Fighting Resistance

News Fighting resistance weekly basis, we decided which patients Sir John Crofton received his medical education at were in most need of hospitalization, Cambridge University and St Thomas’s Hospital in and then decided when patients in London (United Kingdom), and qualified as a doctor the wards had improved enough to go in 1937. During the Second World War, he joined the home and receive outpatient treat- Royal Army Medical Corps with service in France, Egypt, ment. We thus got rid of our waiting Eritrea, Greece, Malta and then Germany. In 1947, he list in a year. Our other main focus became a lecturer at the Royal Postgraduate School of was the treatment effectiveness. We Medicine at Hammersmith Hospital and treated patients concentrated on the reasons for failure. Courtesy of Sir John Crofton at Brompton Hospital, where he participated in ground- We wanted to know why drugs that Sir John Crofton worked well in the test tube didn’t work breaking tuberculosis studies. From 1952 to 1977, in all patients. We looked to see if they Crofton held the Chair of Respiratory Diseases in the University of Edinburgh, were absorbing the drug and if the drug where he and his team developed the Edinburgh Method, which paid obsessive was getting into the tubercle bacilli. We attention to supervision, involving district nurses to follow up patients at home, inherited patients who had been treated as well as the triple-drug approach. From 1984 until 1988, he was Chairman of rather badly by the outpatient doctors, the International Union against Tuberculosis and Lung Disease. He also worked being given drugs alone or in ineffective extensively in tobacco control and is the author of over 170 scientific and other combinations, and it became clear that publications. the failures were due to drug resistance. Meanwhile we noted that with our own careful management of combination therapy – streptomycin and PAS A pioneer in the early identification of drug resistance in tuberculosis patients, Sir John (para-aminosalicyclic acid) – we were Crofton and his colleagues’ seminal research into multidrug therapy for tuberculosis not creating resistance ourselves. But patients in the 1950s laid the groundwork for the WHO-recommended tuberculosis then in these first years, two of my col- treatment today. This is one of the last interviews he gave before he passed away on leagues each had a patient who showed 3 November at the age of 97, after a career that spanned three-quarters of a century. resistance to the two drugs, even when properly administered. Now, the new rather magic drug isoniazid had just Q: Why did you become interested in Q: Why was it grim in Edinburgh? started to be used, and we had partici- tuberculosis? A: I inherited not only the 400 beds pated in Medical Research Council A: During the war I served under Lieu- designated for tuberculosis at the hos- trials of the drug so we decided that tenant Colonel Guy Scadding, who had pital [there] but a waiting list of several the safest course of action would be been a young consultant in London in hundred people. It was a grim situation to give all three drugs together. To our a teaching hospital and had a particular not helped by the fact that there was astonishment we found that we were interest in respiratory diseases. I was one set of doctors handling outpatient curing everyone. very stimulated by him, and we became diagnosis and another set dealing with great friends. When I came out of the the patients. I thought this was a bad Q: And that became known as the army after the war, I worked under him thing from the point of view of conti- “Edinburgh Method”. How was this at the Brompton Hospital in London. nuity of care. There was also a problem received? After a few months the new drug strep- with doctors in the hospital being able A: My colleagues accepted the results tomycin became available and Scadding to pass patients they considered incur- because they had been involved in the invited me to take part in the first clas- able back to the outpatient doctors. In research, but practically nobody else sical controlled trial of streptomycin. other words they were able to get rid of believed us apart from two bacteriolo- their failures. I thought that if they had gists from the Pasteur Institute (in Q: When did you go to Edinburgh? to keep their failures, they would make France). Others even accused us of A: I was offered the vacant position of more of an effort not to have failures fiddling our figures. professor of tuberculosis at the Univer- in the first place. sity of Edinburgh in 1951. I accepted Q: What effect did the new triple therapy under the condition that it dealt with Q: What were the main challenges? have? respiratory diseases in general. I went A: One was how to handle the epi- A: We were curing nearly everyone we to Edinburgh [in 1952] and, from the demic itself. In 1954, there were 1000 treated. For the first time 100% cure tuberculosis point of view, it was grim. new cases in a city of half a million. We was a reasonable goal; in the past it had During the Second World War tuber- divided [Edinburgh] into five areas, only been 50%. New cases dropped culosis increased all over Europe, but and drew up a scale reflecting clini- by 59% in the three years from 1954. after the war things got better nearly cal severity and social aspects, such as Treatment was effective, but it was still everywhere in Europe apart from Por- whether the patient was a child. Using a challenge to get patients to take the tugal and Scotland. this as a reference, and meeting on a drugs. Patients took all three drugs 894 Bull World Health Organ 2009;87:894–895 | doi:10.2471/BLT.09.051209 News when they were terrified of the disease, tuberculosis (MDR-TB), the first such to the supervision of the individual but as soon as they showed improve- guidelines focused on the clinical treat- patients and their treatment. How ef- ment they stopped. We did urine tests ment of patients with these resistant fective this can be varies from country on patients whose sputum had been strains. to country and culture to culture. In declared negative and who had been some countries a family member can discharged home with instructions Q: DOTS 1 is often associated with the supervise treatment. In others, that to continue chemotherapy. Of 100 work of Dr Karel Styblo in Africa. How doesn’t work. Then there is the issue of sampled, 25 patients showed no trace of did the Edinburgh Method influence his private practice and its influence [on having taken the drugs. So we initiated work? tuberculosis control]. Even when you a routine of regular urine testing and A: I first met Styblo in 1960 in Czecho- have a good government programme, follow-up with patients who were not slovakia. He was fairly junior then. The you can still have private practitioners taking the drugs. government had initiated detailed X- using the wrong drug combination raying of the population in one part of and creating resistance. Q: When did the medical establishment the country, and Styblo was in charge. accept the Edinburgh Method? As a result of that visit, they completely Q: How do you see future prospects of A: We initiated a trial in some 23 changed their approach to treatment, tuberculosis control? countries, choosing influential centres following what we had pioneered A: The situation is more hopeful now where if they got good results other in Edinburgh. Later on we worked than 20 years ago. Many years ago people would take up the treatment. together closely at the International when I was on the Medical Research Due to scepticism about our method, Union against Tuberculosis and Lung Council committee, we went to all we called it “a study of the causes of Disease. He was a quiet man, but won- the big pharmaceutical companies and disease in far advanced pulmonary derfully persistent and an enormous asked them if they were doing research tuberculosis”. We specified in the pro- worker. Several east African countries on new tuberculosis drugs. Because tocol that the cases could be moribund, had asked for help with tuberculosis and it was mostly a third-world problem very advanced and very bad, and that Styblo was sent there. He proved to have at that time none of them were doing all the patients would have all three a genius for persuading governments anything. Now with the tremendous drugs. It worked out as we had hoped. that tuberculosis was a major economic priority that politicians have placed on While one or two moribund patients problem as well as a public health con- the problem internationally – that is died a week or two after they came into cern. He was also able to convince them on tuberculosis, HIV and malaria – far the trial, all the other treatment failures that they could handle diagnosis and more money is going into new drugs were because the doctors had failed to treatment through their routine health to cope with resistant strains. adhere to the protocol. So at last we services, without special tuberculosis had acceptance. clinics and services. Above all he stressed Q: So can we expect to control tubercu- the importance of monitoring patients losis in the future? Q: When did you start working with the throughout the course of treatment, as World Health Organization (WHO)? he had seen done in Edinburgh.

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