Effectiveness of equivalent schedules of full-dose inactivated poliovirus vaccine injected into muscle compared to a smaller dose injected into skin

Background

Polio is a disabling disease that is only preventable via vaccination. There are two types of polio vaccines: live poliovirus vaccine delivered orally (by mouth – so-called OPV) and inactivated (killed) poliovirus vaccine (IPV). OPV is the mainstay of polio eradication but carries a risk of causing vaccine-associated polio. This is not the case for IPV, which also has fewer side effects and can be given to people with low immunity, making it vital for the complete elimination of poliovirus. Killed vaccines can be given via injection either into the muscles (intramuscular) or into the skin (intradermal).

Review question

How effective is a small dose of IPV injected into the skin compared to a full dose of IPV injected into muscle in similar schedules?

Study characteristics

The database searches, up-to-date to February 2019, found 13 randomised controlled trials (a type of experiment in which participants are randomly assigned to one of two or more treatment groups). Three studies comprised 890 adult participants; a further 10 studies comprised 6402 infants and children.

Nine studies were conducted in middle-income countries; three studies in high-income countries; and one study in a low-income country. The studies had a duration of 2 to 19 months. Three studies were supported financially by drug companies, and three studies received the vaccines from the pharmaceutical company. There is overall limited confidence in the quality of the included studies since, for example, in most trials the recipient or assessor (or both) were aware of the vaccine being given.

Key results

The review included 13 studies with a total of 7292 participants (6402 children and 890 adults). Where possible, we combined the results of similar studies in a meta-analysis (a statistical method of combining the results of multiple single studies to calculate an overall effect).

There are three types of wild poliovirus: types 1, 2, and 3. We found that the number of antibody responses to the vaccine (measured using something called seroconversion rates) in children was higher in the group that received the vaccine by intramuscular injection compared to the group that had a similar number of injections given intradermally, after one single dose (6 studies, 2571 children) and two doses (3 studies, 981 children) for all three types of poliovirus, and after three doses for type 2 poliovirus (3 studies, 973 children).

The vaccines produce antibodies against all three types of poliovirus. The quantity of antibodies produced by the vaccines (measured as geometric median titres) was higher in children receiving a full dose of IPV via intramuscular route for all three types of poliovirus (7 studies, 4887 children).

Five studies (2217 children) reported more adverse events, such as fever and redness, in the intradermal group, whilst two studies (1904 children) reported more adverse events in the intramuscular group.

None of the included studies reported data on the occurrence of paralytic poliomyelitis.

Certainty of the evidence

Based on the evidence, intramuscular full-dose IPV may result in a slight increase in seroconversion rates for all three types of wild poliovirus when compared with intradermal fractional-dose IPV. We are uncertain if a fractional dose of IPV given intradermally is better than a full dose of IPV given intramuscularly at producing antibodies for all three types of poliovirus or reducing adverse effects.

Authors' conclusions: 

There is low- and very low-certainty evidence that intramuscular full-dose IPV may result in a slight increase in seroconversion rates for all three types of wild poliovirus, compared with intradermal fractional-dose IPV. We are uncertain whether intradermal fractional-dose (one-fifth) IPV has better protective effects and causes fewer adverse events in children than intramuscular full-dose IPV.

Read the full abstract...
Background: 

Poliomyelitis is a debilitating and deadly infection. Despite exponential growth in medical science, there is still no cure for the disease, which is caused by three types of wild polioviruses: types 1, 2, and 3. According to the Global Polio Eradication Initiative (GPEI), wild poliovirus is still in circulation in three countries, and fresh cases have been reported even in the year 2018.

Due to the administration of live vaccines, the risk for vaccine-derived poliovirus (VDPV) is high in areas that are free from wild polioviruses. This is evident based on the fact that VDPV caused 20 outbreaks between 2000 and 2011.

Recent recommendations from the World Health Organization favoured the inclusion of inactivated poliovirus vaccine (IPV) in the global immunisation schedule. IPV can be delivered in two ways: intramuscularly and intradermally. IPV was previously administered intramuscularly, but shortages in vaccine supplies, coupled with the higher costs of the vaccines, led to the innovation of delivering a fractional dose (one-fifth) of IPV intradermally. However, there is uncertainty regarding the efficacy, immunogenicity, and safety of an intradermal, fractional dose of IPV compared to an intramuscular, full dose of IPV.

Objectives: 

To compare the immunogenicity and efficacy of an inactivated poliovirus vaccine (IPV) in equivalent immunisation schedules using fractional-dose IPV given via the intradermal route versus full-dose IPV given via the intramuscular route.

Search strategy: 

We searched CENTRAL, MEDLINE, Embase, 10 other databases, and two trial registers up to February 2019. We also searched the GPEI website and scanned the bibliographies of key studies and reviews in order to identify any additional published and unpublished trials in this area not captured by our electronic searches.

Selection criteria: 

Randomised controlled trials (RCTs) and quasi-RCTs of healthy individuals of any age who are eligible for immunisation with IPV, comparing intradermal fractional-dose (one-fifth) IPV to intramuscular full-dose IPV.

Data collection and analysis: 

We used standard methodological procedures expected by Cochrane.

Main results: 

We included 13 RCTs involving a total of 7292 participants, both children (n = 6402) and adults (n = 890). Nine studies were conducted in middle-income countries, three studies in high-income countries, and only one study in a low-income country. Five studies did not report methods of randomisation, and one study failed to conceal the allocations. Eleven studies did not blind participants, and six studies did not blind outcome assessments. Two studies had high attrition rates, and one study selectively reported the results. Three studies were funded by pharmaceutical companies.

Paralytic poliomyelitis. No study reported data on this outcome.

Seroconversion rates. These were significantly higher for all three types of wild poliovirus for children given intramuscular full-dose IPV after a single primary dose and two primary doses, but only significantly higher for type two wild poliovirus given intramuscularly after three primary doses:
• dose one (six studies): poliovirus type 1 (odds ratio (OR) 0.30, 95% confidence interval (CI) 0.22 to 0.41; 2570 children); poliovirus type 2 (OR 0.43, 95% CI 0.31 to 0.60; 2567 children); poliovirus type 3 (OR 0.19, 95% CI 0.12 to 0.30; 2571 children);
• dose two (three studies): poliovirus type 1 (OR 0.23, 95% CI 0.16 to 0.33; 981 children); poliovirus type 2 (OR 0.41, 95% CI 0.28 to 0.60; 853 children); and poliovirus type 3 (OR 0.12, 95% CI 0.07 to 0.22; 855 children); and
• dose three (three studies): poliovirus type 1 (OR 0.45, 95% CI 0.07 to 3.15; 973 children); poliovirus type 2 (OR 0.34, 95% CI 0.19 to 0.63; 973 children); and poliovirus type 3 (OR 0.18, 95% CI 0.01 to 2.58; 973 children).

Using the GRADE approach, we rated the certainty of the evidence as low or very low for seroconversion rate (after a single, two, or three primary doses) for all three poliovirus types due to significant risk of bias, heterogeneity, and indirectness in applicability/generalisability.

Geometric mean titres. No study reported mean antibody titres. Median antibody titres were higher for intramuscular full-dose IPV (7 studies with 4887 children); although these studies also reported a rise in antibody titres in the intradermal group, none reported the duration for which the titres remained high.

Any vaccine-related adverse event. Five studies (2217 children) reported more adverse events, such as fever and redness, in the intradermal group, whilst two studies (1904 children) reported more adverse events in the intramuscular group.

Share/Save