Thaddeus L. Miller

Personal and Societal Health Quality Lost to Tuberculosis

Background In developed countries, tuberculosis is considered a disease with little loss of Quality-Adjusted Life Years (QALYs). Tuberculosis treatment is predominantly ambulatory and death from tuberculosis is rare. Research has shown that there are chronic pulmonary sequelae in a majority of patients who have completed treatment for pulmonary tuberculosis (PTB). This and other health effects of tuberculosis have not been considered in QALY calculations. Consequently both the burden of tuberculosis on the individual and the value of tuberculosis prevention to society are underestimated. We estimated QALYs lost to pulmonary TB patients from all known sources, and estimated health loss to prevalent TB disease. Methodology/Principal Findings We calculated values for health during illness and treatment, pulmonary impairment after tuberculosis (PIAT), death rates, years-of-life-lost to death, and normal population health. We then compared the lifetime expected QALYs for a cohort of tuberculosis patients with that expected for comparison populations with latent tuberculosis infection and without tuberculosis infection. Persons with culture-confirmed tuberculosis accrued fewer lifetime QALYs than those without tuberculosis. Acute tuberculosis morbidity cost 0.046 QALYs (4% of total) per individual. Chronic morbidity accounted for an average of 0.96 QALYs (78% of total). Mortality accounted for 0.22 QALYs lost (18% of total). The net benefit to society of averting one case of PTB was about 1.4 QALYs. Conclusions/Significance Tuberculosis, a preventable disease, results in QALYs lost owing to illness, impairment, and death. The majority of QALYs lost from tuberculosis resulted from impairment after microbiologic cure. Successful TB prevention efforts yield more health quality than previously thought and should be given high priority by health policy makers. (Refer to Abstracto S1 for Spanish language abstract)

Pulmonary impairment after tuberculosis and its contribution to TB burden

BackgroundThe health impacts of pulmonary impairment after tuberculosis (TB) treatment have not been included in assessments of TB burden. Therefore, previous global and national TB burden estimates do not reflect the full consequences of surviving TB. We assessed the burden of TB including pulmonary impairment after tuberculosis in Tarrant County, Texas using Disability-adjusted Life Years (DALYs).MethodsTB burden was calculated for all culture-confirmed TB patients treated at Tarrant County Public Health between January 2005 and December 2006 using identical methods and life tables as the Global Burden of Disease Study. Years of life-lost were calculated as the difference between life expectancy using standardized life tables and age-at-death from TB. Years lived-with-disability were calculated from age and gender-specific TB disease incidence using published disability weights. Non-fatal health impacts of TB were divided into years lived-with-disability-acute and years lived-with-disability-chronic. Years lived-with-disability-acute was defined as TB burden resulting from illness prior to completion of treatment including the burden from treatment-related side effects. Years lived-with-disability-chronic was defined as TB burden from disability resulting from pulmonary impairment after tuberculosis.ResultsThere were 224 TB cases in the time period, of these 177 were culture confirmed. These 177 subjects lost a total of 1189 DALYs. Of these 1189 DALYs 23% were from years of life-lost, 2% were from years lived-with-disability-acute and 75% were from years lived-with-disability-chronic.ConclusionsOur findings demonstrate that the disease burden from TB is greater than previously estimated. Pulmonary impairment after tuberculosis was responsible for the majority of the burden. These data demonstrate that successful TB control efforts may reduce the health burden more than previously recognized.

The Societal Cost of Tuberculosis: Tarrant County, Texas, 2002

PURPOSE Cost analyses of tuberculosis (TB) in the United States have not included elements that may be prevented if TB were prevented, such as losses associated with TB-related disability, personal and other costs to society. Unmeasured TB costs lead to underestimates of the benefit of prevention and create conditions that could result in a resurgence of TB. We gathered data from Tarrant County, Texas, for 2002, to estimate the societal cost due to TB. METHODS We estimated societal costs due to the presence or suspicion of TB using known variable and fixed costs incurred to all parties. These include costs for infrastructure; diagnostics and surveillance; inpatient and outpatient treatment of active, suspected, and latent TB infection (LTBI); epidemiologic activities; personal costs borne by patients and by others for lost time, disability, and death; and the cost of secondary transmission. A discount rate of 3% was used. RESULTS During 2002, 108 TB cases were confirmed in Tarrant County, costing an estimated

Evidence for chronic lung impairment in patients treated for pulmonary tuberculosis

40,574,953. The average societal cost per TB illness was

Longevity loss among cured tuberculosis patients and the potential value of prevention.

376,255. Secondary transmission created 47% and pulmonary impairment after TB created 35.4% of the total societal cost per illness. CONCLUSIONS Prior estimates have concluded that treatment costs constitute most (86%) TB-related expenditures. From a societal perspective treatment and other direct costs account for little (3.3%) of the full burden. These data predict that preventing infection through earlier TB diagnosis and treatment of LTBI and expanding treatment of LTBI may be the most feasible strategies to reduce the cost of TB.

Allopatric tuberculosis host–pathogen relationships are associated with greater pulmonary impairment

BACKGROUND Patients with pulmonary tuberculosis are likely to develop pulmonary impairment after tuberculosis (PIAT). The stability of PIAT and the relationship of PIAT to the duration of delay in tuberculosis diagnosis and treatment have not been fully characterized. METHODS We performed serial pulmonary function tests (PFTs) in a cohort treated for pulmonary tuberculosis after 20 weeks of tuberculosis therapy and again on or after treatment completion to determine the stability of PIAT. PFTs were compared with the duration of delay in tuberculosis diagnosis and treatment, as well as other demographic variables. RESULTS The median duration between the first and second tests was 15 (interquartile range 9-34) weeks. The mean change in FVC was -0.02l (95% confidence interval [CI] -0.09, 0.06), and the % predicted was -0.02 (95% CI -2.17, 2.12). FEV1 changes were 0l (95% CI -0.05, 0.06), and the % predicted was -0.11 (95% CI -1.82, 1.60). PIAT was not related to the duration of delay in tuberculosis diagnosis or treatment, age or smoking. CONCLUSIONS PIAT was not associated with the duration of delay in tuberculosis diagnosis and treatment and did not significantly change during follow-up. These data demonstrate that, for many individuals, the completion of tuberculosis treatment is the beginning, not the end, of their tuberculosis illness.

Mycobacterium Tuberculosis Infection, Immigration Status, and Diagnostic Discordance: A Comparison of Tuberculin Skin Test and QuantiFERON-TB Gold In-Tube Test Among Immigrants to the U.S.

BACKGROUND Evidence of substantial, quantifiable and preventable burdens of mortality hazard even after anti-tuberculosis treatment and cure would be a compelling, concrete, and useful measure of the value of prevention. METHODS We compared years of potential life lost between a cohort of 3 933 cured tuberculosis (TB) patients and 9 166 persons with latent tuberculous infection. We constructed a regression model to predict the expected years of potential life lost in each cohort and for demographic subgroups. RESULTS Among decedents, a history of fully treated TB is associated with a predicted average 3.6 more years of potential life loss than a comparable population without active TB. Greater longevity losses were predicted among those identified as White and Hispanic than among Black and Asian counterparts. CONCLUSION We found significant differences in predicted longevity of treated TB survivors relative to a similar group without active TB. These excess losses are substantial: a total of 14 158 life-years or the equivalent of more than 188 75-year lifespans. These findings illustrate an important opportunity cost associated with each preventable TB case - an average of 3.6 potential years of life. We conclude that substantial preventable mortality burdens remain despite adequate anti-tuberculosis treatment, a compelling rationale for more widespread and systematic use of prevention.

Mortality Hazard and Survival After Tuberculosis Treatment

BACKGROUND Host pathogen relationships can be classified as allopatric, when the pathogens originated from separate, non-overlapping geographic areas from the host; or sympatric, when host and pathogen shared a common ancestral geographic location. It remains unclear if host-pathogen relationships, as defined by phylogenetic lineage, influence clinical outcome. We sought to examine the association between allopatric and sympatric phylogenetic Mycobacterium tuberculosis lineages and pulmonary impairment after tuberculosis (PIAT). METHODS Pulmonary function tests were performed on patients 16 years of age and older who had received ≥20 weeks of treatment for culture-confirmed M. tuberculosis complex. Forced Expiratory Volume in 1 min (FEV1) ≥80%, Forced Vital Capacity (FVC) ≥80% and FEV1/FVC >70% of predicted were considered normal. Other results defined pulmonary impairment. Spoligotype and 12-locus mycobacterial interspersed repetitive units-variable number of tandem repeats (MIRU-VNTR) were used to assign phylogenetic lineage. PIAT severity was compared between host-pathogen relationships which were defined by geography and ethnic population. We used multivariate logistic regression modeling to calculate adjusted odds ratios (aOR) between phylogenetic lineage and PIAT. RESULTS Self-reported continental ancestry was correlated with Mycobacterium. tuberculosis lineage (p<0.001). In multivariate analyses adjusting for phylogenetic lineage, age and smoking, the overall aOR for subjects with allopatric host-pathogen relationships and PIAT was 1.8 (95% confidence interval [CI]: 1.1, 2.9) compared to sympatric relationships. Smoking >30 pack-years was also associated with PIAT (aOR: 3.2; 95% CI: 1.5, 7.2) relative to smoking <1 pack-years. CONCLUSIONS PIAT frequency and severity varies by host-pathogen relationship and heavy cigarette consumption, but not phylogenetic lineage alone. Patients who had disease resulting from allopatric-host-pathogen relationship were more likely to have PIAT than patients with disease from sympatric-host-pathogen relationship infection. Further study of this association may identify ways that treatment and preventive efforts can be tailored to specific lineages and racial/ethnic populations.

The value of effective public tuberculosis treatment: an analysis of opportunity costs associated with multidrug resistant tuberculosis in Latvia

Objective. We used a recent source of nationally representative population data on tuberculosis (TB) infection to characterize concordance between the tuberculin skin test (TST) and the QuantiFERON®-TB Gold In-Tube (QFT-GIT) blood test for immigrants in the United States. Methods. We used TB screening data from the 2011–2012 National Health and Nutrition Examination Survey to examine concordance between the TST and QFT-GIT—an interferon-gamma release assay (IGRA) blood test—for 7,097 U.S. natives, naturalized citizens, and noncitizens. Results. Consistent with prior findings, one in five immigrants in the survey was identified with latent TB infection (LTBI), a rate 14 times higher than for U.S. natives. We also found higher rates of discordant TST/IGRA results among immigrants than among U.S. natives. Unadjusted discordance between TST and IGRA was 3% among U.S. natives (weighted N=5,684,274 of 191,179,213) but ranged up to 19% for noncitizens (weighted N=3,722,960 of 19,377,147). Adjusting for age, sex, and race/ethnicity, noncitizens had more than nine times the odds of having a positive TST result but negative QFT-GIT result compared with U.S. natives. Conclusions. Our findings suggest that whether and how either of these tests should be deployed is highly context sensitive. Significant discordance in test results when used among immigrants raises the possibility of missed opportunities for harm reduction in this already at-risk population. However, we found little distinction between the tests in terms of diagnostic outcome when used in a U.S. native population, suggesting little benefit to the adoption and use of the QFT-GIT test in place of TST on the basis of test performance alone for this population.

Non-hispanic whites have higher risk for pulmonary impairment from pulmonary tuberculosis

OBJECTIVES We compared mortality among tuberculosis (TB) survivors and a similar population. METHODS We used local health authority records from 3 US sites to identify 3853 persons who completed adequate treatment of TB and 7282 individuals diagnosed with latent TB infection 1993 to 2002. We then retrospectively observed mortality after 6 to 16 years of observation. We ascertained vital status as of December 31, 2008, using the Centers for Disease Control and Preventions National Death Index. We analyzed mortality rates, hazards, and associations using Cox regression. RESULTS We traced 11 135 individuals over 119 772 person-years of observation. We found more all-cause deaths (20.7% vs 3.1%) among posttreatment TB patients than among the comparison group, an adjusted average excess of 7.6 deaths per 1000 person-years (8.8 vs 1.2; P < .001). Mortality among posttreatment TB patients varied with observable factors such as race, site of disease, HIV status, and birth country. CONCLUSIONS Fully treated TB is still associated with substantial mortality risk. Cure as currently understood may be insufficient protection against TB-associated mortality in the years after treatment, and TB prevention may be a valuable opportunity to modify this risk.