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Background: Five major disease eradication initiatives were initiated during the second half of the 20th century. The enabling and constraining factors-political, social, economic, and other-for these previous and current eradication programs can inform decision making regarding a proposed measles eradication initiative., Methods: We reviewed the literature on the yaws, malaria, smallpox, guinea worm, and polio eradication programs and compared enabling and constraining factors for each of these programs with the same factors as they relate to a possible measles eradication initiative., Results: A potential measles eradication program would enjoy distinct advantages in comparison with earlier eradication programs, including strong political and societal support, economic analyses demonstrating a high level of cost-effectiveness, and a rigorous upfront process, compared with previous eradication initiatives, that has validated the feasibility of achieving measles eradication. However, increasing population density, urbanization, and wars/civil conflicts will pose serious challenges., Conclusions: Measles eradication will be very challenging but probably not as difficult to achieve as polio eradication. Measles eradication should be undertaken only if the commitments and resources will be adequate to meet the political, social, economic, and technical challenges., (© The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.)

Background: On the basis of studies from developed countries, the case-fatality ratio (CFR) of poliomyelitis generally ranges from 2%-5% among children <5 years of age to 10%-30% among adults. However, little information is available for poliomyelitis-related CFR in developing countries. We conducted a study to determine the CFR in India, 1 of the 4 remaining countries with endemic wild poliovirus (WPV) circulation, during outbreaks of WPV infection during 2002 and 2006 and during the inter-epidemic years of 2003-2005., Methods: We conducted a descriptive analysis with use of data from the acute flaccid paralysis surveillance system in India. Variables analyzed included age, caregiver-reported vaccination status, date of paralysis onset, laboratory results, final case classification, and survival outcome. Our analysis also accounted for surveillance changes that occurred in 2005, impacting case definitions and final classification., Results: In 2006, 45 deaths occurred among 676 WPV cases in India, yielding a CFR of 6.7%. By comparison, in 2002, there were 66 deaths among 1600 reported WPV cases (CFR, 4.2%) and during 2002-2005, CFR was 1.5%-5.2%. All 45 deaths were among 644 (95%) WPV cases in children aged <5 years (CFR, 7.0%). Among those who died, 33 (73%) were children aged <2 years (CFR, 7.1%)., Conclusions: The CFR among children aged <2 years in India is high compared with previously published CFRs for young children, in part because of improved case finding through enhanced surveillance techniques. Fatal cases emphasize the lethal nature of the disease and the importance of achieving polio eradication in India., (© The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.)

The global polio eradication initiative (GPEI), which started in 1988, represents the single largest, internationally coordinated public health project to date. Completion remains within reach, with type 2 wild polioviruses apparently eradicated since 1999 and fewer than 2000 annual paralytic poliomyelitis cases of wild types 1 and 3 reported since then. This economic analysis of the GPEI reflects the status of the program as of February 2010, including full consideration of post-eradication policies. For the GPEI intervention, we consider the actual pre-eradication experience to date followed by two distinct potential future post-eradication vaccination policies. We estimate GPEI costs based on actual and projected expenditures and poliomyelitis incidence using reported numbers corrected for underreporting and model projections. For the comparator, which assumes only routine vaccination for polio historically and into the future (i.e., no GPEI), we estimate poliomyelitis incidence using a dynamic infection transmission model and costs based on numbers of vaccinated children. Cost-effectiveness ratios for the GPEI vs. only routine vaccination qualify as highly cost-effective based on standard criteria. We estimate incremental net benefits of the GPEI between 1988 and 2035 of approximately 40-50 billion dollars (2008 US dollars; 1988 net present values). Despite the high costs of achieving eradication in low-income countries, low-income countries account for approximately 85% of the total net benefits generated by the GPEI in the base case analysis. The total economic costs saved per prevented paralytic poliomyelitis case drive the incremental net benefits, which become positive even if we estimate the loss in productivity as a result of disability as below the recommended value of one year in average per-capita gross national income per disability-adjusted life year saved. Sensitivity analysis suggests that the finding of positive net benefits of the GPEI remains robust over a wide range of assumptions, and that consideration of the additional net benefits of externalities that occurred during polio campaigns to date, such as the mortality reduction associated with delivery of Vitamin A supplements, significantly increases the net benefits. This study finds a strong economic justification for the GPEI despite the rising costs of the initiative., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Decision analytic modeling of polio risk management policies after eradication may help inform decisionmakers about the quantitative tradeoffs implied by various options. Given the significant dynamic complexity and uncertainty involving posteradication decisions, this article aims to clarify the structure of a decision analytic model developed to help characterize the risks, costs, and benefits of various options for polio risk management after eradication of wild polioviruses and analyze the implications of different sources of uncertainty. We provide an influence diagram of the model with a description of each component, explore the impact of different assumptions about model inputs, and present probability distributions of model outputs. The results show that choices made about surveillance, response, and containment for different income groups and immunization policies play a major role in the expected final costs and polio cases. While the overall policy implications of the model remain robust to the variations of assumptions and input uncertainty we considered, the analyses suggest the need for policymakers to carefully consider tradeoffs and for further studies to address the most important knowledge gaps.

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.

After the global eradication of wild polioviruses, the risk of paralytic poliomyelitis from polioviruses will still exist and require active management. Possible reintroductions of poliovirus that can spread rapidly in unprotected populations present challenges to policymakers. For example, at least one outbreak will likely occur due to circulation of a neurovirulent vaccine-derived poliovirus after discontinuation of oral poliovirus vaccine and also could possibly result from the escape of poliovirus from a laboratory or vaccine production facility or from an intentional act. In addition, continued vaccination with oral poliovirus vaccines would result in the continued occurrence of vaccine-associated paralytic poliomyelitis. The likelihood and impacts of reintroductions in the form of poliomyelitis outbreaks depend on the policy decisions and on the size and characteristics of the vulnerable population, which change over time. A plan for managing these risks must begin with an attempt to characterize and quantify them as a function of time. This article attempts to comprehensively characterize the risks, synthesize the existing data available for modeling them, and present quantitative risk estimates that can provide a starting point for informing policy decisions.

The success of the Global Polio Eradication Initiative promises to bring large benefits, including sustained improvements in quality of life (i.e., cases of paralytic disease and deaths avoided) and costs saved from cessation of vaccination. Obtaining and maintaining these benefits requires that policymakers manage the transition from the current massive use of oral poliovirus vaccine (OPV) to a world without OPV and free of the risks of potential future reintroductions of live polioviruses. This article describes the analytical journey that began in 2001 with a retrospective case study on polio risk management and led to development of dynamic integrated risk, economic, and decision analysis tools to inform global policies for managing the risks of polio. This analytical journey has provided several key insights and lessons learned that will be useful to future analysts involved in similar complex decision-making processes.

Inherent in the decision to launch the Global Polio Eradication Initiative in 1988 was the expectation for many people that immunization against poliomyelitis would eventually simply stop, as had been the case with smallpox following its eradication in 1977. However, the strategies for managing the risks associated with a "polio-free" world must be continuously refined to reflect new developments, particularly in our understanding of the live polioviruses in the oral poliovirus vaccine (OPV) and in the international approach to managing potential biohazards. The most important of these developments has been the confirmation in 2000 that vaccine-derived polioviruses (VDPVs) can circulate and cause polio outbreaks, making the use of OPV after interruption of wild poliovirus transmission incompatible with a polio-free world. A comprehensive strategy has been developed to minimize the risks associated with eventual OPV cessation, centered on appropriate long-term biocontainment of poliovirus stocks (whether for vaccine production, diagnosis, or research), the controlled reintroduction of any live poliovirus vaccine (i.e., from an OPV stockpile), and appropriate use of the inactivated poliovirus vaccine (IPV). Although some aspects of this risk management strategy are still debated, there is wide agreement that no strategy would entirely eliminate the potential risks to a polio-free world. The current strategy for risk management in a polio-free world will continue to evolve with better characterization of these risks and the development of more effective approaches both to reduce those risks and to limit their consequences should they occur.

Although immunization is one of the great public health achievements, continued success depends on an available supply of the vaccines that are recommended for routine use. Beginning in 2000, the United States experienced vaccine supply disruptions of unprecedented scope and magnitude. Although most of the supply disruptions have been resolved, it appears that a fragile vaccine supply will be part of the immunization environment in the United States for the foreseeable future. Here, we describe the perspective of the Centers for Disease Control and Prevention on the recent supply disruptions and the methods used to manage vaccine shortages. The present article focuses on routine pediatric vaccines, including influenza virus vaccine.

Vaccine shortages can result from higher-than-expected demand, interruptions in production/supply, or a lack of resources to purchase vaccines. Each of these factors has played a role in vaccine shortages in the United States during the past 20 years. Since 2000, the United States has experienced an unprecedented series of shortages of vaccines recommended for widespread use against 9 diseases, after more than 15 years without vaccine supply problems. In developing countries, the major cause of vaccine shortages is lack of resources to purchase them. Although there are several steps that could reduce the likelihood of future vaccine shortages, many would take several years to implement. Consequently, we will probably continue to see occasional shortages of vaccines in the United States in the next few years.

Lessons learned from the successful end of endemic measles virus transmission (i.e., elimination) in the United States include the critical roles of strong political commitment, a regionwide initiative, adequate funding, and a broad coalition of partners. Implications of measles elimination in the United States for global measles control and regional elimination efforts include demonstration of the high vaccination coverage and, in turn, population immunity needed for elimination; the importance of accurate monitoring of vaccination coverage at local, state, and national levels; a vaccination strategy that includes at least 2 opportunities for measles immunization; and the essential role of integrated epidemiological and laboratory surveillance. The United States, with a population of 288 million, is, to our knowledge, the largest country to have ended endemic measles transmission. This experience provides evidence that sustained interruption of transmission can be achieved in large geographic areas, suggesting the feasibility of global eradication of measles.

With the interruption of wild poliovirus transmission globally, the need for new policies to deal with the post-certification era will rapidly arise. New policies will be required in four areas: detection and notification of circulating polioviruses; biocontainment of wild, vaccine-derived and attenuated strains of poliovirus; vaccine stockpiles and response mechanisms; and routine immunization against polioviruses. A common understanding of the potential risks of paralytic poliomyelitis in the post-certification period is essential to the development of these policies. Since 2000, there has been increasing international consensus that the risks of paralytic poliomyelitis in the post-certification era fall into two categories: those due to the continued use of the oral poliovirus vaccine (OPV) and those due to future improper handling of wild polioviruses. The specific risks within both categories have now been defined, and an understanding of the frequency and potential burden of disease associated with each is rapidly improving. This knowledge and clarity have provided a framework that is already proving valuable for identifying research priorities and discussing potential policy options with national authorities. However, this framework must be regarded as a dynamic tool, requiring regular updating as additional information on these risks becomes available through further scientific research, programmatic work, and policy decisions.

Objective: An analysis was conducted to estimate the costs of different potential post-polio certification immunization policies currently under consideration, with the objective of providing this information to policy-makers., Methods: We analyzed three global policy options: continued use of oral poliovirus vaccine (OPV); OPV cessation with optional inactivated poliovirus vaccine (IPV); and OPV cessation with universal IPV. Assumptions were made on future immunization policy decisions taken by low-, middle-, and high-income countries. We estimated the financial costs of each immunization policy, the number of vaccine-associated paralytic poliomyelitis (VAPP) cases, and the global costs of maintaining an outbreak response capacity. The financial costs of each immunization policy were based on estimates of the cost of polio vaccine, its administration, and coverage projections. The costs of maintaining outbreak response capacity include those associated with developing and maintaining a vaccine stockpile in addition to laboratory and epidemiological surveillance. We used the period 2005-20 as the time frame for the analysis., Findings: OPV cessation with optional IPV, at an estimated cost of US$ 20,412 million, was the least costly option. The global cost of outbreak response capacity was estimated to be US$ 1320 million during 2005-20. The policy option continued use of OPV resulted in the highest number of VAPP cases. OPV cessation with universal IPV had the highest financial costs, but it also had the least number of VAPP cases. Sensitivity analyses showed that global costs were sensitive to assumptions on the cost of the vaccine. Analysis also showed that if the price per dose of IPV was reduced to US$ 0.50 for low-income countries, the cost of OPV cessation with universal IPV would be the same as the costs of continued use of OPV., Conclusion: Projections on the vaccine price per dose and future coverage rates were major drivers of the global costs of post-certification polio immunization. The break-even price of switching to IPV compared with continuing with OPV immunizations is US$ 0.50 per dose of IPV. However, this doses not account for the cost of vaccine-derived poliovirus cases resulting from the continued use of OPV. In addition to financial costs, risk assessments related to the re-emergence of polio will be major determinants of policy decisions.

In 1988, the World Health Assembly resolved to eradicate poliomyelitis globally by the year 2000. Dramatic progress toward this goal has occurred: three of the six WHO regions (Region of the Americas, European Region, and Western Pacific Region) are now polio free; and the number of polio-endemic countries decreased from over 125 in 1988 to 30 in 1999. Intensified efforts currently are underway to reach the target as soon as possible after 2000 in the three remaining polio-endemic WHO regions (African Region, Eastern Mediterranean Region, and South-East Asia Region). Even in polio-endemic regions, many countries are already polio free as the geographic extent of poliovirus shrinks while others. especially those experiencing conflict and war, pose substantial challenges to implementing the proven polio eradication strategies. Increasing attention and research now are devoted to the certification of polio eradication in the polio-free regions (that will include the first phase of implementing the Global Plan of Action for the laboratory containment of wild poliovirus) and formulating a policy for stopping all polio vaccination once eradication, containment, and global certification have been achieved. This report outlines the progress toward polio eradication and highlights some of the remaining issues and challenges that must be addressed before polio becomes a disease that future generations know only by history.

One of the challenges of the polio eradication initiative over the next few years will be the formulation of an optimal strategy for stopping poliovirus vaccination after global certification of polio eradication has been accomplished. This strategy must maximize the benefits and minimize the risks. A number of strategies are currently under consideration, including: (i) synchronized global discontinuation of use of oral poliovirus vaccine (OPV); (ii) regional or subregional coordinated OPV discontinuation; and (iii) moving from trivalent to bivalent or monovalent OPV. Other options include moving from OPV to global use of IPV for an interim period before cessation of IPV use (to eliminate circulation of vaccine-derived poliovirus, if necessary) or development of new OPV strains that are not transmissible. Each of these strategies is associated with specific advantages (financial benefits for OPV discontinuation) and disadvantages (cost of switch to IPV) and inherent uncertainties (risk of continued poliovirus circulation in certain populations or prolonged virus replication in immunodeficient persons). An ambitious research agenda addresses the remaining questions and issues. Nevertheless, several generalities are already clear. Unprecedented collaboration between countries, regions, and indeed the entire world will be required to implement a global OPV discontinuation strategy Regulatory approval will be needed for an interim bivalent OPV or for monovalent OPV in many countries. Manufacturers will need sufficient lead time to produce sufficient quantities of IPV Finally, the financial implications for any of these strategies need to be considered. Whatever strategy is followed it will be necessary to stockpile supplies of a poliovirus-containing vaccine (most probably all three types of monovalent OPV), and to develop contingency plans to respond should an outbreak of polio occur after stopping vaccination.

Poliomyelitis prevention in the United States has relied virtually exclusively on OPV during the past 30 years. Starting in 1997, a major change in the poliomyelitis vaccination policy occurred, facilitated by substantial progress toward worldwide poliomyelitis eradication. A sequential schedule of IPV followed by OPV became the preferred means to prevent poliomyelitis, although an all-OPV and an all-IPV schedule were considered acceptable alternatives. In 1999, two doses of IPV were recommended to start the primary series, followed by two doses of either poliovirus vaccine. As of January 2000, an all-IPV schedule is currently being implemented in the United States for routine childhood vaccination. Several unusual features are associated with the major public health policy change from an all-OPV to a sequential schedule, including (1) the process of involving a neutral party (i.e., the IOM); (2) the perceived concerns expressed before the change in policy with regard to provider and parent compliance, which could affect the hard-earned gains in raising immunization coverage rates; (3) the ethical issues surrounding the change (e.g., societal versus individual protection) and the influence that a single case of VAPP may have on national policy; (4) the relative lack of importance of cost-effectiveness data; and (5) the weight of progress in the global polio eradication initiative spurring the change in the United States and, increasingly, in other industrialized countries. The IOM assisted in the evaluation of the national poliomyelitis vaccination policy in 1977 and again in 1988. The 1988 review recommended that a sequential IPV-OPV schedule be considered at such time that a combination vaccine becomes available. Also, the IOM raised several important questions. Extensive research to address the questions raised by the IOM had been conducted so that, in 1996, more data were available for the decision-making process. The primary reasons for the change in vaccination policy were (1) the continued occurrence of VAPP in the absence of indigenously acquired wildtype poliovirus-associated paralytic disease, (2) the reduced risk for importation and spread of wild-type poliovirus caused by the progress of the global polio eradication initiative, (3) evidence from vaccine trials that combined IPV-OPV schedules are safe and immunogenic, and (4) maintenance of high levels of population immunity to poliovirus. The global effect of a national change in poliomyelitis vaccination policy was also considered in this policy-making process. Some members of the public health and medical communities raised objections that an increased reliance on IPV in the United States could lead other countries, especially developing countries, to inappropriately abandon OPV and increase reliance on IPV for routine vaccination. Experience from the global smallpox eradication campaign indicated that this scenario was unlikely. The United States ceased vaccinating against smallpox in 1971, 6 years before smallpox was eliminated from the world, without jeopardizing the global smallpox campaign. Subsequently, the effect on the global eradication initiative has been negligible. This article illustrates the potential discrepancy between expressed theoretic concerns about the number of injections and the actual practice once vaccination policy recommendations become the standard of care and that appropriate training and education can overcome these initial concerns. The authors found that compliance with the recommended use of IPV for the first and second doses as part of the sequential schedule was high, independent of socioeconomic status and ethnicity. The need for additional injections did not present a barrier to completion of the recommended childhood immunization schedule. (ABSTRACT TRUNCATED)

In 1989, a localized outbreak of 10 cases of poliomyelitis occurred in Saudi Arabia. Wild poliovirus type 1 was isolated from 5 patients. To determine the patterns of poliovirus circulation, partial nucleotide sequences of the poliovirus isolates were compared. These isolates were remarkably diverse. Two isolates were closely related to each other and to viruses isolated during the 1988 epidemic in Oman. Two other isolates were very similar to viruses found in Egypt. The fifth isolate was distantly related to the latter pair. The molecular data suggest that the 10 cases represented three separate outbreaks. The virologic findings underscore the potential for Saudi Arabia, which receives millions of guest workers and their families each year from countries in which polio is endemic, to be exposed to frequent importations of wild polioviruses. To restrict the circulation of imported polioviruses, Saudi Arabia must maintain high population immunity to poliovirus in all geopolitical divisions.

To compare the immunogenicity of routine versus mass campaign doses of oral poliovirus vaccine (OPV), serum neutralizing antibodies were measured in 254 children before and after two mass vaccination campaigns in Jordan. Precampaign seroprevalences to poliovirus types 1, 2, and 3 in children who had received three, four, or five routine doses of OPV were compared with postcampaign seroprevalences in children who had received one, two, or three routine doses plus two mass campaign doses. Seroprevalences were consistently higher in subgroups that received two doses through mass campaigns than in subgroups that received all doses through the routine program, especially for poliovirus type 3. Geometric mean titers were also consistently higher for mass campaign subgroups, particularly for poliovirus type 3. The findings suggest that adding further doses of OPV to the routine schedule is unlikely to have as great an impact on the immune state of children as administering the same number of doses during mass campaigns.

National immunization days (NIDs) are nationwide mass campaigns to deliver supplemental doses of oral poliovirus vaccine to interrupt the circulation of wild polioviruses. They constitute one of the critical strategies for global poliomyelitis eradication and should be implemented in all countries with widespread poliovirus transmission. The certification of wild poliovirus eradication from the Western Hemisphere in September 1994 verified the effectiveness of this aspect of the World Health Organization's (WHO) overall strategy for polio eradication by the year 2000. NIDs require careful advanced planning and orchestration by each country. WHO provides specific guidelines for NIDs regarding the season, target age group, duration, frequency, inclusion of other interventions, vaccine delivery strategies, and evaluation. With strong routine immunization programs and the effective implementation of NIDs, "mop-up" campaigns, and acute flaccid paralysis surveillance, the goal of global polio eradication will be achieved.

The World Health Organization recommends conducting supplemental immunization activities to eradicate poliomyelitis by the year 2000. Although effective in eliminating poliomyelitis from the Americas, supplemental campaigns require substantial resources. To assess differential campaign effectiveness in eliminating this disease, poliomyelitis occurrence was compared in counties in China that targeted children <3 versus <4 years of age. Counties that targeted children <3 years of age reported poliomyelitis more frequently after the campaigns. This association was observed even after accounting for the effects of previous poliomyelitis occurrence, urban versus rural setting, and population density. While several limitations emphasize the preliminary nature of these findings, these data support targeting the widest possible age group of susceptible children to ensure maximum effectiveness in eliminating poliomyelitis. Thus, while reducing the target age of these activities may result in considerable resource savings, such campaigns may not be as effective in eliminating poliomyelitis.

Problem/condition: CDC monitors the incidence of mumps in the United States through the passive reporting of cases to its National Notifiable Disease Surveillance System (NNDSS)., Reporting Period Covered: 1988-1993., Description of System: Weekly reports to the NNDSS from 48 states and the District of Columbia were used to calculate incidence rates for mumps. State immunization requirements were obtained from the U.S. Department of Health and Human Services., Results: After the licensure of mumps vaccine in the United States in December 1967 and the subsequent introduction of state immunization laws in an increasing number of states, the reported incidence of mumps decreased substantially. The 1,692 cases of mumps reported for 1993 represent the lowest number of cases ever reported to NNDSS and a 99% decrease from the 152,209 cases reported for 1968. During 1988-1993, most cases occurred in children 5-14 years of age (52%) and in persons > or = 15 years of age (36%). Although the incidence decreased in all age groups, the largest decreases (> 50% reduction in incidence rate per 100,000 population) occurred in persons > or = 10 years of age. Overall, the incidence of mumps was lowest in states that had comprehensive school immunization laws requiring mumps vaccination and highest in states that did not have such requirements., Interpretation: Because of the extensive use of mumps vaccine and the increased number of states that had enacted mumps immunization laws, the number of reported mumps cases decreased further since the marked decline that began during the early 1970s. The earlier shift in incidence from children of school ages to older persons that was noted during 1985-1988 continued until 1992, when the proportion of cases occurring in children of school ages increased and exceeded the proportions occurring in other age groups., Actions Taken: All health-care providers are encouraged to a) report mumps cases to their local and state health departments for transmission to NNDSS and b) enact school immunization laws requiring mumps vaccination.

Inactivated and trivalent oral poliovirus vaccines contain either formalin-inactivated or live, attenuated poliovirus, respectively, of the three serotypes. Interference among the three attenuated poliovirus serotypes was minimized with a "balanced-formulation" vaccine, and serologic responses after IPV were optimized by adjusting the antigenic content of each inactivated poliovirus serotype. Seroconversion is dependent on both the relative content as well as the absolute quantity of virus in the vaccine. The "gold standard" method to assess humoral antibody responses following vaccination is the neutralization assay. Any detectable titer of neutralizing antibody against poliovirus is considered protective against clinical paralytic diseases. Recently, standard procedures were adopted for conducting neutralization assays. Efforts are being undertaken now to develop a combined diphtheria and tetanus toxoids and pertussis vaccine and IPV vaccine in the United States using a dual-chambered syringe that mixes the content of both vaccines at the time of injection; this approach is necessary to overcome the potential detrimental effect of thimerosal on IPV (the preservative in DTP). Other vaccines that combine DTP and/or Haemophilus influenzae type b and/or hepatitis B with IPV appear feasible but require further investigation. New combination vaccines should induce similar or superior levels of neutralizing antibody in serum for individual protection against paralytic disease and mucosal immunity that effectively decreases viral replication in the intestine and pharynx for population protection against transmission of poliovirus.

Concurrent outbreaks of illnesses that were manifested by cough and that were suspected to be due to Bordetella pertussis and Mycoplasma pneumoniae infection were investigated in a midwestern town in Illinois. Three studies were conducted: questionnaires on the clinical and epidemiological characteristics of illness were administered to patients; serological tests were performed to confirm the presence of each pathogen and to develop case definitions for each illness; and case definitions were applied to responses to a mail-in questionnaire for estimating the magnitude of both outbreaks. In 135 cases of suspected pertussis and 42 cases of suspected mycoplasmal infection, subjects had a cough for > or = 14 days (the pertussis outbreak case definition). Among 20 laboratory-confirmed cases, a cough for > or = 14 days had a specificity of 20% for pertussis, and a cough for > or = 28 days plus whoop and/or vomiting had a specificity of 90% for pertussis. Six hundred-seventeen pertussis cases per 100,000 population and 1,179 cases of M. pneumoniae infection per 100,000 population occurred. In this setting, the standard outbreak case definition for pertussis lacked adequate specificity to distinguish pertussis from mycoplasmal infection. The magnitude of each outbreak was greater than the number of reported cases suggested.

Background: In Romania the rate of vaccine-associated paralytic poliomyelitis is for unexplained reasons 5 to 17 times higher than in other countries. Long ago it was noted that intramuscular injections administered during the incubation period of wild-type poliovirus infection increased the risk of paralytic disease (a phenomenon known as "provocation" poliomyelitis). We conducted a case-control study to explore the association between intramuscular injections and vaccine-associated poliomyelitis in Romania., Methods: The patients were 31 young children in whom vaccine-associated paralytic poliomyelitis developed from 1988 through 1992. Eighteen were vaccine recipients, and 13 had acquired the disease by contact with vaccine recipients. Each of these children was matched with up to five controls according to health center, age, and in the case of vaccine recipients, history of receipt of the live attenuated oral poliovirus vaccine. Data were abstracted from medical records that documented the injections administered in the 30 days before the onset of paralysis., Results: Of the 31 children with vaccine-associated disease, 27 (87 percent) had received one or more intramuscular injections within 30 days before the onset of paralysis, as compared with 77 of the 151 controls (51 percent) (matched odds ratio, 31.2; 95 percent confidence interval, 4.0 to 244.2). Nearly all the intramuscular injections were of antibiotics, and the association was strongest for the patients who received 10 or more injections (matched odds ratio for > or = 10 injections as compared with no injections, 182.1; 95 percent confidence interval, 15.2 to 2186.4). The risk of paralytic disease was strongly associated with injections given after the oral polio virus vaccine, but not with injections given before or at the same time as the vaccine (matched odds ratio, 56.7; 95 percent confidence interval, 8.9 to infinity). The attributable risk in the population for intramuscular injections given in the 30 days before the onset of paralysis was 86 percent (95 percent confidence interval, 66 to 95 percent); that is, we estimate that 86 percent of the cases of vaccine-associated paralytic poliomyelitis in this population might have been prevented by the elimination of intramuscular injections within 30 days after exposure to oral poliovirus vaccine., Conclusions: Provocation paralysis, previously described only for wild-type poliovirus infection, may rarely occur in a child who receives multiple intramuscular injections shortly after exposure to oral poliovirus vaccine, either as a vaccine recipient or through contact with a recent recipient. This phenomenon may explain the high rate of vaccine-associated paralytic poliomyelitis in Romania, where the use of intramuscular injections of antibiotics in infants with febrile illness is common.

Although poliomyelitis due to wild-virus infection has virtually disappeared from Romania, with no cases having been documented between 1984 and 1989, vaccine-associated paralytic poliomyelitis has been reported at very high rates for over two decades. In November 1990, to decrease the risk of vaccine-associated paralytic poliomyelitis, oral poliovirus vaccine produced in Romania was replaced by imported oral vaccine made by a Western European manufacturer. To better quantify the risk of vaccine-associated paralytic poliomyelitis and the impact of the change in vaccine manufacturer, the authors reviewed clinical, epidemiologic, and laboratory data on poliomyelitis cases that occurred in Romania from 1984 to 1992. Poliovirus isolates were characterized at the US Centers for Disease Control and Prevention. During the period 1984-1992, 132 confirmed cases of paralytic poliomyelitis were reported in Romania, of which 13 were classified as wild-virus-associated, 93 as vaccine-associated, and 26 as "of unknown origin." Wild type 1 poliovirus was isolated during 1990-1992 from nine of 13 (69%) cases in an outbreak that occurred primarily among undervaccinated gypsy children. Vaccine-associated cases were epidemiologically and virologically distinct from wild-virus cases. Of the 93 vaccine-associated cases, 45 children were recipients and 48 were contacts. The overall risk of vaccine-associated paralytic poliomyelitis in Romania (1 case per 183,000 doses of oral poliovirus vaccine distributed) was 14-fold higher than the risk in the United States. The risks of recipient vaccine-associated paralytic poliomyelitis related to the first dose of oral vaccine were similar for Romanian and imported vaccine (1 case per 95,000 doses and 1 case per 65,000 doses, respectively), as were the total risks of vaccine-associated paralytic poliomyelitis. These findings definitively demonstrate a substantially elevated risk of vaccine-associated paralytic poliomyelitis in Romania which was not affected by a change in oral poliovirus vaccine manufacturer.

Vaccination policies for preschool-age children, including those in child day care, have undergone frequent changes within the past several years in response to the development of new vaccines (DTaP, Hib conjugate vaccines), the changing epidemiology of vaccine-preventable diseases (measles), and the establishment of new objectives for the control and elimination of vaccine-preventable diseases (Hib, hepatitis B). The acquisition and spread of vaccine-preventable diseases can be minimized in child day-care settings by vaccinating all children, establishing a continuing system by which all children remain fully vaccinated on schedule, providing educational materials to parents about the recommended schedule of routine childhood vaccines, and implementing new recommendations for vaccine use.

The authors studied the effects of routine varicella immunization of US preschool children and of implementation of a catch-up program in older children on the age distribution of cases and on overall morbidity, with emphasis on the sensitivity of the results to level of vaccine coverage, duration of protection, responsiveness to boosting, relative residual susceptibility and infectiousness, and degree of morbidity among vaccine breakthrough cases. An age-structured theoretical transmission model was used, with values for vaccine efficacy based on a review of the literature by an expert panel. Although implementation of a vaccination program resulted in a shift in the age distribution of remaining varicella cases toward older ages with higher complication rates, the overall reduction in cases resulted in decreased morbidity as measured by overall number of hospitalizations and number of primary cases. Routine immunization with live-virus varicella vaccine would probably result in a substantial reduction in the number of uncomplicated primary cases of chickenpox, as well as a decreased number of complicated cases requiring hospitalization. The number and age distribution of vaccinated cases would depend strongly on the characteristics of the vaccine. Vaccine efficacy studies in the field should be designed to obtain better estimates of residual susceptibility, residual infectiousness, duration of protection, and effects of boosting by wild-type reinfection.

Background: Although the risk of vaccine-associated paralytic poliomyelitis (VAPP) has remained relatively constant during the past 30 years, estimates of VAPP depend largely on the completeness of reporting to the existing passive surveillance system. The National Vaccine Injury Compensation Program constitutes an alternative system for reporting VAPP, and data available from this system permitted us to evaluate the completeness of the national poliomyelitis surveillance system., Methods: We compared cases of paralytic poliomyelitis reported to the national surveillance system (maintained by the Centers for Disease Control and Prevention, Atlanta, Ga) with cases recommended for compensation by the National Vaccine Injury Compensation Program, Rockville, Md, and we calculated the observed completeness of reporting to the national system for 1980 through 1991. A capture-recapture method was also used to estimate completeness of reporting, ie, to account for cases potentially missed by both systems. In addition, we reviewed the epidemiology and updated the risk of VAPP based on the most current information on cases of VAPP., Results: From 1980 through 1991, 105 cases of paralytic poliomyelitis were identified by the Centers for Disease Control and Prevention and National Vaccine Injury Compensation Program systems, 98 (93%) of which were VAPP (average, 8.2 cases per year). The observed completeness of reporting to the Centers for Disease Control and Prevention was 94%, and the estimated completeness of reporting (capture-recapture method) was 81%. The overall risk of VAPP was one case per 2.5 million doses of oral poliovirus vaccine distributed. In the sensitivity analysis, the risk estimates of VAPP remained relatively stable throughout a wide range of assumptions regarding underreporting and specificity of the case definition for paralytic poliomyelitis., Conclusion: The risk of VAPP remains virtually unchanged from previous estimates despite the inclusion of previously unidentified VAPP cases. Despite the potential for both underreporting and misclassification of cases, our risk estimates were relatively insensitive to either of these biases. Since both of these biases were in opposite directions, and both probably occurred with low frequency, the risk estimates provided in this report appear valid and approximate the "true" risk of VAPP in the United States.

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.

Objective: To evaluate the economic consequences of a routine varicella vaccination program that targets healthy children., Methods: Decision analysis was used to compare the costs, outcomes, and cost-effectiveness of a routine vaccination program with no intervention. Clinical outcomes were based on a mathematical model of vaccine efficacy that relied on published and unpublished data and on expert opinion. Medical utilization rates and costs were collected from multiple sources, including the Kaiser Permanente Medical Care Program and the California Hospital Discharge Database., Results: A routine varicella vaccination program for healthy children would prevent 94% of all potential cases of chickenpox, provided the vaccination coverage rate is 97% at school entry. It would cost approximately $162 million annually if one dose of vaccine per child were recommended at a cost of $35 per dose. From the societal perspective, which includes work-loss costs as well as medical costs, the program would save more than $5 for every dollar invested in vaccination. However, from the health care payer's perspective (medical costs only), the program would cost approximately $2 per chickenpox case prevented, or $2500 per life-year saved. The medical cost of disease prevention was sensitive to the vaccination coverage rate and vaccine price but was relatively insensitive to assumptions about vaccine efficacy within plausible ranges. An additional program for catch-up vaccination of 12-year-olds would have high incremental costs if the vaccination coverage rate of children of preschool age were 97%, but would result in net savings at a coverage rate of 50%., Conclusions: A routine varicella vaccination program for healthy children would result in net savings from the societal perspective, which includes work-loss costs as well as medical costs. Compared with other prevention programs, it would also be relatively cost-effective from the health care payer's perspective.

No diagnostic test for pertussis in routine use in the United States has both high sensitivity and high specificity. During a statewide increase in the incidence of pertussis in Missouri, we studied the clinical features of 153 patients with suspected pertussis in the Greater St. Louis area from whom a specimen for pertussis culture had been taken between 15 May and 19 September 1989. In this cross-sectional study, nasopharyngeal cultures were more likely to be positive for persons whose specimens were collected < 21 days after cough onset (adjusted rate ratio [RRa] and 95% confidence interval = 3.4; 1.5-8.0) and who were not receiving erythromycin/sulfamethoxazole prior to the culture [RRa = 5.8; 0.8-40.6], who had received fewer than three prior doses of pertussis vaccine [RRa = 1.8; 0.8-4.2], and whose specimen was in transit to the laboratory for < 4 days [RRa = 2.0; 0.8-5.5]. Among children < 5 years of age, spasmodic cough plus a lymphocytosis of > 10,000/mm3 was the acute symptom complex associated with the highest predictive value for a positive culture result (67%). Cough for > or = 14 days plus whoop was sensitive (81%) and specific (58%) for identifying children with culture-confirmed pertussis. Direct fluorescent antibody staining performed well as a screening test for pertussis but requires substantial commitment of personnel and resources. In the absence of a positive culture result, clinical case definitions should be used for decision making (e.g., initiation of antimicrobial therapy and routine case reporting).

Objective: Effective Haemophilus influenzae type b (Hib) conjugate vaccines were first licensed for use in US children at least 18 months old in December 1987 and for infants at least 2 months old in October 1990. We evaluated trends in Hib disease associated with licensure of Hib conjugate vaccines., Design: Data from two sources, an intensive laboratory-based active surveillance system and the National Bacterial Meningitis Reporting System (NBMRS), were used separately to evaluate disease incidence. Data from vaccine manufacturers on Hib vaccine doses distributed in the United States were compared with trends in Hib disease incidence., Results: The age-specific incidence of Hib disease among children less than 5 years old decreased by 71% from 37 per 100,000 persons in 1989 to 11 per 100,000 persons in 1991 (active surveillance data). Haemophilus influenzae meningitis incidence decreased by 82% between 1985 and 1991 (NBMRS data). Increases in doses of Hib vaccine distributed in the United States coincided with steep declines in Hib disease. Both surveillance systems showed decreased rates of Hib disease in infants less than 1 year old before vaccine was licensed for use in this age group. Haemophilus influenzae type b disease incidence in persons at least 12 years old and pneumococcal meningitis incidence in children less than 5 years old did not change substantially during the same period; therefore, decreased Hib disease in children less than 5 years old is not likely to be explained solely by changes in surveillance sensitivity or decreases in bacterial disease due to changes in medical practice., Conclusion: Our data suggest that conjugate vaccines have already had a marked impact on the incidence of Hib disease in the United States, preventing an estimated 10,000 to 16,000 cases of Hib disease in 1991. The decline of disease in infants less than 1 year old before licensure for this age group warrants further investigation.

Dramatic reductions in the incidence of diphtheria and high levels of childhood vaccination in recent decades have led the United States to establish the goal of diphtheria elimination among persons < or = 25 years of age by the year 2000. In 1990, an unimmunized 25-month-old child died of respiratory diphtheria in Dade County, Florida, before treatment with diphtheria antitoxin could be instituted. Twenty-three asymptomatic household contacts and other close contacts of the child were identified, cultured for Corynebacterium diphtheriae, given antimicrobial prophylaxis, and vaccinated with diphtheria toxoid when indicated. Three contacts (13%) had pharyngeal cultures positive for toxigenic C. diphtheriae of the same type as that causing infection in the deceased child, but no additional cases developed. Although the source of infection was not determined, three other close contacts had recently been to Haiti, where diphtheria is endemic. A serological survey of 396 children < 5 years of age who received care at a medical center in Dade County revealed that 22% lacked protective immunity to diphtheria. Attainment of the goal of diphtheria elimination among persons < or = 25 years of age--and ultimately among all persons--will depend on the maintenance of a high level of clinical awareness of the disease, the prompt institution of preventive measures among close contacts of patients with sporadic cases, and improved vaccination levels among infants, children, and adults.

During the period 1989-1990, 117 cases of tetanus were reported from 34 states, for an average annual incidence of 0.02/100,000 population. Fifty-eight percent of patients were > or = 60 years of age, while seven (6%) were < 20 years of age, including one case of neonatal tetanus. Among adults, the risk of tetanus in those > 80 years of age was more than 10 times the risk in persons ages 20-29 years. The case-fatality rate increased with age, from 17% in persons 40-49 years of age to 50% in those > or = 80 years of age. Only 11% of patients reported having received a primary series of tetanus toxoid before disease onset, while 31% lacked a history of tetanus vaccination. Tetanus occurred following an acute injury in 78% of patients. Of patients who sought medical care, only 58% received tetanus toxoid as part of wound prophylaxis. Tetanus remains a severe disease that primarily affects unvaccinated or inadequately vaccinated older adults. Increased efforts are needed to reduce the risk of tetanus among the elderly. Health-care providers should take every opportunity to review the vaccination status of their patients and provide tetanus vaccine when indicated.

The licensure of whole-cell pertussis vaccine combined with diphtheria and tetanus toxoids as DTP in the 1940s--and its widespread use in infants and children--led to a dramatic decline in the incidence of reported pertussis. In the prevaccine era, the average annual incidence and mortality for reported pertussis were 150 cases and six deaths per 100,000 population, respectively. From 1989 to 1991, pertussis cases were reported by state and local health departments to CDC through two distinct national surveillance systems: the National Notifiable Diseases Surveillance System (NNDSS) and the Supplementary Pertussis Surveillance System (SPSS). During the period 1989-1991, 11,446 pertussis cases were reported to the NNDSS (4,157 in 1989; 4,570 in 1990; and 2,719 in 1991), for an unadjusted annual incidence of 1.7, 1.8, and 1.1 cases per 100,000 population in 1989, 1990, and 1991, respectively. For the period 1989-1991, case reports were received through the SPSS on 9,480 (83%) of the 11,446 patients reported to the NNDSS. Age-specific incidence and hospitalization rates were highest among children < 1 year of age and declined with increasing age. Long-term trends suggest an increase in the reported incidence of pertussis in the United States since 1976. The peak in reported pertussis cases in 1990 represents the highest annual incidence of pertussis since 1970. However, the incidence of pertussis declined 41% from 1990 through 1991. Whether the long-term increase in reported pertussis is a true increase in incidence is unclear; the observed increase may be a function of improved surveillance.(ABSTRACT TRUNCATED AT 250 WORDS)

Although injections administered during the incubation period of wild poliovirus infection have been associated with an increased risk of paralytic poliomyelitis, quantitative estimates of the risk have not been established. During a poliomyelitis outbreak investigation in Oman, vaccination records were reviewed for 70 children aged 5-24 months with poliomyelitis and from 692 matched control children. A significantly higher proportion of cases received a DTP (diphtheria and tetanus toxoids and pertussis vaccine) injection within 30 days before paralysis onset than did controls (42.9% vs. 28.3%; odds ratio, 2.4; 95% confidence interval, 1.3-4.2). The proportion of poliomyelitis cases that may have been provoked by DTP injections was 35% for children 5-11 months old. This study confirms that injections are an important cause of provocative poliomyelitis. Although the benefits of DTP vaccination should outweigh the risk of subsequent paralysis, these data stress the importance of avoiding unnecessary injections during outbreaks of wild poliovirus infection.

From 1980 through 1989, 27,826 cases of pertussis were reported to the Centers for Disease Control, for an average annual crude incidence of 1.2 cases/100,000 population. The incidence of reported disease increased in all age groups during this period, but the increase was disproportionately large among adolescents and adults. Infants between 1 and 2 months of age were at highest risk for pertussis (average annual incidence, 62.8/100,000). Infants less than 2 months of age had the highest reported rates of pertussis-associated hospitalization (82%), pneumonia (25%), seizures (4%), encephalopathy (1%), and death (1%). Rates of complication were generally higher among unvaccinated children than among those who had received three or more doses of diphtheria-tetanus-pertussis vaccine; 64% of children 3 months to 4 years of age who had reported cases of pertussis had not been immunized appropriately for their age. Whereas control of pertussis in the United States may be further improved through increased levels of diphtheria-tetanus-pertussis vaccination among eligible infants and children, the use of acellular vaccines in adolescents and adults may also be needed to reduce the burden of pertussis in very young infants.

To examine the effectiveness of erythromycin therapy and prophylaxis for pertussis, 17 households with one secondary case or more were compared with 20 households without secondary cases following a community-wide pertussis outbreak in Maricopa County, Arizona, in 1988. There were no significant differences between the two household groups in age distribution of members, size, crowding, race, proportion of children aged 7 months to 18 years with three or more diphtheria and tetanus toxoids and pertussis vaccine doses, or in the age distribution, vaccination status, or medical care of patients with primary cases. However, median intervals from onset of illness in primary cases to initiation of erythromycin therapy (for cases) and prophylaxis (for contacts) were 11 and 16 days, respectively, in households without secondary spread, vs 21 and 22 days, respectively, in households with secondary spread. These results provide additional evidence that erythromycin is effective in the medical management of pertussis and should be initiated promptly to minimize secondary spread.

Poliomyelitis caused by wild poliovirus has been virtually nonexistent in the United States since 1980, and vaccine-associated paralytic poliomyelitis (VAPP) has emerged as the predominant form of the disease. We reviewed national surveillance data on poliomyelitis for 1960-1989 to assess the changing risks of wild-virus, vaccine-associated, and imported paralytic disease; we also sought to characterize the epidemiology of poliomyelitis for the period 1980-1989. The risk of VAPP has remained exceedingly low but stable since the mid-1960s, with approximately 1 case occurring per 2.5 million doses of oral poliovirus vaccine (OPV) distributed during 1980-1989. Since 1980 no indigenous cases of wild-virus disease, 80 cases of VAPP, and five cases of imported disease have been reported in the United States. Three distinct groups are at risk of vaccine-associated disease: recipients of OPV (usually infants receiving their first dose), persons in contact with OPV recipients (mostly unvaccinated or inadequately vaccinated adults), and immunologically abnormal individuals. Overall, 93% of cases in OPV recipients and 76% of vaccine-associated cases have been related to administration of the first or second dose of OPV. Our findings suggest that adoption of a sequential vaccination schedule (inactivated poliovirus vaccine followed by OPV) would be effective in decreasing the risk of VAPP while retaining the proven public health benefits of OPV.

Objective: --To determine the magnitude of hospitalizations for pertussis and pertussis mortality and to estimate the total burden of clinically significant pertussis in the United States., Design: --Capture-recapture methods for estimating population size from independent surveillance systems were used to analyze morbidity and mortality data from case report forms received at the Centers for Disease Control (CDC) from the states, and compared these data with pertussis hospitalizations compiled from a database of US hospitals participating in the Commission on Professional and Hospital Activities-Professional Activities Survey (CPHA-PAS) and death certificate reports compiled by the National Center for Health Statistics (NCHS)., Population Studied: --All pertussis hospitalizations and pertussis-related deaths in the United States, 1985 through 1988., Results: --We estimated that 13,557 pertussis hospitalizations (95% confidence interval [CI], 12,953 to 14,162) and 98 pertussis deaths had occurred during the 4-year study period (an average of more than 3300 hospitalizations and 25 deaths per year). The completeness of reporting hospitalizations to the CDC was 32% and to the CPHA-PAS, 23%, while the completeness of reporting pertussis deaths to the CDC was 33% and to NCHS, 23%. Patients who were hospitalized with pertussis and reported to CDC were at a higher risk for developing pneumonia (31.0% vs 20.0%, relative risk [RR], 1.6; 95% CI, 1.4 to 1.7), seizures (3.7% vs 2.1%; RR, 1.9; 95% CI, 1.4 to 2.5) and encephalitis (1.2% vs 0.2%; RR, 5.3; 95% CI, 2.4 to 11.6) compared with patients recorded in the CPHA-PAS system., Conclusions: --Our study suggests that there is substantial underreporting of pertussis, that severe complications of pertussis (including hospitalizations) are reported preferentially to the CDC, and that the national health impact of pertussis based on these indicators is considerably higher than previously published reports have suggested.

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.