Trudy V. Murphy

Intussusception among Infants Given an Oral Rotavirus Vaccine

BACKGROUND Intussusception is a form of intestinal obstruction in which a segment of the bowel prolapses into a more distal segment. Our investigation began on May 27, 1999, after nine cases of infants who had intussusception after receiving the tetravalent rhesus-human reassortant rotavirus vaccine (RRV-TV) were reported to the Vaccine Adverse Event Reporting System. METHODS In 19 states, we assessed the potential association between RRV-TV and intussusception among infants at least 1 but less than 12 months old. Infants hospitalized between November 1, 1998, and June 30, 1999, were identified by systematic reviews of medical and radiologic records. Each infant with intussusception was matched according to age with four healthy control infants who had been born at the same hospital as the infant with intussusception. Information on vaccinations was verified by the provider. RESULTS Data were analyzed for 429 infants with intussusception and 1763 matched controls in a case-control analysis as well as for 432 infants with intussusception in a case-series analysis. Seventy-four of the 429 infants with intussusception (17.2 percent) and 226 of the 1763 controls (12.8 percent) had received RRV-TV (P=0.02). An increased risk of intussusception 3 to 14 days after the first dose of RRV-TV was found in the case-control analysis (adjusted odds ratio, 21.7; 95 percent confidence interval, 9.6 to 48.9). In the case-series analysis, the incidence-rate ratio was 29.4 (95 percent confidence interval, 16.1 to 53.6) for days 3 through 14 after a first dose. There was also an increase in the risk of intussusception after the second dose of the vaccine, but it was smaller than the increase in risk after the first dose. Assuming full implementation of a national program of vaccination with RRV-TV, we estimated that 1 case of intussusception attributable to the vaccine would occur for every 4670 to 9474 infants vaccinated. CONCLUSIONS The strong association between vaccination with RRV-TV and intussusception among otherwise healthy infants supports the existence of a causal relation. Rotavirus vaccines with an improved safety profile are urgently needed.

Methicillin-Resistant Staphylococcus aureus in Two Child Care Centers

Methicillin-resistant Staphylococcus aureus (MRSA) has not been studied in child care centers. The prevalence of MRSA colonization was determined at two centers with an index patient. Two (3%) of 61 children at center X had MRSA; strains from both children and the index illness were pulsed-field gel electrophoresis type B. Nine (24%) of 40 children at center Y had MRSA; strains from 5 children and the index illness were type B, and strains from 4 children were type A. Ten of 11 colonized children were in classes with 2- and 3-year-old children. Colonization with MRSA was not associated with health care contact by subjects or by members of their households. MRSA in child day care centers indicates accelerated spread of MRSA in the community.

Increase in deaths from pertussis among young infants in the United States in the 1990s.

Background. Severe pertussis primarily occurs among infants (<12 months of age). Despite high levels of immunization, reported pertussis cases increased in the United States in the 1990s among all age groups, including infants. Methods. To characterize fatal pertussis cases, we analyzed pertussis deaths reported to CDC in the 1990s and compared these with data on pertussis deaths reported in the 1980s. Data from national surveillance systems and from available medical records were used, including data from analyses of deaths reported in 1992 through 1995. Results. In 1980 through 1989, 77 pertussis deaths were reported; 61 deaths were among infants (1.67 deaths per million), including 49 among infants <4 months of age. In the 1990s 103 pertussis deaths were reported; 93 deaths were among infants (2.40 deaths per million), including 84 among infants <4 months of age. Of 89 infants with ethnicity data, 31 (36%) were Hispanic; the mortality rate among Hispanic infants (4.77 per million) was higher than among non-Hispanic infants (1.80 per million). Of 76 infants with reported gestational age, 40 (53%) were born at <37 weeks, including 22 (29%) who were born at <35 weeks. Severe pulmonary hypertension was a common lethal complication among infants. Conclusions. Pertussis deaths increased among infants too young to be protected by immunization. A disproportionate share of deaths were complicated by pulmonary hypertension and occurred among Hispanic infants and infants born at <37 weeks gestation. New approaches to prevent infection among infants <4 months of age and improved therapies for pertussis complications are needed.

Decreased Haemophilus colonization in children vaccinated with Haemophilus influenzae type b conjugate vaccine

OBJECTIVE The incidence of invasive Haemophilus disease has unexpectedly decreased in unvaccinated children since the introduction of conjugate vaccine in the United States. The purpose of this study was to determine whether conjugate vaccination decreases colonization with Haemophilus influenzae type b. DESIGN This study was a prospective, bimonthly survey of pharyngeal colonization with H. influenzae type b in children attending day care from October 1987 through September 1989. Vaccination status was determined from the medical record. SUBJECTS We obtained 1188 pharyngeal cultures from 283 healthy children, 18 to 59 months of age; 51 children had received unconjugated polysaccharide vaccine (PRP), and 89 had received conjugate vaccine (94% PRP-diphtheria toxoid). MEASUREMENTS AND RESULTS Multivariate analysis was used to test the possibility of an association between vaccination status and the rate of colonization with H. influenzae type b. Among children known to be exposed to at least one child with a positive culture result, the efficacy of conjugate vaccination to prevent H. influenzae type b colonization in an unmatched analysis was 64% (95% confidence interval: 5%, 86%; p = 0.02) and in a matched analysis 81% (95% confidence interval: 7%, 96%; p = 0.02). No effect on colonization was found with PRP vaccination. CONCLUSIONS Conjugate vaccination decreases H. influenzae type b pharyngeal colonization and thereby may decrease transmission of this agent among healthy children.

Societal Costs and Morbidity of Pertussis in Adolescents and Adults

BACKGROUND Since the 1980s, the reported incidence of pertussis among adolescents and adults has been steadily increasing. To understand whether the benefits of an acellular pertussis vaccine formulated for adolescents and adults might offset its costs, policy makers will need information about morbidity and societal (medical and nonmedical) costs of pertussis. METHODS Adolescents (age, 10-17 years) and adults (age, >or=18 years) with confirmed pertussis illness were identified by the Massachusetts enhanced pertussis surveillance system. We evaluated medical costs in a cohort of patients who had confirmed pertussis during the period of January 1998 through December 2000; nonmedical costs, by means of prospective interviews, in a cohort of patients who had confirmed pertussis during the period of December 2001 through January 2003; and morbidity in both cohorts. Our main outcome measures were mean costs per case, in 2002 US dollars. RESULTS In the analysis of medical costs, 1679 adolescents and 936 adults were found to have mean costs of 242 dollars and 326 dollars, respectively (P<.05). In interviews with 314 adolescents and 203 adults, adults had significantly higher nonmedical costs (447 dollars) than those of adolescents (155 dollars). A total of 83% of adolescents missed a mean of 5.5 days from school (range, 0.4-32 days), and 61% of adults missed a mean of 9.8 days from work (range, 0.1-180 days) because of pertussis. Thirty-eight percent of adolescents and 61% of adults were still coughing at the time of the interview, which occurred an average of 106 days and 94 days, respectively, after cough onset. CONCLUSIONS Pertussis causes significant morbidity in and costs for adolescents and adults, with time losses comprising the largest proportion of the cost. Societal costs should be considered when making decisions about potential vaccine use in the future.

Invasive Pneumococcal Disease in Dallas County, Texas: Results from Population-Based Surveillance in 1995

We studied the epidemiology of invasive disease caused by Streptococcus pneumoniae in 1995 among 1.9 million residents of Dallas County, Texas. The sociodemographic characteristics and chronic medical conditions of 432 patients were identified through active, population-based surveillance and review of medical records. The incidence of disease was 22 cases per 100,000 person-years and was highest for children < 2 years of age (136 cases per 100,000 person-years) and for adults > or = 65 years of age (80 cases per 100,000 person-years). Twenty percent of isolates were nonsusceptible to penicillin; the highest rates of resistance were among the youngest and oldest age groups (28% and 22% of isolates, respectively). An increased incidence of disease was associated with low income (42 cases per 100,000 person-years) and black race (39 cases per 100,000 person-years). The frequency of most chronic medical conditions increased with age; smoking, heavy alcohol use, and infection due to human immunodeficiency virus were most common between 30 and 64 years of age. Of otherwise healthy patients 30-64 years of age, 47% were current smokers, an association requiring further investigation. Characterizing groups at risk for invasive pneumococcal disease could aid in the development of prevention programs and increase the benefits from wide use of effective vaccines.

Differences in the immunogenicity of three Haemophilus influenzae type b conjugate vaccines in infants

OBJECTIVE To compare the immunogenicity of three Haemophilus influenzae type b (Hib) conjugate vaccines in infants residing in different geographic areas. DESIGN A multicenter, randomized immunogenicity trial with sera assayed in one laboratory without knowledge of vaccine brand status. In Minneapolis and Dallas, infants were vaccinated at 2, 4, and 6 months of age; in St. Louis, infants were vaccinated at 2 and 4 months of age. SUBJECTS A convenience sample of 458 infants recruited largely from private pediatric practices. MEASUREMENTS AND RESULTS At each of the study sites, the respective trends between the anticapsular antibody responses of the infants assigned to the different conjugate vaccine groups were similar. After one or two doses, Hib polysaccharide conjugated to outer membrane protein complex of Neisseria meningitidis (PRP-OMP) was more immunogenic than Hib polysaccharide-tetanus toxoid conjugate (PRP-T), or Hib oligomers conjugated to the mutant diphtheria toxin CRM197 (HbOC) (p less than 0.001). After two doses, PRP-T was more immunogenic than HbOC (p less than or equal to 0.001). After three doses there was no significant difference in the geometric mean antibody concentrations of the three groups, and 88% to 97% of the infants had greater than 1.0 microgram/ml of antibody. The HbOC vaccine elicited a 10-fold lower antibody response after two doses (0.45 micrograms/ml vs 5.9 micrograms/ml) and a threefold lower antibody response after three doses (6.3 micrograms/ml vs 22.9 micrograms/ml) than observed by us previously with a prelicensure lot of this vaccine (p less than 0.001). Because of these low responses, the infants in St. Louis who received two doses of HbOC were revaccinated with unconjugated PRP at a mean age of 8.9 months. This group was immunologically primed, as evidenced by a 10-fold increase in geometric mean antibody concentration after vaccination at an age when unprimed infants do not normally respond to this vaccine. CONCLUSIONS In infants in three geographic regions, PRP-OMP elicited earlier acquisition of serum antibody than the other two conjugate vaccines; however, after three doses the antibody concentrations of the three groups were not significantly different. The reason for the markedly lower immunogenicity of HbOC vaccine than reported previously is unknown.

Novel Non-mecA-Containing Staphylococcal Chromosomal Cassette Composite Island Containing pbp4 and tagF Genes in a Commensal Staphylococcal Species: a Possible Reservoir for Antibiotic Resistance Islands in Staphylococcus aureus

ABSTRACT Among methicillin-resistant Staphylococcus aureus isolates, a staphylococcal chromosomal cassette containing the mecA gene (SCCmec) is integrated into the chromosome at a unique site. SCCmec also contains unique ccrAB recombinase genes mediating its integration and excision from the genome and is flanked by characteristic left and right direct- and inverted-repeat sequences. A few non-mecA-containing SCC elements that have the other molecular features described above have recently been described. The origin of these cassettes is not clear. We have identified two new members of the SCC family integrated within orfX in Staphylococcus epidermidis strain ATCC 12228, neither of which carries mecA. One is a 57-kb element flanked by a unique 28-bp SCC direct repeat. It was called the SCC composite island (SCC-CI) because it carries a 19-kb SCC element (SCCpbp4) nested within it. SCCpbp4 contains pbp4 and tagF genes, as well as one pair of ccrAB genes (allotype 2) flanked by classical SCC-specific terminal repeats. External to SCCpbp4, SCC-CI contains a second pair of ccrAB genes (allotype 4), three IS431 elements, and genes mediating resistance to heavy metals. Genes mediating restriction-modification that may facilitate horizontal transfer are also present within SCC-CI, both within and outside SCCpbp4. Several novel arrangements of the SCC direct and inverted repeats were identified. Several long stretches of homology with other SCCs were found within and outside SCCpbp4. In view of the fact that SCC-CI was found in a commensal species, it may represent a reservoir for sequences involved in genetic shuffling between staphylococci and may contribute to the diversity found in SCC elements.

Nosocomial Pertussis: Costs of an Outbreak and Benefits of Vaccinating Health Care Workers

BACKGROUND In September 2003, 17 symptomatic cases of pertussis among health care workers (HCWs) resulted from a 1-day exposure to an infant who was later confirmed to have pertussis. These HCWs identified 307 close contacts. The hospital implemented extensive infection-control measures. The objective of this study was to determine direct and indirect costs incurred by the hospital and symptomatic HCWs as a result of the September 2003 outbreak and to estimate possible benefits of vaccinating HCWs from the hospital perspective. METHODS We determined costs by interviewing infection-control and hospital personnel, reviewing billing records, and surveying symptomatic HCWs. We calculated the benefits and costs of a vaccination program for HCWs, using a probabilistic model to estimate the number of pertussis exposures that would require control measures annually. Sensitivity and threshold analyses were performed. RESULTS The outbreak cost to the hospital was 74,870 dollars. The total measured cost of the outbreak was 81,382 dollars, including costs incurred by HCWs (6512 dollars). Our model predicted that vaccinating HCWs against pertussis would prevent >46% of exposures from HCWs with pertussis per year and would provide net savings. The benefit for the hospital was estimated to be 2.38 times the dollar amount invested in vaccinating HCWs. The number of exposures prevented and the benefit-cost ratio were sensitive to the number of exposures identified, the incidence of pertussis among HCWs, and HCW turnover. CONCLUSIONS A single nosocomial pertussis outbreak resulted in substantial disruption and costs to the hospital and to HCWs. Our model suggests that cost savings and benefits could be accrued by vaccinating HCWs against pertussis.

Pertussis in adolescents and adults: should we vaccinate?

Background. The incidence of reported pertussis among adolescents, adults, and young infants has increased sharply over the past decade. Combined acellular pertussis vaccines for adolescents and adults are available in Canada, Australia, and Germany and may soon be considered for use in the United States. Objective. To evaluate the potential health benefits, risks, and costs of a national pertussis vaccination program for adolescents and/or adults. Design, Setting, and Population. The projected health states and immunity levels associated with pertussis disease and vaccination were simulated with a Markov model. The following strategies were examined from the health care payer and societal perspectives: (1) no vaccination; (2) 1-time adolescent vaccination; (3) 1-time adult vaccination; (4) adult vaccination with boosters; (5) adolescent and adult vaccination with boosters; and (6) postpartum vaccination. Data on disease incidence, costs, outcomes, vaccine efficacy, and adverse events were based on published studies, recent unpublished clinical trials, and expert panel input. Main Outcome Measures. Cases prevented, adverse events, costs (in 2004 US dollars), cost per case prevented, and cost per quality-adjusted life-year (QALY) saved. Results. One-time adolescent vaccination would prevent 30800 cases of pertussis (36% of projected cases) and would result in 91000 vaccine adverse events (67% local reactions). If pertussis vaccination cost