A Brief Overview of Mycobacterial Diseases in Children areas.14–16 M. leprae through contact with an adult index case.14


Children in leprosy endemic areas acquire infection with Although the


exact route of transmission remains unclear, the presence of a leprosy index case in a household or neighbourhood increases the risk of infection and disease,14


and the highest disease risk occurs with exposure to a multibacillary index case in the household.14–16


Disease burden Tuberculosis


It is estimated that approximately 12 % of the global TB disease burden (9.4 million cases in 2010/2011) occur in children but accurate figures are only available in some low-burden countries where children contribute approximately 5 % of the TB caseload.18–21 Three-quarters of affected children live in 22 high burden countries, where childhood TB caseloads may exceed 20 % of all cases, with annual incidence rates ranging between 60 and 600 per 100,000.3,19 Childhood TB constituted 4.3 % of the total TB burden in the European Union (EU) in the period 2000–2009, with an average incidence rate of 0.3–29.6 per 100,000 and persistent higher rates in former Soviet Union countries in Eastern Europe.2


Foreign-born immigrant


children constituted about 15 % of the almost 40,000 childhood cases in Europe, mostly in low-incidence countries with sizeable non-European populations.2


young children under five years of age.2,19


The highest disease rates occurred in In a recent Centers for


Disease Control and Prevention (CDC) survey foreign-born children constituted 31 % of all TB cases in the US.1


Non-tuberculous Mycobacteria Disease The annual incidence rates of NTM in different countries varies between 0.30–0.87 cases per 100,000 children.20


There are few


population based studies of NTM disease in children, but there are a few reports from countries where it is a notifiable disease. Of 61 patients with NTM notified in the Netherlands between 2001 and 2003, 80 % were under five years.20


The NTM incidence was estimated to be


0.77 per 100,000 children per annum, with a higher incidence (2.3 cases per 100,000 children) in the youngest children.20


The incidence


NTM was isolated from 6 % of mostly asymptomatic children investigated for TB in a TB vaccine trial in South Africa, but the clinical relevance of this finding remains uncertain.22


of NTM lymphadenitis in children under five years was estimated to be 5.5 per 100,000 in Sweden and between 1.2–3 cases per 100,000 in Israel.13,21


Leprosy


As with TB, leprosy among children is a public health problem reflecting its transmission in the community and the efficacy of leprosy control programmes. A quarter of a million people are identified with leprosy yearly23


Childhood TB is usually caused by MTB transmission from an adult index case in the household or in the community.27–30


The risk of


transmission is dependent on the probability, duration and proximity of exposure to an infectious source case and the infectiousness of the source case.29


Epidemiological risk factors of MTB transmission include local TB prevalence, as well as individual factors such as social interactions, cigarette smoking or passive exposure, living environment and socioeconomic status.3,28–32


Infants and toddlers are


more likely to be infected within the household, due to limited social interaction.29,30


In non-endemic countries, most childhood TB cases are detected through contact tracing, usually within the household. In endemic areas, this remains an important and often underutilised strategy for active case finding. In these settings children often present to health care facilities with symptomatic disease and older children are frequently exposed outside of the household.19,29,30


Transmission


within a community is traditionally measured by the annual risk of TB infection (ARI), based on tuberculin skin test (TST) surveys among school children.31 areas.31–33


ARI’s are estimated at 2–5 % in most endemic


An important limitation of ARI is the reduced specificity of the TST following BCG vaccination or NTM exposure, although this is reduced by using a higher TST cut-off value. A more important and rarely acknowledged limitation is the limited age spectrum of these surveys, which includes primary school children with limited risk of TB exposure compared to adolescents and young adults, thereby limiting its generalisation to high-risk groups within the community.33


and many more people are living with leprosy-induced impairments. The proportion of children among new cases ranged from 2.2–32.0 % in Africa, 0.6–7.8 % in the Americas, 3.7–12.0 % in South East Asia, 4.7–16.5 % in Eastern Mediterranean and 2.0–30.3 % in the Western Pacific Regions.24


reported prevalence rates of 10–17 per 1,000.25


A study from an urban slum in India In another study


9.8 % (306/3,118) of all leprosy cases registered over a 10-year period were children.16


Transmission Tuberculosis


MTB is almost always acquired by inhalation of infected droplets, which are generated by persons with active pulmonary disease. Infection rarely results in active disease, but is contained by the host


EUROPEAN INFECTIOUS DISEASE


An important aspect of childhood TB is the potentially rapid progression from infection to severe disease, which is influenced by various factors such as age, immune and nutritional status, genetic variability, virulence of the TB bacilli and BCG vaccination.3,28,29,32–35 Pre-chemotherapy studies that described the natural history of disease indicated that the risk of disease progression is greatest during the first two years of life, with a nadir between five to 10 years and a second peak during adolescence/early adulthood.34 Especially in young children, nearly all of the risk is concentrated in the first year following infection.34


Children may be at risk of


reactivation disease at a later time point, but this is rare and is usually associated with significant immune compromise. There are indications of increased incidence and severity of disease in HIV infected children.36,37


103


Figure 1: Stages of Mycobacterium tuberculosis Infection


Latent


Airborne inoculum containing Myobacterium tuberculosis


(usually an adult index case) Active


tuberculosis disease


immune response and can either be eradicated (no infection registered) or persist as ‘latent’ TB infection (LTBI), with risk of reactivating many years later (see Figure 1). Due to repeated exposure and high infection pressure within endemic communities, disease in these parts of the world often follow recent infection.26


Childhood


disease usually follows recent primary infection, although a second episode of TB most likely reflects a re-infection event.27,29


tuberculosis infection (LTBI)


Infection/ reinfection


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