Management of bacterial meningitis in adults.

sised the capacity of the immune system to respond effectively to numerous simultaneous antigens. Using data linkage, Miller et al found no evidence for an increase in admissions to hospital for serious bacterial infections following MMR vaccination. 9 One disadvantage of giving vaccines in combination is that it may not always be clear which component is responsible for a particular adverse event. As important as safety is ensuring that combining antigens does not compromise the protection afforded by each antigen. In the study by Schmitt et al, no difference was found in subjects achieving protective concentrations of antibodies against diphtheria, tetanus, hepatitis B, and polio. Concentrations of pertussis antibody were the same for both groups and comparable with those achieved in trials of DTaP alone. However, the concentrations of Hib polyribosylribitol phosphate (PRP) antibody were statistically significantly lower in those children receiving all the antigens mixed together. The clinical significance of this is uncertain. One of the longest established combination vaccines is DTwP. Two Swedish vaccine trials found a significant difference in post-immunisation levels of diphtheria antitoxin depending on the presence and nature of any pertussis antigens in the vaccine. The addition of an efficacious wholecell pertussis (wP) component to diphtheria and tetanus vaccine increased the geometrical mean titre of diphtheria antitoxin in the recipients, whereas the addition of acellular pertussis (aP) or a poorly efficacious wholecell pertussis vaccine produced lower concentrations than only diphtheria and tetanus vaccine. In a few children, the concentrations reached were considered non-protective, confirming the well known adjuvant effect of efficacious wholecell pertussis vaccines. DTwP vaccines can be combined with Hib vaccines with no clinically significant loss in immunogenicity, but when DTaP is used instead lower concentrations of Hib PRP antibodies have been observed, and in some cases these are below protective levels. The clinical significance of this was unclear. However, there has been a rise in Hib cases in fully immunised children in the United Kingdom. This is probably in part due to the use of a combined DTaP/Hib preparation. Dagan et al reported that infants who were given a diphtheria-tetanus-pertussispolio-Hib vaccine, in which the Hib component was conjugated to tetanus, simultaneously with a pneumococcal vaccine also conjugated to tetanus toxoid had lower Hib PRP antibody concentrations than infants who had received pneumococcal vaccine conjugated to diphtheria toxoid. Furthermore, children who had received higher doses of pneumococcal tetanus conjugate had poorer responses. This implies that difficulties may arise in using simultaneous or combined vaccines that have conjugates in common.