The age-specific burden and household and school-based predictors of child and adolescent tuberculosis infection in rural Uganda

Carina Marquez, Mucunguzi Atukunda, Laura B Balzer, Gabriel Chamie, Joel Kironde, Emmanuel Ssemmondo, Theodore D Ruel, Florence Mwangwa, Khai Hoan Tram, Tamara D Clark, Dalsone Kwarisiima, Maya Petersen, Moses R Kamya, Edwin D Charlebois, Diane V Havlir, Carina Marquez, Mucunguzi Atukunda, Laura B Balzer, Gabriel Chamie, Joel Kironde, Emmanuel Ssemmondo, Theodore D Ruel, Florence Mwangwa, Khai Hoan Tram, Tamara D Clark, Dalsone Kwarisiima, Maya Petersen, Moses R Kamya, Edwin D Charlebois, Diane V Havlir

Abstract

Background: The age-specific epidemiology of child and adolescent tuberculosis (TB) is poorly understood, especially in rural areas of East Africa. We sought to characterize the age-specific prevalence and predictors of TB infection among children and adolescents living in rural Uganda, and to explore the contribution of household TB exposure on TB infection.

Methods: From 2015-2016 we placed and read 3,121 tuberculin skin tests (TST) in children (5-11 years old) and adolescents (12-19 years old) participating in a nested household survey in 9 rural Eastern Ugandan communities. TB infection was defined as a positive TST (induration ≥10mm or ≥5mm if living with HIV). Age-specific prevalence was estimated using inverse probability weighting to adjust for incomplete measurement. Generalized estimating equations were used to assess the association between TB infection and multi-level predictors.

Results: The adjusted prevalence of TB infection was 8.5% (95%CI: 6.9-10.4) in children and 16.7% (95% CI:14.0-19.7) in adolescents. Nine percent of children and adolescents with a prevalent TB infection had a household TB contact. Among children, having a household TB contact was strongly associated with TB infection (aOR 5.5, 95% CI: 1.7-16.9), but the strength of this association declined among adolescents and did not meet significance (aOR 2.3, 95% CI: 0.8-7.0). The population attributable faction of TB infection due to a household TB contact was 8% for children and 4% among adolescents. Mobile children and adolescents who travel outside of their community for school had a 1.7 (95% CI 1.0-2.9) fold higher odds of TB infection than those who attended school in the community.

Conclusion: Children and adolescents in this area of rural eastern Uganda suffer a significant burden of TB. The majority of TB infections are not explained by a known household TB contact. Our findings underscore the need for community-based TB prevention interventions, especially among mobile youth.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1. Study flow diagram.
Fig 1. Study flow diagram.
TST = tuberculin skin test.
Fig 2. Histogram of non-zero induration from…
Fig 2. Histogram of non-zero induration from tuberculin skin tests.
Among the 3,121 children who had TSTs placed and read, 2425 (77.7%) had an induration of 0 millimeters (mm) and 696 (22.3%) had a non-zero mm induration. The mode of non-zero indurations was 8mm.
Fig 3. Population-level age-stratified prevalence estimates of…
Fig 3. Population-level age-stratified prevalence estimates of TB infection, defined as a positive tuberculin skin test (TST), in duration >10mm or >5mm if living with HIV.

References

    1. WHO | Roadmap towards ending TB in children and adolescents. In: WHO [Internet]. [cited 24 Nov 2018]. Available:
    1. World Health Organization. Global Tuberculosis Report 2018. Geneva, Switzerland;
    1. Snow KJ, Sismanidis C, Denholm J, Sawyer SM, Graham SM. The incidence of tuberculosis among adolescents and young adults: a global estimate. Eur Respir J. 2018;51 10.1183/13993003.02352-2017
    1. 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: e453–e459. 10.1016/S2214-109X(14)70245-1
    1. Martinez L, Shen Y, Mupere E, Kizza A, Hill PC, Whalen CC. Transmission of Mycobacterium Tuberculosis in Households and the Community: A Systematic Review and Meta-Analysis. Am J Epidemiol. 2017;185: 1327–1339. 10.1093/aje/kwx025
    1. Middelkoop K, Bekker L-G, Morrow C, Lee N, Wood R. Decreasing household contribution to TB transmission with age: a retrospective geographic analysis of young people in a South African township. BMC Infect Dis. 2014;14: 221 10.1186/1471-2334-14-221
    1. Johnstone-Robertson SP, Mark D, Morrow C, Middelkoop K, Chiswell M, Aquino LDH, et al. Social mixing patterns within a South African township community: implications for respiratory disease transmission and control. Am J Epidemiol. 2011;174: 1246–1255. 10.1093/aje/kwr251
    1. Havlir DV, Balzer L, Charlebois ED, Clark TD, Kwarisiima D, Ayieko J, et al. Trial of HIV Test and Treat via A community Health Model in Rural Africa. N Engl J Med. in press.
    1. Center for Disease Control and Prevention. Mantoux tuberculin skin test facillitators guide. 2013. Available:
    1. Balen J, McManus DP, Li Y-S, Zhao Z-Y, Yuan L-P, Utzinger J, et al. Comparison of two approaches for measuring household wealth via an asset-based index in rural and peri-urban settings of Hunan province, China. Emerg Themes Epidemiol. 2010;7: 7 10.1186/1742-7622-7-7
    1. Horvitz DG, Thompson DJ. A Generalization of Sampling Without Replacement from a Finite Universe. J Am Stat Assoc. 2012. [cited 17 Nov 2018]. Available:
    1. Horvitz DG, Thompson DJ. A Generalization of Sampling Without Replacement From a Finite Universe. J Am Stat Assoc. 1952;47: 663–685. 10.2307/2280784
    1. Mansournia MA, Altman D. Population attributable fraction | The BMJ. [cited 31 Oct 2019]. Available:
    1. Uganda National Council for Science and Technology (UNCST). National Guidelines for Research involving Humans as Research Participants. Kampala, Uganda 2014.
    1. Andrews JR, Morrow C, Walensky RP, Wood R. Integrating social contact and environmental data in evaluating tuberculosis transmission in a South African township. J Infect Dis. 2014; jiu138 10.1093/infdis/jiu138
    1. Andrews JR, Morrow C, Wood R. Modeling the role of public transportation in sustaining tuberculosis transmission in South Africa. Am J Epidemiol. 2013;177: 556–561. 10.1093/aje/kws331
    1. Uganda Ministry of Education and Sports. Education and Sports Sector Fact Sheet 2002–2015. 2015.
    1. Bekker L-G, Wood R. The changing natural history of tuberculosis and HIV coinfection in an urban area of hyperendemicity. Clin Infect Dis Off Publ Infect Dis Soc Am. 2010;50 Suppl 3: S208–214. 10.1086/651493
    1. Middelkoop K, Mathema B, Myer L, Shashkina E, Whitelaw A, Kaplan G, et al. Transmission of TB in a high HIV prevalent South African community. J Infect Dis. 2014. 10.1093/infdis/jiu403
    1. Martinez L, Sekandi JN, Castellanos ME, Zalwango S, Whalen CC. Infectiousness of HIV-Seropositive Patients with Tuberculosis in a High-Burden African Setting. Am J Respir Crit Care Med. 2016;194: 1152–1163. 10.1164/rccm.201511-2146OC
    1. Marquez C, Chamie G, Achan J, Luetkemeyer AF, Kyohere M, Okiring J, et al. Tuberculosis Infection in Early Childhood and the Association with HIV-exposure in HIV-uninfected Children in Rural Uganda. Pediatr Infect Dis J. 2016;35: 524–529. 10.1097/INF.0000000000001062
    1. Filteau S. The HIV-exposed, uninfected African child. Trop Med Int Health TM IH. 2009;14: 276–287. 10.1111/j.1365-3156.2009.02220.x
    1. Mumpe-Mwanja D, Verver S, Yeka A, Etwom A, Waako J, Ssengooba W, et al. Prevalence and risk factors of latent Tuberculosis among adolescents in rural Eastern Uganda. Afr Health Sci. 2015;15: 851–860. 10.4314/ahs.v15i3.20
    1. Middelkoop K, Bekker L-G, Liang H, Aquino LDH, Sebastian E, Myer L, et al. Force of tuberculosis infection among adolescents in a high HIV and TB prevalence community: a cross-sectional observation study. BMC Infect Dis. 2011;11: 156 10.1186/1471-2334-11-156
    1. Martinez L, Lo NC, Cords O, Hill PC, Khan P, Hatherill M, et al. Paediatric tuberculosis transmission outside the household: challenging historical paradigms to inform future public health strategies. Lancet Respir Med. 2019;7: 544–552. 10.1016/S2213-2600(19)30137-7
    1. Seddon JA, Paton J, Nademi Z, Keane D, Williams B, Williams A, et al. The impact of BCG vaccination on tuberculin skin test responses in children is age dependent: evidence to be considered when screening children for tuberculosis infection. Thorax. 2016;71: 932–939. 10.1136/thoraxjnl-2015-207687

Source: PubMed

3
Subskrybuj