Healthy survival after tuberculosis

HEALTHY SURVIVAL FROM TUBERCULOSIS. Tuberculosis (TB) is the biggest killer by a single infectious agent, causing disease in 10 million people a year with almost one fifth of patients having unsuccessful antibiotic therapy. The number of deaths, cases, and treatment success, clearly highlights that TB is a global health priority, but they poorly describe the burden that TB has on an individual's health. Health is defined as "a state of complete physical, mental and social well-being, and not merely the absence of disease". Public health strategies that target only traditional epidemiological measurements will not lead to healthy survival from TB, and consequently will have an inadequate impact on the overall burden of TB on society.

WHY?
- TB IS BEYOND PHYSICAL SYMPTOMS. TB predominately affects the lungs leading to symptoms such as cough and shortness of breath. However, directly observed therapy, concerns regarding TB transmission, and its strong association with poverty, consequently diminish peoples' psychological and socio-economic wellbeing in addition to the physical symptoms experienced.
- TB HAS EFFECTS BEYOND PATIENTS. Not only do contacts of people diagnosed with TB have a risk of developing TB disease themselves, but they may also have their daily life disrupted by preventative treatment. Furthermore, healthy members of TB-affected households, especially caregivers, also have their wellbeing affected as they absorb the costs of their loved ones who have the disease.
- TB HAS IMPACTS BEYOND TREATMENT. There is growing awareness that due to the complexities stated above, the impact of TB on a person's health does not stop on the last day of antibiotic treatment. Individuals with TB may be left with residual impairments, remain at high risk of developing TB again, and are at higher risk of dying early compared to people who have not had TB. Despite this increasing awareness, the long-term impacts of TB on health - and the interventions that may alleviate them - are poorly understood.

RESEARCH AIM. To identify the most cost-effective interventions that would support the healthy survival of people affected by TB.

HOW?
- LONG-TERM FOLLOW-UP. In 1999-2002, 411 TB-affected families (2346 people) living in the Pampas shanty-town in Lima, Peru were recruited when a member of their household was diagnosed with TB. These households have been followed-up in regular intervals since recruitment.
- COMPARE WITH PEOPLE NOT AFFECTED BY TB. This MRC Skills Development Fellowship (SDF) will enable the completion of a 20-year follow-up interviews of TB-affected people, and will compare their health, which includes physical, psychological and social wellbeing with the same number of people who live in the same community who did not have any household member with active TB.

THE DATA WILL:
1. DESCRIBE the life-long health impact of TB and consequently quantify the overall burden of disease in TB-affected people;
2. EXPLAIN how TB causes these life-long health impacts;
3. IDENTIFY at which points interventions could have the most effective impact in promoting healthy survival from TB.

BACKGROUND. Health is defined as "a state of complete physical, mental and social wellbeing and not merely the absence of disease". Yet TB treatment outcomes are principally assessed by microbiological indicators immediately after completing antibiotics. Patients who have successfully completed treatment may have residual lung damage, remain at high risk of developing TB again and have a higher risk of early all-cause mortality. In addition, household contacts of patients with TB are at high risk of developing TB disease. Despite increasing awareness that TB affects the life course trajectory, the long-term impacts of TB on health - and the interventions that may mitigate against them - are poorly understood.

HYPOTHESIS. TB-affected people have an unfavourable life trajectory compared with people not affected by TB.

STUDY DESIGN. A prospective case control study with 20-year follow-up in the Pampas shanty-town, Lima, Peru. Data from 411 TB-affected households (2346 individuals) in which the index case was diagnosed, recruited and interviewed multiple times during treatment between 1999-2002 will be compared with the same number of community controls who were recruited into surveys in the same area and time period, who did not have any household member with active TB.

STUDY PLAN. The individual and household-level data collected at multiple time points between recruitment and final follow-up aim to:
- characterise and quantify the long-term impact of TB on the health trajectories of patients and their households, utilising measurements for physical, mental and social components of health;
- identify determinants and causal pathways associated with long-term impacts of TB from the multitude of explanatory variables that have been collected; and
- develop a predictive model of TB-related drivers over the life course and use this to identify cost-effective interventions suitable for diminishing the long-term health and socioeconomic impacts of TB.

The research proposed will quantify and help understand the long-term impact of TB on health, and identify potential points for intervention. Therefore, the direct impacts are academic and will be demonstrated immediately. It is hoped that in the long-term, the proposed research will be the start of multiple projects and collaborations investigating the field of health after TB.

IMMEDIATE IMPACTS.
The immediate impacts are to: (1) advance understanding regarding the impact of TB on long-term health, (2) understand the role of its mediators in the causal pathway, (3) identify interventions that would promote healthy survival; (4) evaluate the tools that will be used to measure the long-term impacts on health, and; (5) contribute towards the "Post TB" research agenda.

RESEARCHERS working in the fields listed in the academic beneficiaries' section will be able to use the tools shown to be able to measure pertinent health outcomes, replicate findings in other sites, evaluate the interventions proposed, and use the results generated as the basis for other research questions. Furthermore, by demonstrating the importance of previous TB in general health status, this will sensitise funders, hopefully opening up more funds for this field of research.

THE POST TB STEERING COMMITTEE is a group of international multi-disciplinary health professionals who are working in the field of improving the health of TB-affected people after treatment has finished. They organised the first symposia and working group for Post TB in June 2019, which highlighted the lack of published evidence to guide this field. I am a member of this committee, and the findings from the research will define problems "Post TB", recommend a new definition of treatment outcome, facilitate consensus in the terms and strategies required, and generate interest in health after TB within researchers and policymakers in international health organisations.

PUBLIC HEALTH PRACTITIONERS working within national public health bodies including TB programs will be interested to understand how and by how much previous TB has a role in other diseases and general health status. This will allow them to take previous TB status into consideration when implementing public health interventions, social programs or carrying out epidemiological investigations.

POLICYMAKERS within international, national, local government will have the potential to declare new programmatic definitions, recommend new public health targets, propose guidelines, and roll out interventions based on the results that will be generated by the research.

LONG-TERM IMPACTS
The long-term impacts of the research will contribute in improving (1) the quality of life of TB affected people; (2) societal wellbeing; and (3) effectiveness of TB programs in restoring people to good health.

TB-AFFECTED FAMILIES will benefit from future interventions that will not only ensure TB cure, but mitigate costs and promote good health once TB treatment has finished. This will impact not only patients that were previously diagnosed and treated for TB, but also their household members regardless of whether they developed secondary TB disease.

TB-AFFECTED SOCIETIES. TB disease affects mainly young adults of working age. Therefore, restoring this group back to good health during their TB treatment, will strengthen the working population of TB-affected societies, with the potential of making it a more productive one.