and rifampicin-resistant strains, the proportions in phylogenetically-inferred clusters were 77.8% (221/284) and 62.1% (174/280), respectively. Nearly half (47.2%, 134/284) of the isoniazid-resistant strains were in six major clades, which contained between 8 and 58 strains with katG S315T, katG S315N, or fabG1 promoter −15 C>T resistance mutations. These major clades exponentially expanded after emerging with isoniazid resistance and stabilized before evolving into MDR-TB twenty years later. Isoniazid-resistant isolates showed an increased risk of accumulating rifampicin resistance compared to isoniazid-susceptible strains, with an adjusted odds ratio of 3.81 (95% confidence interval 2.47-5.95).ConclusionHistorical expansion of isoniazid-resistant strains and their increased likelihood of acquiring rifampicin resistance both contributed to the high burden of MDR-TB in Tibet, highlighting the need to detect INH-resistant strains promptly and to control their transmission.


2017 ◽  
Vol 21 (12) ◽  
pp. 1245-1250 ◽  
Author(s):  
E. L. Sagwa ◽  
N. Ruswa ◽  
F. Mavhunga ◽  
T. Rennie ◽  
A. Mengistu ◽  
...  

SETTING: To compare renal insufficiency among multidrug-resistant tuberculosis (MDR-TB) patients treated with kanamycin (KM) based regimens and those treated concomitantly with tenofovir disoproxil fumarate (TDF) or other antiretroviral therapy (ART) regimens in Namibia.DESIGN: Retrospective review of the treatment records and laboratory tests of patients initiated on MDR-TB treatment (January–December 2014). The glomerular filtration rates (eGFR) estimated pre- and post-treatment were compared using the analysis of variance test. Renal insufficiency was defined as an eGFR of <60 ml/min/1.73 m2. Use of KM or TDF and association with renal insufficiency was assessed using Kaplan-Meier plots and Cox proportional hazards analysis.RESULTS: The baseline mean eGFR for the three groups was similar (P = 0.24): 139.3 ± 25.6 ml/min for the KM group (n = 68), 131.1 ± 25.7 ml/min for the KM+TDF group (n = 44) and 134.2±34.4 ml/min for the KM+Other group (n = 23). After 8 months, the values had declined significantly to respectively 104.8 ± 37.5 ml/min (P < 0.001), 101.5 ± 38.3 ml/min (P < 0.001) and 111.5 ± 41.7 ml/min (P = 0.01). Co-treatment with KM+ART was associated with an increased risk of renal insufficiency (hazard ratio [HR] 1.8, 95%CI 0.7–4.1, P = 0.20 for KM+TDF, and HR 3.5, 95%CI 1.4–8.2, P = 0.005 for KM+Other ART).CONCLUSION: Renal function declined at a similar rate in MDR-TB patients treated with KM-based regimens compared with patients treated concomitantly with TDF-based or other ART. The risk of renal insufficiency was greater for patients on ART.


2020 ◽  
Vol 71 (10) ◽  
pp. e532-e539 ◽  
Author(s):  
Vijay Srinivasan ◽  
Vu T N Ha ◽  
Dao N Vinh ◽  
Phan V K Thai ◽  
Dang T M Ha ◽  
...  

Abstract Background Meta-analysis of patients with isoniazid-resistant tuberculosis (TB) given standard first-line anti-TB treatment indicated an increased risk of multidrug-resistant TB (MDR-TB) emerging (8%), compared to drug-sensitive TB (0.3%). Here we use whole genome sequencing (WGS) to investigate whether treatment of patients with preexisting isoniazid-resistant disease with first-line anti-TB therapy risks selecting for rifampicin resistance, and hence MDR-TB. Methods Patients with isoniazid-resistant pulmonary TB were recruited and followed up for 24 months. Drug susceptibility testing was performed by microscopic observation drug susceptibility assay, mycobacterial growth indicator tube, and by WGS on isolates at first presentation and in the case of re-presentation. Where MDR-TB was diagnosed, WGS was used to determine the genomic relatedness between initial and subsequent isolates. De novo emergence of MDR-TB was assumed where the genomic distance was 5 or fewer single-nucleotide polymorphisms (SNPs), whereas reinfection with a different MDR-TB strain was assumed where the distance was 10 or more SNPs. Results Two hundred thirty-nine patients with isoniazid-resistant pulmonary TB were recruited. Fourteen (14/239 [5.9%]) patients were diagnosed with a second episode of TB that was multidrug resistant. Six (6/239 [2.5%]) were identified as having evolved MDR-TB de novo and 6 as having been reinfected with a different strain. In 2 cases, the genomic distance was between 5 and 10 SNPs and therefore indeterminate. Conclusions In isoniazid-resistant TB, de novo emergence and reinfection of MDR-TB strains equally contributed to MDR development. Early diagnosis and optimal treatment of isoniazid-resistant TB are urgently needed to avert the de novo emergence of MDR-TB during treatment.


2021 ◽  
Vol 5 (10) ◽  
pp. 903-910
Author(s):  
Ricky Septafianty ◽  
Anita Widyoningroem ◽  
M. Yamin S. S ◽  
Rosy Setiawati ◽  
Soedarsono

Introduction: Radiological imaging has a key role in multidrug-resistant (MDR) pulmonary tuberculosis (TB) screening and diagnosis. However, new cases of MDR pulmonary TB are often overlooked; therefore, its transmission might continue before its diagnosis. The most widely used and affordable radiological modality is a chest radiograph. This study aims to describe the characteristics of primary and secondary MDR pulmonary TB chest x-ray findings for differential diagnosis. Methods: This study was an analytic observational study with a retrospective design. Researchers evaluated medical record data of primary and secondary MDR pulmonary TB patients who underwent chest x-ray examinations. The patient's chest x-rays were then evaluated. Evaluated variables were lung, pleural, and mediastinal abnormalities and severity category. Results: The most common chest x-ray finding in primary MDR pulmonary TB was consolidation (96.2%), which was mostly unilateral (52.0%), accompanied by cavities (71.2%), most of which were multiple (83.8%) with a moderate category of severity. The most common chest x-ray finding in secondary MDR pulmonary TB was consolidation (100%), which was mostly bilateral (60.4%), accompanied by cavities (80.2%), most of which were multiple (90.1%) with severe category of severity. Pleural thickening (47.5%) was also found. Conclusion: There was a significant difference between primary and secondary MDR pulmonary TB in terms of mild severity category, and pleural thickening. Mild severity category is mostly found in primary MDR-TB and pleural thickening is mostly found in secondary TB.


2020 ◽  
Vol 24 (1) ◽  
pp. 65-72 ◽  
Author(s):  
H. Hong ◽  
D. W. Dowdy ◽  
K. E. Dooley ◽  
H. W. Francis ◽  
C. Budhathoki ◽  
...  

SETTING: The ototoxic effects of aminoglycosides (AGs) lead to permanent hearing loss, which is one of the devastating consequences of multidrug-resistant tuberculosis (MDR-TB) treatment. As AG ototoxicity is dose-dependent, the impact of a surrogate measure of AG exposure on AG-induced hearing loss warrants close attention for settings with limited therapeutic drug monitoring.OBJECTIVE: To explore the prognostic impact of cumulative AG dose on AG ototoxicity in patients following initiation of AG-containing treatment for MDR-TB.DESIGN: This prospective cohort study was nested within an ongoing cluster-randomized trial of nurse case management intervention across 10 MDR-TB hospitals in South Africa.RESULTS: The adjusted hazard of AG regimen modification due to ototoxicity in the high-dose group (≥75 mg/kg/week) was 1.33 times higher than in the low-dose group (<75 mg/kg/week, 95%CI 1.09–1.64). The adjusted hazard of developing audiometric hearing loss was 1.34 times higher than in the low-dose group (95%CI 1.01–1.77). Pre-existing hearing loss (adjusted hazard ratio [aHR] 1.71, 95%CI 1.29–2.26) and age (aHR 1.16 per 10 years of age, 95%CI 1.01–1.33) were also associated with an increased risk of hearing loss.CONCLUSION: MDR-TB patients with high AG dose, advanced age and pre-existing hearing loss have a significantly higher risk of AG-induced hearing loss. Those at high risk may be candidates for more frequent monitoring or AG-sparing regimens.


2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S277-S278
Author(s):  
Tenzin Desel ◽  
Naonori Tsuda ◽  
Tenzin Tsundue ◽  
Rangjung Lingtsang ◽  
Sonam Topgyal ◽  
...  

Abstract Background Globally, refugee populations face an increased risk for tuberculosis (TB) due to malnutrition, overcrowding, and poor living conditions. Compared with the general Indian population, Tibetan refugees in India display a higher incidence rate of both TB and multidrug-resistant TB (MDR-TB). The high incidence of MDR-TB in younger population is a serious public health concern. Methods We retrospectively reviewed the medical records of patients with MDR-TB treated from January 2010 to December 2013 in Tibetan Delek Hospital, which is the center of TB control among Tibetan refugees. Patients were classified into either new cases (supposed infection by exposure to MDR-TB) or previously treated MDR-TB cases (suspected acquirement of MDR-TB through anti-TB treatment or by MDR-TB exposure after treatment). We compared patients’ age, sex, birthplace, residence type, occupation, contact history, and treatment outcome. Results Of 749 patients with TB, we enrolled 134 patients with MDR-TB [median age, 26 (interquartile range: 22–35) years; males, 55%]. The Tibetan ethnicity comprised 96% of the study population, whereas Indians (trans-Himalayan) comprised 4%. The birthplace was Tibet for 22% patients, India for 75%, and Nepal for 2%. New MDR-TB cases were 28% and previously treated MDR-TB cases were 72%. Failure was observed in 42% patients and cured and completed in 54% patients, during their previous TB treatment. The median age was significantly lower in new cases than in previously treated MDR-TB cases (24 vs. 28.5 years; P &lt; 0.01). Tibet was the birthplace of 34% new cases and 18% in previously treated cases (P = 0.04). The residence was of the congregated type in 58% of new cases and 30% in previously treated MDR-TB cases (P = 0.01). The occupation was “student” and “unemployed” in 58% and 8% in new cases and 33% and 24% in previously treated cases, respectively (P = 0.03). Contact history with TB type and treatment outcome were not considerably different, although the rates of cured and completed were high in both new (82%) and previously treated (84%) MDR-TB cases. Conclusion This study shows that new MDR-TB correlates with younger age, birth in Tibet, congregated residence, and student occupation. Targeting the above-listed characteristics could be effective in further reducing the MDR-TB transmission among Tibetan refugees in India. Disclosures All authors: No reported disclosures.


2016 ◽  
Vol 3 (3) ◽  
Author(s):  
Argita D. Salindri ◽  
Maia Kipiani ◽  
Russell R. Kempker ◽  
Neel R. Gandhi ◽  
Lasha Darchia ◽  
...  

Abstract Background.  Diabetes is a risk factor for active tuberculosis (TB), but little is known about the relationship between diabetes and multidrug-resistant (MDR) TB. We aimed to assess risk factors for primary MDR TB, including diabetes, and determine whether diabetes reduced the rate of sputum culture conversion among patients with MDR TB. Methods.  From 2011 to 2014, we conducted a cohort study at the National Center for Tuberculosis and Lung Diseases in Tbilisi, Georgia. Adult (≥35 years) patients with primary TB were eligible. Multidrug-resistant TB was defined as resistance to at least rifampicin and isoniazid. Patients with capillary glycosylated hemoglobin (HbA1c) ≥ 6.5% or previous diagnosis were defined to have diabetes. Polytomous regression was used to estimate the association of patient characteristics with drug resistance. Cox regression was used to compare rates of sputum culture conversion in patients with and without diabetes. Results.  Among 318 patients with TB, 268 had drug-susceptibility test (DST) results. Among patients with DST results, 19.4% (52 of 268) had primary MDR TB and 13.4% (36 of 268) had diabetes. In multivariable analyses, diabetes (adjusted odds ratio [aOR], 2.51; 95% confidence interval [CI], 1.00–6.31) and lower socioeconomic status (aOR, 3.51; 95% CI, 1.56–8.20) were associated with primary MDR TB. Among patients with primary MDR TB, 44 (84.6%) converted sputum cultures to negative. The rate of sputum culture conversion was lower among patients with diabetes (adjusted hazard ratio [aHR], 0.34; 95% CI, .13–.87) and among smokers (aHR, 0.16; 95% CI, .04–.61). Conclusions.  We found diabetes was associated with an increased risk of primary MDR TB; both diabetes and smoking were associated with a longer time to sputum culture conversion.


Author(s):  
Gyanshankar Mishra ◽  
◽  
Neha Pachbhai ◽  

Cancer patients are at an increased risk of developing active Tuberculosis (TB) disease. Immunosuppression because of cancer or its treatment modalities, including chemo-radiotherapy, places these patients at an increased risk of developing active TB. We describe the case of a fifty-eight-year-old male patient who was diagnosed and treated for carcinoma larynx but later succumbed to pulmonary TB. Active screening and treatment for Latent TB Infection (LTBI) at the start of cancer treatment in these patients may potentially help reduce the reactivation risk of active TB disease among them. Keywords: tuberculosis; TB; cancer; malignancy; mortality; LTBI; chemo-radiotherapy


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