Piotr Kramarz

Influenza and the Rates of Hospitalization for Respiratory Disease among Infants and Young Children

BACKGROUND Young children may be at increased risk for serious complications from influenzavirus infection. However, in population-based studies it has been difficult to separate the effects of influenzavirus from those of respiratory syncytial virus. Respiratory syncytial virus often circulates with influenzaviruses and is the most frequent cause of hospitalization for lower respiratory tract infections in infants and young children. We studied the rates of hospitalization for acute respiratory-disease among infants and children during periods when the circulation of influenzaviruses predominated over the circulation of respiratory syncytial virus. METHODS For each season from October to May during the period from 1992 to 1997, we used local viral surveillance data to define periods in Washington State and northern California when the circulation of influenzaviruses predominated over that of respiratory syncytial virus. We calculated the rates of hospitalization for acute respiratory disease, excess rates attributable to influenzavirus, and incidence-rate ratios for all infants and children younger than 18 years of age who were enrolled in either the Kaiser Permanente Medical Care Program of Northern California or the Group Health Cooperative of Puget Sound. RESULTS The rates of hospitalization for acute respiratory disease among children who did not have conditions that put them at high risk for complications of influenza (e.g., asthma, cardiovascular diseases, or premature birth) and who were younger than two years of age were 231 per 100,000 person-months at Northern California Kaiser sites (from 1993 to 1997) and 193 per 100,000 person-months at Group Health Cooperative sites (from 1992 to 1997). These rates were approximately 12 times as high as the rates among children without high-risk conditions who were 5 to 17 years of age (19 per 100,000 person-months at Northern California Kaiser sites and 16 per 100,000 person-months at Group Health Cooperative sites) and approached the rates among children with chronic health conditions who were 5 to 17 years of age (386 per 100,000 person-months and 216 per 100,000 person-months, respectively). CONCLUSIONS Infants and young children without chronic or serious medical conditions are at increased risk for hospitalization during influenza seasons. Routine influenza vaccination should be considered in these children.

Population-based study of rotavirus vaccination and intussusception

Background. During the first year that the rhesus rotavirus tetravalent vaccine (RRV-TV) was licensed, the Vaccine Adverse Event Reporting System received several reports of intussusception after vaccination. To evaluate the risk of intussusception, we conducted a retrospective cohort study in ten managed care organizations. Methods. Cases of intussusception were identified by searching electronic databases for diagnoses of intussusception (ICD-9 Code 560.0) in infants 1 to 11 months of age and confirmed by medical chart review. Vaccination and enrollment data were obtained from administrative databases. Incidence rate ratios (RR) of intussusception were computed by dividing incidence rates in prespecified risk intervals after vaccination by the background rate of intussusception and adjusted for age by Poisson regression. Cox proportional hazard regression was used to evaluate risk by vaccine dose. Results. Of 463 277 children 56 253 had been vaccinated with a total of 91 371 doses of RRV-TV. The incidence rate of intussusception was 25/100 000 person years among unexposed infants and 340/100 000 person years 3 to 7 days postvaccination. In the interval 3 to 7 days after vaccination, the age-adjusted RR was 16.0 (95% confidence interval, 5.5 to 46.7) for all doses combined and 30.4 (95% confidence interval, 8.8 to 104.9) after the first dose. RRs for the 8- to 14- and 15- to 21-day risk intervals were >1.0, but the confidence intervals substantially overlapped 1.0. The attributable risk was one case of intussusception per 11 073 children vaccinated. Conclusions. RRV-TV is associated with an increased risk of intussusception. The risk is greatest 3 to 7 days after the first vaccination dose.

Influenza vaccination in children with asthma in Health Maintenance Organizations

We assessed vaccination coverage and predictors of influenza vaccination in asthmatic children in four large Health Maintenance Organizations. We studied 68,839 children with asthma at four Health Maintenance Organizations (HMOs) in the 1995-1996 influenza season and 34,032 children at two HMOs in the 1996-1997 influenza season. In both seasons only 9-10% were vaccinated against influenza. Children who were hospitalized, had an emergency department visit for asthma or a prescription for a beta-agonist prior to the influenza season, were more likely to be vaccinated. Overall, 61% of the unvaccinated asthmatic children had made an outpatient clinic visit during months when influenza vaccination would have been appropriate. Vaccination coverage could be increased by taking advantage of all opportunities to vaccinate children with asthma whenever they make clinic visits in the fall and early winter.

Childhood vaccinations and risk of asthma

Background. A few previous studies have suggested that childhood vaccines, particularly whole cell pertussis vaccine, may increase the risk of asthma. We evaluated the suggested association between childhood vaccinations and risk of asthma. Methods. Cohort study involving 167 240 children who were enrolled in 4 large health maintenance organizations during 1991 to 1997, with follow-up from birth until at least 18 months to a maximum of 6 years of age. Vaccinations were ascertained through computerized immunization tracking systems, and onset of asthma was identified through computerized data on medical care encounters and medication dispensings. Results. In the study 18 407 children (11.0%) developed asthma, with a median age at onset of 11 months. The relative risks (95% confidence intervals) of asthma were: 0.92 (0.83 to 1.02) for diphtheria, tetanus and whole cell pertussis vaccine; 1.09 (0.9 to 1.23) for oral polio vaccine; 0.97 (0.91 to 1.04) for measles, mumps and rubella (MMR) vaccine; 1.18 (1.02 to 1.36) for Haemophilus influenzae type b (Hib); and 1.20 (1.13 to 1.27) for hepatitis B vaccine. The Hib result was not consistent across health maintenance organizations. In a subanalysis restricted to children who had at least 2 medical care encounters during their first year, the relative risks decreased to 1.07 (0.71 to 1.60) for Hib and 1.09 (0.88 to 1.34) for hepatitis B vaccine. Conclusion. There is no association between diphtheria, tetanus and whole cell pertussis vaccine, oral polio vaccine or measles, mumps and rubella vaccine and the risk of asthma. The weak associations for Hib and hepatitis B vaccines seem to be at least partially accounted for by health care utilization or information bias.

Challenges and controversies in immunization safety.

No vaccine is perfectly safe or effective. As diseases such as diphtheria and polio fade, vaccine safety concerns, especially alleged links between vaccinations and several chronic illnesses, have become increasingly prominent in the media and to the public. This article reviews the current scientific evidence on several recent vaccine safety controversies. It also provides information on how various safety research is conducted, some of the concurrent challenges, and finally, some guidance on communicating with patients on vaccine risks.