Day 1 :
Keynote Forum
A.D.NAGESWARI
Tagore Medical College and Hospital, India
Keynote: Effect of ripampin with bio-enhancer in the treatment of newly diagnosed sputum positive pulmonary tuberculosis patients: a double –center study
Time : 10.00- 11.00
Biography:
Dr. Arcot Dheenadayalu Nageswari is a Post Graduate in Tuberculosis and Respiratory Diseases. She was Trained by Central Govt. of India in TB Control (1983) She has the prestigious Fellowship award of by WHO in TB control Training at Japan and Korea 1993. She has published 20 papers in Indexed national and international journals. She has more than 25 years of Clinical Experience in Tuberculosis and Chest diseases.
Abstract:
Tuberculosis was declared as global emergency by WHO in 1993. DOTS Therapy recommended by WHO is highly effective in an active drug susceptible TB as long as patient completes the course. Adverse effect of anti TB drugs is one of the most common reason for non-adherence eventually contributing to treatment failure, relapse or emergence of drug resistance. The standard treatment for newly diagnosed tuberculosis patients consists of an intensive phase for two months with 4drugs(HRZE), followed by continuation phase for four months with 2 drugs(HR). Rifampicin , which is very effective against mycobacterium tuberculosis, in both phase of treatment has certain concerns, which included decreased bioavailability with chronic use and hepatotoxicity. To overcome these concerns a new boosted formulation of Rifampicin(Risorine) with bio-enhancer of piparine was developed. Piperine has been found to increase bioavailablity of several drugs including Amoxicillin, Cefotaxime,Theophylline and Propanolol. Risorine is a fixed combination contains Rifampicin 200mg+Isonazid300mg+Piperine 10mg. We conducted study in two centers to validate the therapeutic efficacy and tolerablity of Risorine formulation containing regimen with a conventional regimen. This was a randomized, prospective, parallel group study . All the patients were subjected to sputum examination, biochemical investigations followed by adverse drug event (ADE) monitoring. A Total of 63 patients completed the study. No significant difference was observed in baseline characteristics of patients between the study groups. At the end of the continuous phase, both the groups showed zero bacteria detection. However, in the intervention group, the rate of sputum conversion was much faster than the usual care group. The rate of increase in SGOT and SGPT was much higher in the usual care group (p<0.0001) than the interventional group (p<0.05). Urea and creatinine has also increased from pre-treatment to end visit. The number of patients reported ADEs was less in the intervention care group (22.22%) when compared to the usual care group (36.84%). Rifampicin 200 mg with piperine 10 mg FDC is compatible with the usual CAT-1 regimen
Keynote Forum
Challa Negeri Ruda
Director of Challenge TB Ethiopia, Addis Ababa, Ethiopia
Keynote: Recognizing Contact Investigation as a critical strategy to find more missed TB cases in Ethiopia
Time : 11.00-12.00
Biography:
Challa Negeri has completed his MD at the age of 24 years from University of Gondar and postgraduate studies from Addis Ababa University and University of Roehampton. He is a technical director of Challenge TB Ethiopia, a USAID-funded project implemented by KNCV Tuberculosis Foundation as a prime partner. He has been working in TB control programmes in South Sudan and Ethiopia for Global Fund and USAID TB projects for the last 12 years.
Abstract:
According to WHO (2018), Ethiopia missed about one third of its estimated 180,540 TB patients in 2017. Targeted TB screening, of which Contact Investigation (CI) is one, is one of the priority strategies of finding missed TB in Ethiopia.
CI strategies have been included within the revised national TB guidelines and strategic documents; national SOPs and CI registers have been prepared; a two-days training has been provided to >800 health workers where a one-year-facility-based CI action plan was developed with 1,939 facilities currently implementing CI.In addition to CI at facility, at community level, using 2 Health Extension Workers(HEWs) per health post(over 35,000 HEWs in the country), outreach CI (during weekly house visits) is initiated for contacts identified at health facility.
Evidence of program implementation that CI is a high impact intervention for case detection.USAID /CTB has implemented prospective, reverse and retrospective CI approaches with a markedly observed increase in the detection of TB cases.
Keynote Forum
Mandira Varma-Basil
University of Delhi, India
Keynote: Next generation Sequencing: How useful is it in TB diagnosis and research in resource limited settings
Time : .
Biography:
Prof. Mandira Varma Basil is a Medical Microbiologist currently working at Vallabhbhai Patel chest Institute, Delhi, India where she is incharge of the Mycobacteriology unit . She obtained her MD in Microbiology from the University of Delhi and her DNB from the National Board of Examinations, Delhi, India. She is the recipient of the Department of Biotechnology (Government of India) Overseas Associateship and the Indian Council of Medical Research International Fellowship. Her main areas of interest include TB diagnosis, drug resistance in M. tuberculosis, molecular epidemiology of M. tuberculosis and non tuberculous mycobacteria. Dr. Varma-Basil has several publications and book chapters to her credit.
Abstract:
Tuberculosis (TB), though curable and preventable; is still a major cause of illness and death in most developing countries. TB is one of the top most among highly infectious diseases in the world. Globally, of the 10 million cases of active TB, 1.3 million deaths were reported in 2017. The World health organization (WHO) has stated that of the incident TB cases missed from the TB surveillance system, two thirds were not reported and remaining one third were not detected.
This underscores the importance of rapid and effective methods of TB diagnosis. Traditional laboratory techniques are time consuming and cumbersome and not sufficiently sensitive or specific to fight this menace, especially in the face of increasingly prevalent drug-resistant TB. Though rapid molecular methods such as GeneXpert and line probe assays are vital tools in the fight against TB, major advances in next generation sequencing (NGS) technology are allowing increasingly rapid and accurate sequencing of entire bacterial genomes, providing unprecedented depth of information. NGS has the ability to cause a revolutionary paradigm shift in the diagnosis and epidemiological study of Mycobacterium tuberculosis infection. Current applications of NGS for TB diagnosis include sequencing cultured isolates to predict drug resistance and even direct diagnostic sequencing from clinical samples. The recent increase in cost effectiveness of NGS for whole genome sequencing (WGS) analyses has also rapidly increased the utility of this method for outbreak detection and surveillance. However, certain challenges need to be overcome to enable the use of this promising technology in routine diagnosis and research, especially in resource limited regions of the world.
- Mycobacterial Infections
Location: .
Session Introduction
Silaphet Somphavong
Center for Infectiology Lao-Christophe Merieux, Lao PDR
Title: First insights into the genetic characteristics and drug resistance of Mycobacterium tuberculosis population collected during the first National Tuberculosis Prevalence Survey of Lao PDR (2010–2011)
Time : 12.00-12.40
Biography:
Silaphet Somphavong is currently a PhD student of the École doctorale CBS2 (France), working on “Molecular epidemiology of Mycobacterium tuberculosis and antibiotic resistance in Lao PDR”. This project is collaboration between the Laos, France and Vietnam. She graduated from a medical school and continued her specialist on Tropical diseases at the IFMT (in Lao PDR) in 2010. She jointed the Center for Infectiology Lao-Christophe Merieux in 2011 as a research assistant in charge of TB research.
Abstract:
In Lao PDR, little is known about the genetic characteristics and drug resistance (DR) of the Mycobacterium tuberculosis (M.tb). We aimed to study the genetic characteristics and DR of M. tb collected during the first National TB Prevalence Survey (2010–2011) in order to better understand the TB epidemiology in the country. Using MTBDRplus test for DR detection and spoligotyping and MIRU-VNTR for genotyping.
Of 222 M. tb isolates, 11 were INH mono-resistant, 2 were MDR-TB. Of 206, the proportion of EAI family was 75.7%, Beijing 14.4% and T 5.5%. EAI isolates came from all provinces, Beijing isolates were found mainly in the northern provinces. A proportion of Beijing isolates was higher in people younger than 35 years compared to EAI, the percentage of DR was higher among Beijing (17.2%) than EAI (5.2%) isolates, the two MDR-TB isolates belonged to the Beijing family. The MIRU-VNTR and spoligotyping results revealed an estimated clustering rate of 11% and the occurrence of mini-outbreaks of DR-TB caused by Beijing genotypes.
Zakaria Hmama
Universirty of British columbia, Canada
Title: Improving the efficacy of the Tuberculosis vaccine M. bovis BCG
Biography:
Zakaria received a PhD degree from the University Claude Bernard (Lyon, France) in 1993. He is currently Associate Professor at the University of British Columbia and was the recipient of Scholarship Awards from the Michael Smith Foundation of Health Research and the TB Vet Foundation. Ongoing research in Zakaria’s lab focuses on developing novel gene manipulation technologies to upgrade the current BCG vaccine in order to maximize the induction of protective TB immunity. Of equal importance to the vaccine project, a biology-based study of Mtb persistence has revealed important virulence factors that represent attractive drug targets that could be used for TB treatment.
Abstract:
BCG vaccine, introduced almost 100 years ago, is the only option to prevent tuberculosis (TB) disease. It effectively protects newborns from meningeal TB but fails to prevent adult pulmonary TB. TB kills 1.3million people annually in areas where BCG vaccination is widely practiced. Thus, more effective TB vaccines are urgently needed. Others and we have shown that BCG mimics features of virulent M. tuberculosis, in particular attenuation of essential macrophage functions such as phagosome maturation and antigen presentation. One of these studies revealed that defect in antigen presentation is largely due to down-regulation of the cysteine protease Cathepsin S (CatS), which prevents MHC II molecule maturation and proper antigen peptide loading. Recent studies also suggested a potential role for cysteine proteases in the regulation of apoptosis, a key cellular process used by the macrophage to (i) contain and process ingested bacteria and (ii) facilitate cross-talk antigen presentation between the macrophage and dendritic cells.
To reverse the phenotype of vaccine-mediated macrophage attenuation, we engineered a novel BCG strain that expresses and secretes active CatS (rBCG-CatS) to examine its pro-apoptotic properties in vitro, and subsequently, immunogenicity in mice.
Transcriptomic profiling of macrophages infected with rBCG-CatS, but not BCG, revealed upregulation of key pro-apoptotic genes and downregulation of anti-apoptotic genes, which were further confirmed by RT-qPCR analyses of expression of selected genes. Macrophages infected with rBCG-CatS undergo apoptosis as indicated by increased levels of annexin V staining and intracellular caspase-3 cleavage. Consistent with these findings, mice vaccinated with rBCG-CatS showed increased antigen-specific CD4+ T-cell responses, as well as enhanced cytokine production and proliferation in CD4+ upon ex vivo re-stimulation.
Collectively, this study shows that a pro-apoptotic BCG strain alleviates adverse traits of the wild-type strain, resulting in a highly immunogenic TB vaccine.
- e-poster
Session Introduction
Natcha Sumpansirikul
Medical Student
Title: The prognostic significance of mortality in smear positive elderly pulmonary tuberculosis: studies in Surin hospital, Thailand
Biography:
Medical student in Surin hospital, Affiliated Institutes of Suranaree University of Technology, Thailand
Abstract:
Background: Age-related factors not only increase the risk of TB reactivation but also enhance susceptibility to TB infection, abetting outbreaks, high co-morbidity and high mortality. This study aim to evaluated prognostic factors, that effect mortality in elderly smear positive pulmonary tuberculosis.
Methods: A five years retrospective cohort study of smear positive pulmonary tuberculosis patients from January 2013 to December 2018. This study was conducted at Surin hospital, a secondary-care referral center in Thailand. The inclusion criteria were age 15 years, smear positive. The identified patients were divided into two groups. Patients:age 15-69 years and age higher than 69 year. All of the general data and medical records for the enrolled patients were reviewed. Patients who had diabetes, acquired immunodeficiency syndrome (HIV disease), chronic kidney disease, cirrhosis or age more than 70 years were defined as immune-compromised host. Relative risk was used. Significance testing by chi-square, Fisher’s exact test and time-to-event curves were generated by the Kaplan-Meier method and compared using the log-rank test. Cox proportional hazards regression analysis was performed to identify prognostic factors for 40-day survival after admission.
Results: In 5844 patients of tuberculosis from 2013 to 2018 have 675 patients identified that smear positive pulmonary tuberculosis, 401 were in control group and 134 were in the elderly group, 140 patients die and 535 patients survived. In the elderly age group, female was higher than male.The elderly group had statistically significant difference higher in acute respiratory failure and chronic kidney disease, but lower in HIV disease. The mortality rate increased continuously with age, risk difference 6.5% per 20 years. In elderly group are increase mortality rate, relative risk 1.55 times.There had statistically significant difference between two groups in mortality by univariable cox’s regression analysis (hazards ratio=1.56; 95%confidence interval=1.10-2.20; P=0.012) and by multivariable Cox’s regression analysis (hazards ratio=1.76; 95%confidence interval=1.23-2.54; P=0.002) were associated with 40 days survival. The medial survival was 17 and 35 days in elderly and control group, significant in log rank test (P<0.010).
Conclusion:In the elderly age group, female was higher than male.Mortality in the elderly was remarkably higher than in younger, and increased continuously with age.