The document discusses host-directed therapies (HDTs) for treating tuberculosis (TB). HDTs target host factors like cytokines and immune cell functions, rather than the TB pathogen itself. This approach is beneficial because current TB drugs have limitations and targeting host responses can reduce pathogen proliferation and hyper-inflammation. TB remains a significant global health problem, with about 9.2 million new cases estimated in 2006, especially in India. New and multi-drug resistant strains continue to emerge due to limitations of existing TB treatments.
Tuberculosis is a bacterial infection caused by Mycobacterium tuberculosis that can produce a latent or active disease. It remains a major global health problem, with 9 million new cases and 2 million deaths estimated to occur worldwide in 2008. TB is transmitted through the air when people who are sick with pulmonary or laryngeal TB expel bacteria, and is usually treatable with a standard 6 month drug regimen including isoniazid, rifampin, pyrazinamide, and ethambutol given over 2 months followed by isoniazid and rifampin for 4 months. Patient education and adherence to treatment are important to cure the disease and prevent transmission or development of drug resistance.
This ppt gives you idea about pathophysiology of tuberculosis and the pharmacology of drugs used to treat this infection. And it also give deep introduction of molecular interaction of mycobacteria with body i.e.. immune response by human to this mycobacteria.
it also gives you idea about treatment regimens and strategy for TB. discussed the different types of TB and mechanism of development of resistance by mycobacteria for anti-TB drugs.
This document provides an overview of tuberculosis (TB). It begins with an introduction stating that TB is an infectious disease caused by mycobacteria, usually Mycobacterium tuberculosis. It then covers the definition, signs and symptoms, causes, risk factors, mechanisms of transmission and pathogenesis, diagnosis, treatment including first and second line drugs, prevention including BCG vaccination and DOTS strategy, history of TB discoveries, and the societal impacts. The document aims to comprehensively summarize what is known about TB.
A 42-year-old HIV-positive man presents with symptoms of hemoptysis, weight loss, fever, cough, and chills. Imaging and testing reveal a lung lesion and acid-fast bacilli in a sputum sample, indicating pulmonary tuberculosis. The patient is not taking his HIV medications and has a low CD4 count, placing him at high risk. He is admitted to isolation and started on multidrug TB treatment while drug susceptibility testing is performed.
1) Tuberculosis remains a major global health problem, infecting around 1/3 of the world's population and causing millions of deaths each year, especially in developing countries.
2) Treatment involves a combination of antibiotics over a long period of time to prevent drug resistance, with first-line drugs like isoniazid and rifampin being most effective but also posing toxicity risks.
3) Control efforts face challenges from factors like poverty, HIV co-infection, and the emergence of drug-resistant strains, but expanded treatment programs could prevent over 200 million infections and 35 million deaths by 2020.
The following presentation is only for quick reference. I would advise you to read the theoretical aspects of the respective topic and then use this presentation for your last minute revision. I hope it helps you..!!
Mayur D. Chauhan
This document discusses various topics related to infectious diseases including:
- Types of diseases like acute, chronic, infectious, and non-infectious
- Common microbes that cause diseases like viruses, bacteria, protozoa, and fungi
- Means of disease spread such as airborne, waterborne, and vectors
- Treatment methods including reducing symptoms and killing microbes with medicines/antibiotics
- The immune response and how antibodies and white blood cells help defend against pathogens
- Specific diseases are also discussed like malaria, influenza, hepatitis, rabies, and AIDS.
Tuberculosis is a bacterial infection caused by Mycobacterium tuberculosis that can produce a latent or active disease. It remains a major global health problem, with 9 million new cases and 2 million deaths estimated to occur worldwide in 2008. TB is transmitted through the air when people who are sick with pulmonary or laryngeal TB expel bacteria, and is usually treatable with a standard 6 month drug regimen including isoniazid, rifampin, pyrazinamide, and ethambutol given over 2 months followed by isoniazid and rifampin for 4 months. Patient education and adherence to treatment are important to cure the disease and prevent transmission or development of drug resistance.
This ppt gives you idea about pathophysiology of tuberculosis and the pharmacology of drugs used to treat this infection. And it also give deep introduction of molecular interaction of mycobacteria with body i.e.. immune response by human to this mycobacteria.
it also gives you idea about treatment regimens and strategy for TB. discussed the different types of TB and mechanism of development of resistance by mycobacteria for anti-TB drugs.
This document provides an overview of tuberculosis (TB). It begins with an introduction stating that TB is an infectious disease caused by mycobacteria, usually Mycobacterium tuberculosis. It then covers the definition, signs and symptoms, causes, risk factors, mechanisms of transmission and pathogenesis, diagnosis, treatment including first and second line drugs, prevention including BCG vaccination and DOTS strategy, history of TB discoveries, and the societal impacts. The document aims to comprehensively summarize what is known about TB.
A 42-year-old HIV-positive man presents with symptoms of hemoptysis, weight loss, fever, cough, and chills. Imaging and testing reveal a lung lesion and acid-fast bacilli in a sputum sample, indicating pulmonary tuberculosis. The patient is not taking his HIV medications and has a low CD4 count, placing him at high risk. He is admitted to isolation and started on multidrug TB treatment while drug susceptibility testing is performed.
1) Tuberculosis remains a major global health problem, infecting around 1/3 of the world's population and causing millions of deaths each year, especially in developing countries.
2) Treatment involves a combination of antibiotics over a long period of time to prevent drug resistance, with first-line drugs like isoniazid and rifampin being most effective but also posing toxicity risks.
3) Control efforts face challenges from factors like poverty, HIV co-infection, and the emergence of drug-resistant strains, but expanded treatment programs could prevent over 200 million infections and 35 million deaths by 2020.
The following presentation is only for quick reference. I would advise you to read the theoretical aspects of the respective topic and then use this presentation for your last minute revision. I hope it helps you..!!
Mayur D. Chauhan
This document discusses various topics related to infectious diseases including:
- Types of diseases like acute, chronic, infectious, and non-infectious
- Common microbes that cause diseases like viruses, bacteria, protozoa, and fungi
- Means of disease spread such as airborne, waterborne, and vectors
- Treatment methods including reducing symptoms and killing microbes with medicines/antibiotics
- The immune response and how antibodies and white blood cells help defend against pathogens
- Specific diseases are also discussed like malaria, influenza, hepatitis, rabies, and AIDS.
This document summarizes several bacterial diseases:
Tuberculosis is caused by two types of bacteria and spreads through coughing or sneezing. It is diagnosed using tuberculin tests and treated with long-term antibiotic therapy. Diphtheria is caused by Corynebacterium diphtheriae bacteria and spreads through respiratory droplets. It produces a toxin that kills epithelial cells and blocks the respiratory tract. Pneumonia infects the lungs through inhaled droplets from infected individuals and is treated with antibiotics. Leprosy is a chronic disease caused by Mycobacterium leprae that spreads through direct contact and is communicable.
Tuberculosis is caused by the bacterium Mycobacterium tuberculosis. It primarily affects the lungs but can spread to other organs. TB is transmitted through inhaling respiratory droplets from infected individuals. Most people who are exposed will contain the infection without symptoms, but some will develop active progressive disease. The immune response involves macrophages and T cells forming granulomas to wall off the bacteria. Diagnosis involves tuberculin skin testing and sputum examination. Treatment requires a multi-drug regimen over several months to eliminate the infection.
This document discusses tuberculosis (TB), including its definition, causative agents, spread, epidemiology, pathogenesis, signs and symptoms, diagnosis, and treatment. It notes that TB is caused by bacteria in the Mycobacterium tuberculosis complex that usually affect the lungs. Diagnosis involves tests like smear microscopy, culture, PCR and tuberculin skin testing. Standard treatment involves a combination of antibiotics over 6-9 months. Drug-resistant forms like multi-drug resistant TB and extensively drug-resistant TB require longer and more toxic treatment regimes.
Tuberculosis is a chronic infectious disease caused by the bacterium Mycobacterium tuberculosis that primarily affects the lungs. It spreads through the air and is one of the top infectious killers worldwide. Those at highest risk include those with weakened immune systems, living in areas with high TB rates, abusing alcohol or tobacco, or living with an infected individual. The bacteria are inhaled, travel to the lungs, and can spread throughout the body. Most infections remain latent without symptoms, but active disease can cause coughing, weight loss, fever and other signs. Diagnosis involves sputum tests, chest imaging and tuberculin skin tests. Treatment requires multiple antibiotic drugs over several months to prevent drug resistance. New vaccines and drug
1. Tuberculosis is caused by the bacterium Mycobacterium tuberculosis and primarily affects the lungs. It was a major cause of death in the 19th century but treatable with medicines developed in the 1940s.
2. TB spreads through airborne droplets when people with active TB cough, sneeze or spit. It affects millions worldwide each year, especially in developing countries. Young children are most vulnerable.
3. Diagnosis involves tuberculosis skin testing, chest x-rays, and sputum and tissue samples. Standard treatment combines several front-line antibiotics taken for 6-12 months to kill the bacteria and prevent drug resistance.
Sirturo (bedaquiline) is a new drug approved by the FDA in 2012 for the treatment of multi-drug resistant tuberculosis. It works by inhibiting mycobacterial ATP synthase, which is essential for energy generation in tuberculosis bacteria. Sirturo represents the first new class of tuberculosis drugs approved in over 40 years. It is meant to be used as part of a combination therapy for drug-resistant tuberculosis when alternative treatment options are limited.
- Mycobacterium tuberculosis causes tuberculosis and infects around 1.7 million people annually, causing over 9 million new cases and 1.7 million deaths per year. An estimated 500,000 people are infected with multidrug resistant strains.
- Risk of infection and disease is highest among socioeconomically disadvantaged people with poor housing and nutrition. Tuberculosis is transmitted via respiratory aerosols from people with active, untreated tuberculosis.
- Laboratory diagnosis involves microscopy, culture, and molecular techniques using sputum, gastric washings, urine, tissues or other clinical samples. Staining methods like Ziehl-Neelsen identify acid-fast bacilli. Culturing is needed for species identification and drug
This presentation includes introduction, properties, transmission, epidemiology, pathogenesis, mechanism of infection, immunity and hypersensitivity, clinical manifestations, diagnosis, treatment, prevention and control of MYCOBACTERIUM TUBERCULOSIS.
Tuberculosis (TB) is a bacterial infection caused by Mycobacterium tuberculosis that primarily affects the lungs. It spreads through droplets in the air from coughing or sneezing. Risk factors include HIV/AIDS, diabetes, and malnutrition. Diagnosis involves chest x-rays, sputum smear and culture tests, tuberculin skin tests, and interferon-gamma release assays. Treatment uses a combination of antibiotics over 6-9 months including isoniazid, rifampin, pyrazinamide, and ethambutol. The WHO recommends the DOTS strategy to directly observe treatment and ensure adherence and cure. Drug-resistant TB requires longer and more toxic treatment regimens.
complete information of tuberculosis including OLD RNTCP and new RNTCP with the novel drug that is marketed; classification of tuberculosis (MDR XDR TDR). special population and tuberculosis treatment clinical presentation and diagnosis
This document discusses antimicrobial drugs and infections. It defines different types of infections like acute, chronic, and opportunistic infections. It also describes different causative agents of infections like bacteria, viruses, fungi and protozoa. The document then discusses the classification of antimicrobial drugs based on their chemical structure, mechanism of action, spectrum of activity and more. It provides examples for each category. The principles of antimicrobial therapy and factors considered in selecting antimicrobial agents are also summarized.
Tuberculosis is caused by the bacterium Mycobacterium tuberculosis. It typically affects the lungs but can spread to other organs. Symptoms include cough, fever, night sweats and weight loss. Diagnosis involves tuberculin skin testing, chest x-rays, and sputum smear microscopy. Treatment requires a combination of antibiotics taken for at least 6 months. Isoniazid, rifampin, pyrazinamide, and ethambutol are first-line drugs, while multidrug-resistant TB requires alternative drug regimens. Public health measures like DOTS aim to improve treatment adherence and reduce transmission.
Mechanism of pathogenicity-Exotoxin and endotoxinaiswarya thomas
Brief description on mechanisms of pathogenicity, actions of toxins produced by various bacteria and notable endotoxins and exotoxins. Mechanism of action of some of the commonest endotoxins and exotoxins are explained.
Mycobacterium tuberculosis-importance of TB day,classification of Mycobacterium species,Details on Mycobacterium tuberculosis-morphology,culture,resistance,biochemical reactions,antigenic characters,mode of transmission,pathogenesis,complications,lab diagnosis,treatment,DOTS Strategy and prophylaxis
This document provides information on tuberculosis (TB) including:
1. TB epidemiology statistics for Pakistan which has a high burden of TB with an estimated 250,000 new cases and 64,000 deaths per year.
2. Definitions of key TB terms such as prevalence, incidence, drug resistant cases, and treatment outcomes.
3. Descriptions of diagnostic tests for TB including the tuberculin skin test and its limitations, as well as the QuantiFERON blood test.
4. Overviews of the WHO recommended DOTS strategy for TB control, which involves direct observation of treatment, and the five elements of effective TB programs.
This document provides information about Mycobacterium tuberculosis, the bacteria that causes tuberculosis (TB). It discusses the taxonomy, morphology, antigenic structure, types of TB, biochemical properties, culture characteristics, staining techniques, pathogenesis, symptoms, laboratory diagnosis including sputum and blood tests and skin tests, treatment which involves a combination of antibiotics, and preventive measures. M. tuberculosis was first identified in 1882 by Robert Koch and is transmitted through airborne droplets from the lungs of infected individuals. Proper treatment is essential to prevent active TB from developing.
The document discusses tuberculosis (TB), caused by Mycobacterium tuberculosis. It notes that about 1/3 of the world's population is infected, with around 3 million deaths and 8 million new cases annually. TB is transmitted through airborne droplets and has an incubation period of 4-12 weeks. Diagnosis involves tests like sputum smear microscopy, culture, tuberculin skin test, chest x-ray, and PCR. Standard treatment includes isoniazid, rifampin, ethambutol and pyrazinamide for 2 months, followed by isoniazid and rifampin for 4 more months. Drug resistance is a major problem, with MDR-TB resistant to isoniazid
Specific prophylaxis and therapy of infectious diseases. Vaccines & toxoidesEneutron
Vaccines provide protection against infectious diseases by exposing individuals to antigens from pathogens in a way that does not cause disease. There are several types of vaccines, including live attenuated vaccines which use weakened live pathogens, and inactivated vaccines which use killed pathogens. Live vaccines typically produce stronger and longer-lasting immunity but carry some risk, while inactivated vaccines are safer but may require booster doses to maintain protection. Both vaccine types aim to stimulate the immune system's memory response to future pathogens, protecting individuals and populations through herd immunity when widely adopted.
1. Fungal infections are common in immunocompromised patients and those taking immunosuppressive drugs. They are harder to treat than bacterial infections.
2. There are two main types of fungal infections - superficial infections affecting the skin and mucous membranes, and deep infections affecting internal organs like the lungs and brain.
3. Major antifungal drug classes include azoles like fluconazole and itraconazole, polyenes like amphotericin B, and allylamines like terbinafine. They work by disrupting the fungal cell membrane or inhibiting fungal enzyme activity.
The document provides an overview of tuberculosis (TB) including epidemiology, diagnosis, and laboratory testing. Some key points:
- TB infects millions worldwide each year and is a leading cause of death. Rates are highest in developing countries.
- Diagnosis involves sputum smear microscopy, culture, and molecular testing like PCR. Smear microscopy has low sensitivity but high specificity. Culture is more sensitive but slower.
- Rapid culture methods like BACTEC and MGIT can detect TB in 2-8 days compared to 6-8 weeks for traditional culture.
- Molecular tests like PCR that detect TB DNA sequences like IS6110 can identify TB in smear-negative cases and distinguish TB from
- Tuberculosis is caused by the bacterium Mycobacterium tuberculosis and mainly affects the lungs, but can spread to other organs. It is transmitted through airborne droplets when infected people cough, sneeze or speak.
- China has the second largest tuberculosis epidemic in the world after India, with over 1.3 million new cases reported each year. Risk factors include poverty, malnutrition, HIV infection, and living/working conditions like overcrowding.
- Tuberculosis infection can either remain latent or progress to active disease. Diagnosis involves tuberculin skin tests, chest x-rays, sputum smears, and culture tests. Standard treatment uses a combination of antibiotics like isoniazid and
The treatment of multi drug resistant tuberculosis (mdr-tb) with sirturo (be...Kishore Chinna
This document discusses the treatment of multi-drug resistant tuberculosis (MDR-TB) with bedaquiline. It begins with an introduction on tuberculosis, noting it is caused by mycobacterium tuberculosis and can affect the lungs and other organs. It then covers the epidemiology of TB globally and definitions of MDR-TB and extensively drug resistant TB (XDR-TB), which are harder to treat forms of the disease. The document also discusses the causative organism, pathophysiology of TB infection and lesions, and concludes by focusing on bedaquiline as a treatment for MDR-TB.
This document summarizes several bacterial diseases:
Tuberculosis is caused by two types of bacteria and spreads through coughing or sneezing. It is diagnosed using tuberculin tests and treated with long-term antibiotic therapy. Diphtheria is caused by Corynebacterium diphtheriae bacteria and spreads through respiratory droplets. It produces a toxin that kills epithelial cells and blocks the respiratory tract. Pneumonia infects the lungs through inhaled droplets from infected individuals and is treated with antibiotics. Leprosy is a chronic disease caused by Mycobacterium leprae that spreads through direct contact and is communicable.
Tuberculosis is caused by the bacterium Mycobacterium tuberculosis. It primarily affects the lungs but can spread to other organs. TB is transmitted through inhaling respiratory droplets from infected individuals. Most people who are exposed will contain the infection without symptoms, but some will develop active progressive disease. The immune response involves macrophages and T cells forming granulomas to wall off the bacteria. Diagnosis involves tuberculin skin testing and sputum examination. Treatment requires a multi-drug regimen over several months to eliminate the infection.
This document discusses tuberculosis (TB), including its definition, causative agents, spread, epidemiology, pathogenesis, signs and symptoms, diagnosis, and treatment. It notes that TB is caused by bacteria in the Mycobacterium tuberculosis complex that usually affect the lungs. Diagnosis involves tests like smear microscopy, culture, PCR and tuberculin skin testing. Standard treatment involves a combination of antibiotics over 6-9 months. Drug-resistant forms like multi-drug resistant TB and extensively drug-resistant TB require longer and more toxic treatment regimes.
Tuberculosis is a chronic infectious disease caused by the bacterium Mycobacterium tuberculosis that primarily affects the lungs. It spreads through the air and is one of the top infectious killers worldwide. Those at highest risk include those with weakened immune systems, living in areas with high TB rates, abusing alcohol or tobacco, or living with an infected individual. The bacteria are inhaled, travel to the lungs, and can spread throughout the body. Most infections remain latent without symptoms, but active disease can cause coughing, weight loss, fever and other signs. Diagnosis involves sputum tests, chest imaging and tuberculin skin tests. Treatment requires multiple antibiotic drugs over several months to prevent drug resistance. New vaccines and drug
1. Tuberculosis is caused by the bacterium Mycobacterium tuberculosis and primarily affects the lungs. It was a major cause of death in the 19th century but treatable with medicines developed in the 1940s.
2. TB spreads through airborne droplets when people with active TB cough, sneeze or spit. It affects millions worldwide each year, especially in developing countries. Young children are most vulnerable.
3. Diagnosis involves tuberculosis skin testing, chest x-rays, and sputum and tissue samples. Standard treatment combines several front-line antibiotics taken for 6-12 months to kill the bacteria and prevent drug resistance.
Sirturo (bedaquiline) is a new drug approved by the FDA in 2012 for the treatment of multi-drug resistant tuberculosis. It works by inhibiting mycobacterial ATP synthase, which is essential for energy generation in tuberculosis bacteria. Sirturo represents the first new class of tuberculosis drugs approved in over 40 years. It is meant to be used as part of a combination therapy for drug-resistant tuberculosis when alternative treatment options are limited.
- Mycobacterium tuberculosis causes tuberculosis and infects around 1.7 million people annually, causing over 9 million new cases and 1.7 million deaths per year. An estimated 500,000 people are infected with multidrug resistant strains.
- Risk of infection and disease is highest among socioeconomically disadvantaged people with poor housing and nutrition. Tuberculosis is transmitted via respiratory aerosols from people with active, untreated tuberculosis.
- Laboratory diagnosis involves microscopy, culture, and molecular techniques using sputum, gastric washings, urine, tissues or other clinical samples. Staining methods like Ziehl-Neelsen identify acid-fast bacilli. Culturing is needed for species identification and drug
This presentation includes introduction, properties, transmission, epidemiology, pathogenesis, mechanism of infection, immunity and hypersensitivity, clinical manifestations, diagnosis, treatment, prevention and control of MYCOBACTERIUM TUBERCULOSIS.
Tuberculosis (TB) is a bacterial infection caused by Mycobacterium tuberculosis that primarily affects the lungs. It spreads through droplets in the air from coughing or sneezing. Risk factors include HIV/AIDS, diabetes, and malnutrition. Diagnosis involves chest x-rays, sputum smear and culture tests, tuberculin skin tests, and interferon-gamma release assays. Treatment uses a combination of antibiotics over 6-9 months including isoniazid, rifampin, pyrazinamide, and ethambutol. The WHO recommends the DOTS strategy to directly observe treatment and ensure adherence and cure. Drug-resistant TB requires longer and more toxic treatment regimens.
complete information of tuberculosis including OLD RNTCP and new RNTCP with the novel drug that is marketed; classification of tuberculosis (MDR XDR TDR). special population and tuberculosis treatment clinical presentation and diagnosis
This document discusses antimicrobial drugs and infections. It defines different types of infections like acute, chronic, and opportunistic infections. It also describes different causative agents of infections like bacteria, viruses, fungi and protozoa. The document then discusses the classification of antimicrobial drugs based on their chemical structure, mechanism of action, spectrum of activity and more. It provides examples for each category. The principles of antimicrobial therapy and factors considered in selecting antimicrobial agents are also summarized.
Tuberculosis is caused by the bacterium Mycobacterium tuberculosis. It typically affects the lungs but can spread to other organs. Symptoms include cough, fever, night sweats and weight loss. Diagnosis involves tuberculin skin testing, chest x-rays, and sputum smear microscopy. Treatment requires a combination of antibiotics taken for at least 6 months. Isoniazid, rifampin, pyrazinamide, and ethambutol are first-line drugs, while multidrug-resistant TB requires alternative drug regimens. Public health measures like DOTS aim to improve treatment adherence and reduce transmission.
Mechanism of pathogenicity-Exotoxin and endotoxinaiswarya thomas
Brief description on mechanisms of pathogenicity, actions of toxins produced by various bacteria and notable endotoxins and exotoxins. Mechanism of action of some of the commonest endotoxins and exotoxins are explained.
Mycobacterium tuberculosis-importance of TB day,classification of Mycobacterium species,Details on Mycobacterium tuberculosis-morphology,culture,resistance,biochemical reactions,antigenic characters,mode of transmission,pathogenesis,complications,lab diagnosis,treatment,DOTS Strategy and prophylaxis
This document provides information on tuberculosis (TB) including:
1. TB epidemiology statistics for Pakistan which has a high burden of TB with an estimated 250,000 new cases and 64,000 deaths per year.
2. Definitions of key TB terms such as prevalence, incidence, drug resistant cases, and treatment outcomes.
3. Descriptions of diagnostic tests for TB including the tuberculin skin test and its limitations, as well as the QuantiFERON blood test.
4. Overviews of the WHO recommended DOTS strategy for TB control, which involves direct observation of treatment, and the five elements of effective TB programs.
This document provides information about Mycobacterium tuberculosis, the bacteria that causes tuberculosis (TB). It discusses the taxonomy, morphology, antigenic structure, types of TB, biochemical properties, culture characteristics, staining techniques, pathogenesis, symptoms, laboratory diagnosis including sputum and blood tests and skin tests, treatment which involves a combination of antibiotics, and preventive measures. M. tuberculosis was first identified in 1882 by Robert Koch and is transmitted through airborne droplets from the lungs of infected individuals. Proper treatment is essential to prevent active TB from developing.
The document discusses tuberculosis (TB), caused by Mycobacterium tuberculosis. It notes that about 1/3 of the world's population is infected, with around 3 million deaths and 8 million new cases annually. TB is transmitted through airborne droplets and has an incubation period of 4-12 weeks. Diagnosis involves tests like sputum smear microscopy, culture, tuberculin skin test, chest x-ray, and PCR. Standard treatment includes isoniazid, rifampin, ethambutol and pyrazinamide for 2 months, followed by isoniazid and rifampin for 4 more months. Drug resistance is a major problem, with MDR-TB resistant to isoniazid
Specific prophylaxis and therapy of infectious diseases. Vaccines & toxoidesEneutron
Vaccines provide protection against infectious diseases by exposing individuals to antigens from pathogens in a way that does not cause disease. There are several types of vaccines, including live attenuated vaccines which use weakened live pathogens, and inactivated vaccines which use killed pathogens. Live vaccines typically produce stronger and longer-lasting immunity but carry some risk, while inactivated vaccines are safer but may require booster doses to maintain protection. Both vaccine types aim to stimulate the immune system's memory response to future pathogens, protecting individuals and populations through herd immunity when widely adopted.
1. Fungal infections are common in immunocompromised patients and those taking immunosuppressive drugs. They are harder to treat than bacterial infections.
2. There are two main types of fungal infections - superficial infections affecting the skin and mucous membranes, and deep infections affecting internal organs like the lungs and brain.
3. Major antifungal drug classes include azoles like fluconazole and itraconazole, polyenes like amphotericin B, and allylamines like terbinafine. They work by disrupting the fungal cell membrane or inhibiting fungal enzyme activity.
The document provides an overview of tuberculosis (TB) including epidemiology, diagnosis, and laboratory testing. Some key points:
- TB infects millions worldwide each year and is a leading cause of death. Rates are highest in developing countries.
- Diagnosis involves sputum smear microscopy, culture, and molecular testing like PCR. Smear microscopy has low sensitivity but high specificity. Culture is more sensitive but slower.
- Rapid culture methods like BACTEC and MGIT can detect TB in 2-8 days compared to 6-8 weeks for traditional culture.
- Molecular tests like PCR that detect TB DNA sequences like IS6110 can identify TB in smear-negative cases and distinguish TB from
- Tuberculosis is caused by the bacterium Mycobacterium tuberculosis and mainly affects the lungs, but can spread to other organs. It is transmitted through airborne droplets when infected people cough, sneeze or speak.
- China has the second largest tuberculosis epidemic in the world after India, with over 1.3 million new cases reported each year. Risk factors include poverty, malnutrition, HIV infection, and living/working conditions like overcrowding.
- Tuberculosis infection can either remain latent or progress to active disease. Diagnosis involves tuberculin skin tests, chest x-rays, sputum smears, and culture tests. Standard treatment uses a combination of antibiotics like isoniazid and
The treatment of multi drug resistant tuberculosis (mdr-tb) with sirturo (be...Kishore Chinna
This document discusses the treatment of multi-drug resistant tuberculosis (MDR-TB) with bedaquiline. It begins with an introduction on tuberculosis, noting it is caused by mycobacterium tuberculosis and can affect the lungs and other organs. It then covers the epidemiology of TB globally and definitions of MDR-TB and extensively drug resistant TB (XDR-TB), which are harder to treat forms of the disease. The document also discusses the causative organism, pathophysiology of TB infection and lesions, and concludes by focusing on bedaquiline as a treatment for MDR-TB.
This document provides an overview of tuberculosis (TB), including its definition, causative agents, types, risk factors, pathophysiology, clinical presentation, differential diagnosis, investigation, and treatment. TB is an infectious disease caused mainly by the bacterium Mycobacterium tuberculosis that typically affects the lungs. It can be transmitted through airborne droplets when an infected person coughs or sneezes. There are two main types - pulmonary TB affecting the lungs and extra-pulmonary TB affecting other organs. Risk factors include contact with infected individuals, immunosuppression, and lifestyle factors like drug/alcohol misuse. Treatment involves a two-phase drug regimen over 6-10 months with first-line antibiotics like rifampin,
Tuberculosis is a contagious infection caused by the bacterium Mycobacterium tuberculosis, which usually affects the lungs. It spreads through the air when people with the active respiratory disease cough, sneeze or speak. Common symptoms include weakness, weight loss, fever, night sweats and cough. Diagnosis involves a medical history, physical exam, tuberculin skin test or blood test, chest x-ray and microbiological tests. Treatment requires multiple antibiotics taken for several months and directly observed therapy is recommended to prevent drug resistance and ensure adherence.
This document summarizes a review study on tuberculosis conducted by Bashar M. Khazaal. It defines tuberculosis as an infectious disease caused by mycobacterium tuberculosis, which usually involves the lungs but can spread to other parts of the body. Risk factors, pathophysiology, clinical manifestations, diagnostic methods, complications, management, and drug-resistant forms like MDR-TB and XDR-TB are described. Diagnostic tests discussed include tuberculin skin test, chest X-ray, bacteriological examination, drug susceptibility testing using phenotypic and molecular methods, Quantiferon-TB, T-Spot TB, and PCR. Treatment involves a multi-drug regimen over several months and directly observed therapy to prevent drug resistance
This document provides information about the transmission and pathogenesis of tuberculosis (TB). It discusses:
- The history of TB, including key discoveries such as identifying TB as contagious in 1865 and discovering the bacterium that causes TB (Mycobacterium tuberculosis) in 1882. Antibiotics to treat TB were discovered starting in 1943.
- How TB is transmitted from person to person through droplets expelled from the lungs of someone with infectious pulmonary TB. These droplets contain M. tuberculosis bacteria.
- How TB develops in the body after transmission, including progression from latent TB infection to active TB disease if the immune system is compromised. Classification systems for TB are also described.
1) Tuberculosis is caused by mycobacteria, mainly Mycobacterium tuberculosis, and commonly affects the lungs. It can also affect other body systems when the immune system is weakened.
2) TB spreads through air when a sick person coughs or sneezes, expelling dried bacteria. Close and household contacts are most at risk of infection through inhalation or ingestion.
3) Diagnosis involves tests like chest x-rays, sputum smears, tuberculin skin tests, and culture of bacteria. Treatment requires taking multiple antibiotics like rifampin and isoniazid daily for 6-12 months to fully eliminate the bacteria.
Sam higgimbottom institute of agriculture technology and sciencesAbhishek Sunny
This document discusses tuberculosis (TB) disease management. It defines disease management and lists conditions it covers, including TB. TB is caused by Mycobacterium tuberculosis bacteria, which usually infect the lungs. Only 10% of latent TB infections progress to active disease without treatment. Symptoms include coughing, chest pain, and weight loss. Diagnosis involves tests like chest x-rays, skin tests, and sputum analysis. Standard TB treatment follows the DOTS strategy and uses antibiotics like isoniazid, rifampin and pyrazinamide for 6-8 months to cure the infection and prevent drug resistance. Side effects of the drugs can include liver problems and vision issues.
Tuberculosis (TB) remains a major global health problem. The document discusses TB, including its epidemiology in Pakistan. It describes the etiology, signs and symptoms, diagnosis, and treatment of active TB. TB is caused by the bacterium Mycobacterium tuberculosis. Diagnosis involves sputum smear, culture and chest x-ray. Treatment requires a multi-drug regimen over 6-9 months using drugs like isoniazid and rifampin under direct observation. Drug resistant TB poses a challenge to effective treatment.
Tuberculosis (TB) is a chronic bacterial infection caused by Mycobacterium tuberculosis that typically forms granulomas in the lungs. It is treatable with a combination of anti-TB drugs over a 6-12 month period to kill both actively replicating and dormant bacilli. Diagnosis involves physical exam, chest x-ray, tuberculin skin test, and sputum culture. Risk factors include HIV infection, poverty, and crowded living conditions.
TB, or tuberculosis, is caused by the bacterium Mycobacterium tuberculosis. It is spread through airborne droplets when an infected person coughs or sneezes. Most people who breathe in the bacteria develop a latent TB infection with no symptoms, but they cannot spread the disease. Active TB disease develops when the bacteria multiply causing symptoms like coughing, chest pain, and weight loss. Diagnosis involves tests like the Mantoux skin test, chest x-ray, and sputum culture. Treatment requires a combination of antibiotics taken for 6-9 months to cure the infection. Drug resistance is a major problem, as some strains are resistant to multiple first-line antibiotics.
This document summarizes information about pulmonary tuberculosis. It begins with definitions of tuberculosis and discusses it being a global public health emergency. It then covers the causes, signs and symptoms, transmission routes, risk factors, stages of infection, and diagnostic steps for tuberculosis. The diagnostic steps include history and clinical examination, radiographic features, and bacteriological evaluation including smear, culture, and new diagnostic methods like MGIT and nucleic acid amplification.
1) Tuberculosis remains a major global health problem, causing millions of cases and deaths each year worldwide. It commonly affects the lungs but can spread to other sites.
2) The host immune response to TB involves both innate and acquired immunity. Innate responses include phagocytosis by macrophages and natural killer cells. Acquired responses are primarily cell-mediated, involving CD4 and CD8 T cells that secrete cytokines like IFN-γ.
3) Cytokines play an important role in the immune response, with IL-12 and IFN-γ promoting the protective Th1 response and TNF-α also contributing to immune and pathological responses to TB.
This document provides an overview of tuberculosis (TB), including:
- TB is caused by Mycobacterium tuberculosis and commonly affects the lungs. It can spread through the air.
- Risk factors include HIV coinfection, poverty, and immunosuppression. Diagnosis involves sputum examination and skin testing.
- Treatment involves a combination of antibiotics like isoniazid and rifampin over 6-9 months to prevent drug resistance. Directly observed treatment is recommended to help patients complete therapy.
Tuberculosis is an infectious disease caused by the bacterium Mycobacterium tuberculosis. It most commonly affects the lungs but can affect other parts of the body. The disease spreads through airborne droplets when infected people cough, sneeze or speak. Diagnosis involves medical history, physical exam, tuberculin skin test, chest x-ray and microbiological tests. Treatment requires a combination of antibiotics taken for at least 6-12 months to prevent drug resistance from developing. Prevention strategies include identifying infected individuals and their contacts, testing high-risk groups, and immunizing infants with the BCG vaccine.
Tuberculosis (TB) is caused by the bacterium Mycobacterium tuberculosis. It typically affects the lungs and can cause symptoms like cough, fever, weight loss, and night sweats. Risk factors include HIV/AIDS, drug use, and other conditions that weaken the immune system. Diagnosis involves tests of sputum, chest x-rays, and tuberculin skin tests. Treatment requires multiple antibiotic drugs taken for 6-9 months. Drug-resistant TB requires specialized treatment with second-line drugs.
Tuberculosis is caused by bacteria belonging to the Mycobacterium tuberculosis complex. It usually affects the lungs and can spread to other organs if untreated. The most common causative agent is M. tuberculosis. Transmission typically occurs through airborne droplets produced by patients with infectious pulmonary TB. Common symptoms include cough, fever, night sweats and weight loss. While curable with proper treatment, tuberculosis remains a major global health problem especially in developing countries.
Comparative computational analysis of mycobacterium species by using differen...Alexander Decker
1. The document discusses Mycobacterium tuberculosis, the bacteria that causes tuberculosis. It is spread through the air and infects the lungs.
2. M. tuberculosis has an unusual waxy coating that makes it difficult to stain and allows it to survive outside of the body for weeks. It divides slowly compared to other bacteria.
3. When it infects lungs, M. tuberculosis is taken up by immune cells but is able to avoid being destroyed, allowing it to multiply unchecked inside the cells. Its unusual cell wall structure helps it evade the immune response and is a key virulence factor.
1. The document describes the design of a prodrug for Albendazole to reduce its side effects. It involves synthesizing 5,6-dibromo benzimidazole, which is expected to have less toxicity.
2. The synthesis was carried out using normal techniques and the compound was evaluated using melting point, TLC, chemical tests and solubility studies. It showed less solubility, indicating lower adverse reactions.
3. The aim is to overcome side effects of Albendazole through structural modification via a prodrug approach to reduce adverse drug reactions.
Formulation and evaluation of multipurpose herbal creamMonika Shirke
The document describes the formulation and evaluation of a herbal multipurpose cream. It discusses using various medicinal herbs in cream formulations for their therapeutic benefits. The formulation process and ingredients are outlined. Key evaluation tests are mentioned including appearance, pH, spreadability, and antimicrobial testing. The goal is to design a new herbal cream formula and assess its quality through various physicochemical and microbial parameters.
This document outlines the aim, references, requirements, procedure, and results for preparing a hydroalcoholic eye drop formulation of curcumin. The aim is to overcome challenges in ophthalmic drug delivery. The procedure involves accurately weighing curcumin and adding it to ethanol, then diluting the solution with distilled water to make 5 serial dilutions with concentrations ranging from 20% to 0.002% in Experiment 1 and 50% to 0.005% in Experiment 2.
1. The experiment aims to perform the assay of Ibuprofen as per Indian Pharmacopoeia.
2. Ibuprofen is titrated with 0.1M sodium hydroxide solution using phenolphthalein as indicator.
3. The percentage purity of Ibuprofen is calculated based on the titration results.
The document discusses anti-inflammatory agents known as non-steroidal anti-inflammatory drugs (NSAIDs). NSAIDs work by inhibiting the cyclooxygenase (COX) enzymes that produce prostaglandins, which are inflammatory mediators. There are two main COX isoforms, and most NSAIDs inhibit both COX-1 and COX-2 to varying degrees. Selective COX-2 inhibitors may reduce side effects associated with COX-1 inhibition like gastric irritation. NSAIDs are classified into different categories based on their chemical structure and properties. The most common NSAIDs inhibit COX through different mechanisms of action and metabolic pathways.
Host directing therapy fight against TBMonika Shirke
This document provides an overview of host directed therapies for tuberculosis. It discusses how host directed therapies target host factors like the immune system to help fight M. tuberculosis infection. Some classes of host directed therapies mentioned include repurposed drugs, cytokine therapies, monoclonal antibodies, vitamins, and cellular therapies. Repurposed drugs discussed include metformin, imatinib, and ibuprofen. The document also outlines strategies for developing host directed therapies, such as modulating cytokine responses, inhibiting immune checkpoints, using cellular therapies, and targeting immunomodulatory antigens or pathogen factors. Advantages of host directed therapies include established safety profiles and potential effectiveness against drug-resistant TB.
This presentation includes basic of PCOS their pathology and treatment and also Ayurveda correlation of PCOS and Ayurvedic line of treatment mentioned in classics.
A workshop hosted by the South African Journal of Science aimed at postgraduate students and early career researchers with little or no experience in writing and publishing journal articles.
How to Fix the Import Error in the Odoo 17Celine George
An import error occurs when a program fails to import a module or library, disrupting its execution. In languages like Python, this issue arises when the specified module cannot be found or accessed, hindering the program's functionality. Resolving import errors is crucial for maintaining smooth software operation and uninterrupted development processes.
Main Java[All of the Base Concepts}.docxadhitya5119
This is part 1 of my Java Learning Journey. This Contains Custom methods, classes, constructors, packages, multithreading , try- catch block, finally block and more.
LAND USE LAND COVER AND NDVI OF MIRZAPUR DISTRICT, UPRAHUL
This Dissertation explores the particular circumstances of Mirzapur, a region located in the
core of India. Mirzapur, with its varied terrains and abundant biodiversity, offers an optimal
environment for investigating the changes in vegetation cover dynamics. Our study utilizes
advanced technologies such as GIS (Geographic Information Systems) and Remote sensing to
analyze the transformations that have taken place over the course of a decade.
The complex relationship between human activities and the environment has been the focus
of extensive research and worry. As the global community grapples with swift urbanization,
population expansion, and economic progress, the effects on natural ecosystems are becoming
more evident. A crucial element of this impact is the alteration of vegetation cover, which plays a
significant role in maintaining the ecological equilibrium of our planet.Land serves as the foundation for all human activities and provides the necessary materials for
these activities. As the most crucial natural resource, its utilization by humans results in different
'Land uses,' which are determined by both human activities and the physical characteristics of the
land.
The utilization of land is impacted by human needs and environmental factors. In countries
like India, rapid population growth and the emphasis on extensive resource exploitation can lead
to significant land degradation, adversely affecting the region's land cover.
Therefore, human intervention has significantly influenced land use patterns over many
centuries, evolving its structure over time and space. In the present era, these changes have
accelerated due to factors such as agriculture and urbanization. Information regarding land use and
cover is essential for various planning and management tasks related to the Earth's surface,
providing crucial environmental data for scientific, resource management, policy purposes, and
diverse human activities.
Accurate understanding of land use and cover is imperative for the development planning
of any area. Consequently, a wide range of professionals, including earth system scientists, land
and water managers, and urban planners, are interested in obtaining data on land use and cover
changes, conversion trends, and other related patterns. The spatial dimensions of land use and
cover support policymakers and scientists in making well-informed decisions, as alterations in
these patterns indicate shifts in economic and social conditions. Monitoring such changes with the
help of Advanced technologies like Remote Sensing and Geographic Information Systems is
crucial for coordinated efforts across different administrative levels. Advanced technologies like
Remote Sensing and Geographic Information Systems
9
Changes in vegetation cover refer to variations in the distribution, composition, and overall
structure of plant communities across different temporal and spatial scales. These changes can
occur natural.
This presentation was provided by Steph Pollock of The American Psychological Association’s Journals Program, and Damita Snow, of The American Society of Civil Engineers (ASCE), for the initial session of NISO's 2024 Training Series "DEIA in the Scholarly Landscape." Session One: 'Setting Expectations: a DEIA Primer,' was held June 6, 2024.
How to Setup Warehouse & Location in Odoo 17 InventoryCeline George
In this slide, we'll explore how to set up warehouses and locations in Odoo 17 Inventory. This will help us manage our stock effectively, track inventory levels, and streamline warehouse operations.
BÀI TẬP BỔ TRỢ TIẾNG ANH 8 CẢ NĂM - GLOBAL SUCCESS - NĂM HỌC 2023-2024 (CÓ FI...
Seminar file
1. HOST DIRECTED THERAPIES FOR FIGHT AGAINST T.B.
Page 1
INTRODUCTION:
Recent work on novel TB treatment strategies has suggested that
directly targeting host factors is beneficial for TB treatment. Such strategies,
termed host-directed therapeutics (HDTs), focus on host-pathogen interactions.
HDTs are more beneficial than existed TB drugs, which are limited the long
durations of treatment and the emergence of drug-resistant strains. Targets of
HDTs include host factors such as cytokines, immune check points, immune
cell functions, and essential enzyme activities.
Tuberculosis (TB), which is caused by infection with
Mycobacterium tuberculosis (MTB), is a global health problem that has
significant lethality. Current anti-TB drugs have limitations such as adverse
effects and interactions with other drugs. HDTs also reduce pathogen
proliferation and the hyper-inflammatory response by modulating the host
immune system.
2. HOST DIRECTED THERAPIES FOR FIGHT AGAINST T.B.
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GlobalStatus of TB-
According to WHO estimates that about 9.2 million new cases of TB
occurred in 2006.India is the first rank in incidence.The global status of
TB are as follows:
Fig 1: Global Status of TB
3. HOST DIRECTED THERAPIES FOR FIGHT AGAINST T.B.
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History of TB -
Tuberculosis is an Ancient Disease. Spinal Tuberculosis in Egyptian Mummies
History dates to 1550-1080 BC identified by PCR. TB History Timeline as
shown in fig 2.
Fig 2: TB History Timeline
4. HOST DIRECTED THERAPIES FOR FIGHT AGAINST T.B.
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What is T.B.?
Tuberculosis or TB is a disease caused by -
1. Mycobacterium Tuberculosis
2. Mycobacterium Bovis
3. Mycobacterium Africanum
4. Mycobacterium Microti
5. Mycobacterium Canetti, etc.
Characteristics of Mycobacterium tuberculosis-
Fig 3: Mycobacterium tuberculosis
1. They are non- motile
2. Non -sporing
3. Non -capsulated
4. Mycolic acid present in cell wall makes it acid fast
5. Rod shaped 0.2-0.5 µ in D,2-4 µ in L
6. Divided every 15-20 hrs.
7. Unable to digested by microphages
8. Highly aerobic
Non -tuberculosis mycobacteria –
1. Mycobacteria that do not cause TB disease
2. Not usually spread from person to person
3. Example is M. avium complex
Common Symptoms of TB -
1. Cough(2-3 weeks or more)
2. Coughing up blood
3. Chest pains
4. Fever
5. Night sweats
6. Feeling weak and tired
7. Loss of appetite
5. HOST DIRECTED THERAPIES FOR FIGHT AGAINST T.B.
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Tuberculosis Affects Many Parts of the Body -
1. CNS (brain and meninges)
2. Bones ,Spines
3. Intestine, Middle ear
4. Lung, Liver
5. Spleen ,Pericardium
6. Adrenal glands etc.
Types of TB -
Drug-resistant TB –TB caused by organisms that are able to grow in the presence
of a particular drug; TB that is resistant to at least one first-line anti-tuberculosis drug.
Mono-resistant TB – TB that is resistant to one TB treatment drug.
Poly-resistant TB – TB that is resistant to at least two TB treatment drugs (but not
both isoniazid and rifampin); but is not MDR TB
Primary drug-resistant TB – Drug-resistant TB caused by person-to-person
transmission of drug-resistant organisms.
Secondary drug-resistant TB – Also referredto as acquired drug-resistant TB;
develops during TB treatment, either because the patient was not treated with the
appropriate treatment regimen or because the patient did not follow the treatment
regimen as prescribed.
Multidrug-resistant TB (MDR TB) – TB that is resistant to at least the drugs
isoniazid and rifampin; MDR TB is more difficult to treat than drug-susceptible TB.
Extensively drug resistant TB (XDR TB) – A rare type of MDR TB that is
resistant to isoniazid and rifampin, plus resistant to any fluoroquinolone and at least
one of three injectable second-line drugs (i.e., amikacin, kanamycin, or capreomycin)
Latent TB infection(LTBI) – Refers to the condition when a person is infected with
tubercle bacilli but has not developed TB disease. Persons with LTBI carry the
organism that causes TB but do not have TB disease symptoms and they cannot
spread TB germs to others.
Extrapulmonary TB – TB disease that occurs in places other than the lungs, such as
the lymph nodes, the brain, the kidneys. Extrapulmonary TB are not infectious.
Pulmonary TB – TB disease that occurs in the lungs. It is usually infectious if
untreated.
6. HOST DIRECTED THERAPIES FOR FIGHT AGAINST T.B.
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Pathogenesis of TB :
The pathogenesis of TB in schematic diagram are as following-
1. Inhalation of droplets infected with Mycobacterium
Tuberculosis.
2. It is trapped first in the upper airways, where the primary defences is activated
referring to the mucus-secreating goblet cell & the cilia.
When the initial prevention of infection is not successful, the bacteria reaches and
deposits itself in the lung periphery usually in the lower part of the upper lobe or the
upper part of the lower lobe; specifically in the alveoli.
The bacteria is quickly surrounded by polymorphonuclear leukocytes and engulfed by
the alveolar macrophages.
Some mycobacterial organisms are carried off by the lymphatics to the hilar lymp nodes
3. It is now called as the Ghon Complex , but it rarely results in the spread to other body organs.
As macrophages (epithelial cells) engulf the bacteria, these cells join and form
into giant cells. that encircle the foreign cell.
As a result of hypersensitivity to the organism, inside the giant cells
caseous necrosis occurs (granular chessy appearance)
4. There is then the proliferation of T- lymphocytes in the surrounding of
the central core of the caseous necrosis causing some lesions.
Fibrosis and calcification happens as the lesion ages resulting to granuloma
formation called as tubercle.
5. Collagenous scar tissue encapsulates the tubercle to separate the organisms from the body.
7. HOST DIRECTED THERAPIES FOR FIGHT AGAINST T.B.
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Pathogenesis ofTB - Pathogenesis of TB as shown in fig.4 are as following-
Fig.4:Pathogenesis of TB
8. HOST DIRECTED THERAPIES FOR FIGHT AGAINST T.B.
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Current Anti-TB drugs and their targets :
Table 1- Current Anti-TB drugs and their targets
Classification Drug Name MOA Structure
F
I
R
S
T
L
I
N
E
D
R
U
G
S
Ethambutol Inhibits mycobacterial
arabinosyl transferases.
Arabinosyl transferases
are involved in the
polymerization reaction
of arabinoglycan ,as
essential component of
the mycobacterial cell
wall.
Isoniazid It blocks mycolic acid
synthesis & kills the cell.
Rifampicin It binds to β –subunit of
bacterial DNA dependent
RNA polymerase and
inhibit RNA synthesis.
Pyrazinamide Pyrazinamide converts
into pyrazinoic acid
(POA).POA decreases
the pH below that retards
the growth of M.tb. and
inhibiting the fatty acid
synthesis.
Streptomycin Irreversibly inhibits
bacterial protein
synthesis.
9. HOST DIRECTED THERAPIES FOR FIGHT AGAINST T.B.
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S
E
C
O
N
D
L
I
N
E
D
R
U
G
S
Salicylates-
Para-amino
benzoic
acid(PABA)
To inhibit folic acid
biosynthesis and uptake
of iron.
Ethionamide Similar to isoniazide.
Cycloserine It inhibits the
incarporation of D-
alanine into
peptidoglycan
pentapeptide by inhibiting
alanine racemase. Inhibits
mycobacterial cell wall
synthesis.
Thiacetazone Bacteriostatic inhibits
cyclopropanaton of cell
wall mycolic acid.
Quinolones-
ciprofloxacin
Inhibits bacterial DNA
synthesis by inhibiting
bacterial topoisomerase
Macrolides-
Azithromycin
Bind to 50s ribosomal
subunits and blocks
dissociation of peptidyl t-
RNA from ribosomes
causing RNA –dependent
protein synthesis.
10. HOST DIRECTED THERAPIES FOR FIGHT AGAINST T.B.
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Amino
glycosides-
Kanamycin
Bacteriocidal and
believed to inhibits
protein synthesis by
binding to 30s ribosomes
subunit
Fig 5 : Antitubercular Drugs and Their Targets
11. HOST DIRECTED THERAPIES FOR FIGHT AGAINST T.B.
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New Anti-TB drugs -
Table 2- New Anti-TB drugs
Drug Name MOA Structure
Rifapentine Inhibits DNA -
dependent RNA
polymerase in
susceptible strains of
M.tb
Clofazimine Release of reactive
oxygen species(ROS)
and cell membrane
distruption
Bedaquilline Inhibition of
mitochondrial ATP
synthase
Delamanid Mycolic acid
biosynthesis inhibition
12. HOST DIRECTED THERAPIES FOR FIGHT AGAINST T.B.
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Pretomanid Inhibition of cell wall
of mycolic acid
biosynthesis
Sutezolide Protein synthesis
inhibitor
13. HOST DIRECTED THERAPIES FOR FIGHT AGAINST T.B.
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Diagnostic tests for TB-
A test used to detect TB infection
(see Mantoux tuberculin skin test
in glossary)
Tuberculin skin test (TST) -
A method of testing for TB infection; a
needle and syringe are used to inject 0.1
ml of 5 tuberculin units of liquid
tuberculin between the layers of the skin
(intradermally), usually on the forearm;
the reaction to this test, usually a small
swollen area (induration), is measured 48
to 72 hours after the injection and is
interpreted as positive or negative
depending on the size of the reaction and
the patient’s risk factors for TB.
Mantoux tuberculinskin test
(TST) –
14. HOST DIRECTED THERAPIES FOR FIGHT AGAINST T.B.
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A type of blood test that measures a
person’s immune reactivity to M.
tuberculosis.
Interferon-gamma release
assay (IGRA) –
A blood test used to determine TB
infection. The QFT-G measures the
response to TB proteins when they are
mixed with a small amount of blood.
QuantiFERON®-TB Gold
test (QFT-G) –
15. HOST DIRECTED THERAPIES FOR FIGHT AGAINST T.B.
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Current TB vaccine-
Microscopy-
The BacilleCalmette-Guérin (BCG) is
the ONLY successfulTB vaccine .Was
introduced in 1921.BCG is the world’s
most widely administered vaccine. Only
prevents serious TB disease in children
(TBM and military TB).WHO estimates
that it save the lives of over 40,000
children per year.
Microscopy of specially stained sputum is the
main test for diagnosing TB (1‐2 days)
•TB bacilli seen in the sputum sample using a
microscope(smear positive )
•Detects only ½of all TB and 1/3rd of HIV re
lated TB•PLHIV higher proportionof
sputum negative pulmonary TB –
extrapulmonary TB.
X‐ray also has a role for diagnosing TB if smea
r -ve .Role of culture: (takes 3 ‐4 wks)
•EPTB may require tissue samples/culture.
X ‐ray-
16. HOST DIRECTED THERAPIES FOR FIGHT AGAINST T.B.
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HOST DIRECTED THERAPY:
Host directed therapies (HDTs) are a relatively new & promising
approach to treatment of tuberculosis. HDTs comprise two strategies for
managing TB: manipulate macrophages function & modulate host immune
response. Current HDTs can potentially inhibit TB development via diverse
host pathways such as signal transduction-mediating cytokines, antimicrobial
processes, immune cell regulation, and epigenetic modulation. The use of
HDTs can be expected to reduce the bacterial burden and fine-tune the host
inflammatory response.
HDTs increase the effect of clinical treatment by reducing morbidity,
mortality, organ damage, and TB therapy duration. By directly targeting host
factors, HDTs enhance immune responses and fine-tune inflammation and can
thus be used to treat bacterial, viral, and parasitic infectious diseases. Current
treatment for MTB-mediated TB has several limitations, including the long
period of treatment, emergence of resistant strains, and toxicity of the drug.
These limitations raise the need for developing novel TB treatme nt strategies.
HDTs play a role in the clearance of MTB and regulation of the excess
inflammatory response to protect the host from permanent organ damage.
Furthermore, the combination of HDTs with current TB drugs reduces drug
dosage and improves benefits.
HDTs can target many mechanisms such as verifying anti-
mycobacterial activity of an approved drug (re-purposed drugs), inhibiting
immune checkpoints, and modulating cytokine production. We have shown
that antigens derived from the intracellular parasite T. gondii modulate the
immune response and might be promising for treating MBT infection.
However, HDTs need to be explored further. Because HDTs directly interact
with host factors, various variables need to consider prior to their application.
Furthermore, it is difficult to establish HDTs that manipulate a human factor
using an animal model. Understanding the host immune response in the TB-
mediated-immune pathology is very important in HDT research.
17. HOST DIRECTED THERAPIES FOR FIGHT AGAINST T.B.
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Targets host factor which are usually part of immune system in order to Therapy
that:
1. Potentiate human antimicobacterial effector mechanism.
2. Modulate innate and adaptive immune response.
3. Limit inflammation
4. Reduce tissue damage (Enzyme activity)
5. Limit long term effects of tissue destruction and fibrosis
The following are objectives of HDT-
1. Activity against antibiotic resistant Mtb strains
2. Possibly synergy with antibiotics
3. Possibly activity against non-replicating Mtb
4. Reduced likehood of resistance
5. Inhibit host factors used for Mtb pathogen
6. Augment innate & adaptive immune response to Mtb
7. Inhibit deterious immune response to Mtb
8. Induce novel immune response to Mtb
9. Inhibit bacterial functions & facilate host response
Advantages of HDT by Anti-T.B. drugs/repurposed drug:
1. Well established safety profile.
2. Shorter therapy duration.
3. Lower risk of relapse or re-infection.
4. Effective against drug -resistant cases.
5. Can be adopted to any chronic infection.
18. HOST DIRECTED THERAPIES FOR FIGHT AGAINST T.B.
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ClassesofHDTs-
These are the Classes of HDTs-
1. Monoclonal antibodies
2. Vitamins
3. Repurposed drugs
4. Cytokines
5. Cellular therapy
6. Recombinant proteins
Fig 6- Classes of HDTs
19. HOST DIRECTED THERAPIES FOR FIGHT AGAINST T.B.
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Strategies ofDevelopmentof TB HDT-
1. Repurposeddrugs-
Drug repositioning (also known as drug repurposing, re-profiling, re-tasking
or therapeutic switching) is the application of known drugs and compounds to treat
new indications (i.e., new diseases).A significant advantage of drug repositioning over
traditional drug development is that since the repositioned drug has already passed a
significant number of toxicity and other tests, its safety is known and the risk of
failure for reasons of adverse toxicology are reduced. More than 90% of drugs fail
during development; and this is the most significant reason for the high costs of
pharmaceutical R&D. In addition, repurposed drugs can bypass much of the early cost
and time needed to bring a drug to market. Examples of repurposed drugs- Imatinib,
Verapamil, Metformin and Ibuprofen etc.Difference between traditional drug
discovery process and Drug Repurposing as shown in fig.8.
Fig. 8-Difference between traditional drug discovery process and Drug
Repurposing
20. HOST DIRECTED THERAPIES FOR FIGHT AGAINST T.B.
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I. Metformin-
Metformin (Glucophage), which acts as an autophagy inducer, is
currently approved for the treatment of type 2 diabetes. Metformin activates
adenosine monophosphate-activated protein kinases, which are sensors of cellular
energy levels. Targeting adenosine monophosphate-activated protein kinases
expected as a potential anti-TB treatment. Metformin inhibits MTB growth by
inducing mitochondrial ROS production in vitro. The effect of current anti-TB
drugs can be enhanced by metformin, which was confirmed in acute and chronic
TB mouse models. Furthermore, metformin reduces the TB-mediated tissue
pathology and enhances IFN-γ-secreting CD8+ and CD4+ T-cell populations.
It also reduces the activity of chronic inflammatory genes in TB
patients, in addition to reducing mortality .Clinically, patients with type 2 diabetes
mellitus (T2DM) on statin therapy (as well as anti-diabetic therapy) seem to be at
lower risk of developing active TB. Metformin (MET) is an essential drug used in
the treatment of T2DM, which acts by affecting the mitochondrial respiratory
chain. In a recent preclinical study, MET was evaluated as an adjunct therapeutic
for drug-susceptible (DS)-TB and MDR-TB. MET treatment induced superoxide
anion production in macrophages infected with DS or MDR M. tb in an- adenosine
monophosphate-activated protein kinase (AMPK)-dependent manner.
A retrospective evaluation of patients with T2DM receiving MET
therapy showed that they are less prone to develop cavitary pulmonary TB. In
addition, T cell non-reactivity to ESAT-6 in a T-SPOT IFN-γ assay also suggested
less incidence of latent TB infection among these individuals. The ability of MET
to promote maintenance of memory CD8 T cells via AMPK-driven fatty acid
oxidation, as seen in mouse models of solid tumours, may be an additional avenue
for its potent immunomodulatory properties in TB.
21. HOST DIRECTED THERAPIES FOR FIGHT AGAINST T.B.
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Fig.9- Metformin, an FDA approved drug for type-II diabetes as a potential
combination therapy for Tuberculosis with existing antibiotics.
a) Antibiotic targeting mycolic acid biosynthesis; b) systems-level changes
resulting into the reduction of flux carrying capacity of glycolysis and
citric acid cycle c) resulting re-routing of metabolic fluxes through de
novo NAD biosynthesis pathway and electron transport through NDH-I
d) possibility of targeting NDH-I with metformin.
1. The bacterial respiratory chain complex NADH-Q oxidoreductase is classified
into three main subunits a) proton (H+) translocating subunit, H+ - NADH-Q
oxidoreductase (designated as NDH-I); b) sodium (Na+) translocating subunit,
Na+ - NADH-Q oxidoreductase (designated as Na+ - NADH) and c) NADH-Q
oxidoreductase that lacks energy coupling site and designated as NDH-II [5].
2. Earlier investigations suggest that bacterial NDH-I is encoded by nuoA~N
operon in E.coli, which is also encoded by Mtb genome.
3. A comparative analysis based on subunit sequence, cofactors and various
inhibitors suggest that NDH-I of bacteria is the counter part of mitochondrial
complex-I system.
4. Investigations also suggest that the bacterial NDH-I can be inhibited by
various inhibitors of mitochondrial complex-I such as pericidin A, capsaicin
and rolliniestain-1 thereby suggesting a common mechanism of NDH-I
inhibition by inhibitors of mitochondrial complex – I.
22. HOST DIRECTED THERAPIES FOR FIGHT AGAINST T.B.
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5. Metformin has been recently confirmed as inhibitor of mitochondrial complex
– I in cancer cells both in vitro and in vivo. Study also suggests implications of
Metformin in reducing tumorigenesis.
II. Imatinib -
Imatinib mesylate (Gleevec) is used to treat leukemia and
gastrointestinal stromal tumors. Imatinib is a small-molecule kinase inhibitor that
blocks tyrosine kinase enzymes. The therapeutic administration of imatinib promotes
the acidification and maturation of MTB-infected macrophage phagosomes, reducing
the number of colony-forming units (CFUs) in MTB-infected mice. Furthermore,
imatinib works synergistically with first-line anti-TB drugs to inhibit drug-resistant
mycobacterial strains.At sub therapeutic concentrations, imatinib strengthens host
defenses by increasing neutrophil and monocyte numbers through myeloproliferation.
III. Ibuprofen
Ibuprofen (Advil, Motrin, Nurofen) is a non-steroidal anti-
inflammatory drug normally used as a painkiller and an antipyretic.
23. HOST DIRECTED THERAPIES FOR FIGHT AGAINST T.B.
Page 23
This inhibitor of cyclooxygenase inhibits prostaglandin E2
production and enhances tumor necrosis factor (TNF) production in
macrophages.Although the direct antimycobacterial activity of ibuprofen is not
potent, it reduces lung tuberculous lesions and bacterial burden and enhances the
survival rate in a mouse model that mimics active TB.
24. HOST DIRECTED THERAPIES FOR FIGHT AGAINST T.B.
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2. Modulation of Cytokine Response-
Cytokine therapy can be an alternative method to current TB
chemotherapy limited using. This method uses immunomodulators to boost the
immune system. Cytokines contribute to various cellular responses, including
immune signaling in TB. Cytokine therapy induces the proinflammatory immune
response and antimicrobial activity, which can be beneficial in treating TB. IFN-γ
plays a major role in the host defense against MTB. IFN-γ, as a prototypical
product of Th1 cells, promotes the secretion of Th1 cytokines (such as IL-12) and
inhibits Th2 cytokines (such as IL-4).
In addition, IFN-γ upregulates class I and II antigen-presenting
cells and increases the antimicrobial activity of macrophages. Mutations in the
IFN-γ receptor gene result in high susceptibility to mycobacterial infections.
Granulocyte macrophage colony-stimulating factor (GM-CSF) increases the
number of macrophages, leading to an enhanced inflammatory response. GM-CSF
also shows antimycobacterial activity in human macrophages. Studies on GM-
CSF-deficient mice showed that GM-CSF plays critical immunomodulatory roles
in the host defense against pulmonary TB. Moreover, IL-2 induces the expansion
of T cells. However, recent studies have shown that IL-2 promotes CD4+CD25+
regulatory T-cell expansion, which suppresses the T-cell response. Some clinical
trials checking the effectiveness of IL-2 against TB have been reported.
Excessive proinflammatory cytokine production causes
permanent host tissue damage. Therefore, regulating cytokine production can be an
alternative approach to treat TB by reducing destructive inflammation. The current
monoclonal 23antibody used for cytokine neutralization modulates inflammatory
responses. The anti-TNF therapeutic agent adalimumab has been previously used
to treat TB. 7 IL-6, which accelerates the severity of disease in TB patients, is a
promising candidate. Blockade of the IL-6/IL-6 receptor pathway is considered
therapeutic in treating various diseases. The use of a monoclonal antibody, along
with the IL-6 receptor blockade, enhances anti-TB T-cell responses, decreases the
severe pathology, and reduces the MTB burden in mice. The antivascular
endothelial growth factor (VEGF, bevacizumab) monoclonal antibody inhibits TB
by normalizing vasculature, increasing the delivery of small molecules, and
decreasing hypoxia in tuberculous granuloma.
25. HOST DIRECTED THERAPIES FOR FIGHT AGAINST T.B.
Page 25
Advancing host-directedtherapy for tuberculosis-
Fig 10-Advancing host-directed therapy for tuberculosis
26. HOST DIRECTED THERAPIES FOR FIGHT AGAINST T.B.
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3. Inhibition of Immune Check Points- Immune checkpoints are molecules
in the immune system that either turn up a signal (co-stimulatory molecules) or
turn down a signal. Many cancers protect themselves from the immune system
by inhibiting the T cell signal. Ex..Anti PD-,Anti-LAG3, Anti-CTLA-4.Anti
PD-1-Programmed cell death 1 (PD-1) is a protein on the surface of active T
cells. When programmed death-ligand 1 (PD-L1) and PD-L2.Advantage of
targeting PD1 is that it can restore immune function in tumor
microenvironment. Nivolumab/pembrolizumab are PD-1 inhibitors currently
used to treat melanomas and other cancers.Anti-LAG3- Lymphocyte –
activation gene 3 (LAG3) used in cancer treatment. It works to suppress
an immune response by direct effect on CD8+Tcells.Anti-CTLA-4
Cytotoxic T –Lymphocyte Associated protein 4 .Control T cell proliferation.
4. Cellular therapy –Cell therapy (also called cellular therapy or cytotherapy) is
therapy in which cellular material is injected into a patient; this generally
means intact, living cells. For example, T cells capable of fighting cancer cells
via cell-mediated immunity may be injected in the course of immunotherapy.
Bone marrow-derived mesenchymal stromal cells -Reduction of inflammation
and enhancement tissue regeneration Clinical (late phase).Antigen-specific T
cells Cancer and viral infections Targeted killing of MTB- infected host cells.
5. Immunomodulatory antigen from pathogen-Immunomodulation is
modulation (regulatory adjustment) of the immune system. It has natural and
human-induced forms, and thus the word can refer to the
following:Homeostasis in the immune system, whereby the system self-
regulates to adjust immune responses to adaptive rather than maladaptive levels
(using regulatory T cells, cell signaling molecules, and so forth)
Immunomodulation as part of immunotherapy, in which immune responses are
induced, amplified, attenuated, or prevented according to therapeutic goals
GRA7 antigen driven intra cellular parasite T. gondii.- GRA7 controlled the
innate immune response by interacting with host cell proteins.GRA7 is
essential for the interaction between apoptosis-associated speck-like protein
containing a carboxyl-terminal CARD and phospholipase D1. These
interactions induced antibacterial activity against TB.
27. HOST DIRECTED THERAPIES FOR FIGHT AGAINST T.B.
Page 27
Fig.11-Host-directed therapies aimed at modulating immune responses in the
tuberculous lung. Overt immune responses characterise the pathological outcome in
tuberculosis (TB).
Neutralisation of pro-inflammatory cytokines such as IL-6, TNF-α, VEGF and IFN-αβ, as
well as anti-inflammatory IL-4 during severe pulmonary disease may help reduce ongoing
parenchymal damage in the lung. Alternatively, suboptimal activation of anti-TB immune
responses due to regulatory T cell activity can be reversed by the use of the anti-cancer drug
cyclophosphamide. Drugs with anti-TB potential, such as metformin, imatinib, ibuprofen,
zileuton, valproic acid, and vorinostat as well as nutraceuticals such as vitamin D3 not only
abate bacterial burden via host-dependent mechanisms, but may also fine-tune the immune
response to Mycobacterium tuberculosis (M. tb). These drugs increase phagocytosis of
extracellular bacteria, improved emergency myeloid response and increased autophagic and
apoptotic killing of bacteria, subsequently editing the T cell response in favour of the host.
Immune checkpoint inhibition with blockade of the PD-1/PD-L1, CTLA-4, LAG3 and TIM3
pathways may improve the quality of the cellular immune response to M. tb epitopes, as seen
in cancer. Abbreviations: VPA, valproic acid; PBA, phenylbutyrate; PD-1, programmed cell
death 1; PD-L1, PD-1 ligand 1; CTLA-4, cytotoxic T lymphocyte-associated antigen 4;
LAG3, lymphocyte-activation gene 3; TIM3, T cell immunoglobulin and mucin domain 3.
28. HOST DIRECTED THERAPIES FOR FIGHT AGAINST T.B.
Page 28
Developmentof HDT for TB -
Table 3 - Development of HDT for TB
Category Name Currently approved
indication(s)
Host target
Repurposed
drug
Imatinib Leukemia and
gastrointestinal stromal
tumors
Tyrosine kinase
Verapamil High blood pressure,
chest pain and
supraventricular
tachycardia.
Voltage-dependent calcium
channels
Metformin Diabetes AMP-activated protein
kinase activator
Ibuprofen Pain and fever relief Cyclooxygenase inhibitor
Cytokine
therapy
IL-2 Renal cancer and
melanoma
Cytokine modulation
GM-CSF Acute Myelogenous
Leukemia, after bone
marrow transplantation
Cytokine modulation
IFN-γ Chronic granulomatous
disease
Cytokine modulation
Monoclonal
antibody
Adalimumb
(Anti-TNFα)
Rheumatoid arthritis Cytokine neutralization
Tocilizumab
(Anti-IL6R)
Juvenile arthritis,
Castleman's disease
Cytokine neutralization
Bevacizumv
(Anti-VEGF)
Various cancer types Angiogenesis inhibitor
29. HOST DIRECTED THERAPIES FOR FIGHT AGAINST T.B.
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Monoclonal
antibody
Nivolumab
/pembrolizumab
(Anti-PD-1)
Melanoma, various
other cancers
Immune check point inhibitor
Anti-LAG3 Various cancers Immune check point inhibitor
Ipilimumab
(Anti-CTLA-4)
Melanoma, various
other cancers
Immune check point inhibitor
Cellular
therapy
Bone marrow-
derived
mesenchymal
stromal cells
Various inflammatory
indications
Reduction of inflammation and
enhancement tissue
regeneration
Antigen-
specific T cells
Cancer and viral
infections
Targeted killing of MTB-
infected host cells
30. HOST DIRECTED THERAPIES FOR FIGHT AGAINST T.B.
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Comparisonbetweencurrent anti-TB drugs and potential HDT strategies
for treating TB -
Fig 7 Comparison between current anti-TB drugs and potential HDT strategies for
treating TB
Current anti-TB drugs have been developed by targeting pathogenic
factors such as bacterial proliferation. A spontaneous gene mutation, which is targeted
by these antibiotics, occur drug-resistant TB. To overcome the limitations of current
anti-TB drugs, the development of new drugs is necessary.
HDTs directly affect host factors. Strategies of developing anti-TB
HDTs verify several TB studies. TB, Tuberculosis; HDTs, Host-directed therapeutics;
IL-2, Interleukin-2;GM-CSF,Granulocyte macrophage colony-stimulating factor; IFN-
γ, Interferon gamma; PD-1, Programmed cell death protein 1, LAG3, Lymphocyte
activation gene 3; CTLA-4, Cytotoxic T-lymphocyte-associated antigen 4; GRA7, T.
gondii dense granule antigen 7.
31. HOST DIRECTED THERAPIES FOR FIGHT AGAINST T.B.
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