**2. Epidemiology of paediatric TB**

childhood TB is closely associated with poverty, overcrowding, and malnutrition, with consequently higher death and lower treatment success rates (Nelson and Wells, 2010).

Studies have revealed that children contribute a significant proportion to the disease burden and suffer severe tuberculosis-related morbidity and mortality, particularly in endemic areas. TB is now among the 10 major causes of mortality among children, with a global estimate of 130,000 deaths per year (WHO Report, 2009). Mortality has a strong correlation with socioe‐ conomic status, underlying nutritional status and immunocompetence (Palme, 2002). TB has also been reported to be the third most common cause of death in HIV-infected children with a clinical diagnosis of acute severe pneumonia (Palme, 2002). With roughly a million cases estimated globally each year (Walls and, Shingadia, 2004) and a much higher risk of severe disease and death among young children than adults, paediatric TB remains a public health emergency and this is particularly evident in developing countries with poor public health

As in adults, the majority of cases occur in the 22 high burden countries, where a combination of high transmission rates and a large proportion of the population under the age of 15 years mean children account for up to 25-40% of cases, with incidence rates for paediatric TB ranging from 60-600 per 100,000 per year (Nelson and Wells, 2004). Increasing rates of childhood TB have also been reported in Eastern Europe in the wake of the explosive TB epidemic which followed the break up of the Soviet Union (Walls and Shingadia, 2007). Even traditionally lowburden countries have seen a rise in cases, mainly due to immigration from TB endemic areas. In most countries of Western Europe and North America, where children account for 4-7% cases, paediatric incidence rates vary from about 1 to 15 per 100,000 per year, although much

Despite this huge disease burden, children's access to anti-tuberculosis treatment in most endemic areas remains poor, as tuberculosis control programs focus predominantly on the treatment of sputum smear–positive adults (Starke, 2002). Recent technological advancements in diagnosis of TB in adults have not been validated in children and, similarly, trials of new drugs and development of pediatric formulations of standard first- and second-line drugs are lagging behind. As a result both research and surveillance data in the field of childhood TB have been greatly limited. Further research into the epidemiology, immune mechanisms, diagnosis, treatment and prevention of childhood TB is urgently needed to enhance our understanding of TB in children which may provide wider insights and opportunities to

Another problem is that most programs for TB control are limited because they target and treat only active cases (Graham, et al., 2004) when most TB cases in children present as latent tuberculosis infection (LTBI) with active disease occurring mainly in developing countries (Dogra, et al., 2007). Without treatment, the majority of infants aged under 1 year die due to TB. Even with effective antimicrobial therapy, severe TB continues to occur in young children (Ávalos and Montes de Oca, 2012). Priorities for future research should, therefore, enhance

higher rates are observed in some cities, such as London (Newton et al., 2008).

facilitate efforts to control TB in the population.

collaborations between developing and developed nations.

infrastructure.

372 Tuberculosis - Current Issues in Diagnosis and Management

### **2.1. Global disease burden of paediatric TB**

Poor case ascertainment, lack of resources for active case finding in most settings, and limited paediatric surveillance data from TB control programs all hamper efforts to define accurately the global burden of childhood TB (Nelson and Wells, 2004). Until recently, under the WHO Directly Observed Treatment Short Course (DOTS) strategy, only smear positive cases were being reported for children, yet smears are seldom performed in many high burden settings and most disease in children is smear negative.

Although limited surveillance data prevent reliable estimates of the contribution of TB to childhood mortality, available data indicate that pneumonia is the commonest cause of childhood death globally (Nelson et al., 2004) an implication that TB, being an important cause of pneumonia in many settings (Scott et al., 2008), may contribute significantly to these global childhood deaths. A necropsy study in Zambia found evidence of TB in 18% of HIV-positive and 26% of HIV-negative children dying of pneumonia (Chintu et al., 2002) although more robust regional data on the epidemiology of childhood TB are urgently needed to define the true burden of disease, and to characterize current transmission rates and circulating strains.

#### **2.2. Pathophysiology of TB in children**
