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Theme
Elucidating Mycobacterial Resistance & Driving sustainability for TB control
- Tuberculosis 2017

About

Allied Academic Publication is a union of several esteemed academic and scientific associations known for promoting scientific journals. Established in the year 1997, Andrew John Publishing Group is a specialized Medical publisher that operates in alliance with the association and societies.  This publishing house has been built on the base of esteemed academic and research institutions including The Canadian Vascular Access Association (CVAA), The College of Audiologists & Speech Language Pathologists of Ontario(CASLPO), The Association for Public Safety Communications Officials of Canada (APCO), The Canadian Society of Internal Medicine (CSIM), The Canadian Association of Neurophysiologic Monitoring (CANM). The Canadian Hard of Hearing Association (CHHA), Sonography Canada, Canadian Association of Pathologists (CAP-ACP).

Allied Academies give the opportunity to meet the main experts around the world and invites participants all around the world to attend “Global Summit on Tuberculosis and Mycobacteria” during September 20-21, 2017 in Philadelphia, USA, which includes prompt Keynote Presentations, Oral talks, Special Sessions, Symposiums, Poster Presentations, Workshops and Exhibitions.

Sessions/Tracks

Track 01: Re-Emergence of Tuberculosis 

Tuberculosis is a highly contagious airborne disease caused by the bacteria ‘’Mycobacterium tuberculosis”. Mycobacterium is an obligate pathogenic bacteria and the causative agent of tuberculosis.  M. tuberculosis is highly aerobic and requires high levels of oxygen. Mycobacteria are non-motile, non-capsulated and non-sporing. It was first discovered by Robert Koch, in 1882.M. tuberculosis has an unusual, waxy coating on its cell surface, due to the presence of mycolic acid, which makes the cells unaffected to Gram staining. M. tuberculosis can appear Gram- positive and Gram- negative in clinical settings. The acid-fast stain, Ziehl-Nelsen stain or by fluorescent dyes is used preferably. In liquid cultures they form a mold -like pellicle, hence the name “Mycobacteria”, meaning fungus like bacteria. The most frequently used diagnostic methods for tuberculosis are the tuberculin skin test, acid-fast stain, and chest radiographs.

Track 02: Causes of Tuberculosis

TB is caused by Mycobacterium tuberculosis, a small, aerobic, non-motile bacillus. TB is widespread, deadly and causes the highest number of deaths worldwide. One third of the global population has latent TB infection. Bacteria usually attack lungs. But, TB bacteria can attack any part of the body such as the spine, brain and kidney. Symptoms for TB infection vary according to the organs involved, tuberculosis in kidneys causes blood in urine while, tuberculosis of spine may cause back pain.

Latent TB: This condition of TB infection, in which the bacteria remain in an inactive state and cause no symptoms. It is also called inactive TB or TB infection, isn't contagious, but can turn into active TB, so treatment is mandatory for the person with latent TB and to help limit the spread of TB. 

Active TB: Active TB is highly contagious and can spread to others. It may occur in the first few weeks after infection with the bacteria or it might occur years later.

The M. tuberculosis complex includes four other TB-causing mycobacterial species:

•         M. bovis: It was once a common cause of tuberculosis, but the awakening of pasteurized milk has almost completely eradicated as a public health issue in developed countries.

•        M. africanum: It is not widespread, but it is a significant cause of tuberculosis in parts of A africa. 

•        M. canetti: It is rare and seems to be limited to the Horn of Africa, although a couple of cases have been seen in African emigrants. 

•        M. microti.  It is also rare and is seen only in immunodeficient people, although its utility may be significantly underestimated.

•        M. pinnipedii: is also called as the seal bacillus for causing TB in fish-eating sea animal and on very rare occasions these pathogens were found to cause TB in humans.  

 

Other known pathogenic mycobacteria include M. leprae, M. kansasii., M. avium. and M. pinnipedii. The latter two species are classified as "Non-tuberculous Mycobacteria". NTM neither causes leprosy nor TB, but cause a pulmonary disease that resembles TB.


Track 03: Epidemiology of the Disease

Tuberculosis epidemiology is the field of science that is concerned with the study of health and disease within populations and the various factors that lead to these conditions, with a goal of preventing the spread of disease. One-third of the world's population has been infected with M. tuberculosis. Anyhow, not all infections with M. tuberculosis lead to TB disease. 13.7 million Chronic active cases, were reported by 2007 and 8.8 million new cases were estimated in 2010 and 1.45 million deaths, are often noted in developing countries.  Out of these, 0.35 million deaths occur in those co-infected with HIV. Tuberculosis distribution is not symmetrical across the globe, in many African and Asian countries (about 80% of the population) test positive in tuberculin tests, and in U.S only 5–10% of the population test positive. In 2012, around 450,000 people developed MDR-TB. TB incidence varies with age. In Africa, TB chiefly affects adolescents and young adults. However, in United States, TB has gone from high to low incidence, where TB is mainly a disease of older people, or of the immunosuppressed.

 Track 04: Genetics of M.tuberculosis

In 1998, the genome of the H37Rv strain was published. The size of the genome is 4 million base pairs, and has 3959 genes, out of these 40% of genes have their function characterised and another 44% are postulated with possible functions. Six pseudo genes are present within the genome.

Genome contains 250 genes involved in fatty acid metabolism, with 39 of these involved in the polypeptide metabolism generating the waxy coat. Such vast numbers of conserved genes show the revolutionary importance of the waxy coating to pathogen survival. M. tuberculosis can grow on the lipid cholesterol as a sole source of carbon, as genes involved in the cholesterol use pathways that have been important during various stages of the infection with tuberculosis. Mycobacteria that are isolated from lungs of infected mice were shown to use fatty acids over carbohydrate substrates, especially during the chronic phase of infection when other nutritional sources are not available.

10% of the coding genes are taken up by the amino acids that encode acidic, glycine-rich proteins. These proteins have a conserved N-terminal motif, deletion of which leads to impaired growth in granulomas and macrophages

Track 05: Virulence of M.Tuberculosis

When the mycobacteria reach the pulmonary alveoli, TB infection begins. The bacteria start invading and replicating within endosomes of alveolar macrophages. Macrophages analyse the bacterium as foreign and try to eliminate the bacteria by phagocytosis. During this process, the mycobacterium is surrounded by the macrophage and placed impermanently in a membrane-bound vesicle called phagosome. The phagosome then associates with lysosome to form phagolysosome. In the phagolysosome, the cell intends to use acid and reactive oxygen species to kill the bacterium. However, M. tuberculosis has a broad, waxy coating of mycolic acid that protects the cell from these toxic substances. M. tuberculosis has the ability to multiply and reproduce inside the macrophage until they burst the macrophage and will finally kill the immune cell, which leads to further infection.

 The primary site of infection in lungs, is known as the "Ghon focus", is either located in the lower part of the upper lobe or in the upper part of the lower lobe. Infection through the blood stream may also cause, tuberculosis of the lungs. This is known as Simon focus and is generally found in the upper part of the lungs. The hematogenous transmission may also spread infection to other sites, such as the brain, kidneys, peripheral lymph nodes, and to the bones. Other parts of the body may also be affected by the disease, it may rarely affect the pancreas, heart, thyroid or skeletal muscles.


Track 06: Mycobacterial symptoms

Tuberculosis most commonly occurs in the lungs called as pulmonary tuberculosis. When tuberculosis develops outside of the lungs, then extra pulmonary tuberculosis occurs.

General symptoms of tuberculosis includes: weight loss, fever, night sweats, chills, loss of appetite, and fatigue. 

Pulmonary:

In about 90% of cases, after tuberculosis infection becomes active commonly involves the lungs. Symptoms include chest pain and a prolonged cough producing sputum. About 25% of people remain "asymptomatic" i.e. they may not have any symptoms. Sometimes, people may cough up blood in small amounts, and in rare cases, the infection may lead to pulmonary artery or Rasmussen's aneurysm, resulting in extensive bleeding. Tuberculosis may later become a chronic illness and cause massive scarring in the upper lobes of the lungs. The upper lung lobes are more commonly affected by tuberculosis than the lower lung lobes. If there is either no better air flow, or poor lymph drainage within the upper lungs, then forms Chronic obstructive pulmonary disease.

Extrapulmonary:

In 15–20% cases, the infection spreads outside the lungs, causing other kinds of TB. These are generally known as "extrapulmonary tuberculosis". Extrapulmonary TB occurs most commonly in young children and immunosuppressed persons. In this category, more than 50% of cases are co-infected with HIV.  Extra pulmonary infection sites include the bones and joints (in Pott disease of the spine), pleura (in tuberculous pleurisy), the lymphatic system (in scrofula of the neck), the central nervous system (in tuberculous meningitis), the genitourinary system (in urogenital tuberculosis), and among others. A form of osteomyelitis, occurs when the bacteria spreads to the bones, it is also known as "osseous tuberculosis". "Disseminated tuberculosis", is potentially a more serious, widespread form of TB, also known as miliary tuberculosis. About 10% of extrapulmonary cases are reported by Miliary TB.


Track 07: Impact of Mycobacterial infections

Tuberculosis is a chronic inflammatory infectious disease caused by the bacteria, Mycobacterium tuberculosis. Tuberculosis generally affects the lungs, but can even affect other parts of the body. Most infections are asymptomatic, known as latent tuberculosis. About 10% of latent infections progress to active disease, if left untreated, mostly kills about half of those infected. Symptoms of active TB are chronic cough with blood-containing sputum, night sweats, one weight loss and fever. Infection of other organs can cause a wide range of symptoms including bones and joint pains, chest pain, neurological disorders and chronic pulmonary or respiratory distress etc.


Ø  People with reduced immune systems are at highest risk of producing active tuberculosis and dying of the disease, people infected with HIV are 40 times more likely to develop TB.

Ø  Tuberculin is the mostly used skin test for diagnosis of TB. 

Ø  Some antibiotics fail to kill the bacteria completely, as the bacterium becomes resistant to those antibiotics.  A majority of TB cases can be treated with antibiotics, such as isoniazid and rifampicin, which are the most powerful, anti-TB drugs.

Ø  Fully complete course of DOT treatment can successfully eradicate the infection and reduce the risk of antibiotic resistance developing. 


Track 08:TB Co-infections

TB and HIV co-infection is that where people have both, either latent or active TB disease and also HIV infection. A condition, where someone has both HIV and TB, each disease speeds up the progress of the other disease. In addition to HIV infection is speeding up the progress from latent TB infection to active TB disease, in accordance TB bacteria also enhance the progression of HIV infection. Than many other opportunistic infections, TB occurs earlier in the course of HIV infection. In co-infected individuals, the risk of death is also twice that of HIV infected individuals without TB, even when antiretroviral therapy and CD4 cell count are taken into account. The provision of anti TB drug therapy and HIV antiretroviral treatment at the same time involves a number of potential difficulties including: A high pill burden, Drug – drug interactions, Cumulative drug toxicities

TB and Diabetes co-infection: Poorly controlled diabetes can lead to numerous complications, including neuropathy, vascular disease, and increased susceptibility to infection. Diabetes may also lead to increased susceptibility to the disease via multiple mechanisms that are caused by M. tuberculosis. The mechanisms include those directly related to cellular insulinopenia and hyperglycaemia as well as indirectly effects on macrophages and lymphocyte function, leading to diminished strength to hold the organism.

There are even other co-infections with Tuberculosis such as malaria, Typhoid fever, Dengue, hepatitis. 

Track 9: Advances in Diagnostic Strategies

Diagnosis of TB should be considered with symptoms lasting longer than 2 weeks. A multiple sputum cultures for acid-fast bacilli and chest X-ray are typically part of the initial assessment.  Tuberculin skin tests and Interferon-? release assays are generally used in developing countries. TB diagnosis is made by identifying M. tuberculosis in a clinical sample such as pus, sputum, blood, or tissue biopsy. This slow-growing organism can take two to six weeks for sputum or blood cultures for their process. Hence, treatment is often begun before results of cultures are confirmed.  Adenosine deaminase testing and Nucleic acid amplification tests may allow rapid diagnosis of Tuberculosis, these tests are not regularly recommended. Blood tests to detect antibodies are not very sensitive or specific so they are not recommended.

The Mantoux tuberculin skin test is often used to test people at high risk of Tuberculosis. People who have been earlier immunized may have a false-positive result. The test may be detected falsely negative in those people with malnutrition, Hodgkin's lymphoma, sarcoidosis, and mostly in, active TB. Those who are positive to the Mantoux test, interferon-? release assays (IGRAs), on a blood sample, including the QuantiFERON-TB Gold tests (Cellestis) and T-SPOT, are recommended.  Most environmental mycobacteria are not affected by immunization so they generate fewer false-positive results. Yet, they are affected by M. szulgai, M. marinum, and M. kansasii.  Culture- acid fast detection (Ziel Nielson stain)  


Track 10: TB Clinical Trials

Clinical trials are concerned with diagnosis and Treatment of the disease. The development of drug-resistant TB (XDR-TB) and multidrug-resistant TB (MDR-TB) are extensively a rising global health problem. A recent advance in the progress of new drugs & regimens provides hope that may be well effective, tolerated, and shorter-duration treatment for tuberculosis will become available. During clinical trials they promote research within local TB control programs through association on clinical research of importance to public health settings, and to provide a platform for international collective research of consequence to both domestic and universal TB control.

Rapid urine-based screening for Tuberculosis in hospitalised patients in Africa to reduce AIDS-related mortality. Thibela TB is the mass screening and treatment plan in mining communities, The ZAMSTAR trial is the community TB testing and counselling, Diabetes correlated with increased risk of TB in the United Kingdom are some of the latest clinical trials or the projects going-on to reduce the risk of Tuberculosis.

Track 11: Challenges in TB Diagnostics

Tuberculosis has been a disease touching almost all parts of the globe since ages. Many efforts or strategies came in the past for improving diagnosis and treatment.  An effective vaccine has been desired after for long. With the emergence of resistant strains of Mycobacterium tuberculosis, and complexities emerging due to various associated infections and disease conditions, there is a furious need for further research in the field. Be it the better medication and care or better resistance management, proper diagnostics holds the key to success. It has been observed that a huge burden of the disease was accompanied by poor research set-up and resource limitations. The scenario was the same for several decades. With the renewed vision of funding agencies and resourceful countries, funding has been provided in many areas of research in tuberculosis detection and treatment. 

Track 12: Preventive Approaches for TB

TB prevention and control efforts depend primarily on the vaccination of infants and the detection and treatment of active cases. The World Health Organization (WHO) has achieved some success with rapid diagnostics and improved treatment regimens. US Preventive Services Task Force (USPSTF) endorses screening those who are at high risk for latent tuberculosis with either Mantoux tuberculin skin tests or interferon- ? release assays.

TB education is very much important for the general public awareness. The public needs to know basic information about Tuberculosis for many reasons including their spread through air, reducing the stigma associated with Tuberculosis. 

Prevention of TB consists of two main parts. The first part of preventing TB is to cease the transmission of Tuberculosis from one person to another. This can be done firstly, by identifying people with active TB infection, and then curing them by providing the drug treatment. With the provision of proper TB therapy someone with TB will not be infectious very quickly, and so cannot spread the disease to others. The second main part of preventing TB is to prevent people with latent TB infection from developing active infectious TB disease.

Track 13: Vaccines & Immunization

As of 2011, the only available vaccine is Bacillus Calmette-Guérin (BCG), is a vaccine for (TB) tuberculosis disease. Many people have been BCG-vaccinated. BCG is primarily used as vaccine in many countries with a high aid for preventing TB as childhood tuberculous meningitis and miliary disease. Tuberculosis can be treated by taking several drugs for 6 to 9 months.  There are 10 drugs presently approved by FDA (U.S. Food and Drug Administration) for treating TB. Out of the approved drugs, the first-line anti-TB agents that form the basis of treatment regimens include: isoniazid, pyrazinamide rifampin, ethambutol, streptomycin. Once the TB patient is known to be fully susceptible to ethambutol or streptomycin, it can be discontinued.

Directly observed therapy (DOT) is mainly recommended for all the patients. With DOT treatment, patients with the above regimens can shift to 2 to 3 times per week dosage after an initial 2 weeks of daily dosing. Patients on twice-weekly dosing should not miss any doses. Require daily therapy for patients on self-administered medication.

Track 14: Resistance to TB Drugs

Multidrug-resistant TB (MDR-TB) begins when an antibiotic fails to eradicate all the bacteria that it targets, with the surviving bacteria producing resistance to that antibiotic and usually others at the same time. Primary Multidrug resistant, MDR-TB occurs in patients who was not earlier been infected with TB but who became infected with a strain which is resistant to the treatment. Acquired multidrug resistance for TB occurs in patients during treatment with a drug regimen that is not competent of killing the particular strain of TB with which they have been infected. MDR-TB requires treatment with second-line drugs, often four or more anti-TB drugs for a minimum of 6 months and a maximum for 18–24 months, if rifampin resistance has been identified in the specific strain of TB with which the patient has been infected. Under ideal program conditions, MDR-TB cure rates can approach 70%. In general, second-line drugs are less effective, more toxic and much more expensive than first-line drugs. 

Track 15: Surveillance and Tracking of Drug-Resistant TB

Surveillance and tracking of drug-resistant TB promotes in understanding the overall concern of the disease and can inform research and use in diagnosis, treatment, and infection control. In South Africa, speakers at the symposium described various approaches being taken to advance the tracking of drug-resistant TB. The first section reviews the purpose of genetic fingerprinting methodologies to understand the physiology and genotype of various drug-resistant TB strains found throughout the globe. The second section describes a clinical screening strategy that has been produced to enhance TB case finding. The final section directs the need to increase laboratory capacity. A strengthened information base for TB laboratories could support the diagnosis and treatment of drug-resistant TB. Improved case finding requires improved planning and evaluation, as well as regular, global surveillance for drug-resistant TB. A HIV clinical record combined with a simple TB screening application and routine HIV care aspects can lead to improved tracking and can be beneficial for quality and continuity of care.

Track 16: New Trends for Tuberculosis in R&D

Currently tuberculosis (TB) control methods, does not effectively block transmission of TB, and do not include a competent vaccine.  Research studies show the mass vaccination campaigns using new vaccines could prevent14.5 million deaths from 2015 and 85.9 million new cases through 2050 in southern Asia alone. After many years, it now includes 7 vaccine candidates that are being tested in humans. Two non-replicating viral vectored vaccines have very recently entered the first phase IIb efficacy trial in infants (the first such trial in 80 years) and in human immunodeficiency virus-infected adults. Science is improving, but the scientific advancements need to be guided by political mobilization to ensure that the resources are available to produce, manufacture, and distribute the new vaccines and thus, save billions of lives throughout the world. Researchers are utilizing information retrieved from the entire sequence from the genome of M. tuberculosis and from new genetic & physiological methods to identify targets in M. tuberculosis that will aid in the development of these greatly needed antitubercular agents. 

Goals of TB therapy:

1.      Simplify and shorten the treatment of latent, active, drug-sensitive TB

2.      Improve efficiency, safety and shorten duration of therapy for drug-resistant disease.

3.      Develop drugs for those with TB who are co-infected with HIV that can be readily given with ARVs.

Challenges in reaching these goals

1.      Exemplify the biological mechanisms of mycobacterial latency and persistence.

2.      Develop new preclinical ways for identifying optimized drug combinations and new clinical and regulatory approaches for testing drug combinations in phase 2 and 3 clinical trials.

3.      Discover and develop new drugs that have unusual mechanisms of action and are effective against unremitting bacilli.

4.      Develop and validate animal models that accurately predict human treatment duration.

5.      Strengthen capacity to conduct clinical trials in high-burden countries. 

6.      Develop and validate biomarkers and proxy endpoints that predict efficiency and thereby shorten clinical trial duration.



Market Analysis Report

Market Analysis report:

Health departments of Columbia (DC) verified TB cases in the 50 states and District electronically report that meet the Council of State, CDC and Territorial Epidemiological case defines to the National Tuberculosis Surveillance System. Reports involve the patient’s medical and demographic information, clinical information and social risk factors for TB, and about the TB case. CDC calculates state and overall national TB incidence by using July 1 midyear population estimates from the U.S. Census Bureau. The Current Population Survey provides the population figures for incidence according to race/ethnicity and national origin. TB case tally and incidence during 2015 as per 100,000 population and % change from 2014 were determined for 50 states and for each census division.

TB incidence in the United States during 2013–2015 remained approximately 3.0 cases per 100,000 persons. After 2 decades of progress toward tuberculosis elimination with annual decreases of ?0.2 cases per 100,000 persons have been reported. Initial data stated to the National Tuberculosis Surveillance System display that TB incidence among U.S.-born persons (1.2 cases per 100,000) has remained approximately 13 times the foreign-born persons incidence in the U.S (15.1 cases per 100,000). Proceeding to the progress towards TB elimination will require amassing of efforts both in the U.S and other parts of the world, including, strengthening systems to stop TB transmission in the United States and all around the universe, increasing U.S. efforts to detect and treat latent TB infection, and accelerating reductions in TB globally, particularly in the countries of origin and with highest reported cases.

  Notifications of respiratory tuberculosis cases and incidence to ESMI, 2000-2011*

Year

Number of cases

Incidence (per 100,000 population)

Annual change in numbers (%)

Annual change in incidence (%)

2000

403

8.0

-

-

2001

351

6.9

-12.9

-13.8

2002

393

7.8

12.0

13.0

2003

367

7.3

-6.6

-6.4

2004

392

7.7

6.8

5.5

2005

365

7.2

-6.9

-6.5

2006

381

7.5

4.4

4.7

2007

410

8.0

7.6

5.7

2008

445

8.6

8.5

8.0

2009

486

9.4

9.2

8.8

2010*

503

9.7

3.5

3.2

2011*

453

8.6

-9.9

-11.3

*Data for 2010-11 are provisional and may be subject to change

   


 


FIGURE: Tuberculosis (TB) incidence overall and among U.S. and foreign-born persons, by year, 2000–2015*

 

 

 

 Societies and Associations:

           American Lung Association

          National Tuberculosis Controllers Association

           American Thoracic Society

Companies:

·         AstraZeneca

·         Otsuka

·         Tibotec

·         Vertex

·         GlaxoSmithKline-Tres Cantos Medicines Development Campus

In 2009 the TB-TC (TB- treatment campaign) underwent its third formal external re-competition. In the next decade (2010–2020), TBTC patient enlistment will shift from clinical sites located mostly in North America to sites which are predominantly international. The 2009 championship has expanded TBTC’s international presence from a few clinical sites located outside of North America, to sites in Peru, Spain, South Africa (two sites), Uganda, Kenya, Vietnam, China (Hong Kong).The TBTC 2010–2020 research group also includes U.S. sites in New York, Washington DC, Texas (four sites), Colorado and Tennessee. Some TBTC sites in and outside North America are linked, in that CDC awarded funds for the international study sites to the U.S. based institutions that proposed them as partners in the competitive process.


 

TBTC clinical trials have enrolled more than 14,000 patients and volunteers over the past 20 years. The consortium's annual operating budget is approximately $9,000,000.00.Encounting many challenges to the successful development of new TB drugs and treatment regimens, the TBTC looks forward with optimism. The late plateform of new anti-TB drug candidates is the most promising in 40 years, and advances in TB clinical trials science have promoted the progress of these agents. With commitment and support from CDC, the TBTC provides a unique resource for these clinical studies, and will continue to play an important role in improving TB treatment, prevention and control. Currently the TBTC is conducting an international, multicenter, randomized, controlled, open-label, 3-arm, phase 3 non-inferiority trial. The results of this clinical trial determine the efficacy, using the definitive endpoint of durable cure, of a regimen containing rifapentine substituted for rifampin and administered in combination with other drugs for 17 weeks (approximately four months).   

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