Episode 88      28 min 22 sec
Tuberculosis Resurgent

Infectious diseases expert Prof Graham Brown gives the facts on tuberculosis (TB) and explains why the danger of "the neglected disease" is anything but diminished in the 21st century. We also speak with public health physician Dr Abuchahama Saifodine on site in Mozambique, where he is researching TB's prevalence and devastating effects. With host Jen Cook.

"In some parts of the world there is now almost a double diagnosis. HIV and TB. So, these people are highly infectious, as well as having the problems associated with AIDS." - Prof Graham Brown.




           



Prof Graham Brown
Prof Graham Brown

Professor Graham Brown is the Foundation Director of the Nossal Institute for Global Health,and Head of the Tropical Health and Infectious Diseases unit. A past Head of Infection and Immunity at the Walter and Eliza Hall Institute for Medical Research and of the Victorian Infectious Diseases Service at the Royal Melbourne Hospital, and James Stewart Professorof Medicine, Graham has also worked in education and research in Papua New Guinea and Tanzania. He has served on various national and international review committees, and was amember of the Strategic Advisory Council for The Bill and Melinda Gates Children's Vaccine Program. Graham has held a number of appointments advising the Tropical Disease Research Program of the World Health Organization and is currently Chair of the Malaria Vaccine Advisory Committee. His laboratory research is focussed on immunity to malaria.

Dr Abuchahama Saifodine
Dr Abuchahama Saifodine

Dr. Abuchahama Saifodine is a Mozambican medical doctor and public health physician who is undertaking studies towards a PhD in International Health at the Nossal Institute for Global Health at the University of Melbourne, Australia. Dr. Saifodine obtained his Master's degree in Epidemiology and Biostatistics at the University of Pretoria, South Africa. He spent seven years doing malaria research at the National Institute for Health and worked as a physician at the Maputo Central hospital, in Mozambique. He also spent 6 years at USAID/Mozambique working as an infectious disease advisor, and during that time he focused his work on malaria and tuberculosis control activities and research.

Credits

Host: Jennifer Cook
Producers: Kelvin Param, Eric van Bemmel
Series Creators: Eric van Bemmel and Kelvin Param
Audio Engineer: Russell Evans
Voiceover: Nerissa Hannink

Transcription: Andy Fuller

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Tuberculosis Resurgent

VOICEOVER
Welcome to Up Close: the research, analysis and opinion podcast from The University of Melbourne, Australia.

JENNIFER COOK
Hello, I’m Jennifer Cook. For many of us, our memory of tuberculosis or TB is as one of those nasty little jabs we got as schoolchildren. Along with polio, TB is not a disease most of us readily associate with life in the 21st century. But unfortunately for millions of people around the world, TB – which was once the leading cause of death in the United States – is a very real danger. Or worse, it's a part of their everyday lives, with its debilitating health consequences and long-term drug regime. Complicating matters is the existence of drug resistant strains of the disease. According to the World Health Organisation, someone is infected with TB every second and it estimates a staggering one third of the world’s population is infected with the TB bacillus. In 2005, around 1.6 million people died of TB, with the highest number of deaths in the Africa region. Joining us on Up Close today, to discuss what medical experts have called ‘the neglected disease’ is Prof.Graham Brown from the Nossal Institute for Global Health. We’ll also be talking later in the program by phone to Dr Abu Saifodine, a public health physician in Mozambique, who is undertaking PhD studies in International Health at the Nossal Institute for Global Health, at The University of Melbourne, Australia, on tuberculosis. But, firstly to you Graham, welcome to Up Close.

GRAHAM BROWN
Thank you, Jenny.

JENNIFER COOK
And let’s begin by asking the simplest of questions, just what is TB and how would I know if I had it?

GRAHAM BROWN
That’s quite a complicated question. TB is shorthand for tuberculosis. There are actually many forms of tuberculosis that can affect many animals and cows, but we are mainly talking about the form of tuberculosis known as mycobacterium tuberculosis, the one that mainly affects people. This disease, as you said, has been around a very long time. And it has got certain things about the disease that make it very hard to control. First of all, the disease is usually acquired, we breathe it in, or someone who is infected tuberculosis coughs on us.

JENNIFER COOK
So you don’t get it by touching…

GRAHAM BROWN
No, we usually don’t. Although the form I mentioned in cows you can get from drinking unpasteurised milk. But the one that is the main problem is the one that we breathe in when someone coughs on us. But, fortunately, most people who get coughed on by someone with tuberculosis, they have a very mild illness, they probably don’t even know that they’re sick. But what happens is, their body controls it and then sometimes later in their life, it could re-activate. So, it is lying their dormant and come back. On the other hand, some people get sick on the very first occasion.

JENNIFER COOK
So, how would I feel if I had TB and let’s just say, I haven’t got a mild dose, it has slept in my body for a while and something for some reason has triggered it off, what would my symptoms be?

GRAHAM BROWN
As I mentioned, when you are first infected most people have a mild illness and they’re not aware of it. A smaller proportion get an acute illness with tuberculosis, affecting their lungs and then they can start to cough. And they can be infectious. However, for the other group, it can lie dormant in their body and then come up and the person become[s] very sick, coughing and coughing the germs over everybody else and that’s how they become sick. Now, of course, sometimes tuberculosis can affect other parts of the body, such as the kidneys, the bones, or even the brain to give tuberculous meningitis, which, fortunately, is less common, but a very major problem. So, you mentioned that a third of the world is infected, that doesn’t actually mean that the people are infectious or could infect others. It is just that those germs are lying dormant in the body and can spring up at some time.

JENNIFER COOK
They have the potential.

GRAHAM BROWN
Absolutely. And what makes that potential worse, particularly, is if the immune system is infected. And as you know, in the areas where there is a lot of TB, quite often, there is a lot of HIV. And a major problem with HIV is you can get AIDS, and that hits your immune system.
In some parts of the world there is now almost a double diagnosis. HIV and TB. So, these people are highly infectious, as well as having the problems associated with AIDS. In fact it is how AIDS may present to the hospitals, presenting a major, major challenge.

JENNIFER COOK
And just how do we treat it? What is the regime?

GRAHAM BROWN
Well, I think the first thing is to work out how to diagnose it. And it is not so easy. Because, we can look under a microscope, but in some of the poorest parts of the world, they might not have microscopes to see it. Better still is to take it to the laboratory and culture the organism or grow it and then see if that organism can be killed by the anti-bacterial drugs that we would give.

JENNIFER COOK
So, what you are talking about is a very controlled environment. You need to be able to see the patients. You need to be able to get the samples to the lab, you need, well, the facilities for the testing and you are saying this often isn’t available; isn't the case.

GRAHAM BROWN
That’s correct. There are many different causes for a chronic cough. Not everyone with a chronic cough has TB. So, in order to be able to manage tuberculosis, we need to have efficient diagnostic methods, the person needs to be seen, then we need to make the diagnose and we need to treat them for quite a long time. Many months. Sometimes six months or more. Very difficult to maintain that treatment. And then of course, before they even presented to the hospital, they may have infected many members of the family or community where they live.

JENNIFER COOK
So, how are governments managing this problem?

GRAHAM BROWN
I think you mentioned earlier that the developed countries had this as a major problem a hundred years ago. It is less of a problem now, but it still does exist. If you have good health services it means that if you find a person with tuberculosis, they are appropriately diagnosed, appropriately treated for the right length of time, not only that, you, can go and trace all people who may have been in contact with that person to get early, as to see whether they need to be treated or need to be tested for tuberculosis. If people living in close contact, others are at risk. You might have read in newspapers, if someone, with tuberculosis travels in an airplane, it is necessary to call people in and follow them up just to see if they may have been exposed. And the problem there is it is very hard to diagnose, as I have said, particularly in the early stages. What you can do is a test to see if they have been exposed, either a skin test or a blood test. But it is very complicated and quite sophisticated and demands a lot of follow up.

JENNIFER COOK
Let’s talk about some of these ‘at-risk’ populations. I was quite fascinated and troubled to read about the incidence in the Russian prison system, would you talk to us about that?

GRAHAM BROWN
So, I would imagine in a prison setting, there is a patient with a chronic cough, maybe elderly, a lot of old people have coughs, and someone may not have thought of the possibility of tuberculosis and that is when many others could be at risk.

JENNIFER COOK
And I imagine in a prison population a cough would be very low down on the list of high health priorities or concerns.

GRAHAM BROWN
Well, if people are not thinking about tuberculosis that is an enormous problem. And the very sad thing is that in some of these settings patients have had incomplete treatment or partial treatment and this is the exact setting in which we see resistance to tuberculosis. If we get resistance to tuberculosis, that is an even bigger challenge because we need to use so-called second-line drugs which are extremely expensive and hard to manage.

JENNIFER COOK
You are listening to Up Close, coming to you from The University of Melbourne, Australia. I’m Jennifer Cook. And I’m talking with Prof.Graham Brown from the Nossal Institute of Global Health at The University of Melbourne, Australia, about the often-neglected disease of TB. Now, Graham, talk to us a bit more about these drug-resistant strains and what that actually means.

GRAHAM BROWN
What we mean by drug resistance, it can come in many forms. It is such a difficult disease to treat that we know that if we only use one drug to treat the TB it will rapidly become resistant and the drug is ineffective. So, in fact, we normally commence treatment with four drugs in fact, in the countries of the developed world that can afford such drugs. Four drugs for a period, until we find out from the laboratory whether this particular strain of tuberculosis is sensitive to those drugs and then we can drop down to two drugs, rather than four and continue them for an appropriate time. Now, the problem is, if those drugs are not effective, we need to go to second line drugs and these are very expensive and we call this ‘drug-resistant tuberculosis’. And then we go next stage ‘multi-drug resistant’ and recently, in the past few years we have seen ‘extra drug-resistant TB’ – ‘XDR’. And we really, don’t even know, what drugs we can use, for these patients. And in some patients in Africa, in southern Africa, who were infected with TB and had AIDS they had a very, very rapid deterioration and died very soon of this highly drug resistant tuberculosis. And so, we desperately need new drugs that are effective against this highly resistant form of tuberculosis. And of course the problem is, in those countries or environments where there is not good public health, there are not good facilities and follow-up, this is exactly where it could become a greater problem.

JENNIFER COOK
Which leads to the question, what does the world need to do to eradicate TB? Is it more research, better facilities, more funding? What is it that is needed?

GRAHAM BROWN
I think we need a combined approach. There is no magic bullet for tuberculosis. And as you stated at the beginning, there a lot of the world’s population, maybe a third or a quarter of the world’s population who are chronically infected but not sick. We don’t know how you would get rid of those last few bugs. You can’t imagine treating everyone in the world to get rid of them. But, for the people we know about, we need many strategies. First, we need rapid diagnosis. Better diagnostic tests would be an enormous help. Then, we need those in need, require access to treatment, an appropriate treatment which means they must be able to do testing for drug resistance, then appropriate second line treatment if necessary. Following that, follow up of the person and their community to look for other people who may have been infected. Many people believe that the best way of treating patients with tuberculosis is not to give them a big supply of drugs, but actually go to their house or get them to come to the clinic everyday or a couple of times a week. Once again, an enormous burden on that community. Now, in the places of the world where there is the most tuberculosis, the rate per 100,000 might be highest in Africa, but the absolute numbers might be highest in the Indian subcontinent, the resources required are huge for these type of facilities. So, I’ve mentioned we need better diagnostic methods, better drugs, better follow up. And of course, it would be wonderful if a vaccine could be developed. There is a vaccine for tuberculosis. But it is only partly efficacious. But is given to babies at birth and probably gives them a degree of protection against widespread tuberculosis, but we’d love to have something that is actually better. Once again, you mentioned that it is seen as a neglected disease and many people put it in the category with AIDS, TB and malaria as three grand neglected diseases. And in fact, as part of a global effort, a global fund for AIDS, TB and malaria, is specifically addressing this problem. We have had tremendous support from the Gates Foundation. Their leadership has led many countries to contribute to this fund that is now active in so many countries in the world. Their main drive is to get drugs out to people in greatest need. They have done wonderful things with antiretroviral agents, that is for HIV AIDS. But they also have a program in TB. We believe of course it would be great if it could be larger. There is a global program for ‘Stop TB’. There are programs for the WHO and other organisations for new diagnostic tests. There are new and better drugs, so that we have better way of treating the populations at risk.

JENNIFER COOK
Graham, thank you so much for that insight. We are now going to cross live to Dr Abu Saifodine in Mozambique. Abu is a PhD student and he is studying International Health at the Nossal Institute for Global Health at The University of Melbourne, Australia. He has spent seven years doing malaria research and worked as a physician at the Maputo Central Hospital in Mozambique. He also spent six years USAID Mozambique working as an infectious disease advisor, focussing on malaria and TB. Abu, thank you so much for joining us on Up Close today.

ABU SAIFODINE
Thank you. Thank you, it is a pleasure.

JENNIFER COOK
Can you begin by explaining to us, just what the TB situation is there in Mozambique?

ABU SAIFODINE
Well, Mozambique is one of the 15 countries with the highest prevalence, TB prevalence in the world. So we have a lot of cases of TB. Around 40,000 cases a year in the whole country. And it is a small country relatively to others. There are only 20million people living in Mozambique. So, TB represents a huge burden to our health system.

JENNIFER COOK
Apparently, in a matter of months you have been able to gather more TB cases than the Nossal Institute in Australia has been able to find in years. Is that right?

ABU SAIFODINE
Yes it is. I’m doing my research in Beira City, which is the second largest city in Mozambique. It has a population of around 700,000 people. And I arrived here in August [2009] collecting some data around September [2009], anyway, in two months I was able to recruit 575 patients which is a lot and by the end of my study here, my data collection here, I expect to recruit more than a thousand patients. Or at least to screen more than a thousand patients. So that is a lot.

JENNIFER COOK
And already your preliminary research has produced some very interesting results in relation to the infection rates between men and women. Could you explain that to us?

ABU SAIFODINE
Yes, that is actually a common finding in many countries. We see consistently that men have higher detection rates than women, meaning that we see more men doing treatment for tuberculosis than women. We don’t really understand why there are many mechanisms that can explain this difference. Maybe men have a higher infection rate than women, or maybe it is related to the access to health care – maybe men have more access than women. Or maybe it is much easier to diagnose TB in men than women. We really don’t know what it is. But it is certainly very important from a public health point of view. Because if we are missing women in TB treatment that is very important, especially in Africa, we know that women have a very important role in caring for the family, for the children – we don’t want to miss that group of people. So, it is a very interesting area where we definitely need to try to understand what is going on. And try to help the ministries to implement measures to correct that situation.

JENNIFER COOK
That brings me to my question Abu, could you perhaps explain to us, some of the particular challenges that you are facing in Mozambique and throughout Africa in treating this disease?

ABU SAIFODINE
Actually, it is very challenging, because, first of all TB is a chronic disease. And, our health system in Africa, the primary health care system, it is more adapted to treat acute diseases. I mean, we are very good at treating malaria or diarrhoea, but we really don’t have the right system to treat diseases like TB or HIV AIDS because it implies a very long relationship between the patient and the health care workers. The requirements in terms of logistics, the system, and the training are much, much more complicated. So, it is very challenging. I do believe that Mozambique and other countries have been doing very well in organising these programs. But, as you know, we are facing, also, an HIV AIDS epidemic, which is bringing a very big burden to the health system per se and also by worsening the TB situation. So, there is very high political commitment. I see many people committed to working on TB and HIV AIDS. I mean, we cannot distinguish these two diseases these days. They run together, basically. But there are many structural issues, system issues that need to be dealt with if we want to be successful in TB control.

JENNIFER COOK
Yes, Abu, could you talk to us a bit more about this, the impact that civil unrest and the reality of poverty and also violence can have on the spread of TB?

ABU SAIFODINE
Yeah, it became clear throughout the time that social-economic conditions are an important risk factor for tuberculosis. And we know from Europe and from Africa, from other places that consistently, the poor people face a much higher risk of tuberculosis than the richer people. So, I think that in Africa we have to put much more emphasis on poverty reduction, trying to reduce the gap between poor and the rich – those things take time. So, in the meantime, we are going to have to find more appropriate technology and interventions that can reach the poor people in order to reduce the TB. So, you see this difference amongst countries, richer countries and poor countries. And you see, within countries a very clear difference between richer people and poor people, in terms of TB rates. And it is related to clothing, living conditions, housing. All of these things facilitate the transmission of TB bacteria. And we have to act on those things to be successful.

JENNIFER COOK
You’re listening to Up Close. I’m Jennifer Cook. And I’m talking with Dr Abu Saifodine from the Nossal Institute of Global Health at The University of Melbourne, Australia. He is in Mozambique and he is studying the often-neglected disease of TB. So, Abu, tell us what projects you are doing there and how are you going about tackling this problem?

ABU SAIFODINE
Yes, the focus of our project is actually on trying to understand some of the issues related to TB control. There are two main aspects to TB control. One is diagnosing the disease, tackling as much cases as we can. And the second aspect is trying to treat effectively those patients that we are able to detect. And that is where my project is focussing - is on trying to understand what are the factors that here, in this context, in Mozambique, affect our ability to diagnose TB quickly and then trying to understand what are the factors that contribute to a poor treatment outcome. So, if we can understand these two things, we can move effectively to find interventions that will  help the national  control TB programs, and to improve its performance. The second part of my project is related to drug resistance. Drug resistance is a problem for any bacterial disease, but it became even more problematic for tuberculosis. We used a combination of four or five drugs to treat tuberculosis.

JENNIFER COOK
Yes, Graham was talking to us about those drug resistant treatments. So, you are finding that a real problem there on the ground in Mozambique?

ABU SAIFODINE
Yes, it is a problem because it is a much more complex treatment than treating non-resistant TB. The drugs are more expensive. They have more side effects. So, it is much more complicated to deal with. And the mortality rates for the patients are much, much higher than in drug sensitive TB. Yes, multi-drug resistance is a big problem.

JENNIFER COOK
There is something called ‘directly observed therapy’ – could you explain that to us?

ABU SAIFODINE
Yes, it is basically trying to make sure that the patient takes the pills. So we supervise that process. And that happens at the health facility or at the community. At the health facility, there is usually the nurse that gives the drugs to the patient and observes the patient at that moment taking the pills. Or, you can identify someone in the community, a relative or a neighbour that can do daily to the TB patient’s house. Give him the drugs and observe him taking. And by doing this, firstly we make sure that the patient is taking the drugs, but also, we provide some support to the patient. It doesn’t work very well all the time, but it is a very effective way to ensure treatment.

JENNIFER COOK
Abu, what do you think the rest of the world should be doing to help fight TB?

ABU SAIFODINE
I think, for many years, we have focussed on TB control and we have focussed on diagnosing the treatment, and we have overlooked the issues. The system needs to be in place to be effective. Needs to be controlled. So, I think we need to have better logistics, we need to have more and well-trained health professionals. We need to have availability of drugs and things like that. And not only focussing on making sure that the patient is taking the pills but there are many other things that we need to be doing. And I think we need also to stop having the disease focus too much. I mean, we focus a lot on Malaria per se or TB per se and HIV per se, but the patients I am seeing here don’t only have TB, they have HIV, they have other things. So, if we have a system focus, rather than a disease focus, we will be more effective in providing support to these patients. Sometimes the most important thing for them is not the pill, it is food. So, I’m hoping at the international level, we will more resources and more focus on strengthening health systems in Africa as a way to control TB and other diseases.

JENNIFER COOK
Thank you so much Abu for giving us that much-valued perspective in treating TB. And as you said, tackling so many other health issues in the region. Thank you so much for your time.

ABU SAIFODINE
Thank you very much, it was a pleasure.

JENNIFER COOK
That was Dr Abu Saifodine, a public health physician in Mozambique who is undertaking PhD studies into the effects of tuberculosis. Now, Graham, to bring our discussion around again, I’d like to ask you about the importance of developed nations’ foreign policy on infectious diseases. Do you think it is important and if so, why? Do you agree with Abu that we need a system approach?

GRAHAM BROWN
Yes, Jenny, I completely agree. We need a system approach. In fact, in the time of President Clinton, when he was looking at those great problems of AIDS, TB and malaria, he actually described them as a threat to world peace. If you have these nasty infectious diseases infecting and causing death in the growing population of an emerging nation, the teachers, the nurses, the policemen and all, it means that the society can’t function very well. We can’t have strong states without strong health. So, it is in everybody’s interest to have healthy populations for development. You can’t have development without good health. You can’t have good health without a good strong civil society. So, there are good reasons why the developed countries should try to have healthy neighbours and partners. And in the specific case of tuberculosis, is that tuberculosis can travel with people. People may have come from an area where 30 years ago tuberculosis was common and as we’ve mentioned they may be left carrying the bacteria and it can emerge to affect others. So, we find that as people travel they can take it here and there. So, I think all countries must make a commitment to support the global effort, to strengthen the health systems that will assist with both TB, AIDS, malaria and other important illnesses.

JENNIFER COOK
And Graham, finally, I’d like to just ask you the big question, do you think TB can be eradicated?

GRAHAM BROWN
That is a major challenge. I think we should always think that is something in the long, long term. But, I think, as we have heard the current challenges, I think that a more intermediate objective would be to say, let’s at least get TB treatment to those that need it. Quickly and appropriately. To provide the service, the drugs and the follow up that enable people to live healthy long lives after being treated for tuberculosis. So that the rates are very low and if people are infected they are treated rapidly and we don’t have further outbreaks. It would take a very, very long time to eradicate tuberculosis and we have a lot to do before we have that on the agenda.

JENNIFER COOK
Graham, thank you so much for your time today and for giving us such insight into this disease that impacts upon the lives of millions of people around the world. Thank you.

GRAHAM BROWN
Thank you.

JENNIFER COOK
You’ve been listening to Up Close from The University of Melbourne, Australia. Relevant links, a full transcript and more information on this episode can be found on our website at upclose.unimelb.edu.au. You can leave a comment on any of the Up Close episodes by clicking on the link at the bottom of the page. Melbourne University Up Close is brought to you by Marketing and Communications at The University of Melbourne, Australia. Up Close is created and produced by Eric van Bemmel and Kelvin Param. Our audio engineer is Russell Evans, I’m Jennifer Cook. Until next time, thank you for joining us on Up Close. Goodbye.

VOICEOVER
You’ve been listening to Up Close. For more information visit upclose.unimelb.edu.au. Copyright 2010, The University of Melbourne.


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