Introduction and epidemiology
TB has become a neglected disease, but it is particularly neglected in children. This article introduces the science of TB in children and describes childhood TB epidemics in different parts of the world.
A child is examined at a clinic
Tuberculosis (TB) in children is a major source of childhood illness and death. It is a neglected aspect of the TB epidemic.
Recent estimates for the incidence of childhood TB have not been provided by the World Health Organisation (WHO) due to the many problems with estimating the burden and diagnosing TB in children. Data from 2000 suggest that 11% of the approximately 8.3 million people with TB worldwide are children 14 years and younger.[^Marais][^Ahmed][^Marais2][^Mukherjee][^Nelson]
However, the distribution of cases across the globe is highly skewed with incidence rates ranging from less than 1/100,000 to 400/100,000.[^WHO][^Marais3]
Sub-Saharan Africa has a disproportionate burden of childhood TB. Two thirds of the countries in the world with a rate of childhood TB greater than 5/100,000 are located in the region. WHO cites 22 high-burden countries, and 75% of all childhood TB is within these countries. The burden of childhood TB relative to total cases also varies, from as little as 3% in some countries up to 25% cases in others.[^Ahmed]
TB in children is acquired through contact with an infectious adult. Therefore, the rates of childhood TB reflect the successes or failures of TB infection control programmes. Increasingly, childhood TB rates are used as a proxy measure of TB infection control because cases in children are sentinel or primary, and reflect recent infection and not reactivation of latent disease. While there are cases of children infecting others, it is thought that children do not contribute substantially to the spread of the disease since they develop less infectious types of TB. Previous TB control strategies have therefore not prioritized childhood TB since there focus has been on reducing transmission.[^Ahmed][^WHO][^Zar][^Marais4][^Middelkoop][^Zar2][^Walls][^Lolekha][^Satyanarayana]
There are a number of challenges that contribute to our lack of understanding and knowledge of the burden of childhood TB. Childhood TB does not have a diagnostic gold standard, with at least 80% of childhood TB cases being smear negative. Consequently there is no definitive diagnosis for childhood TB making estimates of incidence very difficult. The clinical and radiological features of childhood TB overlap considerably with both HIV and malnutrition; two key risk factors of childhood TB. Approximately half of children with TB are initially asymptomatic and will require x-rays for diagnosis which is particularly difficult in low resourced settings. All of these factors contribute to under-diagnosis and uncertainty in our estimates of the global burden of childhood TB.[^Marais][^Ahmed][^Walls][^Lolekha][^VanRie][^Brent]
Children differ from adults in how TB is likely to manifest with children much more likely to develop extrapulmonary TB. As many as 25% of childhood TB cases will be extrapulmonary cases, compared with 16% in adults. Children are also more likely to develop other severe forms of TB including disseminated TB and TB meningitis.These manifestations of TB are typical of children under the age of 10. Also, young children under 2 years of age are particularly at risk for disease progression and dissemination.[^WHO][^Walls][^Brent]
Children are also more likely to develop TB disease after infection. While 5-10% of adults will develop TB disease after infection, 15% of adolescents, 24% of children ages 1-5 years and more than 40% of children under 1 year will develop TB disease. Children above 10 years of age, or adolescents, have a transmission risk similar to that of adults and progress to adult-type pulmonary TB. So TB in children is complicated and differs by age. The age group of 0-14 in the WHO figures combines all of these figures into the one category and so does not reflect the spectrum of childhood TB disease including the severity in young children.[^Marais][^WHO][^Middelkoop][^Walls][^VanRie]
In addition to younger children being at increased risk for developing disease, poverty, over-crowding and malnutrition are all associated with childhood TB. Even before the introduction of BCG vaccination and antibiotics, these were known to be associated with an increased risk of TB.[^Ahmed][^Walls]
As socioeconomic status decreases, the proportion of TB cases in children increases (see the graph below).[^WHO]
![Childhood TB incidence graph](/media/uploads/images/tbchildrenincidencegraph-300x236.png "Childhood TB incidence graph")
Proportion of paediatric TB cases by changes in socioeconomic status. Source: World Health Organization.
South African data show that parental education, household income and crowding are risk factors. Data from Turkey show that malnutrition, measles and pertussis increase the risk of childhood TB.[^VanRie][^Gocmen]
HIV not only makes diagnosis of TB more difficult in children, but increases the risk of contracting TB disease 20 times. Estimates suggest that there will be more than 23 new cases of childhood TB for every 100 HIV positive children per year. HIV positive children are at increased risk of TB exposure as they are more likely to be exposed to infectious TB adults, more likely to progress to active disease after infection and have a higher mortality than children without HIV. Childhood TB in developed countries is rare but immigrant children are 12 times more likely to develop childhood TB compared to non immigrant children.[^Marais2][^WHO][^Zar][^Walls]
Awareness is growing that childhood TB represents a large proportion of preventable childhood illness and death in countries with endemic TB. Therefore, the WHO is requiring countries to report on the HIV status among those with TB as well as figures for childhood TB in children under 2 years of age. Also, substantial resources are being allocated to improve TB diagnostics for children.[^Marais2][^WHO2][^WHO3]
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[^Ahmed]: Ahmed T, Sobhan F, Ahmed AMS, Banu S, Mahmood AM, Alam K, et al. Childhood Tuberculosis : a Review of Epidemiology , Diagnosis and Management. Infectious Diseases Journal of Pakistan. 2008;17(2):52-60.
[^Marais2]: Marais BJ, Graham SM, Cotton MF, Beyers N. Diagnostic and management challenges for childhood tuberculosis in the era of HIV. The Journal of infectious diseases. 2007;196 Suppl(Suppl 1):S76-85.
[^Mukherjee]: Mukherjee A, Lodha R, Kabra SK. Changing trends in childhood tuberculosis. Indian journal of pediatrics. 2011;78(3):328-33.
[^Nelson]: Nelson LJ, Wells CD. Global epidemiology of childhood tuberculosis. The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease. 2004;8(5):636-47.
[^WHO]: World Health Organization. A research agenda for childhood tuberculosis. Geneva: WHO; 2007.
[^Marais3]: Marais BJ, Hesseling AC, Gie RP, Schaaf HS, Beyers N. The burden of childhood tuberculosis and the accuracy of community-based surveillance data. Int J Tuberc Lung Dis. 2006 Mar;10(3):259-63.
[^Zar]: Zar HJ, Pai M. Childhood tuberculosis - a new era. Paediatric Respiratory Reviews. 2011;12(1):1-2.
[^Marais4]: Marais BJ, Schaaf HS. Childhood tuberculosis: an emerging and previously neglected problem. Infectious disease clinics of North America. 2010;24(3):727-49.
[^Middelkoop]: Middelkoop K, Bekker L-G, Morrow C, Zwane E, Wood R. Childhood tuberculosis infection and disease: a spatial and temporal transmission analysis in a South African township. South African Medical Journal. 2009;99(10):738-43.
[^Zar2]: Zar HJ. Diagnosis of pulmonary tuberculosis in children--what's new? S Afr Med J. 2007;97:983-5.
[^Walls]: Walls T. Global epidemiology of paediatric tuberculosis. Journal of Infection. 2004;48(1):13-22.
[^Lolekha]: Lolekha R, Anuwatnonthakate A, Nateniyom S, Sumnapun S, Yamada N, Wattanaamornkiat W, et al. Childhood TB epidemiology and treatment outcomes in Thailand: a TB active surveillance network, 2004 to 2006. BMC infectious diseases. 2008;8:94-.
[^Satyanarayana]: Satyanarayana S, Shivashankar R, Vashist RP, Chauhan LS, Chadha SS, Dewan PK, et al. Characteristics and programme-defined treatment outcomes among childhood tuberculosis (TB) patients under the national TB programme in Delhi. PLoS One. 2010;5(10):e13338-e.
[^VanRie]: Van Rie a, Beyers N, Gie RP, Kunneke M, Zietsman L, Donald PR. Childhood tuberculosis in an urban population in South Africa: burden and risk factor. Archives of disease in childhood. 1999;80(5):433-7.
[^Brent]: Brent AJ, Anderson ST, Kampmann B. Childhood tuberculosis: out of sight, out of mind? Transactions of the Royal Society of Tropical Medicine and Hygiene. 2008;102(3):217-8.
[^Gocmen]: Gocmen A, Cengizlier R, Ozcelik U, Kiper N, Senuyar R. Childhood tuberculosis: a report of 2,205 cases. Turk J Pediatr. 1997 Apr-Jun;39(2):149-58.
[^Zar3]: Zar HJ, Cotton MF, Strauss S, Karpakis J, Hussey G, Schaaf HS, et al. Effect of isoniazid prophylaxis on mortality and incidence of tuberculosis in children with HIV: randomised controlled trial. BMJ. 2007;334:136.
[^WHO2]: World Health Organization. Guidelines for HIV surveillance among tuberculosis patients. Geneva: WHO; 2004.
[^WHO3]: World Health Organization. Guidance for national tuberculosis programmes on the management of tuberculosis in children. Geneva: WHO; 2006.