Recommendations for UseFor EPI In 2008 as many as 551 cases of polio (481 P3, 70 P1) have been reported in India of which 530 are in UP and Bihar. This scenario of continuous P1 transmission and resurgence of P3 has been attributed to neglect of routine immunization, poor efficacy of OPV, extremely high force of transmission of wild polio virus in UP and Bihar and operational/political issues. The polio eradication committee of the IAP (IAP-PEC) has suggested certain corrective measures including improvement of routine immunization coverage, utilization of IPV in a campaign mode in the hotbeds of wild polio, improving performance of the NID’s/SNID’s, reducing the frequency and shortening the durations of SIA’s, prompt outbreak response immunization, sensitive surveillance to pick up cVDPV, greater transparency on VAPP cases, rehabilitation of polio victims, conduction of appropriate research, social mobilization, adequate attention to other EPI vaccines and improvement of environmental sanitation. The IAP-PEC has further opined that it will be unsafe to stop vaccination in the post eradication era due to risks of cVDPV and bio terrorism and thus switch to IPV is inevitable. Such a switch cannot happen overnight due to requirement of large number of doses and logistic issues. It therefore, recommends incorporation of IPV as DTPIPV combination in addition to OPV in the routine immunization of states that are currently free of polio so that a gradual switch to IPV is facilitated. For Office Practice IAPCOI recommends continuing OPV use for birth dose, for routine immunization at 6,10 and 14 weeks, 15-18 months and at 5 years and on all NID’s and SNID’s. The IAPCOI also recommends offering additional use of IPV with OPV in all children who can afford the vaccine (Category 2) in the schedule discussed below. Any of the currently licensed brands may be used. The recommendation for wider use of IPV is for the following reasons:
OPV use should be continued at present for the following reasons:
The IAPCOI feels that in the current scenario where polio eradication in India is at the cross roads and a highly sensitive issue, the combined OPV and IPV schedule strives to provide the best of protection to an individual child while not deviating from the national immunization policies. |
The availability of two effective vaccines against poliomyelitis for the past five decades has ensured remarkable decline in the global burden of disease. The Global Polio Eradication initiative was launched in 1988 using oral polio vaccine (OPV) as the eradication tool and employing a four pronged strategy comprising high routine immunization coverage, supplementary immunization activities (SIAs)/pulse immunization, acute flaccid paralysis (AFP) surveillance and outbreak response/“mopping up” immunization.
The initiative was hugely successful with reduction of polio cases from 350,000 in 1988 to less than a 1000 cases in 2007. Only four countries including India, Pakistan, Nigeria and Afghanistan remain endemic today and wild virus type 2 has not been isolated since 1999. However, the last leg of the journey has been difficult consisting of challenges of eradication of polio from the last remaining pockets (especially UP and Bihar), occurrence of cVDPV (circulating vaccine derived polio viruses) and meeting the funding gap.
OPV is a trivalent vaccine consisting of a suspension of attenuated poliovirus types 1, 2 and 3 grown in monkey kidney cell cultures and stabilized with magnesium chloride. It is a very heat sensitive vaccine having a shelf life of 2 years at a temperature of –20°C, 6 months at 2 to 8°C and 1-3 days at room temperature. OPV should be stored at –20° C at the state and district level and in the freezer at the clinic level. The vaccine must reach the outreach facility at 2 to 8° C in vaccine carriers with ice packs. Multiple freeze thaw cycles should be avoided as the virus loses its potency. The dose is 2 drops orally.
When OPV is given by mouth, the vaccine viruses reach the intestines where they must establish infection (vaccine virus “take)” before an immune response may occur. For reasons that are not clearly understood, OPV “take” rates may be somewhat variable. Infection with other enteroviruses and competition between the three polioviruses impair take of the vaccine. Data from clinical trials suggest that seroconversion rates after three doses of OPV average 73%, 90% and 70% for Types I, II and III respectively or roughly 30% per dose. Multiple doses of OPV are necessary before 90-95% of children develop immune responses to all three poliovirus types.
The onset of action of OPV is faster as compared to inactivated poliovirus vaccine (IPV) and thus OPV is the vaccine of choice for outbreak control. The virus is transmissible from the vaccinees to contacts. In settings where vaccine efficacy is high, OPV provides mucosal immunity including intestinal and pharyngeal immunity, reduces transmission of the wild virus and thus offers significant herd protection. Several countries have eradicated polio with use of OPV alone.
IAP has recommended the administration of OPV at birth (OPV0), 3 doses at 6, 10 and 14 weeks and 2 more repeat doses; at 16-18 months and 5 years. In addition to the routine OPV doses, “Pulse OPV doses” every year on National Immunization Days (NID’s) and sub-National Immunization Days (SNID’s) until the age of 5 years are also mandatory. Administration of a dose at birth (zero dose) serves as a priming dose and has been shown to improve the serologic response to future doses. Administration of pulse doses replaces the wild virus from guts of all children with the vaccine virus and hence plays in important role in polio eradication.
However, AFP surveillance data systematically generated since launch of GPEI suggests that several Indian children particularly from Uttar Pradesh (UP) and Bihar develop paralytic poliomyelitis despite having received 15-20 doses of OPV. A case control study based on AFP surveillance data from India has estimated the per dose efficacy of trivalent OPV in India as 13% to as low as 9% in UP. This poor efficacy is attributed to high population densities, malnutrition, poor sanitation that increase the risk of infection with other enteroviruses and NOT due to poor vaccine potency due to breaks in cold chain.
This low efficacy and associated poor mucosal immunity is responsible for poor herd effect of OPV in these settings. Monovalent OPV (mOPV) is presumably 2.5 – 3 times more efficacious than trivalent OPV as competition between different polio viruses is eliminated. Henceforth monovalent OPV containing type1 virus has been introduced in India since 2005 for pulse immunization. The benefits of decline in P1 cases has been partly offset by resurgence of P3. Pulse immunization with monovalent P3 and bivalent OPV (bOPV containing P1 and P3) are strategies to offset this risk.
A rare but serious adverse effect associated with OPV is vaccine associated paralytic poliomyelitis (VAPP). VAPP occurs due to loss of attenuating mutations and reversion to neurovirulence during replication of the vaccine virus in the gut. VAPP is defined as those cases of AFP which have residual weakness 60 days after the onset of paralysis and from whose stool samples, vaccine-related poliovirus but no wild polio virus is isolated. VAPP may occur in the vaccine recipient (recipient VAPP, occurring within 4-40 days of receiving OPV) or contact of the vaccine recipient (contact VAPP). The risk of VAPP is higher with the first dose that “takes,” with P2 virus and in patients with B-cell immunodeficiency.
The incidence of VAPP in developed countries such as US has been reported to be 1 per 2.4 million doses distributed and 1 per 750,000 with first dose. Many countries switched to sequential IPVOPV and then only IPV schedules once the number of VAPP cases exceeded wild polio cases. The risk of VAPP in India has been estimated to be 1 per 4.1 to 4.6 million doses distributed and 1 per 2.8 million first dose recipient risk. This lower risk of VAPP has been attributed to maternal antibodies, birth dose of OPV, early immunization with OPV and most importantly lower “take” of the vaccine (as only the vaccine that takes up can cause VAPP). Nevertheless the absolute numbers of VAPP are significant and it is estimated that 181 cases of VAPP occurred in India in 1999. Unfortunately there is lack of recent data on incidence of VAPP in India with all VAPP cases being reported as non polio AFP.
A recently recognized unanticipated major problem with use of OPV is the emergence of Vaccine Derived Polio Viruses (VDPVs). They arise due to mutation and recombination in the human gut and are 1-15% divergent from the parent vaccine virus. These viruses like those causing VAPP are neurovirulent but additionally are transmissible and capable of causing outbreaks. They have been classified into three groups; circulating VDPV (cVDPV), VDPV in the immunodeficient (iVDPV) and VDPV of ambiguous origin (aVDPV).
VDPV’s have been present since OPV was in use but are recognized now since sensitive surveillance systems are in place. As many as 10 outbreaks in 9 countries affecting 209 individuals have been recognized in the last decade. Risk factors for outbreaks due to cVDPV include dropping immunization coverage (both routine and SIA’s), high population densities, tropical conditions and previous eradication of wild virus. Interestingly, in the recent Nigerian outbreak in 2006-2007 due to P2 strain affecting 71 people, cVDPV coexisted with the wild virus and was less than 1% divergent from the vaccine virus.
India at present is at low risk for cVDPV outbreak due to high immunization coverage. However dropping immunization coverage (especially routine immunization with trivalent vaccine), eradication of wild virus from several sites, high force of transmission and monovalent OPV use are factors conducive to a cVDPV outbreak (possibly type 2) in future. Recognition of VDPV’s is the primary reason why synchronous stopping of OPV use globally and continuing to vaccinate against polio with IPV is mandatory in the post polio eradication scenario.
OPV is contraindicated in immunodeficient patients
(especially humoral immunodeficiencies) and their household
contacts.