Tuberculosis in Children

Tuberculosis (TB) is an infectious disease caused by the bacillus Mycobacterium tuberculosis. Tuberculosis bacilli have lived in symbiosis with mankind since times immemorial. In the western world the clinical features and communicability of tuberculosis were known before 1000 BC). (1)] Tuberculosis has remained a major public health problem since the dawn of civilization. In last 15 years TB control has made good progress globally, however worldwide, 9.6 million people are estimated to have fallen ill with TB in 2014: 5.4 million men, 3.2 million women and 1.0 million children and 1.5 million died of TB (3). Of the 1.0 million estimated cases of TB in children worldwide, 75% occur in the 22 high-burden countries (4). In low-burden countries, childhood TB constitutes <5% of the TB caseload, compared with 20%–40% in high-burden countries (5), 6]. Regional data from the World Health Organization (WHO) in 2007 showed that smear-positive TB in children aged <14 years accounted for 0.6%–3.6% of reported cases [4]. However, because >95% of cases in children <12 years of age are smear negative, these data underestimate the true burden of TB [7]. In low- and middle-income countries, childhood TB is closely associated with poverty, crowding, and malnutrition, with consequently higher death and lower treatment success rates [7]. Another unique aspect of TB in children is rapid progression from infection with Mycobacterium tuberculosis to disease.

A major challenge of childhood TB is establishing an accurate diagnosis. In children <15% of cases are sputum acid-fast bacilli smear positive, and mycobacterial culture yields are 30%–40% [8, 9]. In the absence of bacteriological confirmation, the diagnosis of childhood TB is based on close contact with an infectious index patient, a positive tuberculin skin test (TST) result, and presence of suggestive abnormalities on a chest radiograph[10,11]. Chest radiograph findings may be normal for a significant proportion of children with confirmed pulmonary TB[12]. Collecting an adequate sample for microbiological diagnosis presents a significant challenge, particularly for small children who cannot produce a good sputum specimen [13]. Inducing sputum after hypertonic saline nebulization has also been shown to be feasible for young children, although the most widely used procedure is still the early-morning gastric aspiration or lavage. However, all these procedures involve hospitalization, trained personnel, and attention to infection control. Although culture on Lowenstein-Jensen medium is considered to be the gold standard, liquid culture systems (commercial and noncommercial) offer the possibility of more rapid and more sensitive diagnosis of active TB and drug susceptibility but are not widely available in resource-poor settings [13, 14]

Although serum-based antibody assays offer advantages of easy specimen collection and rapidity, none of the currently available serologic tests are sensitive or specific enough for clinical use. Detection of interferon-gamma (g) production by sensitized mononuclear cells (TSPOT) or whole blood (interferon-gamma (g) release assay) on stimulation by specific M. tuberculosis antigens ESAT-6 and CFP-10 is an alternative to TST [15]. The interferon-gamma (g) release assays have not been shown to have major advantages over the TST in terms of sensitivity or specificity and are more expensive; the advantages are that they do not require a second patient visit, and they reduce the chances of human error in measurement [16–19]

In 2010, the Centers for Disease Control and Prevention (CDC) updated their guidelines for testing for TB infection, concluding that IGRAs “may be used instead of a tuberculin

skin test in all situations in which the CDC recommends the tuberculin skin test as an aid in diagnosing M. tuberculosis infection” [20,21]

currently, the major role of these tests is likely to be for latent TB in countries where TB is not endemic. But, they could potentially play a role in detection of TB in HIV-infected or malnourished children, severe TB disease, and other forms of immune suppression for whom the TST performs poorly; however, this requires further research. In this part our country childhood TB is highly endemic, majority children are malnourished. Considering some conditions like difficult microbiological confirmation, rapid progression from latent to active and severe form of TB in children, majority of TB children are malnourished and studies evaluating IGRAs performance in children are scant particularly in this region, I want to study the diagnostic value of interferon gamma ( release assays (IGRA) in children with tuberculosis.