Diagnosis of childhood tuberculosis and host RNA expression in Africa.

BACKGROUND: Improved diagnostic tests for tuberculosis in children are needed. We hypothesized that transcriptional signatures of host blood could be used to distinguish tuberculosis from other diseases in African children who either were or were not infected with the human immunodeficiency virus (HIV). METHODS: The study population comprised prospective cohorts of children who were undergoing evaluation for suspected tuberculosis in South Africa (655 children), Malawi (701 children), and Kenya (1599 children). Patients were assigned to groups according to whether the diagnosis was culture-confirmed tuberculosis, culture-negative tuberculosis, diseases other than tuberculosis, or latent tuberculosis infection. Diagnostic signatures distinguishing tuberculosis from other diseases and from latent tuberculosis infection were identified from genomewide analysis of RNA expression in host blood. RESULTS: We identified a 51-transcript signature distinguishing tuberculosis from other diseases in the South African and Malawian children (the discovery cohort). In the Kenyan children (the validation cohort), a risk score based on the signature for tuberculosis and for diseases other than tuberculosis showed a sensitivity of 82.9% (95% confidence interval [CI], 68.6 to 94.3) and a specificity of 83.6% (95% CI, 74.6 to 92.7) for the diagnosis of culture-confirmed tuberculosis. Among patients with cultures negative for Mycobacterium tuberculosis who were treated for tuberculosis (those with highly probable, probable, or possible cases of tuberculosis), the estimated sensitivity was 62.5 to 82.3%, 42.1 to 80.8%, and 35.3 to 79.6%, respectively, for different estimates of actual tuberculosis in the groups. In comparison, the sensitivity of the Xpert MTB/RIF assay for molecular detection of M. tuberculosis DNA in cases of culture-confirmed tuberculosis was 54.3% (95% CI, 37.1 to 68.6), and the sensitivity in highly probable, probable, or possible cases was an estimated 25.0 to 35.7%, 5.3 to 13.3%, and 0%, respectively; the specificity of the assay was 100%. CONCLUSIONS: RNA expression signatures provided data that helped distinguish tuberculosis from other diseases in African children with and those without HIV infection. (Funded by the European Union Action for Diseases of Poverty Program and others).

Diagnostic performance of visible severe wasting for identifying severe acute malnutrition in children admitted to hospital in Kenya.

OBJECTIVE: To determine the diagnostic value of visible severe wasting in identifying severe acute malnutrition at two public hospitals in Kenya. METHODS: This was a cross-sectional study of children aged 6 to 59.9 months admitted to one rural and one urban hospital. On admission, mid-upper arm circumference (MUAC), weight and height were measured and the presence of visible severe wasting was assessed. The diagnostic performance of visible severe wasting was evaluated against anthropometric criteria. FINDINGS: Of 11,166 children admitted, 563 (5%) had kwashiorkor and 1406 (12.5%) were severely wasted (MUAC < 11.5 cm). The combined sensitivity and specificity of visible severe wasting at the two hospitals, as assessed against a MUAC < 11.5 cm, were 54% (95% confidence interval, CI: 51-56) and 96% (95% CI: 96-97), respectively; at one hospital, its sensitivity and specificity against a weight-for-height z-score below -3 were 44.7% (95% CI: 42-48) and 96.5% (95% CI: 96-97), respectively. Severely wasted children who were correctly identified by visible severe wasting were consistently older, more severely wasted, more often having kwashiorkor, more often positive to the human immunodeficiency virus, ill for a longer period and at greater risk of death. Visible severe wasting had lower sensitivity for determining the risk of death than the anthropometric measures. There was no evidence to support measuring both MUAC and weight-for-height z-score. CONCLUSION: Visible severe wasting failed to detect approximately half of the children admitted to hospital with severe acute malnutrition diagnosed anthropometrically. Routine screening by MUAC is quick, simple and inexpensive and should be part of the standard assessment of all paediatric hospital admissions in the study setting.