Treatment of Tuberculosis

00:01 The treatment of tuberculosis is actually relatively straightforward, it requires antibiotics.

00:05 However, it requires more than one antibiotic and the standard therapy is 4 antibiotics, and it requires antibiotics for a long period of time. The minimum treatment period is 6 months and if you have central nervous system disease or bone disease it often goes on for at least 12 months. So we ask the patients to take 4 drugs for 2 months and then 2 drugs for 4 months at least, and the actual dose that we give the patient is dictated by their weight. The split being 50kg, if they are below 50kg they get a lower dose, if they are above 50kg they get a higher dose. And the 4 drugs that we use are: Isoniazid, Rifampicin those are the most effective drugs and the ones that are kept going for the 6 months.

00:50 And for the first 2 months we give the patients Pyrazinamide and Ethambutol as well.

00:55 Ethambutol can affect the eyes and therefore we test the eyes before we start that drug. There are other things we may want to do. One is that actually with patients with brains involvement of tuberculosis or pericardial disease, we give them corticosteroids and the reason why we do that is that tuberculosis as it heals it's a very scarring infection, so you get a lot of fibrosis occurring where tuberculosis has been and in the brain that causes neurological deficits and we know that if patients are given corticosteroids then the chance of having long term brain damage is reduced. And the same for pericardial disease, we are worried about the development of constrictive pericarditis and the chances of that are reduced by giving the patients oral corticosteroids as well as their TB therapy. A very very important point is that all the cases of tuberculosis need to be notified. What we mean by that is that they need to be brought to the attention of the authorities so that there can be a screening process of that patient’s close contacts usually the family, the people they live with, but if it is a school child it will also be their school class as well.

02:12 And what happens there is that if a patient with TB is identified then who they live with will be tested to see whether they have active tuberculosis or latent tuberculosis as well.

02:23 By this method we can identify the source by which a patient has been infected and whether they've actually infected somebody else as well. And this is very important for the control of the disease. The testing that we use is this immunological response to infection, the Heaf testing or the IGRA and a chest X ray to look for the active disease. There are major problems for treating tuberculosis. The first we've already mentioned is that diagnosis can be slow, if it’s reliant on culture where in fact we take 6 weeks before we know somebody doesn’t have tuberculosis in a sample that’s been sent for culture.

02:57 And the positive growth is only, it usually occurs within 3 or 4 weeks.

03:03 The second is compliance, you are asking someone to take quite a lot of drugs for 6 months and they don’t like doing that, and in fact when patients feel better they often think they don’t need to take the medication and they feel better within a few weeks of starting the medication, and within two weeks they should be starting to feel considerably better than they have been feeling for weeks, and often patients will say “well, actually I'm feeling better now, I’ll stop taking the tablets”. The third is toxicity. The drugs that we use for tuberculosis, unfortunately several of them are liver toxic, and they cause an inflammation of the liver with an increase in the liver enzyme results and that can prevent those treatments being used. So we have to monitor the liver function test and if they go too high, we have to stop the therapy and then restart the therapy trying to identify which one of the drugs was responsible for causing the liver toxicity. And that's a complex process and delays treatment considerably. And the last is drug resistance, this is a problem if the patient is given single agent therapy. So when we first developed therapies for tuberculosis in the 1950s, only one agent was available and treatments with that led to patients developing resistance to disease very quickly and this is a problem. So this is why we give the patient 4 drugs to start with. It is to prevent resistance developing.

04:31 And if resistance is present to one agent, if you give somebody 4 drugs, then that will prevent the resistance increasing to affect the other drugs as well. If somebody has resistant disease, you suddenly have a problem and that treatment has to go on for at least 12 months, you may be using second line drugs, which are less effective, and they need very close monitoring to ensure they are improving and that they are compliant with the drugs that are being used. If you have extensively resistant disease, those organisms that are resistant to Rifampicin and Isoniazid, and several other drugs, then actually you can get a situation where the tuberculosis is not treatable and there is a very high mortality in those patients.