Haemophilus b disease after vaccination with Haemophilus b polysaccharide or conjugate vaccine.

The reported frequency of invasive Haemophilus influenzae type b disease occurring within 1 year after immunization was compared in American children who received either Praxis Biologics' Haemophilus b polysaccharide vaccine or Connaught Laboratories' Haemophilus b conjugate vaccine during the first year of distribution. All domestic cases reported to the Food and Drug Administration or the Centers for Disease Control were included in the study. An estimated 4.5 million and 2.0 million doses of polysaccharide and conjugate vaccines were administered, respectively. Approximately three cases of early-onset disease (disease developing less than 15 days after vaccination) per million doses were reported for the polysaccharide compared with four cases per million doses for the conjugate vaccine. There were 30.7 reported vaccine failures per million doses of the polysaccharide vaccine compared with 9.0 per million doses of the conjugate vaccine, a 3.4-fold difference. The reporting rate ratios (cases of vaccine failure to cases of early-onset disease) for the polysaccharide and conjugate were 11.5 and 2.3, respectively, a fivefold difference. Thus, compared with recipients of the polysaccharide vaccine, vaccine failures reported among recipients of the conjugate vaccine were 80% fewer than expected.

Spectrum of disease due to Haemophilus influenzae type b occurring in vaccinated children.

Haemophilus b polysaccharide vaccine was first licensed in the United States in April 1985. Between May 1985 and September 1987, 228 reports of disease due to Haemophilus influenzae in vaccinated children were submitted to the Food and Drug Administration, of which 216 were accepted for analysis. We compared the relative frequencies of the different disease entities caused by H. influenzae type b reported in vaccinated children with those reported in unvaccinated children (greater than 1000 cases that occurred between 1973 and 1984, as reported in the literature). Over 90% of the vaccinated children were greater than or equal to 24 mo of age. A higher proportion of cases was reported to have occurred within the first two months after vaccination, with 10 cases occurring within 72 h of vaccination. Vaccination did not alter the expected frequencies of the different clinical entities associated with invasive H. influenzae disease. No estimates of clinical efficacy are possible based on the adverse events submitted to the Food and Drug Administration.

Postmarketing surveillance for neurologic adverse events reported after hepatitis B vaccination. Experience of the first three years.

In 1982, the Centers for Disease Control, the Food and Drug Administration, and the manufacturer created a surveillance system to monitor spontaneous reports of adverse events occurring after inoculation with the new plasma-derived hepatitis B vaccine (Heptavax-B, Merck Sharp and Dohme, West Point, PA). In the three years between June 1, 1982 and May 31, 1985, an estimated 850,000 persons received the vaccine. During that period, a total of 41 reports were received for one of the following neurologic adverse events: convulsions (five cases), Bell's palsy (10 cases), Guillain-Barré syndrome (nine cases), lumbar radiculopathy (five cases), brachial plexus neuropathy (three cases), optic neuritis (five cases), and transverse myelitis (four cases). Half of these occurred after the first of three required vaccine doses. There were no deaths. Calculation of the relative risks of these illnesses after hepatitis B vaccination was highly dependent on diagnostic classification of the cases, estimates of the size of the vaccinated population, background incidence of the diseases, and the length and distribution of the hypothetical at-risk interval used in the analysis. Other factors important in judging the results of the study could not be measured, including underreporting. In some analyses, Guillain-Barré syndrome was reported significantly more often than expected (p less than 0.05, Poisson probability distribution). However, no conclusive epidemiologic association could be made between any neurologic adverse event and the vaccine. Even if such an association did exist, the preventive benefits of the vaccine in persons at high risk for hepatitis B would unequivocally outweigh the risk of any neurologic adverse event.