Community spread, community spread polio, Endemic polio, epidemic polio, eradication of polio, mutated polio vaccine, Mutated vaccine, Nigeria, OPV, Oral polio vaccine, polio, Polio vaccine, poliomyelitis, Post-polio syndrome, Vaccine associated paralytic poliomyelitis, vaccine derived circulating poliovirus, Vaccine derived poliovirus, Vaccine derived virus, VAPP, VDPV
In Nigeria (August 2021), “The Adamawa government has confirmed the detection of the circulating vaccine-derived poliovirus type 2 (cVDPV)….On August 25, 2020, the independent Africa Regional Certification Commission (ARCC) for polio eradication officially declared Nigeria and the rest of Africa free of indigenous wild poliovirus.” See: “Vaccine-derived polio emerges in Adamawa” by August 14, 2021 https://www.radionigeria.gov.ng/2021/08/14/vaccine-derived-polio-emerges-in-adamawa Monkeypox, which recently migrated to the US from Nigeria, may have its origins in a smallpox vaccine gone rogue.
“There are three wild types of poliovirus (WPV) – type 1, type 2, and type 3… Type 2 wild poliovirus was declared eradicated in September 2015, with the last virus detected in India in 1999. Type 3 wild poliovirus was declared eradicated in October 2019. It was last detected in November 2012. Only type 1 wild poliovirus remains… The oral poliovirus vaccine (OPV)… There are different types of oral poliovirus vaccine which may contain one, a combination of two, or all three different types of attenuated, or weakened, vaccine… After wild poliovirus type 2 was declared eradicated in 2015, the world switched from trivalent to bivalent OPV (bOPV). Trivalent OPV contains all three types of poliovirus, while bOPV only contains poliovirus type 1 and 3. This switch means that OPV no longer protects against WPV2…“ https://www.cdc.gov/cpr/polioviruscontainment/diseaseandvirus.htm
According to the US CDC, “It takes only one traveler with polio to bring the disease into the United States”. https://www.cdc.gov/polio/what-is-polio/polio-us.html
“Poliovirus is transmitted person to person by the fecal-oral route and also by the oral-oral route… Major risk factors for poliovirus transmission include poor sanitation and hygiene, tropical and sub-tropical conditions, large birth cohorts, and high population densities” “Vaccine-Derived Polioviruses and the Endgame Strategy for Global Polio Eradication” (Kew et al., 2005)
After vaccination (or natural infection), “the virus replicates inside the child’s intestine and eventually is excreted. In places with poor sanitation, fecal matter can enter the drinking water supply and the virus is able to start spreading from person to person.” See: “Mutant Strains Of Polio Vaccine Now Cause More Paralysis Than Wild Polio” June 28, 2017 By Jason Beaubien. https://www.npr.org/sections/goatsandsoda/2017/06/28/534403083/mutant-strains-of-polio-vaccine-now-cause-more-paralysis-than-wild-polio This is the oral attenuated virus vaccine, which is commonly used in many countries, and was used in the United States. To what extent can this also occur with other types?
Although the cause is considered unknown, the post- WWII outbreak of Polio suggests that a new variant, to which the population lacked immunity, was either imported by soldiers or by post-war immigrants. Hypothetically, it could been a bioweapon, as well. Or was it due to the popularity of tonsillectomies? “A study of more than 2000 case histories in the 1940s by the Harvard Infantile Paralysis Commission concluded that tonsillectomies led to a significant risk of respiratory paralysis due to bulbar polio.” Or related to other vaccinations – a strange hypothesis, which may be true. See: “Polio provocation: solving a mystery with the help of history” by Stephen E Mawdsley, July 26, 2014, https://doi.org/10.1016/S0140-6736(14)61251-4
Most likely it was a combination.
“Between 1915 and the 1960s, T&A was the most frequently performed surgical procedure in the United States.” See: Grob GN. “The rise and decline of tonsillectomy in twentieth-century America”. J Hist Med Allied Sci. 2007 Oct;62(4):383-421 https://pubmed.ncbi.nlm.nih.gov/17426070/
“Tonsillectomy and the Risk of Poliomyelitis” By Percy Barsky and Ronald Lauer, Can Med Assoc J. 1957 Sep 15; 77(6): 576–578. https://europepmc.org/scanned?pageindex=3&articles=PMC1824413
While only a small percentage were paralyzed from polio, because of the large numbers of infected, it impacted a large number of people. Not everyone had access to running water, or indoor plumbing, at this time, either. And, housing was frequently crowded in cities and bathrooms shared: “At its height, from 1950–1954, poliomyelitis resulted in the paralysis of some 22,000 U.S. citizens each year, equivalent to an average annual rate of 14.6 per 100,000. Many thousands were left permanently disabled by the disease, while many others suffocated as a consequence of respiratory paralysis (Langmuir 1963). However, from the mid-1950s, the development and mass administration of first inactivated poliovirus vaccine (IPV) and then, from the early 1960s, oral poliovirus vaccine (OPV) effectively curbed disease activity (Paul 1971)…. While faecal contamination (of fingers, eating utensils, milk or foodstuffs) is considered to be the more common means of transmission (Christie 1987), route (2) is a critical second strand in the person-to-person propagation of the disease. Indeed, among older populations, and where high standards of sanitation are maintained, droplet spread may be the predominant route of poliovirus transmission….” See: “The Spatial Dynamics of Poliomyelitis in the United States: From Epidemic Emergence to Vaccine-Induced Retreat, 1910–1971”, By Barry Trevelyan, Matthew Smallman-Raynor, and Andrew D. Cliff Annals of the Association of American Geographers. Association of American Geographers vol. 95,2 (2005): 269-29 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1473032/
Vaccine-associated paralytic poliomyelitis (VAPP):
“The overall risk for VAPP is approximately one case in 2.4 million doses of OPV vaccine distributed, with a first-dose risk of one case in 750,000 first doses distributed (Table). Among immunocompetent persons, 83% of cases among vaccine recipients and 63% of cases among contacts occurred after administration of the first dose (Table) (3,25,36). Among persons who are not immunodeficient, the risk for VAPP associated with the first dose of OPV is sevenfold to 21-fold higher than the risk associated with subsequent doses (25). Immunodeficient persons, particularly those who have B-lymphocyte disorders that inhibit synthesis of immune globulins (i.e., agammaglobulinemia and hypogammaglobulinemia), are at greatest risk for VAPP (i.e., 3,200-fold to 6,800-fold greater risk than immunocompetent OPV recipients) (45).” (US ACIP-MMWR (CDC), 1999)
“Because the ratio between infection and paralytic disease for poliovirus type 3 exposure can be as high as 1000:1, the detection of five cases in the Netherlands suggests a much larger number of infections has occurred within the country (7). The high degree of homology of this virus and a recent isolate from southern Asia again demonstrates that wild virus can be spread to populations of susceptible persons living far from endemic regions, and reinforces the need to intensify efforts to achieve the World Health Assembly goal of global polio eradication by the year 2000 (8).
At present, the risk for acquiring poliomyelitis in the Netherlands is minimal because of the excellent sanitary conditions and the high nationwide coverage for polio vaccination. Therefore, CDC does not recommend special precautions for U.S. travelers who have received a primary series of poliovirus vaccine as part of the infant vaccination schedule” “Poliomyelitis — Netherlands, 1992” October 16, 1992 / 41(41);775-778 https://www.cdc.gov/mmwr/preview/mmwrhtml/00017784.htm
The term “live virus” is misleading, because virus are not living. Denatured or attenuated or weakened virus seem like a better terms.
Only a small proportion (<1%) of poliovirus infections of suscepti-ble individuals result in paralytic poliomyelitis. Most infections are inapparent, although some infected people experience minor illness (fever, headache, malaise) or aseptic meningitis.
Paralytic poliomyelitis is preceded by minor illness of several days and a symptom-free interval of 1 to 3 days, followed by acute onset of flaccid paralysis with fever. Paralysis, which is usually asymmetric, progresses within a few days and, depending upon the sites of virus replication in the central nervous system, may affect skeletal muscles (spinal poliomyelitis), respiratory muscles (bulbar poliomyelitis), or both (bulbo-spinal poliomyelitis) (159, 185). The loss of motor neurons is permanent and the denervated muscles atrophy…
Poliomyelitis is highly contagious, and wild polioviruses in endemic areas infect virtually the entire population (185). In highly endemic reservoir areas, many children are infected within the first year of life. During the endemic period in developed countries with good sanitation and in isolated populations, exposure often occurred later in life, sometimes during major outbreaks. Polio is a seasonal disease, with peak transmission in the summer and autumn and reduced transmission during winter. Seasonal differences in transmission are far less pronounced in tropical areas (135, 170). Paralytic attack rates vary by serotype, with the highest rates (∼0.5%) associated with poliovirus type 1 and the lowest rates (80% since the mid-1980s, and worldwide eradication of the disease by the end of 2000 or soon after appears feasible (8).
Summary of Recent Polio Vaccination Policy in the United States
Based on the continued occurrence of vaccine-associated paralytic poliomyelitis (VAPP) in the United States, the absence of indigenous disease, and the sharply decreased risk for wild poliovirus importation into the United States, the Advisory Committee on Immunization Practices (ACIP) recommended in June 1996 a change from an all-OPV schedule for routine childhood poliovirus vaccination to a sequential IPV-OPV vaccination schedule (i.e., two doses of IPV at ages 2 and 4 months, followed by two doses of OPV at ages 12–18 months and 4–6 years).
These recommendations were officially accepted by CDC and published in January 1997 (9). The sequential schedule was intended to be a transition policy in place for 3–5 years until eventual adoption of an all-IPV schedule. At the same time that ACIP recommended a sequential schedule, the American Academy of Pediatrics (AAP) and the American Academy of Family Physicians (AAFP) recommended expanded use of IPV, with all-OPV, all-IPV, and sequential IPV-OPV as equally acceptable options (10,11).
After the successful implementation of expanded IPV use without any observed declines in childhood immunization coverage (12,13), AAP and AAFP joined ACIP in January 1999 in recommending that the first two doses of polio vaccine for routine vaccination be IPV in most circumstances (14,15). However, an all-IPV schedule was still needed to eliminate the risk for VAPP while maintaining population immunity. Thus, ACIP recommended in June 1999 that the all-IPV schedule begin January 1, 2000 (16). Although AAFP concurred with this recommendation, AAP recommended only that the all-IPV schedule begin during the first 6 months of 2000 (17,18).
The United States can remain free of polio only by maintaining high levels of population immunity and reducing or eliminating the risk for poliovirus importation. ACIP strongly reaffirms its support for the global polio eradication initiative, which relies on OPV in countries where the disease has recently been endemic. This report provides the scientific and programmatic background for transition to an all-IPV schedule, presents the current recommendations for polio prevention in the United States, and summarizes recommendations for OPV use if the U.S. vaccine stockpile is needed for out break control.
Characteristics of Poliomyelitis
Poliomyelitis is a highly contagious infectious disease caused by poliovirus, an enterovirus. Most poliovirus infections are asymptomatic. Symptomatic cases are typically characterized by two phases — the first, a nonspecific febrile illness, is followed (in a small percentage of cases) by aseptic meningitis or paralytic disease. The ratio of cases of inapparent infection to paralytic disease ranges from 100:1 to 1,000:1.
After a person is exposed to poliovirus, the virus replicates in the oropharynx and the intestinal tract. Viremia follows, which can result in infection of the central nervous system. Replication of poliovirus in motor neurons of the anterior horn and brain stem results in cell destruction and causes the typical clinical manifestations of paralytic polio. Depending on the sites of paralysis, polio can be classified as spinal, bulbar, or spino-bulbar disease. Progression to maximum paralysis is rapid (2-4 days), is usually associated with fever and muscle pain, and rarely continues after the patient’s temperature has returned to normal. Spinal paralysis is typically asymmetric and more severe proximally than distally. Deep tendon reflexes are absent or diminished. Bulbar paralysis can compromise respiration and swallowing. Paralytic polio is fatal in 2%–10% of cases. After the acute episode, many patients recover at least some muscle function and prognosis for recovery can usually be established within 6 months after onset of paralytic manifestations.
After 30–40 years, 25%–40% of persons who contracted paralytic polio during childhood can experience muscle pain and exacerbation of existing weakness or develop new weakness or paralysis. This disease entity, called post-polio syndrome, has been reported only in persons infected during the era of wild poliovirus circulation.
Risk factors for post-polio syndrome include a) the passage of more time since acute poliovirus infection, b) the presence of permanent residual impairment after recovery from the acute illness, and c) being female (19).
Polio is caused by three serotypes of poliovirus — types 1, 2, and 3. In countries where poliovirus is still endemic, paralytic disease is most often caused by poliovirus type 1, less frequently by poliovirus type 3, and least frequently by poliovirus type 2. The virus is transmitted from person to person primarily by direct fecal-oral contact. However, the virus also can be transmitted by indirect contact with infectious saliva or feces, or by contaminated sewage or water.
The first paralytic manifestations of polio usually occur 7–21 days from the time of initial infection (range: 4-30 days). The period of communicability begins after the virus replicates and is excreted in the oral secretions and feces. This period ends with the termination of viral replication and excretion, usually 4–6 weeks after infection. After household exposure to wild poliovirus, >90% of susceptible contacts become infected. Poliovirus infection results in lifelong immunity specific to the infecting viral serotype.
Humans are the only reservoir for poliovirus. Long-term carrier states (i.e., excretion of virus by asymptomatic persons >6 months after infection) are rare and have been reported only in immunodeficient persons (20,21). Risk factors for paralytic disease include larger inocula of poliovirus, increasing age, pregnancy, strenuous exercise, tonsillectomy, and intramuscular injections administered while the patient is infected with poliovirus (22–24).
Secular Trends in Disease and Vaccination Coverage in the United States
In the United States, poliovirus vaccines have eliminated polio caused by wild poliovirus. The annual number of reported cases of paralytic disease declined from >20,000 in 1952 to an average of 8–9 cases annually during 1980–1994 (Figure) (3,25,26). During 1980–1998, a total of 152 cases of paralytic polio were reported, including 144 cases of VAPP, six imported cases, and two indeterminate cases (16).
Until worldwide polio eradication is achieved, epidemics caused by importation of wild virus to the United States remain a possibility unless population immunity is maintained by vaccinating children early in their first year of life. In the United States, outbreaks of polio occurred in 1970, 1972, and 1979 after wild poliovirus was introduced into susceptible populations that had low levels of vaccination coverage. Vaccination coverage among children in the United States is at the highest level in history because of ongoing immunization initiatives. Assessments of the vaccination status of children entering kindergarten and first grade indicated that 95% had completed primary vaccination against polio during the 1980–81 school year, and rates continue to be above that level.
Coverage levels among preschool-aged children are lower than the levels at school entry, but have increased substantially in recent years. Nationally, representative vaccination coverage rates among children aged 19–35 months are derived from the National Immunization Survey (NIS). Vaccination coverage with at least three doses of poliovirus vaccine among children in this age group increased from 88% in 1995 to 91% in 1996 and remained >90% in 1997 and 1998 (13).
Serosurveys have identified high levels of population immunity consistent with these high coverage rates. Based on data from selected surveys, >90% of children, adolescents, and young adults had detectable antibodies to poliovirus types 1 and 2, and >85% had antibody to type 3 (27,28). Data from seroprevalence surveys conducted in two inner-city areas of the United States during 1990–1991 documented that >80% of all children aged 12–47 months had antibodies to all three poliovirus serotypes. Of the children who had received at least three doses of OPV, 90% had antibodies to all three serotypes (29). A serosurvey conducted during 1997–1998 among low-income children aged 19–35 months living in four U.S. cities reported that 96.8%, 99.8%, and 94.5% were seropositive to poliovirus types 1, 2, and 3, respectively (30).
Both laboratory surveillance for enteroviruses and surveillance for polio cases suggest that endemic circulation of indigenous wild polioviruses ceased in the United States in the 1960s. During the 1970s, genotypic testing (e.g., molecular sequencing or oligonucleotide fingerprinting) of poliovirus isolates obtained from indigenous cases (both sporadically occurring and outbreak-associated) in the United States indicated that these viruses were imported (31). During the 1980s, five cases of polio were classified as imported.
The last imported case, reported in 1993, occurred in a child aged 2 years who was a resident of Nigeria; the child had been brought to New York for treatment of paralytic disease acquired in her home country. Laboratory investigations failed to isolate poliovirus among samples taken from this child after she arrived in the United States.
Recent experience in Canada illustrates the continuing potential for importation of wild poliovirus into the United States until global eradication is achieved. In 1993 and 1996, health officials in Canada isolated wild poliovirus in stool samples from residents of Alberta and Ontario. No cases of paralytic polio occurred as a result of these wild virus importations. The strain isolated in 1993 was linked epidemiologically and by genomic sequencing to a 1992 polio outbreak in the Netherlands (32). The isolate obtained in 1996 was from a child who had recently visited India (33).
Inapparent infection with wild poliovirus no longer contributes to either the establishment or maintenance of poliovirus immunity in the United States because these viruses no longer circulate in the population. Thus, universal vaccination of infants and children is the only way to establish and maintain population immunity against polio.
After the widespread use of poliovirus vaccine in the mid-1950s, the incidence of polio declined rapidly in many industrialized countries. In the United States, the number of cases of paralytic polio reported each year declined from >20,000 cases in 1952 to <100 cases in the mid-1960s (3). In 1988, the WHA resolved to eradicate polio globally by 2000 (5). This global resolution followed the regional goal to eliminate polio by 1990, set in 1985 by the countries of the Western Hemisphere. The last case of polio associated with wild poliovirus isolation was reported from Peru in 1991, and the entire Western Hemisphere was certified as free from indigenous wild poliovirus by an International Certification Commission in 1994 (7). The following polio eradication strategies, which were developed for the Americas, were adopted for worldwide implementation in all polio-endemic countries (34):
• Achieve and maintain high vaccination coverage with at least three doses of OPV among infants aged <1 year.
• Develop sensitive systems of epidemiologic and laboratory surveillance, including acute flaccid paralysis (AFP) surveillance.
• Administer supplemental doses of OPV to all young children (usually those aged <5 years) during National Immunization Days (NIDs) to rapidly decrease widespread poliovirus circulation.
• Conduct mopping-up vaccination campaigns (i.e., localized campaigns that include home-to-home [or boat-to-boat] administration of OPV) in areas at high risk to eliminate the last remaining chains of poliovirus transmission.
In 1998, global coverage with at least three doses of OPV among infants aged 80%, except the African Region (AFR), where coverage improved from 32% in 1988 to 53% in 1998 (8). Also in 1998, a total of 90 countries conducted either NIDs (74 countries) or Sub-National Immunization Days (16 countries). These 90 countries provided supplemental doses of OPV to approximately 470 million children aged <5 years (i.e., approximately three quarters of the world's children aged <5 years) (8). In 1999, NIDs were conducted in all 50 polio-endemic countries. NIDs in the AFR targeted approximately 88 million children aged <5 years (35). Synchronized NIDs were conducted in 18 countries of the European Region (EUR) and Eastern Mediterranean Region (EMR), vaccinating 58 million children aged <5 years. Another 257 million children aged 120 in 1988 to approximately 50 in 1998. Approximately 50% of the world’s population resides in areas now considered polio-free, including the Western Hemisphere, WPR (which encompasses China), and EUR.
Two large endemic areas of continued poliovirus transmission exist in South Asia and Sub-Saharan Africa. Priority countries targeted for accelerated implementation of polio eradication strategies include seven reservoir countries (Bangladesh, Democratic Republic of the Congo, Ethiopia, India, Nepal, Nigeria, and Pakistan) and eight countries in conflict (Afghanistan, Angola, Democratic Republic of the Congo, Liberia, Sierra Leone, Somalia, Sudan, and Tajikistan) (8). Progress in these countries will be essential to achieve the goal of global polio eradication by the end of 2000.
Vaccine-Associated Paralytic Poliomyelitis (VAPP) Cases of VAPP were observed almost immediately after the introduction of live, attenuated poliovirus vaccines (43,44). Before the sequential IPV-OPV schedule was introduced, 132 cases of VAPP were reported during 1980–1995 (Figure) (26; CDC, unpublished data, 2000). Fifty-two cases of paralysis occurred among otherwise healthy vaccine recipients, 41 cases occurred among healthy close contacts of vaccine recipients, and 7 cases occurred among persons classified as community contacts (i.e., persons from whom vaccine-related poliovirus was isolated but who had not been vaccinated recently or been in direct contact with vaccine recipients). An additional 32 cases occurred among persons with immune system abnormalities who received OPV or who had direct contact with an OPV recipient (Table).
The overall risk for VAPP is approximately one case in 2.4 million doses of OPV vaccine distributed, with a first-dose risk of one case in 750,000 first doses distributed (Table). Among immunocompetent persons, 83% of cases among vaccine recipients and 63% of cases among contacts occurred after administration of the first dose (Table) (3,25,36). Among persons who are not immunodeficient, the risk for VAPP associated with the first dose of OPV is sevenfold to 21-fold higher than the risk associated with subsequent doses (25). Immunodeficient persons, particularly those who have B-lymphocyte disorders that inhibit synthesis of immune globulins (i.e., agammaglobulinemia and hypogammaglobulinemia), are at greatest risk for VAPP (i.e., 3,200-fold to 6,800-fold greater risk than immunocompetent OPV recipients) (45).
Since implementation of the sequential IPV-OPV schedule in 1997, five cases of VAPP with onset in 1997 and two cases with onset in 1998 were confirmed. Three of these cases were associated with administration of the first or second dose of OPV to children who had not previously received IPV, and one of the 1998 cases was associated with administration of the third dose. Although these data suggest a decline in VAPP after introduction of the sequential schedule, continued monitoring with additional observation time is required to confirm these preliminary findings because of potential delays in reporting (25,46).
Transition to an All-IPV Schedule
Adopting an all-IPV schedule for routine childhood polio vaccination in the United States is intended to eliminate the risk for VAPP. However, this schedule requires two additional injections at ages 6–18 months and 4–6 years because no combination vaccine that includes IPV as a component is licensed in the United States. Because of concerns regarding potential declines in childhood immunization coverage after introduction of the sequential IPV-OPV schedule (which required two additional injections at ages 2 and 4 months), several evaluations were conducted during this transition period. No evidence exists that childhood vaccination coverage declined because of these additional injections. In two West Coast health maintenance organizations (HMOs) with automated recording and tracking systems for vaccination, researchers assessed the up-to-date vaccination status of infants at age 12 months (i.e., two doses of poliovirus vaccine, three doses of diphtheria and tetanus toxoids and acellular pertussis vaccine [DTaP], two doses of Haemophilus influenzae type b vaccine [Hib], and two doses of hepatitis B vaccine [HepB]). The proportion of children who started the routine vaccination schedule with IPV ranged from 36%–98% across the HMOs by the third quarter of 1997. Infants starting with IPV were as likely to be up-to-date as were infants starting with OPV (12).
Available data from other public-sector clinics showed similar results. In one inner-city clinic in Philadelphia, 152 children due for their first dose of polio vaccine received IPV. Of the 145 children who returned to the clinic, 144 received a second dose of IPV. More than 99% of children due for their third and fourth injections (including IPV) during a single visit received them as indicated (47). An evaluation conducted at six public health clinics in one Georgia county also concluded that, of 567 infants who received their first dose of polio vaccine by age 3 months, 534 (94%) received IPV. Among these infants, 99.6% were also up-to-date for their first doses of diphtheria and tetanus toxoids vaccine (DTP), DTaP, Hib, and HepB (48). More detailed data on compliance with the recommended vaccination schedules is available from state immunization registries.
Another study reviewed immunization data from children born in Oklahoma during January 1, 1996–June 30, 1997 (i.e., 36,391 children seen at one of 290 facilities). The percentage of children who received IPV as their first dose of polio vaccine increased from 2 months after the onset of paralytic manifestations are unlikely to yield poliovirus. Throat swabs are less often positive than stool samples, and virus is rarely detected in CSF. In addition, an acute-phase serologic specimen should be obtained as early in the course of illness as possible, and a convalescent-phase specimen should be obtained at least 3 weeks later.
The following tests should be performed on appropriate specimens collected from persons who have suspected cases of polio: a) isolation of poliovirus in tissue culture; b) serotyping of a poliovirus isolate as serotype 1, 2, or 3; and c) intratypic differentiation using DNA/RNA probe hybridization or polymerase chain reaction to determine whether a poliovirus isolate is associated with a vaccine or wild virus.
Acute-phase and convalescent-phase serum specimens should be tested for neutralizing antibody to each of the three poliovirus serotypes. A fourfold rise in antibody titer between appropriately timed acute-phase and convalescent-phase serum specimens is diagnostic for poliovirus infection. The recently revised standard protocol for poliovirus serology should be used (50).
Commercial laboratories usually perform complement fixation and other tests. However, assays other than neutralization are difficult to interpret because of inadequate standardization and relative insensitivity. The CDC Enterovirus Laboratory is available for consultation and will test specimens from patients who have suspected polio (i.e., patients with acute paralytic manifestations). The telephone number for this lab is (404) 639-2749.
INACTIVATED POLIOVIRUS VACCINE (IPV)
IPV was introduced in the United States in 1955 and was used widely until OPV became available in the early 1960s. Thereafter, the use of IPV rapidly declined to <2% of all poliovirus vaccine distributed annually in the United States. A method of producing a more potent IPV with greater antigenic content was developed in 1978 and is the only type of IPV in use today (51). The first of these more immunogenic vaccines was licensed in the United States in 1987. Results of studies from several countries have indicated that the enhanced-potency IPV is more immunogenic for both children and adults than previous formulations of IPV (52).
Two IPV vaccine products are licensed in the United States,*** although only one (IPOL®) is both licensed and distributed in the United States. These products and their descriptions are as follows:
• IPOL®. One dose (0.5 mL administered subcutaneously) consists of the sterile suspension of three types of poliovirus: type 1 (Mahoney), type 2 (MEF-1), and type 3 (Saukett). The viruses are grown on Vero cells, a continuous line of monkey kidney cells, by the microcarrier method. After concentration, purification, and formaldehyde inactivation, each dose of vaccine contains 40 D antigen units of type 1 poliovirus, 8 D antigen units of type 2, and 32 D antigen units of type 3. Each dose also contains 0.5% of 2-phenoxyethanol and up to 200 ppm of formaldehyde as preservatives, as well as trace amounts of neomycin, streptomycin, and polymyxin B used in vaccine production. This vaccine does not contain thimerosal.
• POLIOVAX®. One dose (0.5 mL administered subcutaneously) consists of the sterile suspension of three types of poliovirus: type 1 (Mahoney), type 2 (MEF-1), and type 3 (Saukett). The viruses are grown on human diploid (MRC-5) cell cultures, concentrated, purified, and formaldehyde inactivated. Each dose of vaccine contains 40 D antigen units of type 1 poliovirus, 8 D antigen units of type 2, and 32 D antigen units of type 3, as well as 27 ppm formaldehyde, 0.5% of 2-phenoxyethanol, 0.5% of albumin (human), 20 ppm of Tween 80™, and 90% of vaccinated persons had serum antibodies to poliovirus 25 years after the fourth dose (57). One dose of IPV administered to persons during an outbreak of poliovirus type 1 in Senegal during 1986–1987 was 36% effective; the effectiveness of two doses was 89% (58).
Several European countries (e.g., Finland, Netherlands, Sweden, and Iceland) have relied exclusively on enhanced-potency IPV for routine poliovirus vaccination to eliminate the disease. More recently, all Canadian provinces have adopted vaccination schedules relying exclusively on IPV (i.e., five doses at ages 2, 4, 6, and 18 months and 4–6 years), and Ontario has used an all-IPV schedule since 1988 (59). In addition, France has used only IPV since 1983 (60).
In countries relying on all-IPV schedules, no increased risk for serious adverse events has been observed. An extensive review by the Institute of Medicine (IOM) of adverse events associated with vaccination suggested that no serious adverse events have been associated with the use of IPV in these countries (61). Since expanded use of IPV in the United States in 1996, no serious adverse events have been linked to use of IPV (CDC, unpublished data, 1999).
RECOMMENDATIONS FOR IPV VACCINATION
Recommendations for IPV Vaccination of Children
All children should receive four doses of IPV at ages 2, 4, and 6–18 months and 4–6 years. The first and second doses of IPV are necessary to induce a primary immune response, and the third and fourth doses ensure “boosting” of antibody titers to high levels. If accelerated protection is needed, the minimum interval between doses is 4 weeks, although the preferred interval between the second and third doses is 2 months (see Recommendations for IPV Vaccination of Adults). All children who have received three doses of IPV before age 4 years should receive a fourth dose before or at school entry. The fourth dose is not needed if the third dose is administered on or after the fourth birthday.
Incompletely Vaccinated Children
The poliovirus vaccination status of children should be evaluated periodically. Those who are inadequately protected should complete the recommended vaccination series. No additional doses are needed if more time than recommended elapses between doses (e.g., more than 4–8 weeks between the first two doses or more than 2–14 months between the second and third doses).
Scheduling IPV Administration
Until appropriate combination vaccines are available, the administration of IPV will require additional injections at ages 2 and 4 months. When scheduling IPV administration, the following options should be considered to decrease the number of injections at the 2- and 4-month patient visits:
• Administer HepB at birth and ages 1 and 6 months.
• Schedule additional visits if there is reasonable certainty that the child will be brought back for subsequent vaccination at the recommended ages.
• Use available combination vaccines.
Interchangeability of Vaccines
Children who have initiated the poliovirus vaccination series with one or more doses of OPV should receive IPV to complete the series. If the vaccines are administered ac cording to their licensed indications for minimum ages and intervals between doses, four doses of OPV or IPV in any combination by age 4–6 years is considered a complete series, regardless of age at the time of the third dose. A minimum interval of 4 weeks should elapse if IPV is administered after OPV. Available evidence indicates that persons primed with OPV exhibit a strong mucosal immunogloblulin A response after boosting with IPV (62).
Administration with Other Vaccines
IPV can be administered simultaneously with other routinely recommended childhood vaccines. These include DTP, DTaP, Hib, HepB, varicella (chickenpox) vaccine, and measles-mumps-rubella vaccine.
Recommendations for IPV Vaccination of Adults
Routine poliovirus vaccination of adults (i.e., persons aged >18 years) residing in the United States is not necessary. Most adults have a minimal risk for exposure to polioviruses in the United States and most are immune as a result of vaccination during childhood. Vaccination is recommended for certain adults who are at greater risk for exposure to polioviruses than the general population, including the following persons:
• Travelers to areas or countries where polio is epidemic or endemic.
• Members of communities or specific population groups with disease caused by wild polioviruses.
• Laboratory workers who handle specimens that might contain polioviruses.
• Health-care workers who have close contact with patients who might be excreting wild polioviruses.
• Unvaccinated adults whose children will be receiving oral poliovirus vaccine.
Unvaccinated adults who are at increased risk should receive a primary vaccination series with IPV. Adults without documentation of vaccination status should be considered unvaccinated. Two doses of IPV should be administered at intervals of 4–8 weeks; a third dose should be administered 6–12 months after the second. If three doses of IPV cannot be administered within the recommended intervals before protection is needed, the following alternatives are recommended:
• If more than 8 weeks are available before protection is needed, three doses of IPV should be administered at least 4 weeks apart.
• If fewer than 8 weeks but more than 4 weeks are available before protection is needed, two doses of IPV should be administered at least 4 weeks apart.
• If fewer than 4 weeks are available before protection is needed, a single dose of IPV is recommended.
The remaining doses of vaccine should be administered later, at the recommended intervals, if the person remains at increased risk for exposure to poliovirus. Adults who have had a primary series of OPV or IPV and who are at increased risk can receive another dose of IPV. Available data do not indicate the need for more than a single lifetime booster dose with IPV for adults.
Precautions and Contraindications
Hypersensitivity or Anaphylactic Reactions to IPV or Antibiotics Contained in IPV
IPV should not be administered to persons who have experienced a severe allergic (anaphylactic) reaction after a previous dose of IPV or to streptomycin, polymyxin B, or neomycin. Because IPV contains trace amounts of streptomycin, polymyxin B, and neomycin, hypersensitivity reactions can occur among persons sensitive to these antibiotics. No serious adverse events related to use of enhanced-potency IPV have been documented.
Although no adverse effects of IPV have been documented among pregnant women or their fetuses, vaccination of pregnant women should be avoided on theoretical grounds. However, if a pregnant woman is at increased risk for infection and requires immediate protection against polio, IPV can be administered in accordance with the recommended schedules for adults (see Recommendations for IPV Vaccination of Adults).
IPV is the only vaccine recommended for vaccination of immunodeficient persons and their household contacts. Many immunodeficient persons are immune to polioviruses as a result of previous vaccination or exposure to wild virus when they were immunocompetent. Administration of IPV to immunodeficient persons is safe. Although a protective immune response in these persons cannot be ensured, IPV might confer some protection.
Breastfeeding does not interfere with successful immunization against polio. A dose of IPV can be administered to a child who has diarrhea. Minor upper respiratory illnesses with or without fever, mild to moderate local reactions to a previous dose of vaccine, current antimicrobial therapy, and the convalescent phase of an acute illness are not contraindications for vaccination (63).
ORAL POLIOVIRUS VACCINE (OPV)
Routine production of OPV in the United States has been discontinued. However, an emergency stockpile of OPV for polio outbreak control is maintained. Because OPV is the only vaccine recommended to control outbreaks of polio, this section describes OPV and indications for its use.
Trivalent OPV contains live attenuated strains of all three poliovirus serotypes. The viruses are propagated in monkey kidney cell culture. Until introduction of the sequential IPV-OPV schedule in 1997, OPV was the nation’s primary poliovirus vaccine, after its licensing in the United States in 1963. One dose of OPV (0.5 mL administered orally from a single dose dispenser) is required to contain a minimum of 106 TCID50 (tissue culture infectious dose) Sabin strain of poliovirus type 1 (LSc 2ab), 105.1 TCID50 Sabin strain of poliovirus type 2 (P712 Ch 2ab), and 105.8 TCID50 Sabin strain of poliovirus type 3 (Leon 12a1b), balanced in a formulation of 10:1:3, respectively. The OPV formerly manufactured in the United States**** contained approximately threefold to tenfold the minimum dose of virus necessary to meet these requirements consistently (64). Each dose of 0.5 mL also contained 95% of recipients develop long-lasting (probably lifelong) immunity to all three poliovirus types. Approximately 50% of vaccine recipients develop antibodies to all three serotypes after a single dose of OPV (53). OPV consistently induces immunity of the gastrointestinal tract that provides a substantial degree of resistance to reinfection with poliovirus. OPV interferes with subsequent infection by wild poliovirus, a property that is important in vaccination campaigns to control polio epidemics. Both IPV and OPV induce immunity of the mucosa of the gastrointestinal tract, but the mucosal immunity induced by OPV is superior (65,66). Both IPV and OPV are effective in reducing pharyngeal replication and subsequent transmission of poliovirus by the oral-oral route.
RECOMMENDATIONS FOR OPV VACCINATION
Recommendations for OPV Vaccination for Outbreak Control
As affirmed by ACIP, OPV remains the vaccine of choice for mass vaccination to control polio outbreaks (16). Data from clinical trials and empirical evidence support the effectiveness of OPV for outbreak control. The preference for OPV in an outbreak setting is supported by a) higher seroconversion rates after a single dose of OPV compared with a single dose of IPV; b) a greater degree of intestinal immunity, which limits community spread of wild poliovirus; and c) beneficial secondary spread (intestinal shedding) of vaccine virus, which improves overall protection in the community.
As a live attenuated virus, OPV replicates in the intestinal tract and induces
antibodies in more recipients after a single dose. Thus, OPV can protect more persons who are susceptible in a population, making it the preferred vaccine for rapid intervention during an outbreak (53,67). Among persons previously vaccinated with three doses of IPV or OPV, excretion of poliovirus from the pharynx and the intestine appears most closely correlated with titers of homologous humoral antibody (68). Three doses of either IPV or OPV induce protective antibody levels (neutralizing antibody titers >1:8) to all three serotypes of poliovirus in >95% of infant recipients (9). Therefore, boosting of immunity with a single dose of OPV or IPV is likely to reduce both pharyngeal and intestinal excretion of poliovirus, effectively stopping epidemic transmission of wild poliovirus.
Use of OPV for Outbreak Control
OPV has been the vaccine of choice for polio outbreak control. During a polio outbreak in Albania in 1996, the number of cases decreased 90% within 2 weeks after administration of a single dose of OPV to >80% of the population aged 0–50 years. Two weeks after a second round of vaccination with OPV, no additional cases were observed (69). Rapidly implemented mass vaccination campaigns resulting in high coverage appears to have been similarly effective in interrupting wild poliovirus outbreaks in other countries (70).
European countries that rely solely on IPV for routine poliovirus vaccination (e.g., the Netherlands and Finland) have also used OPV for primary control of outbreaks. During the 1992–93 polio outbreak in the Netherlands, OPV was offered to members of a religious community affected by the outbreak (who were largely unvaccinated before the outbreak) and other persons living in areas affected by the outbreak. IPV was given to immunized persons outside the outbreak areas to ensure protection in this population (71). During a 1984–85 polio outbreak in Finland, 1.5 million doses of IPV initially were administered to children <18 years for immediate boosting of protection (72). Later, approximately 4.8 million doses of OPV were administered to 95% of the population. In contrast, mass vaccination with IPV exclusively has had little impact on outbreaks and has rarely been used since OPV became available (70,73).
Recommendations for Other Uses of OPV
For the remaining nonemergency supplies of OPV, only the following indications are acceptable for OPV administration:
• Unvaccinated children who will be traveling in fewer than 4 weeks to areas where polio is endemic. If OPV is not available, IPV should be administered.
• Children of parents who do not accept the recommended number of vaccine injections. These children can receive OPV only for the third or fourth dose or both. In this situation, health-care providers should administer OPV only after discussing the risk for VAPP with parents or caregivers.
Precautions and Contraindications
Hypersensitivity or Anaphylactic Reactions to OPV
OPV should not be administered to persons who have experienced an anaphylactic reaction to a previous dose of OPV. Because OPV also contains trace amounts of neomycin and streptomycin, hypersensitivity reactions can occur in persons sensitive to these antibiotics.
Although no adverse effects of OPV have been documented among pregnant women or their fetuses, vaccination of pregnant women should be avoided. However, if a pregnant woman requires immediate protection against polio, she can receive OPV in accordance with the recommended schedules for adults (see Use of OPV for Outbreak Control).
OPV should not be administered to persons who have immunodeficiency disorders (e.g., severe combined immunodeficiency syndrome, agammaglobulinemia, or hypogammaglobulinemia) (74–76) because these persons are at substantially increased risk for VAPP. Similarly, OPV should not be administered to persons with altered immune systems resulting from malignant disease (e.g., leukemia, lymphoma, or generalized malignancy) or to persons whose immune systems have been compromised (e.g., by therapy with corticosteroids, alkylating drugs, antimetabolites, or radiation or by infection with human immunodeficiency virus [HIV]). OPV should not be used to vaccinate household contacts of immunodeficient patients; IPV is recommended. Many immunodeficient persons are immune to polioviruses as a result of previous vaccination or exposure to wild virus when they were immunocompetent. Although their risk for paralytic disease could be lower than for persons with congenital or acquired immunodeficiency disorders, these persons should not receive OPV.
Inadvertent Administration of OPV to Household Contacts of Immunodeficient Persons
If OPV is inadvertently administered to a household contact of an immunodeficient person, the OPV recipient should avoid close contact with the immunodeficient person for approximately 4–6 weeks after vaccination. If this is not feasible, rigorous hygiene and hand washing after contact with feces (e.g., after diaper changing) and avoidance of contact with saliva (e.g., sharing food or utensils) can be an acceptable but probably less effective alternative. Maximum excretion of vaccine virus occurs within 4 weeks after oral vaccination.
Breastfeeding does not interfere with successful immunization against polio. A dose of OPV can be administered to a child who has mild diarrhea. Minor upper respiratory illnesses with or without fever, mild to moderate local reactions to a previous dose of vaccine, current antimicrobial therapy, and the convalescent phase of an acute illness are not contraindications for vaccination (63).
Vaccine-Associated Paralytic Poliomyelitis (VAPP)
In rare instances, administration of OPV has been associated with paralysis in healthy recipients and their contacts. No procedures are available for identifying persons (other than those with immunodeficiency) who are at risk for such adverse reactions. Although the risk for VAPP is minimal, vaccinees (or their parents) and their susceptible, close, personal contacts should be informed of this risk (Table). Administration of OPV can cause VAPP that results in death, although this is rare (3,45).
Guillain-Barré Syndrome (GBS)
Available evidence indicates that administration of OPV does not measurably increase the risk for GBS, a type of ascending inflammatory polyneuritis. Preliminary findings from two studies in Finland led to a contrary conclusion in a review conducted by IOM in 1993 (77,78). Investigators in Finland reported an apparent increase in GBS incidence that was temporally associated with a mass vaccination campaign during which OPV was administered to children and adults who had previously been vaccinated with IPV. However, after the IOM review, these data were reanalyzed, and an observational study was completed in the United States. Neither the reanalysis nor the new study provided evidence of a causal relationship between OPV administration and GBS (79).
REPORTING OF ADVERSE EVENTS AFTER VACCINATION
The National Childhood Vaccine Injury Act of 1986 requires health-care providers to report serious adverse events after poliovirus vaccination (80). Events that must be reported are detailed in the Reportable Events Table of this act and include paralytic polio and any acute complications or sequelae of paralytic polio. Adverse events should be reported to the Vaccine Adverse Events Reporting System (VAERS). VAERS reporting forms and information are available 24 hours a day by calling (800) 822-7967.
Vaccine Injury Compensation Program
The National Vaccine Injury Compensation Program, established by the National Childhood Vaccine Injury Act of 1986, provides a mechanism through which compensation can be paid on behalf of a person who died or was injured as a result of receiving vaccine. A Vaccine Injury Table lists the vaccines covered by this program and the injuries, disabilities, illnesses, and conditions (including death) for which compensation can be paid (81). This program provides potential compensation after development or onset of VAPP in a) an OPV recipient (within 30 days), b) a person in contact with an OPV vaccinee (no time frame specified), or c) an immunodeficient person (within 6 months). Additional information is available from the National Vaccine Injury Compensation Program ( 338-2382) or CDC's National Immunization Program Internet site at the following address: .
In 1997, ACIP recommended using a sequential schedule of IPV followed by OPV for routine childhood polio vaccination in the United States, replacing the previous all-OPV vaccination schedule. This change was intended to reduce the risk for VAPP. Since 1997, the global polio eradication initiative has progressed rapidly, and the likelihood of poliovirus importation into the United States has decreased substantially. The sequential schedule has been well accepted, and no declines in childhood immunization coverage have been observed. On the basis of these data, ACIP recommended on June 17, 1999, an all-IPV schedule for routine childhood polio vaccination in the United States to eliminate the risk for VAPP. ACIP also reaffirms its support for the global polio eradication initiative and the use of OPV as the only vaccine recommended to eradicate polio from the remaining countries where polio is endemic.
1 Kim-Farley RJ, Bart KJ, Schonberger LB, et al. Poliomyelitis in the USA: virtual elimination of disease caused by wild virus. Lancet 1984;2:1315–7.
2 Nathanson N, Martin JR. The epidemiology of poliomyelitis: enigmas surrounding its appearance, epidemicity, and disappearance. Am J Epidemiol 1979;110:672–92.
3 Strebel PM, Sutter RW, Cochi SL, et al. Epidemiology of poliomyelitis in the United States one decade after the last reported case of indigenous wild virus-associated disease. Clin Infect Dis 1992;14:568–79.
4 Pan American Health Organization. PAHO director announces campaign to eradicate poliomyelitis from the Americas by 1990. Bull Pan Am Health Organ 1985;19:213–5.
5 World Health Assembly. Global eradication of poliomyelitis by the year 2000. Geneva: World Health Organization, 1988 (Resolution WHA 41.28).
6 CDC. Update: eradication of paralytic poliomyelitis in the Americas. MMWR 1992;41:681–3.
7 CDC. Certification of poliomyelitis elimination—the Americas, 1994. MMWR 1994;43:720–2.
8 CDC. Progress toward global poliomyelitis eradication, 1997–1998. MMWR 1999;48:416–21.
9 CDC. Poliomyelitis prevention in the United States: introduction of a sequential vaccination schedule of inactivated poliovirus vaccine followed by oral poliovirus vaccine. Recommendations of the Advisory Committee on Immunization Practices. MMWR 1997;46(No. RR-3).
10 American Academy of Pediatrics Committee on Infectious Diseases. Poliomyelitis prevention: recommendations for use of inactivated and live oral poliovirus vaccines. Pediatrics 1997;99:300–5.
11 Prevots DR, Strebel PM. Poliomyelitis prevention in the United States: new recommendations for routine childhood vaccination place greater reliance on inactivated poliovirus vaccine. Pediatric Annals 1997;26:378–83.
12 CDC. Impact of the sequential IPV/OPV schedule on vaccination coverage levels—United States, 1997. MMWR 1998;47:1017–9.
13 CDC. National vaccination coverage levels among children aged 19–35 months—United States,1998. MMWR 1999;48:829–30.
14 American Academy of Pediatrics Committee on Infectious Diseases. Poliomyelitis prevention: revised recommendations for use of inactivated and live oral poliovirus vaccines. Pediatrics 1999;103:171–2.
15 CDC. Recommended childhood immunization schedule—United States, 1999. MMWR 1999;48:12–6.
16 CDC. Notice to readers. Recommendations of the Advisory Committee on Immunization Practices: revised recommendations for routine poliomyelitis vaccination. MMWR 1999;48:590.
17 CDC. Recommended childhood immunization schedule—United States, 2000. MMWR 2000;49:35–8, 47.
18 American Academy of Pediatrics Committee on Infectious Diseases. Prevention of poliomyelitis: recommendations for use of only inactivated poliovirus vaccine for routine immunization. Pediatrics 1999;104:1404–6.
19 Ramlow J, Alexander M, LaPorte R, Kaufman NC, Kuller L. Epidemiology of the post-polio syndrome. Am J Epidemiol 1992;136:769–86.
20 CDC. Prolonged poliovirus excretion in an immunodeficient person with vaccine-associated paralytic poliomyelitis. MMWR 1997;46:641–3.
21 Khetsuriani N, Prevots DR, Pallansch M, Kew O. Vaccine-derived poliovirus (VDPV) persistence among immunodeficient persons with vaccine-associated paralytic poliomyelitis (VAPP) [Abstract no. 675]. Presented at the 39th Interscience Conference on Antimicrobial Agents and Chemotherapy, September 26–29, 1999.
22 Sutter RW, Patriarca P, Suleiman AJM, et al. Attributable risk of DTP (diphtheria and tetanus toxoids and pertussis vaccine) injection in provoking paralytic poliomyelitis during a large outbreak in Oman. J Infect Dis 1992;165:444–9.
23 Strebel PM, Ion-Nedelcu N, Baughman AL, et al. Intramuscular injections within 30 days of immunization with oral poliovirus vaccine—a risk factor for vaccine-associated paralytic poliomyelitis. N Engl J Med 1995:332:500–6.
24 Gromeier M, Wimmer E. Mechanism of injury-provoked poliomyelitis. J Virology 1998;72:5056–60.
25 Prevots DR, Sutter RW, Strebel PM, Weibel RE, Cochi SL. Completeness of reporting for paralytic poliomyelitis, United States, 1980 through 1991. Arch Pediatr Adolesc Med 1994;148:479–85.
26 CDC. Paralytic poliomyelitisUnited States, 19801994. MMWR 1997;46:79–83.
27 Kelley PW, Petruccelli BP, Stehr-Green P, Erickson RL, Mason CJ. The susceptibility of young adult Americans to vaccine-preventable infections: a national serosurvey of US army recruits. JAMA 1991;266:2724–9.
28 Orenstein WA, Wassilak SGF, Deforest A, Rovira EZ, White J, Etkind P. Seroprevalence of polio virus antibodies among Massachusetts schoolchildren [Abstract no. 512]. In: Program and abstracts of the 28th Interscience Conference on Antimicrobial Agents and Chemotherapy. Washington, DC: American Society for Microbiology, 1988.
29 Chen RT, Hausinger S, Dajani AS, et al. Seroprevalence of antibody against poliovirus in inner-city preschool children: implications for vaccination policy in the United States. JAMA 1996:275:1639–45
30 Prevots R, Pallansch MW, Angellili M, et al. Seroprevalence of poliovirus antibodies among low SES children aged 19–35 months in 4 cities, United States, 1997–1998 [Abstract no.158]. Presented at the 39th Interscience Conference on Antimicrobial Agents and Chemotherapy, September 26–29, 1999.
31 Rico-Hesse R, Pallansch MA, Nottay BK, Kew OM. Geographic distribution of wild poliovirus type 1 genotypes. Virology 1987;160:311–22.
32 CDC. Isolation of wild poliovirus type 3 among members of a religious community objecting to vaccination—Alberta, Canada, 1993. MMWR 1993;42:337–9.
33 Ministry of Health Ontario. Wild type poliovirus isolated in Hamilton. Public Health and Epidemiology Report Ontario 1996;7:1-2.
34 Hull HF, Ward NA, Hull BP, Milstien JB, de Quadros C. Paralytic poliomyelitis: seasoned strategies, disappearing disease. Lancet 1994;343:1331-7.
35 CDC. Progress toward poliomyelitis eradication—African Region, 1998–April 1999. MMWR 1999;48:513–8.
36 CDC. Progress toward poliomyelitis eradication in Europe and Central Asian Republics, 1997–May 1998. MMWR 1998;47:504–8.
37 CDC. Wild poliovirus transmission in bordering areas of Iran, Iraq, Syria, and Turkey, 1997–June 1998. MMWR 1998;47:588–92.
38 CDC. Final stages of poliomyelitis eradication—Western Pacific Region, 1997–1998. MMWR 1999;48:29–33.
39 CDC. Progress toward poliomyelitis eradication—Pakistan, 1994–1998. MMWR 1999;48:121–6.
40 CDC. Progress toward poliomyelitis eradication—South East Asia Region, 1997–1998. MMWR 1999;48:230–2, 39.
41 CDC. Progress toward poliomyelitis eradication—India, 1998. MMWR 1998;47:778–81.
42 CDC. Status of the Global Laboratory Network for poliomyelitis eradication, 1994–1996. MMWR 1997;46:692–4.
43 Terry LL. The association of cases of poliomyelitis: with the use of type III oral poliomyelitis vaccines—a technical report. Washington, DC: US Department of Health, Education and Welfare, 1962.
44 Henderson DA, Witte JJ, Morris L, Langmuir AD. Paralytic disease associated with oral polio vaccines. JAMA 1964;190:41–8.
45 Sutter RW, Prevots DR. Vaccine-associated paralytic poliomyelitis among immunodeficient persons. Infect Med 1994;11:426, 429–30, 435–8.
46 Prevots DR, Khetsuriani N, Wharton M. Evidence for a decline in the number of vaccine-associated paralytic poliomyelitis cases in the United States following implementation of a sequential poliovirus vaccination schedule, 1997–1998. Presented at the 36th annual meeting of the Infectious Disease Society of America, Denver, Colorado, November 12–15, 1998.
47 Melman ST, Ehrlich ES, Klugman D, Nguyen TT, Anbar RD. Parental compliance with initiation of sequential schedule for infant immunization [Abstract no. 104]. In: Abstracts of the 1998 Pediatric Academic Societies’ Annual Meeting. The Woodlands, Texas: American Pediatric Society/Society for Pediatric Research, 1998.
48 Kolasa MS, Desai SN, Bisgard KM, Dibling K, Prevots DR. Impact of the sequential poliovirus vaccination schedule: a demonstration project. Am J Prev Med 2000;18:1–6.
49 Stevenson JM, Chen W, Brown P, Maley M. Implementation and impact of the ACIP recommended sequential schedule for IPV/OPV [Abstract no. 363]. In: Abstracts of the 1998 Pediatric Academic Societies’ Annual Meeting. The Woodlands, Texas: American Pediatric Society/Society for Pediatric Research, 1998.
50 World Health Organization. Report of a WHO informal consultation on polio neutralizing antibody assays. Geneva: World Health Organization, 1991; publication no. WHO/EPI/RD/91.3.
51 van Wezel AL, van der Velden-de-Groot CAM, van Herwaarden JAM. The production of inactivated poliovaccine on serially cultivated kidney cells from captive-bred monkeys. 3rd General Meeting of ESACT, Oxford, 1979. Dev Biol Stand 1980;46 (special issue):151–8.
52 International Association of Biological Standardization. International Symposium on Reassessment of Inactivated Poliomyelitis Vaccine. Dev Biol Stand 1981;47(special issue).
53 McBean AM, Thoms ML, Albrecht P, Cuthie JC, Bernier R. Serologic response to oral polio vaccine and enhanced-potency inactivated polio vaccines. Am J Epidemiol 1988;128:615–28.
54 Faden H, Modlin JF, Thoms ML, McBean AM, Ferdon MB, Ogra PL. Comparative evaluation of immunization with live attenuated and enhanced-potency inactivated trivalent poliovirus vaccines in childhood: systemic and local immune responses. J Infect Dis 1990;162:1291–7.
55 Modlin JF, Halsey NA, Thoms ML, et al. Humoral and mucosal immunity in infants induced by three sequential inactivated poliovirus vaccine-live attenuated poliovirus vaccine immunization schedules. J Infect Dis 1997;175(suppl 1):S228–S234.
56 Faden H, Duffy L, Sun M, Shuff C. Long-term immunity to poliovirus in children immunized with live attenuated and enhanced-potency inactivated trivalent poliovirus vaccine. J Infect Dis 1993;168:452–4.
57 Bottiger M. A study of the sero-immunity that has protected the Swedish population against poliomyelitis for 25 years. Scand J Infect Dis 1987;19:595–601.
58 Robertson SE, Traverso HP, Drucker JA, et al. Clinical efficacy of a new, enhanced-potency, inactivated poliovirus vaccine. Lancet 1988;1:897–9.
59 Varughese P, Carter A, Acres S, Furesz J. Eradication of indigenous poliomyelitis in Canada: impact of immunization strategies. Can J Public Health 1989;80:363–8.
60 Malvy D, Drucker J. Elimination of poliomyelitis in France: epidemiology and vaccine status. Public Health Rev 1993–94;21:41–9.
61 Institute of Medicine. Polio vaccines. In: Stratton KR, Howe CJ, eds. Adverse events associated with childhood vaccines. Evidence bearing on causality. Washington, DC: National Academy Press 1994:187210.
62 Herremans MPT Tineke, Reimerink JHJ, Buisman AM, Kimman TG, Koopmans MPG. Induction of mucosal immunity by inactivated poliovirus vaccine is dependent on previous mucosal contact with live virus. J Immunol 1999;162:5011–8.
63 CDC. General recommendations on immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 1994;43(No. RR-1).
64 Patriarca PA, Wright PF, John TJ. Factors affecting the immunogenicity of oral poliovirus vaccine in developing countries [Review]. Rev Infect Dis 1991;13:926–39.
65 Onorato IM, Modlin JF, McBean AM, Thomas ML, Losonsky GA, Bernier RH. Mucosal immunity induced by enhanced-potency inactivated and oral polio vaccines. J Infect Dis 1991;163:1–6.
66 Henry JL, Jaikaran ES, Davies JR, et al. A study of poliovaccination in infancy: excretion following challenge with live virus by children given killed or living poliovaccine. J Hyg (Cambridge) 1966;64:105–20.
67 Ion-Nedelcu N, Strebel PM, Toma F, et al. Sequential and combined use of inactivated and oral poliovirus vaccines: Dolj District, Romania, 1992–1994. J Infect Dis 1997;175(suppl 1):S241–S246.
68 Nishio O, Ishihara Y, Sakae K, et al. The trend of acquired immunity with live poliovirus vaccine and the effect of revaccination: follow-up of vaccinees for ten years. J Biol Stand 1984;12:1–10.
69 Prevots DR, Ciofe M, Sallabanda A, et al. Outbreak of paralytic poliomyelitis in Albania, 1996: high attack rate among adults and apparent interruption of transmission following a nationwide mass vaccination. Clin Infect Dis 1998;26;419–25.
70 Patriarca PA, Sutter RW, Oostvogel PM. Outbreaks of paralytic poliomyelitis, 1976–1995. J Infect Dis 1997;175(suppl 1):S165–S172.
71 Oostvogel PM, van Wijngaarden JK, van der Avoort HGAM, et al. Poliomyelitis outbreak in an unvaccinated community in the Netherlands, 1992–1993. Lancet 1994;344:665–70.
72 Hovi T, Cantell K, Huovilainen A, et al. Outbreak of paralytic poliomyelitis in Finland: widespread circulation of antigenically altered poliovirus type 3 in a vaccinated population. Lancet 1986;1:1427–32.
73 Poos RS, Nathanson N. Use of poliomyelitis vaccine under epidemic conditions. Report of outbreak of poliomyelitis among naval personnel and dependents in Hawaii. JAMA 1956;162:85–92.
74 Nightingale EO. Recommendations for a national policy on poliomyelitis vaccination. N Engl J Med 1977;297:249–53.
75 CDC. Poliomyelitis prevention: recommendations of the Immunization Practices Advisory Committee (ACIP). MMWR 1982;31:22–6, 31–4.
76 CDC. Recommendations of the Immunization Practices Advisory Committee (ACIP). Poliomyelitis prevention: enhanced-potency inactivated poliomyelitis vaccine—supplementary statement. MMWR 1987;36:795–8.
77 Uhari M, Rantala M. Cluster of childhood Guillain-Barré cases after an oral polio vaccine campaign. Lancet 1989;2:440–1.
78 Kinnunen E, Farkkila M, Hovi T, Juntunen J, Weckstrom P. Incidence of Guillain-Barré syndrome during a nationwide oral poliovirus vaccine campaign. Neurology 1989;39:1034–6.
79 Rantala H, Cherry JD, Shields WD, Uhari M. Epidemiology of Guillain-Barré syndrome in children: relationship of oral polio vaccine administration to occurrence. J Pediatr 1994;124:220–3.
80 Chen RT, Rastogi SC, Mullen JR, et al. The Vaccine Adverse Event Reporting System (VAERS). Vaccine 1994;6:542–50.
81 Kitch EW, Evans G, Gopin R. U.S. law. In: Plotkin SA, Orenstein WA, eds. Vaccines. Third edition. Philadelphia, PA: W.B. Saunders Company, 1998:1165–86.
* Anguilla, Antigua and Barbuda, Argentina, Aruba, Bahamas, Barbados, Belize, Bermuda, Bolivia, Brazil, Canada, Cayman Islands, Chile, Colombia, Costa Rica, Cuba, Dominica, Dominican Republic, Ecuador, El Salvador, French Guiana, Grenada, Guadeloupe, Guatemala, Guyana, Haiti, Honduras, Jamaica, Martinique, Mexico, Montserrat, Netherlands Antilles, Nicaragua, Panama, Paraguay, Peru, Puerto Rico, Saint Kitts and Nevis, Saint Lucia, Saint Vincent and the Grenadines, Suriname, Trinidad and Tobago, Turks and Caicos Islands, United States of America, Uruguay, Venezuela, United Kingdom Virgin Islands, and United States Virgin Islands.
** African Region (AFR), Region of the Americas (AMR), Eastern Mediterranean Region (EMR), European Region (EUR), South East Asia Region (SEAR), and Western Pacific Region (WPR).
*** Official names: IPOL® (enhanced-inactivated poliomyelitis vaccine), manufactured and distributed by Aventis-Pasteur, Swiftwater, Pennsylvania; and POLIOVAX,® manufactured by Aventis-Pasteur, Ontario, Canada (licensed but not distributed in the United States).
**** Official name: Orimune® (poliovirus vaccine, live, oral, trivalent types 1,2,3 [Sabin]), manufactured by Lederle Laboratories, Division of American Cyanamid Company, Pearl River, New York.
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