• Tuberculosis

The number of cases of active tuberculosis (TB) continues to rise in the UK and in many other parts of the world.1 2 In analysing the reasons behind this rise, it needs to be kept in mind that only a small proportion of those who become infected with TB will progress to become ill with active TB disease in the weeks and months after infection. They do, however, remain at risk of reactivation of their latent TB infection in the years (and indeed decades) to come. Clearly, a co-existing medical condition which impairs the immune response to the TB bacterium might increase the likelihood of direct progression to active disease shortly after infection, or increase the likelihood of latent TB infection in later life. Co-infection with HIV is a striking example; the relative risk of developing TB in HIV-positive individuals compared with HIV-negative individuals (the incidence rate ratio) is between about 20 and 35.2

In this issue of Thorax, Walker and Unwin (see page 578) consider the impact on numbers of TB cases in England of another increasingly common condition—namely, diabetes mellitus.3 A link has long been suggested, the authors pointing out that combined clinics for those with diabetes and TB were being held more than half a century ago,4 and recent analyses suggest that the association is indeed genuine.5 Walker and Unwin focus their attention on pulmonary TB, choosing this because they consider the evidence for an association to be strongest for this type of TB. They constructed an epidemiological model using data on the incidence of TB, the prevalence of diabetes, the population structure and data on the age-specific relative risk of TB associated with diabetes from a cohort study. They acknowledge that there are limitations to their approach: the estimate of the total prevalence of diabetes in England is based on old and relatively small population-based studies and the age-specific relative risks for TB in those with diabetes are derived from a Korean study. The authors point out, however, that these appear to be the best tools available for the job they wished to do, and it is indeed arguable that a line of scientific enquiry should not be ignored simply because the available techniques for its investigation are as yet imperfect.

With the frank admission that ‘given the nature of the data available, considerable uncertainty surrounds these estimates’, the authors go on to suggest that the population attributable fraction (PAF) of diabetes for pulmonary TB in England is 19.6% for Asian men (95% CI 10.9% to 33.1%) and 14.2% for Asian women (95% CI 7.1% to 26.5%). The figures for white and black men are similar to each other at around 7%, and about 8.5% for white and black women. Expressed differently, the authors estimate that about 11% of the new cases of pulmonary TB which occurred in England in 2005 may be attributed to diabetes.

These figures are—or should be—of even greater concern than they may appear. It is pulmonary TB which is potentially infectious to others, and public health efforts to control TB have focused on the early identification and treatment of infectious pulmonary cases. Perhaps more importantly, we are confronted with an explosive and apparently inexorable rise in the prevalence of diabetes.6 7 This rise in diabetes is, moreover, particularly marked in ethnic minority populations8—that is, those who are in any case most at risk of having pre-existing latent TB infection and of fresh exposure to other infectious cases. It is also associated with a sharp rise in the numbers of individuals with chronic renal failure, an independent risk factor for TB.9 Even if the figures from Walker and Unwin are an overestimate, it seems likely that they soon won't be. If they are already an underestimate, then the interaction between diabetes and TB is rapidly becoming a major issue for TB control and one which, as the authors point out, appears to be receiving little attention. Diabetes does not achieve a mention in the ‘TB Action Plan’10 nor, indeed, in the 2009 Annual Report.1

What can be done? TB services in most countries—even wealthy ones—are hard pressed, and tackling the rising tide of obesity (the principal cause of the rise in diabetes) may be a task too far. This means dealing with the consequences while others struggle, probably unsuccessfully, with the underlying cause. Walker and Unwin suggest that, based on their figures, around one-third of Asians with newly diagnosed TB in England will have diabetes. There seems no reason to suspect that the figure would be markedly lower in other parts of the UK nor, probably, in other socioeconomically similar countries. In the UK there are probably around half a million undiagnosed diabetics11 and, although their rates of TB may well be less than among diagnosed diabetics, we can at least ensure that newly diagnosed TB patients have a documented assessment of the presence or absence of diabetes. Active screening for evidence of latent TB in diabetics is part of US guidelines,12 but not those from the National Institute for Health and Clinical Excellence (NICE).13 Indeed, the NICE guidelines suggest that, although the relative risk of TB is increased in diabetics, the absolute risk of TB in diabetics is sufficiently low that there is no need to educate them about symptoms suggestive of disease (section 10.2.4 of the NICE guidelines).

Given the calculations set out in Walker and Unwin's paper in this issue of Thorax, these two issues—specific screening for latent TB in diabetics and health education regarding TB—are ones which should be reviewed by NICE or another expert group. Indeed, an expectation that those healthcare professionals who deal with diabetic patients should educate them about the symptoms suggestive of TB would mean that the professionals themselves would have to have the possibility of TB in mind, and this secondary effect may actually turn out to be of more importance than the apparent primary aim of such education. Whatever steps are taken, it seems highly likely that, at least for the foreseeable future, TB services will be managing increasing numbers of diabetics with tuberculosis.