United States-Tennessee. Griffin and others (1992) examined the association between DTwP immunization and the risk of invasive bacterial infection. The incidence of invasive bacterial diseases (H. influenzae, N meningitidis, Streptococcus pneumoniae, group B Streptococcus, or Listeria monocytogenes) was measured in a cohort of 64,591 children who received at least one dose of DTwP vaccine through any of the four largest Tennessee county health clinics from 1986 to 1987. Based on surveillance data, 158 children diagnosed with invasive bacterial infection after receiving DTwP vaccine were identified in this cohort. Using a Poisson regression model and controlling for age, the relative risk for infections during the early post-immunization periods (0–7, 8–14, 15–28 days) compared with the later period (29 or more days) was nonsignificant. The authors concluded that there was no increase in the risk for invasive bacterial infection following receipt of DTwP vaccine, especially during the early post-immunization period. Interpretation of the study is limited by the lack of an unvaccinated comparison group. In addition, the analysis was limited to cases of serious culture-confirmed infections.

United States-Kaiser Permanente Northern California. In a case-control study, Black and colleagues (1991) examined the relationship between vaccination and the risk of heterologous invasive bacterial disease. Cases and controls were identified from member records in the Kaiser Permanente Medical Care Program of Northern California. As cases, 223 children between 1 month and 2 years of age who were diagnosed with invasive bacterial disease (Pneumococcus, H. influenzae, E. coli, and Meningococcus) between 1986 and 1988. Invasive bacterial disease status was identified from a computerized microbiology laboratory database. The 446 controls were matched according to age, sex, zip code, and length of plan membership. For cases, all vaccines received within three months prior to disease onset were identified through medical chart review. For matched controls, the date of diagnosis for the corresponding case was the reference date used to obtain vaccination histories. Children had received one or more of the following vaccines: DTP, OPV, and MMR.

A conditional logistic regression model was used to estimate the effect of recent immunization on disease; odds ratios were calculated from the regression results for each vaccine. A separate analysis controlled for the effect of well care visits and day care attendance (information available for 72 percent of the subjects). Odds ratios were calculated for separate time intervals from date of vaccine receipt to date of disease diagnosis: 0–7 days, 8–30 days, 31–60 days, and 61–90 days. Receipt of individual vaccines was associated with a lower risk of disease in all time intervals, with significant effects for DTP at any interval after 7 days and for OPV at 8–30 days and 31–60 days. After adjustment for day-care attendance and well-care visits, however, no individual vaccine had a significant effect on risk of disease. But there was a significant protective effect in the adjusted analysis from the receipt of any vaccine within 30 days (OR = 0.26, 95% CI 0.09–0.76) or 90 days (OR = 0.31, 95% CI 0.13–0.73).

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