Immunoglobulin deficiency in children with Hib vaccine failure.

Immunoglobulin deficiency has been reported in 21% of UK children with Hib vaccine failure but its clinical significance and long-term consequences are not known. This study aimed to estimate the prevalence of immunoglobulin deficiency in children with Hib vaccine failure several years after infection and to determine their risk of recurrent infections. The families of children who developed invasive Hib disease after prior immunisation were identified through national surveillance. A completed questionnaire and blood sample was provided by 170 children at a median of 4 years after infection, equivalent to 1035 child-years of follow-up. Nineteen (11.2%) children had immunoglobulin deficiency, including IgA (n=12), IgM (n=5) and all three immunoglobulin classes (n=2). Immunoglobulin deficiency was associated with younger age (<2 years) at initial Hib disease (12/19 [63.2%] vs. 60/151 [39.7%], P=0.05) and parental reporting of their child receiving >2 antibiotic courses annually in early childhood (11/19 [57.9%] vs. 39/151 [25.8%], P=0.004].). In a logistic regression model, Hib vaccine failure cases that had received multiple antibiotic courses in early childhood were 3.8 times (95% CI, 1.4-10.6; P=0.01) more likely to be immunoglobulin deficient at follow-up than those with fewer or no antibiotic courses. Thus, the prevalence of immunoglobulin deficiency in children with Hib vaccine failure at a median of four years after infection is half that reported at the time of the original infection. A proportion of children with Hib vaccine failure, especially where it occurs at a young age, appear to have a maturational delay in development of normal immunoglobulin concentrations.

Revaccination with measles, tetanus, poliovirus, Haemophilus influenzae type B, meningococcus C, and pneumococcus vaccines in children after hematopoietic stem cell transplantation.

BACKGROUND: There is a decrease in antibody levels after hematopoietic stem cell transplant (HSCT), and such patients may be at increased risk of acquiring vaccine-preventable infection. A simple and validated revaccination schedule is required. The aim of this study was to evaluate the immunogenicity of a revaccination schedule for pediatric HSCT recipients. METHODS: Thirty-eight children (age, 1-18 years) who had undergone autologous or allogeneic HSCT for malignant diseases were recruited. All children received vaccinations in accordance with a predefined schedule. Antibody concentrations were measured before and 2-4 weeks after vaccination against tetanus; Haemophilus influenzae type b (Hib); meningococcus C; measles; poliovirus serotypes 1, 2, and 3; and 9 pneumococcus serotypes. RESULTS: Before vaccination, protective antibody levels were found for tetanus in 95% of patients (geometric mean concentration [GMC], 0.07 IU/mL; 95% CI, 0.05-0.1 IU/mL), for Hib in 63% (GMC, 0.34 microg/mL; 95% CI, 0.21-0.57 microg/mL), for measles in 60% (GMC, 102 mIU/mL; 95% CI, 41-253 mIU/mL), for meningococcus C in 11% (geometric mean titer [GMT], 1:4; 95% CI, 1:2-1:8.4), for all 3 poliovirus serotypes in 29%, and for all 9 pneumococcal serotypes in 0%. Vaccination resulted in a significant increase (P < or = .05) in antibody levels to each vaccine antigen studied, with 100% of patients achieving protection against tetanus (GMC, 2.2 IU/mL; 95% CI, 1.8-2.7 IU/mL), 100% achieving protection against Hib (GMC, 8.4 microg/mL; 95% CI, 7.6-9.3 microg/mL), 100% achieving protection against measles (GMC, 2435 mIU/mL; 95% CI, 1724-3439 mIU/mL), 100% achieving protection against meningococcus C (GMT, 1:5706; 95% CI, 1:3510-1:9272), 92% achieving protection against the 3 poliovirus serotypes, and > or = 80% achieving protection against each of the heptavalent pneumococcal conjugate vaccine-associated serotypes. No factors relevant to age, underlying disease, or treatment type were found to significantly influence responses. CONCLUSION: Revaccination of pediatric HSCT recipients in accordance with this revaccination schedule provides a high level of protection against these vaccine-preventable diseases.

Revaccination of children after completion of standard chemotherapy for acute leukemia.

BACKGROUND: After the treatment of patients with acute leukemia, there is a decrease in vaccine-specific antibody and an increased susceptibility to certain vaccine-preventable diseases. A simple revaccination schedule is warranted. METHOD: Fifty-nine children (age, 1-18 years) who had completed standard chemotherapy in accordance with Medical Research Council of United Kingdom protocols were recruited. All children received a single dose of Haemophilus influenzae type b (Hib), tetanus, diphtheria, acellular pertussis, meningococcus C, polio, measles, mumps, and rubella vaccines > or = 6 months after completion of treatment. Antibody concentrations were measured before vaccination and 2-4 weeks and 12 months after vaccination. RESULTS: Prevaccination antibody levels were protective for all patients for tetanus (geometric mean concentration [GMC], 0.13 IU/mL; 95% CI, 0.1-0.17 IU/mL), for 87% for Hib (GMC, 0.5 microg/mL; 95% CI, 0.37-0.74 microg/mL), for 71% for measles (GMC, 301 mIU/mL; 95% CI, 163-557 mIU/mL), for 12% for meningococcus C (geometric mean titer [GMT], 1:2.9; 95% CI, 1:2.2 to 1:3.9), and for 11% for all 3 poliovirus serotypes. Revaccination resulted in a significant increase in levels of antibody to each vaccine antigen, with 100% of patients achieving optimal antitetanus antibody concentrations (defined as > 0.1 IU/mL; 1.5 IU/mL; 95% CI, 1.1-2.1 IU/mL), 93% achieving optimal antibody concentrations to Hib (defined as > 1.0 microg/mL; 6.5 microg/mL; 95% CI, 5.1-8.2 microg/mL), 94% achieving optimal antibody concentrations to measles (defined as > or = 120 mIU/mL; 2720 mIU/mL; 95% CI, 1423-5198 mIU/mL), 96% achieving optimal antibody concentrations to meningococcus C (defined as > or = 1:8; 1:1000; 95% CI, 1:483-1:2064), and 85% achieving optimal antibody concentrations to all the 3 poliovirus serotypes (defined as > or = 1:8). For the majority of subjects, protection persisted for at least 12 months after vaccination. CONCLUSION: Revaccination of children after standard chemotherapy is important, and protection can be achieved in the majority of these children using a simple schedule of 1 vaccine dose at 6 months after completion of leukemia therapy.