The Gambian Haemophilus influenzae type b vaccine trial: what does it tell us about the burden of Haemophilus influenzae type b disease?

The true burden of disease caused by Haemophilus influenzae type b (Hib) remains a mystery in many parts of the developing world. The most frequent manifestations of Hib disease are pneumonia and meningitis. In developing countries where it has been studied, Hib has proved to be a major cause of infant meningitis, generally occurring with greater frequency, in younger infants and with a worse outcome than in industrialized countries in the prevaccine era. The burden of Hib pneumonia is more difficult to define. Studies from developing countries of pneumonia etiology suggested that Hib was responsible for 5 to 10 of episodes of severe pneumonia. A Gambian study found Hib to be responsible for 7% of cases. However, a recently published trial of a Hib conjugate vaccine in Gambian infants showed that the vaccine prevented 21% of episodes of severe pneumonia in vaccine recipients, suggesting that this is the true contribution of Hib to the burden of severe pneumonia. The same trial demonstrated a mild herd effect, so this figure may be an underestimate. The biases that lead to the underestimation of the contribution of Hib to the pneumonia burden also apply to estimates of the proportion of severe pneumonia caused by Streptococcus pneumoniae. Vaccine trials may reveal the true burden of that pathogen also.