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Measles eradication would avert the current annual 1 million deaths and save the $1.5 billion in treatment and prevention costs due to measles in perpetuity. The authors evaluate the biological feasibility of eradicating measles according to 4 criteria: (1) the role of humans in maintaining transmission, (2) the availability of accurate diagnostic tests, (3) the existence of effective vaccines, and (4) the need to demonstrate elimination of measles from a large geographic area. Recent successes in interrupting measles transmission in the United States, most other countries in the Western Hemisphere, and selected countries in other regions provide evidence for the feasibility of global eradication. Potential impediments to eradication include (1) lack of political will in some industrialized countries, (2) transmission among adults, (3) increasing urbanization and population density, (4) the HIV epidemic, (5) waning immunity and the possibility of transmission from subclinical cases, and (6) risk of unsafe injections. Despite these challenges, a compelling case can be made in favor of measles eradication, and the authors believe that it is in our future. The question is when. [ABSTRACT FROM AUTHOR]

Disease eradication as a public health strategy was discussed at international meetings in 1997 and 1998. In this article, the ongoing poliomyelitis eradication initiative is examined using the criteria for evaluating candidate diseases for eradication proposed at these meetings, which covered costs and benefits, biological determinants of eradicability (technical feasibility) and societal and political considerations (operational feasibility). The benefits of poliomyelitis eradication are shown to include a substantial investment in health services delivery, the elimination of a major cause of disability, and far-reaching intangible effects, such as establishment of a 'culture of prevention'. The costs are found to be financial and finite, despite some disturbances to the delivery of other health services. The 'technical' feasibility of poliomyelitis eradication is seen in the absence of a non-human reservoir and the presence of both an effective intervention and delivery strategy (oral poliovirus vaccine and national immunization days) and a sensitive and specific diagnostic tool (viral culture of specimens from acute flaccid paralysis cases). The certification of poliomyelitis eradication in the Americas in 1994 and interruption of endemic transmission in the Western Pacific since March 1997 confirm the operational feasibility of this goal. When the humanitarian, economic and consequent benefits of this initiative are measured against the costs, a strong argument is made for eradication as a valuable disease control strategy. [ABSTRACT FROM AUTHOR]

Background: The Global Polio Eradication Initiative (GPEI) Strategic Plan for 2019-2023 includes commitments to monitor the quality of immunization campaigns using lot quality assurance sampling surveys (LQAS) and to support poliovirus surveillance in Pakistan and Afghanistan., Methods: We analyzed LQAS and poliovirus surveillance data between 2016 and 2020, which included both acute flaccid paralysis (AFP) case-based detection and the continued expansion of environmental surveillance (ES). Using updated estimates for unit costs, we explore the costs of different options for future poliovirus monitoring and surveillance for Pakistan and Afghanistan., Results: The relative value of the information provided by campaign quality monitoring and surveillance remains uncertain and depends on the design, implementation, and performance of the systems. Prospective immunization campaign quality monitoring (through LQAS) and poliovirus surveillance will require tens of millions of dollars each year for the foreseeable future for Pakistan and Afghanistan., Conclusions: LQAS campaign monitoring as currently implemented in Pakistan and Afghanistan provides limited and potentially misleading information about immunization quality. AFP surveillance in Pakistan and Afghanistan provides the most reliable evidence of transmission, whereas ES provides valuable supplementary information about the extent of transmission in the catchment areas represented at the time of sample collection., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2021.)

Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: To examine the impact of different bivalent oral poliovirus vaccine (bOPV) supplemental immunization activity (SIA) strategies on population immunity to serotype 1 and 3 poliovirus transmission and circulating vaccine-derived poliovirus (cVDPV) risks before and after globally-coordinated cessation of serotype 1 and 3 oral poliovirus vaccine (OPV13 cessation)., Methods: We adapt mathematical models that previously informed vaccine choices ahead of the trivalent oral poliovirus vaccine to bOPV switch to estimate the population immunity to serotype 1 and 3 poliovirus transmission needed at the time of OPV13 cessation to prevent subsequent cVDPV outbreaks. We then examine the impact of different frequencies of SIAs using bOPV in high risk populations on population immunity to serotype 1 and 3 transmission, on the risk of serotype 1 and 3 cVDPV outbreaks, and on the vulnerability to any imported bOPV-related polioviruses., Results: Maintaining high population immunity to serotype 1 and 3 transmission using bOPV SIAs significantly reduces 1) the risk of outbreaks due to imported serotype 1 and 3 viruses, 2) the emergence of indigenous cVDPVs before or after OPV13 cessation, and 3) the vulnerability to bOPV-related polioviruses in the event of non-synchronous OPV13 cessation or inadvertent bOPV use after OPV13 cessation., Conclusion: Although some reduction in global SIA frequency can safely occur, countries with suboptimal routine immunization coverage should each continue to conduct at least one annual SIA with bOPV, preferably more, until global OPV13 cessation. Preventing cVDPV risks after OPV13 cessation requires investments in bOPV SIAs now through the time of OPV13 cessation., Competing Interests: Competing Interests None

Background: Following successful eradication of wild polioviruses and planned globally-coordinated cessation of oral poliovirus vaccine (OPV), national and global health leaders may need to respond to outbreaks from reintroduced live polioviruses, particularly vaccine-derived polioviruses (VDPVs). Preparing outbreak response plans and assessing potential vaccine needs from an emergency stockpile require consideration of the different national risks and conditions as they change with time after OPV cessation., Methods: We used an integrated global model to consider several key issues related to managing poliovirus risks and outbreak response, including the time interval during which monovalent OPV (mOPV) can be safely used following homotypic OPV cessation; the timing, quality, and quantity of rounds required to stop transmission; vaccine stockpile needs; and the impacts of vaccine choices and surveillance quality. We compare the base case scenario that assumes aggressive outbreak response and sufficient mOPV available from the stockpile for all outbreaks that occur in the model, with various scenarios that change the outbreak response strategies., Results: Outbreak response after OPV cessation will require careful management, with some circumstances expected to require more and/or higher quality rounds to stop transmission than others. For outbreaks involving serotype 2, using trivalent OPV instead of mOPV2 following cessation of OPV serotype 2 but before cessation of OPV serotypes 1 and 3 would represent a good option if logistically feasible. Using mOPV for outbreak response can start new outbreaks if exported outside the outbreak population into populations with decreasing population immunity to transmission after OPV cessation, but failure to contain outbreaks resulting in exportation of the outbreak poliovirus may represent a greater risk. The possibility of mOPV use generating new long-term poliovirus excretors represents a real concern. Using the base case outbreak response assumptions, we expect over 25% probability of a shortage of stockpiled filled mOPV vaccine, which could jeopardize the achievement of global polio eradication. For the long term, responding to any poliovirus reintroductions may require a global IPV stockpile. Despite the risks, our model suggests that good risk management and response strategies can successfully control most potential outbreaks after OPV cessation., Conclusions: Health leaders should carefully consider the numerous outbreak response choices that affect the probability of successfully managing poliovirus risks after OPV cessation.

Background: The Global Polio Eradication Initiative plans for coordinated cessation of oral poliovirus vaccine (OPV) after interrupting all wild poliovirus (WPV) transmission, but many questions remain related to long-term poliovirus risk management policies., Methods: We used an integrated dynamic poliovirus transmission and stochastic risk model to simulate possible futures and estimate the health and economic outcomes of maintaining the 2013 status quo of continued OPV use in most developing countries compared with OPV cessation policies with various assumptions about global inactivated poliovirus vaccine (IPV) adoption., Results: Continued OPV use after global WPV eradication leads to continued high costs and/or high cases. Global OPV cessation comes with a high probability of at least one outbreak, which aggressive outbreak response can successfully control in most instances. A low but non-zero probability exists of uncontrolled outbreaks following a poliovirus reintroduction long after OPV cessation in a population in which IPV-alone cannot prevent poliovirus transmission. We estimate global incremental net benefits during 2013-2052 of approximately $16 billion (US$2013) for OPV cessation with at least one IPV routine immunization dose in all countries until 2024 compared to continued OPV use, although significant uncertainty remains associated with the frequency of exportations between populations and the implementation of long term risk management policies., Conclusions: Global OPV cessation offers the possibility of large future health and economic benefits compared to continued OPV use. Long-term poliovirus risk management interventions matter (e.g., IPV use duration, outbreak response, containment, continued surveillance, stockpile size and contents, vaccine production site requirements, potential antiviral drugs, and potential safer vaccines) and require careful consideration. Risk management activities can help to ensure a low risk of uncontrolled outbreaks and preserve or further increase the positive net benefits of OPV cessation. Important uncertainties will require more research, including characterizing immunodeficient long-term poliovirus excretor risks, containment risks, and the kinetics of outbreaks and response in an unprecedented world without widespread live poliovirus exposure.

Background: Frequent supplemental immunization activities (SIAs) with the oral poliovirus vaccine (OPV) represent the primary strategy to interrupt poliovirus transmission in the last endemic areas., Materials and Methods: Using a differential-equation based poliovirus transmission model tailored to high-risk areas in Nigeria, we perform one-way and multi-way sensitivity analyses to demonstrate the impact of different assumptions about routine immunization (RI) and the frequency and quality of SIAs on population immunity to transmission and persistence or emergence of circulating vaccine-derived polioviruses (cVDPVs) after OPV cessation., Results: More trivalent OPV use remains critical to avoid serotype 2 cVDPVs. RI schedules with or without inactivated polio vaccine (IPV) could significantly improve population immunity if coverage increases well above current levels in under-vaccinated subpopulations. Similarly, the impact of SIAs on overall population immunity and cVDPV risks depends on their ability to reach under-vaccinated groups (i.e., SIA quality). Lower SIA coverage in the under-vaccinated subpopulation results in a higher frequency of SIAs needed to maintain high enough population immunity to avoid cVDPVs after OPV cessation., Conclusions: National immunization program managers in northwest Nigeria should recognize the benefits of increasing RI and SIA quality. Sufficiently improving RI coverage and improving SIA quality will reduce the frequency of SIAs required to stop and prevent future poliovirus transmission. Better information about the incremental costs to identify and reach under-vaccinated children would help determine the optimal balance between spending to increase SIA and RI quality and spending to increase SIA frequency.

Background: Most poliovirus infections occur with no symptoms and this leads to the possibility of silent circulation, which complicates the confirmation of global goals to permanently end poliovirus transmission. Previous simple models based on hypothetical populations assumed perfect detection of symptomatic cases and suggested the need to observe no paralytic cases from wild polioviruses (WPVs) for approximately 3-4 years to achieve 95% confidence about eradication, but the complexities in real populations and the imperfect nature of surveillance require consideration., Methods: We revisit the probability of undetected poliovirus circulation using a more comprehensive model that reflects the conditions in a number of places with different characteristics related to WPV transmission, and we model the actual environmental WPV detection that occurred in Israel in 2013. We consider the analogous potential for undetected transmission of circulating vaccine-derived polioviruses. The model explicitly accounts for the impact of different vaccination activities before and after the last detected case of paralytic polio, different levels of surveillance, variability in transmissibility and neurovirulence among serotypes, and the possibility of asymptomatic participation in transmission by previously-vaccinated or infected individuals., Results: We find that prolonged circulation in the absence of cases and thus undetectable by case-based surveillance may occur if vaccination keeps population immunity close to but not over the threshold required for the interruption of transmission, as may occur in northwestern Nigeria for serotype 2 circulating vaccine-derived poliovirus in the event of insufficient tOPV use. Participation of IPV-vaccinated individuals in asymptomatic fecal-oral transmission may also contribute to extended transmission undetectable by case-based surveillance, as occurred in Israel. We also find that gaps or quality issues in surveillance could significantly reduce confidence about actual disruption. Maintaining high population immunity and high-quality surveillance for several years after the last detected polio cases will remain critical elements of the polio end game., Conclusions: Countries will need to maintain vigilance in their surveillance for polioviruses and recognize that their risks of undetected circulation may differ as a function of their efforts to manage population immunity and to identify cases or circulating live polioviruses.

In 1988, the World Health Assembly resolved to eradicate polio worldwide. Since then, four of the six World Health Organization (WHO) regions have been certified as polio-free: the Americas in 1994, the Western Pacific Region in 2000, the European Region in 2002, and the South-East Asia Region in 2014. Currently, nearly 80% of the world's population lives in areas certified as polio-free. Certification may be considered when ≥3 years have passed since the last isolation of wild poliovirus (WPV) in the presence of sensitive, certification-standard surveillance. Although regional eradication has been validated in the European Region and the Western Pacific Region, outbreaks resulting from WPV type 1 (WPV1) imported from known endemic areas were detected and controlled in these regions in 2010 and 2011, respectively. The last reported case associated with WPV type 2 (WPV2) was in India in 1999, marking global interruption of WPV2 transmission. The completion of polio eradication was declared a programmatic emergency for public health in 2012, and the international spread of WPV1 was declared a public health emergency of international concern in May 2014. The efforts needed to interrupt all indigenous WPV1 transmission are now being focused on the remaining endemic countries: Nigeria, Afghanistan, and Pakistan. WPV type 3 (WPV3) has not been detected in circulation since November 11, 2012. This report summarizes the evidence of possible global interruption of transmission of WPV3, based on surveillance for acute flaccid paralysis (AFP) and environmental surveillance.

In 1988, the World Health Assembly resolved to interrupt wild poliovirus (WPV) transmission worldwide. By 2006, the annual number of WPV cases had decreased by more than 99%, and only four remaining countries had never interrupted WPV transmission: Afghanistan, India, Nigeria, and Pakistan. The last confirmed WPV case in India occurred in January 2011, leading the World Health Organization (WHO) South-East Asia Regional Commission for the Certification of Polio Eradication (SEA-RCC) in March 2014 to declare the 11-country South-East Asia Region (SEAR), which includes India, to be free from circulating indigenous WPV. SEAR became the fourth region among WHO's six regions to be certified as having interrupted all indigenous WPV circulation; the Region of the Americas was declared polio-free in 1994, the Western Pacific Region in 2000, and the European Region in 2002. Approximately 80% of the world's population now lives in countries of WHO regions that have been certified polio-free. This report summarizes steps taken to certify polio eradication in SEAR and outlines eradication activities and lessons learned in India, the largest member state in the region and the one for which eradication was the most difficult.

Background: Global efforts to eradicate wild polioviruses (WPVs) continue to face challenges due to uninterrupted endemic WPV transmission in three countries and importation-related outbreaks into previously polio-free countries. We explore the potential role of including older children and adults in supplemental immunization activities (SIAs) to more rapidly increase population immunity and prevent or stop transmission., Methods: We use a differential equation-based dynamic poliovirus transmission model to analyze the epidemiological impact and vaccine resource implications of expanding target age groups in SIAs. We explore the use of older age groups in SIAs for three situations: alternative responses to the 2010 outbreak in Tajikistan, retrospective examination of elimination in two high-risk states in northern India, and prospective and retrospective strategies to accelerate elimination in endemic northwestern Nigeria. Our model recognizes the ability of individuals with waned mucosal immunity (i.e., immunity from a historical live poliovirus infection) to become re-infected and contribute to transmission to a limited extent., Results: SIAs involving expanded age groups reduce overall caseloads, decrease transmission, and generally lead to a small reduction in the time to achieve WPV elimination. Analysis of preventive expanded age group SIAs in Tajikistan or prior to type-specific surges in incidence in high-risk areas of India and Nigeria showed the greatest potential benefits of expanded age groups. Analysis of expanded age group SIAs in outbreak situations or to accelerate the interruption of endemic transmission showed relatively less benefit, largely due to the circulation of WPV reaching individuals sooner or more effectively than the SIAs. The India and Nigeria results depend strongly on how well SIAs involving expanded age groups reach relatively isolated subpopulations that sustain clusters of susceptible children, which we assume play a key role in persistent endemic WPV transmission in these areas., Conclusions: This study suggests the need to carefully consider the epidemiological situation in the context of decisions to use expanded age group SIAs. Subpopulations of susceptible individuals may independently sustain transmission, which will reduce the overall benefits associated with using expanded age group SIAs to increase population immunity to a sufficiently high level to stop transmission and reduce the incidence of paralytic cases.

Objectives: The United States eliminated indigenous wild polioviruses (WPVs) in 1979 and switched to inactivated poliovirus vaccine in 2000, which quickly ended all indigenous live poliovirus transmission. Continued WPV circulation and use of oral poliovirus vaccine globally allow for the possibility of reintroduction of these viruses. We evaluated the risk of a U.S. polio outbreak and explored potential vaccine needs for outbreak response., Methods: We synthesized information available on vaccine coverage, exemptor populations, and population immunity. We used an infection transmission model to explore the potential dynamics of a U.S. polio outbreak and potential vaccine needs for outbreak response, and assessed the impacts of heterogeneity in population immunity for two different subpopulations with potentially low coverage., Results: Although the risk of poliovirus introduction remains real, widespread transmission of polioviruses appears unlikely in the U.S., given high routine coverage. However, clusters of un- or underimmunized children might create pockets of susceptibility that could potentially lead to one or more paralytic polio cases. We found that the shift toward combination vaccine utilization, with limited age indications for use, and other current trends (e.g., decreasing proportion of the population with immunity induced by live polioviruses and aging of vaccine exemptor populations) might increase the vulnerability to poliovirus reintroduction at the same time that the ability to respond may decrease., Conclusions: The U.S. poliovirus vaccine stockpile remains an important resource that may potentially be needed in the future to respond to an outbreak if a live poliovirus gets imported into a subpopulation with low vaccination coverage.

In most developing countries, rubella vaccine has not been included in the Expanded Programme on Immunization because of lack of information on the burden of disease caused by rubella virus, increased cost associated with adding rubella vaccine, and the concern that if high vaccine coverage cannot be achieved and maintained, the risk of congenital rubella syndrome (CRS) may increase. Data for 2009 reported by countries to the World Health Organization (WHO) and United Nations Children's Fund through the annual Joint Reporting Form were used to indicate patterns in the worldwide use of rubella vaccines, describe the number of reported rubella and CRS cases by WHO Region, and explore factors associated with decisions by countries to introduce rubella vaccine in their national childhood immunization programs. The number of WHO Member States using rubella-containing vaccine (RCV) in their national childhood immunization schedule increased from 83 (43%) in 1996 to 130 (67%) in 2009. Although scheduled ages for rubella vaccination vary across countries and regions, most countries have a 2-dose schedule using a combined measles-mumps-rubella vaccine. Among 130 countries using RCV in 2009, median coverage with the first dose of measles-containing vaccine (MCV1) was 95% (interquartile range [IQR], 90%-98%), compared with a median MCV1 coverage of 76% (IQR, 64%-88%) in countries not using RCV. The median per capita gross national income among 130 countries using RCV was US $6300 (IQR, $3227-$20 916), compared with $635 (IQR, $337-$1027) for 63 countries not using RCV. In 2009, 121 344 rubella cases from 167 countries were reported to WHO. However, only 165 CRS cases were reported globally, of which 67 were in the Eastern Mediterranean Region. Further improvements in surveillance are needed to better document the burden of CRS, and new financing mechanisms will be required to catalyze the introduction of rubella vaccine in developing countries that currently meet the coverage criteria for introduction of rubella vaccine.

Background: The Millennium Development Goal 4 (MDG4) to reduce mortality in children aged <5 years by two-thirds from 1990 to 2015 has made substantial progress. We describe the contribution of measles mortality reduction efforts, including those spearheaded by the Measles Initiative (launched in 2001, the Measles Initiative is an international partnership committed to reducing measles deaths worldwide and is led by the American Red Cross, the Centers for Disease Control and Prevention, UNICEF, the United Nations Foundation, and the World Health Organization)., Methods: We used published data to assess the effect of measles mortality reduction on overall and disease-specific global mortality rates among children aged <5 years by reviewing the results from studies with the best estimates on causes of deaths in children aged 0-59 months., Results: The estimated measles-related mortality among children aged <5 years worldwide decreased from 872,000 deaths in 1990 to 556,000 in 2001 (36% reduction) and to 118,000 in 2008 (86% reduction). All-cause mortality in this age group decreased from >12 million in 1990 to 10.6 million in 2001 (13% reduction) and to 8.8 million in 2008 (28% reduction). Measles accounted for about 7% of deaths in this age group in 1990 and 1% in 2008, equal to 23% of the global reduction in all-cause mortality in this age group from 1990 to 2008., Conclusions: Aggressive efforts to prevent measles have led to this remarkable reduction in measles deaths. The current funding gap and insufficient political commitment for measles control jeopardizes these achievements and presents a substantial risk to achieving MDG4., (© The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.)

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.)

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.

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.

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 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.

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.

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).

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.

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.

We compared outer membrane protein (OMP) patterns of Haemophilus influenzae isolated in metropolitan Atlanta, Ga., from July 1983 to June 1985. Of 74 randomly selected H. influenzae serotype b, biotype I, isolates (24% of the total number of H. influenzae, and 32% of the total number of H. influenzae serotype b, biotype I, isolates), 66 (89.2%) had the same OMP pattern. Of the remaining eight, five (6.7%) had an identical OMP pattern. The other three isolates had separate and distinct patterns. A greater diversity of OMP patterns was found with H. influenzae serotype b, biotype II, and nonserotypeable H. influenzae. Of the 18 H. influenzae serotype b, biotype II, isolates (5.8% of the total number of H. influenzae isolates), 1 had an OMP pattern similar to that of the predominate biotype I OMP type, 6 (33% of the biotype II) had the same pattern, and 11 had heterogeneous patterns. Of the 19 recoverable, nonserotypeable biotype II isolates (6.8% of the total number of H. influenzae), 18 had different OMP patterns, and no pattern was similar to those observed with serotype b. These findings indicate that most H. influenzae strains isolated during this 2-year period were indistinguishable by serotype, biotype, or OMP patterns.

Cases of rubella continue to occur among adults in the United States because 10-20 per cent of persons in this age group remain susceptible. To evaluate the potential preventability of these cases, we present a method for assessing missed opportunities for rubella immunization, based on immunization recommendations of the Immunization Practices Advisory Committee (ACIP) of the US Public Health Service (PHS). Immunization programs faced with limited resources can use analysis of missed opportunities to focus on those gaps in implementation contributing most to the remaining rubella cases.

An epidemiologic classification of paralytic poliomyelitis cases (ECPPC) has been in use in the United States since 1976. In 1985, this classification system was reviewed because of recent changes in the epidemiology of paralytic poliomyelitis and improved laboratory capability to definitively characterize poliovirus strains. An alternative classification system was devised, the epidemiologic and laboratory classification of paralytic polio cases (ELCPPC), that incorporated virus isolation and strain characterization with epidemiologic information. Reported paralytic poliomyelitis cases for 1980-86 were classified by both the ECPPC and the ELCPPC classification systems. The new ELCPPC system classified 91 per cent of the reported cases as vaccine-associated, while the ECPPC system classified only 71 per cent of the reported cases as vaccine-associated. The proposed classification system provides more specific and useful information particularly concerning vaccine-associated paralytic poliomyelitis.

The availability of new data regarding the risk of invasive Haemophilus influenzae type b (Hib) among day care attendees allows the formulation of a practical public health approach to this problem. It is now clear that day care attendees are at significantly increased risk for development of primary invasive Hib disease. While the risk of secondary Hib disease for most is low, risk is substantially increased when young day care attendees are exposed to a primary case to a degree analogous to that of household contacts. Because risk for primary Hib disease is increased among day care attendees, immunization of these children with Hib polysaccharide vaccine is of the highest priority and may be appropriate for children as young as 18 months of age. In light of new data documenting the efficacy of rifampin in prevention of secondary disease, the use of this medication is indicated when unvaccinated day care attendees younger than two years old have had significant contact with a primary case.

During a county-wide mumps outbreak in Nashville, Tennessee, 332 cases of mumps were identified at a public high school (attack rate, 18.8%). A pep rally 17 d before the peak of the outbreak at a single public high school may have provided an opportunity for point-source exposure. A case-control study demonstrated that vaccine efficacy was 75% (we used provider-verified records and excluded students with a history of mumps disease). Although school records were nonuniform, mumps immunization status was correct, compared with provider-verified records, in at least 85% of both cases and controls. Parental reports were much less reliable. The cost of the outbreak was estimated at $154/case. Receiving mumps vaccine at a vaccine clinic held after the outbreak had peaked was associated with a decrease in risk of mumps disease. Thus, these clinics may have a role in the control of such outbreaks.