Serotype-specific immunoglobulin G antibody responses to pneumococcal polysaccharide vaccine in children with sickle cell anemia: effects of continued penicillin prophylaxis. Prophylaxis with oral penicillin in children with sickle cell anemia. A randomized trial. Prevention of pneumococcal infection in children with homozygous sickle cell disease.
(1) To determine serotype-specific IgG antibody responses to reimmunization with pneumococcal polysaccharide vaccine at age 5 years in children with sickle cell anemia and (2) to determine whether continued penicillin prophylaxis had any adverse effects on these responses.
                Children with sickle cell anemia, who had been treated with prophylactic penicillin for at least 2 years before their fifth birthday, were randomly selected at age 5 years to continue penicillin prophylaxis or to receive placebo treatment. These children had been immunized once or twice in early childhood with pneumococcal polysaccharide vaccine and were reimmunized at the time of randomization.
                Serotype-specific IgG antibody responses to reimmunization varied according to pneumococcal serotype but in general were mediocre or poor; the poorest response was to serotype 6B. The antibody responses were similar in subjects with continued penicillin prophylaxis or placebo treatment, and in subjects who received one or two pneumococcal vaccinations before reimmunization. The occurrence of pneumococcal bacteremia was associated with low IgG antibody concentrations to the infecting serotype.
                Reimmunization of children with sickle cell anemia who received pneumococcal polysaccharide vaccine at age 5 years induces limited production of serotype-specific IgG antibodies, regardless of previous pneumococcal vaccine history. Continued penicillin prophylaxis does not interfere with serotype-specific IgG antibody responses to reimmunization. Children with sickle cell anemia have an increased susceptibility to bacterial infections, especially to those caused by Streptococcus pneumoniae. We therefore conducted a multicenter, randomized, double-blind, placebo-controlled clinical trial to test whether the regular, daily administration of oral penicillin would reduce the incidence of documented septicemia due to S.pneumoniae in children with sickle cell anemia who were under the age of three years at the time of entry. The children were randomly assigned to receive either 125 mg of penicillin V potassium (105 children) or placebo (110 children) twice daily. The trial was terminated 8 months early, after an average of 15 months of follow-up, when an 84 percent reduction in the incidence of infection was observed in the group treated with penicillin, as compared with the group given placebo (13 of 110 patients vs. 2 of 105; P = 0.0025), with no deaths from pneumococcal septicemia occurring in the penicillin group but three deaths from the infection occurring in the placebo group. On the basis of these results, we conclude that children should be screened in the neonatal period for sickle cell hemoglobinopathy and that those with sickle cell anemia should receive prophylactic therapy with oral penicillin by four months of age to decrease the morbidity and mortality associated with pneumococcal septicemia. The efficacy of prophylactic penicillin and of 14 valent pneumococcal vaccine in preventing pneumococcal infection in homozygous sickle cell (SS) disease was investigated in 242 children aged 6 months to 3 years at entry. In the first five years of the trial there were 11 pneumococcal infections in the pneumococcal vaccine treated group, 10 by serotypes present in the vaccine. Type 23 accounted for five of these, and there was evidence of higher infection rates in those given the vaccine before age 1. No pneumococcal isolations occurred in the penicillin group while receiving penicillin, although four isolations occurred within one year of stopping penicillin. Probably the most effective prophylaxis against pneumococcal infection requires penicillin beyond the age of 3. The age at which pneumococcal vaccine should be given must await further data on antibody response and clinical efficacy in these patients.