thesis topic on tuberculosis

132 Tuberculosis Essay Topics

🏆 best essay topics on tuberculosis, ✍️ tuberculosis essay topics for college, 👍 good tuberculosis research topics & essay examples, 🎓 most interesting tuberculosis research titles, 💡 simple tuberculosis essay ideas, ❓ research questions on tuberculosis.

• Tuberculosis, Health Determinants and Nurse’s Role
• Tuberculosis and Epidemiologic Triangle
• Tuberculosis, Its Causes and Symptoms
• Mycobacterium Tuberculosis: Causes and Treatment
• Tuberculosis: Desciption and Role of Nursing
• The Characteristics of Tuberculosis
• Epidemiology and Communicable Diseases: Tuberculosis
• Tuberculosis as Global Health Risk The global annual TB cases are falling at a rate of 2 percent, which could be increased to 4 percent to address this problem in line with End TB Strategy milestones.
• Tuberculosis Infections and Healthcare in Brunei Tuberculosis infections are a major health concern in Brunei, just like is the case for other South Asian countries. This paper discusses the aspects of the problem.
• Tuberculosis: Diagnostics and Treatment This disease is caused by Mycobacterium tuberculosis, which is a pathogenic bacteria belonging to the order Actinomycetales, family Mycobacteriaceae, and genus Mycobacterium.
• Tuberculosis: Family Medicine and Disease Prevention This essay focuses on tuberculosis infection, prevention and control, surveillance, epidemiology, and significant events.
• Tuberculosis and Post-Exposure Prophylaxis Tuberculosis is a common infectious disease caused by Mycobacterium tuberculosis. Tuberculosis is now a significant problem in many countries around the world.
• Tuberculosis Under Epidemiological Analysis Tuberculosis is a highly contagious disease, and it has airborne transmission. Due to its rapid spread, it remains a global problem nowadays, and humanity cannot cope with it.
• Tuberculosis and Preventive Measures in India This paper aims to develop, propose, and describe several measures to prevent the TB epidemic in India during the COVID-19 crisis.
• Drug-Resistant Mycobacterium Tuberculosis Strains As with any other infectious disease, TB exhibits specific signs and symptoms that help distinguish it from other illnesses.
• Tuberculosis Transmission, Manifestations and Social Concerns The paper states that Tuberculosis is preventable and curable and individuals should seek immediate medical attention when they feel they are infected.
• The U.S. Government and the Global Fund: Fight AIDS, Tuberculosis and Malaria The United States participates in a range of international health programs, in particular, and contributes financially to the Fund to Fight AIDS, Tuberculosis, and Malaria.
• Tuberculosis as an Infectious Disease The paper discusses tuberculosis. It is an infectious disease because it spreads through tiny droplets when released through coughs and sneezes.
• Tuberculosis: Diagnostics, Prevention, and Management Nurses play an essential role in the diagnostics and treatment of tuberculosis patients: doing the screening, reporting the cases, acting prompt with diagnosis establishment, etc.
• Tuberculosis Desease: Symptoms and Prevention This paper seeks to explore one of the re-emerging infectious diseases the world faces. Tuberculosis (TB) is a re-emerging infectious disease affecting the world’s population.
• Tuberculosis: Control of Non-Endemic Communicable Diseases Tuberculosis is an infectious disease that is traditionally considered a disease of poverty. It influences mainly adults of the productive age.
• Diabetes and Tuberculosis: Review of Articles in Nursing This paper discusses articles in nursing about different issues related to diabetes, trends in prevalence and control, and also about tuberculosis treatment.
• Antimicrobial Resistance in Mycobacterium Tuberculosis: A Review Antimicrobial resistance is a factor that steadily nullifies the efforts put into the attempts to triumph over tuberculosis.
• Epidemiology. Tuberculosis as Communicable Disease This paper aims to investigate TB’s core properties, as it still presents a substantial danger for human health with several issues not fully resolved by contemporary researchers.
• Mycobacterium Tuberculosis: Pathogenesis and Epidemiology This paper discusses M. tuberculosis with a special focus on its structure and physiology, pathogenesis, epidemiology of the disease, treatment, and prevention of the infection.
• Researching the Issue of Tuberculosis Disease in the World Tuberculosis (TB) is among the serious infectious diseases reported in countries across the world. It mainly affects individuals’ lungs.
• Global Health Issues, Tuberculosis Tuberculosis is often latent and reveals itself when the immune system is weak. The TB incidence rates in Southeast Asia and Africa remain the highest in the world.
• Tuberculosis: Risks, Implications, and Prevention The research question is: What are the key risk factors, health implications, and appropriate prevention strategies for TB infections?
• Tuberculosis and Control Programs The present paper offers an overview of tuberculosis and reviews the recommendations and guidelines of effective disease control programs.
• Tuberculosis Education and Cooperation in Mumbai This paper discusses tuberculosis causes with specific regard to the current achievements and challenges observed in Mumbai, the west coast of India.
• Tuberculosis Education in Mumbai, India In this paper, the promotion of healthy living through the reduction of epidemic cases of tuberculosis (TB) will be discussed with specific regard to the current achievements and challenges.
• Tuberculosis as a Highly Contagious Infection The purpose of this paper is to explain the elements that influence the infectiousness of a tuberculosis patient.
• AIDS, Tuberculosis, Hepatitis in Miami Community AIDS, tuberculosis, and hepatitis have been marked as the most dangerous in the list of the most spread communicable illnesses that citizens of Miami suffer from.
• Tuberculosis, Mumps, Influenza in Miami The recent events of Hurricane Irma created an increasingly unhealthy environment for Miami. The three diseases that require containment are tuberculosis, mumps, and influenza.
• Malaria, AIDS, and Tuberculosis in Miami, Florida The paper will discuss and analyze AIDS, Tuberculosis, and Malaria and how they influence the community in Miami, Florida.
• Tuberculosis: Case Study Assessment This paper gives an assessment of the case study Jose and Jill that concern tuberculosis, how its transmitted, prevention strategies and barriers, and their elimination.
• Influenza, Tuberculosis, AIDS Prevention in Miami Three population-based communicable illnesses have been chosen for analysis: influenza, tuberculosis, and AIDS.
• Tuberculosis Rates and Related Issues in Miami Although tuberculosis is not a new threat to patients’ well-being, it remains a tangible threat to U.S. communities, the one in Miami, FL not being an exception.
• Tuberculosis, AIDS, and Influenza A Virus in Miami The communicable diseases, which strongly affect the life of the population of the Miami-Dade County community are tuberculosis, AIDS, and influenza A virus.
• HIV, Gonorrhea, and Tuberculosis in Miami HIV, STDs such as gonorrhea, and tuberculosis are among those diseases that have the highest rates and thus the most influence on the community life in Miami.
• Tuberculosis Epidemiology in Global Public Health Tuberculosis (TB) is one of the most widespread infectious diseases all over the world. More than 95% of TB deaths happen in low- and middle-income countries.
• Tuberculosis, Its Description and Epidemiology Tuberculosis (abbreviated as TB) is one of the common communicable diseases in different parts of the world. This disease affects the human lungs.
• Tuberculosis, Influenza A, AIDS in Healthy People 2020 This discussion explains how HIV/AIDS, influenza A, and tuberculosis affect Miami city. The paper also describes how the community deals with these communicable illnesses.
• The Nurse-Patient Ratios: Tuberculosis in Elderly The main purpose of the paper is to discuss the nurse-patient ratios as the aspect for the concern and highlight the reasons elder people are at the highest risk for tuberculosis.
• Analysis of Extensively Drug-Resistant Tuberculosis: Characteristics, Treatment and Prevention Tuberculosis is one of the most contagious diseases. This paper gives a detailed analysis of Extensively Drug-Resistant Tuberculosis.
• Nurse-Patient Ratio and Tuberculosis A drop in the number of nurses and increase in the number of the patients presupposes the quality of the services declines correspondingly.
• Macrophage Polarization: Convergence Point Targeted by Mycobacterium Tuberculosis and HIV
• Tuberculosis and Compliance With Medical Protocols
• HPLC: Techniques Used for the Diagnostic of Ancient Tuberculosis Remains
• Anti-tuberculosis Drug-induced Liver Injury (ATLI) Effects
• Morphoproteomic-guided Host-directed Therapy for Tuberculosis
• Tuberculosis Market Share, Trends, H2 2016
• The Causes and Treatment of the Disease of Tuberculosis
• Advancing Immunotherapeutic Vaccine Strategies Against Pulmonary Tuberculosis
• The Zebrafish Breathes New Life Into the Study of Tuberculosis
• Tuberculosis: Most Lethal Bacterial Pathogen
• Diagnosis for Latent Tuberculosis Infection: New Alternatives
• Multidrug Resistant Tuberculosis
• South Africa and Tuberculosis
• Monocyte Subsets: Phenotypes and Function in Tuberculosis Infection
• The Differences and Similarities of Pneumonia and Tuberculosis
• Challenging the Drug-Likeness Dogma for New Drug Discovery in Tuberculosis
• Tuberculosis: Infectious Disease and TB Patients
• Tuberculosis and New Tuberculosis Vaccines
• Fair Regulates Fatty Acid Biosynthesis and Is Essential for Virulence of Mycobacterium Tuberculosis
• Clinical Presentations and Outcomes Related to Tuberculosis in Children Younger Than 2 Years of Age in Catalonia
• Tuberculosis: Immune System and Ongoing Research
• Artificial Neural Networks for Prediction of Tuberculosis Disease
• Epidemiology, Tuberculosis, and the Homeless Population
• Drug Resistance Rising Among Mycobacterium Tuberculosis
• Tuberculosis Among Native Americans
• Gut Dysbiosis Thwarts the Efficacy of Vaccine Against Mycobacterium Tuberculosis
• BCG Vaccination and Who’s Global Strategy for Tuberculosis Control 1948-1983
• Tuberculosis Vaccine May Help Stop Multiple Sclerosis Development
• Aid and the Control of Tuberculosis in Papua New Guinea: Is Australia’s Assistance Cost-effective
• Tuberculosis: Infectious Disease and Health Care Facilities
• Tuberculosis and Its Pathogenic Processes
• Examining Mycobacterium Tuberculosis, Its Spread, and Effect
• Tuberculosis and Its Effects on the Body System
• Host Antimicrobial Peptides: The Promise of New Treatment Strategies Against Tuberculosis
• United States Constitution and TB Patients
• Tuberculosis and New Types of Testing
• HIV and Tuberculosis Infection in Sub- Saharan Africa
• Reassessing Twenty Years of Vaccine Development Against Tuberculosis
• Tuberculosis and Its Effects on the Lungs
• Wild Animal Tuberculosis: Stakeholder Value Systems and Management of Disease
• Relationship Between Traveling and Infections of Tuberculosis
• Foam Cells Control Mycobacterium Tuberculosis Infection
• Examining the Complex Relationship Between Tuberculosis and Other Infectious Diseases in Children
• Extra-pulmonary Tuberculosis (EPTB) Treatment
• Host-directed Therapeutic Strategies for Tuberculosis
• Tuberculosis and Its Treatment
• Cost-Effectiveness and Addressing Tuberculosis
• Tuberculosis and Its Severity
• Harnessing the mTOR Pathway for Tuberculosis Treatment
• Tuberculosis, Important Determinants, and the Health System
• Historians Blamed Columbus for Spreading Tuberculosis to the World
• Tuberculosis and New Mexico
• Public Health Disease Management of Tuberculosis
• Factors Influencing the Perceived Priority of Tuberculosis in India
• Current and Novel Approaches to Vaccine Development Against Tuberculosis
• Tuberculosis and Its Effects on Society
• Cellular and Molecular Mechanisms of Mycobacterium Tuberculosis Virulence
• Tuberculosis and Antibiotic Resistance
• Animal Models for Tuberculosis in Translational and Precision Medicine
• Granulomas and Inflammation: Host-directed Therapies for Tuberculosis
• What Are the Organs Not Affected in Tuberculosis?
• What Is Bone Tuberculosis and What Is the Cure of Bone Tuberculosis?
• Why Is the Tuberculosis Epidemic So Hard to Stop?
• How Long Can Tuberculosis Patients Survive Without Treatment?
• Why Does Tuberculosis Appear in the Upper Lung?
• What Should Be the Diet for Someone With Tuberculosis Meningitis?
• Why Is There an Evening Rise of Temperature in Cases of Tuberculosis?
• Is It Possible That Tuberculosis Medication Cause Skin Problem?
• Will Intestinal Tuberculosis Spread From One Person to Another?
• What Are the Factors Responsible for the Re-Emergence of Tuberculosis?
• Is Tuberculosis Considered to Be Hereditary?
• Can Tuberculosis Happen Twice, Even if It Was Properly Cured Earlier?
• What’s the Link Between Tuberculosis and COVID-19?
• Is There Anyone Who Is Suffering From Lymph Nodes Tuberculosis?
• Is There Any Permanent Way to Eradicate Tuberculosis by Any Vaccines?
• Is There Any Ayurvedic Medicine to Cure Tuberculosis Completely?
• Does a Tuberculosis Patient on Treatment for a Month Infect Others With Tuberculosis?
• What Are the Different Types of Tuberculosis?
• What Are Causes, Symptoms, Signs and Treatment for Tuberculosis?
• Did Doctors Burn the Hearts of Tuberculosis Vitctims in the Late 1800s?
• What Killed More People Last Century: War, Tuberculosis or Influenza?
• Is It Possible to Get Tuberculosis a Second Time?
• Without Access to Antibiotics, What’s the Best Treatment for Tuberculosis?
• Is It That Tuberculosis Follows Pneumonia or Pneumonia Follows Tuberculosis?
• Is the Tuberculosis Blood Test the Same as the Tuberculosis Skin Test?

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StudyCorgi . "132 Tuberculosis Essay Topics." March 1, 2022. https://studycorgi.com/ideas/tuberculosis-essay-topics/.

StudyCorgi . 2022. "132 Tuberculosis Essay Topics." March 1, 2022. https://studycorgi.com/ideas/tuberculosis-essay-topics/.

These essay examples and topics on Tuberculosis were carefully selected by the StudyCorgi editorial team. They meet our highest standards in terms of grammar, punctuation, style, and fact accuracy. Please ensure you properly reference the materials if you’re using them to write your assignment.

This essay topic collection was updated on December 27, 2023 .

103 Tuberculosis Essay Topic Ideas & Examples

🏆 best tuberculosis topic ideas & essay examples, 💡 interesting topics to write about tuberculosis, ⭐ good essay topics on tuberculosis, 📌 simple & easy tuberculosis essay titles.

• 🥇 Most Tuberculosis Abortion Topics to Write about
• Pulmonary Tuberculosis: Case Study Tuberculosis (TB) is considered one of the oldest contagious diseases. As of 2010, World Health Organization estimated that there were 8.8 million of people infected.
• The History of Tuberculosis To prove the contagiousness of the infection, the French doctor Jean-Antoine Villemain collected the sputum of the infected and placed it in a container with guinea pigs.
• The Misinformation Associated With Tuberculosis Diagnosis The head of HR should also be interviewed to assess how workers’ data is being stored and whether the method is secure.
• The Concepts of Epidemiology and Nursing Research to Tuberculosis A typical sign of tuberculosis of the spine is back pain, but a sign of TB of the kidneys is blood in the urine.
• Tuberculosis: Epidemiology, Prevention, and Control Approximately 920,000 cases of TB and HIV coinfection were accounted for in 2017, representing 9% of the total TB cases observed.
• Strategy Against Tuberculosis in US Children Tuberculosis in children and adolescents in the US remains a serious medico-biological and social problem, the significance of which has significantly increased in the conditions of the tuberculosis epidemic.
• Tuberculosis Presentation Supplement As a result, policies for the prevention and control of tuberculosis are still in use and are vital for the population.
• Tuberculosis in the Late 19th Century Tuberculosis became a dangerous challenge for the society of the Gilded Age and was inscribed in the public culture through the works of art.
• Tuberculosis: Transmission, Clinical Manifestations and Treatment When inhaled, the Tubercle bacilli are carried to the alveolar, where they cause infection. LTBI patients do not manifest any symptoms and are unable to spread the infection.
• Tuberculosis in Older Adults: Epidemiological Analysis Despite the decrease in TB cases, the number of older adults affected by it remains stable throughout the years, signifying that the current measures need to be tailored for this specific group.
• The Tuberculosis Medication: Patient Compliance Various methods have been used to ensure patient compliance during TB treatment; most of the methods have focused on: home based care and hospital based care where the health officials have developed mechanisms to ensure […]
• Discussion of Tuberculosis Epidemiology These two sources offer relevant and credible information about smoking patterns in the area and causes leading to the emergence of new addicted people.
• The Problem of Co-Morbidity: Alcohol and Tuberculosis The problem of alcohol abuse as one of the main factors for the emergence and amplification of tuberculosis is widely discussed in medical circles and social organizations as well.
• Tuberculosis: Symptoms and Treatment The development of the disease is gradual with only an eighth of those infected with the mild form of the disease developing secondary infection.
• Tuberculosis: Diagnosis, X-Ray Radiography Tuberculosis is among the disease category of rare bone diseases, and the problem is estimated to occur in the range of 1 to 3 %.
• Reduction of Tuberculosis in Brockton, Massachusetts The other objectives include reduction of infections of contagious diseases and development of vaccinations through an increase in the number of people vaccinated for these disorders. The social and economic statuses of the disadvantaged people […]
• Tuberculosis: Causes and Prevention For women between the ages of 14 and 45, TB infection is the leading cause of death. Poverty is a localized environmental factor that directly aggravates the onset and development of TB.
• Tuberculosis: Demographics & Epidemiological Triangle The primary source of the bacteria is the sputum emanating from the larynx or the lungs of untreated tuberculosis patients. During the treatment of tuberculosis, the first step is to isolate the patients in a […]
• Respiratory Isolation Teaching for Tuberculosis The patients and their family members should be provided with the right information and guidelines on how to organize the appropriate isolation rooms and maintain the patient in order to prevent the spread of the […]
• Recognizing Health Care Worker With Tuberculosis in the Workplace On the other hand, workers that are aware of the health policies do not understand them because of the complex language, and terminologies used in the health documents.
• Pharmacology of the Tuberculosis Epidemic With over a third of the global population contracting TB infections, paradigmatic questions, such as the origin of TB, its treatment, demographics and frequency remain unexplored in-depth.
• Epidemiology: Tuberculosis in India The health status of a nation is one of the key indicators of the level of growth or the economic status of a given nation since a healthy nation automatically results to a wealthy nation.
• Peter Crosta: What Is Tuberculosis? What Causes Tuberculosis? The name of the bacterium causing tuberculosis is Mycobacterium Tuberculosis. The article also discusses the various treatment options that can be used to treat patients infected with tuberculosis.
• Prevalence of Tuberculosis and Malaria in Africa and Middle East Globally the epidemiological distribution of Malaria and Tuberculosis disease worldwide is greatly skewed with majority of the cases occurring in Africa; 90% of all malaria related deaths for instance take place in Africa which is […]
• Tuberculosis Surveillance Program: Evaluation Design Participation of the users and the application of the information in guiding future prevention, research and control programs will be adhered to.
• The Global Impact of Tuberculosis and Malaria Again the whole of Africa shows the maximum incidence when compared to the rest of the world. The HAART therapy in HIV infections allows the treatment period to be free of TB infection.
• Pathophysiology and Management of Tuberculosis Infection This, though, is in sharp contrast to the limited development of BCG in the first two decades of the 20th century.
• The Problem of Tuberculosis in South Africa Consequently, high treatment interruption rates, the HIV epidemic, low cure rates have contributed to the emergence of multi drug resistance tuberculosis in South Africa; this has been blamed on the adoption of inappropriate treatment programmes […]
• Mycobacterium Tuberculosis Intervention As a BSN-prepared community health nurse, Debbie needs to implement measures that reduce the danger of a tuberculosis outbreak in the community.
• Tuberculosis Control and Prevention in Prisons It is widely accepted that the overall conditions in the US correction facilities, along with the background lifestyles of some inmates, lead to a dramatic disease rate in cells.
• HR Department Steps to Provide Health Information: Tuberculosis The first step, or lecturing, should include the causes and conditions for the occurrence of pulmonary diseases with the emphasis on tuberculosis, as well as the results and consequences of treatment.
• Tuberculosis: Health Behaviors, Surveillance System, and Risk Communication In the case of TB, risk communication, especially between ordinary people, is essential, since some people may be ashamed of their disease and even prefer not to treat it rather than make it known.
• Tuberculosis: History and Current State of a Disease A breakthrough in understanding the nature of tuberculosis occurred in the XIX century. The recent figures indicate quite a high level of disease spread in Georgia.
• Tuberculosis as the Health Problem in New Jersey New Jersey has a health policy that postulates the actions of physicians and medical personnel in cases of new cases of tuberculosis.
• Communicable Diseases: Tuberculosis The explication following herein describes tuberculosis as an infectious disease including details such as the disease’s incidence in the World and in Cobb County, GA, agent characteristics, environmental characteristics, signs and symptoms, treatment, and how […]
• Culture and Disease: Tuberculosis and African Americans In this paper we will discuss in details about tuberculosis and why the African Americans have been thinking of the disease and how different treatment options, cultural beliefs and values have been impacting on the […]
• An Overview of Tuberculosis The coming into existence of deadly diseases and the escalation of the already existing epidemics, to name but a few, are some of the key characteristics of this century.
• Tuberculosis: The Symptoms, Pathogenesis, and Treatment The cell wall is however, due to the presence of concentration of lipids, thought to be the main contributor for the virulence of the bacterium.
• Tuberculosis Treatment in Clinical Practice This paper briefly discusses the agent and environmental characteristics of the disease, its signs, symptoms, and treatment, providing a basis for the public health nurse’s clinical practice.
• Tuberculosis and How to Prevent Its Dissemination Due to an easy way of spreading and the gravity of the consequences, it is necessary to prevent the dissemination of tuberculosis.
• Tuberculosis Employee Assistance Program As a part of them, TB tests, training for employees about tuberculosis and other infections, and HR policies should help to prevent such situations in the future.
• Tuberculosis: Epidemiology and Health Statistics Nevertheless, access to health care and the quality of treatment are not the only factors contributing to the resurgence of TB. As compared to the worldwide statistics, the U.S.is not included in the list of […]
• Descriptive and Analytical Epidemiology: Tuberculosis and HIV The establishment of trends in the epidemic process for the rapid introduction of adjustments helps optimize preventive and anti-epidemic measures alongside the evaluation of the effectiveness of the activities.
• Descriptive and Analytical Epidemiology: Tuberculosis in Pennsylvania To obtain a comprehensive picture of the issue, it is necessary to identify the main categories of the population at risk.
• Tuberculosis in Nigeria: Policy Brief Considering this, the present policy brief will discuss the nature of the infection, its risk factors and the populations it affects most, the scope of infection spread in Nigeria, and the consequences of the problem […]
• Examining Chest X-Rays of a Tuberculosis Patient This microbial infection of the respiratory parts of the lung proceeds with the development of intraalveolar exudation and inflammatory infiltration of the pulmonary parenchyma, fever, and productive cough with mucopurulent sputum.
• Tuberculosis and Human Immunodeficiency Coinfection Moreover, TB is a sensitive illness because the improper medication is dangerous as it can result in the illness becoming resistant to drugs to both the patient and the person to who the patient transmits […]
• Tuberculosis: Prevention, Diagnosis and Treatment In this case, it means that the incubation period will be counted from the introduction of the ‘causal’ microbe, as opposed to the initial infection.
• Tuberculosis Epidemiology Worldwide in 2015 Despite multiple attempts to eliminate the most dangerous diseases and improve the epidemiologic situation, there are many illnesses or other health issues that deteriorate the health of the nation and result in the appearance of […]
• EFI Testing to Detect Drug Resistance of Tuberculosis The article that was selected for the review introduces the problem of antibiotics resistance and the causes of it in humans.
• Tuberculosis Outbreak Investigation When investigating whether a disease is a cluster, a researcher should gather adequate information, which will help him/her to make a conclusion. When investigating whether a disease is an outbreak, a good researcher should gather […]
• Tuberculosis: Community and National Response Most commonly, three or four antibiotics are taken during the initial months of the treatment, and the number is decreased to two for the rest of the process.
• Tuberculosis Statistics Among Cigarette Smokers The proposal outlines the statistical applications of one-way ANOVA, the study participants, the variables, study methods, expected results and biases, and the practical significance of the expected results.
• Tuberculosis and Infectious Disease Slogan The level of awareness about sexually transmitted diseases among people is higher compared to that of tuberculosis, owing to the fact the risk factors of the latter are hard to identify. The risk population of […]
• Epidemiological Studies of Tuberculosis The United States The prevalence rate of tuberculosis in the United States is the lowest when compared to the prevalence rates in Sub-Saharan Africa and Asia.
• Prevention and Treatment of Tuberculosis Although a strong immune system can contain the pathogen, in an immunosuppressed individual, the MTB is capable of multiplying and rupturing the host’s macrophages, resulting in the destruction of the body’s primary line of defense […]
• Control of Tuberculosis in Swaziland This is a programme plan for controlling the TB epidemic in Swaziland as one of the developing countries with highest prevalence of TB infections in the world.
• The Problem of Tuberculosis in the American Local Community The public health ministry is in charge of curtailing the effects of the disease, but it is reluctant to liaise with the community to resolve the issue.
• The Role of Vitamin D for Tuberculosis Treatment This study investigates the use of vitamin D for the deterrence and cure of tuberculosis and other contagious infections. The unearthing of vitamin D as a therapeutic agent begins with the detection of rickets as […]
• The Evolutionary Genetics of Mycobacterium Tuberculosis The aim of the study was to define the prevalence of the various genotypes, drug resistance isolates and cluster patterns of Mycobacterium tuberculosis in Taipei in order to present information on the possible methods and […]
• The Impact of Tuberculosis on the Work of Anton Chekhov
• The Second Greatest Cause of Death Due to a Single Infectious Agent: Tuberculosis
• Tuberculosis: The Most Common Bacterial Infection Worldwide
• The Differences and Similarities of Pneumonia and Tuberculosis
• Modern Methods of Tuberculosis Diagnosis
• Prevention of the Tuberculosis Epidemic
• Global Tuberculosis Testing Market Finds Encouragement in Growing Healthcare Efforts
• Risk-Based Disease Management in the Fight Against to Bovine Tuberculosis
• People Centered Tuberculosis Care Verses Standard Directly
• The Signs, Symptoms and Treatment of Tuberculosis
• The Diagnosis of Cancer, Pulmonary Tuberculosis, and HIV AIDS
• Living in the Shadow of Death Tuberculosis and the Social Experience of Illness in American History
• The Pathogenesis of Mycobacterium Tuberculosis
• Tuberculosis: Most Lethal Bacterial Pathogen
• The Relationship Between Cystic Fibrosis and Tuberculosis
• Tuberculosis Vaccine May Help Stop Multiple Sclerosis Development
• The Role of Race and Economic Disadvantage in the Incidence of Tuberculosis
• Factors Influencing the Perceived Priority of Tuberculosis in India
• Why Is Tuberculosis Coming Back With a Vengeance
• Immigrants and the Spread of Tuberculosis in the United States: A Hidden Cost of Immigration

🥇 Most Interesting Tuberculosis Topics to Write about

• Innovation Dynamics in Tuberculosis Control in India: The Shift to New Partnerships
• Tuberculosis: Infectious Disease and Health Care Facilities
• What Is Tuberculosis, and How Serious Is This Disease
• The Background of Common Infection, Pulmonary Tuberculosis
• The Development of The Tuberculosis Vaccine
• The Effects of Tuberculosis on the Health and Lives of Humans
• The Spread of Tuberculosis in Ancient Egypt and Europe
• The Success of Mycobacterium Tuberculosis
• Ontology With SVM Based Diagnosis of Tuberculosis and Statistical Analysis
• The Causes and Treatment of the Disease of Tuberculosis
• Techniques Used for the Diagnostic of Ancient Tuberculosis Remains
• Positive Tuberculosis Blood Test as a Predictor of Health Status Among HIV-Infected Persons
• The Incidence of Tuberculosis Among Low Income People
• The History of the Tuberculosis and Research on Its Vaccine
• Performance-Based Incentives for Health: A Way to Improve Tuberculosis Detection and Treatment Completion
• Historians Blamed Columbus for Spreading Tuberculosis to the World
• Tuberculosis: Causes, Symptoms, and Treatment
• MDR Tuberculosis in Georgia: Problem in Prevention and Control
• Evolution of Drug Resistant Mycobacterium Tuberculosis
• Investigation of Bovine Tuberculosis in Rangpur Division of Bangladesh
• HPLC: Techniques Used for the Diagnostic of Ancient Tuberculosis Remains
• Impacts of Tuberculosis and AIDS on Society
• Ethics Ideas
• Infection Essay Ideas
• Hygiene Essay Topics
• SARS Topics
• Vaccination Research Topics
• Immunization Paper Topics
• Viruses Research Topics
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Tuberculosis articles from across Nature Portfolio

Tuberculosis (TB) is an infectious disease caused by strains of bacteria known as mycobacteria. The disease most commonly affects the lungs and can be fatal if not treated. However, most infected individuals show no disease symptoms. One third of the world’s population is thought to have been infected with TB.

Latest Research and Reviews

Waxing and waning course of X-linked bullous retinoschisis

• Simar Rajan Singh
• Sandepan Bandopadhyay

Artificial intelligence-based radiographic extent analysis to predict tuberculosis treatment outcomes: a multicenter cohort study

• Hyung-Jun Kim
• Nakwon Kwak
• Jae-Joon Yim

Chest ultrasound is better than CT in identifying septated effusion of patients with pleural disease

• Linhui Yang

Mycobacterium tuberculosis suppresses host antimicrobial peptides by dehydrogenating L-alanine

In this work, authors mechanistically investigate the reduced induction of antimicrobial peptides in Mycobacterium tuberculosis infected macrophages.

• Yuanna Cheng

Dynamic microfluidic single-cell screening identifies pheno-tuning compounds to potentiate tuberculosis therapy

Tuberculosis is a major global health threat. Here, the authors develop a single-cell drug discovery approach and identify a compound that tunes bacterial phenotypic variation. This enhances the activity of anti-tubercular drugs against the pathogen.

• Maxime Mistretta
• Mena Cimino
• Giulia Manina

B cell heterogeneity in human tuberculosis highlights compartment-specific phenotype and functional roles

Using flow cytometry and transcriptomic analyses, the authors characterize the functional diversity of B cell subsets in the lungs of patients with tuberculosis.

• Robert Krause
• Paul Ogongo

News and Comment

Restocking the tuberculosis drug arsenal

After many lean years, important progress has been made in updating the anti-tuberculosis drug armamentarium; a new drug that targets bacterial protein synthesis is one of several that could help transform the treatment of this neglected and deadly disease.

• Eric L. Nuermberger
• Richard E. Chaisson

Digital intervention improves tuberculosis treatment outcomes

An intervention that incorporates electronic pill boxes and remote adherence monitoring improved treatment success in patients with tuberculosis in Tibet — making this a promising strategy for low-resource settings.

• Karen O’Leary

A spotlight on the tuberculosis epidemic in South Africa

Tuberculosis is the leading cause of death from a single infectious agent, with over 25% of these occurring in the African region. Multi-drug resistant strains which do not respond to first-line antibiotics continue to emerge, putting at risk numerous public health strategies which aim to reduce incidence and mortality. Here, we speak with Professor Valerie Mizrahi, world-leading researcher and former director of the Institute of Infectious Disease and Molecular Medicine at the University of Cape Town, regarding the tuberculosis burden in South Africa. We discuss the challenges faced by researchers, the lessons that need to be learnt and current innovations to better understand the overall response required to accelerate progress.

Presumed ocular tuberculosis – need for caution before considering anti-tubercular therapy

• Rohan Chawla
• Urvashi B. Singh
• Pradeep Venkatesh

Transforming tuberculosis diagnosis

Diagnosis is the weakest aspect of tuberculosis (TB) care and control. We describe seven critical transitions that can close the massive TB diagnostic gap and enable TB programmes worldwide to recover from the pandemic setbacks.

• Madhukar Pai
• Puneet K. Dewan
• Soumya Swaminathan

B cells and T follicular helper-like cells within lung granulomas are required for TB control

We show a crucial protective function for T follicular helper (T FH )-like cells localized within granuloma-associated lymphoid tissue for Mycobacterium tuberculosis control in mouse models of tuberculosis. Antigen-specific B cells contribute to this strategic localization and the maturation of cytokine-producing T FH -like cells.

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Title: phd thesis. computer-aided assessment of tuberculosis with radiological imaging: from rule-based methods to deep learning.

Abstract: Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb.) that produces pulmonary damage due to its airborne nature. This fact facilitates the disease fast-spreading, which, according to the World Health Organization (WHO), in 2021 caused 1.2 million deaths and 9.9 million new cases. Fortunately, X-Ray Computed Tomography (CT) images enable capturing specific manifestations of TB that are undetectable using regular diagnostic tests. However, this procedure is unfeasible to process the thousands of volume images belonging to the different TB animal models and humans required for a suitable (pre-)clinical trial. To achieve suitable results, automatization of different image analysis processes is a must to quantify TB. Thus, in this thesis, we introduce a set of novel methods based on the state of the art Artificial Intelligence (AI) and Computer Vision (CV). Initially, we present an algorithm to assess Pathological Lung Segmentation (PLS). Next, a Gaussian Mixture Model ruled by an Expectation-Maximization (EM) algorithm is employed to automatically. Chapter 3 introduces a model to automate the identification of TB lesions and the characterization of disease progression. Chapter 4 extends the classification of TB lesions. Namely, we introduce a computational model to infer TB manifestations present in each lung lobe of CT scans by employing the associated radiologist reports as ground truth. In Chapter 5, we present a DL model capable of extracting disentangled information from images of different animal models, as well as information of the mechanisms that generate the CT volumes. To sum up, the thesis presents a collection of valuable tools to automate the quantification of pathological lungs. Chapter 6 elaborates on these conclusions.

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• Research article
• Open access
• Published: 07 April 2021

Knowledge about tuberculosis, treatment adherence and outcome among ambulatory patients with drug-sensitive tuberculosis in two directly-observed treatment centres in Southwest Nigeria

• Rasaq Adisa 1 ,
• Teju T. Ayandokun 1 &
• Olusoji M. Ige 2  

BMC Public Health volume  21 , Article number:  677 ( 2021 ) Cite this article

9388 Accesses

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Tuberculosis (TB) remains one of the most common infectious diseases worldwide. Although TB is curable provided the treatment commenced quickly, appropriately and uninterrupted throughout TB treatment duration. However, high default rate, treatment interruption and therapy non-adherence coupled with inadequate disease knowledge significantly contribute to poor TB treatment outcome, especially in developing countries. This study therefore assessed knowledge about TB and possible reasons for treatment non-adherence among drug-sensitive TB (DS-TB) patients, as well as evaluated treatment outcomes for the DS-TB managed within a 5-year period.

A mixed-method design comprising a cross-sectional questionnaire-guided survey among 140-ambulatory DS-TB patients from January–March 2019, and a retrospective review of medical-records of DS-TB managed from 2013 to 2017 in two WHO-certified TB directly-observed-treatment centres. Data were summarized using descriptive statistics, while categorical variables were evaluated with Chi-square at p  < 0.05.

Among the prospective DS-TB patients, males were 77(55.0%) and females were 63(45.0%). Most (63;45.0%) belonged to ages 18-34 years. A substantial proportion knew that TB is curable (137;97.9%) and transmittable (128;91.4%), while 107(46.1%) accurately cited coughing without covering the mouth as a principal mode of transmission. Only 10(4.0%) mentioned adherence to TB medications as a measure to prevent transmission. Inaccessibility to healthcare facility (33;55.0%) and pill-burden (10,16.7%) were topmost reasons for TB treatment non-adherence. Of the 2262-DS-TB patients whose treatment outcomes were evaluated, 1211(53.5%) were cured, 580(25.6%) had treatment completed, 240(10.6%) defaulted, 54(2.3%) failed treatment and 177(7.8%) died. Overall, the treatment success rate within the 5-year period ranged from 77.4 to 81.9%.

Conclusions

Knowledge about TB among the prospective DS-TB patients is relatively high, especially with respect to modes of TB transmission and preventive measures, but a sizeable number lacks the understanding of ensuring optimal TB medication-adherence to prevent TB transmission. Inaccessibility to healthcare facility largely accounts for treatment non-adherence. Outcomes of treatment within the 5-year period show that nearly half were cured, while almost one-tenth died. Overall treatment success rate is about 12% below the WHO-defined target. There is generally a need for concerned stakeholders to step-up efforts in ensuring consistent TB enlightenment, while improving access to TB care is essential for better treatment outcome.

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Tuberculosis (TB) remains one of the most common infectious diseases worldwide [ 1 , 2 , 3 ]. It is estimated that about 10 million people were infected with TB in 2017 with 1.3 million deaths among HIV negative people and an additional 350,000 deaths among HIV positive [ 4 , 5 ]. Tuberculosis incidence rates in Africa have been decreasing at a rate of 4% per year between 2013 and 2017, however, TB incidence rates in Nigeria have remained steady from 2000 through 2017 [ 4 , 6 ]. About 429,000 people in Nigeria have TB each year, while the total TB incidence rate was reported as 219 per 100,000 population [ 1 , 4 , 6 ]. Nigeria ranked number one in Africa and sixth globally among the 30 high TB burden countries and is also among the 14 countries in the world with the triple high burden of TB, TB/HIV and MDR-TB [ 1 , 3 , 6 ]. The global TB treatment success rate was reported as 85% among all new tuberculosis cases, and in Nigeria, TB treatment success rate progressed from 79 to 86% between year 2000 and 2017 [ 5 , 7 ].

Although TB is curable if treatment commenced quickly, appropriately and uninterrupted throughout the 6–9 months course of treatment [ 1 , 4 , 5 ]. However, high default rate, treatment interruption and therapy non-adherence coupled with inadequate disease knowledge significantly contribute to poor TB treatment outcomes among TB patients [ 5 , 7 , 8 ]. Therefore, accurate diagnosis, use of effective anti-TB medications and optimal adherence are priority tools for minimizing morbidity and mortality, as well as mitigating the spread of TB among the population [ 8 , 9 , 10 , 11 ]. In Nigeria, the standard short-course therapy for all categories of drug-sensitive tuberculosis (DS-TB) comprised a 6-month regimen, with 2-month intensive phase of four medications (HRZE) viz. Isoniazid (H), Rifampicin (R), Pyrazinamide (Z) and Ethambutol (E), and a 4-month continuation phase of two medications viz. Isoniazid and Rifampicin (i.e. 2HRZE/4HR) [ 10 , 12 , 13 , 14 , 15 ]. The treatment remained free of charge through the donor support funds, particularly the Damien foundation, and the regimen is administered daily to TB patients in the clinic under the direct supervision of healthcare workers who observe and record patient taking each TB dose (i.e. health facility-based directly observed therapy (DOT) [ 10 , 13 , 14 , 15 ]. Also, the treatment guideline or recommendation for TB patients co-infected with HIV indicated that antiretroviral therapy (ART) should be initiated in all TB-HIV co-infected patients regardless of the CD4 cell counts, within the first 8 weeks of TB treatment (intensive phase), while HIV positive patients with profound immunosuppression (CD4 cell counts < 50 cells /mm3) should receive ART within the first 2 weeks of initiating TB treatment [ 5 , 10 , 16 , 17 , 18 ].

The directly observed therapy concept is one of the five components of DOTs strategy endorsed by the World Health Organisation to create the basis for standard TB care and management [ 10 , 19 , 20 ]. The DOTs strategy had been widely promoted and implemented in many developed and developing countries [ 10 , 21 ]. Nigeria adopted the DOT concept in 1993, as a proactive core management approach to address non-adherence problem among TB patents [ 12 , 14 , 19 ]. However, despite the significant progress made in the control of TB through DOTs strategy, as well as potential advantages of DOT approach in enhancing adherence, TB has remained prevalent, while treatment outcomes and success rate still falls below the WHO defined target especially in low and middle-income countries (LMICs) including Nigeria [ 3 , 4 , 14 , 22 ].

The WHO Global Tuberculosis Report 2020 identified the latest challenges to TB management to include equitable access to quality and timely diagnosis, prevention, treatment and care [ 5 ]. However, non-adherence to TB treatment had also been consistently recognised as a principal factor linked to poor treatment outcomes and suboptimal TB control globally [ 21 , 23 , 24 , 25 ]. Treatment adherence among TB patients is challenging given the complexity, modest tolerability and long duration of treatment regimen currently available for both drug-susceptible and drug-resistant TB [ 23 , 26 ]. Adherence to TB medications is estimated to be as low as 40% in developing countries including Nigeria [ 25 ]. Low adherence may result in failure of initial treatment, emergence of multidrug resistant tuberculosis (MDR-TB), prolonged infectiousness and poor TB treatment outcomes [ 23 , 26 , 27 , 28 ]. In addition, TB patients who are not cured due to treatment non-adherence may pose a serious risk for individuals and community [ 24 , 26 , 29 ]. The WHO recommends at least 85 to 90% treatment success rate for all diagnosed TB cases [ 1 , 7 ]. However, to achieve the target among TB patients, there may be a need for better understanding of the particular barriers to TB treatment adherence, as well as patients’ knowledge and experience about TB and its management [ 30 ]. This may become necessary since adherence to treatment is critical for cure of TB, as well as controlling the spread of TB infection, while minimising the development of drug resistance [ 27 ]. Also, possession of adequate knowledge of the disease may aid the uptake of TB services [ 28 ].

Though, there are studies from many developed and some developing countries that had evaluated knowledge, attitude and practice about TB, as well as barriers to TB treatment adherence [ 30 , 31 , 32 , 33 , 34 , 35 ]. However, most of these studies still left gaps that underscore the necessity for continuous monitoring and evaluation of patient-specific reasons for TB treatment non-adherence, while making consistent efforts to evaluate the knowledge deficits of patients about TB may be essential in finding appropriate solution to the low TB treatment success rate. This study therefore assessed knowledge about TB and the possible reasons for suboptimal treatment adherence among ambulatory drug-sensitive TB (DS-TB) patients in two WHO-certified TB-DOT hospitals in Ibadan, southwest, Nigeria. Also, the treatment outcomes documented in the medical records of DS-TB patients managed in the hospitals between 2013 and 2017 were evaluated.

Study design

The study employed a mixed-method design comprising a prospective questionnaire-guided cross-sectional survey among DS-TB patients for eight consecutive weeks, between January and March, 2019, and a retrospective review of medical records of DS-TB patients managed within the 5-year period in the two hospitals.

Study setting

The tuberculosis DOT clinic of the University College Hospital (UCH) and Government Chest Hospital Jericho (GCHJ) Ibadan. Both hospitals are WHO-certified TB-DOT centres of excellence, supported by Damien Foundation, Belgium, and they both have fully equipped and functional DOT clinic for management of TB patients.

Study population

Adult outpatients (> 18 years) with DS-TB and who were registered with the TB-DOT clinic of the hospitals.

Inclusion and exclusion criteria

All consenting DS-TB outpatients, aged over 18 years, who were on TB treatment for at least one month prior to the commencement of the study were included. Patients with MDR-TB, as well as pregnant women whose condition may necessitate adjustment of standard TB dosage regimen were excluded. Also, case notes of DS-TB patients with incomplete data, especially with respect to treatment outcomes were excluded.

Sample size determination

Representative sample size for the study was calculated using Raosoft® sample size calculator ( www.raosoft.com/samplesize.html ). Eligible population of adult outpatients with DS-TB attending the TB-DOT clinic in UCH and GCHJ were estimated as 55 and 125, respectively for the 8-weeks study period. Thus, with the estimated population of 180 from both hospitals, and assumptions of 95% confidence level, 5% margin of error, as well as 50% conservative estimate to represent the proportion in the target population estimated to have a particular characteristics, a sample size of 125 was obtained. However, adjusting for 10% attrition rate, gave a target sample size of approximately 138 (rounded off to 140) patients. Subsequently, the proportion of participants recruited from each hospital was determined as follows: UCH: (55 ÷ 180) × 140 = 42.7; GCHJ: (125 ÷ 180) × 140 = 97.2. Approximately 40 patients from UCH and 100 from GCHJ were used as target sample size to guide participants’ enrolment. Also, the medical records of all DS-TB patients managed between 2013 and 2017 were selected and reviewed accordingly.

Data collection instrument

The questionnaire and data collection form were designed by the investigators following extensive review of relevant studies [ 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 ], as well as previous practice experience. The prospective cross-sectional survey consisted of 25-item questions, including open-ended, closed-ended and open-ended questions with relevant prompts. The questionnaire has three sections, with the primary outcomes measured in Section A included socio-demographic characteristics such as age, sex, educational qualification, occupation and marital status, as well as clinical characteristics including duration on TB treatment, family history of TB, as well as symptoms experienced at the onset of TB infection. Section B contained questions that evaluated patients’ knowledge about TB, modes of TB transmission and suggested preventive measures, as well as TB medications and other adjuncts being taking by the patients. Section C focused largely to explore the patients about possible reason(s) for TB treatment non-adherence, side effects experienced with TB medications and reporting of such side effects to healthcare provider (See additional file  1 ).

The retrospective review of medical records of DS-TB patients was guided by data collection form to retrieve information on demographic characteristics especially age, sex and year of treatment. Also retrieved were disease-specific clinical parameters including sputum smear acid-fast bacilli (AFB) results and any other diagnostic options, as well as patients’ HIV status and outcomes of treatment. In this study, treatment outcomes explored for the DS-TB retrospective cohort included: cured defined as pulmonary TB patients with smear or culture negative in the last month of treatment and in at least one previous occasion; completed treatment defined as pulmonary TB patients with smear or culture negative in the last month of treatment and in at least one previous occasion; failed treatment defined as a positive sputum smear or culture at the month 5 or later during treatment; defaulted defined as an interruption of TB treatment for 2 or more consecutive months; and died defined as TB patients who dies for any reason before starting or during the course of treatment. The definitions were in accordance with the WHO TB treatment guidelines and National Tuberculosis and Leprosy Control Programme (NTBLCP) classifications of TB treatment outcomes [ 7 , 10 , 12 ]. In our study, transferred out was defined as TB patients for whom no treatment was assigned, and which include those transferred out to another facility or treatment unit. The transferred out patients were only captured in the review and documentation, but were not considered as part of treatment outcomes.

Also, successful treatment was defined as the sum of TB patients who were cured and those who completed treatment, while unsuccessful treatment was defined as the sum total of TB patients who defaulted, failed treatment and died [ 7 , 10 , 12 ].

Pre-test and validation of data collection instrument

The questionnaire was assessed for content validity by a panel of consultant pulmonologist working in each of the DOT clinics and a clinical pharmacist in the academia. Subsequently, a pre-test of the instrument was done among 14 randomly selected TB patients from the GCHJ, representing 10% of the total number of patients enrolled for the study. These patients were excluded from the main study. Feedback from pre-test and validity assessment led to minor modifications in the questionnaire including some closed-ended questions which were rephrased in open-ended format with relevant prompts to guide patients’ opinion.

Sampling and recruitment procedure

Eligible DS-TB patients were consecutively enrolled on daily TB-DOT clinic of the hospitals while waiting for their turn of directly observed TB medication-taking or consultation with the attending healthcare provider. Individual patient was courteously approached by the investigators on the daily DOT clinic while strictly observing the TB precautionary measures. Procedure and objectives of the study were comprehensively explained to participants, after which verbal/oral informed consent was obtained from individual patient. The informed consent form and questionnaire were translated into Yoruba, the local language for majority of participants. Patients who do not understand English language were interacted with using the Yoruba version of the questionnaire. Back-translation was subsequently done to ensure response consistency. Patients were assured of confidentiality and anonymity of their responses, while they were informed that participation is entirely voluntary. The questionnaire was interviewed-administered to consented patients on every clinic day by the investigators. All the targeted eligible patients consented for participation and they were all enrolled and administered the questionnaire. Also, the medical records of DS-TB patients from January 2013 to December 2017 in each hospital were chronologically arranged according to the respective year, with relevant parameters retrieved and reviewed.

Data analysis

Data obtained were sorted, coded and entered into the Statistical Package for Social Sciences (SPSS) version 23 for analysis. Descriptive statistics including frequency and percentage were used to summarise the data for prospective and retrospective cohorts. Treatment outcome rates for the retrospective cohort, including cure rate, treatment failure and default rate, as well as mortality or death rate were determined as total number each of TB patients who were cured, failed treatment, defaulted and died divided by the total number of patients who were commenced on TB treatment, multiply by 100 (e.g. cure rate = number of DS-TB patients cured ÷ total number of DS-TB patients placed on TB treatment × 100). Subsequently, treatment success rate was calculated as the sum total of all the patients who were cured and completed treatment (i.e. successful treatment) divided by the total number of patients who were commenced on TB treatment (i.e. successful and unsuccessful treatment) multiply by 100. Transferred out TB patients were excluded as component of unsuccessful treatment since they were not placed on any form of TB treatment. Person Chi-square (χ2) was used to investigate association between relevant patients’ characteristics and those with or without successful TB treatment outcome. Priori level of significance was set at p  < 0.05.

Prospective participants

All the participants enrolled from both hospitals within the study period consented to partake in the study, giving a response rate of 100%.

Socio-demographic characteristics

Out of the 140 DS-TB patients who were administered the questionnaire, 40 (28.6%) were from UCH and 100 (71.4%) from GCHJ. Seventy seven (55.0%) were males and 63 (45.0%) were females. Most (63; 45.0%) patients were within the ages of 18–34 years, while secondary education was highest (66; 47.1%). Fifty-one (36.4%) of the DS-TB patients were in the intensive phase of treatment, while 89 (63.6%) were in the continuous phase (Table l). Of the presenting symptoms reported by patients at the onset of TB infection, cough was the highest manifestation in different combinations (140; 33.7%) Table  1 .

Knowledge of tuberculosis, modes of transmission and suggested preventive measure

A total of 137 (97.9%) patients knew that TB is a curable disease, with most (76; 55.5%) patients obtained the information from healthcare professionals, mostly nurses (42; 32.7%) and physicians (34; 24.8%), while pharmacists were not cited. Also, 128 (91.4%) knew that TB can be transmitted to another person, while 107 (46.1%) accurately cited coughing without covering the mouth as a principal mode of TB transmission. Covering of mouth when coughing (123; 49.6%) topped the list of suggested measures to prevent TB transmission, while 10 (4.0%) mentioned adherence to TB medications (Table  2 ).

Anti-tuberculosis and adjunct medications taken by patients

All the DS-TB patients (51; 100%) in the intensive phase were prescribed quadruple combination of isoniazid (H), rifampicin (R), pyrazinamide (Z) and ethambutol (E), while the 89 (100.0%) patients in continuation phase were on the dual combination of rifampicin and isoniazid. The class of adjunct medications taken by the patients were haematinics (50; 52.1%), antibacterial (13; 13.5%), antiretroviral therapy (12; 12.5%), antihypertensive (6; 6.3%), antidiabetic (4; 4.2%), cough syrup (4; 4.2%), anticonvulsant (3; 3.1%), antipsychotic (2; 2.1%), antiasthmatic (1; 1.0%), and one (1.0%) mentioned herbal preparation.

Reasons for TB treatment non-adherence and side effects experienced with tuberculosis medications

Forty-nine (35.0%) indicated reasons for TB treatment non-adherence, while 91 (65.0%) gave no specific reason. Inaccessibility to healthcare facility (33; 55.0%) topped the list of reasons for TB treatment non-adherence. Other reasons mentioned included too much medications to take at once (10; 16.7%) and size of the tablet being taken (8; 13.9%) Table  3 . Sixty-seven (47.9%) reported to have experienced side effect(s) with TB medications, while 73 (52.1%) did not. Of this, 37 (55.2%) reported the experienced reaction(s) to their physician, while 30 (44.8%) did not report (Table 3 ).

Retrospective participants

Treatment outcomes among the ds-tb patients managed between 2013 and 2017.

Of the 2400 medical records of DS-TB patients reviewed between 2013 and 2017, a total of 2389 (99.5%) had the required information documented, comprising 934 (39.1%) from UCH and 1455 (60.9%) from GCHJ. Also, the case notes reviewed for each year were 431 (18.0%) in 2013; 523 (21.9%) in 2014; 393 (16.5%) in 2015; 516 (21.6%) in 2016 and 526 (22.0%) in 2017. Out of the 2389 eligible case notes, 2262 (94.7%) patients had sputum smear AFB results documented in their case notes before the commencement of TB treatment. This comprised 1596 (70.6%) who had positive AFB sputum smear, and 666 (29.4%) with negative AFB sputum smear but chest X-ray and clinical presentation suggestive of active TB infection. The reminder 127 (5.3%) had neither AFB sputum smear nor chest X-ray results recorded, and were considered as transferred out patients. There was no documentation on TB culture test in the case notes of the DS-TB patients reviewed. Also, of the 2389 patients, 2117 (88.6%) had their HIV status documented, with 427 (20.2%) who had HIV positive status, while 1690 (79.8%) were HIV negative.

Table  4 shows details of treatment outcomes between 2013 and 2017. Of the 2262 (94.7%) whose treatment outcomes were retrieved from the case notes, 1211 (53.5%) DS-TB patients were cured, 580 (25.6%) had their treatment completed, 240 (10.6%) defaulted, 54 (2.3%) failed treatment, while 177 (7.8%) deaths were recorded. The treatment success rate between 2013 and 2017 ranged from 77.4 to 81.9%, and overall 1791 (79.2%) had successful treatment outcome (cured + completed treatment) within the 5-year period. Associations between relevant socio-demographic characteristics and TB treatment outcomes are shown in Table  5 . There were significant associations between sex (χ2 = 8.780, p  = 0.003), HIV status (χ2 = 29.110, p  < 0.001), DOT clinic attended (χ2 = 18.215, p  < 0.001) and patients’ with or without successful treatment outcome. Treatment were significantly successful among males TB patients (57.4%) compared to their female counterparts (42.6%), p  = 0.003, also TB patients with HIV negative status (82.2%) versus HIV positive status (17.8%), p  < 0.001.

In this study, we evaluated knowledge about TB and possible reasons for TB treatment non-adherence among prospective ambulatory DS-TB patients, as well as reviewed the trend in treatment outcomes for DS-TB outpatients managed within a 5-year period in two WHO certified TB-DOT centres. Our study revealed that nearly 98 and 91%, respectively, succinctly understood TB to be curable, as well as being a disease transmittable from one person to another. Previous studies had reported between 76 and 95% of TB patients who knew about the curable nature of TB [ 36 , 37 , 38 , 39 , 40 , 41 ]. Higher values of 96.3 and 97.6% about patients’ awareness of the curability of TB had also been reported in other studies [ 42 , 43 ]. In addition, coughing without covering the mouth, sharing of cutleries and indiscriminate spitting by TB-infected individuals were copiously cited by patients in our study as common modes of TB transmission. This is consistent with previous studies where varying proportions, 25, 53.6 and 63.4% of their patients were reported to be aware of cough hygiene, as an important TB preventive measure [ 42 , 43 , 44 ].

Noteworthy to mention that, only 1.2% of the TB patients in our study expressed some level of misconceptions about TB preventive measures, such as short-term abstinence from sexual intercourse during TB treatment, as well as avoiding clothes sharing. This proportion is far less than 10.8, 15.5, and 22.7% in previous studies [ 39 , 44 , 45 ], where avoiding food and utensils were cited as modes of TB prevention. Surprisingly, 4.3% of the patients could correctly mentioned the current medications for treating TB infection, while only 4% cited adherence to TB medications as a measure to prevent TB transmission. The low proportion of patients with correct response in these regards is a concern that may underscore the need for concerned stakeholders, especially the National Tuberculosis and Leprosy Control Programme (NTBLCP) and TB primary care providers to step-up counselling and enlightenment efforts for TB patients, especially in the areas of core TB preventive measures and modes of transmission, of which adherence to TB medications is most essential. Though, our study did not directly assign score in quantifying patients’ knowledge about TB, rather we focused largely to explore the depth of patients’ understanding of some basic aspects in TB management. However, the perceived good knowledge of patients in some TB preventive measures and modes of transmission seems encouraging and may further emphasise the necessity for continuous public education and enlightenment on TB prevention, treatment and care among the patients. Incidentally, in our study, nurses and physicians were the healthcare providers who were largely cited as source of knowledge information about TB, with no mention of pharmacists. Amazingly, pharmacists are expected to be the core healthcare provider to dispense and counsel patients on their TB medication usage. This perhaps reveals that pharmacists might not have been in direct contact with TB patients at the DOT service point in the hospitals. Thus, a call for concern among relevant stakeholders in the pharmacy profession in Nigeria, of the need to ensure and encourage pharmacists to be more proactively engaged in TB care, whether in the hospital or community pharmacy setting.

Topmost of the reasons cited by patients for TB treatment non-adherence were inaccessibility to healthcare facility, perhaps in terms of travel costs for daily DOT at the clinic, and the idea of taking many anti-TB medicines at once. Lack of access to formal health services, and the consequent non-clinic attendance, as well as poor socio-economic status among many patients with TB have been reported in previous studies [ 46 , 47 ], as key factors hindering continuous progress of DOT concept in enhancing TB treatment adherence. Generally, the two studied TB-DOT facilities largely rely on healthcare-facility or clinic-based DOT, in which TB patients report to the clinic on a daily basis (opening hours 8a.m to 2p.m, in most cases) for their daily dose of TB medications under the direct observation of the attending primary care provider, who monitor and record the TB dose taken. As a result, many TB patients asides from tackling other competing routine demands such as job schedule overlapping with clinic appointment time [ 46 ], may also face the burden of daily transportation/travel costs to the clinic. Nevertheless, the challenge of healthcare inaccessibility may be partly overcome through consideration of non-healthcare facility or clinic-based DOT, perhaps the community-based DOT, where the healthcare provider visit the TB patients in their community to deliver the DOT service [ 10 ]. Although, community-based DOT may involve extra costs to the institution and other supporting partners, however, evidence has shown that community or home-based DOT had higher rates of treatment success in terms of cure, treatment completion and 2-month sputum conversion, as well as having lower rates of mortality and unfavourable outcomes compared with health facility-based DOT [ 10 , 26 ]. In addition, decentralization of TB-DOT service to peripheral facilities closer to the people may also be a vital option to improve access to TB treatment. Many developed and developing countries have embraced decentralization of TB-DOT services, with a positive report of increased access to TB care [ 10 , 11 , 48 , 49 ]. The WHO and NTBLCP have also advocated that further strengthening and decentralization of TB services may be a way forward to achieve the WHO End TB strategy [ 48 , 49 ]. In Nigeria, the major drawback to the TB-DOT decentralization advocacy, may be the lack of competent healthcare personnel at the peripheral facilities to deliver the DOT services [ 19 , 33 , 48 ]. Thus, government and other concerned stakeholders may need to step-up their political and financial commitments toward TB treatment and care, in order to achieve the third united nation sustainable development goals and the WHO End TB strategy of eradicating TB globally by the year 2030 target [ 1 , 50 ]. More importantly, institution of appropriate support systems, specifically, material support including financial incentives such as transport subsidies or financial bonus to TB patients may be essential, to at least take care of the indirect costs that are incurred by patients when attending the daily DOT clinic. In addition, consideration of fixed dose combination (FDC) tablets for TB medications may be useful to overcome the issue of pill burden raised by the patients. The FDC for TB medications is now a conditional recommendation in the 2017 update of WHO TB treatment guidelines, for DS-TB patients [ 10 , 11 ].

A sizeable proportion of the patients claimed to have experienced side effect(s) with their TB medications, but only 5% cited fear of medication side effects as a reason for TB treatment non-adherence. More than one-third of the patients reported that the side effects experienced were expected reactions which they have been pre-informed by their primary care physician. Thus, they probably do not consider such side effect(s) as a barrier to TB treatment adherence. The overwhelming positive response of patients on pre-knowledge information about expected medication side effects is noteworthy and commendable. Therefore, such counselling role and value-added services should be continuous and consistently done at every TB patient-provider encounters. However, our study finding in this regard is in contrast with report from previous studies stating that patients were not informed about side effects and what to do to counter it [ 51 , 52 ]. Providing counsel on possible adverse drug events in language the patient best understand may be helpful in preparing patients towards better appreciation and commitment to their treatment. Typically, the healthcare providers and supporting staff working in the TB-DOT centres used to undergo periodic TB care-related training, as well as seminars organised either by the respective hospital or the funding partners, largely to enhance job performance and competence. This might have helped the TB primary care providers in the efficient discharge of their clinical roles and duties in TB care and management. In general, TB primary care providers should continuously explore the possible reasons for poor TB treatment adherence at every patient-provider encounters, thereby making effort to offer necessary assistance, especially psychological support through robust counselling session or peer group support, with a view to collectively enhance treatment adherence and outcome [ 52 , 53 , 54 ].

Precisely, 54% of TB patients evaluated between 2013 and 2017 were cured, and nearly one-quarter had treatment completed, with close to one-tenth deaths recorded. An overall treatment success rate of approximately 79% was achieved within the 5-year period reviewed, which is about 12% below the WHO-defined target of 90% for new TB cases [ 1 , 7 , 10 ]. The treatment success rate noted in our study is higher than the values recorded in some developing countries [ 55 , 56 , 57 , 58 ], while studies conducted in high-income countries reported a higher treatment success rates [ 7 , 26 ] . Varying TB treatment success rates ranging from 34 to 85% in the low- and middle-income countries have earlier been reported [ 1 , 50 ]. In addition, the default rate of about 10% obtained in our study is three times the WHO target of 3% default rate among TB patients [ 7 , 10 ], but the value is still lower than that reported in previous studies in Nigeria [ 57 , 58 ]. Also, the TB default rates in other studies conducted in South Africa [ 59 ] and Brazil [ 60 ] reported higher rates of default than found in our study. Thus, as previously suggested, there may be a need for institution of appropriate support systems, which may include material, structural and psychological supports [ 61 ] for all categories of DS-TB patients, as this may go a long way to relief the patients’ disease burdens, with greater likelihood of facilitating optimal commitment to TB treatment, and subsequently, there may be improved treatment outcomes and success rate.

In our study, we observed that 8.6% among the prospective DS-TB participants reported antiretroviral therapy (ART) as adjunct medications taking alongside the core anti-TB medications. Although, we may not be able to directly assume this percent prevalence as proportion who may genuinely have HIV positive status. The use of ART drugs with anti-TB medications may perhaps indicate a greater possibility that the concerned patients may be managing or treating a TB co-infected HIV infection. In addition, a value of 20.2% HIV positive status documented in the medical records of DS-TB patients in the retrospective cohort may seem more reliable than the indirect prediction of patient’s HIV status from the self-report mentioning of antiretroviral medications taking by the patients. Nevertheless, a carefully considered future study to further explore the precise prevalence of TB/HIV co-infection may be necessary, in order to make a far-reaching conclusion. The HIV prevalence observed among the DS-TB patients in the retrospective cohort is lower that the HIV prevalence of between 27.2 and 61% reported among TB patients in Eastern and Southern Africa countries [ 53 , 59 , 62 ]. It is noted that TB treatment outcomes was significantly successful among TB patients with HIV negative status, compared to the HIV positive counterparts. Poor treatment outcome among HIV co-infected TB patients has been corroborated by other studies, where HIV co-infection was found to increase the chance of unsuccessful treatment outcome among TB patients [ 57 , 63 , 64 , 65 ]. In general, the low treatment success rates perhaps further reiterates the necessity for concerned stakeholders in tuberculosis control in LMICs including Nigeria, to step-up efforts at ensuring institutionalization of functional and robust TB patients’ support systems, increased advocacy and enlightenment on TB control, as well as consistent availability of anti-TB and relevant adjunct medications at the TB-DOT service centres.

Despite the useful information from our study, the following limitations are worthy of mentioning. This includes the possibility of documentation bias that may arise from patients’ medical records. In the studied facilities, all the DS-TB patients were placed on the same standard 6-month short-course regimen of 2HRZE/4HR, with no discrimination into category 1 (new TB cases) or category II (retreatment TB cases). This was consistent all through the period of review, and this treatment approach conforms to the 2017 update of the WHO TB treatment guidelines [ 10 ]. Also, the cross-sectional nature of our study may not concisely permit the establishment of a causal relationship, while the inherent limitation(s) such as recall bias from the self-report measure [ 37 ] may not be totally excluded. Nevertheless, the use of non-judgemental and non-threatening question-items may probably allow for a sincere opinion among the patients. In addition, the representativeness of sampled population, as well as conduct of the study in two WHO-certified TB-DOT centres may perhaps ensure collection of a more reliable data on TB management, thus a useful strength for our study. Another limitation may be linked to the non-availability of the reasons for treatment non-adherence among the DS-TB patients whose case notes were retrospectively reviewed. Also, patients in the prospective cohort were not explored on other useful patients’ characteristics such as living condition, monthly income, residence area/distance from the DOT facility, lifestyles especially smoking and alcohol intake, which were largely considered to be outside the scope of our study objectives. We focused generally on gaps that may not have been concisely captured in the previous related studies. In addition, the prospective patients were not follow-up to explore their treatment outcomes. These limitations may therefore need to be carefully considered when making generalisation about our study findings.

It can be concluded that knowledge about TB among the prospective DS-TB patients is relatively high, especially with respect to common modes of TB transmission and preventive measures, but a sizeable number lacks the understanding of ensuring optimal TB medication-adherence to prevent TB transmission. Inaccessibility to healthcare facility largely accounts for TB treatment non-adherence. Treatment outcomes within the 5-year period show that nearly half were cured, while almost one-tenth died. Overall treatment success rate of 79% achieved is about 12% below the WHO-defined target. There is generally a need for concerned stakeholders to step-up efforts in ensuring consistent TB enlightenment, while improving access to TB care is essential, perhaps by instituting necessary support systems including financial incentives/subsidies for TB patients generally. Also, the TB primary care provider should consistently re-evaluate the possible reason(s) for TB treatment non-adherence during provider-patient encounters and endeavour to offer essential psychological support through value-added counselling, with a view to increase treatment outcomes and success rate.

Availability of data and materials

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Abbreviations

Tuberculosis

Drug sensitive tuberculosis

Directly Observed Treatment Short-course

Institution Review Board

Ethics Review Committee

National Health Research and Ethics Committee

Isoniazid-H, Rifampicin-R, Pyrazinamide-Z and Ethambutol-E

Acid Fast Bacilli

Multidrug Resistance Tuberculosis

Low and middle income countries

World Health Organisation

Tuberculosis and Leprosy Control Programme

Human Immunodeficiency Virus

Antiretroviral Therapy

Statistical Package for Social Sciences

University of Ibadan

University College Hospital

Government Chest Hospital, Jericho

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Acknowledgements

We sincerely acknowledge the medical record staff in the chest clinics of the University College Hospital and Government Chest Hospital Jericho, Ibadan for their assistance during the retrospective data collection, while we appreciate the patients who consented to partake in this study for their cooperation and perseverance.

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RA and TTA designed the study, conduct the statistical analysis, developed the manuscript and completed the final write up of the manuscript. OMI proofread and edit the study instruments and the completed manuscript. The authors read and approved the final submission.

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Rasaq Adisa is a Ph. D holder, Senior Lecturer and the Head of Department, Clinical Pharmacy and Pharmacy Administration, Faculty of Pharmacy, University of Ibadan, Ibadan, Nigeria. Teju T. Ayandokun is a postgraduate student in the department of Clinical Pharmacy and Pharmacy Administration, Faculty of Pharmacy, University of Ibadan, and superintendent pharmacist in a community pharmacy in Ibadan, Nigeria . Olusoji M. Ige is a consultant pulmonologist and Head of chest unit in the department of Medicine, College of Medicine, University of Ibadan and University College Hospital, Ibadan, Nigeria.

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The University of Ibadan/University College Hospital (UI/UCH) and the Oyo State Ministry of Health (OYMOH) Ethics Review Committees (ERCs) approved the study protocol, consent form and other participants’ information vide the approval numbers, NHREC/05/01/2008a and AD13/479/957, respectively. We confirm that the oral/verbal inform consent was approved by the UI/UCH and OYMOH ethics committees for consent taken from the participants in our study, especially after the protocol has been duly translated to the local language (Yoruba), to ensure adequate comprehension by participants who did not understand English Language. Also, the consent information as contained in the informed consent form was read and explained to individual participant prior to their enrolment. In addition, the preliminary information on the study questionnaire contained a section with a caption ‘Do you consent to partake in this study’ with a Yes/NO response option, so as to clearly capture participant’s intention to partake in the study before the commencement of interview-administered questionnaire. An affirmative response of Yes, was taken as consent for participation and noted on individual coded questionnaire as a documented evidence for reference purpose.

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Questionnaire for the prospective cohort

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Adisa, R., Ayandokun, T.T. & Ige, O.M. Knowledge about tuberculosis, treatment adherence and outcome among ambulatory patients with drug-sensitive tuberculosis in two directly-observed treatment centres in Southwest Nigeria. BMC Public Health 21 , 677 (2021). https://doi.org/10.1186/s12889-021-10698-9

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Adherence to treatment

Arts and humanities, behavioural research, biology of host and pathogen, capacity development & training, clinical management, clinical trials, computational genomics, diagnostics, digital health, drug development, drug-resistant tb, gene regulation, host-directed therapies, latent and sub-clinical tb, migrant tb / tb in mobile populations, non-tuberculous mycobacterial disease (ntms), pharmacology, whole genome sequencing.

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Example outputs:

People: Amy Clarke , Rob Horne , Annie Jones

See also: Adherence to treatment

See sub-themes: Computational Genomics ; Drug Development,  Gene regulation ; Immunology ; Pharmacology

People: Kristine Arnvig , Francois Balloux , Sanjib Bhakta ,  Frank Kloprogge , Camus Nimmo , Gillian Tomlinson , Lucy van Dorp

The body is complex, and infection and our immune response to it are complex processes that we only partly understand.  However, we can now collect enormous amounts of information about the activity going on in our bodies, and use computers to identify signatures that are found (for example) in a group of people with known disease, but not in people we know not to be infected.  These signatures can then be used as biomarkers for disease in people of unknown status.  For example, this approach is analysing mRNA expression in the blood for biomarker signatures that identify people who don’t yet have clinical TB, but in whom TB bacteria that were latent/inactive have now become active. In addition, we are investigating TB-specific cytokine profiles that may aid to distinguish between latent and active TB, as well as functional T cell profiling. 

• Blood transcriptional biomarkers for active pulmonary tuberculosis in a high-burden setting: a prospective, observational, diagnostic accuracy study. (2020) Turner, C. T. et al. Lancet Respir Med 8(4): 407-419 https://doi.org/10.1016/S2213-2600(19)30469-2
• Blood transcriptomic biomarkers for tuberculosis screening: time to redefine our target populations? (2021) Gupta, R.K. and M. Noursadeghi. Lancet Glob Health https://doi.org/10.1016/S2214-109X(21)00088-7
• Blood transcriptomic stratification of short-term risk in contacts of tuberculosis. (2020) Roe, J. et al. Clin Infect Dis 70(5): 731-737 https://doi.org/10.1093/cid/ciz252
• Concise whole blood transcriptional signatures for incipient tuberculosis: a systematic review and patient-level pooled meta-analysis. (2020) Gupta, R. K. et al. Lancet Respir Med 8(4): 395-406 https://doi.org/10.1016/S2213-2600(19)30282-6
• Mycobacteria-Specific Mono- and Polyfunctional CD4+ T Cell Profiles in Children With Latent and Active Tuberculosis: A Prospective Proof-of-Concept Study.   (2019) Tebruegge, M. et al.   Front Immunol 10: 431 https://doi.org/10.3389/fimmu.2019.00431 .

People: Ibrahim Abubakar , Rishi Gupta , Isobella Honeyborne , Maddy Noursadeghi ,   Marc Tebruegge

Most TB is found in the Global South, where overall scientific infrastructure and support is most insecure for multiple historical and economic reasons.  We strongly support the idea that these countries should be enabled to develop high quality science with highly trained workforces.  We are both part of large programmes explicitly aiming to improve capacity development, and we also bring capacity development into other work wherever we can. As a university, we see the importance of academic and practical education, and have expertise in delivering it.  This includes supporting individuals to visit UCL for varying periods of time, carrying out workshops in London and abroad, training laboratory workers in diagnostic laboratories, and being part of bigger capacity development programmes.

Projects: PanACEA ; UK-Korean partnership for a TB cohort

People: Frank Kloprogge , Tim McHugh , Ali Zumla  

Although standard treatments are published for patients with TB, working with individual patients to apply those treatments is a long process that is often far from smooth.  TB as a disease is different in every patient in terms of where the infection is active, whether the bacteria are resistant to any antibiotics, how the patient responds to drugs they are given, their personal situation, and other complicating conditions or factors.  Treatment is long, and many of these factors may change, while stopping the treatment early may lead to new drug resistance developing. All this happens in the context of a changing NHS and Social Services with limited resources. Clinical management is therefore never routine, and developing processes that are flexible and robust enough is challenging.

People: Helen Booth , Hanif Esmail , Marc Lipman , Maddy Noursadeghi , Jacqui White

The way we can improve treatment for TB, and be confident that it will be safe and effective, is through stringent clinical trials.  For TB, which is a disease that can be slow to develop and to treat, where the drug resistance patterns are changing, and manifests most in the poorest parts of the world, these trials are particularly challenging. They involve a large team of people with different skills over a long period of time, so are costly, and those we run have to be carefully selected.  The MRC Clinical Trials Unit at UCL – which formed originally as the MRC Tuberculosis Research Unit in 1948 has an unprecedented track record in TB trials.  As well as their leadership, management,  statistical and analysis expertise, they work with others at UCL who carry out TB microbiology and train and monitor participating laboratories, and an army of people throughout the world who recruit and work with the trial participants.  UCL also works with other trial sponsors such as the Global TB Alliance, and the University of Stellenbosch.

Sub-themes: Clinical trial design

Projects: SimpliciTB , STREAM 2.0 , TB-CHAMP , TB-PRACTECAL , ZeNix ; ( MRC-CTU TB project page )

People: Suzanne Anderson ,  Robindra Basu Roy , Angela Crook , Hanif Esmail , Diana Gibb ,  Ruth Goodall , Tim McHugh ,  Sarah Meredith , Andrew Nunn , Lele Rangaka ,  Anna Turkova , Conor Tweed  

Studying the spread of M. tuberculosis strains can identify local outbreaks, identify sub-strains with particular properties, inform on genotypic predictors of disease pathology, tell us how drug resistance develops and spreads, and inform us about human history. Computational genomics relies on the ability to differentiate isolates based on their evolutionary relatedness, typically employing the fields of phylogenetics and population genomics.  These days, this is mostly done through Whole Genome Sequencing .

• Dynamics of within-host Mycobacterium tuberculosis diversity and heteroresistance during treatment. (2020) Nimmo, C. et al. EBioMedicine 55: 102747 https://doi.org/10.1016/j.ebiom.2020.102747
• Population-level emergence of bedaquiline and clofazimine resistance-associated variants among patients with drug-resistant tuberculosis in southern Africa: a phenotypic and phylogenetic analysis. (2020) Nimmo, C. et al. Lancet Microbe 1(4): e165-e174 https://doi.org/10.1016/S2666-5247(20)30031-8

People: Francois Balloux , Camus Nimmo , Lucy van Dorp

Despite many technical advances in diagnostics in the last two decades diagnosing TB is often challenging, especially in children. Existing tests have suboptimal sensitivity, which means that many TB patients have false-negative results. Diagnosing TB in children has additional challenges, as collecting adequate samples is often difficult and most children have paucibacillary disease (meaning that few mycobacteria are present in their clinical samples, making it hard to detect them). We are conducting studies on existing immune-based TB tests, including the tuberculin skin test and interferon-gamma release assays, and are working towards designing novel immunological TB tests that perform better across all age groups.

• Diagnostic accuracy of QuantiFERON-TB Gold Plus assays in children and adolescents with tuberculosis disease. (2020) Soler-Garcia, A. et al.   J Pediatr 223: 212-215 e211 https://doi.org/10.1016/j.jpeds.2020.02.025
• Tuberculosis disease in children and adolescents on therapy with antitumor necrosis factor-a agents: A collaborative, multicenter Paediatric Tuberculosis Network European Trials Group (ptbnet) study. (2020) Noguera-Julian, A. et al . Clin Infect Dis 71(10): 2561-2569 https://doi.org/10.1093/cid/ciz1138
• TB-PRACTECAL
• Comparison of Cepheid Xpert MTB/XDR and GenoScreen Deeplex Myc-TB for MDR and XDR M. tuberculosis (Giovanni Satta).  

People: Tim McHugh , Giovanni Satta ,  Marc Tebruegge

Return to main research page | top  

• Knowledge, attitudes, and behaviors on utilizing mobile health technology for TB in Indonesia: A qualitative pilot study. (2020) Aisyah, D. N. et al . Front Public Health 8: 531514 https://doi.org/10.3389/fpubh.2020.531514
• Management and control of tuberculosis control in socially complex groups: a research programme including three RCTs. (2020) Story, A., et al. Programme Grants for Applied Research 8(9) https://doi.org/http://doi.org/10.3310/pgfar08090
• TB Mentor app for clinical decision support

People: Hanif Esmail , Andrew Hayward , Patty Kostkova , Al Story  

After the success of early drugs against TB, starting in the 1940s with streptomycin, there was a long period where no new antibiotics were developed, due to lower priority, cost and time to develop these, and lack of biological understanding. The rise of antibiotic resistance has shown this to be short-sighted, and at last there is a renewed pipeline of drugs, some of which have moved into clinical use.  We are looking for novel drugs, coming both from the biology, and also from direction of large collections of chemical derivatives.

• Analogues of Disulfides from Allium stipitatum Demonstrate Potent Anti-tubercular Activities through Drug Efflux Pump and Biofilm Inhibition. (2018) Danquah, C. A. et al. . Sci Rep 8(1): 1150 https://doi.org/10.1038/s41598-017-18948-w
• Carprofen elicits pleiotropic mechanisms of bactericidal action with the potential to reverse antimicrobial drug resistance in tuberculosis. (2020) Maitra, A. et al. J Antimicrob Chemother 75(11): 3194-3201 https://doi.org/10.1093/jac/dkaa307
• Cell wall peptidoglycan in Mycobacterium tuberculosis: An Achilles' heel for the TB-causing pathogen. (2019) Maitra, A., T. Munshi, J. Healy, L. T. Martin, W. Vollmer, N. H. Keep and S. Bhakta. FEMS Microbiol Rev 43(5): 548-575 https://doi.org/10.1093/femsre/fuz016
• Characterization of the MurT/GatD complex in Mycobacterium tuberculosis towards validating a novel anti-tubercular drug target. (2021) Maitra, A., S. Nukala, R. Dickman, L. T. Martin, T. Munshi, A. Gupta, A. J. Shepherd, K. B. Arnvig, A. B. Tabor, N. H. Keep and S. Bhakta. JAC Antimicrob Resist 3(1): dlab028 https://doi.org/10.1093/jacamr/dlab028
• Ertapenem and Faropenem against Mycobacterium tuberculosis : in vitro testing and comparison by macro and microdilution. (2020) Gonzalo, X. et al. BMC Microbiol 20(1): 271 https://doi.org/10.1186/s12866-020-01954-w
• Improving the potency of N-Aryl-2,5-dimethylpyrroles against multidrug-resistant and intracellular mycobacteria. (2020) Touitou, M. et al. ACS Med Chem Lett 11(5): 638-644 https://doi.org/10.1021/acsmedchemlett.9b00515
• Polymersomes eradicating intracellular bacteria. (2020) Fenaroli, F. et al. ACS Nano 14(7): 8287-8298 https://doi.org/10.1021/acsnano.0c01870
• Role of whole-genome sequencing in characterizing the mechanism of action of para-aminosalicylic acid and its resistance. (2020) Satta, G. et al . Antimicrob Agents Chemother 64(9) https://doi.org/10.1128/AAC.00675-20
• See also Tuberculomucin in 'Host-directed therapies', below
• Inhibitors of cell-wall peptidoglycan as novel anti-TB drugs

People: Sanjib Bhakta ,  Dimitris Evangelopoulos , Tim McHugh , Mat Todd

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Antibiotics are one of the cornerstones of the modern world, curing once-fatal diseases, and this is true for TB.  Yet resistance to these antibiotics develops  - in the case of M. tuberculosis , through the bacteria acquiring mutations in their chromosomes one at a time.  Reducing the risk of this happening is one major reason that TB is always treated with combination drug therapy. With TB the problem is worsened by the long period of treatment and side effects of drugs, which can lead to patients not completing their full courses. It is an aspect of TB that affects almost everything else: diagnosis, clinical management, and drug development to name a few.

People and sub-themes:

• Clinical management of patients ( Marc Lipman )
• Clinical trials ( MRC CTU at UCL , Angela Crook , Diana Gibb ,  Tim McHugh , Andrew Nunn )
• Development and spread of resistance ( Francois Balloux , Camus Nimmo , Lucy van Dorp )
• Monitoring resistance of isolates in clinical trials for new drug combinations ( Tim McHugh ) 
• Repurposing Non-Steroidal Anti-inflammatory Drugs to Reverse Drug resistance in TB ( Sanjib Bhakta )
• Bedaquiline resistance in drug-resistant tuberculosis HIV co-infected patients. (2020) Nimmo, C. et al . Eur Respir J 55(6) https://doi.org/10.1183/13993003.02383-2019
• Carprofen elicits pleiotropic mechanisms of bactericidal action with the potential to reverse antimicrobial drug resistance in tuberculosis. (2020) Maitra, A.  et al. J Antimicrob Chemother 75(11): 3194-3201 https://doi.org/10.1093/jac/dkaa307

Projects: SimpliciTB , STREAM 2.0 , TB-CHAMP , TB-PRACTECAL , ZeNix

Although we have known the genetic structure of Mycobacterium tuberculosis for over 20 years, much of its biology relates to how and when genes are switched on and off, but our understanding of the underlying mechanisms remains incomplete.  The development of high-throughput sequencing (HTS) techniques, has revealed the abundance and importance of regulatory RNAs such as small RNAs and so-called riboswitches in bacterial gene expression control, and we can now monitor expression of all genes in an effort to understand their role in different activity states and in different locations within the host.

• Coupling of peptidoglycan synthesis to central metabolism in mycobacteria: Post-transcriptional control of CwlM by aconitase. (2020) Bancroft, P. J. et al. Cell Rep 32(13): 108209 https://doi.org/10.1016/j.celrep.2020.108209
• Riboswitches: choosing the best platform.  (2019) Arnvig, K. B.  Biochem Soc Trans 47(4): 1091-1099 https://doi.org/10.1042/BST20180507

People: Kristine Arnvig

Classically we think of treating bacterial disease with antibiotics – molecules that kill or damage the bacteria, and ideally don’t affect the patient at all. A complementary approach is to use molecules that modulate the host’s immune response. An effective immune response aims to kill pathogen but not its own cells. Pathology caused by infectious agents can either be a direct effect of the pathogen, or arise indirectly from an inappropriate immune response that causes damage. Host-directed therapies, therefore, can both be developed to stimulate the immune response, and dampen autoimmune damage depending on what is needed.

• Host-directed therapies and holistic care for tuberculosis. (2020) Zumla, A. et al. Lancet Respir Med 8(4): 337-340 https://doi.org/10.1016/S2213-2600(20)30078-3
• Tuberculomucin - a substance first developed by Dr Friedrich Weleminsky in the early part of the 20th century (Friedrich Weleminsky, Ueber die Bildung von Elweiss und Mucin durch Tuberkelbacillen,  Berliner klinische Wochenschr 28 (1912): 1-8. Translated by Stephanie Eichberg (SE)).  Long term TB culture following his protocol has resulted in a product similar in characteristics to that described by Weleminsky and testing of its efficacy is planned. Reeves, CA; Tuberculomucin: a forgotten treatment for tuberculosis, (2014)  The Transactions of the Medical Society of London 131 pp. 106-112, available at UCL Discovery

People: Ali Zumla , Judy Weleminsky ,  Dimitris Evangelopoulos

• Analysis tools to quantify dissemination of pathology in zebrafish larvae. (2020) Stirling, D. R. et al. Sci Rep 10(1): 3149 https://doi.org/10.1038/s41598-020-59932-1

People: David Lowe , Gillian Tomlinson

When people are infected with M. tuberculosis, if not cleared by the immune response, the bacteria will most often stay in the body – often the lungs – in a quiescent state.  At some point, which could be soon after infection or many years later, it can reactivate to cause disease.  Only 10% of infections move to disease, so most infection is latent.  Identifying people with latent infection, and those where the bacteria are starting to reactivate but not yet clinically apparent, is an important part of controlling disease. However this is not only technically difficult, but it also raises issues of what is appropriate to do, and often requires engaging with particular at-risk communities.

• Discovery and validation of a personalized risk predictor for incident tuberculosis in low transmission settings. (2020) Gupta, R. K. et al. Nat Med 26(12): 1941-1949  https://doi.org/10.1038/s41591-020-1076-0
• Exaggerated IL-17A activity in human in vivo recall responses discriminates active tuberculosis from latent infection and cured disease. (2021) Pollara, G. et al. Sci Transl Med 13(592) https://doi.org/10.1126/scitranslmed.abg7673
• The relationship between social risk factors and latent tuberculosis infection among individuals residing in England: a cross-sectional study. (2020) Lule, S. A. et al . BMJ Glob Health 5(12) https://doi.org/10.1136/bmjgh-2020-003550
• Subclinical tuberculosis disease - a review and analysis of prevalence surveys to inform definitions, burden, associations and screening methodology. (2020) Frascella, B. et al . Clin Infect Dis https://doi.org/10.1093/cid/ciaa1402

Projects: RID-TB

People: Ibrahim Abubakar , Hanif Esmail , Rishi Gupta , Marc Lipman , Maddy Noursadegh i , Gabriele Pollara , Lele Rangaka , Ali Zumla  

Like most infectious diseases, TB is more prevalent in populations who have fewer resources, less access to good and stable healthcare.  Furthermore, the long periods needed for treatment means that mobile populations of all sorts are less likely to enter a treatment programme, or are liable to default, while migrants are more likely to come from countries where TB is endemic.  Yet lack of adequate treatment not only affects those individuals, but their communities and the wider public. We have been working to support different mobile populations, such as migrants, the homeless, and people in prison.

• Integrated screening of migrants for multiple infectious diseases: Qualitative study of a city-wide programme. (2020) Eborall, H. et al . EClinicalMedicine 21: 100315 https://doi.org/10.1016/j.eclinm.2020.100315

People: Ibrahim Abubakar ,  Rob Aldridge , Andrew Hayward , Lele Rangaka , Al Story  

Although TB, caused by Mycobacterium tuberculosis and other highly related organisms in what is called the M. tuberculosis complex, may be considered the most important disease caused by mycobacteria, other mycobacteria do cause significant human disease. These are grouped essentially as ‘everything that is not tuberculosis or leprosy: non-tuberculous mycobacteria (NTMs).  These mycobacteria, such as M. abscessus   and M. avium , survive in the environment or other animals, and disease in humans is usually opportunistic.  However these infections are increasingly common and are seen in people who are generally not thought of as being at risk of such infections. NTM infections can be debilitating, and hard to diagnose and treat. Our work looks at both at how these bacteria (including M. abscessus , M. avium , M. marinum and M. ulcerans ) cause disease, and how infections can be effectively managed in patients.

• Cross-transmission is not the source of new Mycobacterium abscessus infections in a multicenter cohort of cystic fibrosis patients. (2020) Doyle, R. M. et al. Clin Infect Dis 70(9): 1855-1864 https://doi.org/10.1093/cid/ciz526
• Current and future management of non-tuberculous mycobacterial pulmonary disease (NTM-PD) in the UK. (2020) Lipman, M. et al. BMJ Open Respir Res 7(1) https://doi.org/10.1136/bmjresp-2020-000591
• Engineered bacteriophages for treatment of a patient with a disseminated drug-resistant Mycobacterium abscessus . (2019) Dedrick, R. M. et al. Nat Med 25(5): 730-733 https://doi.org/10.1038/s41591-019-0437-z
• Interferon-Gamma release assays differentiate between Mycobacterium avium complex and tuberculous lymphadenitis in children. (2021) Martinez-Planas, A. et al. J Pediatr 236: 211-218 e212 https://doi.org/10.1016/j.jpeds.2021.05.008
• Mycobacterium ulcerans -specific immune response after immunisation with bacillus Calmette-Guerin (BCG) vaccine. (2021) Pittet, L. F. et al. Vaccine 39(4): 652-657 https://doi.org/10.1016/j.vaccine.2020.11.045
• The mycobactin biosynthesis pathway: A prospective therapeutic target in the battle against tuberculosis . (2021) Shyam, M. et al. J Med Chem 64(1): 71-100 https://doi.org/10.1021/acs.jmedchem.0c01176
• Mycobactin Analogues with Excellent Pharmacokinetic Profile Demonstrate Potent Antitubercular Specific Activity and Exceptional Efflux Pump Inhibition. (2022) Shyam, M.  et al . J Med Chem 65(1): 234-256 https://doi.org/10.1021/acs.jmedchem.1c01349
• Cell-wall and Iron-acquisition mechanisms in Mycobacterium abscessus  (Sanjib Bhakta)
• European Non-tuberculouS Mycobacterial Lymphadenitis in childrEn (ENSeMBLE) study (Marc Tebruegge)
• Evolution of mycobacterial drug resistance (Naomi Fuller, Tim McHugh)
• M. abscessus rapid diagnosis of resistance with whole genome sequencing (Giovanni Satta, Garth Dixon)
• M. abscessus new treatment options, including bacteriophages (Giovanni Satta)
• Post-transcriptional regulation in M. abscessus (Kristine Arnvig)
• The Hollow-Fibre Model of M. abscessus disease to test new antibiotics and combination therapy (Steve Morris-Jones, Giovanni Satta)

People: Ibrahim Abubakar , Kristine Arnvig , Sanjib Bhakta ,  Helen Booth ,  Hanif Esmail , Naomi Fuller , Frank Kloprogge , David Lowe , Marc Lipman , Tim McHugh , Rob Miller , Steve Morris-Jones , Giovanni Satta , Helen Spencer ,  Marc Tebruegge , Gillian Tomlinson , Jacqui White

Determining the best combinations and levels of drugs for TB treatment to effectively kill bacteria, and minimise side effects, is challenging. By investigating the relationship between how much drug is used and how effective they are  (the pharmacokinetic-pharmacodynamic relationships), we can optimise the combinations of drugs that we use to treat TB. We use two approaches: the first is the hollow-fibre laboratory model, in which we investigate drug effects of treatment combinations against  M. tuberculosis  in a controlled way by mimicking antibiotic profiles to human conditions. A second approach is to evaluate antibiotic effects of drug combinations in the context of the whole body and immune system using data from patients.

• Can phenotypic data complement our understanding of antimycobacterial effects for drug combinations?  (2019) Kloprogge, F. et al.   J Antimicrob Chemother 74(12): 3530-3536 https://doi.org/10.1093/jac/dkz369
• Emergence of phenotypic and genotypic antimicrobial resistance in  Mycobacterium tuberculosis . (2022) Kloprogge, F. et al.  Sci Rep 12(1): 21429  https://doi.org/10.1038/s41598-022-25827-6
• Exploring a combined biomarker for tuberculosis treatment response: protocol for a prospective observational cohort study. (2021) Kloprogge, F et al. . BMJ Open 11(7): e052885 https://doi.org/10.1136/bmjopen-2021-052885
• Longitudinal pharmacokinetic-pharmacodynamic biomarkers correlate with treatment outcome in drug-sensitive pulmonary tuberculosis: A population pharmacokinetic-pharmacodynamic analysis. (2020) Kloprogge, F., et al . Open Forum Infect Dis 7(7): ofaa218 https://doi.org/10.1093/ofid/ofaa218
• Population pharmacokinetics and pharmacodynamics of investigational regimens' drugs in the TB-PRACTECAL clinical trial (the PRACTECAL-PKPD study): a prospective nested study protocol in a randomised controlled trial. (2021) Nyang'wa, B. T., F. Kloprogge, D. A. J. Moore, A. Bustinduy, I. Motta, C. Berry and G. R. Davies. BMJ Open 11(9): e047185 https://doi.org/10.1136/bmjopen-2020-047185
• Exploring a combined bio-marker for tuberculosis treatment response
• Exploring a biomarker for phenotypic variants of TB to map antimicrobial response

People: Frank Kloprogge , Arundhati Maitra , Zahra Sadouki

Sequencing the entire genome of M. tuberculosis has in recent years changed from a major enterprise, to being quick and a fraction of the previous cost.  Knowing the genome sequence allows the spread of the bacteria to be studied, the success of clinical trials to be measured, and genetic changes that lead to antibiotic resistance to be identified.

• Association between bacterial homoplastic variants and radiological pathology in tuberculosis. (2020) Grandjean, L. et al. Thorax 75(7): 584-591 https://doi.org/10.1136/thoraxjnl-2019-213281
• From Theory to Practice: Translating Whole-Genome Sequencing (WGS) into the Clinic. (2018) Balloux, F. et al . Trends Microbiol 26(12): 1035-1048 https://doi.org/10.1016/j.tim.2018.08.004
• Mycobacterium tuberculosis and whole-genome sequencing: how close are we to unleashing its full potential? (2018) Satta, G. et al. Clin Microbiol Infect 24(6): 604-609 https://doi.org/10.1016/j.cmi.2017.10.030 .

People: Francois Balloux , Louis Grandjean , Tim McHugh , Giovanni Satta , Lucy van Dorp

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Thesis and dissertations examining tuberculosis in Brazil between 2013 and 2019: an overview

Ana júlia reis.

1 Universidade Federal do Rio Grande, Faculdade de Medicina, Núcleo de Pesquisa em Microbiologia Médica, Rio Grande, RS, Brasil.

Juliana Lemos Dal Pizzol

Rúbia gattelli.

2 Universidade Federal do Rio Grande, Biblioteca Setorial da Área Acadêmica da Saúde, Rio Grande, RS, Brasil.

Andrea von Groll

Daniela fernandes ramos, ivy bastos ramis, afrânio kritski.

3 Universidade Federal do Rio de Janeiro, Faculdade de Medicina, Programa Acadêmico de Tuberculose, Rio de Janeiro, RJ, Brasil.

José Roberto Lapa e Silva

Pedro eduardo almeida da silva.

Authors' contribution: AJR, JLDP, RG, IBR, PEAS: Paper conception and planning, as well as the evidence interpretation; AJR, JLDP, RG, AvG, DFR, IBR, AK, JRLS, PEAS: Writing and/or reviewing the preliminary and definitive versions; AJR, JLDP, RG, AvG, DFR, IBR, AK, JRLS, PEAS: Final version approval.

Background:

Tuberculosis (TB) remains a serious public health problem, with approximately 10 million new cases reported annually. Knowledge about the quantitative evolution of theses and dissertations (T&Ds) examining human TB in Brazil can contribute to generating strategic planning for training professionals in this field and disease control. Therefore, this study highlights the role of T&Ds on TB in national scientific disclosures.

An integrative review related to TB was performed, including T&Ds produced in Brazil and completed between 2013 and 2019.

A total of 559,457 T&Ds were produced, of which 1,342 were associated with TB, accounting for 0.24% of the total number of T&Ds in Brazil. This was evidenced by a predominance of themes such as attention/health care, epidemiology, and TB treatment, and 80.2% of the T&Ds on TB were related to the large areas of health and biological sciences. Only 19.7% of T&Ds were associated with groups of patients considered at risk for TB, and 50.9% were produced in southeastern Brazil. The 1,342 T&Ds on TB were developed in 416 postgraduate programs linked to 121 higher education institutions (HEIs). We highlight that 72.7% of T&Ds on TB were produced in federal HEIs, 27.4% in state HEIs, and 8.5% in private HEIs.

Conclusions:

Strategic themes, such as TB control, require public policies that aim to increase the number of doctors and masters with expertise in TB, with geographic uniformity, and in line with the priorities for disease control.

INTRODUCTION

Tuberculosis (TB) remains a serious public health problem and is responsible for approximately 10 million new cases and 1.5 million deaths annually. Moreover, it is one of the main causes of death caused by a single infectious agent. Brazil is a priority country for this public health problem 1 , with approximately 90,000 new cases per year and a TB/human immunodeficiency virus (HIV) coinfection proportion of 11% 2 .

At the World Health Assembly in 2014, the World Health Organization approved the End Tuberculosis Strategy. Their main objectives were to reduce 90% of TB cases and 95% of TB deaths by 2035. In addition, the strategy aims to eliminate or minimize the economic impact on families affected by TB 3 . In the following year, the United Nations launched the Sustainable Development Goals, which included a 90% reduction in deaths caused by TB by 2030 4 , 5 .

Brazil's National Tuberculosis Control Program has used several strategies to control the disease, most of which are consistent with scientific evidence and guidelines recommended by the World Health Organization. This effort has resulted in improvements in epidemiological indicators, such as a reduction in the incidence and mortality of TB 6 , 7 . However, there are still many challenges, such as TB in prisons, TB/HIV coinfection, drug-resistant TB, other comorbidities (e.g., diabetes mellitus, mental health disorder, alcohol, illicit drugs, and tobacco use), a high proportion of treatment abandonment, low adherence to directly observed treatment, low contact evaluation, latent TB diagnosis and treatment, low coverage of rapid molecular diagnosis, and a low proportion of patients and family members who receive social protection 6 , 8 .

The success of actions that support global and national TB control and elimination strategies depends on qualified professionals generating, evaluating, and correctly using scientific knowledge. In Brazil, doctors and masters (D&M) are formed within the National Postgraduate System, whose Postgraduate Programs (PGPs) are accredited and periodically evaluated using the Coordination of Higher-level Personnel Improvement (CAPES) evaluation system 9 .

Knowledge about the quantitative evolution of theses and dissertations (T&Ds) produced in the area of human TB, as well as information about the spatiotemporal, thematic, and institutional distribution and its relationship with the TB burden in different populations and regions of Brazil, can contribute to generating strategic planning for the training of professionals in this theme. In addition, this study highlights the essential role of T&Ds in national scientific disclosures.

An integrative review was performed, including T&Ds related to TB, completed between January 1, 2013 and December 31, 2019, and made available in the CAPES database. This study was carried out based on the principles of scientometrics, which consist of “Quantitative assessment and analysis of intercomparisons of activity, productivity, and scientific progress 10 . ”

T&Ds identification and classification were performed independently by two researchers using the T&Ds catalog made available using the CAPES (Ministry of Education, Federal Government, Brazil) in Portuguese at https://dadosabertos.capes.gov.br/dataset.

The search for T&Ds was performed using the following Portuguese terms: Mycobacterium tuberculosis, Mycobacteria , antituberculostatics, isoniazid, and rifampicin. In addition, authorized descriptors in Portuguese, synonyms/alternative terms, related terms, and generic terms were used (DeCS/MeSH Health Sciences Descriptors - https://decs.bvsalud.org/) ( Supplementary Material Table 1S ). T&Ds that had any of these terms in the title, abstract, or keywords I were selected.

After the initial screening, the selected T&Ds were individually analyzed by two researchers, and those that mentioned any of the terms used in the search ( Supplementary Material Table 1S ) but whose work content was not associated with TB were excluded. The data were analyzed considering each thesis and dissertation equivalent to a doctorate and master's degree (professional and academic), respectively. In addition, the following variables were evaluated: T&Ds theme, the total number of T&Ds on TB produced in Brazil, period of time for D&M academic formation, CAPES assessment area, CAPES large knowledge areas, CAPES knowledge areas, subareas, risk groups for TB included in T&Ds, and T&Ds geographic and institutional distribution.

According to the CAPES, the assessment areas are grouped into a large knowledge area, which in turn are grouped into knowledge areas and subareas (first level: large knowledge area: gathering of different knowledge areas, due to the affinity of their objects, cognitive methods, instrumental resources, and reflecting specific sociopolitical contexts; second level: knowledge area: set of interrelated knowledge, collectively constructed, gathered according to the nature of the investigation object, and for the purposes of teaching, research, and practical applications; and third level: subarea: segmentation of the knowledge area established according to the object of study and recognized and widely used methodological procedures) 11 .

T&Ds were classified into the following themes: attention/health care, biochemistry, diagnosis, drugs, epidemiology, genetics, immunology, resistance, and treatment. The classification was performed by searching for keyword II in Portuguese associated with different themes ( Supplementary Material List 1S ). For T&Ds related to more than one theme, the main theme and its associated themes were independently defined by two researchers.

Data were tabulated in Microsoft Excel and analyzed using International Business Machine (IBM) Statistical Package for the Social Sciences (SPSS) software version 20.0 (International Business Machines Corporation - IBM - Armonk - New York - USA). The absolute and relative frequencies were determined.

Between 2013 and 2019, considering all PGPs and knowledge areas, 559,457 T&Ds were produced in Brazil, of which 2,665 were initially selected as being associated with TB using the terms described in the Supplementary Material Table 1S . After an individual analysis, 1,342 T&Ds were selected for their association with TB, accounting for 0.24% of the total number of T&Ds produced in Brazil, of which 31.8% (427/1,342) were theses and 68.2% (915/1,342) were dissertations.

The total number of completed T&Ds in Brazil increased by 38.7% between 2013 and 2019, while the number of T&Ds on TB was proportionally reduced annually, beginning in 2014. When comparing 2013 and 2019, there was a 24.5% reduction in academic dissertations associated with TB, whereas the number of theses increased by 26%. Despite this, the number of theses concluded showed a 9% reduction between 2018 (the year with the greatest production) and 2019 ( Table 1 ).

* Total production and percentage of each production type per year in Brazil. ** Total productions and percentage of each type of production per year, associated with TB.

Between 2013 and 2019, there was a 77% increase in the number of professional dissertations. In 2016, professional master’s degrees represented 20.7% (41/198) of the T&Ds on TB produced in Brazil ( Table 1 ). Of these, 48.8% (20/41) were carried out in Rio de Janeiro, with 85% (17/20) linked to the PGP of Family Health and Epidemiology in public health, coordinated by the Fundação Oswaldo Cruz (Fiocruz); 29.3% (12/41) were carried out in the state of Pernambuco, with 66.7% (8/12) linked to the PGP of public health of the Fiocruz.

When evaluating the necessary time to complete the postgraduate course, only approximately half of the T&Ds - doctorate 52.5% (224/427), academic master's degree 52.5% (404/770), and professional master's degree 48.3% (70/145) - were completed within 48 (doctorate) and 24 (master’s) months, the periods expected for presenting T&Ds in Brazil.

Regarding the large knowledge areas, among the 1,342 T&Ds produced during the study period, 67.9% and 12.3% were related to health sciences and biological sciences, respectively. The remaining T&Ds (19.8%) were multidisciplinary (8.4%), exact and earth sciences (6.8%), engineering (1.3%), applied social sciences (1.0%), human sciences (1.1%), agricultural sciences (1.0%), and linguistics, letters, and arts (0.3%).

When the knowledge areas were evaluated, 67.4% of the T&Ds associated with TB were concentrated in medicine (27.8%), public health (16.7%), and nursing (13.5%) ( Table 2 ).

*administration (0.1% - 02/1,342); agronomy (0.4% - 06/1,342); botany (0.1% - 01/1,342); computer science (0.2% - 03/1,342); information science (0.1% - 02/1,342); food science and technology (0.1% - 01/1,342); political science (0.1% - 01/1,342); communication (0.1% - 01/1,342); ecology (0.1% - 01/1,342); economy (0.4% - 05/1,342); education (0.1% - 01/1,342); biomedical engineering (0.1% - 01/1,342); materials and metallurgical engineering (0.1% - 02/1,342); production engineering (0.1% - 02/1,342); mechanical engineering (0.1% - 01/1,342); nuclear engineering (0.1% - 01/1,342); chemical engineering (0.1% - 01/1,342); physics (0.3% - 04/1,342); geography (0.4% - 05/1,342); history (0.4% - 06/1,342); language (0.2% - 03/1,342); linguistics (0.1% - 01/1,342); mathematics (0.1% - 01/1,342); materials (0.4% - 05/1,342); veterinary medicine (0.4% - 05/1,342); morphology (0.1% - 01/1,342); nutrition (0.1% - 01/1,342); odontology (0.4% - 06/1,342); urban and regional planning (0.1% - 02/1,342); social service (0.1% - 01/1,342); sociology (0.1% - 02/1,342); zootechnics (0.1% - 01/1,342). **public and business administration, accounting science and tourism (0.1% - 02/1,342); astronomy/physics (0.3% - 04/1,342); biodiversity (0.1% - 02/1,342); computer science (0.2% - 03/1,342); food science (0.1% - 01/1,342); political science and international relations (0.1% - 01/1,342); agrarian sciences I (0,4% - 06/1342); biological sciences II (0.1% - 01/1,342); communication and information (0.2% - 03/1,342); economy (0.4% - 05/1,342); education (0.1% - 01/1,342); engineering II (0.3% - 04/1,342); engineering III (0.2% - 03/1,342); engineering IV (0.1% - 01/1,342,); geography (0.4% - 05/1,342); history (0.4% - 06/1,342); language/linguistics (0.1% - 01/1,342); linguistics and literature (0.2% - 03/1,342); mathematics/probability and statistics (0.1% - 01/1,342); materials (0.4% - 05/1,342); veterinary medicine (0.4% - 05/1,342); nutrition (0.1% - 01/1,342); odontology (0.4% - 06/1,342); urban and regional planning/demography (0.1% - 02/1,342); social service (0.1% - 01/1,342); sociology (0.1% - 02/1,342); zootechnics/fishing resources (0.1% - 01/1,342).

Almost all T&Ds within the knowledge area of medicine were related to the assessment areas of Medicine I and II. In the Medicine II assessment area, 209 T&Ds were concluded, with 38.8% on the infectious and parasitic diseases or tropical and infectious disease subareas. In the Medicine I assessment area, 162 T&Ds were concluded, with 53.7% distributed among the subareas of pulmonology, infectious diseases, and pneumological sciences. In addition to the subareas mentioned above, 26 other subareas were observed in the assessment area of Medicine I and 38 in Medicine II.

Thematic classification

T&Ds on TB were developed within a wide range of themes. Although 50.3% (675/1,342) of T&Ds could be classified as a single theme, 49.7% (667/1,342) were related to more than one theme, which was named “associated themes” in this study. With a predominance of themes, such as attention/health care, epidemiology, and treatment ( Supplementary Material Table 2S ), the association frequency between the main and associated themes was evaluated ( Figure 1 ).

T&Ds on TB were also classified according to the type of study, with 50.1% related to basic research (drugs, genetics, immunology, resistance, and biochemistry), 33.9% to translational research (attention/healthcare), 30.5% to epidemiological research, 26.7% to TB treatment, and 19.4% to TB diagnosis.

T&Ds associated with groups of patients at risk for tuberculosis development

Only 19.7% (264/1,342) of T&Ds cases were associated with groups of patients considered at risk for TB development ( Table 3 ), with 5.7% (15/264) associated with more than one risk group.

Source: National Congress, Federal Government. BRASIL, 1990: According to the Child and Teenagers Statute, were considered children those aged up to 12 years and teenagers those aged up to 18 years. Source: National Congress, Federal Government. BRASIL, 2003: According to the Elderly Statute, all patients aged > 60 years were considered. & Source: SINAN, 2021. Calculation based on the average per year of all TB cases in Brazil between 2013 and 2019 (89,104): # 12 children and teenagers (< 1 year, 1-4, 5-9, 10-14, and 15-19 years); * 13 and older adults (60-64, 65-69, 70-79, and ≥ 80 years).

T&Ds geographical and institutional distribution

The 1,342 T&Ds on TB were produced in 416 PGPs and linked to 121 higher education institutions (HEIs) ( Figure 2 ): 48.8% were federal, 19.8% were state, and 31.4% were private HEIs. Although approximately 1/3 (31.4%) of the HEIs were private, only 8.5% of the T&Ds on TB were produced in this type of institution, while 72.7% were in federal HEIs, and 27.4% were in state HEIs.

Overall, 50.9% of T&Ds on TB are produced in southeast Brazil. The state of Rio de Janeiro was responsible for 23% of T&Ds on TB produced in Brazil between 2013 and 2019, and 17.6% of T&Ds were produced in southern Brazil. Rio Grande do Sul produced 10% and 55.9% of T&Ds on TB in the country and southern Brazil, respectively. Finally, 16.8% and 8.2% of T&Ds were produced in the northeast and northern Brazil, respectively ( Supplementary Material Table S3 ).

Between 2013 and 2019, 0.24% of T&Ds produced in Brazil were associated with TB. According to a previous study, Brazil ranked sixth among countries that published the most on TB between 2007 and 2016, representing 3.8% of global publications associated with this theme 15 .

The total number of T&Ds in Brazil increased by 38.7% between 2013 and 2019, while the number of T&Ds on TB was proportionally reduced annually beginning in 2014, showing a reduction in the generation of D&M. This reduced formation of human capital in this area could put Brazilian TB control efforts at risk, harming the promotion, assistance, management, research, development, and innovation related to TB.

It is important to emphasize that the number of professional master's degree dissertations showed significant growth during the study period, which may be related to the fact that this is the newest modality of stricto sensu postgraduate study in recent years. For example, in 2016, the number of professional master's degrees represented 20.7% of the T&Ds on TB produced in Brazil, with a 77% increase when comparing 2013 and 2019.

In general, professional and academic master's degrees differ primarily in the formation of professionals who meet specific needs and have immediate applicability of the generated knowledge (professional) from those who will follow an academic career with a doctorate as their next goal (academic).

Regarding scholarships offered by the CAPES, there was an 11% increase in master's scholarships between 2011 and 2017 and a 23% increase in doctorate scholarships between 2010 and 2014 16 . Although there is a dissociation between the number of T&Ds on TB and the increase in scholarship offerings, the ratio between academic dissertations and theses decreased from 2.3 to 1.5 between 2013 and 2019, while the ratio between academic and professional dissertations decreased from 8.8 to 4.1 during the same period. These results indicate a policy to encourage the development of doctors and professional masters in relation to academic masters.

Although the CAPES recommended (before the coronavirus disease 2019 [COVID-19] pandemic) a maximum time for the training of masters and doctors of 24 and 48 months, respectively, only approximately half of the T&Ds on TB were completed within this time. Even though there is not necessarily a direct relationship between the deadline to complete the postgraduate course and the quality of T&Ds or the formation process, the time to complete a doctorate could be reduced through the implementation of strategies such as reducing the time for a master's degree to 1 year, as was recently proposed to the CAPES 17 .

As mentioned above, TB remains a serious public health problem in Brazil, with a high number of cases, a high proportion of TB/HIV coinfection, underreporting of cases (10-20% of undetected and/or untreated cases), high proportions of treatment abandonment, and a high incidence in vulnerable populations 1 , 6 , 18 . In this demanding scenario of needs and questions, T&Ds on TB were developed within a wide range of themes. There was a greater association between different themes, indicating an important multi-disciplinarity in the formation of D&M in the area of TB. This combination of themes boosts the formation of D&M with diverse skills and a broader view of problems.

Furthermore, according to previous studies 19 , 20 , T&Ds on TB were classified according to the type of study, with 50.1% related to basic research, 33.9% to translational research, 30.5% to epidemiological research, 26.7% to TB treatment, and 19.4% to TB diagnosis. A study evaluating publications on TB from BRICS countries (Brazil, Russia, India, China, and South Africa) indicated that 29.6% of publications were associated with epidemiological research, 33.8% with basic research, 13.1% with operational research, 10.1% with TB diagnosis, and 6.6% with TB treatment 15 .

When the groups of patients considered at risk for TB development were evaluated, we observed that only 19.7% of the T&Ds on TB were associated with these groups of patients, with 5.7% being associated with more than one risk group. Among the priority groups for TB control are people with positive serology for HIV (HIV+), prisoners, children/teenagers, indigenous individuals, health professionals, patients with diabetes mellitus, older adults, homeless populations, alcohol, drugs, and tobacco users 2 , 18 , only 8.2%, 2.9%, 2.5%, 1.6%, 1.5%, 1.3%, 0.8%, and 0.8% of T&Ds on TB were associated with these groups of patients, respectively. This dissonance between the main risk groups for TB development and the production of scientific knowledge, as well as the formation of professionals related to these essential issues, shows a precarious balance between academic needs and solutions, limiting the transfer of scientific benefits to the society. A significant number of TB cases in Brazil are among HIV+ patients, prisoners, children/teenagers, elderly people, and patients with diabetes mellitus 6 ; however, only 16% of the T&Ds on TB were associated with these groups of patients.

Brazil is a continental country with profound inter- and intra-regional social, economic, educational, and public health asymmetries. This diversity of scenarios is also observed in relation to the T&Ds produced within the TB theme. Most T&Ds were concentrated in southeastern and southern Brazil and were produced in PGPs from public HEIs, particularly federal HEIs. The necessary impetus for the formation of D&M in regions such as northern and northeastern Brazil can be facilitated by public policies using connections established by the Brazilian Tuberculosis Research Network (REDE-TB) 21 .

In southeast Brazil, where 45.2% of TB cases occur, with a prevalence of 45.9 cases per 100,000 inhabitants, which is higher than that of the overall prevalence in Brazil (41.9 cases per 100,000 inhabitants), 50.9% of T&Ds on TB were produced. The state of Rio de Janeiro, with a TB prevalence of 79.5 cases per 100,000 inhabitants, was responsible for 23% of T&Ds on TB produced between 2013 and 2019. In southern Brazil, where 12.7% of TB cases occurred, with a TB prevalence of 37.4 cases per 100,000 inhabitants, 17.6% of T&Ds on TB were produced. Interestingly, 26% of T&Ds produced in southern Brazil were associated with private HEIs. The state of Rio Grande do Sul has approximately 50% of the HEIs and PGPs in southern Brazil and produces 10% and 55.9% of T&Ds on TB in the country and southern region, respectively 2 , 14 .

Northeast Brazil, which was home to 26.3% of TB cases in Brazil between 2013 and 2019, produced 16.8% of T&Ds on TB. Despite having 10.9% of TB cases with a prevalence of 51.6 cases per 100,000 inhabitants, Northern Brazil produced only 8.2% of the T&Ds on TB. Finally, we highlight the state of Amazonas, which has the highest TB prevalence in Brazil, with 81.2 cases per 100,000 inhabitants, and produces only 3.1% of the T&Ds on TB. In both regions, northeast and northern Brazil, unlike in southeast and southern Brazil, there is a dissonance between the TB burden and the number of D&M formed in the TB theme, which is likely related to the lowest number of PGPs in these regions 2 , 14 .

D&M can act in government institutions and civil society, both public and private, as a protagonist in the promotion, production, evaluation, and implementation of scientific knowledge. Scientific knowledge generation, which is necessary to overcome the challenges faced by society, depends on investments in infrastructure, the provision of money for research, and the formation of human capital. Furthermore, strategic themes, such as disease control, including TB, should be prioritized. Therefore, it is necessary to create public policies that can integrate PGPs, public health agencies, and entities representing civil society, among others, aiming for an expansion in the number of D&M with expertise in TB as well as a greater geographic uniformity in D&M formation, in line with the priorities for TB control.

Despite this, we highlight that a limitation of this study is related to the number and themes of T&Ds associated with TB may not reflect the quality of the research and product generation in Brazil, as this is evaluated through article impact factors and patent registration.

Finally, the development, evaluation, and implementation of new diagnostic platforms, more effective vaccines, new antimicrobials, evaluation of new therapies, and management strategies are essential and constitute the pillar of research and innovation in the End Tuberculosis Strategy. Despite this, the formation of D&M in knowledge areas with a technological profile that can meet the technological demands of the Brazilian Unified Health System has decreased, not exceeding 1/5 of the titled D&M. This scenario puts efforts for TB control at risk and jeopardizes technological sovereignty promotion, foreign exchange savings, and the universalization of academic knowledge benefits 22 .

SUPPLEMENTARY MATERIAL. 

LIST S1: KEYWORDS USED TO CLASSIFY THESES AND DISSERTATIONS IN THEMES.

ATTENTION/HEALTH CARE: healthcare access; assistance; attention to the person with tuberculosis; attitudes and practices; basic health care; basic health indicators; basic health unit/units; brief intervention; capacity building; collective health; committee methods; communicators; community councils; community health agent; comprehensive health care; contacts; control measures; control program; cost/costs; cost-effectiveness; disease control; educational material/materials; educational technology; interventions effectiveness; family health; fight against tuberculosis; healthcare promotion; healthcare; health communication; health conditions analysis; health education; health evaluation; health policies; health service/services; health surveillance; health teaching; health training; health unic system; health unit/units; home contact; home visit; income; inequalities/inequality; infection control; information source; information system/systems; integrated management; knowledge about tuberculosis; knowledge evaluation; living condition/conditions; management; meanings and experiences; medical education; nurses' actions/appointment; nursing practice; health professionals' performance; permanent education; pharmaceutical attention; post-discharge management; prevention and control; primary health care; public health; public health policies; service qualification; life quality; information quality; reference center/laboratory/unit; referral hospital/service; referral outpatient clinic; respiratory symptomatic; route; sanitary service; social condition/conditions; social determinants; social development; social indicators; social inequity; social mobilization; social protection; social representations; social security; social support; stigma; trajectories/trajectory; tuberculosis control; tuberculosis indicators; undernotification; vulnerability.

BIOCHEMISTRY: acetyltransferase/acetyltransferases; ATP: biochemicals; biochemistry; cathepsin; enzymatic; enzyme/enzymes; glycation; leptina; lipid mediators; metalloproteinase/metalloproteinases; oxidative stress; phospholipase; protease; proteolysis; reductase/reductases; shikimate; transferase; transpeptidase/transpeptidase.

DIAGNOSIS: accuracy; bacilloscopy/BAAR; biomarker/biomarkers; clinical decision; clinical laboratory; detection; diagnosis; diagnoses/diagnosis; GeneXPERT/XPERT; signs and symptoms identification; IGRA; immunodiagnostic; molecular rapid test; mpt64; multiplex/multiplex PCR; mycobacteria identification; point-of-care; quantiferon/quantiferon-TB; radiography; screening exam; tomographic features; tuberculin proof; tuberculin test/skin test; X-ray.

EPIDEMIOLOGY: age/age and sex effects; associated determinants/factors; association measures; case analysis; case-control; clinical and laboratory profile; clinical-epidemiological; determinant factors; epidemiological; epidemiology; genotyping; geoepidemiological; geographic aspects; health geography; hospitalization time; incidence; lethality; MIRU/MIRU-VNTR; molecular characterization; morbidity; mortality; notification; notified; pharmacoepidemiological; prevalence; probabilistic correlation; related factors; risk factor/factors; score; spatial analysis/distribution; spatio-temporal; sociodemographic; socioeconomic; spoligotyping; survival; systematic review; temporal analysis.

GENETICS: alleles; beijing; chemogenomics; epigenetic/epigenetics; gene/genes; gene expression; gene transcription; genetic/genetics; genome; genotype/genotypes; hemeproteins; lineage/lineages; metabolomics; microRNA; mutation/mutations; polymorphism/polymorphisms; protein/proteins; protein subunit; proteomics; transcriptional regulation; transcriptional repressor; sequencing; sub-lineage.

IMMUNOLOGY: antibodies; antigen/antigens; apolipoprotein; BCG; CD cells; cytokine/cytokines; dendritic cells; epitopes; granuloma; HLA; humoral response; IFN; immune; immunodiagnostic; immunological; immunomodulation; immunomodulator/immunomodulators; immunomodulatory; immunopathogenesis; immunopathology; inflammatory markers; inflammasome/inflammasomes; interleukin/IL; interferon; lymphocyte/lymphocytes; lysosome; macrophage; monocytes; neutrophils; T-cells; toll-like; tumor necrosis factor/TNF; vaccine/vaccines.

DRUGS: activity evaluation; anti- Mycobacterium tuberculosis activity/activities; antimicrobial action/activity/potential; antimycobacterial activity/potential; antituberculosis activity; biocomposites; biological activity/activities; biological evaluation; biological prospecting; bioprospecting; biosynthesis; chemical and biological study; computational modeling; computational simulation; cytotoxicity; cytotoxicity; cytotoxicological evaluation; drug development; drug planning; extract/extracts; formulation/formulation development; inhibitor development; medicine innovation; microparticles; nanocarriers; nanocomposite/nanocomposites; nanofibers; nanomaterials; nanoparticle/nanoparticles; nanoreservoir; new derivatives; new drugs/molecules; obtaining and characterization; pharmaceutical excipient; pharmaceutical innovations; pharmacokinetic studies; pharmacophore; pharmacophoric; phytochemical study; physical stability; physicochemical characterization; potential action; potential activity; randomized clinical trial; rational drug design; molecule reuse; secondary metabolites; solubility; drug structural characterization; structure activity; synthesis; synthetic and antimicrobial potential; tuberculostatic activity.

RESISTANCE: antibiofilm; biofilm/biofilm; drug resistant; efflux; MDR-TB: minimal inhibitory concentration; modulatory effect: monoresistant; multidrug resistant/resistance; multi-resistant; resistance to drugs; sensitivity test/tests.

TREATMENT: abandonment; acetylation; adverse reactions; anti-tuberculosis drugs; anti-tuberculosis therapy; anti-tuberculosis regimens; bacteriological conversion; blood concentrations; case outcomes; chemoprevention; chemoprophylaxis; clinical/clinical and therapeutic evolution; combined therapy; cure; directly observed therapy; drug exposure; drug interaction/interactions; drug therapy; fixed combined dose; hepatotoxicity; isoniazid; quadruple scheme; plasmatic concentrations; post-treatment; medicines rational use; retreatment; rifampicin; serum concentrations; therapeutic adherence; therapeutic effect; therapeutic intervention; therapeutic itinerary/itineraries; therapeutic outcomes; therapeutic scheme; treaties; treatment; tuberculosis therapy.

Supplementary Material Table 1S:

Supplementary Material Table 2S:

* Based on total T&D. ** T&D not classified in any of the themes.

Supplementary Material Table 3S:

I = Keywords of T&D; II = Keywords used to classify T&D by theme.

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Tuberculosis research questions identified through the WHO policy guideline development process

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WHO guideline development groups identify research questions using systematic reviews, economic analyses and stakeholder consultations during policy guidance development to identify urgent research gaps in the policy/implementation interface http://ow.ly/lUUw30nQZRO

High-quality research evidence is critical for improving global health and health equity, and for achieving the World Health Organization (WHO)'s objective of the attainment of the highest possible level of health by all peoples [ 1 ]. This need is most apparent when responding to complex epidemics such as tuberculosis (TB). TB is the leading killer among diseases caused by an infectious agent worldwide, the leading killer of people with HIV infection and a leading cause of death from airborne anti-microbial resistant infections, taking heavy tolls on human lives, communities and health systems at large [ 2 , 3 ]. WHO estimates that TB caused illness in 10 million people and claimed an estimated 1.6 million lives in 2017 alone [ 2 ]. The WHO End TB Strategy, in the context of the Sustainable Development Goals (SDGs), lays ambitious goals and milestones to end the epidemic by reducing incidence and mortality by 80% and 90% in 2030 compared to 2015: such reductions can only be achieved if there are major technological breakthroughs by 2025 [ 4 ].

Critical research is needed to acquire rapid point-of-care TB diagnostics, including for drug resistance; shorter, safer and simpler regimens effective against drug-susceptible and drug-resistant TB, as well as latent TB infection (LTBI) that are appropriate for treatment of TB/HIV co-infection; and a new TB vaccine that is effective both before and after exposure. These require scientific advances in the discovery and development of new biomedical tools, together with innovative delivery mechanisms to effectively adapt and adopt new technologies and optimise the necessary linkages and integrations with other health services and sectors. For this reason, “Intensified research and innovation” has been identified as one of the three essential pillars of the End-TB Strategy. This editorial summarises the research questions identified through recent WHO TB policy guidance to increase the quality of evidence for policy-making. Based on evidence arising from research, WHO is mandated to produce recommendations to guide clinical practice and public health policy for TB prevention and care in response to demand from public health decision makers. WHO guideline development groups (GDGs), which include researchers, the health workforce, civil society, as well as end-users of the guidelines, such as policymakers from government, professional associations and other constituencies, are appointed by WHO to develop policy guidelines [ 5 ]. A GDG meets with the primary objective of agreeing on the scope of recommendations by reviewing evidence, structured according to the standard framework of population, intervention, control, outcomes (PICO). This permits a systematic study of relevant evidence, the formulation of recommendations and the identification of knowledge gaps that need to be addressed through high quality research conducted in various epidemiological, demographic and geographic settings. The research questions highlighted in this document arose because the respective GDGs agreed they were critical for increasing the certainty/strength of existing recommendation, and/or for stimulating the development or optimisation of new recommendations that can lead to improvement in patient health and welfare. This step is an integral part of the WHO guideline development process (see, for example, the discussion section of F alzon et al . [ 6 ]).

Among the major challenges facing global policy guidance development in TB are the shortage of good quality evidence exacerbated, for example, by lack of sufficient clinical trials with direct evidence of clinical benefit or improvement in an established surrogate for clinical benefit; data inaccessibility including for programmatic experiences of benefits and safety of interventions in real world setting; or when the evidence being presented does not address broader questions of values and priorities that go beyond medical interventions ( e.g. acceptability, feasibility, resource distribution and health equity). Evidence obtained from well-designed, large scale multidisciplinary studies with robust testing of interventions are therefore needed to improve the strength of future guidance.

The most up-to-date WHO policy guidance documents for TB prevention and care are summarised in a Compendium of TB Guidelines and Associated Standards [ 7 , 8 ]. Using this compendium as a reference, we compiled a list of 155 research questions across the continuum of TB prevention, diagnosis, treatment and care (also summarised in table 1 ): three related to early detection; 35 related to diagnosis of TB disease, 10 related to the diagnosis and management of latent TB infection, 38 related to treatment of TB disease, including drug-resistant TB; 38 related to the management of TB/HIV and malnutrition; and 31 related to childhood TB management [ 10 ]. Because these research questions are limited in scope to needs identified during guideline development processes, the majority of the questions highlight gaps at the policy/implementation interface ( figure 1 ). Systematically linking such research questions to public health goals requires collaboration among funders, researchers and end users to ensure that funded research represents value for money, not only through the generation of new knowledge but also by contributing to health and economic outcomes. There are several ways of accomplishing that. The National Institute for Health Research Public Health Research Programme (NIHR PHR Programme) in the UK, for example, includes public health decision makers in its decision-making committee, and subsequently, the research it funds has been shown to align with priorities highlighted in national guidelines [ 11 ]. However, this is not the practice across all research funders. An exploratory qualitative study of funding strategy among five high-profile public health research funding organisations showed limited involvement from end users/policymakers in the prioritisation of research questions for funding [ 12 ]. Considering the need for well-funded, timely and high quality research for policy, funders should capitalise on opportunities to strengthen participation of policymakers and other end users in generating priority-driven research funding streams.

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Representation of the research questions documented in World Health Organization tuberculosis (TB) policy guidance documents. BCG: bacille Calmette–Guerin; LTBI: latent TB infection; MDR-TB: multidrug-resistant TB; Hr-TB: isoniazid-resistant TB.

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Research questions from the World Health Organization (WHO) tuberculosis (TB) policy guidance documents

At a time when there are many competing demands on limited resources, the WHO and its partners, countries, civil society and affected communities have a joint responsibility to ensure that TB research investments help achieve the goals and targets of the End TB Strategy and the SDGs. In recognition of this need, a TB resolution adopted at the World Health Assembly in May 2018 requested WHO to develop a global strategy for TB research and innovation, “to make further progress in enhancing cooperation and coordination in respect of tuberculosis research and development” [ 13 ]. Considering the significant funding gap for TB research (USD 1.3 billion gap in 2017 when benchmarked against the targets outlined in the Global Plan to End TB 2016–2020: the Paradigm Shift ), such coordination and collaboration is envisioned to help direct time and resources to the most urgent evidence needs faced by TB policymakers [ 14 – 16 ].

Conflict of interest: N. Gebreselassie has nothing to disclose.

Conflict of interest: D. Falzon has nothing to disclose.

Conflict of interest: M. Zignol has nothing to disclose.

Conflict of interest: T. Kasaeva has nothing to disclose.

• Received November 6, 2018.
• Accepted February 8, 2019.
• The content of this work is copyright of the authors or their employers. Design and branding are copyright ©ERS 2019.
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The DHS Program

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• Alcohol and Tobacco
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• Household and Respondent  Characteristics
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• Tuberculosis

What is tuberculosis?

Tuberculosis, or TB, is an infectious bacterial disease caused by Mycobacterium tuberculosis, which most commonly affects the lungs. It is transmitted from person to person via droplets from the throat and lungs of people with the active respiratory disease. But people infected with TB bacilli will not necessarily become sick with the disease. The immune system "walls off" the TB bacilli which, protected by a thick waxy coat, can lie dormant for years. When someone's immune system is weakened, the chances of becoming sick are greater.

• Overall, one-third of the world's population is currently infected with the TB bacillus.
• 5-10% of people who are infected with TB bacilli (but who are not infected with HIV) become sick or infectious at some time during their life.
• People with HIV and TB infection are much more likely to develop TB.
• TB is the leading killer of people who are HIV infected.

If properly treated, tuberculosis caused by drug-susceptible strains is curable in virtually all cases. If untreated, more than half the cases may be fatal within five years.

What data does DHS collect about TB?

The DHS collects data on women's and men's knowledge and attitudes concerning TB. Over 90 surveys have included TB questions.

What are the DHS indicators related to TB knowledge and attitudes?

• Percentage who have heard of TB
• Percentage who report that TB is spread through the air by coughing
• Percentage who believe that TB can be cured
• Percentage who would want a family member's TB kept secret

What data does SPA collect about TB?

The Service Provision Assessment ( SPA ) survey collects data on TB diagnostic services, TB treatment, and/or follow-up services and facilities following DOTS (Directly-observed Treatment, Short-course) strategy and any treatment other than DOTS strategy.

Photo credit: © 2008 Anil Gulati, Courtesy of Photoshare. Wall paintings on a TB hospital in Nowgaon, District Chhatarpur, Madhya Pradesh, India, illustrate DOTS tuberculosis medication therapy.

• Stop TB Partnership - resources page
• WHO - TB indicators
• The Lancet - special series on TB
• WHO - Status of the global TB epidemic
• WHO - Stop TB Strategy
• World Bank - TB data by country
• CDC - Find TB Resources
• US Global Health Policy (data by topic: TB)
• Tuberculosis Control Assistance Program (2005-2010) toolbox

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MSc Public Health DISSERTATION: 'Determinants of tuberculosis transmission in Sub-Saharan Africa prisons and control strategies: A systematic review.' SUBMITTED IN PART FULFILMENT FOR THE AWARD OF

Related Papers

BMC Infectious Diseases

Desmond Kuupiel

Adane Worku

Tuberculosis Research and Treatment

Peter Nyasulu

Introduction. Correctional facilities house large number of inmates who are at high risk of developing tuberculosis (TB); however factors associated with TB among inmates at Mangaung Correctional Centre have not been studied.Study Population and Methods. We undertook a case control study and reviewed a total of 1140 medical records of inmates treated for TB between 2009 and 2010. Cases were selected randomly from the medical records of inmates who were treated. Data collected were analysed using STATA version 12.0 and determinants of TB were evaluated using multiple logistic regression analyses. Factors withP&lt;0.05were considered significant.Results. Prevalence of TB was 8.8% and 52% of inmates with TB were aged 31–40 years; 58% of the TB cases were HIV positive and 34% of them had CD4 cell count 350 cells/mm3. Factors associated with TB among inmates were HIV coinfection (OR: 4.2; 95% CI: 2.64–7.00); previous history of TB disease (OR: 3.58; 95% CI: 2.25–5.70); and smoking (OR: 2...

BMC infectious diseases

Everton Lemos

Globally, prison inmates are a high-risk population for tuberculosis (TB), but the specific drivers of disease and impact of mass screening interventions are poorly understood. We performed a prospective cohort study to characterize the incidence and risk factors for tuberculosis infection and disease in 12 Brazilian prisons, and to investigate the effect of mass screening on subsequent disease risk. After recruiting a stratified random sample of inmates, we administered a questionnaire to ascertain symptoms and potential risk factors for tuberculosis; performed tuberculin skin testing (TST); collected sera for HIV testing; and obtained two sputum samples for smear microscopy and culture, from participants reporting a cough of any duration. We repeated the questionnaire and all tests for inmates who remained incarcerated after 1 year. TST conversion was defined as TST ≥10 mm and an induration increase of at least 6 mm in an individual with a baseline TST &lt;10 mm. Cox proportional ...

Justin O'Grady

Habtamu Woldeamanuel

BackgroundPulmonary Tuberculosis (PTB) is a major health problem in prisons. Multiple studies of TB in regional Ethiopian prisons have assessed prevalence and risk factors but have not examined recently implemented screening programs for TB in prisons. This study compares bacteriologically-confirmed PTB (BC-PTB) prevalence in prison entrants versus residents and identifies risk factors for PTB in Kality prison, a large federal Ethiopian prison located in Addis Ababa, through a study of an enhanced TB screening program.MethodsParticipating prisoners (n = 13,803) consisted of 8,228 entrants screened continuously and 5,575 residents screened in two cross-sectional waves for PTB symptoms, demographics, TB risk factors, and medical history. Participants reporting at least one symptom of PTB were asked to produce sputum which was examined by microscopy for acid-fast bacilli, Xpert MTB/RIF assay and MGIT liquid culture. Prevalence of BC-PTB, defined as evidence of Mycobacterium tuberculosis (MTB) in sputum by the above methods, was compared in entrants and residents for the study. Descriptive analysis of prevalence was followed by bivariate and multivariate analyses of risk factors.ResultsPrisoners were mainly male (86%), young (median age 26 years) and literate (89%). Prevalence of TB symptoms by screening was 17% (2,334/13,803) with rates in residents >5-fold higher than entrants. Prevalence of BC-PTB detected by screening in participating prisoners was 0.16% (22/13,803). Prevalence in residents increased in the second resident screening compared to the first (R1 = 0.10% and R2 = 0.39%, p = 0.027), but remained higher than in entrants (4.3-fold higher during R1 and 3.1-fold higher during R2). Drug resistance (DR) was found in 38% (5/13) of culture-isolated MTB. Risk factors including being ever diagnosed with TB, history of TB contact and low Body Mass Index (BMI) (<18.5) were significantly associated with BC-PTB (p<0.05).ConclusionsBC-PTB prevalence was strikingly lower than previously reported from other Ethiopian prisons. PTB appears to be transmitted within this prison based on its higher prevalence in residents than in entrants. Whether a sustained program of PTB screening of entrants and/or residents reduces prevalence of PTB in prisons is not clear from this study, but our findings suggest that resources should be prioritized to resident, rather than entrant, screening due to higher BC-PTB prevalence. Detection of multi- and mono-DR TB in both entrant and resident prisoners warrants regular screening for active TB and adoption of methods to detect drug resistance.

Markos Abebe

The Journal of infectious diseases

Stephanie M Topp

The International Journal of Tuberculosis and Lung Disease

Frederick Altice

Celestine Ameh

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New Approaches Against Drug-Resistant M. tuberculosis

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Tuberculosis (TB) is a contagious and deadly disease caused by Mycobacterium tuberculosis bacillus, which has reached pandemic proportions. About 1.7 billion people (23% of the world’s population) are estimated to have a latent TB infection, and are thus at risk of developing active TB disease during ...

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Search for dissertations about: "thesis in tuberculosis"

Showing result 1 - 5 of 210 swedish dissertations containing the words thesis in tuberculosis .

1. Interplay of human macrophages and Mycobacterium tuberculosis phenotypes

Author : Johanna Raffetseder ; Maria Lerm ; Olle Stendahl ; Vesa Loitto ; Trude Helen Flo ; Linköpings universitet ; [] Keywords : MEDICIN OCH HÄLSOVETENSKAP ; MEDICAL AND HEALTH SCIENCES ; MEDICIN OCH HÄLSOVETENSKAP ; MEDICAL AND HEALTH SCIENCES ; NATURVETENSKAP ; NATURAL SCIENCES ; NATURVETENSKAP ; NATURAL SCIENCES ; MEDICIN OCH HÄLSOVETENSKAP ; MEDICAL AND HEALTH SCIENCES ; Mycobacterium tuberculosis ; tuberculosis ; macrophage ; innate immunity ; host-pathogen interaction ; antibiotic tolerance ; phagosomal maturation ; bacterial phenotype ; dormancy ; persistence ; virulence factor ; ESAT-6 ; ESX-1 ;

Abstract : Mycobacterium tuberculosis (Mtb) is the pathogen causing tuberculosis (TB), a disease most often affecting the lung. 1.5 million people die annually due to TB, mainly in low-income countries. READ MORE

2. Tuberculosis infection in pregnant women

Author : John Walles ; Klinisk infektionsmedicin ; [] Keywords : MEDICIN OCH HÄLSOVETENSKAP ; MEDICAL AND HEALTH SCIENCES ; Tuberculosis ; Pregnancy ; Latent ; stillbirth ; preeclampsia ; QuantiFERON ;

Abstract : .... READ MORE

3. Dynamics of tuberculosis infection in Sweden

Author : Niclas Winqvist ; Enheten för infektionssjukdomar ; [] Keywords : MEDICIN OCH HÄLSOVETENSKAP ; MEDICAL AND HEALTH SCIENCES ; Tuberculosis ; latent tuberculosis infection ; long-term follow-up ; Øresund region ; interferon-gamma release assay ; tuberculin skin test ;

Abstract : Sweden provides a special setting for epidemiological and demographic studies of tuberculosis (TB) infection over time for principally two reasons; first, the Swedish TB epidemic has undergone a tremendous transition since the end of the 19th century, when TB was highly endemic, to the current situation with practically interrupted indigenous transmission since several decades. Second, an increasing proportion of persons who grew up before TB transmission virtually disappeared in the 1960s are reaching advanced age, and thus creating conditions that predispose to reactivation of latent TB infection (LTBI). READ MORE

4. Fighting Tuberculosis – : Structural Studies of Three Mycobacterial Proteins

Author : Alina Castell ; Torsten Unge ; Manfred Weiss ; Uppsala universitet ; [] Keywords : NATURVETENSKAP ; NATURAL SCIENCES ; Mycobacterium tuberculosis ; Rv0216 ; Rv0130 ; Mycobacterium smegmatis ; branched chain aminotransferase ; X-ray crystallography ; fatty acid metabolism ; Structural biology ; Strukturbiologi ;

Abstract : This thesis presents the cloning, purification, crystallization, and structural studies of two unknown proteins from Mycobacterium tuberculosis, and of an aminotransferase from Mycobacterium smegmatis. Structural knowledge of these proteins is of highest interest for structure-based drug design, which is one of the approaches that can be used in order to fight tuberculosis (TB). READ MORE

5. Pharmacometric models to inform dose selection and study design : Applied in hemophilia and tuberculosis

Author : Alan Faraj ; Ulrika S. H. Simonsson ; Joakim Nyberg ; Ron Mathot ; Uppsala universitet ; [] Keywords : MEDICIN OCH HÄLSOVETENSKAP ; MEDICAL AND HEALTH SCIENCES ; drug development ; pharmacometrics ; pharmacokinetics ; pharmacodynamics ; non-linear mixed effect models ; hemophilia ; tuberculosis ; dose selection ; study design ; pediatric extrapolation ;

Abstract : While tuberculosis is a global pandemic, hemophilia is a rare disease which many have not heard of. Due to tuberculosis mainly being a problem in developing countries and hemophilia being a rare disease, they are not as heard of as other diseases such as cancer or metabolic diseases which are on the rise in Western societies. READ MORE

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Mantoux Tuberculin Skin Test Toolkit

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What to know

CDC has free training materials on reading and administering the TB skin test. The Mantoux TB skin test toolkit includes a fact sheet, wall chart, video, and ruler.

About this toolkit

Training is essential for health care providers to gain proficiency in the administration and interpretation of the TB skin test.

The TB skin test should be placed (administered) and read by a designated, trained health care provider. Consult with your state and local public health authorities to determine who can place and read TB skin tests in your state.

CDC materials are available for download or to order (within the United States).

Mantoux Tuberculin Skin Testing Fact Sheet

Mantoux Tuberculin Skin Testing Wall Chart

Mantoux Tuberculin Skin Test Toolkit: Video

Mantoux Tuberculin Skin Testing Ruler

Baseline Tuberculosis Screening and Testing for Health Care Personnel

What You Need to Know About the TB Skin Test Fact Sheet

Tuberculosis (TB)

Tuberculosis is caused by bacteria called Mycobacterium tuberculosis . The bacteria usually attack the lungs but can attack any part of the body.

For Everyone

Health care providers, public health.

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