Is passive diagnosis enough? The impact of subclinical disease on diagnostic strategies for tuberculosis

Am J Respir Crit Care Med. 2013 Mar 1;187(5):543-51. doi: 10.1164/rccm.201207-1217OC. Epub 2012 Dec 21.


Rationale: Tuberculosis (TB) is characterized by a subclinical phase (symptoms absent or not considered abnormal); prediagnostic phase (symptoms noticed but diagnosis not pursued); and clinical phase (care actively sought). Diagnostic capacity during these phases is limited.

Objectives: To estimate the population-level impact of TB case-finding strategies in the presence of subclinical and prediagnostic disease.

Methods: We created a mathematical epidemic model of TB, calibrated to global incidence. We then introduced three prototypical diagnostic interventions: increased sensitivity of diagnosis in the clinical phase by 20% ("passive"); early diagnosis during the prediagnostic phase at a rate of 10% per year ("enhanced"); and population-based diagnosis of 5% of undiagnosed prevalent cases per year ("active").

Measurements and main results: If the subclinical phase was ignored, as in most models, the passive strategy was projected to reduce TB incidence by 18% (90% uncertainty range [UR], 11-32%) by year 10, compared with 23% (90% UR, 14-35%) for the enhanced strategy and 18% (90% UR, 11-28%) for the active strategy. After incorporating a subclinical phase into the model, consistent with population-based prevalence surveys, the active strategy still reduced 10-year TB incidence by 16% (90% UR, 11-28%), but the passive and enhanced strategies' impact was attenuated to 11% (90% UR, 8-25%) and 6% (90% UR, 4-13%), respectively. The degree of attenuation depended strongly on the transmission rate during the subclinical phase.

Conclusions: Subclinical disease may limit the impact of current diagnostic strategies for TB. Active detection of undiagnosed prevalent cases may achieve greater population-level TB control than increasing passive case detection.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Disease Progression*
  • Early Diagnosis
  • Epidemiological Monitoring*
  • Humans
  • Models, Statistical*
  • Multivariate Analysis
  • Prevalence
  • Sensitivity and Specificity
  • Tuberculosis / diagnosis*
  • Tuberculosis / epidemiology*
  • Tuberculosis / prevention & control