Dataset Information

Immunogenicity of Different Routine Poliovirus Vaccination Schedules: A Randomized, Controlled Trial in Karachi, Pakistan.

ABSTRACT: Background:We assessed immunity against polioviruses induced with a new Pakistani poliovirus immunization schedule and compared it to alternative poliovirus immunization schedules. Methods:Newborns were randomized to undergo vaccination based on 1 of 5 vaccination schedules, with doses administered at birth and at 6, 10, and 14 weeks of age. Arm A received inactivated poliovirus vaccine (IPV) at all time points. Arm B received bivalent oral poliovirus vaccine (bOPV) at all time points. Arms C and D received bOPV at the first 3 time points and bOPV plus IPV at the final time point (the current schedule). Arm E received trivalent OPV (tOPV) at all time points. At 22 weeks of age, all children received 1 challenge dose of tOPV, and children in arm D received 1 additional IPV dose. Sera were analyzed for the presence of poliovirus neutralizing antibodies at birth and 14 and 22 weeks of age. Results:Seroconversion for poliovirus type 1 (PV1) at 22 weeks of age was observed in 80% of individuals in arm A, 97% in arm B, 94% in arm C, 96% in arm D, and 94% in arm E; for PV2, seroconversion frequencies were 84%, 19%, 53%, 49%, and 93%, respectively; and for PV3, seroconversion frequencies were 93%, 94%, 98%, 94%, and 85%, respectively. Conclusions:The current immunization schedule in Pakistan induced high seroconversion rates for PV1 and PV3; however, it induced PV2 seroconversion in only half of study subjects. There is a growing cohort of young children in Pakistan who are unprotected against PV2; and this creates an increasing risk of a large-scale outbreak of poliomyelitis caused by circulating vaccine-derived PV2.

SUBMITTER: Saleem AF

PROVIDER: S-EPMC7191618 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Immunogenicity of Different Routine Poliovirus Vaccination Schedules: A Randomized, Controlled Trial in Karachi, Pakistan.

Saleem Ali F AF Mach Ondrej O Yousafzai Mohammad T MT Khan Asia A Weldon William C WC Steven Oberste M M Zaidi Syed S SS Alam Muhammad M MM Quadri Farheen F Sutter Roland W RW Zaidi Anita K M AKM

The Journal of infectious diseases 20180101 3

<h4>Background</h4>We assessed immunity against polioviruses induced with a new Pakistani poliovirus immunization schedule and compared it to alternative poliovirus immunization schedules.<h4>Methods</h4>Newborns were randomized to undergo vaccination based on 1 of 5 vaccination schedules, with doses administered at birth and at 6, 10, and 14 weeks of age. Arm A received inactivated poliovirus vaccine (IPV) at all time points. Arm B received bivalent oral poliovirus vaccine (bOPV) at all time po ...[more]

PMID: 29126173

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Project description:BackgroundWe assessed immunogenicity of three-dose and two-dose immunization schedules with a Sabin-strain inactivated poliovirus vaccine (sIPV) produced by one Chinese vaccine manufacturer.MethodsThis was an open label, randomized, controlled trial conducted in 16 vaccination clinics in Shandong province. Infants were allocated randomly to either a 3-dose study arm (sIPV administered at 2, 3, and 4 months of age) or a 2-dose arm (sIPV administered at 4 and 8-11 months of age). Poliovirus neutralizing antibodies were measured in sera collected prior to the first sIPV dose and one month after the last dose.FindingsWe enrolled 560 infants; 536 (95.7%) completed the study. Final seropositivity rates were >98% for all three serotypes in both study arms. There were no statistically significant differences in seropositivity between the 2-dose and the 3-dose schedule. Final median reciprocal titres of polio antibodies were high overall (>1:768 for all serotypes) and statistically significantly higher in 2-dose recipients compared with 3-dose recipients (p < 0.001).InterpretationThis study offers evidence that two doses of sIPV administered at 4 and 8-11 months of age and three doses of sIPV administered at 2, 3, and 4 months of age both provide serological protection against poliomyelitis. Median reciprocal titres of polio antibodies were high overall, and were more related to the interval between doses than the number of doses, with the longer interval of the 2-dose schedule producing higher reciprocal titres than the shorter-interval 3-dose schedule. The protection provided by the 3-dose schedule is achieved earlier in life than the protection with the 2-dose schedule. Countries planning to use an IPV-only schedule in the post-eradication era can consider this 2-dose sIPV option as an immunogenic and dose-sparing strategy.FundingWorld Health Organization (from a grant from International PolioPlus Committee, Rotary International, Evanston, IL, USA).

Project description:BACKGROUND:The type 2 component of the oral poliovirus vaccine is targeted for global withdrawal through a switch from the trivalent oral poliovirus vaccine (tOPV) to a bivalent oral poliovirus vaccine (bOPV). The switch is intended to prevent paralytic polio caused by circulating vaccine-derived poliovirus type 2. We aimed to assess the immunogenicity and safety profile of 6 vaccination schedules with different sequential doses of inactivated poliovirus vaccine (IPV), tOPV, or bOPV. METHODS:A randomized controlled trial was conducted in China in 2015. Healthy newborn babies randomly received one of the following 6 vaccination schedules: cIPV-bOPV-bOPV(I-B-B), cIPV-tOPV-tOPV(I-T-T), cIPV-cIPV-bOPV(I-I-B), cIPV-cIPV-tOPV(I-I-T), cIPV-cIPV-cIPV(I-I-I), or tOPV-tOPV-tOPV(T-T-T). Doses were administered sequentially at 4-6 week intervals after collecting baseline blood samples. Patients were proactively followed up for observation of adverse events after the first dose and 30 days after all doses. The primary study objective was to investigate the immunogenicity and safety profile of different vaccine schedules, evaluated by seroconversion, seroprotection and antibody titer against poliovirus types 1, 2, and 3 in the per-protocol population. RESULTS:Of 600 newborn babies enrolled, 504 (84.0%) were included in the per-protocol population. For type 1 poliovirus, the differences in the seroconversion were 1.17% (95% CI = -2.74%, 5.08%) between I-B-B and I-T-T and 0.00% (95% CI: -6.99%, 6.99%) between I-I-B and I-I-T; for type 3 poliovirus, differences in the seroconversion were 3.49% (95% CI: -1.50%, 8.48%) between I-B-B and I-T-T and -2.32% (95% CI: -5.51%, 0.86%) between I-I-B and I-I-T. The non-inferiority conclusion was achieved in both poliovirus type 1 and 3 with the margin of -10%. Of 24 serious adverse events reported, no one was vaccine-related. CONCLUSIONS:The vaccination schedules with bOPV followed by one or 2 doses of IPV were recommended to substitute for vaccinations involving tOPV without compromising the immunogenicity and safety in the Chinese population. The findings will be essential for policy formulation by national and global authorities to facilitate polio elimination.

Project description:Reaching high population immunity against polioviruses (PV) is essential to achieving global polio eradication. Efficacy of oral poliovirus vaccine (OPV) varies and is lower among children living in tropical areas with impoverished environments. Malnutrition found as a risk factor for lower serological protection against PV. We compared whether inactivated polio vaccine (IPV) can be used to rapidly close the immunity gap among chronically malnourished (stunted) infants in Pakistan who will not be eligible for the 14 week IPV dose in routine EPI schedule. A phase 3, multicenter 4-arm randomized controlled trial conducted at five Primary Health Care (PHC) centers in Karachi, Pakistan. Infants, 9-12 months were stratified by length for age Z score into chronically malnourished and normally nourished. Infants were randomized to receive one dose of either bivalent OPV (bOPV) alone or bOPV+IPV. Baseline seroprevalence of PV antibodies and serum immune response to study vaccine dose were assessed by neutralization assay. Vaccine PV shedding in stool was evaluated 7 days after a bOPV challenge dose. Sera and stool were analyzed from 852/928 (92%) enrolled children. At baseline, the seroprevalence was 85.6% (n=386), 73.6% (n=332), and 70.7% (n=319) in malnourished children against PV types 1, 2 and 3 respectively; and 94.1% (n=448), 87.0% (n=441) and 83.6% (n=397) in the normally nourished group (p<0.05). Children had previously received 9-10 doses of bOPV (80%) or tOPV (20%). One dose of IPV+bOPV given to malnourished children increased their serological protection (PV1, n=201, 97.6%; PV2, n=198, 96.1% and PV3, n=189, 91.7%) to parity with normally nourished children who had not received IPV (p=<0.001). Seroconversion and boosting for all three serotypes was significantly more frequent in children who received IPV+bOPV than in those with bOPV only (p<0.001) in both strata. Shedding of polioviruses in stool did not differ between study groups and ranged from 2.4% (n=5) to 7.1% (n=15). In malnourished children the shedding was reduced after bOPV+IPV compared to bOPV only. Chronically malnourished infants were more likely to be unprotected against polioviruses than normal infants. bOPV+IPV helped close the immunity gap better than bOPV alone.

Project description:Postpartum hemorrhage (PPH) remains a major killer of women worldwide. Standard uterotonic treatments used to control postpartum bleeding do not always work and are not always available. Misoprostol's potential as a treatment option for PPH is increasingly known, but its use remains ad hoc and available evidence does not support the safety or efficacy of one particular regimen. This study aimed to determine the adjunct benefit of misoprostol when combined with standard oxytocics for PPH treatment.A randomized controlled trial was conducted in four Karachi hospitals from December 2005 - April 2007 to assess the benefit of a 600 mcg dose of misoprostol given sublingually in addition to standard oxytocics for postpartum hemorrhage treatment. Consenting women had their blood loss measured after normal vaginal delivery and were enrolled in the study after losing more than 500 ml of blood. Women were randomly assigned to receive either 600 mcg sublingual misoprostol or matching placebo in addition to standard PPH treatment with injectable oxytocics. Both women and providers were blinded to the treatment assignment. Blood loss was collected until active bleeding stopped and for a minimum of one hour after PPH diagnosis. Total blood loss, hemoglobin measures, and treatment outcomes were recorded for all participants.Due to a much lower rate of PPH than expected (1.2%), only sixty-one patients were diagnosed and treated for their PPH in this study, and we were therefore unable to measure statistical significance in any of the primary endpoints. The addition of 600 mcg sublingual misoprostol to standard PPH treatments does, however, suggest a trend in reduced postpartum blood loss, a smaller drop in postpartum hemoglobin, and need for fewer additional interventions. Women who bled less overall had a significantly smaller drop in hemoglobin and received fewer additional interventions. There were no hysterectomies or maternal deaths among study participants. The rate of transient shivering and fever was significantly higher among women receiving misoprostolA 600 mcg dose of misoprostol given sublingually shows promise as an adjunct treatment for PPH and its use should continue to be explored for its life-saving potential in the care of women experiencing PPH.Clinical trials.gov, Registry No. NCT00116480.

Project description:BackgroundCost-effective demand-side interventions are needed to increase childhood immunization. Multiple studies find tying income support programs (≥USD 50 per year) to immunization raises coverage. Research on maximizing impact from small mobile-based conditional cash transfers (mCCTs) (≤USD 15 per fully immunized child) delivered in lower-income settings remains sparse.MethodsParticipants in Karachi, Pakistan, were individually randomized into a seven arm, factorial open label study with five mCCT arms, one reminder (SMS) only arm, and one control arm. The mCCT arms varied by amount (high ∼USD 15 per fully immunized child versus low ∼USD 5 per fully immunized child), schedule (flat versus rising payments over the schedule), design (certain versus lottery payments), and payment method (airtime or mobile money). Children were enrolled at BCG, pentavalent-1 (penta-1) or pentavalent-2 (penta-2) vaccination and followed until at least 18 months of age. A serosurvey in 15% sub-sample validated reported study coverage. The full immunization coverage (FIC) at 12 months (primary outcome) was analyzed using logit regression. ClinicalTrials.gov (NCT03355989), 3ie registry (58f6ee7725fc1), and AEA RCT Registry (AEARCTR-0001953).FindingsBetween November 6, 2017, and October 10, 2018, a total of 11,197 caregiver-child pairs were enrolled, with 1598-1600 caregiver-child pairs per arm. FIC at 12 months was statistically significantly higher for any mCCT versus SMS (OR:1.18, 95% CI: 1.05-1.33; p = 0.005). Within the mCCT arms, FIC was statistically significantly higher for high versus low amount (OR: 1.16, 95% CI: 1.04-1.29; p = 0.007), certain versus lottery payment (OR: 1.30, 95% CI: 1.17-1.45; p < 0.001) and airtime versus mobile money (OR: 1.17, 95% CI:1.01-1.36; p = 0.043). There was no statistically significant difference between a flat and increasing schedule (OR: 1.03, 95% CI: 0.93-1.15; p = 0.550). SMS had a marginally statistically significant impact on FIC versus control (OR: 1.16, 95% CI: 1.00-1.35; p = 0.046). Findings were similar for up-to-date coverage of penta-3, measles-1 and measles-2 at 18 months.InterpretationSmall mCCTs (USD 0.8-2.4 per immunization visit) can increase FIC at 12 months and up-to-date coverage at 18 months at USD 23 per additional fully immunized child, in resource-constrained settings like Pakistan. Design details (certainty, schedule and delivery method of mCCTs) matter as much as the size of payments.FundingGlobal Innovation Fund, GiveWell.

Dataset Information

Immunogenicity of Different Routine Poliovirus Vaccination Schedules: A Randomized, Controlled Trial in Karachi, Pakistan.

Publications

Immunogenicity of Different Routine Poliovirus Vaccination Schedules: A Randomized, Controlled Trial in Karachi, Pakistan.

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