Total Tuberculosis Research Articles

A mixed method study to assess notification of tuberculosis patients by private practitioners in New Delhi, India.

A staggering one million tuberculosis (TB) cases are missing from notification, most of them being diagnosed and treated in the private sector. To curb this issue, the Government of India declared TB as a notifiable disease and NIKSHAY was launched in 2012. However, even after years of implementation, as per the report published by TB India 2020, the proportion of private case notification of total TB cases is very low. The objectives of the study were to assess the current practices related to TB Notification being followed by private practitioners of Delhi and to explore the enablers and barriers to TB notification among private-sector treatment providers. This cross-sectional study was done from January 2019 to January 2020. Six hundred doctors were line listed under the chosen TB unit, 375 gave consent and in depth interview was conducted among them. Data were collected on the reporting status and facilitators and barrier toward NIKSHAY reporting were assessed. For the qualitative component, focused group discussions were done. Out of 375 private practitioners, over two-third (68%) practitioners reported that they were not treating TB patients. Out of 108 doctors treating patients only 50% were reporting the cases. Major reason cited for not reporting was "don't know how to" and major barrier considered was "lack of training." Strategies such as training and retraining, and one-to-one sensitization of private practitioners to address barriers may enhance TB notification.

Whole Genome Sequence Analysis of a Mycobacterium iranicum, a Newly Identified Non-Tuberculosis Mycobacteria, Strain SBH312 Isolated in Sabah, Malaysia

In 2021, tuberculosis (TB) incidence partially rebounded but remained 12% lower compared with 2019, in which 10 million new TB cases have been reported worldwide. In Malaysia, 20 – 30% of the total TB cases were reported in Sabah. In this communication, we are reporting the whole genome sequence of Mycobacterium iranicum strain SBH312, isolated from a 49-year-old male suffering from a pulmonary infection. This is the first report of M. iranicum, non-tuberculous mycobacteria infecting humans, from Sabah, state of Malaysia. Phylogenetic analysis showed that the M. iranicum strain SBH312 was closely related to strains from Iran and Peninsular Malaysia.

Epidemiology of tuberculosis in the Pacific island countries and areas, 2000-2020.

Tuberculosis (TB) is one of the most important infectious diseases with an estimated 9.9 million people falling ill globally in 2020. We describe the epidemiology of TB in the Pacific island countries and areas (PICs) to inform potential priority actions to implement the Western Pacific Regional Framework to End TB 2021-2030. A descriptive analysis was conducted using annual TB surveillance data submitted by national TB programmes to the World Health Organization (WHO) and TB burden estimates (incidence rates and number of deaths) generated by WHO for the PICs, for the period 2000-2020. We also analysed TB case numbers, multidrug-resistant/rifampicin-resistant TB (MDR/RR-TB), recent risk factor indicators and treatment outcomes. The estimated TB incidence rate in the PICs increased between 2000 and 2020 from 62 to 69 per 100 000 population, with an 8% reduction observed since 2015. TB cases increased by 29% during 2000-2020, with 1746 cases in 2020 and a high proportion in children (19%). Bacteriological diagnosis was used for 58% of total TB cases, although some countries reported clinical diagnoses in over 60% of cases. From 2015 to 2019, 52 MDR/RR-TB cases were reported and there were 94 TB/HIV coinfected cases in 2015-2020. Treatment success was 74% in 2019 due to 18% of cases being unevaluated. In 2020, the estimated proportion of TB cases attributable to smoking, malnutrition, alcohol abuse and diabetes was 17%, 16%, 11% and 9%, respectively. There was an increasing trend in TB cases, estimated incidence and deaths between 2000 and 2020. Laboratory services were scaled up in some PICs and case-finding activities greatly contributed to the detection of cases. To end the incidence of TB, continued efforts on case finding, contact investigation and scaling up TB preventive treatment should be prioritized. At the same time, collaboration with other sectors for risk factor management and decentralized management need to be considered.

Interferon Gamma Release Assay Results and Testing Trends Among Patients Younger Than 2 Years Old at Two US Health Centers.

Interferon-gamma release assays (IGRAs) are approved for children ≥2 years old to aid in diagnosis of Mycobacterium tuberculosis (TB) infection and disease. Tuberculin skin tests (TSTs) continue to be the recommended method for diagnosis of TB infection in children <2 years, in part due to limited data and concern for high rates of uninterpretable results. We performed a retrospective cohort study of IGRA use in patients <2 years old in 2 large Boston healthcare systems. The primary outcome was the proportion of valid versus invalid/indeterminate IGRA results. Secondary outcomes included concordance of IGRAs with paired TSTs and trends in IGRA usage over time. A total of 321 IGRA results were analyzed; 308 tests (96%) were valid and 13 (4%) were invalid/indeterminate. Thirty-seven IGRAs were obtained in immunocompromised patients; the proportion of invalid/indeterminate results was significantly higher among immunocompromised (27%) compared with immunocompetent (1%) patients ( P < 0.001). Paired IGRAs and TSTs had a concordance rate of 64%, with most discordant results in bacille Calmette-Guérin-vaccinated patients. The proportion of total TB tests that were IGRAs increased over the study period (Pearson correlation coefficient 0.85, P < 0.001). The high proportion of valid IGRA test results in patients <2 years of age in a low TB prevalence setting in combination with the known logistical and interpretation challenges associated with TSTs support the adoption of IGRAs for this age group in certain clinical scenarios. Interpretation of IGRAs, particularly in immunocompromised patients, should involve consideration of the broader clinical context.

Analysis on medical care seeking of local and non-local pulmonary tuberculosis patients reported in Beijing, 2016-2021

Objective: To analyze the medical care seeking of local and non-local pulmonary tuberculosis (TB) patients in Beijing from 2016 to 2021 and provide evidence for TB prevention and control in Beijing. Methods: The reported pulmonary TB data from 2016 to 2021 were collected from tuberculosis management information system and standard code management system of Chinese information system for disease control and prevention. The map data were obtained from the Institute of Geographic Sciences and Natural Resources Research. Excel 2016, SPSS 19.0, Python 3.9 and ArcGIS 10.6 softwares were used for data analysis and visualization for the inter-provincial mobility and inter-district mobility of pulmonary TB patient's medical care seeking in Beijing. Results: Among the reported pulmonary TB patients in Beijing from 2016 to 2021, 35.27%(24 307/68 926) were from 30 provinces (autonomous regions, municipalities) and Xinjiang Production and Construction Corps. The top 5 provinces with pulmonary TB patients medical care seeking in Beijing were Hebei (39.58%,9 620/24 307), Shanxi (8.82%,2 145/24 307), Inner Mongolia Autonomous Region (8.66%,2 105/24 307), Heilongjiang (6.95%,1 690/24 307) and Henan (6.88%,1 672/24 307). Patients from these 5 provinces accounted for 70.89% (17 232/24 307) of total pulmonary TB patients from other provinces. The pulmonary TB patients from other provinces mainly flowed to Tongzhou district of Beijing, accounting for 46.72% (11 356/24 307). These pulmonary TB patients mainly visited grade Ⅲ (A) hospitals, such as Beijing Chest Hospital of Capital Medical University with the highest proportion of 44.76% (10 880/24 307). Among pulmonary TB patients with current residence in Beijing, those sought medical care in other districts accounted for 55.06% (24 566/44 619). The outflow and inflow of TB cases' medical care seeking occurred in 16 districts of Beijing. The median proportion of cross district medical care seeking in 16 districts was 59.30% (56.05%, 65.13%). The inflow of the medical care seeking in Tongzhou, Haidian and Xicheng district was greater than the outflow, and the outflow was greater than the inflow in the other 13 districts. The pulmonary TB patients in Beijing mainly went to Beijing Chest Hospital in Tongzhou for medical care seeking, accounting for 42.18%(18 822/44 619). Conclusions: The proportions of non-local pulmonary TB patients seeking medical care in Beijing from 2016 to 2021 and local pulmonary TB patients seeking medical care in other districts in Beijing were high, and the hospitals where non-local pulmonary TB patients and local pulmonary TB patients sought medical care respectively belonged to grade Ⅲ (A) and municipal designated medical institutions of TB.

Use of Pleural Fluid Digital PCR Analysis to Improve the Diagnosis of Pleural Tuberculosis.

The diagnosis of pleural tuberculosis (TB) remains difficult due to the paucity of Mycobacterium tuberculosis in pleural fluid (PF). This study aimed to improve pleural TB diagnosis using highly sensitive digital PCR (dPCR) technique. A total of 310 patients with evidence of PF were consecutively enrolled, 183 of whom suffered from pleural TB and 127 from non-TB. PF samples were prospectively collected and total DNA was extracted. The copy numbers of M. tuberculosis insertion sequence (IS) 6110 and IS1081 in DNA were quantified using dPCR. The overall area under the curve of IS6110-dPCR was greater than that of IS1081-dPCR (0.85 versus 0.79). PF IS6110 OR IS1081-dPCR (according to their cut-off values, "positive" was defined as either of them was positive, while "negative" was defined as both of them were negative) had higher sensitivity and equal specificity compared with single target-dPCR. The sensitivity of PF IS6110 OR IS1081-dPCR for total, definite, and probable pleural TB was 59.0% (95% CI = 51.5% to 66.2%), 72.8% (95% CI = 62.6% to 81.6%), and 45.1% (95% CI = 34.6% to 55.8%), respectively. Its specificity was 100% (95% CI = 97.1% to 100.0%). PF IS6110 OR IS1081-dPCR showed a higher sensitivity than smear microscopy (57.4% versus 7.1%), mycobacterial culture (55.3% versus 31.8%), and Xpert MTB/RIF (57.6% versus 23.0%). Long antituberculosis treatment time (>1 month) was found to be associated with negative dPCR results in pleural TB patients. This study indicates that PF IS6110 OR IS1081-dPCR is an accurate molecular assay, which is more sensitive than routine etiological tests and has the potential to enhance the definite diagnosis of pleural TB. IMPORTANCE Pleural TB is one of the most frequent causes of pleural effusion, especially in areas with high burden of TB. Due to the paucibacillary nature of the disease, the diagnostic sensitivities of all available bacteriological and molecular tests remain poor. There is an urgent need to develop new efficient methods. Digital PCR (dPCR) is the third generation of PCR that enables the exact quantification of trace nucleic acids in samples. This study evaluates the diagnostic performance of pleural fluid (PF) dPCR analysis for pleural TB, and shows that PF IS6110 OR IS1081-dPCR has a higher sensitivity than routine etiological tests such as smear microscopy, mycobacterial culture, and Xpert MTB/RIF. This work provides a new choice for improving the definite diagnosis of pleural TB.

Investigation of 3-year inpatient TB cases in Zunyi, China: Increased TB burden but improved bacteriological diagnosis.

BackgroundAs one of the top three high tuberculosis (TB) burden countries, China is a country where the overall TB incidence continues to decline. However, due to its large population and area, the increased TB burden exists in regional areas.MethodsThis retrospective study analyzed local inpatient pulmonary TB cases in the Affiliated Hospital of Zunyi Medical University (AHZMU) from January 2016 to December 2018 in a high TB incidence and economically-less-developed area of China. Four methods, acid-fast bacilli stain, culture, Xpert and LAMP, were used to detect Mycobacterium tuberculosis (M.tb), while proportional method and Xpert were used to identify rifampicin-resistant TB (RR-TB). Case number, treatment history, M.tb confirmed TB and rifampicin resistant proportion were analyzed to investigate the local TB epidemic.ResultsTotal 3,910 local inpatient cases with pulmonary TB were admitted to AHZMU during this study period. The annual numbers of total TB cases increased 26.4% (from 1,173 to 1,483), while new cases increased 29.6% (from 936 to 1,213) and RR-TB cases increased 2.7 times (from 31 to 84). Meanwhile, the percentage of previously treated cases declined from 20.2 to 18.2% and the M.tb confirmed TB proportion increased from 34.7 to 49.7%.ConclusionThe elevated M.tb confirmed TB proportion and the declined percentage of previously treated cases indicated the improved TB diagnosis and treatment of AHZMU. However, the increasing number of total TB cases, new and RR-TB cases showed an upward trend and increased TB burden in a relatively underdeveloped area of China.

Appraisal on patient compliance and factors influencing the daily regimen of anti-tubercular drugs in Mangalore city: A cross-sectional study.

Background: Globally, India is the country with the highest tuberculosis (TB) burden with respect to the number of new cases occurring each year. Annual incident cases of TB in India accounts for more than 25% of total TB morbidity and mortality worldwide. Several factors have been associated with the adherence of TB medication, which can be broadly classified as patient/personal, social, structural and health service. The aims of the present study were to determine the compliance to daily regimen of directly observed treatment, short-course (DOTS) therapy among TB patients registered at the Tuberculosis Unit (TU) of Mangalore and to identify the factors influencing non-compliance for treatment. Methods: A cross sectional study was performed. The study sample was drawn from the TUs, General Hospital, Mangalore, after taking permission from District TB Officer. The names and addresses of TB patients were collected from treatment cards. The TB patients were approached at their homes/DOTS centers/Primary Health Centre's (PHCs) with the help of senior treatment supervisors. Results: It was found that patients positive for human immunodeficiency virus (HIV) were more likely to be non-adherent, which was statistically significant. Amongst the participants, 66 (33%) were diabetic and 28.8% of them were found to be non-adherent. The proportion of non-adherence was 27 times higher in those with poor patient provider relationships. Patients who reported to have side effects of TB medication were 5.23 times more likely to be non-adherent. Conclusions: Advice on routine consultation with the health care facility, adherence to treatment regimen and education about its benefits should be the prime focus of providing health education to all TB patients, both at the individual and community levels.

Appraisal on patient compliance and factors influencing the daily regimen of anti-tubercular drugs in Mangalore city: A cross-sectional study

Background: Globally, India is the country with the highest tuberculosis (TB) burden with respect to the number of new cases occurring each year. Annual incident cases of TB in India accounts for more than 25% of total TB morbidity and mortality worldwide. Several factors have been associated with the adherence of TB medication, which can be broadly classified as patient/personal, social, structural and health service. The aims of the present study were to determine the compliance to daily regimen of directly observed treatment, short-course (DOTS) therapy among TB patients registered at the Tuberculosis Unit (TU) of Mangalore and to identify the factors influencing non-compliance for treatment. Methods: A cross sectional study was performed. The study sample was drawn from the TUs, General Hospital, Mangalore, after taking permission from District TB Officer. The names and addresses of TB patients were collected from treatment cards. The TB patients were approached at their homes/DOTS centers/Primary Health Centre’s (PHCs) with the help of senior treatment supervisors. Results: It was found that patients positive for human immunodeficiency virus (HIV) were more likely to be non-adherent, which was statistically significant. Amongst the participants, 66 (33%) were diabetic and 28.8% of them were found to be non-adherent. The proportion of non-adherence was 27 times higher in those with poor patient provider relationships. Patients who reported to have side effects of TB medication were 5.23 times more likely to be non-adherent. Conclusions: Advice on routine consultation with the health care facility, adherence to treatment regimen and education about its benefits should be the prime focus of providing health education to all TB patients, both at the individual and community levels.

Prevalence and Drug Resistance Pattern of Mycobacterium tuberculosis Isolated from Tuberculosis Patients in Basra, Iraq.

Drug-resistant Mycobacterium tuberculosis (DR-MTB) is a major health threat to human beings. This study aimed to evaluate the prevalence and drug resistance profile of MTB. Data were collected from 2,296 newly diagnosed, and 246 retreated tuberculosis (TB) patients who attended the Advisory Clinic for Chest Diseases and Respiratory in Basra province from January 2016 to December 2020. Both new diagnostic and retreated TB cases showed that DR-MTB cases were significantly higher at age 15–34 years, pulmonary TB, and urban residents but with no significant difference regarding gender. The drugs resistance was significantly higher among the retreated cases compared with the new diagnostic patients (20.3% vs. 2.4%, p < 0.0001), with the percentage of the resistance to first-line drugs in primary and secondary cases including isoniazid (1% and 17.1%), rifampicin (0.78% and 15.8%), ethambutol (0.56% and 8.5%), streptomycin (1.3% and 9.75%). Notice that the most common drug resistance was against streptomycin with 1.3% in new patients and against isoniazid (17.1%) in retreated patients. The rate of total drug-resistant TB, multi-drug resistant TB, mono-drug resistant TB, and rifampicin-resistant TB among new tuberculosis cases increased in this period from 2.2 to 6.7%, 0.17 to 1.6%, 0.85 to 4%, and 0.17 to 4%, with a percentage change of 204.54, 841.17, 370.58, 22.5%, respectively. The rates of poly drug-resistant TB and ethambutol-resistant-TB dropped in this period by 15.96%, and 0.7%, with a decrease from 1.19 to 1% and from 1 to 0.3%, respectively. Similarly, the increase of drug-resistant TB among secondary cases has also occurred. In conclusion, the temporal trend showed an increase in the rate of drug resistance of M. tuberculosis since 2016, with a predominant multi-drug-resistant TB and isoniazid-resistant TB.

Appraisal on patient compliance and factors influencing the daily regimen of anti-tubercular drugs in Mangalore city: A cross-sectional study

Background: Globally, India is the country with the highest tuberculosis (TB) burden with respect to the number of new cases occurring each year. Annual incident cases of TB in India accounts for more than 25% of total TB morbidity and mortality worldwide. Several factors have been associated with the adherence of TB medication, which can be broadly classified as patient/personal, social, structural and health service. The aims of the present study were to determine the compliance to daily regimen of directly observed treatment, short-course (DOTS) therapy among TB patients registered at the Tuberculosis Unit (TU) of Mangalore and to identify the factors influencing non-compliance for treatment. Methods: A cross sectional study was performed. The study sample was drawn from the TUs, General Hospital, Mangalore, after taking permission from District TB Officer. The names and addresses of TB patients were collected from treatment cards. The TB patients were approached at their homes/DOTS centers/Primary Health Centre's (PHCs) with the help of senior treatment supervisors. Results: It was found that patients positive for human immunodeficiency virus (HIV) were more likely to be non-adherent, which was statistically significant. Amongst the participants, 66 (33%) were diabetic and 28.8% of them were found to be non-adherent. The proportion of non-adherence was 27 times higher in those with poor patient provider relationships. Patients who reported to have side effects of TB medication were 5.23 times more likely to be non-adherent. Conclusions: Advice on routine consultation with the health care facility, adherence to treatment regimen and education about its benefits should be the prime focus of providing health education to all TB patients, both at the individual and community levels.

A Novel Cross-Priming Amplification-Based Assay for Tuberculosis Diagnosis in Children Using Gastric Aspirate.

Low detection rates of Mycobacterium tuberculosis (MTB) by culture and smear microscopy prevent early diagnosis of tuberculosis (TB) in children. Therefore, developing rapid and accurate diagnostic techniques are critical to achieving the global aim of minimizing childhood TB. The present study was performed to evaluate the diagnostic effectiveness of the novel cross-priming amplification-based EasyNAT MTB complex assay (EasyNAT) in childhood TB. Five hundred and six children with suspected TB were enrolled from January 2018 to October 2021. Gastric aspirate (GA) samples were tested by bacterial culture, acid-fast bacillus microscopy, EasyNAT, Xpert MTB/RIF (Xpert), or Xpert MTB/RIF Ultra (Xpert Ultra). Among 239 children simultaneously tested by EasyNAT and Xpert methods, both assays showed similar sensitivities in total active TB cases [22.6% (31/137) vs. 26.3% (36/137), p = 0.441] and in bacteriologically confirmed TB cases [both 60.0% (9/15)]. The two assays presented similar specificities of 98.0% (100/102) and 99.0% (101/102), respectively (p = 1.000). Among 267 children who were simultaneously tested with EasyNAT and Xpert Ultra, Xpert Ultra demonstrated higher sensitivity than EasyNAT in total active TB cases [50.9% (89/175) vs. 30.3% (53/175), p < 0.001]. EasyNAT and Xpert Ultra yielded similar specificities, at 97.8% (90/92) and 100.0% (92/92), respectively (p = 0.155). These findings indicated that Xpert Ultra was superior to EasyNAT despite its higher cost and EasyNAT was not inferior to Xpert in the diagnosis of childhood TB using GA samples. EasyNAT may therefore be a suitable alternative diagnostic method for childhood TB based on its cost-effectiveness, speed, and accuracy.

Diagnosis and Antimicrobial Susceptibility of Mycobacterium Tuberculosis in a Tertiary Care Hospital in Bangladesh

Background: Tuberculosis (TB) is a common condition all over the world but more common in developing countries like Bangladesh38. This is second only to HIV/AIDS as the greatest killer worldwide due to a single infectious agent. In 2013, 9 million people fell ill with TB and 1.5 million died from the disease globally. Approximately 15-20 % of total TB cases are extrapulmonary in non-HIV patients. Among extrapulmonary TB, abdominal tuberculosis (ATB) accounts for 11%-16%. Abdominal TB is difficult to diagnose because of its lack of specific symptoms, low yield of acid-fast bacilli (AFB) on smear and culture due to paucibacillary lesion; and variable manifestations depending upon anatomical localization of the disease. The diagnosis of abdominal TB classically requires histopathological, microbiological and culture confirmation of Mycobacterium tuberculosis. Investigations like Imaging (Ultrasound, Barium X-Rays, and CT scan) and the Mantoux test have only supportive value. Aim of the study: The aim of the study was to diagnose modalities and antimicrobial susceptibility in abdominal tuberculosis patients.Material &amp; Methods:This cross-sectional hospital-based observational study was carried out among 73 adult patients with the diagnosis of abdominal TB who met the selection criteria and attended in Gastroenterology department of DMCH through either admission or referral from May 2015 to April 2016.Results:The most frequent symptoms were weight loss (96.9%), abdominal pain (75%), and fever (75%). The most frequent signs were anaemia (34.4%), followed by ascites (27.9%). Basis of diagnosis in abdominal tuberculosis was histolopathogy in 37.5%, Gene Xpert in 28.1%, Positive AFB on culture in 9.4%, ADA value in ascitic fluid (Cutoff &gt;40 IU/L) in 25%, and good clinical response (Based on weight gain and general improvement in wellbeing) to a therapeutic trial of anti-TB treatment in 18.7% patients. Drug sensitivity pattern was analyzed in all three AFB culture-positive patients; resistance was detected in one which showed multidrug resistance (MDR TB).Conclusions:The result of this study highlighted the diagnostic yield of various investigation modalities, particularly newer modalities (Gene Xpert, culture sensitivity in Bactec MGIT 960) and basis of diagnosis in abdominal TB. This study also determined the MTB culture positivity from tissue biopsies in patients with abdominal TB and demonstrated drug-resistant MTB in culture-confirmed abdominal TB.

Cross-sectional community-based assessment of knowledge, attitude and practices on tuberculosis in Osun State, South-west, Nigeria.

Tuberculosis (TB) has continued to be a global public health issue, especially in developing countries, where Nigeria accounts for 4% of the global TB burden. However, to achieve the Sustainable Development Goals targets for 2030, there is a need for adequate and robust awareness campaigns to ensure that individuals in the communities are aware of the total TB program package. This study assessed the knowledge, attitudes and practices (KAP) towards TB of the residents of two communities affected by the TB scourge in Osun State, Nigeria. An interviewer-administered, semi-structured questionnaire adapted from the WHO-KAP study guide was employed, and the data generated were analysed using the SPSS statistical package. A total of 280 respondents participated in the study comprising 162 (57.9%) males and 118 (42.1%) females, a large percentage of the respondents (273/97.5%) know about TB and know that anybody can be infected (63.6%). However, in this study, we obtained the following KAP scores: overall good knowledge of TB: 60% (Iwo- 54.7% and Ikire-65.2%), overall good attitude towards TB: 50% (Iwo- 53.3% and Ikire- 46.7%) and overall good TB preventive practices 65.2% (Iwo- 66.6% and Ikire- 63.8%). Ikire respondents were significantly more knowledgeable than Iwo respondents (p=.002), while Iwo respondents had better TB attitudes than Ikire respondents (p=.03). Predictors of good KAP scores were accommodation type, education, age and main source of income of respondents. This study assessed the level of community TB-KAP and reinforced the need for a more robust awareness campaign for better TB health service utilisation.

Impact of COVID-19 pandemic on TB prevention and care in Addis Ababa, Ethiopia: a retrospective database study

ObjectiveThe current COVID-19 pandemic in Ethiopia could cause severe dysfunction in tuberculosis (TB) treatment, diagnostic services, and prevention and control efforts. In this study, we evaluated the effect of COVID-19...

An Integrative Network Approach to Identify Common Genes for the Therapeutics in Tuberculosis and Its Overlapping Non-Communicable Diseases.

Tuberculosis (TB) is the leading cause of death from a single infectious agent. The estimated total global TB deaths in 2019 were 1.4 million. The decline in TB incidence rate is very slow, while the burden of noncommunicable diseases (NCDs) is exponentially increasing in low- and middle-income countries, where the prevention and treatment of TB disease remains a great burden, and there is enough empirical evidence (scientific evidence) to justify a greater research emphasis on the syndemic interaction between TB and NCDs. The current study was proposed to build a disease-gene network based on overlapping TB with NCDs (overlapping means genes involved in TB and other/s NCDs), such as Parkinson’s disease, cardiovascular disease, diabetes mellitus, rheumatoid arthritis, and lung cancer. We compared the TB-associated genes with genes of its overlapping NCDs to determine the gene-disease relationship. Next, we constructed the gene interaction network of disease-genes by integrating curated and experimentally validated interactions in humans and find the 13 highly clustered modules in the network, which contains a total of 86 hub genes that are commonly associated with TB and its overlapping NCDs, which are largely involved in the Inflammatory response, cellular response to cytokine stimulus, response to cytokine, cytokine-mediated signaling pathway, defense response, response to stress and immune system process. Moreover, the identified hub genes and their respective drugs were exploited to build a bipartite network that assists in deciphering the drug-target interaction, highlighting the influential roles of these drugs on apparently unrelated targets and pathways. Targeting these hub proteins by using drugs combination or drug repurposing approaches will improve the clinical conditions in comorbidity, enhance the potency of a few drugs, and give a synergistic effect with better outcomes. Thus, understanding the Mycobacterium tuberculosis (Mtb) infection and associated NCDs is a high priority to contain its short and long-term effects on human health. Our network-based analysis opens a new horizon for more personalized treatment, drug-repurposing opportunities, investigates new targets, multidrug treatment, and can uncover several side effects of unrelated drugs for TB and its overlapping NCDs.

STERNUM: RARE SITE OF PRIMARY TUBERCULOSIS

Sternum is one of the least common bones of the body to get infected. Sternal tuberculosis or sternal osteomyelitis are known to occur secondary to the primary pulmonary tuberculosis, trauma, are commonly identied [2] in the sternum and sternoclavicular joints. Sternal tuberculosis has been reported after open heart surgery, in heroin addicts and in HIV positive [3] [1] patients , thalassemia, after BCG vaccination and with disseminated and miliary tuberculosis. [4] Extra-pulmonary tuberculosis constitutes 15-20% of total tuberculosis (TB) case load in immuno-competent patients. Occurrence of primary [2] sternal tuberculosis in absence of primary tuberculosis, trauma, immunocompromised status and operative history is even more rare. [4] Sternal uberculosis accounts for less than 2% of cases of osteomyelitis. Two immunocompetent patients who came with complaints of lump over chest with pain were examined and HRCT was done.

The Spatial-Temporal Epidemiology Analysis of Tuberculosis Disease in Pakistan

In spite of significant progress, Tuberculosis (TB) remains a severe national health issue in Pakistan. However, very few studies have been done on the spatial-temporal appraisal of tuberculosis in Pakistan. The current research is based on the TB disease dataset obtained from the Pakistan Bureau of Statistics from 2015 to 2019. The study has focused on assessing Spatial epidemiology statistics and spatial autocorrelation to detect the cluster of TB disease incidence rate (IR) for New, Male, Female and total TB patients at the provincial and territorial levels in Pakistan. The spatial epidemiology statistics and spatial autocorrelation have been measured the temporal trends of TB IR as per 100,000 population. The global and local spatial autocorrelation of TB IR has been analyzed by the global Moran's I and Anselin's Local Moran's using GeoDa software and ArcGIS tool. Results show that the IR in Pakistan exhibited a progressive decrease from 2015 to 2018 but showed an unexpected increase in 2019. It is also critically analyzed that the Punjab, Sindh, Khyber Pakhtunkhwa, and Azad Jammu Kashmir provinces and territories (Federally Administered Tribal Areas (FATA) were at high risk with a higher rate of IR. Despite this, the fact is that the global spatial autocorrelation has not been identified across provincial and territorial levels in Pakistan. In the five-year study, datasets have been observed the individual provinces and territories that indicate negative local spatial autocorrelation of Low-high provinces and territories, such as Balochistan and Islamabad Capital Territory (ICT).

The efficacy of isoniazid prophylaxis in renal transplant recipients in a high tuberculosis burden country.

Renal transplant recipients are at high risk of tuberculosis (TB). We started isoniazid (INH) prophylaxis of 1 year duration in all renal transplant recipients from April 2009. Our aim was to assess the incidence of TB on INH prophylaxis and its tolerability. This was a retrospective observational study. The files of renal transplant recipients from April 2009 to December 2011 were reviewed till June 2015. We noted the incidence of TB, INH tolerability, and development of resistance. We compared the incidence of TB with the historical controls who never received the prophylaxis. A total of 910 patients were reviewed and followed up for 4.8 years. INH prophylaxis was completed by 825 (91%) patients. A total of 46 patients (5%) developed active TB as compared to 15% in the historical controls. The median time of TB diagnosis from transplantation was 2.8 years. In the first-year post transplant, out of total TB cases, 52% occurred in the historical controls whereas 13% occurred in study cohort. Around 67% had TB>2 years after transplant. Overall 1.43% had hepatotoxicity. There was a significant reduction in TB among those who completed prophylaxis to those who did not (p<0.001). Of 14 cultures, one isolate was INH resistant (7%). INH prophylaxis was well tolerated. The incidence of TB decreased in the first 2 years. However there was a surge in TB cases 1 year after stopping INH therapy. We should consider prolonging the duration of INH prophylaxis in high TB burden countries in renal transplant recipients.

Relationship between total cholesterol level and tuberculosis risk in a nationwide longitudinal cohort

The association between the total cholesterol level and tuberculosis (TB) risk has been controversial. Our study aimed to evaluate whether total cholesterol level can predict the risk of TB. Data from 5,000,566 subjects who participated in a health screening exam in 2009 were investigated using the Korean National Health Insurance Service database (2009–2018). Cox hazard regression analyses were used to evaluate TB risk according to the quartile of total cholesterol levels. During an average of 8.2 years of follow-up, 32,078 cases of TB occurred. There was a significant inverse association between the total cholesterol level and TB risk. Compared with subjects in the highest quartile, those in the lowest quartile had a 1.35-fold increased TB risk (95% confidence interval = 1.31–1.39). The association between total cholesterol level and TB risk was more apparent in young subjects (age < 65 years), those without diabetes mellitus (DM), and those without obesity (p for interaction < 0.001 for age group, DM, and body mass index). Although there was a significant inverse association between total cholesterol level and TB risk in subjects who did not use a statin, no significant association was observed between the total cholesterol level and TB risk in subjects who used a statin. A low total cholesterol level was significantly associated with an increased risk of TB, even after adjusting for confounders, especially in patients younger than 65 years, those without DM or obesity, and those who did not use a statin.