Skip to main content
Top
Published in: BMC Medicine 1/2019

Open Access 01-12-2019 | Tuberculosis | Research article

Profiling Mycobacterium tuberculosis transmission and the resulting disease burden in the five highest tuberculosis burden countries

Authors: Romain Ragonnet, James M. Trauer, Nicholas Geard, Nick Scott, Emma S. McBryde

Published in: BMC Medicine | Issue 1/2019

Login to get access

Abstract

Background

Tuberculosis (TB) control efforts are hampered by an imperfect understanding of TB epidemiology. The true age distribution of disease is unknown because a large proportion of individuals with active TB remain undetected. Understanding of transmission is limited by the asymptomatic nature of latent infection and the pathogen’s capacity for late reactivation. A better understanding of TB epidemiology is critically needed to ensure effective use of existing and future control tools.

Methods

We use an agent-based model to simulate TB epidemiology in the five highest TB burden countries—India, Indonesia, China, the Philippines and Pakistan—providing unique insights into patterns of transmission and disease. Our model replicates demographically realistic populations, explicitly capturing social contacts between individuals based on local estimates of age-specific contact in household, school and workplace settings. Time-varying programmatic parameters are incorporated to account for the local history of TB control.

Results

We estimate that the 15–19-year-old age group is involved in more than 20% of transmission events in India, Indonesia, the Philippines and Pakistan, despite representing only 5% of the local TB incidence. According to our model, childhood TB represents around one fifth of the incident TB cases in these four countries. In China, three quarters of incident TB were estimated to occur in the ≥ 45-year-old population. The calibrated per-contact transmission risk was found to be similar in each of the five countries despite their very different TB burdens.

Conclusions

Adolescents and young adults are a major driver of TB in high-incidence settings. Relying only on the observed distribution of disease to understand the age profile of transmission is potentially misleading.
Appendix
Available only for authorised users
Literature
1.
go back to reference WHO. Global Tuberculosis Report 2018. Geneva, Switzerland: World Health Organization; 2018. WHO. Global Tuberculosis Report 2018. Geneva, Switzerland: World Health Organization; 2018.
2.
go back to reference Dodd PJ, Gardiner E, Coghlan R, Seddon JA. Burden of childhood tuberculosis in 22 high-burden countries: a mathematical modelling study. Lancet Glob Health. 2014;2(8):e453–9.CrossRef Dodd PJ, Gardiner E, Coghlan R, Seddon JA. Burden of childhood tuberculosis in 22 high-burden countries: a mathematical modelling study. Lancet Glob Health. 2014;2(8):e453–9.CrossRef
3.
go back to reference Lillebaek T, Dirksen A, Baess I, Strunge B, Thomsen VO, Andersen AB. Molecular evidence of endogenous reactivation of Mycobacterium tuberculosis after 33 years of latent infection. J Infect Dis. 2002;185(3):401–4.CrossRef Lillebaek T, Dirksen A, Baess I, Strunge B, Thomsen VO, Andersen AB. Molecular evidence of endogenous reactivation of Mycobacterium tuberculosis after 33 years of latent infection. J Infect Dis. 2002;185(3):401–4.CrossRef
4.
go back to reference Houben RM, Dodd PJ. The global burden of latent tuberculosis infection: a re-estimation using mathematical modelling. PLoS Med. 2016;13(10):e1002152.CrossRef Houben RM, Dodd PJ. The global burden of latent tuberculosis infection: a re-estimation using mathematical modelling. PLoS Med. 2016;13(10):e1002152.CrossRef
5.
go back to reference Gomes MG, Franco AO, Gomes MC, Medley GF. The reinfection threshold promotes variability in tuberculosis epidemiology and vaccine efficacy. Proc Biol Sci. 2004;271:617–23.CrossRef Gomes MG, Franco AO, Gomes MC, Medley GF. The reinfection threshold promotes variability in tuberculosis epidemiology and vaccine efficacy. Proc Biol Sci. 2004;271:617–23.CrossRef
6.
go back to reference Ferguson NM, Cummings DA, Cauchemez S, Fraser C, Riley S, Meeyai A, et al. Strategies for containing an emerging influenza pandemic in Southeast Asia. Nature. 2005;437(7056):209–14.CrossRef Ferguson NM, Cummings DA, Cauchemez S, Fraser C, Riley S, Meeyai A, et al. Strategies for containing an emerging influenza pandemic in Southeast Asia. Nature. 2005;437(7056):209–14.CrossRef
7.
go back to reference Geard N, Glass K, McCaw JM, McBryde ES, Korb KB, Keeling MJ, et al. The effects of demographic change on disease transmission and vaccine impact in a household structured population. Epidemics. 2015;13:56–64.CrossRef Geard N, Glass K, McCaw JM, McBryde ES, Korb KB, Keeling MJ, et al. The effects of demographic change on disease transmission and vaccine impact in a household structured population. Epidemics. 2015;13:56–64.CrossRef
9.
go back to reference Mossong J, Hens N, Jit M, Beutels P, Auranen K, Mikolajczyk R, et al. Social contacts and mixing patterns relevant to the spread of infectious diseases. PLoS Med. 2008;5(3):e74.CrossRef Mossong J, Hens N, Jit M, Beutels P, Auranen K, Mikolajczyk R, et al. Social contacts and mixing patterns relevant to the spread of infectious diseases. PLoS Med. 2008;5(3):e74.CrossRef
10.
go back to reference Horby P, Pham QT, Hens N, Nguyen TT, Le QM, Dang DT, et al. Social contact patterns in Vietnam and implications for the control of infectious diseases. PLoS One. 2011;6(2):e16965.CrossRef Horby P, Pham QT, Hens N, Nguyen TT, Le QM, Dang DT, et al. Social contact patterns in Vietnam and implications for the control of infectious diseases. PLoS One. 2011;6(2):e16965.CrossRef
11.
go back to reference Grijalva CG, Goeyvaerts N, Verastegui H, Edwards KM, Gil AI, Lanata CF, et al. A household-based study of contact networks relevant for the spread of infectious diseases in the highlands of Peru. PLoS One. 2015;10(3):e0118457.CrossRef Grijalva CG, Goeyvaerts N, Verastegui H, Edwards KM, Gil AI, Lanata CF, et al. A household-based study of contact networks relevant for the spread of infectious diseases in the highlands of Peru. PLoS One. 2015;10(3):e0118457.CrossRef
12.
go back to reference Eames KT. Modelling disease spread through random and regular contacts in clustered populations. Theor Popul Biol. 2008;73(1):104–11.CrossRef Eames KT. Modelling disease spread through random and regular contacts in clustered populations. Theor Popul Biol. 2008;73(1):104–11.CrossRef
13.
go back to reference McCreesh N, White RG. An explanation for the low proportion of tuberculosis that results from transmission between household and known social contacts. Sci Rep. 2018;8(1):5382.CrossRef McCreesh N, White RG. An explanation for the low proportion of tuberculosis that results from transmission between household and known social contacts. Sci Rep. 2018;8(1):5382.CrossRef
14.
go back to reference Siler W. A competing-risk model for animal mortality. Ecology. 1979;60(4):750–7.CrossRef Siler W. A competing-risk model for animal mortality. Ecology. 1979;60(4):750–7.CrossRef
15.
go back to reference Prem K, Cook AR, Jit M. Projecting social contact matrices in 152 countries using contact surveys and demographic data. PLoS Comput Biol. 2017;13(9):e1005697.CrossRef Prem K, Cook AR, Jit M. Projecting social contact matrices in 152 countries using contact surveys and demographic data. PLoS Comput Biol. 2017;13(9):e1005697.CrossRef
16.
go back to reference Goeyvaerts N, Santermans E, Potter G, Torneri A, Van Kerckhove K, Willem L, Aerts M, Beutels P and Hens N. Household members do not contact each other at random: implications for infectious disease modelling. Proc R Soc B. 2018;285(1893). http://doi.org/10.1098/rspb.2018.2201. Goeyvaerts N, Santermans E, Potter G, Torneri A, Van Kerckhove K, Willem L, Aerts M, Beutels P and Hens N. Household members do not contact each other at random: implications for infectious disease modelling. Proc R Soc B. 2018;285(1893). http://​doi.​org/​10.​1098/​rspb.​2018.​2201.
17.
go back to reference Ragonnet R, Trauer JM, Scott N, Meehan MT, Denholm JT, McBryde ES. Optimally capturing latency dynamics in models of tuberculosis transmission. Epidemics. 2017;21:39–47.CrossRef Ragonnet R, Trauer JM, Scott N, Meehan MT, Denholm JT, McBryde ES. Optimally capturing latency dynamics in models of tuberculosis transmission. Epidemics. 2017;21:39–47.CrossRef
18.
go back to reference 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(4):e17601.CrossRef 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(4):e17601.CrossRef
19.
go back to reference Behr MA, Warren SA, Salamon H, Hopewell PC, Ponce de Leon A, Daley CL, et al. Transmission of Mycobacterium tuberculosis from patients smear-negative for acid-fast bacilli. Lancet. 1999;353(9151):444–9.CrossRef Behr MA, Warren SA, Salamon H, Hopewell PC, Ponce de Leon A, Daley CL, et al. Transmission of Mycobacterium tuberculosis from patients smear-negative for acid-fast bacilli. Lancet. 1999;353(9151):444–9.CrossRef
20.
go back to reference Tostmann A, Kik SV, Kalisvaart NA, Sebek MM, Verver S, Boeree MJ, et al. Tuberculosis transmission by patients with smear-negative pulmonary tuberculosis in a large cohort in the Netherlands. Clin Infect Dis. 2008;47(9):1135–42.CrossRef Tostmann A, Kik SV, Kalisvaart NA, Sebek MM, Verver S, Boeree MJ, et al. Tuberculosis transmission by patients with smear-negative pulmonary tuberculosis in a large cohort in the Netherlands. Clin Infect Dis. 2008;47(9):1135–42.CrossRef
21.
go back to reference Donald PR. Childhood tuberculosis: the hidden epidemic. Int J Tuberc Lung Dis. 2004;8(5):627–9.PubMed Donald PR. Childhood tuberculosis: the hidden epidemic. Int J Tuberc Lung Dis. 2004;8(5):627–9.PubMed
22.
go back to reference Marais BJ, Gie RP, Schaaf HS, Beyers N, Donald PR, Starke JR. Childhood pulmonary tuberculosis: old wisdom and new challenges. Am J Respir Crit Care Med. 2006;173(10):1078–90.CrossRef Marais BJ, Gie RP, Schaaf HS, Beyers N, Donald PR, Starke JR. Childhood pulmonary tuberculosis: old wisdom and new challenges. Am J Respir Crit Care Med. 2006;173(10):1078–90.CrossRef
23.
go back to reference Nguipdop-Djomo P, Heldal E, Rodrigues LC, Abubakar I, Mangtani P. Duration of BCG protection against tuberculosis and change in effectiveness with time since vaccination in Norway: a retrospective population-based cohort study. Lancet Infect Dis. 2016;16(2):219–26.CrossRef Nguipdop-Djomo P, Heldal E, Rodrigues LC, Abubakar I, Mangtani P. Duration of BCG protection against tuberculosis and change in effectiveness with time since vaccination in Norway: a retrospective population-based cohort study. Lancet Infect Dis. 2016;16(2):219–26.CrossRef
24.
go back to reference Abubakar I, Pimpin L, Ariti C, Beynon R, Mangtani P, Sterne JA, et al. Systematic review and meta-analysis of the current evidence on the duration of protection by bacillus Calmette-Guerin vaccination against tuberculosis. Health Technol Assess. 2013;17(37):1–372 v-vi.CrossRef Abubakar I, Pimpin L, Ariti C, Beynon R, Mangtani P, Sterne JA, et al. Systematic review and meta-analysis of the current evidence on the duration of protection by bacillus Calmette-Guerin vaccination against tuberculosis. Health Technol Assess. 2013;17(37):1–372 v-vi.CrossRef
25.
go back to reference Colditz GA, Brewer TF, Berkey CS, Wilson ME, Burdick E, Fineberg HV, et al. Efficacy of BCG vaccine in the prevention of tuberculosis. Meta-analysis of the published literature. JAMA. 1994;271(9):698–702.CrossRef Colditz GA, Brewer TF, Berkey CS, Wilson ME, Burdick E, Fineberg HV, et al. Efficacy of BCG vaccine in the prevention of tuberculosis. Meta-analysis of the published literature. JAMA. 1994;271(9):698–702.CrossRef
26.
go back to reference Andrews JR, Noubary F, Walensky RP, Cerda R, Losina E, Horsburgh CR. Risk of progression to active tuberculosis following reinfection with Mycobacterium tuberculosis. Clin Infect Dis. 2012;54(6):784–91.CrossRef Andrews JR, Noubary F, Walensky RP, Cerda R, Losina E, Horsburgh CR. Risk of progression to active tuberculosis following reinfection with Mycobacterium tuberculosis. Clin Infect Dis. 2012;54(6):784–91.CrossRef
29.
go back to reference Shaweno D, Karmakar M, Alene KA, Ragonnet R, Clements AC, Trauer JM, et al. Methods used in the spatial analysis of tuberculosis epidemiology: a systematic review. BMC Med. 2018;16(1):193.CrossRef Shaweno D, Karmakar M, Alene KA, Ragonnet R, Clements AC, Trauer JM, et al. Methods used in the spatial analysis of tuberculosis epidemiology: a systematic review. BMC Med. 2018;16(1):193.CrossRef
32.
go back to reference Pakistan Education Statistics. Number of schools. 2016. Pakistan Education Statistics. Number of schools. 2016.
34.
go back to reference Zumla A, Raviglione M, Hafner R, von Reyn CF. Tuberculosis. N Engl J Med. 2013;368(8):745–55.CrossRef Zumla A, Raviglione M, Hafner R, von Reyn CF. Tuberculosis. N Engl J Med. 2013;368(8):745–55.CrossRef
35.
go back to reference WHO. Global tuberculosis report 2017. Geneva: World Health Organization; 2017. WHO. Global tuberculosis report 2017. Geneva: World Health Organization; 2017.
38.
go back to reference Belkina TV, Khojiev DS, Tillyashaykhov MN, Tigay ZN, Kudenov MU, Tebbens JD, et al. Delay in the diagnosis and treatment of pulmonary tuberculosis in Uzbekistan: a cross-sectional study. BMC Infect Dis. 2014;14:624.CrossRef Belkina TV, Khojiev DS, Tillyashaykhov MN, Tigay ZN, Kudenov MU, Tebbens JD, et al. Delay in the diagnosis and treatment of pulmonary tuberculosis in Uzbekistan: a cross-sectional study. BMC Infect Dis. 2014;14:624.CrossRef
39.
go back to reference Sreeramareddy CT, Qin ZZ, Satyanarayana S, Subbaraman R, Pai M. Delays in diagnosis and treatment of pulmonary tuberculosis in India: a systematic review. Int J Tuberc Lung Dis. 2014;18(3):255–66.CrossRef Sreeramareddy CT, Qin ZZ, Satyanarayana S, Subbaraman R, Pai M. Delays in diagnosis and treatment of pulmonary tuberculosis in India: a systematic review. Int J Tuberc Lung Dis. 2014;18(3):255–66.CrossRef
40.
go back to reference Asefa A, Teshome W. Total delay in treatment among smear positive pulmonary tuberculosis patients in five primary health centers, southern Ethiopia: a cross sectional study. PLoS One. 2014;9(7):e102884.CrossRef Asefa A, Teshome W. Total delay in treatment among smear positive pulmonary tuberculosis patients in five primary health centers, southern Ethiopia: a cross sectional study. PLoS One. 2014;9(7):e102884.CrossRef
41.
go back to reference Jurcev-Savicevic A, Mulic R, Kozul K, Ban B, Valic J, Bacun-Ivcek L, et al. Health system delay in pulmonary tuberculosis treatment in a country with an intermediate burden of tuberculosis: a cross-sectional study. BMC Public Health. 2013;13:250.CrossRef Jurcev-Savicevic A, Mulic R, Kozul K, Ban B, Valic J, Bacun-Ivcek L, et al. Health system delay in pulmonary tuberculosis treatment in a country with an intermediate burden of tuberculosis: a cross-sectional study. BMC Public Health. 2013;13:250.CrossRef
42.
go back to reference Trauer JM, Moyo N, Tay EL, Dale K, Ragonnet R, McBryde ES, et al. Risk of active tuberculosis in the five years following infection . . . 15%? Chest. 2016;149(2):516–25.CrossRef Trauer JM, Moyo N, Tay EL, Dale K, Ragonnet R, McBryde ES, et al. Risk of active tuberculosis in the five years following infection . . . 15%? Chest. 2016;149(2):516–25.CrossRef
43.
go back to reference Sloot R, Schim van der Loeff MF, Kouw PM, Borgdorff MW. Risk of tuberculosis after recent exposure. A 10-year follow-up study of contacts in Amsterdam. Am J Respir Crit Care Med. 2014;190(9):1044–52.CrossRef Sloot R, Schim van der Loeff MF, Kouw PM, Borgdorff MW. Risk of tuberculosis after recent exposure. A 10-year follow-up study of contacts in Amsterdam. Am J Respir Crit Care Med. 2014;190(9):1044–52.CrossRef
44.
go back to reference WHO. Latent tuberculosis infection: updated and consolidated guidelines for programmatic management. Geneva, Switzerland: World Health Organization; 2018. WHO. Latent tuberculosis infection: updated and consolidated guidelines for programmatic management. Geneva, Switzerland: World Health Organization; 2018.
46.
go back to reference Huynh GH, Klein DJ, Chin DP, Wagner BG, Eckhoff PA, Liu R, et al. Tuberculosis control strategies to reach the 2035 global targets in China: the role of changing demographics and reactivation disease. BMC Med. 2015;13:88.CrossRef Huynh GH, Klein DJ, Chin DP, Wagner BG, Eckhoff PA, Liu R, et al. Tuberculosis control strategies to reach the 2035 global targets in China: the role of changing demographics and reactivation disease. BMC Med. 2015;13:88.CrossRef
Metadata
Title
Profiling Mycobacterium tuberculosis transmission and the resulting disease burden in the five highest tuberculosis burden countries
Authors
Romain Ragonnet
James M. Trauer
Nicholas Geard
Nick Scott
Emma S. McBryde
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Medicine / Issue 1/2019
Electronic ISSN: 1741-7015
DOI
https://doi.org/10.1186/s12916-019-1452-0

Other articles of this Issue 1/2019

BMC Medicine 1/2019 Go to the issue