2^nd World Congress on Advancements in Tuberculosis and Lung Diseases July 02-03, 2020 Amsterdam, Netherlands

Esther Uwimaana Makerere University College of Health Sciences Department Immunology and Molecular Biology1, Infectious Diseases Institute Makerere University2, Makerere University School of Public Health 3, University of Georgia USA

Tuberculosis(TB) diagnosis in the presence of HIV co-infection remains challenging. Heme oxygenase (HO-1) and neopterin have shown to be as potential biomarkers for TB diagnosis. Infection of macrophages with Mycobacterium tuberculosis (M. tb) causes the production of HO-1 and neopterin and previous studies have shown these to be markers of immune activation This study was conducted to determine the levels of HO-1 and neopterin and their utility in the diagnosis of TB among individuals enrolled in the Community Health and Social Network of Tuberculosis(COHSONET) study and the Kampala TB Drug Resistance Survey(KDRS). Methods: A total of 210 participants were enrolled in a study of a diagnostic method aimed at determining the levels of HO-1 and neopterin, and determine their diagnostic accuracy as biomarkers in TB diagnosis from March to May 2019. M. tb culture was performed on sputum to confirm active TB(ATB) and QuantiFERON TB gold test to confirm latent TB infection(LTBI). ELISAs were performed to determine the levels of HO-1 and neopterin. Data analysis was done using Kruskal Wallis and Receiver Operating Characteristic curves to determine the diagnostic accuracy. Results: HO-1 levels among ATB/HIV patients, LTBI/HIV patients and TB negative individuals were 10.7ng/ml (IQR: 7.3-12.7ng/ml), 7.5ng/ml (IQR: 5.4-14.1ng/ml), 3.3ng/ml (IQR: 2.0- 7.1ng/ml) respectively. Neopterin levels among ATB/HIV patients, LTBI/HIV patients and TB negative individuals were 11.7ng/ml (IQR: 5.219.4ng/ml), 8.8ng/ml (IQR: 2.4-19.8ng/ml), and 5.9ng/ml (IQR: 3.410.2ng/ml) respectively. HO-1 showed a sensitivity of 78.57% and a specificity of 71.43% with area under the curve(AUC) of 0.839 when used to diagnose ATB. HO-1 showed AUC of 0.79, sensitivity of 70% and specificity 70% when used to diagnose LTB. Neopterin showed a sensitivity of 61.43% and a specificity of 74.29% with AUC 0.71 when used to diagnose ATB. Neopterin as a biomarker in LTB diagnosis showed AUC of 0.56 which was not significant. Conclusion: HO-1 and neopterin are valuable diagnostic biomarkers for ATB and LTB which could be further utilized to develop less costly rapid diagnostic tools to overcome current TB diagnostic challenges.

Dr. Francis Louis M. Alcachupas graduated with a degree of Bachelor of Science in Nursing at the Cebu Normal University in 2011. He then pursued the study of medicine and graduated with the degree of Doctor of Medicine in 2017 under the Regionalization Program of the University of the Philippines – Manila, College of Medicine. Afterwhich, he immersed in community service as a local health officer in the Municipality of San Miguel, Zamboanga del Sur through the Doctors to the Barrios Program of the Department of Health, Philippines. Concurrently during his tour of duty, he pursued his graduate studies at the Development Academy of the Philippines and received a degree of Master in Public Management, Major in Health Systems and Development in 2019.

The Municipality of San Miguel, Zamboanga del Sur has a significant number of non-compliant TB patients averaging to 13.70% in the past three years. The community based Directly Observed Treatment Short Course (DOTS) has been modified to address the issue but has been falling short from its targets. Efforts to reintegrate non-compliant TB patients is imperative to prevent worsening of the condition of the patient, the transmission of the disease, development of multi-drug resistant tuberculosis (MDRTB) and ultimately poorer health outcomes. Reintegrating issues, however, involves addressing the reason for non-compliance in order to ensure completion of treatment. This study, therefore, aimed to determine and assess the factors influencing patient’s non-compliance to treatment and the circumstances revolving around it in order to determine an appropriate and effective strategy to address the problem. A qualitative study was carried out utilizing structured interview questionnaires. All defaulters (n=31) were traced and those still present in the municipality were enrolled in this study. This Action Plan and Project utilized the Bridging Leadership Framework Approach and was analyzed using IPOO model with the outputs further analyzed utilizing the Control Knobs of Health Systems Reform. Defaulters had a number of factors influencing non-compliance and the interplay of these factors brought about their non-compliance. Local governance and the establishment of a Local TB Council brought about health systems reform in the TB program of the Municipality of San Miguel.

Basha is currently a 4th year PhD student at Aklilu Lemma Institute of pathobiology, Addis Ababa University, Ethiopia. He is a young researcher and has 2 publications.

Tuberculosis (TB) remains a major global public health issue and WHO has also set the ambitious target of a 90% reduction in the incidence of new TB cases by 2035. However, LTBI is a major obstacle to eliminate TB because of different risk factors. Hence, in order to reduce the number of new TB cases, WHO adapted from End TB strategy that states screening and treating of LTBI; particularly, in prison environment. This is because that globally, prisons represent a major institutional amplifier for TB. The aim of the present study was to investigate the prevalence and associated risk factors of LTBI in East Wollega Zonal prison, Nekemte town, Western Oromia, Ethiopia. Methods: A cross-sectional study design and systematic sampling technique was used to select a sample of 352 from a total of 2620 prisoners aged ≥18 years during one month (May–June, 2019) in East Wolllega prison, Western Oromia, Ethiopia. The selected inmates were interviewed using a structured pre-tested questionnaire; blood samples were collected from the study participants and screened for LTBI using interferon-gamma release assay (IGRA). The Data were analyzed using SPSS version 25 and logistic regression was used to model the likelihood of LTBI occurrence and to identify risk factors associated with LTBI. Results: Overall prevalence of LTBI among prisoners was 51.17 % (95% CI: 46.45-57%) and with high prevalence in men, rather than women (53.0% vs. 43.5%, respectively), although no significant difference was highlighted. Using multiple logistic regressions, a prisoner’s age (age ≥45 years; AOR=2.48[1.04-5.9]), khat chewers (AOR=2.27[1.27-4.19]), staying >12 month in current incarceration (AOR=1.81[1.04-3.18]) and overcrowding (>100 individuals per cell; AOR=1.91[1.002-3.65]) were found to be statistically significant (P < 0.05) predictors of LTBI. Conclusions: The high prevalence of LTBI among the prisoners requires immediate steps be taken to identify and treat LTBI and counsel those found to be positive in this setting. Routine screening of prisoners for both TB and LTBI up on entry was highly recommended intervention to halt TB transmission in prisons. Similarly, reduction of overcrowding per cells, educating not to chew khat in overcrowded, unhygienic and unventilated area and intensive monitoring of those stayed longer in prison may help reduce the TB transmission in this setting and in the community at large.

Vagolu Siva Krishna School of Chemistry and Molecular Biosciences and Australian Infectious Disease Research Centre, University of Queensland, Brisbane, Australia

In view of the emergence and frequency of multidrug-resistant tuberculosis, we undertook the design and biological evaluation of novel inhibitors. Ketol-acid reductoisomerase (KARI; EC 1.1.1.86) is the second enzyme in the branched-chain amino acid biosynthesis pathway, which is present in the bacteria, fungi, and the plant makes it as an attractive target for antibacterial activity. In present work, we attempted to identify the lead through high throughput virtual screening of Birla Institute of Technology and Science in-house database. This study led to the identification of 17 compounds with good docking score, which make important interactions with the protein active site. Compounds NR-107 and ASIM-F from the study were distinguished from the others by their promising activity profiles with IC50 for KARI of 18.47µM and 27.02 µM respectively. The 10 ns molecular dynamics simulations of two potential leads with protein confirmed that the structural complex was stable with an average RMSD less than 2.5 Å. Selected two compounds further evaluated for antitubercular potency in the active and dormant models like nutrient starved and biofilm. Additionally, the NR-107 showed a logarithmic reduction of 1.8 fold against Mtb infected macrophage model. Both the compounds were lacking toxicity against RAW cell lines 264.7 at concentrations of 25 µM. Outcomes of the study suggest that NR-107 is a potential candidate for further drug development.

Dr.A.Keerthi Prakash Institute of Thoracic Medicine, Madras Medical College, Chennai

Genitourinary tuberculosis(20%) is a common type of extra-pulmonary Tuberculosis .The kidneys, ureter, bladder or genital organs are usually involved. Tuberculosis of the prostate has becoming more common in immune-compromised patients. However, it could be rarely found as an isolated lesion in immune-competent patients. Case Report: A 42yr oldnon diabetic male presented with c/o burning micturition, weight loss(4kgs in 2month) and nocturia for past 2 month. He has no other co morbidities or immunodeficiencies.No h/o prior ATT and contact. BCG vaccinated. Digital rectal examination showed nodule over prostate. Lab investigation showed ICTC – negative; PSA 2.23ng/ml (normal <1.3).His urine AFB(3 samples) absent and urine culture showed no growth. CXR – No abnormality detected. USG abdomen and scrotum normal.CT chest showed no parenchymal or mediasternal lesion. MRI pelvis showed Multiple T1 and T2 hypointense nodules, largest in the left lobe of the prostrate in the peripheral zone in the mid gland. Trans Rectal Ultrasound (TRUS) guided biopsy was done and HPE shows extensive areas of necrosis and multiple caseatingepitheloid granulomata.Tissue CBNAAT – MTB detected low and rifampicin sensitive. ATT was initiated. Discussion : The Genitourinary tuberculosis represents 20% of all locations of extra-pulmonary tuberculosis. Prostate involvement, especially if it is isolated, is rare. Its incidence is estimated at 6.6% of the urogenital tuberculosis.It can be primary or secondary to epididymal tuberculosis or bladder. The hematogenous spreading is one of the common way contaminations. This infection is promoted by some immunosuppressive diseases such as AIDS and taking of corticosteroid and chemotherapy. The clinical signs of lower urinary tract obstruction such as dysuria, urinary frequency and perineal heaviness can be observed. Digital rectal examination can enjoy enlarged prostate, elastic consistency, firm or stony or nodular as in our case.Tuberculosis of the prostate may be difficult to differentiate from carcinoma of the prostate and the chronic prostatitis when the prostate is hard and nodular on digital rectal examination and the urine is negative for tuberculosis bacilli. In many cases, a diagnosis of tuberculous prostatitis is made by the pathologist, or the disease is found incidentally after trans-urethral resection Conclusion: Though the incidence of isolated prostate TB is rare condition, TB prostate should be borne as differential diagnosis for Prostatitis even in immunocompetent. Therefore,Transrectal ultrasound-guided needle biopsy of the prostate for TB molecular testing can yield a reliable diagnosis andis recommended as the method of choice for diagnosis.