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.

Immune function in six patients with Evans syndrome (Coombs-positive hemolytic anemia and immune thrombocytopenia) was compared to that in seven with chronic ITP. The two groups differed in measurements of T-cell subsets and immunoglobulin production. Evans syndrome patients had decreased T4 (T-helper) (P = 0.025), increased T8 (T-suppressor) (P = 0.008), and a decreased ratio of T4:T8 cells (P = 0.0009) when compared to controls. Results in chronic ITP patients were similar to those in controls. Serum IgG, IgM, and IgA levels and in vitro synthesis of IgG and/or IgM were decreased in most Evans syndrome patients. Diminished in vivo and in vitro immunoglobulin synthesis in Evans syndrome is consistent with the decreased T4:T8 ratio in these patients. The altered T4:T8 ratio may represent an unsuccessful response to an autoimmune process in which the trigger is unknown.

ABSTRACT. Objective. We studied the prevalence of nasopharyngeal (NP) carriage, antimicrobial susceptibilities, and serotypes of Streptococcus pneumoniae (SP) in children with sickle cell disease (SCD) in the Mid-South. In addition, we examined risk factors for NP carriage of penicillin-resistant SP (PRSP).Study Design. Between July 1994 and December 1995, we obtained NP cultures from 312 children with SCD followed at the Mid-South Sickle Cell Center, 208 (67%) of whom were receiving penicillin prophylaxis.Results. Among the 312 patients, colonization with SP occurred in 42 (13%), 30 (71%) of whom were receiving penicillin prophylaxis. Twenty-three of the 42 SP isolates (55%) were resistant to penicillin; 5 of the 23 (22%) were highly resistant. PRSP organisms were also resistant to cefotaxime (43%), trimethoprim-sulfamethoxazole (57%), and erythromycin (22%). Serotypes 6A, 6B, 14, 19A, and 23F accounted for 19 (90%) of 21 resistant strains. Children who were treated with antibiotics during the preceding month were more likely to carry PRSP than children who were not treated.Conclusions. There is a high prevalence of NP carriage of PRSP in children with SCD in the Mid-South, which raises concerns regarding the continued effectiveness of penicillin prophylaxis in these children. Further studies on the antimicrobial susceptibilities of resistant organisms and the relationship between NP carriage of SP and invasive disease are needed before developing new recommendations for prophylaxis and treatment. Pediatrics 1997;99(4). URL: http://www.pediatrics.org/cgi/ content/full/99/4/e7; Streptococcus pneumoniae, penicillin resistance, colonization, sickle cell disease.

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 younger than 3 years of age at the time of entry. The children were randomly assigned to receive either 125 mg of penicillin 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% 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 v 2 of 105; P = .0025). There were no deaths from pneumococcal septicemia in the penicillin-treated group but three deaths from the infection occurred 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 4 months of age to decrease the morbidity and mortality [SEE FIGURE IN SOURCE PDF.] associated with pneumococcal septicemia. (Previously published in N Engl J Med 1986;314:1593-1599.

Immunologic studies were performed on mononuclear cells from ten chronically transfused children with sickle cell disease, and the results were compared with those from five other groups: 21 sickle cell patients who were not receiving regular transfusions, 6 chronically transfused children with other forms of refractory anemia, 10 previously splenectomized children, 5 boys with hemophilia A, and 27 normal adult controls. The helper:suppressor T cell ratios (T4:T8) in all groups except hemophiliacs were normal, were unrelated to the number of units transfused, and were not suggestive of findings reported for patients with the acquired immune deficiency syndrome (AIDS) or groups at risk for the syndrome. Percentages of T3, T4, and T8 cells were low in sickle cell and splenectomized patients, but not in chronically transfused patients with other anemias. Serum IgG was frequently elevated, and IgG synthesis in vitro was increased relative to IgM synthesis in sickle cell patients. Coculture experiments indicated that such findings may stem from a selective increase in IgG synthesis by B cells. Thus, transfused sickle cell patients have a particular pattern of immunologic abnormalities that is distinct from that seen in AIDS.