title: Diagnosis of tuberculosis in South African children with a T-cell-based assay: a prospective cohort study.
abstract: BACKGROUND
  Childhood tuberculosis often presents non-specifically and is a common differential diagnosis in high prevalence areas. Current diagnostic tools have poor sensitivity and cannot reliably exclude tuberculosis, so overdiagnosis is common. HIV co-infection exacerbates this problem and accounts for an increasing proportion of paediatric tuberculosis worldwide.
  
  
  METHODS
  We assessed the usefulness of a T-cell-based rapid blood test for Mycobacterium tuberculosis infection, the enzyme-linked immunospot assay (ELISPOT), in routine clinical practice. We did a prospective blinded study of 293 African children with suspected tuberculosis in kwaZulu-Natal, a region with high HIV prevalence. Children had full clinical assessment, ELISPOT, and a tuberculin skin test. Test results were compared with final clinical and microbiological diagnoses.
  
  
  RESULTS
  In children with tuberculosis, sensitivity of ELISPOT was 83% (95% CI 75-89, n=133), significantly higher (p<0.001) than the 63% (54-72) sensitivity of tuberculin skin test (n=116). Sensitivity of tuberculin skin test fell significantly in children younger than 3 years (to 51%), with HIV co-infection (36%), or with malnutrition (44%). Sensitivity of ELISPOT, which was not significantly adversely affected by these factors, was 85%, 73%, and 78%, respectively in these subgroups. In 116 children with both test results available, sensitivity of the two tests combined was 91% (85-95).
  
  
  CONCLUSIONS
  Diagnostic sensitivity of ELISPOT is higher than that of the skin test and is less affected by factors frequently associated with childhood tuberculosis in developing countries. Used together with the skin test, ELISPOT provides a clinically useful diagnostic sensitivity in African children with suspected tuberculosis.
authors.affiliation: Ngwelezana Hospital, Empangeni, kwaZulu-Natal, South Africa.
authors.forename: Susan
authors.initials: S
authors.lastname: Liebeschuetz
authors.forename: Sheila
authors.initials: S
authors.lastname: Bamber
authors.forename: Katie
authors.initials: K
authors.lastname: Ewer
authors.forename: Jonathan
authors.initials: J
authors.lastname: Deeks
authors.forename: Ansar A
authors.initials: AA
authors.lastname: Pathan
authors.forename: Ajit
authors.initials: A
authors.lastname: Lalvani
mesh_terms: D000293:Adolescent; D000942:Antigens, Bacterial / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006679:HIV Seropositivity / Q000150:complications; D006801:Humans; D007223:Infant; D008297:Male; D009169:Mycobacterium tuberculosis / Q000276:immunology / Q000302:isolation & purification; D012680:Sensitivity and Specificity; D013019:South Africa; D013601:T-Lymphocytes / Q000382:microbiology*; D014374:Tuberculin Test; D014397:Tuberculosis, Pulmonary / Q000150:complications / Q000175:diagnosis*
chemical_list: D000942:Antigens, Bacterial