TBNET - RESEARCH PROJECT #9

The value of interferon-gamma release assays in the management of peripheral

lymphadenopathy in children

Principal Investigator: Anne K Detjen (G), Klaus Magdorf (G), Bolette Søborg (D), Pernille Ravn (D)

Project title: The value of Interferon-g release assays in the management of peripheral lymphadenopathy in children

Key words: Interferon-g release assays, children, lymphadenopathy, NTM

Investigators (PI), participating centres (address and email):

Anne K Detjen _^1,3 (Germany), Klaus Magdorf _¹(Germany), Bolette Søborg _²(Denmark), Pernille Ravn (Denmark)_²

_^1,3 Desmond Tutu TB Centre, Stellenbosch University, PO Box , Tygerberg 7505, South Africa, +27 21 9389177; This e-mail address is being protected from spam bots, you need JavaScript enabled to view it
_² STATENS SERUM INSTITUT - 5, Artillerivej - DK-2300 Copenhagen S +45 3268 3268; This e-mail address is being protected from spam bots, you need JavaScript enabled to view it
_³ Charité Universitätsmedizin, Klinik f. Pädiatrie m.S: Pneumologie und Immunologie; Augustenburger Platz 1, 13353 Berlin; This e-mail address is being protected from spam bots, you need JavaScript enabled to view it '; document.write( '' ); document.write( addy_text94839 ); document.write( '<\/a>' ); //-->\n This e-mail address is being protected from spam bots, you need JavaScript enabled to view it

Rationale for the study: Infections with either Mycobacterium tuberculosis (M. tb) or non-tuberculous mycobacteria (NTM) play an important role in the differential diagnosis of peripheral lymphadenopathy in children. Differentiation between TB- and NTM-lymphadenitis has therapeutic implications, since TB is treated with anituberculous chemotherapy, whereas NTM-lymphadenitis is treated by lymph node excision biopsy. Interferon-g release assays (IGRAs) can, in contrast to the tuberculin skin test (TST) exclude TB in unclear lymphadenitis.

Hypothesis: By excluding tuberculosis, IGRAs are of additional value for the management of peripheral lymphadenopathy of unknown origin, e.g. NTM lymphadenitis.

Aims: To assess the value of IGRAs in the differential diagnosis of lymphadenitis as well as to gain epidemiologic data on incidence, treatment, outcome of NTM-lymphadenitis.

Setting: Germany: Charité University Hospital and referral pediatricians and hospitals. The incidence of lymph node TB in children was 5.4% (12/223) in 2005 (Incidence of childhood TB 2.3/100 000 in 2005). The estimated incidence of NTM-lymphadenitis in children <3 years Germany was 0.9/100 000 in 2004.

Denmark: University Hospital of Rigshospitalet, pediatric and infectious disease ward and pediatric wards at several Community Hospitals. In Denmark 2005 the incidence of childhood TB was 4/100.000. Lymphnode TB cases, among all childhood TB, cases came to 22,3% (9/40). There is no official number of NTM-lymphadenitis in children in Denmark.

Approach: Prospective analysis. 2 years recruitment and 2 years follow-up of children with either TB- or NTM-lymphadenitis. Eligible are children with peripheral lymphadenitis of unknown origin and without response to standard antibiotic therapy will be recruited prospectively. Data on ethnicity, BCG-vaccination status, TB exposure, immune status (e.g. HIV-infection, basic T-cell function) will be collected.

The children will be evaluated with TST and two IGRAs, QuantiFERON^®-TB Gold In-Tube and T SPOT^®.TB. The children will undergo lymph node excision biopsy for TB culture and histology. EBV, Toxoplasmosis or other reasons for peripheral lymphadenitis will be excluded.

Analysis:

1. Epidemiologic data on incidence of TB and NTM-lymphadenitis, influence of BCG vaccination, immunocompetent versus immunocompromised children. Bacteriologic yield,

2. Incidence of TB-lymphadenitis, Incidence of NTM-lymphadenitis in the study population (comparison of incidence in the differenc participating countries –correct for BCG vaccination status?). Age distribution.

3. Collection of data on therapy/outcome/complications/relapses.

4. Comparision of number of positive results in TST and IGRAs by using Cohen’s Kappa Coefficient.

Perspectives: Exclusion of TB in TST posititive children with unclear lymphadenitis by IGRAs can guide management of those children towards excision biopsy.

In addition, this study will give epidemiologic data on the incidence, management, outcome of TB and NTM-lymphadenitis in children from different european countries.