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Multidrug-resistant tuberculosis (MDR-TB, defined as resistance to at least both rifampicin and isoniazid) has become a serious problem in the United Kingdom. As it is uncommon, no one clinician has sufficient experience of it to be confident in providing the best management for the patient. The model of a centralised system of management, such as is used in the Baltic countries, would seem a suitable method to adapt to the United Kingdom. With the agreement of the relevant professional organisations, a virtual electronic expert panel, the UK Multidrug-Resistant Tuberculosis Service, has been developed. This body gives advice via a secure website on MDR-TB patients referred by e-mail by clinicians across the country managing MDR-TB cases. In the first 2 years of operation, advice was sought on 60 patients with culture-proven MDR-TB (54% of the UK total). The number of clinicians accessing the advisory service increased from 27 in 2008 to 33 in 2009. Patients of non-UK origin accounted for 90% of all cases, including all four extensively drug-resistant tuberculosis cases. A central electronic virtual committee providing advice via a secure website has proved to be practical, economical and efficient. It could provide a model for MDR-TB management in other countries and for the management of other uncommon diseases.

OBJECTIVES To determine the levels of resistance to first-line tuberculosis drugs in three cities in three geopolitical zones in Nigeria. METHODS A total of 527 smear-positive sputum samples from Abuja, Ibadan and Nnewi were cultured on BACTEC- MGIT 960. Drug susceptibility tests (DST) for streptomycin, isoniazid, rifampicin and ethambutol were performed on 428 culture-positive samples on BACTEC-MGIT960. RESULTS Eight per cent of the specimens cultured were multi-drug-resistant Mycobacterium tuberculosis (MDR-TB) with varying levels of resistance to individual and multiple first-line drugs. MDR was strongly associated with previous treatment: 5% of new and 19% of previously treated patients had MDR-TB (OR 4.1 (95% CI 1.9-8.8), P = 0.001) and with young adult age: 63% of patients with and 38% without MDR-TB were 25-34 years old (P = 0.01). HIV status was documented in 71%. There was no association between MDR-TB and HIV coinfection (P = 0.9) and gender (P > 0.2 for both). CONCLUSIONS MDR-TB is an emerging problem in Nigeria. Developing good quality drug susceptibility test facilities, routine monitoring of drug susceptibility and improved health systems for the delivery of and adherence to first- and second-line treatment are imperative to solve this problem.

The recent publicity surrounding tuberculosis (TB) in both the medical and the lay press, particularly in reference to a number of outbreaks of the disease in British schools, is a timely reminder of a 'forgotten' disease that has never really gone away. Following a marked decrease in notification rates in developed counties in the 1960s and 1970s, TB control and treatment programmes were downgraded in the West, and soon both medical professionals and the lay public ceased to be able to identify early symptoms of the infection. Meanwhile, poorer countries continued to struggle to provide even basic medical resources, and death and sickness from TB continued unchecked. More recently, however, there has been a rise in the number of new cases of TB in industrialised nations, together with the emergence of multi-drug-resistant strains of the bacillus. This article reviews these and other aspects of the effectiveness of both UK and international TB control programmes.

Summary Objective: To study the relative bioavailabilities of two generic rifampicin preparations with Rimactane. Method: Each of nineteen healthy volunteers received a single oral dose of 600 mg of rifampicin in an open cross-over randomised three-way single-dose design with a washout period of 7 days between each doses. Plasma concentrations of rifampicin were determined by HPLC. In vitro dissolution profiles of the same drugs were determined and compared with human bioavailability study results. Results:No statistically significant difference was found in main bioavailability parameters between Rimactane and generic preparations studied. Both generic preparations also fulfilled the bioequivalence criteria based on the 90% confidence intervals. There was a good correlation between in vivo and in vitro results: faster dissolution time corresponded to the lower Tmax value; lower percentage of released compound to the lower AUC value. Significant intersubject variations were found in main bioavailability parameters; significant negative correlation was found between average AUC values and body weight of the volunteer. Conclusion: All three products were bioequivalent. Our results also suggest the suitability of one-compartmental model with lag time, first order input and first order output to describe the kinetics of rifampicin.

Mycobacterium tuberculosis remains the most important global cause of mycobacterial disease in humans. The central roles of consistent delivery, adherence to therapy, and built-in audit of practice have recently received heavy emphasis in the treatment of M. tuberculosis, particularly in new guidelines from the World Health Organization. The management of mycobacterial disease in the context of HIV infection continues to pose problems, particularly in resource-poor settings. The most significant development for the clinical management of HIV-associated M. tuberculosis infection in the past year has been the establishment of the efficacy of isoniazid monotherapy as preventive therapy, after the publication of three new randomized, placebo-controlled trials.

A lack of reliable statistics makes tuberculosis (TB) trends in developing countries difficult to estimate. Nonetheless the World Health Organization and the International Union against Tuberculosis and Lung Disease estimated in 1990 that one-third of the worlds population was infected with the tubercle bacillus and that there were 7-8 million new cases of TB annually. 95% of the new cases occurred in the developing world with more than 5 million in Asia and the Western Pacific and more than 1 million in sub-Saharan Africa. Almost 80% of TB cases in developing countries occur among those under age 50 years. The global annual mortality was estimated at 2.5 million with 98% of deaths occurring in developing countries. Worldwide TB is believed to be responsible for 25% of avoidable deaths in young adults. There has been no significant decline in the average annual risk of infection in most developing countries due to incomplete coverage by control programs and inadequate cure rates. The interaction of HIV infection with TB is another factor which contributes to the deteriorating TB situation in many developing countries. Countries with a high population growth rate and little decline in the annual risk of infection should expect either a static or increasing level of TB disease. Immigration from developing countries HIV infection poverty unemployment homelessness overcrowding and population aging contribute to the spread of TB in developed countries. Drug resistance thwarts the control of TB worldwide.

To determine the levels of resistance to first-line tuberculosis drugs in three cities in three geopolitical zones in Nigeria.A total of 527 smear-positive sputum samples from Abuja, Ibadan and Nnewi were cultured on BACTEC- MGIT 960. Drug susceptibility tests (DST) for streptomycin, isoniazid, rifampicin and ethambutol were performed on 428 culture-positive samples on BACTEC-MGIT960.Eight per cent of the specimens cultured were multi-drug-resistant Mycobacterium tuberculosis (MDR-TB) with varying levels of resistance to individual and multiple first-line drugs. MDR was strongly associated with previous treatment: 5% of new and 19% of previously treated patients had MDR-TB (OR 4.1 (95% CI 1.9-8.8), P = 0.001) and with young adult age: 63% of patients with and 38% without MDR-TB were 25-34 years old (P = 0.01). HIV status was documented in 71%. There was no association between MDR-TB and HIV coinfection (P = 0.9) and gender (P0.2 for both).MDR-TB is an emerging problem in Nigeria. Developing good quality drug susceptibility test facilities, routine monitoring of drug susceptibility and improved health systems for the delivery of and adherence to first- and second-line treatment are imperative to solve this problem.

Differences in clinical presentation of tuberculosis (TB) have been reported in different age groups, gender and in different parts of the world. Study of gender differences in clinical presentation of patients will assist in targeting those at higher risk and ensure successful TB control planning.To describe the differences in clinical presentation and risk factors for TB in male and female Nigerian patients with pulmonary tuberculosis (PTB).Patients with cough of more than three weeks duration attending hospitals in Abuja, Nigeria were interviewed with a structured questionnaire. After clinical examination, sputum samples were examined by smear microscopy and one sample was cultured. Haematological examination, serum chemistries, HIV serology, and chest X-ray evaluation were also evaluated.Of 1186 patients who had sputum culture, 731 (62%) were positive for TB: 437 (60%) males and 394 (40%) females. The mean (SD) age of males was significantly greater than that of females, 34 (11) vs. 31 (12) years, rp = 0.001. Male patients were more likely to be employed and better educated than women. More men than women smoked cigarettes. Women were more likely to be co-infected with HIV and less likely to be smear-positive than men. Male patients had more severe radiological disease.More men than women appear to present with TB at hospitals in Abuja. Male patients were older and are more likely to have smear-positive TB, whereas, female patients were more likely to be co-infected with HIV.

There are two worlds when it comes to the diagnosis of tuberculosis (TB). One world has only smear microscopy at its disposal. There may also be some radiological facilities, usually at the patients' expense. The other world has all modern techniques available, including culture, nucleic acid amplification, molecular diagnostics and sophisticated radiological techniques such as computed tomography and positron emission tomography scanning. The ability to diagnose or misdiagnose TB will vary across these two worlds. In this review, we provide an overview of clinical, radiological, molecular and immunological diagnosis of TB and highlight the common difficulties and pitfalls in TB diagnosis.

As recently as 3 yrs ago, a colleague complained that after 100 yrs the only way to detect tuberculosis (TB) infection was still to measure “bumps on arms”. Now, at last, we have a genuine improved alternative: the ex vivo cellular interferon (IFN)-γ-based blood tests. The crucial questions we need to ask are how good they are at detecting infection with the TB bacterium and whether they are cost-effective? Unfortunately, determining the answers to these questions is not easy. The new ex vivo cellular IFN-γ assays (CIGAs) have been developed based on the release of IFN-γ from a patient’s T-cells when exposed to mycobacterial antigens. These novel assays rely on the principle that the genes encoding the secretory proteins early secretory antigenic target (ESAT)6/culture filtrate protein (CFP)10 are absent in the bacille Calmette–Guerin (BCG) vaccine strain and most environmental mycobacteria 1. Two commercial cellular immunological assays have been developed in which IFN-γ output from the patient’s whole blood or peripheral blood mononuclear cells are measured following treatment with ESAT6/CFP10 antigens 1. Different assay formats have been developed. One method relies on the relatively straightforward ELISA detection after a fixed volume of whole blood is incubated in a tube with ESAT6/CFP10 antigens (Quantiferon Gold; Cellestis Limited, Carnegie, Australia). The other method currently available commercially is the T-Spot.TB assay (Oxford Immunotec, Oxford, UK) based on the enzyme-linked immunospot (ELISPOT) principle. The methods appear to be both sensitive and specific. These assays have the potential to change the face of the diagnosis of latent TB infection (LTBI) and active TB at an early stage in the disease process. Their use is also likely to transform the screening of new migrants and other population groups. These tests require only a single blood sample without the repeat visit required for the tuberculin skin …

Despite declining tuberculosis mortality per head of population, there was little change in tuberculosis case fatality in England and Wales from 1974 to 1987.To determine the trend in tuberculosis case fatality for England and Wales from 1988 to 2001.Annual deaths to notifications ratios (DNRs) for tuberculosis were calculated using published notification and mortality data, and analysed by age group and three disease sites (central nervous system [CNS], respiratory and other). DNRs for seven disease sites (miliary, bone and joint, CNS, respiratory, genitourinary, gastrointestinal and other) were calculated for 1998 and 1999 combined, using additional data from the enhanced tuberculosis surveillance programme.DNR for all ages and disease sites combined fell from 9.26% in 1988 to 5.59% in 2001 (r = -0.90; 95%CI -0.97 - -0.70). DNRs for 1998-1999 combined were 41% for miliary disease, 17% for bone and joint disease, 8% for CNS disease, 7% for respiratory disease, 2% for genitourinary and gastrointestinal disease and 0.6% for other disease.Some of the decrease in DNRs may be due to improving notification rates. True declines in overall case fatality reflect increases in the proportion of tuberculosis patients in younger age groups and with low mortality extra-pulmonary disease.

The most important challenge for tuberculosis (TB) care in the UK today is the re-education of the medical and allied professions in diagnosis and management of the disease. In the first half of 2001 there were an exceptionally large number of outbreaks of TB, one of which with over 70 secondary cases (and still counting) is the largest since the advent of specific chemotherapy. 1 I often see patients with a diagnosis of TB who have at some point been told by a doctor that they do not have TB. One was even told that nobody gets TB these days. A missed diagnosis of lung infection, specifically TB, is the second most common cause of litigation from a respiratory cause after pulmonary embolus (Evans CC, personal communication). TB is usually missed because it is not considered.

This editorial is based on a conference entitled ‘Multi-drug Resistant Tuberculosis—Molecules to Macroeconomics’, held at the RSM on March 29-30. Multi-drug resistant tuberculosis (MDRTB) is defined as resistance to the two principal drugs used in treatment—isoniazid and rifampicin—whether or not there is resistance to other drugs. The terms ‘primary’ and ‘acquired’ resistance have been changed to ‘resistance in new patients’ and ‘resistance in previously treated patients’. The main causes of MDRTB are poor patient management, non-adherence to the prescribed regimen, a poor national programme or some combination of these three.

Introduction Although laboratory culture of Mycobacterium tuberculosis (M TB) remains the gold standard for the diagnosis of active tuberculosis (TB), only 66% of pulmonary and 46% of extra-pulmonary cases of TB in the UK are culture confirmed.1 The Health Protection Agency9s Strategic Plan aims for at least 70% of pulmonary TB cases to be confirmed by positive culture. The aim of this study was to identify the reasons for not obtaining culture confirmation in a cohort of active TB patients. Methods A retrospective study of all patients with active tuberculosis in a TB centre between January and December 2009. Results 69 patients (46 male) with a mean age of 42 years (range 3–83) were diagnosed. 36 (52%) had pulmonary TB with or without extra-pulmonary disease and 33 (48%) had extra-pulmonary TB only. 29 (81%) cases of pulmonary TB were culture positive and 4 (11%) had no growth on culture. 3 (8%) cases had no sample obtained. These were all children aged 3–5 years who had a positive Mantoux test, evidence of TB on chest radiograph and a history of close contact. 17 (52%) cases of extra-pulmonary TB were culture positive. 10 (30%) had samples taken but no growth on culture. 2 (6%) had samples obtained but not sent for culture while 4 (12%) had no sample obtained. Conclusion The commonest reason for not obtaining culture confirmation was a negative growth (20%). Failure to obtain a microbiological sample (10%) and failure to send the collected sample for mycobacterial culture (3%) were the other reasons. A positive culture of M TB is important because it not only confirms the diagnosis but also provides the drug susceptibility profile of the organism. Our finding that the largest proportion of cases not confirmed by positive culture was due to no growth from a specimen suggests that the current microbiological methods for growing M TB may be inadequate and further research is needed to increase the diagnostic yield. Secondly, there is a need to educate those sending samples, including surgeons and radiologists performing biopsies, so that specimens are sent correctly.

It was no coincidence that a meeting on the problem of tuberculosis in humans and animals, and the potential mutual threat we are to each other, was held in the last week of the Department for Environment, Food and Rural Affairs consultation on badger culling. The same day an A4 sized picture of a badger appeared on the front of a daily broadsheet. Historically the link between animal and human tuberculosis (TB) has always been strong. From the early 1800s TB has been described in cattle in slaughterhouses. In 1865 Villemin showed that infected tuberculous material could be injected from one species to another to cause disease and, in 1882, Koch pointed out that there was a danger that TB could be transmitted from animals to humans. In 1902 Ravenel demonstrated Mycobacterium bovis in a child with tuberculous meningitis. Yet it was not until 1929 that the danger of animal to human transmission of TB received Government debate. In Victorian times most of a city's milk supply would come from cows living in sheds within the city limits, increasing the risk of direct spread of TB, either by milk or airborne infection, to city dwellers. Even today in developing countries 15% of food is likely to be produced within cities. It was likely that TB transmitted from infected milk to humans was a major cause of morbidity and mortality from Victorian times up to about the Second World War.1,2 During the 1930s tuberculin testing was introduced in cattle in the UK; 40% were found to be reactors. With the introduction of pasteurization, initially to prolong the shelf life of milk, came the full control of the transmission of bovine disease to humans. At that time bovine TB was a major source of disease to humans but between 1931 and 37 deaths from bovine TB declined from 6.1% to 5.6% of the total. Today TB in animals is a word wide problem. In England and Wales it is increasing rapidly. The same strains of M. bovis demonstrated by spoligotyping have been found in cattle and badgers living in close confines. Infection in cattle leads to economic harm to agriculture as animals cannot be traded. The clinical and economic importance of TB in cattle is as great as for bovine spongiform encephalitis and foot and mouth disease. Fatality from TB can result directly in cattle and infection means slaughter. In this situation a farmer's insurance may be terminated, with resulting loss of earnings and bankruptcy. The main means of spread between cattle is probably due to translocation of cattle as those with infection are moved to a non-infected heard. The spread to and from wildlife is also likely to be important. Though human TB had increased by 20% in England and Wales, since 1987 the geographical distribution of human TB is very different from the distribution of TB in cattle.3 Disease in humans from M. bovis has occurred in no more than 25 cases a year for the last 5 years. As most of disease is in the older age groups it is likely that infection had occurred sometime, perhaps decades, in the past. The implication is that there is no current cattle to human transmission. However, cases in younger patients in the UK do occur in the foreign born, which suggests that cattle to human transmission could be a problem in some developing countries. There have been a handful of documented cases where infection of a human had probably arisen by airborne spread from cattle. (J Watson, F Drobniweski, personal communication). TB in cattle is a human health issue. If TB is being transmitted from wildlife to cattle, then this too is a human health issue. Wildlife, farm animals, pets, food and milk all pose a potential threat to our health. The conflict in control is between the cost of an eradication programme and the safety of less than complete eradication in European states. A number of new problems are now presenting themselves such as the importation of exotic pets which are not covered by current law.4 Internationally, TB is a world threat.5 A large number of cattle have TB in the developing world where there are neither schemes for compensation nor government policies of eradication. Bovine TB is probably increasing in Africa as a result of farming policies allowing free movement of cattle. In a study of 967 cows carried out in Nigeria, 14% were found to be tuberculin positive. Of these, 12% had infected milk as shown by culture positivity for M. bovis and 13% diseased tissues at slaughter. (Aishatu Abubakr, personal communication.) Until now evidence of infection in cattle has depended on the old fashioned tuberculin skin test. The new gamma-interferon blood tests which had been pioneered in cattle can detect infection earlier than the skin test. Used together they could form a more sensitive test for infection than either alone.6 Vaccines offer the best prospect of control but at an estimated cost of $1.8 billion to develop. The plan is to have a vaccine ready by 2015. The human vaccine development would provide the best hope for a cattle vaccine which might also be used on wildlife. This might have application to the badger population to prevent spread to cattle.7 Though control of TB in cattle is a public health measure, the stark reality is that only 22 cases of M. bovis in humans had been identified in the UK in 2004 yet 30 000 cattle had been slaughtered to prevent the risk to humans. The cost of bovine TB in cattle has been rising steeply. In 1986, 88 herds had been found to carry the infection. By 1996 the number had risen to 476, by 2000 to 1044 and by 2005 there were 5539 infected herds. In the latest year 30 000 cattle had been slaughtered. Against this it had been suggested that a total of 12 000 badgers be culled over the next 10 years. Evidence form post mortems done on road kill badgers showed that the incidence had increased from a 5% infection rate in 1972 to 15% in 2002-2004. In the light of an infection rate of up to 38% found in culled badgers, this was probably an underestimate. Eradication should be the aim. To see what had gone wrong with TB control in cattle since its nadir in the 1970s it is necessary to ask what is being done differently now compared with then. There are four areas to examine: increase in herd size, increase in movement of cattle, an increase in the badger population and the absence of control measures for wildlife. Special herds which were entirely isolated from other cattle are being infected by probable transmission from wildlife.8 It is necessary to apply the same rigorous control to wildlife as is currently being applied to cattle. And this of necessity would include a badger cull. Though animals with TB pose some risk to humans, within the confines of the UK this is probably very small indeed. Evidence suggests that no more than a handful of humans may have acquired disease from animals in the last decade; M. bovis having been transmitted by airborne spread. In contrast, spread from animals to humans in developing countries remains a very real danger, mostly from infected milk. This seems to be a danger, which is being entirely ignored. Within the UK, the real battle in TB control in the animal world is in transmission from wildlife, principally badgers, to cattle. Here there is strong circumstantial evidence of spread and a measure to reduce infection in wild life by a badger cull is now a realistic proposition.

EDITOR,—Concern is growing over the spread of drug resistant Mycobacterium tuberculosis. New evidence suggests that this spread may be increasing in certain sections of the British population. The recent advances in molecular techniques have equipped us with the means to make substantial inroads into the possible impact of drug resistant tuberculosis.1 A central laboratory to which samples could be sent would provide us with an important means of combating the …

Four simple multiple-choice questions about tuberculosis (TB) were posted on a non-medical internet site for a 2-month period. A total of 564 responses were received. Sixty-two were excluded as individuals had made multiple attempts at the questions. Sixty-five per cent of responses were from North America, 14·5% from Europe and 12% from Australia and New Zealand, with only a small number of responses from Africa, the Indian subcontinent and South America. Of the respondents 49·5% correctly answered that cough is the commonest symptom of TB, 45% knew that TB was transmitted mainly by air-borne droplets, 37·8% knew that TB was caused by a bacterium. Only 19·5% knew that the most important risk factor for developing TB was HIV infection and only 4% answered all questions correctly. This survey suggests that knowledge about tuberculosis is limited in computer-literate individuals throughout the world.

Introduction There is a wide variation in the provision of TB screening services for migrants worldwide. New entrant screening for TB helps to identify and treat active and latent TB at an early stage, reduce risk of transmission and identifies those at a high-risk. It is common practice to screen new entrants from countries where the prevalence is high. However, it is sometimes perceived that screening for immigrants can be stigmatising. In addition, there is a poor understanding of this disease and large cultural differences in perceptions exist. This study explores the different attitudes towards screening and the current awareness, perceptions and attitudes towards TB, in order to tailor the current screening programme to different cultural backgrounds. Methods 27 participants (63% male) were recruited at the weekly multi-disciplinary Liverpool TB contact-tracing clinic. Semi-structured interviews (18% interpreter help) exploring the attitudes towards screening and the disease were conducted. Results 59% of participants were aware of the causative agent, 74% identified at least 1 associated symptom and 89% recognised that transmission was air borne. 89% considered TB curable, 33% were aware of the link with HIV and 44% stressed that a greater awareness of TB among the general public is needed. The main source of information about the disease was family and friends (43%) and clinic (42%). The majority (59%) felt there was a stigma attached with fear of social isolation and an impact on occupation. 59% expressed a positive attitude towards screening and perceived it to be acceptable due to the availability of free treatment. The majority of the participants regarded screening as prevention of transmission and felt it was their responsibility in society. 22% of the participants thought it was unnecessary or were unsatisfied with the current screening process. Seven per cent of the participants demonstrated poor understanding of the screening process, having already undergone screening. Conclusions The majority of the migrants found TB screening to be acceptable and demonstrated a positive attitude, although some barriers still exist. Improving TB awareness in the communities will help increase the acceptability of screening.

BACKGROUND: A study was designed to determine the extent of the interaction between tuberculosis and human immunodeficiency virus infection in England and Wales. METHODS: Data were obtained from the United Kingdom national AIDS surveillance and the Medical Research Council tuberculosis notification surveys in England and Wales (1983 and 1988). The proportion of patients reported with AIDS known to have had tuberculosis and the proportion of patients notified with tuberculosis known to have HIV infection were estimated. RESULTS: Of the 4360 patients with AIDS reported by 30 June 1991, 200 (4.6%) were in patients reported to have had tuberculosis. Only one of the 3002 patients (0.03%) reported in the 1983 survey of tuberculosis notifications in England and Wales was known to be infected with HIV compared with nine of 2163 patients (0.42%) in the 1988 survey. CONCLUSION: Although the reported number of cases of HIV infection with tuberculosis in this country is increasing it remains small. Complete reporting of cases of AIDS and notification of cases of tuberculosis are essential to enable the two infections to be monitored as the HIV epidemic develops. Special studies, such as those reported here, will need to be undertaken regularly to assess the future extent of the interaction.

Introduction The low incidence in the UK means that few specialists treating tuberculosis have much experience of managing patients with MDRTB. To attempt to overcome this gap, the MDRTB Service was established at the Liverpool Heart and Chest Hospital in January 2008. Method The service offers ready access to expert advice on the management of patients with MDRTB via an electronic virtual committee of TB experts. The advice given offers the likely best treatment for patients and by doing so prevents the emergence of Extreme drug resistant TB (XDRTB). The second function of the Service is to collect data on all MDRTB cases identified in the UK and record outcomes. Results From 2008, the MDRTB Service has been approached for advice on 93 TB cases. Of these 70 were confirmed as MDR and 6 XDRTB whilst the remainder either could not be confirmed as MDR, were Isoniazid OR Rifampicin mono resistant or were more general requests for advice. The initial resistant patterns of 76 MDRTB cases showed resistance to Isoniazid and Rifampicin, 52% of the cases were resistant to Streptomycin, 41% to Ethambutol and 31% to Pryazinamide. Indeed 33% of cases were resistant to three Group 1 drugs and 29% to 4 drugs in this category. In the 6 XDR-TB patients, three were resistant to one group 2 drug only whilst the other three cases were resistant to more than one group 2 drug. All XDRTB cases were resistant to more than one group 3 drug, and 3 (50%) had more than one resistance in both drug groups. Patients of non-UK origin accounted for 86% of cases (male: 48%) of which 5 (8%) were XDR-TB, the rest MDR-TB. India (28%) and Sub Saharan Africa (26%) were the most prevalent countries of origin. 57% of patients had pulmonary disease, of which 82% were known to be sputum smear positive and therefore infectious. Three patients are known to have died and the rest are continuing on treatment. Conclusion The MDRTB service is an important means of providing expert advice on management of these cases. Streptomycin resistance was present in the majority.

To determine current trends in mortality from tuberculosis according to age the published data on notification and deaths from tuberculosis from 1974 to 1987 have been analysed. The ratio of deaths to notifications per year was assessed over this period as a measure of case fatality from tuberculosis. The mean annual decline in the ratio for each age group was as follows: 0-14 years 6.7% (95% confidence interval 4.00 to 9.6%), 15-34 years 1.4% (-0.2 to 3.0%), 35-54 years 4.5% (2.2 to 6.9%), 55-74 years 2.8% (1.8 to 3.7%), and 75+ years 3.2% (2.1 to 4.2%). Because the incidence of disease in the 75+ group has declined much more slowly than in the rest of the population and because the size of this age group has increased in relation to the other groups, the overall annual mortality from tuberculosis has declined by only 0.13% (95% CI -1.3 to 1.3%). The total number of deaths from tuberculosis declined from 996 in 1974 to 430 in 1987, whereas deaths in the 75+ age group remained relatively constant at around 200 a year.

We report the results of a double-blind control crossover trial of slow release theophylline Nuelin S.A. in improving symptoms of 'morning-dipping' in twelve asthmatic patients. Sleep disturbance was lessened and 'morning-dipping', though not abolished, was improved by 24% (P less than 0.01). Mean peak expiratory flow-rate (PEFR) on waking was significantly higher on active drug (262 l/min vs 226 l/min, P less than 0.001) as were the evening PEFRs (316 l/min vs 285 l/min, P less than 0.05). Seven of the 12 patients achieved 26% improvement in mean PEFR (P less than 0.05) with plasma theophylline levels in the range 28-44 mumol/l. The other five patients improved by 9% (P less than 0.02) with levels in the range 55-66 mumol/l. Mean plasma cyclic AMP 4-6 h after theophylline was significantly higher than with placebo (27.0 nmol/l vs 17.6 nmol/l, P less than 0.05) but significant correlations between cyclic AMP and theophylline levels, and cyclic AMP and PEFR were not demonstrated. A total of nine patients, 33% of those originally recruited for this study, withdrew prior to the double-blind phase because of unacceptable side-effects of theophylline, namely nausea and headache.

A survey of the smoking habits and attitudes towards smoking of all staff working in a teaching hospital with a specialist thoracic department has been carried out. Six hundred and sixty three (70%) of the 949 members of staff returned a voluntary self completed questionnaire. Completion rates were highest among medical, administrative, and clerical staff, and lowest among domestic and catering staff. Of the 663 responders, 136 (23%) admitted to being current smokers and 135 (19%) to being ex-smokers. The great majority of responders (81-94%, depending on area of work) believed that more areas of the hospital should be entirely smoking free. Most responders, however, believed that some accommodation should be made available to staff (70%), patients (52%), or visitors (59%) who wished to smoke. About a quarter of smokers expressed interest in joining a group to help them give up smoking.

Of the 4172 patients in a survey of all cases of tuberculosis notified in a six-month period in England and Wales in 1978-79, 198 had a bone or joint lesion; 79 were white and 108 were of Indian subcontinent (Indian, Pakistani or Bangladeshi) ethnic origin. The estimated annual notification rates for orthopaedic tuberculosis were 29 per 100 000 for the Indian subcontinent group and 0.34 per 100 000 in the white group, a ratio of 85 to 1. Rates increased with age in both groups. The spine was the most common site, and was affected in 30% of the white patients and 43% of the Indian subcontinent patients; the distribution of other sites was similar in both groups. Positive culture from a bone or joint lesion was obtained in 99 (50%) of the 198 patients (58% of white patients and 47% of the Indian subcontinent patients). Bacteriological or histological confirmation of tuberculosis either from a bone or joint lesion or from another site was obtained in 68% of the patients. Mycobacterium tuberculosis was isolated from the orthopaedic lesions in 79 of the 82 patients with identification test results and M. bovis in the 3 remaining patients. Of the 61 patients with M. tuberculosis and with no history of previous chemotherapy, 5 had resistant strains compared with 1 of the 18 patients who had previously received chemotherapy. All 6 patients with resistant strains were of Indian subcontinent ethnic origin.

In a survey of the chemotherapy prescribed for 1312 adult patients of white or Indian subcontinent ethnic origin with pulmonary tuberculosis only, notified in the 6 months from October 1978 to March 1979, it was found that 163 (12%) patients died before they had completed chemotherapy. Of the 163 patients who died 96% were of white ethnic origin; 15% of the 1022 white patients died compared with 2% of the 290 Indian subcontinent patients. According to the death certificate, approximately half the white patients died from tuberculosis, and in a further 31% tuberculosis was a contributory factor. Death from tuberculosis most frequently occurred in the older age groups, accounting in part for the different findings in these two ethnic groups, because of the excess of older white patients. In a step-wise multivariate discriminant analysis death from tuberculosis was found to be significantly associated in the white patients with the radiographic extent of disease before treatment, and with age, extent of cavitation and a positive sputum smear result, but not sex. Most of the deaths from tuberculosis occurred early, 38% before the end of the first week of chemotherapy and 69% by the end of 4 weeks. There was a further group of 51 adult patients with pulmonary tuberculosis notified in the same 6-month period in whom the diagnosis was not made until after death, 25 of them dying from tuberculosis. It is concluded that there is still a substantial risk of death from tuberculosis in patients with extensive disease in the older age groups.