Delayed Sputum Conversion Research Articles

A study on factors influencing delayed sputum conversion in newly diagnosed pulmonary tuberculosis based on bacteriology and genomics

Conversion of sputum from positive to negative is one of the indicators to evaluate the efficacy of anti-tuberculosis treatment (ATT). We investigate the factors associated with delayed sputum conversion after 2 or 5 months of ATT from the perspectives of bacteriology and genomics. A retrospective study of sputum conversion in sputum positive 1782 pulmonary tuberculosis (PTB) was conducted from 2021 to 2022 in Beijing, China. We also designed a case-matched study including 24 pairs of delayed-sputum-conversion patients (DSCPs) and timely-sputum-conversion patients (TSCPs), and collect clinical isolates from DSCPs before and after ATT and initial isolates of TSCPs who successfully achieved sputum conversion to negative after 2 months of ATT. A total of 75 strains were conducted drug sensitivity testing (DST) of 13 anti-TB drugs and whole-genome sequencing (WGS) to analyze the risk factors of delayed conversion and the dynamics changes of drug resistance and genomics of Mycobacterium tuberculosis (MTB) during ATT. We found TSCPs have better treatment outcomes and whose initial isolates show lower levels of drug resistance. Clinical isolates of DSCPs showed dynamically changing of resistance phenotypes and intra-host heterogeneity. Single nucleotide polymorphism (SNP) profiles showed large differences between groups. The study provided insight into the bacteriological and genomic variation of delayed sputum conversion. It would be helpful for early indication of sputum conversion and guidance on ATT.

A time-to-event modelling of sputum conversion within two months after antituberculosis initiation among drug-susceptible smear positive pulmonary tuberculosis patients: Implementation of internal and external validation

Delayed sputum conversion has been associated with a higher risk of treatment failure or relapse among drug susceptible smear-positive pulmonary tuberculosis patients. Several contributing factors have been identified in many studies, but the results varied across regions and countries. Therefore, the current study aimed to develop a predictive model that explained the factors affecting time to sputum conversion within two months after initiating antituberculosis agents among Malaysian with drug-susceptible smear-positive pulmonary tuberculosis patients. Retrospective data of pulmonary tuberculosis patients followed up at a tertiary hospital in the Northern region of Malaysia from 2013 until 2018 were collected and analysed. Nonlinear mixed-effect modelling software (NONMEM 7.3.0) was used to develop parametric survival models. The final model was further validated using Kaplan-Meier-visual predictive check (KM-VPC) approach, kernel-based hazard rate estimation method and sampling-importance resampling (SIR) method. A total of 224 patients were included in the study, with 34.4 % (77/224) of the patients remained positive at the end of 2 months of the intensive phase. Gompertz hazard function best described the data. The hazard of sputum conversion decreased by 39 % and 33 % for moderate and advanced lesions as compared to minimal baseline of chest X-ray severity, respectively (adjusted hazard ratio (aHR), 0.61; 95 % confidence intervals (95 % CI), (0.44–0.84) and 0.67, 95 % CI (0.53–0.84)). Meanwhile, the hazard also decreased by 59 % (aHR, 0.41; 95 % CI, (0.23–0.73)) and 48 % (aHR, 0.52; 95 % CI, (0.35–0.79)) between active and former drug abusers as compared to non-drug abuser, respectively. The successful development of the internally and externally validated final model allows a better estimation of the time to sputum conversion and provides a better understanding of the relationship with its predictors.

IJCM_276A: Determinants of Delayed Sputum Conversion among Tuberculosis Patients in Malappuram District: A Case Control Study

Background: Treatment of drug-sensitive TB consists of an intensive phase of 2 months followed by a continuation phase of 4 months. After completion of intensive phase of therapy, sputum AFB smear microscopy is repeated and presence of smear conversion is suggested as a significant early predictor of treatment effectiveness. Delay in sputum conversion will lead to prolongation of the period of time that patients remain contagious. Objectives: To study the determinants of delayed sputum conversion among Tuberculosis patients in Malappuram district Methodology: A Case control study was conducted among tuberculosis patients residing in Malappuram district of Kerala and registered under NTEP in District Tuberculosis Centre (DTC), Manjeri, Malappuram. After satisfying inclusion and exclusion criteria, 90 tuberculosis patients who failed to achieve sputum smear negativity after completion of 2 months of intensive phase multi drug therapy were taken as cases. Another 90 tuberculosis patients those who achieved sputum smear negativity after completion of 2 months of intensive phase therapy were selected as control group. Data was collected by interview method. Results: Patients with lower socio-economic status (OR = 3.59, 95% CI 1.92- 6.73), low BMI or underweight (OR = 1.98, 95% CI 1.1 - 3.6), multiple symptoms (OR= 5.50, 95% CI 1.98 - 15.28), increased duration of symptoms (OR=4.54, 95% 2.24-9.19), co-morbid condition of diabetes mellitus (OR = 2.25, 95% CI 1.24 - 4.09) are at statistically significant risk of delay in sputum smear conversion after intensive phase of anti-tubercular therapy. Conclusion: Patients with lower socio-economic status, low BMI or underweight, multiple symptoms, increased duration of symptoms, co-morbid condition of diabetes mellitus are at statistically significant risk of delay in sputum smear conversion after intensive phase of anti-tubercular therapy. Treating physicians and public health experts should give special attention to TB patients with these risk factors.

Immune-endocrine network in diabetes-tuberculosis nexus: does latent tuberculosis infection confer protection against meta-inflammation and insulin resistance?

Tuberculosis patients with diabetes, have higher sputum bacillary load, delayed sputum conversion, higher rates of drug resistance, higher lung cavitary involvement and extra-pulmonary TB infection, which is called as "Diabetes-Tuberculosis Nexus". However, recently we have shown a reciprocal relationship between latent tuberculosis infection and insulin resistance, which has not been reported before. In this review, we would first discuss about the immune-endocrine network, which operates during pre-diabetes and incipient diabetes and how it confers protection against LTBI. The ability of IR to augment anti-TB immunity and the immunomodulatory effect of LTBI to quench IR were discussed, under IR-LTB antagonism. The ability of diabetes to impair anti-TB immunity and ability of active TB to worsen glycemic control, were discussed under "Diabetes-Tuberculosis Synergy". The concept of "Fighter Genes" and how they confer protection against TB but susceptibility to IR was elaborated. Finally, we conclude with an evolutionary perspective about how IR and LTBI co-evolved in endemic zones, and have explained the molecular basis of "IR-LTB" Antagonism" and "DM-TB Synergy", from an evolutionary perspective.

Risk factors for delayed sputum conversion: A qualitative case study from the person-in-charge of TB program's perspectives.

One of the indicators to determine the success of TB treatment is the conversion of sputum from smear positive to negative. However, several factors can lead to this failure of sputum conversion. To investigate the risk factors for delayed sputum conversion from the person-in-charge (PIC) of the TB program's perspective. This qualitative case study was conducted on September 7th, 2022. Thirty-one PICs of the TB program from 31 public health centers (Puskesmas) in Bandar Lampung, Indonesia, were recruited purposively. All participants were grouped into three FGDs. Developed semi-structured interview questions were used for data collection. Thematic analysis was used to synthesize and cross-reference emerging topics. Three themes emerged in our study: (1) individual factors with the sub-themes of medication adherence, education, initial laboratory examination, comorbid disease, nutrition, and lifestyle; (2) environmental factors with the sub-themes of types of support, sources of support, environmental conditions and stigma; and (3) health service factors with the sub-theme of access to health service facilities. Problems related to TB management are not only the individual's responsibility but need to strengthen support from the environment and health services.

Glycemic Control Effect on Acid-Fast Bacteria Conversion in Diabetic Patients with Tuberculosis

Background Diabetic people have a 2-3 times higher risk of tuberculosis than non-diabetic people. Immunocompromised conditions due to diabetes increase the risk of therapeutic failure and delayed sputum conversion, which may cause by poor glycemic control. This study was conducted to determine the glycemic control effect on AFB conversion in diabetic patients with tuberculosis. Methods A cross-sectional study has been conducted on 100 diabetic patients with the new emergence of pulmonary tuberculosis. All patients were in intensive phase treatment of tuberculosis for two months at Bhayangkara R. Said Sukanto's Hospital. Data collected from medical records were random blood glucose level, percentage of random blood glucose decrement, HbA1C, and the microscopic AFB sputum smear. Fisher exact test analysis was conducted to determine the effect of random blood glucose level, percentage of blood glucose decrement and HbA1C to AFB smear results using SPSS V25.0 software for Windows with a significance level of 0.05. Results The analysis between glycemic control and AFB sputum smear conversion using random blood glucose, percentage of random blood glucose decrement and HbA1C showed a p-value of 0.000, indicating a significant relationship (p<0.05), so it showed that glycemic control affects AFB sputum smear conversion. Conclusions A significant relationship exists between glycemic control and AFB-negative conversion in patients with DM and TB. RBG showed the best sensitivity and specificity as a glycemic control parameter compared to others.

Prevalence and associated factors of delayed sputum smear conversion in patients treated for smear positive pulmonary tuberculosis: A retrospective follow up study in Sabah, Malaysia.

Tuberculosis remains a major health problem globally and in Malaysia, particularly in the state of Sabah. Delayed sputum conversion is associated with treatment failure, drug-resistant tuberculosis and mortality. We aimed to determine the prevalence of delayed sputum conversion among smear positive pulmonary tuberculosis (PTB) patients and its associated factors in Sabah, Malaysia. A retrospective follow up study on all patients newly diagnosed with smear positive pulmonary tuberculosis from 2017 to 2019 was conducted at three government health clinics in Sabah, utilizing data from a national electronic tuberculosis database and medical records. Descriptive statistics and binary logistic regression were applied for data analysis. The outcome of the study was the sputum conversion status at the end of the two-month intensive treatment phase with either successful conversion to smear negative or non-conversion. 374 patients were included in the analysis. Our patients were generally younger than 60 years old with no medical illness and varying proportions of tuberculosis severity as judged by radiographic appearance and sputum bacillary load upon diagnosis. Foreigners constituted 27.8% of our sample. 8.8% (confidence interval: 6.2-12.2) did not convert to smear negative at the end of the intensive phase. Binary logistic regression showed that older patients ≥60 years old (adjusted odds ratio, AOR = 4.303), foreigners (AOR = 3.184) and patients with higher sputum bacillary load at diagnosis [2+ (AOR = 5.061) and 3+ (AOR = 4.992)] were more likely to have delayed sputum smear conversion. The prevalence of delayed sputum conversion in our study was considerably low at 8.8% with age ≥60 years old, foreigners and higher pre-treatment sputum bacillary load associated with delayed conversion. Healthcare providers should take note of these factors and ensure the patients receive proper follow up treatment.

Impact of anemia on sputum smear conversion and treatment outcomes among newly diagnosed tuberculosis patients in Southern India.

Tuberculosis (TB) is a leading cause of mortality worldwide. The higher prevalence of anemia among TB patients is concerning due to its association with delayed sputum conversion and poor treatment outcomes. The present study aimed to evaluate the association of anemia with sputum smear conversion and treatment outcomes among TB patients. In a prospective community-based cohort study, TB patients were recruited from 63 primary health centers in the district. Blood samples were collected at baseline, at 2 months, and at the end of 6 months. Data were analyzed using SPSS software version 15. Out of 661 patients recruited, anemia was observed among 503 (76.1%) participants. Prevalence of anemia was more among males 387 (76.9%) than 116 (23.1%) females. Out of 503 anemic patients, 334 (66.4%) had mild, 166 (33.0%) had moderate, and 3 (0.6%) had severe anemia at baseline. At 6-month treatment completion, 16 (6.3%) were still anemic. Among 503 anemic patients, 445 (88.4%) were given iron supplements and remaining 58 (11.6%) were managed with diet modifications. After completion of TB treatment, 495 (98.4%) patients had favorable treatment outcomes, whereas 8 (1.6%) patients had died. Severe anemia was not associated with poor outcomes. The presence of anemia among newly diagnosed TB patients, especially pulmonary TB was high. Increased risk of anemia was noted among males who were alcohol and tobacco consumers. There was no significant association between the presence of anemia and sputum conversion from baseline to 6 months of treatment completion.

Pulmonary tuberculosis and diabetes mellitus: Clinical profile and outcomes.

India is endemic for Tuberculosis (TB), contributing to the world's highest number of active cases. Diabetes (DM), with its increasing burden in India, could contribute to adverse outcomes among patients with TB. Consecutive patients with sputum smear positive pulmonary tuberculosis were included in the study. We defined cases as those patients with diabetes at recruitment. Controls were non diabetics (NDM). Sputum samples for AFB smears, AFB culture and Xpert PCR along with blood samples for glycosylated Haemoglobin and glucose levels were collected at recruitment and at 6 months from patients with sputum positive pulmonary TB. Blood glucose levels and sputum smears were repeated at 2 months and monthly till they tested negative. The primary outcome studied was mortality at 6 month follow-up. The secondary outcomes included the time to conversion of sputum smears and cure rates between cases and controls. We recruited 124 patients of which 68 were cases. Mortality after therapy was 15% in cases and 7% in controls, however, the difference was not statistically significant. Equal proportions in each group (Diabetics: 9% vs. NDM 9%) had persistent smear positivity at 2 months. There was no association between delayed sputum conversion and uncontrolled diabetes. Only about 57% of cases and 50% of controls were documented to have completed treatment or been cured. A significant reduction in HbA1c after 6 months of Antituberculous therapy was noted among the cases. [Mean difference - 1.76, P-value - 0.001, 95% CI of difference - (1.01 - 2.52)]. Diabetes did not have adverse outcomes in the form of increased mortality or delayed sputum conversion rates. The high proportion of loss to follow-up seems to be a trend of concern, which should be addressed emergently.

High Pretreatment Level of Neutrophil to Lymphocyte Ratio, Monocyte to Lymphocyte Ratio and Other Factors Associated with Delayed Sputum Conversion in Patients with Pulmonary Tuberculosis.

IntroductionPatients with delayed intensive phase sputum conversion have a higher risk of multidrug resistant-tuberculosis (MDR-TB) and poorer treatment outcomes. Both, host (immune response and comorbidity) and pathogen factors play important roles in determining sputum conversion after treatment initiation. Impaired host immune response, especially the cellular components, as defined by the increased pre-treatment level of neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR) and other additional factors, were associated with severe active TB.PurposeTo evaluate whether impaired immune responses (high pre-treatment level of NLR and MLR) and other factors associate with delayed sputum conversion at the end of the intensive phase treatment.Patients and MethodsThis was a case–control study from 2016 to 2020, which retrospectively analyzed the pre-treatment level of NLR, MLR and other factors among patients with new cases of pulmonary tuberculosis (PTB).ResultsA total of 62 patients (31 cases and 31 control). The cut-off value of high pretreatment level of NLR and MLR was 5.065 and 0.585, respectively. Bivariate analysis showed that pretreatment NLR ≥5.065 (OR 8.23, CI 95% 2.48–27.32, p < 0.001), MLR ≥0.585 (OR 10.18, 95% CI 3.13–33.18, p < 0.001) and BMI <18.5 (OR 2.91, 95% CI 1.03–8.20, p = 0.041) were associated with an increased risk of delayed sputum conversion. Multivariate analysis, however, showed that pretreatment NLR ≥5.065 was not significantly associated with delayed sputum conversion (AOR 3.370, 95% CI 0.71–15.91, p value 0.125). A high pretreatment of MLR (AOR 30.802, 95% CI 3.22–287.55, p value 0.003) and lower BMI (AOR 10.942, 95% CI 1.121–98.563, p value 0.033) were significantly associated with an increased risk of delayed intensive phase sputum conversion.ConclusionHigh MLR pretreatment and a low BMI were significantly associated with an increased risk of delayed sputum conversion at the end of the PTB intensive phase treatment. High NLR pretreatment, smoking, diabetes, and HIV were not associated with sputum conversion.

Development and validation of a nomogram for the prediction of late culture conversion among multi-drug resistant tuberculosis patients in North West Ethiopia: An application of prediction modelling.

Multi-drug resistant tuberculosis has impeded tuberculosis prevention and control due to its low treatment efficiency and prolonged infectious periods. Early culture conversion status has long been used as a predictor of good treatment outcomes and an important infection control metric, as culture-negative patients are less likely to spread tuberculosis. There is also evidence that suggests that delayed sputum conversion is linked to negative outcomes. Therefore, this study was aimed at developing a nomogram to predict the risk of late culture conversion in patients with multi-drug resistant tuberculosis using readily available predictors. The objective of this study was to develop and validate a risk prediction nomogram for the prediction of late culture conversion among multi-drug resistant tuberculosis patients in North-West Ethiopia. Multi-drug resistant tuberculosis data from the University of Gondar and the Debre Markos referral hospitals have been used and a total of 316 patients were involved. The analysis was carried out using STATA version 16 and R version 4.0.5 statistical software. Based on the binomial logistic regression model, a validated simplified risk prediction model (nomogram) was built, and its performance was evaluated by assessing its discriminatory power and calibration. Finally, decision curve analysis (DCA) was used to assess the generated model's clinical and public health impact. Registration group, HIV co-infection, baseline BMI, baseline sputum smear grade, and radiological abnormalities were prognostic determinants used in the construction of the nomogram. The model has a discriminating power of 0.725 (95% CI: 0.669, 0.781) and a P-value of 0.665 in the calibration test. It was internally validated using the bootstrapping method, and it was found to perform similarly to the model developed on the entire dataset. The decision curve analysis revealed that the model has better clinical and public health impact than other strategies specified. The developed nomogram, which has a satisfactory level of accuracy and good calibration, can be utilized to predict late culture conversion in MDR-TB patients. The model has been found to be useful in clinical practice and is clinically interpretable.

Risk factors for early TB treatment interruption among newly diagnosed patients in Malaysia

TB treatment interruption has resulted in delayed sputum conversion, drug resistance, and a high mortality rate and a prolonged treatment course, hence leading to economic and psychosocial affliction. To date, there are limited studies investigating the physico-social risk factors for early treatment interruptions. This prospective multicenter cohort study aimed to investigate the risk factors for early treatment interruption among new pulmonary tuberculosis (TB) smear-positive patients in Selangor, Malaysia. A total of 439 participants were recruited from 39 public treatment centres, 2018–2019. Multivariate Cox proportional hazard analyses were performed to analyse the risk factors for early treatment interruption. Of 439 participants, 104 (23.7%) had early treatment interruption, with 67.3% of early treatment interruption occurring in the first month of treatment. Being a current smoker and having a history of hospitalization, internalized stigma, low TB symptoms score, and waiting time spent at Directly Observed Treatment, Short-course centre were risk factors for early treatment interruption. An appropriate treatment adherence strategy is suggested to prioritize the high-risk group with high early treatment interruption. Efforts to quit smoking cessation programs and to promote stigma reduction interventions are crucial to reduce the probability of early treatment interruption.

Prevalence of anaemia and associated factors among people with pulmonary tuberculosis in Uganda.

Anaemia predicts delayed sputum conversion and mortality in tuberculosis (TB). We determined the prevalence and factors associated with anaemia among people with TB at the National Tuberculosis Treatment Centre in Uganda. People with bacteriologically confirmed TB were consecutively enrolled in a cross-sectional study between August 2017 and March 2018. Blood samples were tested for a full blood hemogram, HIV infection, and CD4+ and CD8+ T-cell counts. Anaemia was defined as a haemoglobin level of <13.0 grams per decilitre (g/dl) for males and <12.0 g/dl for females. Of 358 participants, 210 (58.7%, 95% confidence interval (CI) 53.4-63.8) had anaemia. Anaemia was associated with night sweats, a longer duration of fever, low body mass index (BMI), hyperthermia, high sputum bacillary loads, HIV co-infection, and low CD4 and CD8 counts at bivariate analysis. Factors associated with anaemia at multivariable analysis were low BMI (odds ratio (OR) 2.93, 95% CI 1.70-5.05, P < 0.001), low CD4:CD8 ratio (OR 2.54, 95% CI 1.07-6.04, P = 0.035) and microcytosis (OR 4.23, 95% CI 2.17-8.25, P < 0.001). Anaemia may be associated with the features of severe TB disease and should be considered in TB severity scores.

Factors Associated with Acid Fast Bacilli and Sputum Culture Conversion in Patients with Multidrug-Resistant Tuberculosis in Surabaya

Introduction: Indonesia is a high incidence country of multidrug-resistant tuberculosis. There are approximately 11,000 MDR TB cases, 2.8% of them are new cases and 16% of them are relapse cases. Although guidelines for MDR-TB are frequently designed, medication freely provided, and centers for treatment duly expanded, studies on time to sputum culture conversion have been very limited in Indonesia. Therefore the aim of the study is to identify risk factors that effect on sputum and culture conversion.Methods: Data on short-term regimen for MDR TB in Dr. Soetomo General Hospital from January 1st – December 31st, 2018 were collected with a total sampling approach, and fulfill the inclusion and exclusion. Data were analyzed by computer software IBM SPSS Statistic 24 for windows. Results: Male is more likely to have delayed sputum conversion and culture conversion but no statistical difference is observed (p&gt;0.05). Smoking history is more likely to have delayed sputum and culture conversion but only in sputum smear test shows a significant difference (p≤ 0.05). Alcohol consumption has delay effect on sputum and culture conversion but there is statistically difference in only culture conversion (p&lt;0.05). The high baseline smear test also affects delay the sputum and culture conversion but only in sputum smear reveals a significant effect (p&lt;0.05).Conclusion: In this present study, we identified sex, smoking history, high bacillary loads as significant factors on sputum conversion. In addition, we revealed that alcohol-consumption history is a significant factor affecting on culture conversion.

Determining the risk factors associated with delayed sputum conversion at the end of the intensive phase among tuberculosis patients.

In pulmonary tuberculosis (PTB), the sputum conversion rate at 2 months is frequently used to evaluate treatment outcomes and effectiveness of a TB control programme. The study aimed to estimate the rate of delayed sputum conversion and explore its predicting factors at the end of the intensive phase among smear-positive PTB (PTB +ve) patients. A 3-year retrospective study was conducted in the government hospital in Pulau Pinang from 2016 to 2018. During the study, a standardized, data collection form was used to collect data from the patient record. Patients aged over 18 years were recruited. Multivariable logistic regression analysis was used to identify significant independent variables associated with delayed sputum conversion. A total 1128 of PTB patients were recorded visiting the TB clinic, 736 (65.2%) were diagnosed as PTB +ve; of these, 606 (82.3%) PTB +ve had a record of sputum conversion at the end of the intensive phase. Age ≥ 50 years, blue-collar jobs, smoking, heavy bacillary load, relapsed and treatment interrupted were significantly (P < 0.05) associated with delayed sputum conversion. Delayed sputum conversion rate at the end of the intensive phase was 30.5%. The rate of sputum smear conversion in the intensive phase of treatment was independently associated with high sputum smear grading at diagnosis, relapsed and treatment interrupted categories, old age and blue-collar occupations.

Efficacy of smoking cessation intervention delivered through mobile tele-counseling among smokers with tuberculosis in a Revised National Tuberculosis Control Program

BackgroundIndia has high burden of tuberculosis and smokers. Prevalence of tuberculosis is three times higher in smokers than non-smokers. Active smoking causes severe disease, delay in seeking treatment, lost to treatment follow up, delayed sputum conversion and drug resistance. WHO advocates mobile phone technology to improve health outcomes (mHealth). We used mobile tele-counseling as a smoking cessation intervention in smokers with tuberculosis (TB) receiving treatment under tuberculosis control program. AimTo determine smoking quit rate at six months of TB treatment among smokers receiving mobile tele-counseling versus brief advice and to estimate smoking quit rates and relapse rates during the tele-counseling period. MethodsOpen label randomized controlled trial. Newly detected pulmonary tuberculosis or pleural effusion patients received brief advice on smoking cessation as per The UNION's guiding framework. Subjects were then randomly allocated to intervention or control group. Intervention group was contacted telephonically at 2,3,4,5 and 6 months to assess smoking quit rates and provide continued smoking cessation advice. ResultsIntervention group had 80 and 82 in the control group, mean (SD) age was 40.6(12.6), 43.5(12.7) p = 0.53. Quit rate at six months was 54 (67.5%) in intervention group versus 34 (42%) in control group; RR 1.60 (95% CI 1.19, 2.16) p = 0.001. Trend in smoking quit rates in intervention group was 81.3%, 61.3%, 55%, 73.8% at 2,3,4 and 5 months respectively. Smoking relapse rate was 43.1%, 53.1%, 20.5%,15.3% at 3,4,5 and 6 months respectively. 27.5%, 43.8% were abstinent for last three, two months. ConclusionsMobile tele-counseling is an effective strategy for smoking cessation among TB patients.

Whole Genome DNA Methylation Analysis of Active Pulmonary Tuberculosis Disease Identifies Novel Epigenotypes: PARP9/miR-505/RASGRP4/GNG12 Gene Methylation and Clinical Phenotypes.

We hypothesized that DNA methylation patterns may contribute to the development of active pulmonary tuberculosis (TB). Illumina’s DNA methylation 450 K assay was used to identify differentially methylated loci (DML) in a discovery cohort of 12 active pulmonary TB patients and 6 healthy subjects (HS). DNA methylation levels were validated in an independent cohort of 64 TB patients and 24 HS. Microarray analysis identified 1028 DMLs in TB patients versus HS, and 3747 DMLs in TB patients after versus before anti-TB treatment, while autophagy was the most enriched signaling pathway. In the validation cohort, PARP9 and miR505 genes were hypomethylated in the TB patients versus HS, while RASGRP4 and GNG12 genes were hypermethylated, with the former two further hypomethylated in those with delayed sputum conversion, systemic symptoms, or far advanced lesions. MRPS18B and RPTOR genes were hypomethylated in TB patients with pleural involvement. RASGRP4 gene hypermethylation and RPTOR gene down-regulation were associated with high mycobacterial burden. TB patients with WIPI2/GNG12 hypermethylation or MRPS18B/FOXO3 hypomethylation had lower one-year survival. In vitro ESAT6 and CFP10 stimuli of THP-1 cells resulted in DNA de-methylation changes of the PARP9, RASGRP4, WIPI2, and FOXO3 genes. In conclusions, aberrant DNA methylation over the PARP9/miR505/RASGRP4/GNG12 genes may contribute to the development of active pulmonary TB disease and its clinical phenotypes, while aberrant DNA methylation over the WIPI2/GNG12/MARPS18B/FOXO3 genes may constitute a determinant of long-term outcomes.

Malezya'da Tüberkülozda Beslenme Yükü ve Sektörler Arası Beslenme Yönetimi: Malezya'da Bir Gözden Geçirme

Undernutrition and tuberculosis (TB) are a vital issue in most developing countries of the world. Both of these medical problems tend to have interacted with each other and bidirectional. The undernutrition creates a more significant problem in patients with active TB rather than among healthy individuals. Despite that, there is no protocol available on nutritional support in Malaysia to tackle on this issue. The objective of this review is to explore the nutrition burden of TB disease and the management available in Malaysia. The treatment for TB lasts for six months and above. Hence, it causes a financial burden not only for the healthcare provider but for the patient and the family members. If treatment is not successful and extends to a few months, it will increase the cost of the treatment. Malnutrition in TB patients will cause a problem in the outcome of TB treatment. It includes worsening of the disease, delayed sputum conversion, and increased risk of mortality. Other problems include malabsorption of Rifampicin, drug-induced hepatotoxicity, increased rate of relapse, and persistent of positive cultures in MDR-TB. Benefits of nutritional support for tuberculosis patients include improved body weight, increase in adherence/ compliance to the tuberculosis treatment and increase in the success of the treatment. Implementation of nutritional support protocol by the government and Non-profit organization (NGO) will be beneficial and improve the quality of life of tuberculosis patients.

A high C-reactive protein level and poor performance status are associated with delayed sputum conversion in elderly patients with pulmonary tuberculosis in Japan.

Although the aging population had been increasing in many countries, the factors associated with sputum conversion in elderly patients with pulmonary tuberculosis have not been fully elucidated. We aimed to identify the predictors of delayed sputum conversion and to assess the impact of non-conversion on mortality during tuberculosis treatment in elderly patients. Elderly patients (>65 years) admitted at our hospital in Japan for sputum smear-positive pulmonary tuberculosis were included. The risk factors for sputum non-conversion after 2 months of treatment were determined using multiple logistic regression. Cox hazard regression was used to assess the influence of non-conversion on mortality. We included 185 patients, with median age of 82 years (IQR, 79-88 years). The median time to conversion was 47 (95% CI 43-51) days, and 62 (34%) were identified as non-converters. Multivariate analysis showed that high pretreatment smear grade, high C-reactive protein level and poor performance status were associated with non-conversion. Non-conversion did not contribute to death during treatment. In elderly patients, inflammation level and physical activity level, along with initial smear grade may have a significant impact on delayed sputum conversion. Non-conversion after two months of treatment might not be related with mortality.

Predominant Determinants of Delayed Tuberculosis Sputum Conversion in Indonesia.

Context:Sputum conversion in the first 2 months of tuberculosis (TB) treatment is closely related to successful treatment and a decrease in the likelihood of relapse. In 2015, there were 76% high TB burden countries with low rate of TB successful treatment.Aims:This study aims to evaluate the correlation between delayed sputum conversion and several determinants including social determinants, smoking, malnutrition, and type II diabetes mellitus (DM).Settings and Design:A case–control approach was used to study the potential determinants. A case sample group consisted of smear-positive TB patients with delayed sputum conversion (31 patients) at community health centers in Bandar Lampung, Indonesia. Meanwhile, a control sample group consisted of smear-positive TB patients with sputum conversion (62 patients).Subjects and Methods:Primary data consisted of social determinants and smoking, were collected through in-depth interviews. Meanwhile, secondary data consisted of malnutrition, DM, and sputum conversion were obtained from the medical record.Statistical Analysis Used:Data were analyzed using Chi-square and multivariate logistic regression.Results:Low education (odds ratio [OR]: 5.313; 95% (confidence interval [CI]: 1.711–16.503), low social class (OR: 4.993; 95% CI: 1.430–17.430), smoking (OR: 7.457; 95% CI: 1.757–31.640), and DM (OR: 7.168; 95% CI: 1.746–29.431) influenced delayed sputum conversion.Conclusions:TB control programs in high TB burden countries with low rate of TB successful treatment, should be integrate TB treatment education, smoking cessation programs and follow-up treatments for TB patients with DM to improve the probability of sputum conversion and successful treatment.