Monovalent type-1 oral poliovirus vaccine given at short intervals in Pakistan: a randomised controlled, four-arm, open-label, non-inferiority trial

Abstract

Background: Supplementary immunisation activities with oral poliovirus vaccines (OPVs) are usually separated by 4 week intervals; however, shorter intervals have been used in security-compromised areas and for rapid outbreak responses. We assessed the immunogenicity of monovalent type-1 oral poliovirus vaccine (mOPV1) given at shorter than usual intervals in Karachi, Pakistan.

Methods: This was a multicentre, randomised, controlled, four-arm, open-label, non-inferiority trial done at five primary health-care centres in low-income communities in and around Karachi, Pakistan. Eligible participants were healthy newborn babies with a birthweight of at least 2·5 kg, for whom informed consent was provided by their parent or guardian, and lived less than 30 km from the study clinic. After receiving a birth dose of trivalent OPV, we enrolled and randomly assigned newborn babies (1:1:1:1) to receive two doses of mOPV1 with an interval of 1 week (mOPV1-1 week), 2 weeks (mOPV1-2 weeks), or 4 weeks (mOPV1-4 weeks) between doses, or two doses of bivalent OPV (bOPV) with an interval of 4 weeks between doses (bOPV-4 weeks). We gave the first study dose of OPV at age 6 weeks. We did the randomisation with a centrally generated, computerised allocation sequence with blocks of 16; participants' families and study physicians could not feasibly be masked to the allocations. Trial participants were excluded from local supplementary immunisation activities during the study period. The primary outcome was non-inferiority (within a 20% margin) between groups in seroconversion to type-1 poliovirus. The primary and safety analyses were done in the per-protocol population of infants who received all three doses of vaccine. This trial is registered with ClinicalTrials.gov, number NCT01586572, and is closed to new participants.

Findings: Between March 1, 2012, and May 31, 2013, we enrolled 1009 newborn babies, and randomly assigned 829 (82%) to treatment. 554 (67%) of the 829 babies were included in the per-protocol analysis. Proportions of seroconversion to type-1 poliovirus were 107/135 (79%, 95% CI 72·4-86·1) with mOPV1-1 week, 108/135 (80%, 73·2-86·8) with mOPV1-2 weeks, 129/148 (87%, 80·9-92·0) with mOPV1-4 weeks, and 107/136 (79%, 71·8-85·6) with bOPV-4 weeks. Non-inferiority was shown between groups and no significant differences were noted. Ten participants died during the trial. Seven of these deaths occurred during the lead-in period before randomisation (two from diarrhoea, five from unknown causes). Three infants died from sepsis after random assignment. No deaths were attributed to the procedures or vaccines. Additionally, we noted no events of vaccine-associated paralysis.

Interpretation: We identified no significant differences in responses to mOPV1 given with shorter intervals between doses than with the standard 4 week intervals. The short-interval strategy could be particularly beneficial when temporary windows of opportunity for safe access can be granted in areas of conflict--eg, during cease-fire periods. In such situations, we recommend shortening the interval between OPV doses to 7 days.

Funding: World Health Organization.

Conflict of interest statement

Declaration of interests

We declare no competing interests.

Copyright © 2015 World Health Organization. Published by Elsevier Ltd/Inc/BV. All rights reserved. Published by Elsevier Ltd.. All rights reserved.

Figures

Figure 1. Trial profile

tOPV=trivalent oral polio vaccine. mOPV1=monovalent oral polio vaccine type 1. bOPV=bivalent OPV type 1 and 3. SIA=supplementary immunisation activity.

Figure 2. Seroconversion after three doses of oral polio vaccine

Data are proportions (95% CIs) from per-protocol population (n=554). Type-1 poliovirus: mOPV1-1 week 95% CI 72.4–86.1. mOPV1-2 week 73.2–86.8. mOPV1-4 week 80.9–92.0. bOPV (1&3)-4 week 71.8–85.6. Type 2 poliovirus: mOPV1-1 week 95% CI 44.9–61.8. mOPV1-2 week 47.1–64.0. mOPV1-4 week 56.4–72.0. bOPV(1&3)-4 week 54.3–70.7. Type 3 poliovirus: mOPV1-1 week 95% CI 18.5–33.4. mOPV1-2 week 17.8–32.6. mOPV1-4 week 23.6–38.6. bOPV (1&3)-4 week 59.7–75.6. mOPV1=monovalent oral polio vaccine type 1. bOPV=bivalent oral polio vaccine type 1 and 3.

Figure 3. Seroconversion after two doses of oral polio vaccine

Data from per-protocol population who did not show seroconversion after being vaccinated at birth.mOPV1=monovalent oral polio vaccine type 1. bOPV(1and 3) =bivalent oral polio vaccine type 1 and 3. *p=0.001 for mOPV1–1 week vs bOPV1 and 3–4 weeks. †p=0.013 for mOPV1–2 weeks vs bOPV1 and 3–4 weeks. ‡p<0.0001 for mOPV1–1 week, mOPV1–2 weeks, and mOPV1–4 weeks vs bOPV1 and 3–4 weeks.