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.

Haemophilus influenzae type b reemergence after combination immunization.

An increase in Haemophilus influenzae type b (Hib) in British children has been linked to the widespread use of a diphtheria/tetanus/acellular pertussis combination vaccine (DTaP-Hib). We measured anti-polyribosyl-ribitol phosphate antibody concentration and avidity before and after a Hib booster in 176 children 2-4 years of age who had received 3 doses of DTP-Hib (either DT whole cell pertussis-Hib or DTaP-Hib) combination vaccine in infancy. We also measured pharyngeal carriage of Hib. Antibody concentrations before and avidity indices after vaccination were low (geometric mean concentration 0.46 mug/mL, 95% confidence interval [CI] 0.36-0.58; geometric mean avidity index 0.16, 95% CI 0.14-0.18) and inversely related to the number of previous doses of DTaP-Hib (p = 0.02 and p<0.001, respectively). Hib was found in 2.1% (95% CI 0.7%-6.0%) of study participants. Our data support an association between DTaP-Hib vaccine combinations and clinical Hib disease through an effect on antibody concentration and avidity.

IFN-gamma at the site of infection determines rate of clearance of infection in cryptococcal meningitis.

In animal models, immunity to cryptococcal infection, as in many chronic fungal and bacterial infections, is associated with a granulomatous inflammatory response, intact cell-mediated immunity, and a Th1 pattern of cytokine release. To examine the correlates of human immunity to cryptococcal infection in vivo, we analyzed immune parameters at the site of infection over time and assessed the rate of clearance of infection by serial quantitative cerebrospinal fluid (CSF) fungal cultures in 62 patients in a trial of antifungal therapy for HIV-associated cryptococcal meningitis. CSF IL-6, IFN-gamma, TNF-alpha, and IL-8 were significantly higher in survivors compared with nonsurvivors. There were negative correlations between log TNF-alpha, IFN-gamma, and IL-6 levels and baseline cryptococcal CFU. Log IFN-gamma, G-CSF, TNF-alpha, and IL-6 were correlated positively with the rate of fall in log CFU/ml CSF/day. In a linear regression model including antifungal treatment group, baseline CFU, and these cytokines, only treatment group and log IFN-gamma remained independently associated with rate of clearance of infection. The results provide direct in vivo evidence for the importance of quantitative differences in IFN-gamma secretion in human immune control of granulomatous infections, and increase the rationale for adjunctive IFN-gamma in the treatment of refractory HIV-associated cryptococcosis.