Mucosal immunity following oral poliovirus vaccine and enhanced potency inactivated poliovirus vaccine immunization.

Mucosal immunity is considered to be an important barrier for inhibiting person-to-person transmission of naturally occurring (wild type) poliovirus infection. This review briefly summarizes the results of a previously published study in which 79 oral poliovirus vaccine (OPV) vaccinated children and 93 enhanced-potency inactivated poliovirus vaccine (IPV) children were challenged with one of two doses of type 1 OPV virus to test the oropharyngeal and gastrointestinal mucosal immunity conferred by each type of poliovirus vaccine. Although both OPV and IPV produced excellent oropharyngeal immunity, OPV was clearly superior in decreasing fecal shedding of the challenge virus.     

The humoral immune response to type 1 oral poliovirus vaccine in children previously immunized with enhanced potency inactivated poliovirus vaccine or live oral poliovirus vaccine

Sixty-one children who had previously received three doses of enhanced potency inactivated poliovirus vaccine (epIPV) at 2, 4, and 18 months of age and 56 children who had previously received oral poliovirus vaccine (OPV) according to the same schedule were challenged with a single dose of monovalent, type 1 oral poliovirus vaccine (OPV1) between 19 and 52 months of age. Before the OPV1 challenge, the previously epIPV-immunized recipients had a geometric mean poliovirus type 1 microneutralization antibody titer (geometric mean titer [GMT]) of 11.1 IU, which was significantly higher than the prechallenge GMT of 2.2 IU among the children who had previously received OPV. Three weeks after the OPV1 challenge, the GMTs for the epIPV-immunized recipients and the OPV-immunized recipients were 35.3 IU and 5.1 IU, respectively. For the epIPV-immunized recipients, both the prechallenge GMT and the postchallenge GMT were dependent on the D antigen content of the vaccine that they had previously received. A fourfold or greater rise in poliovirus type 1 antibody occurred after the OPV1 challenge in 50.9% of the epIPV-immunized children and in 28.6% of the OPV-immunized children; this difference was statistically significant. For both groups, antibody boosts were inversely correlated with the pre-challenge serum antibody titer. However, the epIPV-immunized children consistently were more likely to boost than the OPV-immunized children at equivalent levels of prechallenge antibody. This experience indicated that OPV1 administration effectively raises the level of serum antibody in children previously immunized with three doses of epIPV, especially in children with lower levels of preexisting antibody. This booster response was superior to the booster response of children who received three doses of OPV.     

Diminution of the anti-polyribosylribitol phosphate response to a combined diphtheria-tetanus-acellular pertussis/Haemophilus influenzae type b vaccine by concurrent inactivated poliovirus vaccination

BACKGROUND: Prelicensure studies of Haemophilus influenzae type b vaccines (Hib) and diphtheria-tetanus-acellular pertussis vaccines (DTaP) were evaluated with concurrent oral poliovirus vaccine (OPV). However, inactivated poliovirus vaccine (IPV) is now recommended. A trial was conducted in which infants received a DTaP and Hib vaccine, separately (+) or combined (/), with either all OPV, all IPV or sequential IPV-OPV for the primary series of vaccinations. METHODS: In this protocol 567 infants were equally randomized to receive one of the following: Reference Arm A, DTaP + Hib + OPV; Treatment Arm B, DTaP/Hib + OPV; Treatment Arm C, DTaP/Hib + IPV at 2 and 4 months and OPV at 6 months; or Treatment Arm D, DTaP/Hib + IPV. antibodies against all administered antigens were measured at 7 months of age. Children with an antibody response to Hib (anti-polyribosylribitol phosphate (anti-PRP) <0.15 microg/ml had an antibody titer repeated after the toddler booster immunization. RESULTS: A significant diminution in the anti-PRP response was observed at 7 months of age in children given two or three doses of IPV concurrently with DTaP/Hib, compared with the groups given OPV. The geometric mean concentration of anti-PRP, percentage of children with > or = 0.15 microg/ml and percentage of children with > or = 1.0 microg/ ml, respectively, were: A, 4.4, 98%, 81%; B, 3.2, 94%, 78%; C, 1.3, 86%, 58% and D, 1.2, 84%, 53%. CONCLUSION: In this trial concurrent IPV appeared to interfere with the anti-PRP response to DTaP/Hib vaccine, suggesting that introduction of new vaccines may require evaluation of immune responses to all concurrently administered vaccines.     

Rationale for the sequential use of inactivated poliovirus vaccine and live attenuated poliovirus vaccine for routine poliomyelitis immunization in the United States

Despite the concerns mentioned in the last section, there are many reasons to believe that a polio immunization schedule that incorporates sequential doses of inactivated poliovirus vaccine and live attenuated poliovirus vaccine would provide both humoral and intestinal immunity to the fully immunized person that is at least as good, if not better, than the immunity achieved by the use of IPV or OPV alone. A substantial degree of protection should also extend to partially immunized and unimmunized preschool aged children in the community. Furthermore most of the cases of OPV-associated paralytic poliomyelitis could be prevented. Because the reasons for these beliefs are based on data from small studies and on inferences from related research, specific recommendations for a change from current polio immunization policy must depend on additional clinical research. Well-designed trials comparing several different options for sequencing both inactivated and live vaccines are needed, and these studies should focus carefully on both humoral and intestinal immunity conferred by the various vaccine schedules.     

Prevention of poliomyelitis: recommendations for use of only inactivated poliovirus vaccine for routine immunization. Committee on Infectious Diseases. American Academy of Pediatrics

Since 1997, when the American Academy of Pediatrics (AAP) initially recommended expanded use of inactivated poliovirus vaccine (IPV) for routine childhood immunization against poliovirus infection, the occurrence of vaccine-associated paralytic poliomyelitis (VAPP) has decreased in the United States. However, VAPP will not be eliminated until oral poliovirus vaccine (OPV) no longer is given. As a result of continuing progress toward global eradication of poliomyelitis, the risk of imported infection has continued to decrease. Concomitantly, the use of IPV has increased substantially with the corresponding decrease in the use of OPV, indicating widespread acceptance by health care professionals and parents of the sequential or all-IPV immunization schedule previously recommended by the AAP. In addition, availability of OPV will be substantially diminished beginning in early 2000. To eliminate VAPP in the context of decreasing risk of wild-type poliovirus importation, the AAP recommends an all-IPV schedule for routine childhood immunization beginning in early 2000. The AAP further recommends that, effective immediately, OPV no longer should be purchased for routine use. Guidelines are given for utilization of remaining supplies of OPV during the transition in early 2000 to the all-IPV schedule.     

Safety and immunogenicity of a pentavalent diphtheria, tetanus, pertussis, hepatitis B and polio combination vaccine in infants

INTRODUCTION: The objectives of this study were to evaluate the safety and immunogenicity of a new combination vaccine (DTaP-HB-IPV) containing diphtheria, tetanus, acellular pertussis and hepatitis B (HB) and a new inactivated poliovirus vaccine (IPV) manufactured by GlaxoSmithKline (GSK). This vaccine was given in an all IPV or sequential IPV and oral polio vaccine (OPV) schedule. Another combination vaccine, DTaP-HB (GSK), was similarly evaluated given with OPV or IPV. METHODS: Four hundred infants were randomized into one of four study groups and immunized at 2, 4 and 6 months of age. Group A received three doses of DTaP-HB-IPV; Group B received DTaP-HB-IPV at 2 and 4 months and DTaP-HB with OPV (Orimune) at 6 months; Group C received three doses of DTaP-HB with licensed IPV (IPOL) administered separately; Group D received separate doses of OPV, DTaP (Infanrix; GSK) and HB (Engerix; GSK). All subjects received conjugate Haemophilus influenzae type b vaccine (Hib) (OmniHIB) at 2, 4 and 6 months of age given at a separate injection site. Subjects who returned at 12 to 18 months of age (229) received booster immunization with DTaP and Hib. Safety was evaluated after each vaccine dose. Blood was drawn before the first dose and one month after the third dose as well as before and after the booster dose. RESULTS: There were no vaccine-related serious adverse events in any group after any vaccine dose. Minor systemic and local adverse events were also not significantly different among the four groups after any dose. There were no differences in the immune response rates for Hib, HB, polio (types 1, 2 and 3), diphtheria, tetanus or pertussis antigens (pertussis toxin, filamentous hemagglutinin, pertactin) among groups, although there were some quantitative differences in specific antibody titers among groups. DTaP-HB-IPV and DTaP-HB combination vaccines had safety and immunogenicity equivalent to those of standard individually administered vaccines. The new IPV was not inferior to IPOL. CONCLUSION: Use of the pentavalent combination vaccine would greatly reduce the number of required injections during the first 2 years of life, thereby simplifying the immunization schedule, enhancing compliance and facilitating acceptance of additional injections engendered by introduction of newer vaccines.     

Ensuring preparedness for potential poliomyelitis outbreaks: Recommendations for the US poliovirus vaccine stockpile from the National Vaccine Advisory Committee (NVAC) and the Advisory Committee on Immunization Practices (ACIP)

Paralytic poliomyelitis was once endemic in the United States; however, because of high vaccination levels, the last case of wild disease occurred in 1979. Although worldwide polio eradication may be achieved in the near future, the presence of undervaccinated children in urban areas and among groups who refuse vaccination creates an outbreak risk, should importation of wild virus occur. In 1999, the Advisory Committee on Immunization Practices (ACIP) recommended that inactivated poliovirus vaccine (IPV) be used for routine immunization of the US population and that oral poliovirus vaccine (OPV) be reserved for "mass vaccination campaigns to control outbreaks of paralytic polio." Subsequently, the sole US manufacturer of OPV withdrew from the market. In 2003, a joint National Vaccine Advisory Committee (NVAC)/ACIP working group was charged with reporting to its parent bodies concerning the need for a poliovirus vaccine stockpile. Based on that working group's report, the NVAC and ACIP have concluded that stockpiles of both IPV and OPV should be maintained. In the event of an outbreak in which OPV continues not to be available, IPV should be used for control, and a stockpile of 8 million doses seems to be sufficient. Should IPV be manufactured only in combination with other vaccines, appropriate procurement actions should be taken to ensure that uncombined IPV continues to be stockpiled. Under circumstances of diminished population immunity, OPV may offer outbreak control advantages. The NVAC and ACIP recommend that the United States collaborate with international agencies to provide guaranteed and rapid access to at least 8 million doses of trivalent OPV or 8 million doses of each of the 3 types of monovalent OPV. The regulatory and practical obstacles to implementation of this recommendation will require assertive facilitation at high levels of the federal government and careful planning at the state and local levels.     

Comparison of serum and salivary antibodies in children vaccinated with oral live or parenteral inactivated poliovirus vaccines of different antigen concentrations.

A new antigen-rich inactivated poliovirus vaccine (IPV) in ordinary (IPV1), double (IPV2) and quadruple (IPV4) antigen concentrations was given in 2 doses to 6 and 18 week old Pakistani infants. The immune responses to poliovirus types 1 and 3 were compared to those in infants given three doses of oral poliovirus vaccine (OPV) at 6, 12 and 18 weeks of age. Enzyme-linked immunosorbent assay, ELISA, was used to estimate IgG and IgA in serum and secretory IgA (SIgA) in saliva. Two to three years later, a follow-up of the serum antibody response was carried out in the same infants using a microneutralization test. Serum IgG antibody responses to poliovirus type 1 antigen after two doses of IPV1, IPV2 and IPV4 were not significantly higher than the response after three doses of OPV at 21 weeks of age (p greater than 0.05). The serum IgG responses to poliovirus type 3 were similar to those against type 1 in all the groups. Mean neutralizing antibody titres to poliovirus type 1 was significantly higher in the IPV2 group than the rest of the groups (p less than 0.01). For type 3, these titres were highest but not significantly, in the IPV4 group (p greater than 0.05). This study shows that two doses of a new antigen-rich IPV can give similar immediate serum antibody responses as OPV but higher late responses. SIgA antibodies in saliva were more efficiently induced by OPV after three doses than after 2 doses of IPV (p less than 0.05).     

Diphtheria-tetanus-acellular pertussis and inactivated poliovirus vaccines given separately or combined for booster dosing at 4-6 years of age

BACKGROUND: In the United States, diphtheria-tetanus-acellular pertussis (DTaP) and inactivated poliovirus (IPV) booster vaccinations are recommended for children 4-6 years of age. A combined DTaP-IPV vaccine is being developed, which would reduce by one the number of injections in this age group. METHODS: Children 4-6 years of age were randomized (1:1:1:1) to receive booster vaccination with 1 of 3 combined DTaP-IPV lots plus the measles, mumps, and rubella vaccine (N = 3156 for pooled lots) or separate doses of DTaP + IPV + measles, mumps, and rubella vaccine (N = 1053). Immunogenicity was assessed in a subset of children (N = 1331). Safety (solicited and unsolicited symptoms) including detailed assessment of local swelling reactions, was assessed in all children. RESULTS: Increases in antibody geometric mean concentrations/titers 1 month after vaccination were observed for the diphtheria, tetanus, acellular pertussis, and polio antigens. At least 92.2% of combined DTaP-IPV subjects and 92.6% of separate DTaP + IPV subjects had a postvaccination booster response for one or more DTaP antigens. Booster responses to one or more poliovirus antigens were observed in at least 96.6% of combined DTaP-IPV subjects and 92.8% of separate DTaP + IPV subjects. The combined DTaP-IPV vaccine was noninferior to separately administered DTaP and IPV vaccines with respect to DTaP antigen booster response rates and poliovirus antibody geometric mean titers ratios. Reporting of solicited local and systemic events was comparable between both groups. CONCLUSIONS: The combination DTaP-IPV vaccine provided immunogenicity and reactogenicity that is comparable to separately administered DTaP and IPV vaccines, with the advantage of requiring one less injection.     

Simultaneous administration of rhesus rotavirus vaccine and oral poliovirus vaccine: immunogenicity and reactogenicity

Rotavirus vaccine could be administered most efficiently if it were incorporated into routine childhood immunizations and did not interfere with the immune response to the other vaccines, principally oral poliovirus vaccine (OPV). We conducted a placebo-controlled randomized trial giving oral rhesus rotavirus vaccine (RRV) (strain MMU 18006) alone and together with a child's first dose of OPV and diphtheria-tetanus toxoids-pertussis to examine the possible interaction of these vaccines. A total of 102 infants 2 to 3 months of age were randomized into 3 groups to receive (1) RRV with OPV, (2) placebo with OPV and (3) RRV 2 weeks after OPV. All infants were given diphtheria-tetanus toxoids-pertussis. Serum samples were collected at the time of OPV immunization and 3 to 5 weeks later. Three to 5 weeks after OPV immunization 60% of infants had a 4-fold rise in neutralization titer to at least one of the three poliovirus serotypes. The rate of antibody response to poliovirus did not differ by RRV groups but a lower rate was correlated with a shorter interval (3 vs. 5 weeks) between OPV vaccination and antibody measurement. Fifty-six percent of infants had a 4-fold rise of IgA and 62% had a 4-fold rise of neutralizing antibody to RRV; this rise did not differ according to time of OPV immunization. RRV was not associated with side effects and may be safely given with OPV to infants 2 to 3 months of age.     

Absence of a significant interaction between a Haemophilus influenzae conjugate vaccine combined with a diphtheria toxoid, tetanus toxoid and acellular pertussis vaccine in the same syringe and inactivated polio vaccine

BACKGROUND: We compared the antibody response to Haemophilus influenzae type b capsular polysaccharide (PRP) after three doses of a diphtheria toxoid, tetanus toxoid and acellular pertussis vaccine (DTaP) combined with a PRP-tetanus conjugate (PRP-T) in infants randomized to receive oral polio vaccine (OPV) or inactivated polio vaccine (IPV). The polio vaccine was given separately at the same visit. METHODS: Three hundred fifty-six infants from pediatric practices in suburban Chicago and New Orleans were randomized into two groups. Group A received OPV at 2 and 4 months of age; Group B received IPV at 2 and 4 months of age. Both groups received DTaP/PRP-T at 2, 4 and 6 months of age and hepatitis B vaccine at 2 and 4 months of age. A serum sample was obtained before immunization (age 2 months) and 1 month after 3 doses of DTaP/PRP-T (age 7 months). Sera were assayed for antibody responses to all relevant vaccine antigens. RESULTS: No significant vaccine antigen interference was found when polio immunization was provided by IPV or OPV for anti-PRP, diphtheria, tetanus or pertussis antibodies. OPV recipients had a significantly higher mean antibody response to serotype 1 (P = 0.03) and 2 (P = 0.0001) poliovirus. CONCLUSION: Whether polio immunization was accomplished with IPV or OPV did not significantly influence the antibody responses in sera obtained at 7 months of age for anti-PRP, anti-diphtheria and anti-tetanus toxoid antibodies and antibodies to pertussis antigens, when DTaP/PRP-T was given in the primary series.     

Paralytic poliomyelitis associated with the Sabin 3 revertant strain of poliovirus in Bahrain

We report a case of vaccine-associated paralytic poliomyelitis (VAPP) in Bahrain. The case occurred in an 8-week-old infant who had received a dose of oral polio vaccine (OPV) 7 days after birth. She was in contact with two vaccinees who had received OPV during the national immunisation campaign conducted 10 days before her birth. Specimens from the infant were sent to the WHO Collaborating Centre for Virus Reference and Research Laboratory for serological testing and virus detection, including genomic sequencing. Clinical and virological features are presented of a case of VAPP caused by the Sabin 3 strain of poliovirus that had reverted towards neurovirulence. The case represents one in 51,879 first doses of OPV distributed between 1995 and 1998. In order to reduce further the risk of VAPP, the dose of OPV at birth has been discontinued and a sequential schedule of inactivated polio vaccine (IPV) followed by OPV will be recommended.     

Comparison of Serum and Salivary Antibodies in Children Vaccinated with Oral Live or Parenteral Inactivated Poliovirus Vaccines of Different Antigen Concentrations

ABSTRACT. A new antigen-rich inactivated poliovirus vaccine (IPV) in ordinary (IPV1), double (IPV2) and quadruple (IPV4) antigen concentrations was given in 2 doses to 6 and 18 week old Pakistani infants. The immune responses to poliovirus types 1 and 3 were compared to those in infants given three doses of oral poliovirus vaccine (OPV) at 6, 12 and 18 weeks of age. Enzyme-linked immunosorbent assay, ELISA, was used to estimate IgC and IgA in serum and secretory IgA (SIgA) in saliva. Two to three years later, a follow-up of the serum antibody response was carried out in the same infants using a microneutralization test. Serum IgG antibody responses to poliovirus type 1 antigen after two doses of IPV1, IPV2 and IPV4 were not significantly higher than the response after three doses of OPV at 21 weeks of age ( p > 0.05). The serum IgC responses to poliovirus type 3 were similar to those against type 1 in all the groups. Mean neutralizing antibody titres to poliovirus type 1 was significantly higher in the IPV2 group than the rest of the groups ( p <0.01). For type 3, these titres were highest but not significantly, in the IPV4 group ( p > 0.05). This study shows that two doses of a new antigen-rich IPV can give similar immediate serum antibody responses as OPV but higher late responses. SIgA antibodies in saliva were more efficiently induced by OPV after three doses than after 2 doses of IPV ( p <0.05).     

Adult formulation of a five component acellular pertussis vaccine combined with diphtheria and tetanus toxoids and inactivated poliovirus vaccine is safe and immunogenic in adolescents and adults

BACKGROUND: Pertussis is increasingly recognized as an important cause of cough illness in adolescents and adults. PURPOSE: To evaluate the safety and antibody response to a single dose of an adult formulation of a five component (pertussis toxoid, filamentous hemagglutinin, pertactin, fimbriae 2 and 3) acellular pertussis vaccine (aP) combined with diphtheria and tetanus toxoids (TdaP) and inactivated poliovirus vaccine (TdaP-IPV) in adolescents and adults and to assess the response to a second dose of the acellular pertussis vaccine in a subset of the adults. POPULATION AND SETTING: The study addressed 1207 healthy participants (736 adults and 466 adolescents) recruited in five Canadian communities. STUDY DESIGN: In a randomized, observer-blind, controlled clinical trial, adult participants received Td followed at a separate visit by aP, TdaP followed by IPV or TdaP-IPV; adolescents received Td-IPV followed at a separate visit by aP or TdaP-IPV. A subgroup of adults was given a booster of aP 1 month after TdaP. OUTCOME MEASURES: Antibody titers measured before and 1 month after each immunization; adverse events enumerated at 24 h, 72 h and 8 to 10 days. RESULTS: The aP vaccine given by itself was associated with adverse events less frequently than were Td, Td-IPV, TdaP or TdaP-IPV vaccines, but reaction rates did not differ significantly among the latter products. The antibody response against Bordetella pertussis antigens was vigorous in all groups, although adults given the TdaP-IPV vaccine had lower antibody titers against filamentous hemagglutinin, pertactin, diphtheria and tetanus antibodies than those given TdaP vaccine. Similarly adolescents given TdaP-IPV had lower antibody titers against pertussis toxin, filamentous hemagglutinin, fimbriae and agglutinins than those given Td-IPV and aP alone. A second dose of acellular pertussis vaccine was not associated with increased adverse events in adults but elicited increased antibody titers over that achieved by a single dose only against pertussis toxin. CONCLUSIONS: This adult formulation five component aP vaccine given as TdaP-IPV is safe and immunogenic in adolescents and adults and is a candidate vaccine for adolescent and adult immunization programs.     

Seroconversion following killed polio vaccine in neonates

The study was carried out to evaluate the efficacy of IPV in neonates and to study the additive effect of IPV or OPV at birth on seroconversion with three subsequent doses of OPV. Addition of IPV or OPV at birth to the conventional OPV schedule resulted in significantly higher seroconversion rates than in the controls, who received three doses of OPV. Three doses of IPV beginning from birth resulted in significantly better seroconversion rates than in the control group. Children receiving 3 doses of IPV showed significantly greater seroconversion rates against type III polio virus than those receiving IPV/OPV at birth followed by 3 doses of OPV. The difference in the seroconversion rates against the other virus types was not significant. A significantly greater number of children who received some vaccine at birth (IPV or OPV) were protected against poliomyelitis by 6 weeks age as compared to those who received no immunization at birth. The study recommends that seroconversion rates following three doses of IPV are satisfactory. Addition of IPV or OPV at birth to the conventional schedule markedly increases the seroconversion rates. Immunization can be started at birth to ensure early protection against poliomyelitis.     

Population immunity to polioviruses among preschool children from four urban underserved low income communities, United States, 1997-2001

BACKGROUND: In 1997, the Advisory Committee for Immunization Practices (ACIP) recommended a change in polio vaccination policy, the first in 30 years, from the oral poliovirus vaccine (OPV) to a combined OPV/inactivated poliovirus vaccine (IPV) sequential schedule for routine childhood vaccination. To evaluate the impact of the change in polio vaccination schedule on population immunity, we conducted a seroprevalence survey among low income preschool children from selected urban areas. METHODS: A repeat cross-sectional serosurvey was conducted during 1997-2001. Children 19-35 months of age receiving well-child care were recruited from outpatient clinics of academic medical centers. Serum samples were obtained and tested for neutralizing antibodies to polioviruses types 1, 2 and 3. A standardized questionnaire was administered to the parents or guardians of enrolled children. RESULTS: Seroprevalence remained high and stable during the study period. Among children sampled in the last study year (initiating their vaccinations from August 1997 through September 2000), seroprevalence was >/=95% to poliovirus serotypes 1 and 2 and >/=94% to serotype 3. Overall coverage with >/=3 doses of polio vaccine was 82-95% across sites during this period. The proportion initiating their vaccination schedule with IPV increased from 2.6% in study year 1 (children born October 1994-January 1997) to 80% in study year 4 (children born October 1997-January 2000). CONCLUSIONS: Children in these underserved low income communities are well-protected against the spread of polioviruses; the introduction of IPV did not adversely impact coverage or seroprevalence. Continued monitoring is needed to evaluate population immunity in the absence of OPV circulation.     

Towards global poliomyelitis eradication: the successes and challenges for a developed country

Abstract:    The Sabin oral polio vaccine (OPV) has been remarkably successful, with three major regions of the world declared polio free. Mutations of the live attenuated poliovirus during genomic replication have resulted in polioviruses with increased neurovirulence. Recently, mutated vaccine-derived polioviruses have circulated in countries with low OPV vaccination coverage causing outbreaks of poliomyelitis in the islands of Haiti, the Dominican Republic, the Philippines and Madagascar. Ultimately the total eradication of poliomyelitis requires the cessation of OPV use. The current questions of how best to continue polio immunisation and when OPV should be withdrawn are addressed. Prolonged excretion of poliovirus in stools following cessation of vaccination has the potential to infect unimmunized susceptible children. In Australia the change to the use of inactivated polio vaccine (IPV), while more costly, will avoid the very low risk of vaccine associated paralytic poliomyelitis (one case per 2.5 million doses) and maintain immunity against polio. In the future, new vaccines may provide the solution to the problem of OPV cessation.     

Simultaneous administration of measles-mumps-rubella vaccine with booster doses of diphtheria-tetanus-pertussis and poliovirus vaccines

The safety and efficacy of simultaneous administration of measles-mumps-rubella (MMR), diphtheria-tetanus-pertussis (DTP), and trivalent oral poliovirus (OPV) vaccines in a test group of 405 children were compared with the safety and efficacy of sequential administration of the same vaccines in a control group of 410 children given MMR followed by booster doses of DTP and OPV 2 months later. The study was double blind and placebo controlled with respect to DTP and OPV. Seroconversion rates to measles, mumps, and rubella exceeded 96% in both groups. Geometric mean titers to measles (P = .05) and rubella (P = .004) were higher in the test group, and titers of antibodies to the other seven antigens were similar in both groups. Clinical reaction data were analyzed in 248 of 405 test children and 249 of 410 control children. The rates of serious vaccine-associated reactions were low and similar in the two groups. Some minor side effects were reported more frequently in the test group, but these differences were judged to be related to study design rather than to differences in the safety of the two vaccine schedules. The results indicate that the safety and serologic efficacy of administering MMR simultaneously with reinforcing doses of DTP and OPV in the second year of life is equivalent to the safety and efficacy observed after administering these antigens separately.     

Controlled trial of immune response of preterm infants to recombinant hepatitis B and inactivated poliovirus vaccines administered simultaneously shortly after birth

AIM: The study was conducted to evaluate the immunogenicity of an early, extra dose of enhanced inactivated poliovirus vaccine (IPV) administered simultaneously with recombinant hepatitis B vaccine (HBV) to preterm infants shortly after birth. METHODS: Three groups were studied. Fifty preterm infants received IPV intramuscularly within 24 hours of birth, in addition to routine recommended childhood immunisations. Fifty two preterm infants and 35 full term infants received routine immunisations only (routine vaccination timing: HBV at birth, 1 and 6 months of age; IPV at 2 and 4 months; oral polio vaccine (OPV) at 4 and 6 months; diphtheria-tetanus-pertussis (DTP) at 2, 4, and 6 months; and Haemophilus influenzae B vaccine at 2 and 4 months). Blood samples were taken at birth, 3 and 7 months of age from all infants, and at 1 month of age from preterm infants only. RESULTS: At birth, a lower percentage of both study and control preterm infants had antipoliovirus type 3 titres >/= 1:8 than full term infants. At 1 and 3 months of age significantly more early IPV infants had antipoliovirus type 3 titres >/= 1:8 than routinely vaccinated preterm infants (p < 0.05). At 7 months of age there were no significant differences in percentage of antipoliovirus titres >/= 1:8 or geometric mean times (GMTs) between the early IPV group and the routinely vaccinated preterm group. At 3 and 7 months of age, the percentage of positive antihepatitis B titres (>/= 1:10) and the GMT of the early IPV preterm group did not differ significantly from those of preterm controls. There was no significant difference in percentage of positive antihepatitis B titres between the early IPV group and full term controls at any time. GMTs for hepatitis B antibodies were significantly lower in the early IPV preterm group than in full term controls at 3 and 7 months of age. CONCLUSIONS: Administration of an additional dose of IPV simultaneously with routine HBV to preterm infants shortly after birth provides early protection from poliovirus and hepatitis B infection, and does not interfere with poliovirus antibody production at the age of 7 months.     

Recommendations of 2nd National Consultative Meeting of Indian Academy of Pediatrics (IAP) on polio eradication and improvement of routine immunization

JUSTIFICATION: Persistence of intense wild poliovirus (WPV) transmission, particularly type 3 in northern India necessitated the Indian Academy of Pediatrics (IAP) to convene a National Consultative Meeting to review its earlier recommendations on polio eradication and improvement of routine immunization. PROCESS: More than thirty experts were invited and intense deliberations were held over two days to draw consensus statements on various issues related with polio eradication. OBJECTIVES: To review the ongoing strategy, identify the existing challenges, and suggest modifications to the current strategy for eradication of poliomyelitis in India. RECOMMENDATIONS: IAP reiterates its support to ongoing efforts on polio eradication but demand some flexibility in the strategy. The immediate challenges identified include persistent WPV type 1 transmission in Uttar Pradesh (UP) and Bihar, intense type 3 transmission also in UP and Bihar, and maintaining polio-free status of all other states. Circulating vaccine derived poliovirus (cVDPV), particularly type 2, was identified as a great future threat. Neglect of routine immunization (RI), poor efficacy of oral polio vaccine (OPV), operational issues, and inadequate uptake of OPV in the 2 endemic states are the main reasons of failure to interrupt transmission of WPV 1 and 3. However, for the first time in history the intensity of WPV 1 circulation is very low in western UP. IAP suggests that high-quality, uniform and consistent performance of supplementary immunization activities (SIAs) in all districts of western UP, particularly using mOPV1(monovalent OPV1) should be maintained to avoid reestablishment of circulation of type 1 poliovirus. A judicious mix of mOPV1 and mOPV3, given sequentially or even simultaneously (after validating the efficacies) will be necessary to address the upsurge of WPV3. Re-establishing routine immunization should be the foremost priority. IAP strongly recommends to Government of India (GOI) to take urgent measures to attain coverage of a minimum of 90% against all UIP antigens in all the states by the end of 2008. In view of the need to simultaneously raise immunity levels to protect against WPVs 1, 3 and cVDPV2, IPV may be given immediate consideration as an additional tool. IPV will be essential in the postWPVeradication phase; it can play a useful role even in the current WPV eradication phase. IAP urges the GOI to urgently sort out various issues associated with implementation of the proposal to use IPV. More transparency is needed on cases of vaccine associated paralytic poliomyelitis (VAPP). Further improvement in stool collection rates is also warranted to minimize the tally of compatible cases. IAP urges the social mobilization network to address the issues of waning interest and shifting focus and negative media coverage. Alternate tactics like reduced numbers of SIAs applied in the low transmission season, along with IPVDTP combination vaccine in RI can also be considered. IAP believes it will be risky to stop vaccination against poliomyelitis in postWPV eradication phase. The best option is to gradually introduce IPV starting now, so that a switch to IPV following high-performance national immunization days (NIDs) can be made to ensure sustained high immunity against all polioviruses, wild and vaccine derived. IAP requests the global polio eradication initiative (GPEI) to continue relevant research to inform on various aspects related to polio eradication, defined as zero incidence of any poliovirus infection. IAP also urges GOI to take immediate measures for improvement of environmental sanitation.