Stephen L. Cochi

Pasteurized milk as a vehicle of infection in an outbreak of listeriosis.

Between June 30th and August 30th, 1983, 49 patients in Massachusetts acquired listeriosis. Seven cases occurred in fetuses or infants and 42 in immunosuppressed adults; 14 patients (29 per cent) died. Of 40 Listeria monocytogenes isolates available for testing, 32 were serotype 4b. Two case-control studies, one matching for neighborhood of residence and the other for underlying disease, revealed that the illness was strongly associated with drinking a specific brand of pasteurized whole or 2 per cent milk (odds ratio = 9, P less than 0.01 for the neighborhood-matched study; odds ratio = 11.5, P less than 0.001 for the illness-matched study). The association with milk was further substantiated by four additional analyses that suggested the presence of a dose-response effect, demonstrated a protective effect of skim milk, associated cases with the same product in an independent study in another state, and linked a specific phage type with the disease associated with milk. The milk associated with disease came from a group of farms on which listeriosis in dairy cows was known to have occurred at the time of the outbreak. Multiple serotypes of L. monocytogenes were isolated from raw milk obtained from these farms after the outbreak. At the plant where the milk was processed, inspections revealed no evidence of improper pasteurization. These results support the hypothesis that human listeriosis can be a foodborne disease and raise questions about the ability of pasteurization to eradicate a large inoculum of L. monocytogenes from contaminated raw milk.

The Vaccine Adverse Event Reporting System (VAERS).

Immunizations against most vaccine-preventable diseases will be needed indefinitely unless the disease is eradicated. Public acceptance of immunizations may be threatened as vaccine coverage increases and disease decreases, however, due to the increase in both causally and coincidentally related vaccine adverse events. The post-marketing surveillance for such events in the USA in response to the mandatory reporting requirements of the National Childhood Injury Act of 1986. While VAERS has many methodological limitations intrinsic to such systems, it can play an important role in helping to monitor vaccine safety and maintain public confidence in immunizations.

Primary invasive Haemophilus influenzae type b disease: A population-based assessment of risk factors

We performed a population-based case-control study of risk factors for primary invasive Haemophilus influenzae type b (Hib) disease in metropolitan Atlanta from July 1, 1983, through June 30, 1984. Active surveillance identified 102 cases in children less than 5 years of age, 89 of whom lived in households with telephones. We used random digit dialing to select 530 controls who were postmatched to cases by age. Multivariate analysis showed a significant association between Hib disease and two independent exposure factors, household crowding (odds ratio (OR) 2.7, 95% confidence limits (CL) 1.3 to 5.6) and day-care attendance. For day-care attendance, relative risk was highest in 2- to 5-month-old infants (OR 17.7, 95% CL 5.8 to 54.4) and declined to 9.4 (4.3 to 20.9) at ages 6 to 11 months, 5.0 (2.7 to 9.3) at 12 to 23 months, 2.7 (1.3 to 5.5) at 24 to 35 months, and 1.4 (0.5 to 4.0) in 36- to 59-month-old children. Fifty percent of all invasive Hib disease that occurred during the study period was attributable to exposure to day-care; the attributable risk for household crowding was 18%. Dose-response effects were observed for hours per week of day-care attendance and extent of household crowding. Breast-feeding was protective for infants less than 6 months of age (OR 0.08, 95% CL 0.01 to 0.59). After controlling for socioeconomic and other confounding factors, we could demonstrate no effect of black race on cumulative risk of invasive Hib disease. Our study defines high-risk groups and provides a population-based model of the interrelationship between risk factors associated with invasive Hib disease.

Mumps outbreak in a highly vaccinated population

From October 1988 to April 1989, a large mumps outbreak occurred in Douglas County, Kansas. Of the 269 cases, 208 (77.3%) occurred among primary and secondary school students, of whom 203 (97.6%) had documentation of mumps vaccination. Attack rates were highest for students attending junior high school (8.0%), followed by high school (2.0%) and elementary school (0.7%). A retrospective cohort study conducted at one junior high school with an attack rate of 12.9% did not find age at vaccination or type of vaccine received (single or combined antigen) to be risk factors for vaccine failure. Students vaccinated more than 4 years before the outbreak appeared to have a higher attack rate than those vaccinated more recently (relative risk (RR) = 4.3; 95% confidence interval (CI) = 0.6, 30.0); however, this association did not exist when risk was evaluated based on number of vaccine doses received. Students who had documentation of receiving only one dose of vaccine were at greater risk than those who had received two doses (RR = 5.2; 95% CI = 1.0, 206.2). Overall, vaccine effectiveness among Douglas County junior high school students was estimated to be 83% (95% CI = 57%, 94%). These data suggest that mumps vaccine failure and the failure to vaccinate have contributed to the relative resurgence of mumps observed in the United States since 1986. The recent change in immunization policy to recommend a two-dose schedule of measles-mumps-rubella vaccine should help reduce the occurrence of mumps outbreaks in highly vaccinated populations.

Outbreak of paralytic poliomyelitis in Oman: evidence for widespread transmission among fully vaccinated children

From January, 1988, to March, 1989, a widespread outbreak (118 cases) of poliomyelitis type 1 occurred in Oman. Incidence of paralytic disease was highest in children younger than 2 years (87/100,000) despite an immunisation programme that recently had raised coverage with 3 doses of oral poliovirus vaccine (OPV) among 12-month-old children from 67% to 87%. We did a case-control study (70 case-patients, 692 age-matched controls) to estimate the clinical efficacy of OPV, assessed the immunogenicity of OPV and extent of poliovirus spread by serology, retrospectively evaluated the cold chain and vaccine potency, and sought the origin of the outbreak strain by genomic sequencing. 3 doses of OPV reduced the risk of paralysis by 91%; vaccine failures could not be explained by failures in the cold chain nor on suboptimum vaccine potency. Cases and controls had virtually identical type 1 neutralising antibody profiles, suggesting that poliovirus type 1 circulation was widespread. Genomic sequencing indicated that the outbreak strain had been recently imported from South Asia and was distinguishable from isolates indigenous to the Middle East. Accumulation of enough children to sustain the outbreak seems to have been due to previous success of the immunisation programme in reducing spread of endemic strains, suboptimum efficacy of OPV, and delay in completing the primary immunisation series until 7 months of age. Additionally, the estimated attack rate of infection among children aged 9-23 months exceeded 25% in some regions, suggesting that a substantial proportion of fully vaccinated children had been involved in the chain of transmission.

Expert review on poliovirus immunity and transmission.

Successfully managing risks to achieve wild polioviruses (WPVs) eradication and address the complexities of oral poliovirus vaccine (OPV) cessation to stop all cases of paralytic poliomyelitis depends strongly on our collective understanding of poliovirus immunity and transmission. With increased shifting from OPV to inactivated poliovirus vaccine (IPV), numerous risk management choices motivate the need to understand the tradeoffs and uncertainties and to develop models to help inform decisions. The U.S. Centers for Disease Control and Prevention hosted a meeting of international experts in April 2010 to review the available literature relevant to poliovirus immunity and transmission. This expert review evaluates 66 OPV challenge studies and other evidence to support the development of quantitative models of poliovirus transmission and potential outbreaks. This review focuses on characterization of immunity as a function of exposure history in terms of susceptibility to excretion, duration of excretion, and concentration of excreted virus. We also discuss the evidence of waning of host immunity to poliovirus transmission, the relationship between the concentration of poliovirus excreted and infectiousness, the importance of different transmission routes, and the differences in transmissibility between OPV and WPV. We discuss the limitations of the available evidence for use in polio risk models, and conclude that despite the relatively large number of studies on immunity, very limited data exist to directly support quantification of model inputs related to transmission. Given the limitations in the evidence, we identify the need for expert input to derive quantitative model inputs from the existing data.

Prevention of pertussis among adolescents: Recommendations for use of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine

The purpose of this statement is to provide the rationale and recommendations for adolescent use of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccines. Despite universal immunization of children with multiple doses of pediatric diphtheria and tetanus toxoids and acellular pertussis (DTaP) vaccine, pertussis remains endemic with a steady increase in the number of reported cases. Two peaks in the incidence of pertussis occur in pediatric patients: infants younger than 6 months of age who are inadequately protected by the current immunization schedule and adolescents 11 through 18 years of age whose vaccine-induced immunity has waned. Significant medical and public health resources are being consumed in postexposure management of adolescent cases, contacts, and outbreaks with little beneficial effect on individuals or the epidemiology of disease. Two Tdap products were licensed in 2005 for use in people 10 through 18 years of age (Boostrix) and 11 through 64 years of age (Adacel). The American Academy of Pediatrics recommends the following:

When is a disease eradicable? 100 years of lessons learned.

Since the 1915 launch of the first international eradication initiative targeting a human pathogen, much has been learned about the determinants of eradicability of an organism. The authors outline the first 4 eradication efforts, summarizing the lessons learned in terms of the 3 types of criteria for disease eradication programs: (1) biological and technical feasibility, (2) costs and benefits, and (3) societal and political considerations.

Expert Review on Poliovirus Immunity and Transmission

Successfully managing risks to achieve wild polioviruses (WPVs) eradication and address the complexities of oral poliovirus vaccine (OPV) cessation to stop all cases of paralytic poliomyelitis depends strongly on our collective understanding of poliovirus immunity and transmission. With increased shifting from OPV to inactivated poliovirus vaccine (IPV), numerous risk management choices motivate the need to understand the tradeoffs and uncertainties and to develop models to help inform decisions. The U.S. Centers for Disease Control and Prevention hosted a meeting of international experts in April 2010 to review the available literature relevant to poliovirus immunity and transmission. This expert review evaluates 66 OPV challenge studies and other evidence to support the development of quantitative models of poliovirus transmission and potential outbreaks. This review focuses on characterization of immunity as a function of exposure history in terms of susceptibility to excretion, duration of excretion, and concentration of excreted virus. We also discuss the evidence of waning of host immunity to poliovirus transmission, the relationship between the concentration of poliovirus excreted and infectiousness, the importance of different transmission routes, and the differences in transmissibility between OPV and WPV. We discuss the limitations of the available evidence for use in polio risk models, and conclude that despite the relatively large number of studies on immunity, very limited data exist to directly support quantification of model inputs related to transmission. Given the limitations in the evidence, we identify the need for expert input to derive quantitative model inputs from the existing data.

The Risks, Costs, and Benefits of Possible Future Global Policies for Managing Polioviruses

OBJECTIVES We assessed the costs, risks, and benefits of possible future major policy decisions on vaccination, surveillance, response plans, and containment following global eradication of wild polioviruses. METHODS We developed a decision analytic model to estimate the incremental cost-effectiveness ratios and net benefits of risk management options for polio for the 20-year period and stratified the world according to income level to capture important variability between nations. RESULTS For low-, lower-middle-, and upper-middle-income groups currently using oral poliovirus vaccine (OPV), we found that after successful eradication of wild polioviruses, OPV cessation would save both costs and lives when compared with continued use of OPV without supplemental immunization activities. We found cost-effectiveness ratios for switching from OPV to inactivated poliovirus vaccine to be higher (i.e., less desirable) than other health investment opportunities, depending on the actual inactivated poliovirus vaccine costs and assumptions about whether supplemental immunization activities with OPV would continue. CONCLUSIONS Eradication promises billions of dollars of net benefits, although global health policy leaders face difficult choices about future policies. Until successful eradication and coordination of posteradication policies, health authorities should continue routine polio vaccination and supplemental immunization activities.