Prior estimates of DALYs lost from TB included negative health effects from YLD-acute, and years-of-life-lost, but did not include YLD-chronic [2, 14–16, 20, 22, 23]. Using methods recommend by the World Bank and used by Murray et al in the Global Burden of Disease Study we estimated the burden of TB including YLD-chronic. In the urban area of Tarrant County, Texas, with reported 0.06/1000 incidence of TB , we calculated the burden to be 0.37 DALYs lost /1000 population, per year. Prior estimates of the TB burden in areas with similar TB incidence, using the same methods but only measuring YLD-acute and years-of-life-lost were 0.07 DALYs lost /1000 population, per year [3, 16, 20]. Our data from this study show that disability is a major component of TB burden, and that prior estimates of the DALYs lost from TB accounted for only 25% of the total loss (table 2; figure 1).
Each occurrence of pulmonary TB illness results in both YLD-acute and YLD-chronic from pulmonary sequelae. We found that only 2% of the TB burden resulting was due to acute disease. This YLD-acute estimate was similar to previously reported WHO estimates of TB burden (approximately 0.1 DALY per case for areas with very low adult and child mortality) [16, 20].
Prior estimates of DALYs lost to TB do not consider pulmonary impairment after tuberculosis. Pulmonary impairment after tuberculosis is a common, life-long condition [8–10], Vecino ME, Pasipanodya JG, Slocum PC, Bae S, Munguia G, Miller TL, Drewyer G, Weis SE. 2010]. Evidence for chronic lung impairment in patients cured of tuberculosis; Submitted]. Nearly 60% of patients have measurable impairment after microbiological cure that ranges from mild impairment to severe disability [8–10]. Exclusion of YLD-chronic from previous TB burden estimates has led to recommendations that are incompletely informed, namely that when TB incidence is stable or declining in a population, passive intervention is more cost-effective than active case finding or treatment of latent TB infection [4, 33–35]. Such arguments support reduced resource allocation for TB programs and that policy action may have contributed to resurgence in U.S. TB incidences seen in the early 1990s. Exclusion of PIAT in estimates of TB burden undervalues the cost-effectiveness of TB prevention activities leading to inadequate resources allocated to prevention .
Mortality due to TB is an important component of the overall burden [1–5, 14]. Years-of-life-lost accounted for 1.55 of the total 6.72 DALY lost per TB patient (table 2). Previous estimates of the TB burden from low-incidence areas reported 0.85 DALY lost from years-of-life-lost per TB patient [16, 20]. We believe the higher years-of-life-lost found in this analysis was due to our study population including only culture-confirmed TB. Clinical cases of TB are less likely to suffer mortality and their inclusion would have lowered years-of-life-lost . The relationship between illness-related mortality and disability is often expressed as YLD: YLL ratio and has been used to estimate DALYs lost from TB [19, 21]. This ratio can be used to estimate disability from an illness in a community from mortality statistics. We found the YLD: YLL ratio for TB to be 3.34. When this ratio was calculated for TB without including YLD-chronic, the ratio was 0.08. Not including YLD-chronic would have resulted in YLD: YLL ratios that would have underestimated the TB burden. Additionally these data demonstrated that in low-incidence countries TB causes more DALYs lost from disability than death.
The use of DALY to assess TB burden highlights previously recognized TB racial disparities that are less apparent when either notification or mortality rates alone are used . Figure 3 illustrating the TB burden in the <5 years age group is consistent with recent TB transmission to children among non-Caucasians. Substantial health loss occurred to other racial groups at earlier ages than to Caucasians in our cohort, a disparity that has social and other implications, and indicates that practices to reduce transmission or to prevent mortality may yield disproportionate benefits to these populations. Ranking burden of disease by DALY loss gives information beyond the usual disease descriptors of incidence, mortality, and age at illness. As an illustration of the added information from using DALY to calculate disease burden is aseptic meningitis. Aseptic meningitis is far more common in Tarrant County than TB. However mortality and long-term sequelae are extremely rare. Therefore the disease burden measured in DALY loss from aseptic meningitis is much less than that due to tuberculosis. Without combining the disease incidence, mortality, and impairment into a single number, it is difficult to compare the respective disease burdens from the two diseases.
There are emerging technologies for diagnosis and treatment of TB that are close to clinical implementation. These include the use of gamma interferon release assays to diagnose LTBI, isoniazid and rifapentine to shorten treatment of LTBI, and moxifloxacin containing regimes to shorten treatment of active TB . These data suggests that the greatest health savings may be achieved through strategies to prevent TB rather than strategies to shorten its treatment.
This study gives insight into their potential effect on health lost from TB. Interventions that result in more persons completing LTBI therapy will prevent 6.72 DALY per case of TB averted. In contrast, interventions for shortening treatment of TB would result in little DALYs saved. Reducing TB treatment duration by 50% would have minimal effect on TB burden, as it would save <0.02 DALYs per patient. In addition shorter TB treatment duration, assuming current costs of between US$5 and US$350 per DALY gained, would not reduce the chronic pulmonary impairment associated with TB [8–10, 33]. If preventing pulmonary impairment after tuberculosis is considered, costs of current standard latent tuberculosis infection therapy (daily isoniazid for 9 months) falls to under US$2500 per DALY gained. The benefit of treating latent tuberculosis infection becomes comparable to those of treating non-infectious TB .
The use of discounting in economic health evaluations and appropriate discount rates are controversial [13, 18, 32, 37–39]. We analyzed our results using the discount rate recommend by the CDC and the U.S Preventive Services Task Force (USPSTF) of 3% [13, 14, 32]. Irrespective of the discount rates used the present value of DALYs lost to the cohort was significantly greater than previous estimates. To improve the validity and precision of the TB burden estimates, we tested disability weights derived directly from the same TB-afflicted population in sensitivity analysis . Using these locally derived disability weights did not change our conclusions. This analysis indicates that the increased TB burden identified in this study is independent of the discount rates or disability weight used.
There are limitations to these estimates. We did not adjust for co-morbidity including relapses, re-infections drug-resistance, or acquired immuno-deficiency syndrome (AIDS). Additionally these results should be considered a conservative measure of tuberculosis burden, as they do not include the contribution of clinical or extra pulmonary tuberculosis or possible excess mortality after cure. In addition, current DALY computation does not weigh-in the effects of epidemiological parameters other than age and gender. Pediatric and adolescent TB are infrequent in Tarrant County, as in other low-incidence areas; we were therefore unable to adequately test the effects of age or the interaction of age and ethnicity in the final analysis.
Even though the DALY is widely used and possibly one of the best ways to quantify and estimate measurement of morbidity and mortality for a given disease in a population; there has been controversy over the appropriateness of its use in the past especially when applied to certain disadvantaged communities . For example, DALY assumptions are limited when applied to societies that have clearly different life-tables from Japan [14, 28, 30]. We found a 14% difference in tuberculosis burden when DALY was calculated using Texas life tables (figure 4). For comparison of local burden disease, certainly use of local life tables would account for this important difference. One of the aims of this study was comparison of tuberculosis burden with or without inclusion of PIAT using prior established methods. When these data are combined PIAT contributed significantly to overall tuberculosis burden. Differential age weights would increase importance of pediatric and adolescent mortality [14, 21]. While the results are from a single geographic area we included consecutive subjects within the defined period to reduce selection bias and the population was heterogeneous. As a result we feel that despite these limitations the results are representative of the TB burden in similar populations.