Detection of tuberculosis in HIV-infected children using an enzyme-linked immunospot assay.
OBJECTIVE
To evaluate an enzyme-linked immunospot assay (ELISPOT) for the diagnosis of tuberculosis (TB) in HIV-infected children with suspected TB and to compare the performance of ELISPOT with the tuberculin skin test (TST).


METHODS
Interferon-gamma responses to Mycobacterium tuberculosis-specific antigens were measured by ELISPOT in HIV-infected children with suspected TB. HIV-infected and HIV-uninfected children without TB were taken for comparison.


RESULTS
Results were available for 188 children, of whom 139 (74%) were HIV-infected. Of these, 22 were classified as having definite TB: 24 probable TB, 14 possible TB and 128 not having TB. The median (range) age of patients was 20 (10-54.1) months. Median interferon-gamma responses to early-secreted antigenic target-6 and culture filtrate protein-10 were higher in children with definite or probable TB compared with children without TB (P < 0.002). In HIV-infected children with an interpretable ELISPOT result, the ELISPOT was positive in 14/21 (66%) with definite TB. A significantly higher proportion of HIV-infected children with definite or probable TB had a positive ELISPOT compared with a positive TST [25/39 (64%) vs. 10/34 (29%), P = 0.005]. In contrast to TST, results from ELISPOT were not affected by young age or severe immunosuppression. In HIV-infected children without active TB disease, 27% had a positive ELISPOT, suggesting latent TB infection.


CONCLUSIONS
ELISPOT is more sensitive than TST for the detection of active TB in HIV-infected children. However, the sensitivity of current ELISPOT assays is not sufficiently high to be used as a rule out test for TB.
Davies
Mary-Ann
MA
Red Cross Children's Hospital and School of Child and Adolescent Health, University of Cape Town, Cape Town, South Africa.|School of Public Health and Family Medicine, University of Cape Town, South Africa.
Connell
Tom
T
Department of Paediatrics, University of Melbourne; Infectious Diseases Unit, Department of General Medicine; and Murdoch Children's Research Institute; Royal Children's Hospital Melbourne, Parkville, Australia.|Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, South Africa.
Johannisen
Christine
C
Red Cross Children's Hospital and School of Child and Adolescent Health, University of Cape Town, Cape Town, South Africa.
Wood
Kathryn
K
Red Cross Children's Hospital and School of Child and Adolescent Health, University of Cape Town, Cape Town, South Africa.|Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, South Africa.
Pienaar
Sandy
S
Red Cross Children's Hospital and School of Child and Adolescent Health, University of Cape Town, Cape Town, South Africa.
Wilkinson
Katalin A
KA
Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, South Africa.|National Institute for Medical Research, Mill Hill, London NW7 1AA, UK.
Wilkinson
Robert J
RJ
Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, South Africa.|National Institute for Medical Research, Mill Hill, London NW7 1AA, UK.|Division of Medicine, Imperial College London, W2 1PG, UK.
Zar
Heather J
HJ
Red Cross Children's Hospital and School of Child and Adolescent Health, University of Cape Town, Cape Town, South Africa.
Eley
Brian
B
Red Cross Children's Hospital and School of Child and Adolescent Health, University of Cape Town, Cape Town, South Africa.
Beatty
David
D
Red Cross Children's Hospital and School of Child and Adolescent Health, University of Cape Town, Cape Town, South Africa.
Curtis
Nigel
N
Department of Paediatrics, University of Melbourne; Infectious Diseases Unit, Department of General Medicine; and Murdoch Children's Research Institute; Royal Children's Hospital Melbourne, Parkville, Australia.
Nicol
Mark P
MP
Red Cross Children's Hospital and School of Child and Adolescent Health, University of Cape Town, Cape Town, South Africa.|Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, South Africa.
D000367:Age Factors; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000276:immunology*; D006801:Humans; D016867:Immunocompromised Host / Q000276:immunology*; D007223:Infant; D007371:Interferon-gamma / Q000097:blood; D055985:Latent Tuberculosis / Q000150:complications / Q000175:diagnosis / Q000276:immunology; D008297:Male; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D009752:Nutritional Status; D012680:Sensitivity and Specificity; D013019:South Africa; D014374:Tuberculin Test / Q000379:methods; D014397:Tuberculosis, Pulmonary / Q000150:complications / Q000175:diagnosis* / Q000276:immunology
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C117940:CFP-10 protein, Mycobacterium tuberculosis; C525005:ESAT-6 antigen, Mycobacterium leprae; D007371:Interferon-gamma