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Cost-effective Immunization Against Hemophilus Influenzae
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Am Fam Physician. 1998 Sep 15;58(4):988-989.
The incidence of invasive infection attributed to Hemophilus influenzae type b (Hib) has been dramatically reduced in industrialized countries as a result of immunization with conjugate vaccines. Because a single dose of Hib vaccine costs more than the combined cost of all other vaccines routinely given in the first two years of life, protocols reducing the cost without compromising the efficacy of Hib immunization are important, particularly in developing countries. Lagos and colleagues conducted a randomized trial comparing the immunogenic response in Chilean infants given vaccination regimens other than the three standard doses of Hib vaccine.
The study included healthy infants presenting to public clinics for immunization. Infants with low birth weight (less than 2,500 g [5 lb, 8 oz]), a major chronic disease, a congenital condition, a known immunologic disorder or contraindication to vaccination were excluded from the study. Two Hib vaccines that were commercially available in Chile were used: polysaccharidetetanus toxoid conjugate vaccine (PRP-T) and oligosaccharide-diphtheria mutant toxoid conjugate vaccine (PRP-CRM). The infants were randomly allocated to one of eight vaccination regimens. The regimens included three full doses, three fractional doses consisting of one half or one third of the full dose, and a regimen of two full doses. The infants in the three-dose regimens were vaccinated at two, four and six months of age, and the infants in the two-dose regimens were vaccinated at four and six months of age. For each of the Hib vaccines, approximately 78 infants received two full doses, 78 infants received three full doses, 78 infants received three vaccinations containing one half of the standard dose and 78 infants received three vaccinations containing one third of the standard dose. Levels of antibody to type b capsular polysaccharide were measured in all infants at eight months of age. Levels of 0.15 μg per mL or higher were regarded as seroprotective.
All four regimens of the PRP-T vaccines produced seroprotective levels in at least 93 percent of the infants. The highest geometric mean antibody concentration, 6.3 μg per mL, resulted from the two full-dose regimen, followed by 5.3 μg per mL for the three one-half dose regimen; 5.0 μg per mL for the three one-third dose regimen and 3.8 μg per mL for the standard three-dose regimen. Seroprotective antibody levels were achieved using the PRP-CRM vaccine in 93, 91 and 94 percent of the infants receiving three full doses, three one-half doses and three one-third doses, respectively. Two doses of full-strength vaccine produced seroprotection in 87 percent of the infants. The highest geometric mean antibody level for PRP-CRM vaccines was 3.2 μg per mL, occurring in infants receiving three full doses of the vaccine. Other levels were 3.1 μg per mL for infants receiving three half doses and 2.0 μg per mL for infants receiving two full doses. By 12 months of age, 84 to 93 percent of the infants who had received PRP-T vaccines and 77 to 92 percent of those receiving PRP-CRM vaccines still had seroprotective levels of antibodies, but the geometric mean antibody concentration had dropped substantially in all groups. When challenged with unconjugated PRP polysaccharide, antibody concentrations rose substantially, with the lowest rise being sixfold. These increases were particularly marked for nonstandard doses of PRP-T.
The authors conclude that three vaccinations with one half or one third of the standard dose provide equivalent or superior seroprotection against Hib compared with standard doses. This correlates with other studies, which stress that the optimal antigen dose must be neither too low nor too high, since excessive doses may cause “high tolerance.” Two-dose regimens, although the least satisfactory, still provided substantial protection in this study and could be useful in endemic areas. The authors believe this study has implications for improving the efficacy and reducing the cost of immunization against Hib in all countries.
Lagos R, et al. Economisation of vaccination against Haemophilus influenzae type b: a randomised trial of immunogenicity of fractional-dose and two-dose regimens. Lancet. May 16, 1998;351:1472–6.
Copyright © 1998 by the American Academy of Family Physicians.
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