Evolving epidemiology of poliovirus serotype 2 following withdrawal of the serotype 2 oral poliovirus vaccine.

Although there have been no cases of serotype 2 wild poliovirus for more than 20 years, transmission of serotype 2 vaccine-derived poliovirus (VDPV2) and associated paralytic cases in several continents represent a threat to eradication. The withdrawal of the serotype 2 component of oral poliovirus vaccine (OPV2) was implemented in April 2016 to stop VDPV2 emergence and secure eradication of all serotype 2 poliovirus. Globally, children born after this date have limited immunity to prevent transmission. Using a statistical model, we estimated the emergence date and source of VDPV2s detected between May 2016 and November 2019. Outbreak response campaigns with monovalent OPV2 are the only available method to induce immunity to prevent transmission. Yet our analysis shows that using monovalent OPV2 is generating more paralytic VDPV2 outbreaks with the potential for establishing endemic transmission. A novel OPV2, for which two candidates are currently in clinical trials, is urgently required, together with a contingency strategy if this vaccine does not materialize or perform as anticipated.

Mass vaccination campaigns for polio eradication: an essential strategy for success.

Effective vaccines against poliomyelitis became available in the mid-1950s and early 1960s. Mass campaigns were an integral part of early control efforts. Thereafter, polio vaccines were used largely in routine childhood programs. The resolution in 1988 to eradicate polio globally led to the development of appropriate strategies to achieve this goal, including mass vaccination campaigns (i.e., national immunization days, sub-national immunization days and mop-up activities), to achieve the highest possible coverage in the shortest possible time. Unlike other vaccines, mass campaign use of oral poliovirus vaccine enhances the immunogenicity of this vaccine, primarily due to: (1) the decrease in the prevalence of other enteroviruses that potentially interfere with seroconversion; and (2) the secondary spread of vaccine virus from vaccinees to close contacts, resulting in seroconversion of some unvaccinated contacts. To reach the highest possible coverage, detailed planning, meticulous execution, careful supervision and standardized monitoring are critical. A number of innovative approaches to improve the quality and/or coverage have become the 'standard' of supplemental immunization activities. These mass campaigns have led to dramatic decreases in the incidence of polio. This chapter reviews the scientific, operational and programmatic data on mass campaign use of polio vaccines, and summarize the lessons learnt from implementing the mass vaccination strategies used to eradicate poliomyelitis globally.

Zinc supplementation fails to increase the immunogenicity of oral poliovirus vaccine: a randomized controlled trial.

BACKGROUND: Polio eradication remains a challenge in Pakistan and the causes for the failure to eradicate poliomyelitis are complex. Undernutrition and micronutrient deficiencies, especially zinc deficiency, are major public health problems in Pakistan and could potentially affect the response to enteric vaccines, including oral poliovirus vaccine (OPV). OBJECTIVE: To assess the impact of zinc supplementation among infants on immune response to oral poliovirus vaccine (OPV). METHODS: A double-blind, randomized placebo-controlled trial was conducted in newborns (aged 0-14 days). Subjects were assigned to either receive 10mg of zinc or placebo supplementation daily for 18 weeks. Both groups received OPV doses at birth, at 6 weeks, 10 weeks and 14 weeks. Data was collected on prior immunization status, diarrheal episodes, breastfeeding practices and anthropometric measurements at recruitment and at 6 and 18 weeks. Blood samples were similarly collected to determine the antibody response to OPV and for micronutrient analysis. Logistic regression was used to determine the relationship between seroconversion and zinc status. RESULTS: Overall, 404 subjects were recruited. At recruitment, seropositivity was already high for poliovirus (PV) serotype 1 (zinc: 91.1%; control: 90.5%) and PV2 (90.0%; 92.7%), with lower estimates for PV3 (70.0%; 64.8%). By week 18, the proportion of subjects with measured zinc levels in the normal range (i.e. ≥60 µg/dL) was significantly greater in the intervention group compared to the control group (71.9%; 27.4%; p<0.001). No significant difference in seroconversion was demonstrated between the groups for PV1, PV2, or PV3. CONCLUSIONS: There was no effect of zinc supplementation on OPV immunogenicity. These conclusions were confirmed when restricting the analysis to those with measured higher zinc levels.

Vaccine-associated paralytic poliomyelitis in the United States: no evidence of elevated risk after simultaneous intramuscular injections of vaccine.

During the past 30 years, Romania reported rates of vaccine-associated paralytic poliomyelitis (VAPP) approximately 10-fold higher than in the United States. The elevated VAPP risk was largely caused by multiple intramuscular (im) injections with antibiotics given within 30 days of onset of paralysis. Because it is not known whether im injections contribute to the VAPP risk in the United States, we examined VAPP cases reported since 1980. We reviewed injection histories of VAPP cases reported to the Centers for Disease Control and Prevention from 1980 to 1993: with vaccines for 1980 to 1987; and for all substances for 1988 to 1993. Rates of VAPP by number of im injections with vaccines were calculated from 1988 to 1993 with estimated vaccine coverage data from the National Health Interview Survey. From 1980 to 1993 a total of 119 cases of poliomyelitis were reported to the Centers for Disease Control and Prevention. Of these, 87 (73%) were vaccine-associated and immunologically normal: 41 were oral polio vaccine (OPV) recipient cases; 40 were OPV contact cases; and 6 were community-acquired cases. A history of im injections in the 45 days before onset of paralysis was obtained from 28 (72%) of 39 recipient cases reported from 1980 to 1993 for which dates of paralysis onset could be determined and from 1 (8%) of 13 contact cases reported from 1988 to 1993. With one exception all substances administered intramuscularly were routine childhood vaccines. No clustering of im injections in the "high risk" windows, 0 to 3 and 8 to 21 days before onset of paralysis, was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Paralytic poliomyelitis in Oman: association between regional differences in attack rate and variations in antibody responses to oral poliovirus vaccine.

Variation in attack rates of paralytic disease by region during the 1988-1989 epidemic of type 1 poliomyelitis in Oman provided the stimulus to test the hypothesis that these observations were due to regional differences in the response of infants to trivalent oral poliovirus vaccine (OPV). Seroprevalence studies of 394 children born during the outbreak were conducted in six different regions of Oman and in two socioeconomic status (SES) groups in the capital city of Muscat; a seroconversion study was also carried out in 105 infants born after the outbreak. Seroprevalence rates by region after receipt of at least three doses of OPV ranged from 90% to 100% (median 94%) to poliovirus type 1, and from 86% to 100% (median 97%) to type 2, and from 47% to 79% (median 72%) to type 3, with the lowest rates observed in regions with the highest incidence of type 1 paralytic disease. In Muscat, seroprevalence rates were also significantly lower in low versus high SES groups (type 1: 84% versus 98%, respectively [P = 0.006]; type 3: 59% versus 86%, respectively [P = 0.001]). In the seroconversion study conducted after the outbreak, 89%, 100% and 50% of infants had detectable antibodies to types 1, 2, and 3, respectively, after four doses of OPV. Low responses to type 3 were also associated with the occurrence of sporadic cases of type 3 poliomyelitis in 1991, in spite of high rates of coverage with at least four doses of OPV (> 96%) throughout the country.(ABSTRACT TRUNCATED AT 250 WORDS)

Persistence of vaccine-derived poliovirus following a mass vaccination campaign in Cuba: implications for stopping polio vaccination after global eradication.

BACKGROUND: With substantial progress made toward polio eradication, developing the appropriate strategy for discontinuing global oral poliovirus vaccine (OPV) after global eradication becomes increasingly important. At issue is the theoretical risk of independent circulation of potentially virulent OPV-derived strains. Because Cuba uses OPV only in mass campaigns, it represents an ideal site to assess vaccine-derived poliovirus persistence. METHODS: Infants born after the 1997 biannual mass campaigns were evaluated for past (neutralizing antibody) or current (virus excretion) evidence of vaccine-derived poliovirus exposure. We obtained sera and/or stool specimens from 861 infants; a second serum from 218 infants. RESULTS: All stool specimens were poliovirus negative. Of 762 infants, 113 (14.8%) had initially detectable poliovirus type 1 antibody, 193 (25.3%) type 2, and 94 (12.3%) type 3. A precipitous antibody decline occurred in initially positive sera. CONCLUSIONS: Our results suggest that in a country with high population immunity, vaccine-derived virus is unlikely to establish ongoing circulation.

Defining surrogate serologic tests with respect to predicting protective vaccine efficacy: poliovirus 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.

Completeness of reporting for paralytic poliomyelitis, United States, 1980 through 1991. Implications for estimating the risk of vaccine-associated disease.

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.

Poliomyelitis eradication: progress, challenges for the end game, and preparation for the post-eradication era.

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.

Poliovirus vaccines. Progress toward global poliomyelitis eradication and changing routine immunization recommendations in the United States.

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)

Possible global strategies for stopping polio vaccination and how they could be harmonized.

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.

A study evaluating poliovirus antibodies and risk factors associated with polio seropositivity in low socioeconomic areas of Pakistan.

BACKGROUND: Seroprevalence studies provide important data on performance of immunization programs, susceptible groups and populations at-risk of future outbreaks. Identifying risk factors that affect seroconversion of the oral polio vaccine (OPV) will enable the polio eradication initiatives to increase seroprevalence. This paper describes the first population-based seroprevalence survey in Pakistan. METHODS: This study evaluated the seroprevalence of poliovirus (PV) types 1, 2, and 3 antibodies to OPV in an illustrative sample of 554 subjects 6-11 months of age in three geographic locations of Pakistan (Lahore, Karachi, and Peshawar) representing a low socioeconomic at-risk populations. Antibody titers were measured and sero protection rates and geometric median titers were compared among different geographic regions and populations, as were demographics and OPV vaccination history collected by questionnaire. Univariate and multivariate analyses were conducted on subject characteristics to assess for potential risk factors for failure to sero-convert. RESULTS: The average seroprevalence of PV1, PV2, and PV3 was 96.0%, 87.9% and 86.7%, respectively. The lowest sero protection rate for all three serotypes was for Karachi with 90.2%, 73.8%, and 78.8% for PV1, PV2, and PV3, respectively. Significant regional variation in PV3 seroprevalence was found (range: 74.2-100%). In the univariate analysis, age, total and campaign OPV doses were associated with higher seroprevalence, whereas stunting, respondent education and diarrhea in the past six months were significant risk factors for failure to sero-convert. CONCLUSIONS: These findings demonstrate consistently high levels of antibody response to PV1 and more geographically varied response to PV2 and PV3. Additionally, important risk factors affecting seropositivity were identified.

Pertussis hospitalizations and mortality in the United States, 1985-1988. Evaluation of the completeness of national reporting.

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.

Tuberculosis morbidity and infection in Vietnamese in Southeast Asian refugee camps.

During the last decade, the refugee population in less-developed countries has undergone unprecedented growth. High tuberculosis rates have been documented in refugees, particularly among those from Asia and Africa, generating interest in tuberculosis control efforts. To assess the tuberculosis burden among Vietnamese refugees, we screened refugees within 1 or 2 days after arrival in camps in Thailand and in the Philippines. Refugees in camps in Thailand were screened with chest radiographs. Persons with radiographic findings consistent with tuberculosis received microscopic and culture examination of sputum specimens. The prevalence of bacteriologically confirmed pulmonary tuberculosis was 5.8 per 1,000 refugees. Males had a higher risk than females (relative risk RR = 1.7, 95% confidence interval CI = 1.2 to 2.4). Refugees in the Philippines were given a tuberculin skin test. An annual risk of infection of 2.2% was calculated for this group. Males had a higher risk of infection (RR = 1.9, 95% CI = 1.5 to 2.4) than females. The age-specific prevalence of tuberculosis and the tuberculous infection increased with age. A high proportion of refugees (85%) with positive tuberculin skin tests were eligible for preventive therapy. Special efforts may be necessary to target Vietnamese refugees, as well as other persons originating from countries of high tuberculosis prevalence, for enhanced diagnostic and preventive intervention against tuberculosis to achieve the national goal of tuberculosis elimination by the year 2010.

Sabin monovalent oral polio vaccines: review of past experiences and their potential use after polio eradication.

After global eradication of polio is achieved, there will be a need for stockpiles of vaccine to combat potential outbreaks of poliomyelitis caused by (1) unforeseen release of polioviruses, (2) continued circulation of vaccine-derived strains, or (3) prolonged replication of polioviruses in immunodeficient persons. We conducted a review of the literature to document the immunogenicity and safety of monovalent Sabin vaccines, considered ideal candidates for these situations. The National Library of Medicine archives were searched for the keywords "polio," "monovalent," and "vaccine." Seroconversion rates for monovalent Sabin type 1 ranged from 53% to 100% (median, 95%); for type 2, 77%-100% (median, 93%); and for type 3, 52%-100% (median, 85%). The risk of vaccine-associated poliomyelitis per million persons vaccinated ranged from.05 to 0.99 (type 1), 0-0.65 (type 2), and 1.18-8.91 (type 3). Single-dose monovalent Sabin vaccines are highly immunogenic and safe and should be considered for stockpiles of vaccine to provide an effective response to potential outbreaks of poliomyelitis in the post-eradication period.

Status of poliomyelitis eradication in Europe and the Central Asian republics of the former Soviet Union.

In the European Region of the World Health Organization, all countries in which polio is endemic have adopted the following strategies: achievement of high routine vaccination coverage, implementation of supplemental immunization activities, and enhancement of surveillance for poliomyelitis. In 1995, 205 cases of poliomyelitis were reported. Routine coverage among 1-year-olds with three doses of poliovirus vaccine was 89% in 1995. Ten countries conducted national immunization days (NIDs). Twenty-four countries (48%) adopted acute flaccid paralysis (AFP) surveillance. Use of NIDs has decreased poliomyelitis incidence in the seven countries in which polio is endemic (Armenia, Azerbaijan, Kazakhstan, Turkey, Turkmenistan, Tajikistan, Uzbekistan) from 203 cases in 1994 to 47 in 1995, a 77% reduction. Full implementation of the strategies to achieve eradication in the countries in which polio is endemic, including those countries with epidemic poliovirus transmission during 1995, is likely to accomplish regional eradication of poliomyelitis by the year 2000 or earlier.

Assessment of Guillain-Barré syndrome mortality and morbidity in the United States: implications for acute flaccid paralysis surveillance.

To estimate age-specific incidences and assess the national morbidity and mortality burden for Guillain-Barre syndrome (GBS) in the United States, a national hospital discharge database compiled by the Commission on Professional and Hospital Activities (CPHA) and national death certificate data reported to the National Vital Statistics System were reviewed. During 1985-1991, 10,453 patients with GBS were discharged from CPHA-participating hospitals (estimated annual incidence, 3.0/100,000 population). The age-specific incidence of GBS increased with age from 1.5/100,000 in persons <15 years old to 8.6/100,000 in persons 70-79 years old. The total estimated number of GBS-related deaths from 1985 through 1990 was 3770 (95% confidence interval, 3506-4034), for an average of 628 GBS deaths per year. These rates suggest that the proposed national surveillance system for acute flaccid paralysis should capture at a minimum the 796 GBS cases in persons <15 years old. GBS remains a significant health burden among older adults in the United States, with a marked increase in risk after age 40.

Factors determining prevalence of maternal antibody to measles virus throughout infancy: a review.

The effectiveness of vaccination against measles, the leading cause of vaccine-preventable deaths in infants globally, is greatly impacted by the level of maternal antibody to measles virus (or "measles maternal antibody"; MMA) during infancy. Variation in the prevalence of maternal antibody to measles virus between infant populations across countries and sociodemographic strata is poorly understood. We reviewed the literature on the prevalence of MMA, focusing on 3 principal determinants: starting level of maternal antibody, placental transfer of maternal antibody, and rate of decay of maternal antibody after birth. Our review identified placental transfer as an important determinant, with greater efficiency found in studies performed in developed countries. Placental transfer was influenced by gestational age, human immunodeficiency virus infection, and malaria. Antibody levels in mothers varied widely between countries, although predictably according to vaccination status within populations. Rates of antibody decay across studies were similar. Future studies should evaluate the utility of the cord blood level of MMA as a predictor of vaccine efficacy in infancy; inclusion of World Health Organization international reference sera will facilitate comparisons. Greater understanding of the determinants of the prevalence of MMA will help national policy makers determine the appropriate age for measles vaccination.