Tuberculosis: a disease of the poor

So civil society can play a very important role, creating pressure, advocacy and giving a clear and strong message. We need to raise the profile of this disease all together

Tuberculosis is mainly a social problem: it is related to extreme poverty and spreads easily in crowded places, where light is dimmer and air barely circulates. In Brazil, the four vulnerable populations are the homeless, prison inmates, HIV patients and indigenous populations, who usually live in poverty situations and are three times as susceptible to become infected. Other groups can also be considered susceptible: black or brown populations, who usually live in worse conditions, are twice as likely to contract the disease as white person. In addition, those who live in poverty and extreme poverty situations and usually live in slums.

Brazil has progressed preventing diseases by acting especially on social protection (social programs to combat tuberculosis), innovation and research. Despite the last years not having reported significant changes in the disease’s indicators, there is a bright change in the political picture around the disease, where the civil society has played its role. According to the TB Observatory, the civil society became active in 2003 when the Rio de Janeiro TB Forum for NGOs was created. In 2003, the STOP TB Brazil was launched, and, in 2009, the Tuberculosis Brazil Observatory was launched. Most recently, the Brazilian Network of Tuberculosis Committees was created, forming the national movement against tuberculosis.

To talk more about the matter, the Brazilian Society of Tropical Medicine (BSTM) press interviewed Professor Luis Cuevas, who since 1985 has dedicated his interest to Clinical Epidemiology in Tropical Diseases. He is a member of the European Forum for Tuberculosis Innovation, European Respiratory Society; Founding member at TB Diagnostic Research Forum, National Institute of Health (NIH)/NIAID and “CoChair”, NIH Expert for TB diagnosis in children. Doctor Cuevas has wide experience within epidemiology, especially implementing diagnostic methods for infectious diseases in low-income countries, especially for Tuberculosis.

BSTM: According to the 2016 global report on tuberculosis by the World Health Organization (WHO), the outbreak is greater than previously estimated, reaching 10.4 million new infections in 2015, from which 60% in India, China, Indonesia, Nigeria, Pakistan and South Africa. What do you find responsible for such high numbers?

Dr. Luis Cuevas: Tuberculosis is a disease of poverty, which has been neglected for many decades. The populations most affected often live in locations with poor access to diagnostic and treatment services and come late to the services. By the time they come, they will have spread the disease to other contacts for several weeks. Unless we make the services and diagnosis more rapidly available to these populations, we will not be able to stem the number of cases that occur in what we call high burden countries. These are countries that have large populations, high TB incidence or both. Although much progress has been made in the last decades decentralizing services, most of the centers that have diagnostic facilities are still relatively distant from the people who need them most. Drug resistance is also increasing. The main cause for the increase in drug resistance is due to weak health services. Patients who abandon tuberculosis treatment are more likely to return later with drug resistance. This is why in countries like Eastern Europe, where the health system was disrupted at the time of the collapse of the socialist system, drug resistance increased dramatically over this period. On the contrary, the high rate of drug resistance in New York was controlled by strengthening a weak health system and strict follow up of patients who abandoned treatment. Once the system had been put right, drug resistance decreased substantially.

BSTM: TB kills over 1.8 million people per year – more than any other disease – and the drug resistance is very high in many countries. Which are the main causes for high TB incidence and resistance? In your opinion, why is the diagnosis of drug resistant TB still a much-delayed process?

Dr. Luis Cuevas: Diagnosing mycobacterial drug resistance is often a delayed process. Phenotypic methods require culturing the bacteria, which might require two months and then re-culturing isolates in the presence of selected drugs to see if the bacteria is resistant.  We have made much progress in the last decade. Now we have liquid culture, which is faster than the previous solid culture methods, and we can use molecular methods to screen sputum directly  to identify rifampicin resistance in less than an hour using Xpert MTB/RIF. We can also screen for mutations for first line drug resistance using Line Probe assays and we have made progress for assays for second line drugs using LPAs. It would be ideal to have rapid/molecular tests that identify rifampicin and INH resistance simultaneously and some of these tests may be on the way. However the solution is larger than better diagnostics.  A major factor that delays the diagnosis of drug resistance is the lack of accessibility to some of these tests. Molecular diagnostics are currently only available in laboratories that have a good infrastructure and remote places, rural areas or locations with limited laboratory facilities need to refer patients. Also, patients with drug resistance are often patients who have a higher frequency of social problems. They are more likely to have abandoned treatment before, suffer drug and alcohol addiction or to live in the street. The high prevalence of drug resistance is the result of a combination of health system and social issues and conversely, countries with strong public health and social support programs often have a low prevalence of drug resistance.

BSTM: Do you think gaps by under notified and underdiagnosed tests are a great challenge today?

Dr. Luis Cuevas: I assume that your question refers to the large number of cases that are not notified to the national tuberculosis control programs; and whether there are many cases in the community that are not diagnosed. It is currently estimated that about 4 million cases are not notified to the national programs. This is an enormous figure. We now know that in countries like Nigeria only about 15% of the cases that occur in the country are really found by the health services and notified to the national control programs. That means that 85% of the cases are missed! Many of these ‘missing’ cases may access services through private practitioners or maybe they access the services but are not notified by a weak surveillance system. Whatever it is (and there are studies underway to understand this better), this is still an enormous figure. It is not possible to talk of eliminating tuberculosis or even controlling it, unless we make major changes in the way that we identify cases and dramatically increase the access to diagnostics and treatment. This is one of the international priorities for tuberculosis control.

BSTM: Prioritizing tuberculosis control in Brazilian prisons – where the diseases index is 28 times greater than among the general population – is not only essential to reduce the incidence among inmates, but also in the entire community. Do you agree with this statement? Why?

Dr. Luis Cuevas: I agree that tuberculosis in prisons is often high, and in Brazil it is unacceptably high. Brazil should develop approaches to screen and identify individual with tuberculosis at the time of admission to the prisons to avoid the infections spreading to other inmates. I disagree with your hypothesis that controlling tuberculosis in prisons would significantly reduce the incidence of tuberculosis in the community. This is just because of numbers, really. The number of cases identified in prisons is much smaller than the overall number of cases in the community. It is much more likely that a person in the community will be infected from another person in the community rather than from a prisoner. Although this is a basic human right and prisoners should have the right to access diagnostic and proper treatment, in terms of epidemiological control of the infection, this is not as important for disease transmission as identifying the majority of cases in the community.

BSTM: The current lag diagnosing and treating the disease, besides affecting the patients life, also puts the lives of relatives and close people around at risk, since the disease is transmitted through the air. Could the global project known as CRyPTIC (Comprehensive Resistance Prediction for Tuberculosis: an International Consortium) help reverse this picture?

Dr. Luis Cuevas: Your question assumes that most of the infections of tuberculosis occur after a patient is diagnosed with TB. Unfortunately, this is not the case. We only screen patients for tuberculosis after they have had symptoms for about two weeks. That really means that contacts and relatives are exposed to the mycobacteria for quite a long time before the patient is diagnosed. This is why it is important to examine and screen contacts of new cases, as some may have the disease and many will need to take prophylaxis to stop a recent infection progressing to overt disease. The project you mention is an international alliance coordinated by Oxford and the CRyPTIC consortium aims to sequence a large number of specimens to identify genomic the markers of drug resistance. This information could allow scientists to develop new diagnostic methods to rapidly identify drug resistance. This is an information that is very valuable and is highly needed and may well shorten the time between the patient’s first consultation and diagnosis. Whoever, remember we screen patients two weeks after their start of symptoms. So to shorten the likelihood of infection we really need to focus on screening much earlier to identify patients earlier in the course of the illness. We currently do not have suitable screening tests.

BSTM: The report also found that spending on TB this year fell almost $2 billion (£1.6 billion) short of the $8.3 billion needed to combat the disease; this gap is expected to widen to $6 billion in 2020 if funding is not increased. This difference should reach USD 6 billion in 2020 if funding is not increased. How do you see this?

Dr. Luis Cuevas: It is true that funding is decreasing. This is a tragedy. This is a reflection of a complex international funding situation and international institutions that monitor the investment of TB control have shown a decreasing trend for the last three years. There is donor fatigue, there are many competing international priorities and a high dependence of national control programs on external funding. The decrease in funding will result in what was already a major gap in resources for research, will jeopardize the sustainability of programs and will limit our ability to reach the TB targets of the Sustainable Development Goals. The solution is not simple and we should all highlight the major funding gaps we are facing, the importance of the research and development that is needed to control TB, and that TB is not a problem just about to be solved. I hope you can help us raise awareness.

BSTM: In your opinion, how could the scientific community contribute to improve the TB situation?

Dr. Luis Cuevas: We still need better diagnostics. Without proper diagnostics it is not possible to be confident of a good diagnosis and to provide the treatment to only those who need it, we will also continue to miss many patients. We need diagnostics that can be used in children, individuals with immunosuppression and in the elderly; tests that work in all samples, not only in sputum, and tests that can be used at the point of need, where most of the patients attend the services. We also need better treatments. Currently if the infection is due to drug sensitive mycobacteria, the ‘short’ treatment still requires six months. If the patient is infected with a drug resistant mycobacteria, the treatment is many times more expensive and lasts a much longer period, often requiring injectables and drugs that have  more side effects. Drug resistance is also increasing. So we need new and better drugs that work effectively, that require a shorter duration of therapy and that can treat patients with MDR-TB. We also need vaccines. This is an infection that spreads easily within the household and close contacts via the respiratory route. In most of the industrialized countries, the incidence of tuberculosis decreased at the time that the living standards improved.  But this is a long term goal and the only way we can reduce the incidence in the short to medium term is through the use of vaccines. One day, with good nutrition, less overcrowding and better ventilation, the incidence of tuberculosis will decrease.  This is what happened in the industrialized countries of Europe after the second WW, even before TB treatment was available. Until this happens, as this is a long-term goal, we will need other methods to prevent infection. Current vaccines have only limited efficacy, as they only prevent the most severe forms of the disease. We need vaccines that work in children and that prevent the development of all forms of the disease. We also need further research to develop approaches that are effective to find and treat cases of tuberculosis; mechanisms to support patients while they are on treatment so that they have continued access to services. So we need research on health systems, on how to extend the reach of the health system so that services are accessible to all the population, how to make them friendlier, equitable and patients centered, independently of the patients’ ability to pay. All these are major topics of a wide research agenda, so the scientific community has a major task ahead.

BSTM: And what can the civil society do to help? A recent article published on The Guardian says it would be fundamental to have more people engaged about the disease, a movement among the civil society compared to HIV. Do you think this action could bring results?

Dr. Luis Cuevas: I agree with your question. If we have more people engaged, civil society can generate an important pressure to change. Although many of us believe that tuberculosis should have high priority and that it should be at the forefront of the mind of politicians and policy makers, this is sadly often not the case. Tuberculosis is often neglected by policy makers and it has a much lower priority. Many politicians in Europe had the impression that TB was a problem of the past.   I also participated in discussions with members of parliament in Nigeria on why tuberculosis funding was so difficult. And several of them said “if I put the top 10 priorities in my list, tuberculosis will not be there. There will be security, education, infrastructure, employment roads, police and so on before tuberculosis”. So the question is how do we increase the profile of tuberculosis? This is one of the diseases that kill a large proportion of adults, that we cannot diagnose in children and that we have really limited diagnostic measures and treatments to control it. So this is not an issue only for the scientific community and for disease control programs. It is an issue that affects us all. Go and ask your family, and you may be surprised.  It is very likely that some of your relatives died from tuberculosis in the past, as it happened to my great-grandparents. Ask your friend if he or she knows anybody with tuberculosis. Ask your neighbor, whether anybody in their family has experienced tuberculosis. In fact, you will notice very soon that this is a disease that we often keep silent, we are ashamed of having tuberculosis, and we fear its stigma. We try not to tell our neighbors. So civil society can play a very important role, creating pressure, advocacy and giving a clear and strong message. We need to raise the profile of this disease all together.…