Background to the question
Poliomyelitis (most commonly called Polio) mainly affects children under the age of five who have not been vaccinated against it. Polio causes permanent paralysis and even death. Polio can be prevented by vaccines, which provide defence against the disease (antibodies) in body fluids (also called humoral immunity) and also gut mucosal immunity. Polio-related paralysis is caused by wild polio virus (WPV) and also in rare cases by the weakened live vaccine virus in the oral polio vaccine (OPV). The number of wild polio cases has gone down dramatically since the introduction and widespread use of the OPV and inactivated polio vaccine (IPV). However, the cases of paralysis linked to the OPV are currently more frequent than those related to the WPV. Since 2016 the World Health Organization has started to recommend that before a child is given the OPV immunisation they must have had at least one dose of the IPV mainly to limit the incidence of cases of paralysis linked to the OPV until polio is wiped out worldwide.
Are polio vaccine schedules that include both IPV and OPV as effective and safe as either OPV or IPV alone?
We searched databases of scientific studies and found 21 studies to include in this review. Studies included 16 randomised trials with 6407 infants, one additional study followed 28330 infants over time and another four were nationwide studies.
Certainty of the evidence
We assessed the included evidence for how certain we are that the effects are true and would not be altered with the addition of more evidence. In general, the certainty of the evidence was judged to be low to moderate but it was very low for some outcomes.
IPV-OPV compared to OPV may reduce the cases of paralysis linked to OPV by 54% to 100% without affecting vaccination coverage, the number of serious adverse events, and humoral immunity. However, it may worsen mucosal immunity for some types of polio.
IPV-OPV compared to IPV may make little or no difference on serious adverse events, probably makes little or no difference in the number of persons with protective humoral immunity, may increase neutralising antibodies and probably improves intestinal mucosal immunity of vaccinated people.
Three doses of IPV followed by OPV appears to be no different than two IPV doses followed by OPV on the number of people with protective humoral and gut immunity.
The main potential benefit of IPV-OPV, compared to OPV, is that may reduce cases of paralysis linked to OPV. It could be a more affordable option to IPV during the final stages of polio eradication, hence reducing inequities between countries.
IPV-OPV compared to OPV may reduce VAPPs without affecting vaccination coverage, safety or humoral response, except P2 with sequential schemes without P2 components, but increase poliovirus faecal excretion after OPV challenge for some polio serotypes. Compared to IPV-only schedules, IPV-OPV may have little or no difference on SAEs, probably has little or no effect on persons with protective humoral response, may increase neutralising antibodies, and probably reduces faecal excretion after OPV challenge of certain polio serotypes.
Using three IPV doses as part of a IPV-OPV schedule does not appear to be better than two IPV doses for protective humoral response.
Sequential schedules during the transition from OPV to IPV-only immunisation schedules seems a reasonable option aligned with current WHO recommendations. Findings could help decision-makers to optimise polio vaccination policies, reducing inequities between countries.
Poliomyelitis mainly affects unvaccinated children under five years of age, causing irreversible paralysis or even death. The oral polio vaccine (OPV) contains live attenuated virus, which can, in rare cases, cause a paralysis known as vaccine-associated paralytic polio (VAPP), and also vaccine-derived polioviruses (VDPVs) due to acquired neurovirulence after prolonged duration of replication. The incidence of poliomyelitis caused by wild polio virus (WPV) has declined dramatically since the introduction of OPV and later the inactivated polio vaccine (IPV), however, the cases of paralysis linked to the OPV are currently more frequent than those related to the WPV. Therefore, in 2016, the World Health Organization (WHO) recommended at least one IPV dose preceding routine immunisation with OPV to reduce VAPPs and VDPVs until polio could be eradicated.
To assess the effectiveness, safety, and immunogenicity of sequential IPV-OPV immunisation schemes compared to either OPV or IPV alone.
In May 2019 we searched CENTRAL, MEDLINE, Embase, 14 other databases, three trials registers and reports of adverse effects on four web sites. We also searched the references of identified studies, relevant reviews and contacted authors to identify additional references.
Randomised controlled trials (RCTs), quasi-RCTs, controlled before-after studies, nationwide uncontrolled before-after studies (UBAs), interrupted time series (ITS) and controlled ITS comparing sequential IPV-OPV schedules (one or more IPV doses followed by one or more OPV doses) with IPV alone, OPV alone or non-sequential IPV-OPV combinations.
We used standard methodological procedures expected by Cochrane.
We included 21 studies: 16 RCTs involving 6407 healthy infants (age range 96 to 975 days, mean 382 days), one ITS with 28,330 infants and four nationwide studies (two ITS, two UBA). Ten RCTs were conducted in high-income countries; five in the USA, two in the UK, and one each in Chile, Israel, and Oman. The remaining six RCTs were conducted in middle-income countries; China, Bangladesh, Guatemala, India, and Thailand. We rated all included RCTs at low or unclear risk of bias for randomisation domains, most at high or unclear risk of attrition bias, and half at high or unclear risk for conflict of interests. Almost all RCTs were at low risk for the remaining domains. ITSs and UBAs were mainly considered at low risk of bias for most domains.
IPV-OPV versus OPV
It is uncertain if an IPV followed by OPV schedule is better than OPV alone at reducing the number of WPV cases (very low-certainty evidence); however, it may reduce VAPP cases by 54% to 100% (three nationwide studies; low-certainty evidence). There is little or no difference in vaccination coverage between IPV-OPV and OPV-only schedules (risk ratio (RR) 1.01, 95% confidence interval (CI) 0.96 to 1.06; 1 ITS study; low-certainty evidence). Similarly, there is little or no difference between the two schedule types for the number of serious adverse events (SAEs) (RR 0.88, 95% CI 0.46 to 1.70; 4 studies, 1948 participants; low-certainty evidence); or the number of people with protective humoral response P1 (moderate-certainty evidence), P2 (for the most studied schedule; two IPV doses followed by OPV; low-certainty evidence), and P3 (low-certainty evidence).
Two IPV doses followed by bivalent OPV (IIbO) may reduce P2 neutralising antibodies compared to trivalent OPV (moderate-certainty evidence), but may make little or no difference to P1 or P2 neutralising antibodies following an IIO schedule or OPV alone (low-certainty evidence). Both IIO and IIbO schedules may increase P3 neutralising antibodies compared to OPV (moderate-certainty evidence). It may also lead to lower mucosal immunity given increased faecal excretion of P1 (low-certainty evidence), P2 and P3 (moderate-certainty evidence) after OPV challenge.
IPV-OPV versus IPV
It is uncertain if IPV-OPV is more effective than IPV alone at reducing the number of WPV cases (very low-certainty evidence). There were no data regarding VAPP cases. There is no clear evidence of a difference between IPV-OPV and OPV schedules for the number of people with protective humoral response (low- and moderate-certainty evidence). IPV-OPV schedules may increase mean titres of P1 neutralising antibodies compared to OPV alone (low- and moderate-certainty evidence), but the effect on P2 and P3 titres is not clear (very low- and moderate-certainty evidence).
IPV-OPV probably reduces the number of people with P3 poliovirus faecal excretion after OPV challenge with IIO and IIOO sequences (moderate-certainty evidence), and may reduce the number with P2 (low-certainty evidence), but not with P1 (very low-certainty evidence). There may be little or no difference between the schedules in number of SAEs (RR 0.92, 95% CI 0.60 to 1.43; 2 studies, 1063 participants, low-certainty evidence).
The number of persons with P2 protective humoral immunity and P2 neutralising antibodies are probably lower with most sequential schemes without P2 components (i.e. bOPV) than with trivalent OPV or IVP alone (moderate-certainty evidence).
IPV (3)-OPV versus IPV (2)-OPV
One study (137 participants) showed no clear evidence of a difference between three IPV doses followed by OPV and two IPV doses followed by OPV, on the number of people with P1 (RR 0.98, 95% CI 0.93 to 1.03), P2 (RR 1.00, 95% CI 0.97 to 1.03), or P3 (RR 1.01, 95% CI 0.97 to 1.05) protective humoral and intestinal immunity; all moderate-certainty evidence. This study did not report on any other outcomes.