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Summary Objective To assess the efficacy of weekly zinc or zinc plus retinol as adjuncts for the treatment of pulmonary tuberculosis. Methods Double-blind, randomized, placebo-controlled trial in 350 patients >15 years old with smear-positive tuberculosis in Nigeria (ISRCTN36636609). In addition to antituberculous treatment, patients were randomly allocated to weekly supplements of zinc (90 mg), zinc plus retinol (5000 IU) or placebos for 6 months. Primary outcomes were time to sputum smear conversion and resolution of radiographic abnormalities. Results After 8 weeks of treatment, 68% had achieved sputum smear conversion, and the median conversion time was 6.5 weeks. Hazard ratios (HR, 95%CI) for sputum conversion relative to the placebo group were not significant for zinc (1.07, 0.92–1.29) or zinc plus retinol (0.89, 0.76–1.07). Significant predictors of time to sputum conversion were lung abnormality score, sputum smear grade, age and serum C-reactive protein. HIV co-infection and gender were not independent predictors of time to sputum conversion. There were no significant differences between supplement groups in clinical, radiological or laboratory outcomes at 2 months or 6 months. There were 9, 9 and 2 deaths in patients receiving zinc, zinc plus retinol or placebos, respectively. Mortality in those who received zinc (HR 1.71, 0.88–3.58) or zinc plus retinol (HR 1.54, 0.78–3.26) did not differ significantly from those who received placebos. Most deaths occurred in patients co-infected with HIV. Conclusions Supplementation with zinc or zinc plus retinol did not lead to better outcomes than placebos, and caution is warranted regarding routine micronutrient supplementation, particularly in patients co-infected with HIV. Essai randomise controle de l’utilisation du zinc et de vitamine A comme co-adjuvants dans le traitement de la tuberculose pulmonaire Objectif: Evaluer l’efficacite de la prise hebdomadaire de zinc ou de zinc plus du retinol comme complements dans le traitement de la tuberculose (TB) pulmonaire. Methodes: Essai randomise, placebo controlee en double-aveugle chez 350 patients de plus de 15 ans atteints de TB a frottis positif au Nigeria (ISRCTN36636609). En plus du traitement antituberculeux, les patients ont ete randomises pour des supplements hebdomadaires de zinc (90 mg), zinc plus retinol (5000 UI) ou de placebo durant 6 mois. Les objectifs primaires consistaient au temps pour la conversion des frottis de crachats et la resolution des anomalies radiologiques. Resultats: Apres 8 semaines de traitement, 68% des patients avaient atteint une conversion des frottis d’expectoration et le temps median de conversion etait de 6,5 semaines. Les rapports de risque (HR; IC95%) pour la conversion des expectorations par rapport au groupe placebo n’etaient pas significatifs pour le zinc (1,07; 0,92 a 1,29) ou le zinc plus retinol (0,89; 0,76 a 1,07). Les facteurs predictifs significatifs pour le temps a la conversion des expectorations etaient les scores d’anomalie des poumons, le degre de positivite du frottis, l’âge et la proteine C reactive. La coinfection avec le VIH et le sexe n’etaient pas des predicteurs independants du temps de conversion des crachats. Il n’y avait pas de differences significatives entre les groupes recevant des supplements pour les resultats cliniques, radiologiques ou de laboratoire a 2 mois ou 6 mois. Il y avait 9, 9 et 2 deces chez les patients recevant le zinc, le zinc plus retinol et le placebo, respectivement. La mortalite chez ceux ayant recu du zinc (HR: 1,71; 0,88 a 3,58) ou du zinc plus retinol (HR: 1,54; 0,78 a 3,26) ne differait pas significativement de celle chez qui ont recu du placebo. La plupart des deces sont survenus chez des patients coinfectes par le VIH. Conclusions: La supplementation en zinc ou zinc plus retinol n’a pas conduit a de meilleurs resultats que le placebo, la prudence est justifiee pour ce qui concerne la supplementation en micronutriments en routine, en particulier chez les patients coinfectes par le VIH. Mots-cles: micronutriments, infection, tuberculose, adultes, Nigeria, essai clinique Ensayo aleatorizado y controlado de zinc y vitamina A como coadyuvantes en el tratamiento de la tuberculosis pulmonar Objetivo: Evaluar la eficacia del zinc y del zinc mas retinol como adyuvantes en el tratamiento de la tuberculosis pulmonar. Metodos: Ensayo doble ciego, aleatorizado y controlado con placebo en 350 pacientes >15 de anos con frotis positivo para tuberculosis en Nigeria (ISRCTN36636609). Ademas del tratamiento anti-tuberculoso, las pacientes fueron aleatorizados para recibir suplementos semanales de zinc (90 mg), zinc mas retinol (5000 IU), o placebo durante 6 meses. Los resultados primarios fueron el tiempo hasta la conversion del frotis de esputo y la resolucion de las anormalidades radiograficas. Resultados: Tras 8 semanas de tratamiento, un 68% habian alcanzado la conversion del esputo, y el tiempo medio hasta la conversion era de 6.5 semanas. La tasa de riesgo relativo (HR, 95% IC) para la conversion del frotis de esputo con relacion al grupo placebo no eran significativas para el zinc (1.07, 0.92-1.29) o el zinc mas retinol (0.89, 0.76-1.07). Los vaticinadores significativos para el tiempo hasta la conversion del esputo eran el grado de anormalidad pulmonar, la graduacion de los resultados de la baciloscopia, la edad, y la proteina C-reactiva en suero. La co-infeccion con VIH y el genero no eran vaticinadores independientes del tiempo hasta la conversion del esputo. No habia diferencias significativas entre los grupos de suplementos en cuanto a resultados clinicos, radiologicos o de laboratorio a los 2 o 6 meses. Hubo 9, 9, y 2 muertes entre pacientes recibiendo zinc, zinc mas retinol, o placebo, respectivamente. La mortalidad entre aquellos que recibieron zinc (HR 1.71, 0.88-3.58) o zinc mas retinol (HR 1.54, 0.78-3.26) no difirio significativamente de aquellos que recibieron placebo. La mayoria de las muertes ocurrieron en pacientes co-infectados con VIH. Conclusiones: La suplementacion con zinc o zinc mas retinol no llevo a mejores resultados que los placebos, y se debe asegurar cautela en la suplementacion rutinaria con micronutrientes, especialmente en pacientes coinfectados con VIH. Palabras clave: micronutrientes; infeccion; tuberculosis; adulto; Nigeria; ensayo clinico

Although tuberculosis (TB) has its highest burden among young adults, especially since the advent of HIV infection, two other groups with low immunity, the very young ( 65 years) with waning immunity, are vulnerable groups not to be forgotten. This review describes the epidemiology, clinical aspects, public health aspects and outcome of TB in patients at the extremes of age. The epidemiology differs therein that TB in infants occurs in developing countries with high incidences of TB and HIV, while TB in the elderly occurs in developed countries with ageing populations. The clinical presentation may be non-specific, history of contact with TB is often not known and TB is often not considered at these age extremes, and when the diagnosis is considered, disease progression may already be advanced. Anti-TB treatment regimens are the same as in other age groups, but drug dosages may need adjustment according to weight, renal function, liver function and other potentially complicating factors. Adverse events are more difficult to observe and both the young and the elderly are reliant on others for adherence to treatment. Mortality at both age extremes is higher than in the general TB population. For all the above reasons, public health measures to: prevent transmission of infection; identify those infected and providing preventive therapy; high index of suspicion in order to make an early diagnosis; and timely initiation of treatment are important in both the very young and the elderly.

There is increasing evidence of a link between tuberculosis and smoking. This paper reviews the epidemiological evidence from the UK, China, India and the USA, summarizing some of the main papers which indicate an association. Where an association has been found there seems to be an increase in tuberculosis case rates of between two- and four-fold for those smoking in excess of 20 cigarettes a day, but it may be difficult to control for other factors, particularly alcohol consumption. The final part of the paper reviews possible mechanisms. A likely possibility is that nicotine turns off the production of TNF-alpha by the macrophages in the lungs, rendering the patient more susceptible to the development of progressive disease from latent Mycobacterium tuberculosis infection.

The history of chemotherapy of tuberculosis commenced in 1944 with the discovery of streptomycin. Currently, short-course chemotherapy comprising rifampicin, isoniazid, pyrazinamide and ethambutol/streptomycin administered under directly observed settings for 6 months (initially all four drugs followed by the former two drugs), constitutes the cornerstone treatment for pulmonary tuberculosis. Multi-drug resistant tuberculosis requires alternative chemotherapy, ideally in the form of individualised regimens, for management. To improve on the duration of chemotherapy for drug-susceptible tuberculosis and to achieve better treatment for multi-drug resistant tuberculosis as well as latent tuberculosis infection, there arises a genuine need for new drugs. The quest for new agents is, however, impeded by obstacles. Hopefully, tackling these through collaborative public-private partnerships on an international scale will lead to a fruitful outcome.

The aim of this study was to identify the subtle influences of exposure and individual lifestyles on the risk of developing tuberculosis. A retrospective case-control study (with matching by sex, age, postcode and ethnicity) of all tuberculosis cases notified over a 7-yr period in Liverpool, UK, was carried out. Multiple logistic regression showed that, before diagnosis, cases were 7.4 times more likely to have had visitors from abroad; 4.0 times more likely to have been born abroad; and 3.8 times more likely to have lived with someone with tuberculosis. Subtle socioeconomic factors were also evident with cases 4.0 times less likely to have additional bathrooms. Lifestyle factors emerged with cases 2.3 times more likely to have smoked for at least 30 yrs, 3.8 times less likely to eat dairy products every week and 2.6 times less likely to have had high blood pressure. At interview, these factors were still evident, but cases, unlike controls, had reduced their smoking and alcohol consumption and were less likely to go out of the home or exercise than before their illness. Within individuals, lifestyle consequences of tuberculosis lead to a "healthier" lifestyle on the one hand (less smoking and alcohol consumption), but a reduced quality of life (social activity) on the other.

Worldwide, tuberculosis (TB) causes 1.3 million deaths each year, and there are at least 9.27 million new cases annually.1 Global population mobility on a scale never seen before means that the UK, along with many other countries with a previously low incidence of the disease, has over the last two decades seen a sharp rise in TB. Indeed most doctors are probably more likely to see a case of TB in the next year than at any other time in their professional lives. In the UK, there are now in excess of 8400 new cases per annum, >70% of them occurring in individuals born outside the country,2 and the picture is similar in the USA, where over half of all cases occur in those born abroad.3 The annual UK rate of TB for those born abroad (87/100 000) is >20 times higher than that for the UK-born population (including UK-born members of ethnic minority groups). For the Black African population in the UK who were born outside this country the rate (at 309/100 000) is 75 times higher than in the UK-born population generally, reflecting the very high TB rates associated with HIV co-infection in sub-Saharan Africa.2 Clearly, current methods of TB screening for new entrants, largely for active TB only, are not working, and debate about how they might be improved has spread beyond health professionals to become the focus of media comment, often hostile, and the subject of political attention and debate.4 We discuss the limitations of current UK screening methods, suggest that the natural history of infection with the TB bacterium means that they cannot succeed and consider alternative approaches. Since 1971 the UK has had a mechanism (the Port of Arrival Scheme) aimed at screening immigrants from countries with an annual TB incidence …

The problem with the emergence of HIV-associated tuberculosis (which usually occurs in young adults) is that attention has been diverted away from the fact that, in the developed world, the elderly represent the biggest pool of tubercular disease and therefore the greatest pool of infection within the community. Although the incidence rate of tuberculosis continues to decline in most countries, there is evidence from parts of the developing world that rates may be beginning to increase. The presentation of the disease in the elderly is often uncharacteristic, e.g. disease tending to be more insidious in onset, pyrexia often absent and haemoptysis less common. Chest x-ray changes may also mislead the clinician in that disease is frequently present in the mid or lower zones. The elderly are probably at greater risk of extrapulmonary tuberculosis, which also presents in uncharacteristic ways. The diagnosis remains based on clinical presentation and the presence of smear and culture positivity, although some patients may be treated in the absence of microbiological proof. Standard treatment is with a combination of isoniazid, rifampicin and pyrazinamide, with or without a fourth drug such as ethambutol. The incidence of adverse effects in the elderly is much greater than that in younger patients, often resulting in the need to change the medication to drugs which are better tolerated. This may require changing to regimens which are less effective and therefore have to be taken for a longer period of time. The presence of concomitant disease such as liver or renal failure may also necessitate the administration of a suboptimal regimen. Mortality in elderly patients with tuberculosis is considerably higher than that in younger patients, even when treatment appears to have been started on time; even in the developed world mortality exceeds 30% in those patients over 70 years of age.

Although the cause of the steady increase in tuberculosis (TB) notifications in England and Wales since 1987 is multifactorial, the elderly have made an appreciable contribution. From 1987-1989 the increase was 6% for all ages combined, but 13% in females and 16% in males over the age of 75. Tuberculosis in the elderly therefore remains an appreciable problem. Although the characteristic presentation of chronic cough, malaise and weight loss, with cavitatory changes in the upper lobes still predominates in the elderly, there has been an increased incidence of cryptic miliary disease in which the onset is insidious and chest X-ray often normal. The diagnosis must often be made on suspicion and treatment started before a positive diagnosis is obtained. The elderly are more likely to suffer adverse effects from the anti-tuberculous chemotherapy than the younger population and greater care must be taken. Drug resistance is uncommon in the elderly in the UK. Isoniazid, rifampicin and pyrazinamide are appropriate for the initial two months of treatment. Rifampicin and isoniazid should be continued for a further four months for disease at virtually any site, with the exception of TB meningitis, when a further 10 months therapy should be given. In the UK, preventative therapy in the form of isoniazid or rifampicin and isoniazid probably has no place in disease control in an elderly population; tuberculin tests are frequently negative, even in the presence of active disease, as elderly patients are often anergic.

Tuberculosis has long been overshadowed in the media by HIV, malaria and now ‘sexy’ new pandemics such as swine flu. Why has tuberculosis been forgotten by the UK public and how can we move it into the media spotlight to raise awareness and improve funding? After HIV, tuberculosis is the world's second most lethal infectious disease, but in this country the public has consigned it to history and novels such as Jane Eyre. Indeed when asked about tuberculosis by former BBC health correspondent Glenda Cooper, one journalist said ‘consumption has been eradicated in the developed world’. This is not a rare assumption; many of my own contemporaries, working in politics, journalism and education, are similarly ignorant of the facts. According to the World Health Organization (WHO), roughly one-third of the world's population are infected with tuberculosis bacilli, with a new infection occurring every second. Of those with latent tuberculosis, one in 10 will go on to get active disease; 9.4 million people in 2008. In 2007, according to estimates, $1.1 billion went into research and development funding for HIV and malaria, which led to an estimated 863,000 deaths in 2008,1 received $468.5 million; tuberculosis, meanwhile, received just $410.4 million.2 Drug resistance is spreading, with half a million people now infected with MDR-tuberculosis. Extensively drug-resistant (XDR) tuberculosis is an even more frightening phenomenon. At the start of this year, 58 countries had reported cases of XDR-tuberculosis and many more countries cannot survey the extent of drug resistance due to inadequate laboratory facilities.3 The medications used to treat tuberculosis have barely changed since the 1970s and are associated with side-effects which threaten adherence. Treatment is over an extended period with high levels of morbidity and money is needed for medical, social and psychological support.

BACKGROUND--Evidence from the United States has shown that tuberculin sensitivity increases with length of stay among residents in homes for the elderly, implying an increasing risk of infection. There is no evidence as to whether or not residents in homes in the United Kingdom have a similar risk. METHODS--A study was undertaken to determine whether residence in a home for the elderly increases the risk of tuberculosis infection. Over a six month period all residents in homes for the elderly in Liverpool received a tuberculin test. A health questionnaire was completed by the field team for each resident. A total of 2665 residents in homes for the elderly were surveyed. RESULTS--Heaf test grade positivity declined with age, the odds ratio being 0.71 for each 10 year period. Adjusting for age, there was no change in Heaf test grade with length of stay in the home. Heaf test positivity was stronger in smokers (odds ratio 1.59) than ex-smokers (odds ratio 1.20) and non-smokers. Heaf test grade positivity was directly related to pack years. Allowing for age and smoking, the odds ratio for men compared with women for a positive test was 1.62 (95% confidence interval 1.32 to 1.99). CONCLUSIONS--Heaf test positivity declines with age. Residence in a home for the elderly is not associated with increased rate of tuberculosis sensitivity. Smoking and male gender is associated with increased Heaf test positivity.

To assess the efficacy of weekly zinc or zinc plus retinol as adjuncts for the treatment of pulmonary tuberculosis. Double-blind, randomized, placebo-controlled trial in 350 patients15 years old with smear-positive tuberculosis in Nigeria (ISRCTN36636609). In addition to antituberculous treatment, patients were randomly allocated to weekly supplements of zinc (90 mg), zinc plus retinol (5000 IU) or placebos for 6 months. Primary outcomes were time to sputum smear conversion and resolution of radiographic abnormalities.After 8 weeks of treatment, 68% had achieved sputum smear conversion, and the median conversion time was 6.5 weeks. Hazard ratios (HR, 95%CI) for sputum conversion relative to the placebo group were not significant for zinc (1.07, 0.92-1.29) or zinc plus retinol (0.89, 0.76-1.07). Significant predictors of time to sputum conversion were lung abnormality score, sputum smear grade, age and serum C-reactive protein. HIV co-infection and gender were not independent predictors of time to sputum conversion. There were no significant differences between supplement groups in clinical, radiological or laboratory outcomes at 2 months or 6 months. There were 9, 9 and 2 deaths in patients receiving zinc, zinc plus retinol or placebos, respectively. Mortality in those who received zinc (HR 1.71, 0.88-3.58) or zinc plus retinol (HR 1.54, 0.78-3.26) did not differ significantly from those who received placebos. Most deaths occurred in patients co-infected with HIV. Supplementation with zinc or zinc plus retinol did not lead to better outcomes than placebos, and caution is warranted regarding routine micronutrient supplementation, particularly in patients co-infected with HIV.

Although tuberculosis (TB) has its highest burden among young adults, especially since the advent of HIV infection, two other groups with low immunity, the very young (1 year) with immature immunity and the elderly (65 years) with waning immunity, are vulnerable groups not to be forgotten. This review describes the epidemiology, clinical aspects, public health aspects and outcome of TB in patients at the extremes of age. The epidemiology differs therein that TB in infants occurs in developing countries with high incidences of TB and HIV, while TB in the elderly occurs in developed countries with ageing populations. The clinical presentation may be non-specific, history of contact with TB is often not known and TB is often not considered at these age extremes, and when the diagnosis is considered, disease progression may already be advanced. Anti-TB treatment regimens are the same as in other age groups, but drug dosages may need adjustment according to weight, renal function, liver function and other potentially complicating factors. Adverse events are more difficult to observe and both the young and the elderly are reliant on others for adherence to treatment. Mortality at both age extremes is higher than in the general TB population. For all the above reasons, public health measures to: prevent transmission of infection; identify those infected and providing preventive therapy; high index of suspicion in order to make an early diagnosis; and timely initiation of treatment are important in both the very young and the elderly.

Guidelines have been compiled by the Joint Tuberculosis Committee of the British Thoracic Society for the prevention and management of Mycobacterium tuberculosis infection and disease in patients with all grades of renal impairment.

Objective. To describe the yield of smear-microscopy and radiological findings by male and female patients with symptoms of tuberculosis in Abuja, Nigeria.Methods. Patients ≥15 years old with cough for >3 weeks submitted 3 sputum samples for smear microscopy. One specimen was cultured using MGIT-960. All patients had lung X-rays and screened for HIV.Results. were more likely to be smear-positive than females (262/774 [34%] and 137/547 [25%],P<.01), but similar proportions of males and females were culture-positive (437/691 [63%] and 294/495 [59%],P=.09). 317/626 (50.6%) males and 249/419 (59.4%) females were HIV-positive (P<.005). Among culture-positives patients, HIV-infected males were less likely to have positive smears than HIV-negative males (49.2% versus 66%,P=.001). Among females, smear positivity did not vary with HIV (46.4% for HIV-positive and 52.9% for HIV-negative,P=.38). Of 274 culture-confirmed TB cases, 226 (82.5%) had cavities, and 271 (99%) had ≥1 lung areas affected. HIV-positive males were more likely to have lung cavities than HIV-positive females (85% versus 69%,P<.04) and to have ≥3 lung areas affected (P=.03).Conclusion. Differences in the yield of smear-microscopy, culture and X-rays on presentation are due to several factors including HIV coinfection and gender.

Mayfield’s plea for the return of universal BCG to the UK deserves a serious response.1 The problem with the government’s decision to discontinue routine BCG in UK teenagers was its timing. It was announced on 6 July 2005, the day before 7/7. The reasons for the policy change were therefore not properly made …

So far the United Kingdom seems to be keeping clear of most of the international increase in drug resistant tuberculosis, in particular multidrug resistant tuberculosis (MDR-TB).1 2 But how long can this be maintained?3 The problem with drug resistant tuberculosis is that it is still relatively uncommon but gradually increasing. …

Background: Nucleic acid amplification tests (NAAT) based on PCR provide rapid identification of Mycobacterium tuberculosis and the detection of rifampicin resistance. Indications for their use in clinical samples are now included in British tuberculosis guidelines. Methods: A retrospective audit of patients with suspected mycobacterial infection in a Liverpool hospital between 2002 and 2006. Documentation of the impact of NAAT usage in acid fast bacillus (AFB) microscopy positive samples on clinical practice and the influence of a multidisciplinary group on their appropriate use, compared with British guidelines. Results: Mycobacteria were seen or isolated from 282 patients and identified as M tuberculosis in 181 (64%). NAAT were indicated in 87/123 AFB positive samples and performed in 51 (59%). M tuberculosis was confirmed or excluded by this method in 86% of tested samples within 2 weeks, compared with 7% identified using standard methods. The appropriate use of NAAT increased significantly over the study period. The NAAT result had a clinical impact in 20/51 (39%) tested patients. Culture results suggest the potential for a direct clinical impact in 8/36 (22%) patients in which it was indicated but not sent and 5/36 (14%) patients for whom it was not indicated. Patients managed by the multidisciplinary group had a higher rate of HIV testing and appropriate use of NAAT. Conclusions: There were significant clinical benefits from the use of nucleic acid amplification tests in this low prevalence setting. Our data suggest that there would be additional benefit from their use with all AFB smear positive clinical samples.

Our aim was to describe the frequency of HIV infection among patients with tuberculosis and compare their characteristics with patients with TB but not infected with HIV. Patients with cough3 weeks duration attending 8 hospitals in Abuja, Nigeria were screened with smear microscopy and culture and tested for HIV. Chest X-rays were graded by 2 readers. 731 (62%) of 1186 patients had positive cultures and 353 (48%) of these 731 patients were smear positive. 1002 (85%) patients were tested for HIV and 546 (55%) were positive. 53% (329/625) of the culture positive patients and 58% (217/377) of the culture negative patients were HIV positive. Anorexia, weight loss, low BMI (18.5), haemoglobin (11 gm/dl) and albumin and high ESR and liver enzymes were more frequently observed among patients with TB coinfected with HIV than in patients without HIV. Coinfected patients had less cavitations and lung involvement on X-rays than patients without HIV. In conclusion, the prevalence of HIV is very high among patients with TB in Abuja, Nigeria. The presence of HIV decreases the sensitivity of smear microscopy and complicates the diagnosis of TB. Selected clinical and laboratory parameters could be used to identify individuals with TB who are likely to be coinfected with HIV.

The bleach digestion of sputum may improve the yield of smear microscopy but has not been validated in patients with HIV. Therefore we assessed the performance of bleach-digested smear microscopy among patients with HIV. One thousand three hundred and twenty one patients with chronic cough submitted three sputum samples for direct smear microscopy and were offered HIV tests. One sample was selected for a bleach-digested smear and another one was cultured. Patients were classified as having 'definite' (>= 2 positive smears), 'very likely' (smear-negative, culture- positive), 'less likely' (one smear-positive, culture-negative) and 'unlikely' (smear and culture negative) tuberculosis (TB). In all, 566/1045 (54%) patients were HIV positive and 731/1186 (62%) were culture positive. The digested smears were positive in 123/125 (98%) 'definite', 4/118 (3%) 'very likely' and 1/174 'unlikely' TB patients with HIV and in 125/127 (98%) 'definite', 2/74 (3%) 'very likely', 4/4 'less likely' and 2/127 'unlikely' TB without HIV. Three direct smears identified 252 (57%) and one digested smear 254 (57%) of the 444 patients with 'definite' or 'very likely' TB. One bleach-digested smear performed similarly to three direct smears. Both methods were less sensitive in HIV-positive patients. Further studies are needed to compare the performance of the two methods under operational conditions. (c) 2007 Elsevier Ltd. All rights reserved.

Soon after my appointment to a consultant post in Liverpool I made a domicilliary visit to a lady who addressed me as Mister. I took it upon myself to give her a short homily as to why I should be addressed as Doctor, pointing out that only surgeons, who were really trumped up barbers, assumed the title Mister on gaining their surgical qualification. Furthermore, I added that the medical or physicians' qualification went back over 2000 years and that the Hypocratic oath forbade us from cutting ‘even for the stone’. I was rather proud of myself for such a clear didactic account of how we physicinas should be addressed until her daughter came into the room. ‘Let me introduce you to Dr Davies,’ said my patient, ‘he's not a Mr yet.’ Since then I have been content with any title my patients may wish to confer on me.

The risk of developing tuberculosis is dependent on both the risk of being infected and the risk of infection leading on to active disease. The former will depend on the incidence of tuberculosis in the community where the individual lives or works. The latter will depend on many factors impinging on the individual both genetic and environmental. The greatest single risk factor for developing tuberculosis from infection is concurrent HIV infection. Where these two infections are prevalent tuberculosis case rates have risen dramatically and will continue to do so unless either infection can be curtailed.

EDITOR—Richards and Tumwine ask for discussion on the subject of poor countries making the best teachers.1 When will the postgraduate tutors and royal colleges recognise that medical experience in developing countries should be counted towards …

Summary Background Smear microscopy is relatively insensitive for the diagnosis of TB. The digestion of sputum with household bleach prior to smear preparation has been reported to improve its sensitivity. This method has not been validated. Methods Seven hundred and fifty six patients with symptoms suggestive of pulmonary TB (PTB) were asked to submit 3 sputum specimens for direct microscopy. One specimen was selected at random for culture and another specimen was digested to prepare a further smear. The WHO case definition (⩾2 positive smears or one positive smear and positive culture) was used to compare the sensitivity and specificity of the smears. Findings Four hundred and fifty five (60%) patients were culture-positive. Of these, 235 (31%) had “definite” PTB and 223 (29%) “very likely” PTB (smear-negative, culture-positive). The WHO case definition identified 51% (235/458) of the patients with “definite” or “very likely” PTB. One digested smear detected 219 (93%) of the 235 patients with “definite” PTB and 10 patients with “very likely” PTB (sensitivity (95%CI) 50% (45–55%); specificity 99% (97–100%)). The positive and negative predictive values for one digested smear were 98% (95–99%) and 56% (52–60%) respectively, which were not different ( p > 0.5 ) to the WHO case definition (100% and 57%, respectively). Interpretation One bleach-digested smear is as sensitive and specific as the WHO case definition for the diagnosis of PTB.

Directly Observed Therapy Shortcourse (DOTS) is composed of five distinct elements: political commitment; microscopy services; drug supplies; surveillance and monitoring systems and use of highly efficacious regimens; and direct observation of treatment. The difference in the way the term 'DOTS' as defined by WHO and interpreted by many observers has led to some misunderstanding. WHO generally uses the term to mean the five components of DOTS. But the word 'DOTS' is an acronym for Directly Observed Therapy Shortcourse. Many workers therefore interpret DOTS purely as direct supervision of therapy. DOTS is not an end in itself but a means to an end. In fact it has two purposes, to ensure that the patient with tuberculosis (TB) completes therapy to cure and to prevent drug resistance from developing in the community. The main criticism of DOTS rightly derives from the fact that some properly conducted randomized, controlled trials of directly observed therapy with or without the other components have shown no benefit from it. The problem is that it is impossible to design a study of modern directly observed therapy against the previous self-administered, poorly-resourced programs. As soon as a study is implemented, the attention to patients in the control (non-directly observed therapy) arm inevitably improves from the previous non-trial service situation. What is of concern is that in some trials less than 70% cure rates were achieved even in the direct observation arm. With no new drugs or adjuvant treatment available to bring the length of treatment down to substantially less than 6 months, DOTS offers the best means we have at our disposal for TB control.

After more than a century of decline, in the mid 1980s tuberculosis began to increase in some developed countries. Health care workers were then forced to look to the developing world, where they found tuberculosis to be out of control, in many countries. It is now appreciated that tuberculosis is not only increasing globally but is likely to do so beyond the next decade for three principal reasons. First, demographically as the expected population increase will be greatest in areas of the world where tuberculosis is most prevalent, particularly middle Africa and South Asia. Secondly, the increase of HIV, which renders the host uniquely susceptible to tuberculosis, is occurring in the same areas of the world and is already causing an increase in tuberculosis case rates of up to tenfold. Thirdly, as more and more people are forced to live in poverty, where poor nutrition and crowded conditions lead to the spread of tuberculosis, the disease risk will be compounded. Sound medical management, particularly the use of the five components of directly observed therapy, will relieve the situation. But until world conditions of poverty and HIV spread are addressed, it is unlikely that tuberculosis can be controlled.

Introduction Recent data from The Health Protection Agency (HPA) UK indicates a further rise in the incidence of TB and about 15% cases of newly diagnosed cases of TB occur in those aged =65. Within the indigenous white population in the UK, it is the elderly population in whom TB is principally an issue. In contrast to previous studies looking at TST positivity, the application of IGRAs to detect infected cases of TB across various ethnic groups has not yet been reported. In addition to further quantify TB infection in the UK white population, this study also looked at IGRA positivity in the elderly population. Methodology Retrospective study of IGRAs which were performed in cases where latent or active TB was suspected. Data were collected from regional IGRA database and individual hospital audit departments were approached to obtain ethnicity data. Results Ethnicity data was available in 575/1119 cases and comprised 482 white British, 26 Asian/Asian British, 34 black/black British and 33 other. IGRAs results in the UK population are shown in the Abstract P16 table 1 below: The difference in the prevalence of a positive IGRA between the ethnic groups was statistically significant (p Conclusions IGRA positivity was found to be lowest in the white British population compared with other ethnic groups. Interestingly, of the UK indigenous white elderly population almost 1/3 are infected with TB (latent or active) highlighting significant disease burden among older age groups. With IGRAs heralded as the more specific and reliable diagnostic test, such results may aid future planning and policy making for the management of TB in the UK.

The caseload of tuberculosis in developing countries is increasingly associated with the elderly. This is possibly due to increased longevity today and a change in the lifetime risk of tuberculosis within birth cohorts. Published data for tuberculosis notifications for Hong Kong and England and Wales have been used to calculate age-specific rates of disease by different age groups for different birth cohorts. In Hong Kong, each birth cohort showed a similar pattern of disease by age, with rates peaking in the 25 to 39-yr age groups and gradually declining thereafter. After 1978, regardless of age at that time, all age cohorts showed an increase in tuberculosis rates with increasing age. This trend was more marked in males than females. A similar pattern was seen for birth cohorts in England and Wales except that the peak occurred earlier in life (before 25 yr of age) and the decline with age ceased in 1984. Thereafter, rates increased in males born before 1930 but showed only a leveling off in females. If these data represent a true increase in tuberculosis rates, rather than resulting from a change in reporting accuracy and completeness, the burden of tuberculosis in the elderly is likely to continue to increase substantially.

BACKGROUND: Tuberculin testing remains the standard method for assessing infection due to tuberculosis in the UK. However, there are no data on the incidence of tuberculin positivity among the general adult population in the UK and consequently interpretation of Heaf test results is often difficult. METHODS: During the investigation of an outbreak of tuberculosis in a Liverpool social club 198 members were interviewed and Heaf tested and 171 members of a second social club in Liverpool were similarly screened as a control group. Comparisons between the results from the two populations provided both an estimate of baseline Heaf test positivity in indigenous white adults from a British inner city population, and a measure of the effect on this baseline of recent exposure to tuberculosis. RESULTS: In both club populations the proportion of positive Heaf tests increased with age. Independent of age, the tuberculosis exposed population had a higher proportion of positive Heaf grade results (40.9%) than those in the control group (26.9%). Multivariate analysis confirmed both the differences in Heaf results between clubs and between age groups but identified no other behavioural or medical factors which affected Heaf test results. CONCLUSIONS: Heaf test positivity increases with age at least up to 54 years, and recent exposure to tuberculosis increases the proportion of positive Heaf tests in each age group. Interpretation of positive Heaf tests when assessing the effects of a tuberculosis outbreak should take account of background levels of Heaf positivity.

BACKGROUND--Although mortality from tuberculosis has continued to fall in recent years, there has been little change in the case fatality rate for tuberculosis over the same period. This has previously been shown to be due to the increasing proportion of cases of tuberculosis occurring in the elderly. Tuberculosis mortality and case fatality were therefore analysed to determine if this disappointing trend in case fatality rate has occurred from disease in all or only certain sites. METHODS--A retrospective analysis of the tuberculosis mortality and case fatality rates in England and Wales for the period 1972-92 was carried out. The average annual percentage change in tuberculosis was calculated for each disease site and by age group and the results were compared. RESULTS--The analysis showed that, although the mortality rate fell steadily by 5.6% per annum, the case fatality rate decreased by only 0.9% (95% CI -1.7 to -0.1) per annum. The case fatality rate for respiratory and central nervous system disease declined, but no decline in tuberculosis at "other" sites was observed (1.01% (+2.2 to -0.2) for all age groups combined). In the group aged 75 and over, however, the proportion of deaths due to disease at other sites increased by 3.2% (2.2 to 4.3) per annum whilst in the other age groups the mortality rate declined. CONCLUSIONS--This analysis suggests that clinicians may be becoming less able to recognise non-respiratory presentations of tuberculosis, particularly in the elderly, and underlines the need to consider tuberculosis as a diagnosis to avoid delay in treatment.

Summary Setting: A retrospective study of tuberculosis notifications in England and Wales published by the Office of Population Censuses and Surveys. Objective: To analyse the rise in tuberculosis notifications in England and Wales by different sub groups over the time period 1982–91. Design: The average annual percentage change in tuberculosis notification rates (per 100 000) for the groups were analysed by age, sex, standard region and disease site. Results: The average annual increase in tuberculosis notifications from 1987–91 in females was +2.55 (95% confidence interval [CI] 0.5–4.7); males showed no significant change (−0.6%, 95% CI: −2.9 to +2.7). The increase was greater in younger subjects: 3.2% in females aged 25–44 (95% CI 0.9–5.5) and 4.3% in males aged 15–24 (95% CI 1.7–6.9). Only three standard regions showed an increase: the South East, the West Midlands, Yorkshire and Humberside. This increase was significant only in females from the South East, and was predominantly in non-respiratory tuberculosis. Conclusion: The rise in tuberculosis notification rates from 1987–91 has been predominantly in females, in those under 65, has occurred in 3 regions, and predominantly in non-respiratory tuberculosis. The analysis highlights some of the inadequacies of the present notification system for tuberculosis.

Standard short-course regimens for tuberculosis are used worldwide with very few problems. Unfortunately, the emergence of multiple drug-resistant tuberculosis in many parts of the world is leading to a diversification of drug regimens and to the use of drugs that are more toxic per se and more likely to interact with others. In addition, the treatment of HIV/AIDS patients with tuberculosis or disease due to Mycobacterium avium-intracellulare complex (MAC) infection with new drugs and multidrug regimens has added to the problem of drug interactions, especially as such patients may often be receiving concomitant treatment for a range of bacterial, fungal and viral infections. In general, there are very few clinically significant interactions between the first-line antituberculosis drugs themselves, although problems of bioavailability, notably of rifampicin (rifampin), have been encountered in the manufacture of combination tablets. Of the first-line drugs used to treat tuberculosis, i.e. rifampicin, isoniazid and pyrazinamide, rifampicin is particularly likely to cause clinically significant drug interactions as it is a potent inducer of the cytochrome P450 enzyme group, which is involved in the metabolism of many drugs, in particular oral contraceptives, corticosteroids, oral anticoagulants and cyclosproin. The use of quinolones to treat multiple drug-resistant tuberculosis and AIDS-related MAC disease raises further problems of drug interactions as, in contrast to rifampicin, these drugs inhibit some cytochrome isoenzymes, leading to reduced metabolism of certain drugs.

OBJECTIVE--To examine whether the historical link between tuberculosis and poverty still exists. DESIGN--Retrospective study examining the notifications of all forms of tuberculosis by council ward over a six year period and correlating this with four indices of poverty; council housing, free school meals, the Townsend overall deprivation index, and the Jarman index. SETTING--The 33 electoral wards of the city of Liverpool. SUBJECTS--344 residents of Liverpool with tuberculosis. RESULTS--The rate of tuberculosis was correlated with all measures of poverty, the strongest correlation being with the Jarman index (r = 0.73, p < 0.0001). This link was independent of the high rates of tuberculosis seen in ethnic minorities. CONCLUSION--Tuberculosis remains strongly associated with poverty.