Evaluation of vaccines to prevent childhood pneumonia: lessons relevant to planning tuberculosis vaccine trials.

Bacterial pneumonia in children is usually caused by one of the two leading pathogens, Streptococcus pneumoniae (pneumococcus) and Haemophilus influenzae, either type b (Hib) or nonencapsulated types. Hib conjugate vaccines suitable for use in infants have been available for about a decade, and experience with a trial of one of these vaccines in Africa showed that the vaccines can prevent Hib pneumonia, as well as other manifestations of Hib disease. It also showed that vaccine trials can provide useful estimates of the role of Hib in childhood pneumonia. Trials of pneumococcal conjugate vaccines that are currently under way have been designed to estimate disease burden and efficacy. A major risk of vaccine trials that use bacteriologic end points is that the vaccine may affect the diagnostic test itself, creating a misleading impression of efficacy. Trials of future tuberculosis vaccines are discussed in light of these experiences. It is important that the trials are designed to measure the effect on all clinical disease, as well as strict microbiological end points. The existence of bacille Calmette-Guérin (BCG) complicates future trials, and such trials should take into account possible nonspecific effects of BCG in addition to its effect on tuberculosis.