Tuberculosis
Tuberculosis (TB) is an infectious disease caused by the Mycobacterium tuberculosis. The term ‘tuberculosis’ is also used for other similar diseases caused by M. bovis and M. africanum (Fitzgerald, 2005; Comstock, 1998). However, for the purposes of the disease report, outcome tree and model presented here, only those infections caused by M. tuberculosis complex are considered.
Tuberculosis bacteria are transmitted via droplets – by coughing, sneezing or talking – and mostly affect the lungs of humans, although they can also result in a systemic disease, affecting virtually all organs (Fitzgerald, 2005). The course of TB can be split into several phases. The first phase after infection, ‘primary TB’, is observed in a minority of patients. The majority of infected (asymptomatic) persons proceed to a ‘latent’ stage, lasting from months to several years or even for the rest of their life. Due to endogenous or exogenous reactivation, people may develop active TB after a certain time spent in the latent stage of the disease.
According to published literature only 5–10% of all infected individuals develop symptoms of active (primary) TB (cough, fever, lethargy, and weight loss) in their lifetime (Castillo-Chavez & Feng, 1997; Gideon & Flynn, 2011, Lin & Flynn, 2010, North & Jung, 2004).
Health outcomes and health states associated with tuberculosis infection
The main health outcomes associated with TB infection are active (primary) TB, MDR (multidrug-resistant) TB and XDR (extensively drug-resistant) TB. After initial infection with M. tuberculosis, an immuno-competent person is generally able to stop the replication and spread of bacilli and thus does not develop any symptoms. Primary TB can be split in pulmonary TB (the majority of cases) and extra-pulmonary TB, affecting different sites of the human organism. Given the complexity of the disease course, all TB cases are considered in the model, with a focus on the distinction between drug-susceptible (DS TB), MDR and XDR TB and their relative case fatality proportions (CFP), irrespective of the site of infection.
Of all laboratory-confirmed TB cases notified to ECDC/WHO between 2009 and 2013, on average 4.5% were multidrug-resistant and 14.6% of these cases were extensively drug resistant (ECDC/WHO, 2015). Therefore, in our model of all symptomatic infections 4.5% are considered to be MDR TB and 0.64% are considered to be XDR TB. However, it should be noted that these proportions vary widely across countries and users are advised to tailor them according to the epidemiology of the population under study.
Transition probabilities
In a cost-effectiveness analysis performed by Tseng and colleagues the authors used various assumptions on the progression of TB. Their model estimates the risk of active TB to be about 5% within the first two years of TB infection. Spontaneous resolution without treatment was set to 25%. Cure rates of TB with treatment and cure rates of MDR TB with treatment were 62.4% and 68.6% respectively (Tseng, 2011).
Tiemersma and colleagues estimated CFP and assessed durations of untreated pulmonary TB in HIV-negative patients and stated an overall case-fatality proportion of 30.7% in the first year of follow-up. The highest proportions were observed shortly after diagnosis. The 5-year and 10-year averages for case fatalities were 58% and 73% respectively (Tiemersma, 2011). In their review they also included the study conducted by Berg, estimating sex- and age-specific 10-year mortality rates. For men aged 15–29, 30–49 and >50 years, the 10-year mortality rates were 66%, 70% and 94% respectively. For women aged 15–29, 30–49 and >50 years, 10-year mortality rates were 70%, 69% and 92% respectively (Berg, 1951). Assuming that detected TB cases are treated in Europe, the case fatality proportions cited above overestimate current TB mortality patterns. Duration of pulmonary TB and TB is difficult to estimate due to difficulties in establishing onset of disease; based on estimates from prevalence and incidence studies an average duration of three years was suggested (Tiemersma, 2011).
A cost-effectiveness analysis using Markov models estimated active TB progression rates from underlying latent TB on the basis of disease duration and age-dependent case-fatality rates. Base case rates for developing active TB from latent TB within 1–2 years, 3–5 years and 6–7 years of exposure were estimated at 0.74%, 0.31% (0–2.5%), and 0.16% respectively. Age-specific death rates for people aged 35, 50 and 70 years were 1%, 5% and 10% respectively (Pisu, 2009).
Based on an international TB network, the US Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO) estimated that in 2004, of 17 960 TB isolates, 20% were MDR and 2% XDR. In population-based trials in the US, Latvia and South Korea 4%, 19% and 15% of all MDR TB cases were XDR in 2004. The studies in the US and Latvia also provided additional information on the progression of MDR and XDR TB in 2004. In the US study 55% of MDR patients completed treatment/were cured and 25% died during treatment. With regard to XDR, 31% completed treatment/were cured and 23% died. Results from Latvia show the percentage of completed treatment/cases cured of MDR TB to be 69% and that of deaths/failures to be 17%. For XDR 61% completed treatment/were cured and 17% died/or had failed treatment (CDC, 2006).
Jaquet and colleagues estimated the impact of DOTS[*] in Haiti and therefore conducted a cost-effectiveness analysis with probability estimates and outcome features of TB taken from literature. For reactivation of latent TB they estimated a probability of 0.1% per year for infection present for more than two years. Within two years of a new TB infection they estimated a base case rate of 5% (2–15%) for developing TB. Cure rates of treated smear positive (drug-sensitive) TB were estimated at 62.4%. For MDR TB, authors assumed a cure rate of 48% (base case; range 48–73%) and the proportion of deaths to be 12% (base case; range 12–26%) (Jacquet, 2006).
Outcome tree parameters
Given the changes in TB epidemiology in Europe during recent decades, the situation has not been sufficiently stable to enable incidence of infection to be estimated from active TB case data. It was therefore decided not to consider latent TB in the model.
Duration of symptomatic TB is set to 0.2–2 years, irrespective of whether it is active, MDR or XDR TB (WHO, 2014).
The case fatality proportion for active TB cases is estimated to be 43% in cases not on TB treatment (Corbett, 2003; Tiemersma, 2011) and 3% in cases on TB treatment (Straetemans, 2011). Given that the estimated incidence of active TB (non-MDR or XDR) in EU/EEA is 10% higher than the notification rate (ECDC/WHO, 2015) and, assuming that all notified cases are being treated, the CFP of active TB (non-MDR or XDR) cases was set at 7%.
The case fatality proportion for MDR TB was set at 12.8% (2.3–23.3%) (Straetemans, 2011). Given the lack of evidence on the case fatality ratio for XDR TB, we used the treatment outcome result category ‘Died’, notified in the EU/EEA, as a proxy for estimating the XDR TB case fatality proportion and set the value at 27% (ECDC/WHO, 2015).
Model input summary
Table 1. Transition probabilities and distributions used in the outcome tree
Health outcome |
Distribution of health states in health outcome |
Transition probability |
Source/assumption |
Active TB |
94.86% |
|
ECDC/WHO, 2015 |
Fatal cases following remaining active cases |
|
7% |
Modelled based on Corbett, 2003; Tiemersma, 2011; Straetemans, 2011 |
Fatal cases following MDR TB |
|
12.8% (2.3–23.3%) |
Straetemans, 2011 |
Fatal cases following XDR TB |
|
27% |
ECDC/WHO, 2015 |
Table 2. Disability weights and duration
Health outcome |
Disability Weight (DW) (Haagsma, 2015) |
Duration |
||
DW |
Label |
In years |
Source |
|
Active TB |
0.308 (0.264–0.353) 0.308 (0.264–0.353) 0.308 (0.264–0.353) |
Tuberculosis, not HIV infected Tuberculosis, not HIV infected Tuberculosis, not HIV infected |
2 2 2 |
WHO, 2013 WHO, 2013 WHO, 2013 |
References
Berg G. Statistik über die Tuberkulosemortalität in Kriegszeiten. Beiträge zur Klinik der Tuberkulose 1951, 106:1-9.
Castillo-Chavez C, Feng Z. To treat or not to treat: the case of tuberculosis. J Math Biol 1997, 35:629-656.
Centers for Disease Control and Prevention: Emergence of Mycobacterium tuberculosis with extensive resistance to second-line drugs - worldwide, 2000–2004. MMWR Morb Mortal Wkly Rep 2006, 55:301-305.
Comstock G, O'Brian R. Tuberculosis. In Bacterial Infections in Humans - Epidemiology and Control. Volume 3rd edition. Edited by Evans A, Brachman P. New York: Plenum Publishing Corporation; 1998: 777-804
Corbett EL, Watt CJ, Walker N, Maher D, Williams BG, et al. (2003) The growing burden of tuberculosis: global trends and interactions with the HIV epidemic. Arch Intern Med 163: 1009-1021.
Dye C, Scheele S, Dolin P, Pathania V, Raviglione M (for the WHO Global Surveillance Monitoring Project). Global burden of tuberculosis: Estimated incidence, prevalence, and mortality by country. JAMA 1999, 282:677-686.
European Centre for Disease Prevention and Control/WHO Regional Office for Europe. Tuberculosis surveillance and monitoring in Europe 2015.
European Centre for Disease Prevention and Control, WHO Regional Office for Europe: Tuberculosis surveillance and monitoring in Europe. In: Tuberculosis surveillance and monitoring in Europe. Stockholm: European Centre for Disease Prevention and Control; 2012.
Fitzgerald D, Haas D. Mycobacterium tuberculosis. In: Principles and Practice of Infectious Diseases. Sixth edition. Edited by Mandell G, Bennett J, Dolin R. Philadelphia: Elsevier Churchill Livingstone; 2005: 2852-2886
Gideon HP, Flynn JL. Latent tuberculosis: what the host "sees"? Immunol Res 2011, 50:202-212.
Global Tuberculosis Report 2013. 1.Tuberculosis – epidemiology. 2.Tuberculosis, Pulmonary – prevention and control. 3.Tuberculosis – economics. 4.Tuberculosis, Multidrug-Resistant. 5. Annual reports. World Health Organization. ISBN 978 92 4 156465 6. Available at: http://apps.who.int/iris/bitstream/10665/91355/1/9789241564656_eng.pdf
Global Tuberculosis Report 2014. 1.Tuberculosis – epidemiology. 2.Tuberculosis, Pulmonary – prevention and control. 3.Tuberculosis – economics. 4.Tuberculosis, Multidrug-Resistant. 5. Annual reports. World Health Organization. ISBN 978 92 4 156480 9. Available at: http://www.who.int/tb/publications/global_report/gtbr14_main_text.pdf?ua=1
Haagsma JA, Maertens de Noordhout C, Polinder S, Vos T, Havelaar AH, Cassini A, Devleesschauwer B, Kretzschmar ME, Speybroeck N, Salomon JA. Assessing disability weights based on the responses of 30,660 people from four European countries. Population Health Metrics 2015; 13: 10
Jacquet V, Morose W, Schwartzman K, Oxlade O, Barr G, Grimard F, et al. Impact of DOTS expansion on tuberculosis related outcomes and costs in Haiti. BMC Public Health 2006, 6:209.
Jassal M, Bishai WR. Extensively drug-resistant tuberculosis. Lancet Infect Dis 2009, 9:19-30.
Lin PL, Flynn JL. Understanding Latent Tuberculosis: A Moving Target. The Journal of Immunology 2010, 185:15-22.
Murray CJL, Lopez AD, World Health Organization, World Bank, Harvard School of Public Health. The global burden of disease: a comprehensive assessment of mortality and disability from diseases, injuries, and risk factors in 1990 and projected to 2020. Geneva: World Health Organization; 1996.
North RJ, Jung YJ. Immunity to tuberculosis. Annu Rev Immunol 2004, 22:599-623.
Pisu M, Gerald J, Shamiyeh JE, Bailey WC, Gerald LB. Targeted tuberculosis contact investigation saves money without sacrificing health. J Public Health Manag Pract 2009, 15:319-327.
Raviglione M. Tuberculosis - the essentials. New York: Informa Health Care; 2010.
Straetemans M, Glaziou P, Bierrenbach AL, Sismanidis C, van der Werf MJ. Assessing tuberculosis case fatality ratio: a meta-analysis. PLoS One 2011, 6:e20755.
Tiemersma EW, van der Werf MJ, Borgdorff MW, Williams BG, Nagelkerke NJ. Natural history of tuberculosis: duration and fatality of untreated pulmonary tuberculosis in HIV negative patients: a systematic review. PLoS One 2011, 6:e17601.
Tseng CL, Oxlade O, Menzies D, Aspler A, Schwartzman K. Cost-effectiveness of novel vaccines for tuberculosis control: a decision analysis study. BMC Public Health 2011, 11:55.
World Health Organization: Global tuberculosis control: epidemiology, planning, financing. WHO report 2009. Geneva: World Health Organization; 2009.