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Evaluation of vaccine derived poliovirus type 2 outbreak response options: A randomized controlled trial, Karachi, Pakistan.

ABSTRACT: BACKGROUND:Outbreaks of circulating vaccine derived polioviruses type 2 (cVDPV2) remain a risk to poliovirus eradication in an era without live poliovirus vaccine containing type 2 in routine immunization. We evaluated existing outbreak response strategies recommended by the World Health Organization (WHO) for control of cVDPV2 outbreaks. METHODS:Seronegative children for poliovirus type 2 (PV2) at 22?weeks of life were assigned to one of four study groups and received respectively (1) one dose of trivalent oral poliovirus vaccine (tOPV); (2) monovalent OPV 2 (mOPV2); (3) tOPV together with a dose of inactivated poliovirus vaccine (IPV); or (4) mOPV2 with monovalent high-potency IPV type 2. Stool and blood samples were collected and assessed for presence of PV2 (stool) and anti-polio antibodies (sera). RESULTS:We analyzed data from 265 children seronegative for PV2. Seroconversion to PV2 was achieved in 48, 76, 98 and 100% in Groups 1-4 respectively. mOPV2 was more immunogenic than tOPV alone (p?

SUBMITTER: Saleem AF

PROVIDER: S-EPMC5869272 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Evaluation of vaccine derived poliovirus type 2 outbreak response options: A randomized controlled trial, Karachi, Pakistan.

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

Vaccine 20180221 13

<h4>Background</h4>Outbreaks of circulating vaccine derived polioviruses type 2 (cVDPV2) remain a risk to poliovirus eradication in an era without live poliovirus vaccine containing type 2 in routine immunization. We evaluated existing outbreak response strategies recommended by the World Health Organization (WHO) for control of cVDPV2 outbreaks.<h4>Methods</h4>Seronegative children for poliovirus type 2 (PV2) at 22 weeks of life were assigned to one of four study groups and received respectivel ...[more]

PMID: 29477307

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Project description:BackgroundSince July 2019, Pakistan and Afghanistan have been facing an outbreak of serotype-2 circulating vaccine derived poliovirus (cVDPV2) in addition to continued transmission of serotype-1 wild poliovirus (WPV1) and SARS-CoV-2 in 2020. Understanding the risks of cVDPV2 transmission due to pause of global vaccination efforts and the impact of potential vaccination response strategies in the current context of COVID-19 mitigation measures is critical.MethodsWe developed a stochastic, geographically structured mathematical model of cVDPV2 transmission which captures both mucosal and humoral immunity separately and allows for reversion of serotype-2 oral polio vaccine (OPV2) virus to cVDPV2 following vaccine administration. The model includes geographic heterogeneities in vaccination coverage, population immunity and population movement. The model was fitted to historic cVDPV2 cases in Pakistan and Afghanistan between January 2010-April 2016 and July 2019-March 2020 using iterated particle filtering. The model was used to simulate spread of cVDPV2 infection from July 2019 to explore impact of various proposed vaccination responses on stopping transmission and risk of spread of reverted Sabin-2 under varying assumptions of impacts from COVID-19 lockdown measures on movement patterns as well as declines in vaccination coverage.ResultsSimulated monthly incidence of cVDPV2 from the best-fit model demonstrated general spatio-temporal alignment with observed cVDPV2 cases. The model predicted substantial spread of cVDPV2 infection, with widespread transmission through 2020 in the absence of any vaccination activities. Vaccination responses were predicted to substantially reduce transmission and case burden, with a greater impact from earlier responses and those with larger geographic scope. While the greatest risk of seeding reverted Sabin-2 was predicted in areas targeted with OPV2, subsequent spread was greatest in areas with no or delayed response. The proposed vaccination strategy demonstrated ability to stop the cVDPV2 outbreak (with low risk of reverted Sabin-2 spread) by February 2021.ConclusionOutbreak response vaccination campaigns against cVDPV2 will be challenging throughout the COVID-19 pandemic but must be implemented urgently when feasible to stop transmission of cVDPV2.

Project description:Delays in achieving polio eradication have led to ongoing risks of poliovirus importations that may cause outbreaks in polio-free countries. Because of the low, but non-zero risk of paralysis with oral poliovirus vaccines (OPVs), countries that achieve and maintain high national routine immunization coverage have increasingly shifted to exclusive use of inactivated poliovirus vaccine (IPV) for all preventive immunizations. However, immunization coverage within countries varies, with under-vaccinated subpopulations potentially able to sustain transmission of imported polioviruses and experience local outbreaks. Due to its cost, ease-of-use, and ability to induce mucosal immunity, using OPV as an outbreak control measure offers a more cost-effective option in countries in which OPV remains in use. However, recent polio outbreaks in IPV-only countries raise questions about whether and when IPV use for outbreak response may fail to stop poliovirus transmission and what consequences may follow from using OPV for outbreak response in these countries. We systematically reviewed the literature to identify modeling studies that explored the use of IPV for outbreak response in IPV-only countries. In addition, applying a model of the 2022 type 2 poliovirus outbreak in New York, we characterized the implications of using different OPV formulations for outbreak response instead of IPV. We also explored the hypothetical scenario of the same outbreak except for type 1 poliovirus instead of type 2. We find that using IPV for outbreak response will likely only stop outbreaks for polioviruses of relatively low transmission potential in countries with very high overall immunization coverage, seasonal transmission dynamics, and only if IPV immunization interventions reach some unvaccinated individuals. Using OPV for outbreak response in IPV-only countries poses substantial risks and challenges that require careful consideration, but may represent an option to consider for some outbreaks in some populations depending on the properties of the available vaccines and coverage attainable.

Project description:BackgroundTo inform response strategies, we examined type 1 humoral and intestinal immunity induced by 1) one fractional inactivated poliovirus vaccine (fIPV) dose given with monovalent oral poliovirus vaccine (mOPV1), and 2) mOPV1 versus bivalent OPV (bOPV).MethodsWe conducted a randomized, controlled, open-label trial in Dhaka, Bangladesh. Healthy infants aged 5 weeks were block randomized to one of four arms: mOPV1 at age 6-10-14 weeks/fIPV at 6 weeks (A); mOPV1 at 6-10-14 weeks/fIPV at 10 weeks (B); mOPV1 at 6-10-14 weeks (C); and bOPV at 6-10-14 weeks (D). Immune response at 10 weeks and cumulative response at 14 weeks was assessed among the modified intention-to-treat population, defined as seroconversion from seronegative (<1:8 titers) to seropositive (≥1:8) or a four-fold titer rise among seropositive participants sustained to age 18 weeks. We examined virus shedding after two doses of mOPV1 with and without fIPV, and after the first mOPV1 or bOPV dose. The trial is registered at ClinicalTrials.gov (NCT03722004).FindingsDuring 18 December 2018 - 23 November 2019, 1,192 infants were enrolled (arms A:301; B:295; C:298; D:298). Immune responses at 14 weeks did not differ after two mOPV1 doses alone (94% [95% CI: 91-97%]) versus two mOPV1 doses with fIPV at 6 weeks (96% [93-98%]) or 10 weeks (96% [93-98%]). Participants who received mOPV1 and fIPV at 10 weeks had significantly lower shedding (p < 0·001) one- and two-weeks later compared with mOPV1 alone. Response to one mOPV1 dose was significantly higher than one bOPV dose (79% versus 67%; p < 0·001) and shedding two-weeks later was significantly higher after mOPV1 (76% versus 56%; p < 0·001) indicating improved vaccine replication. Ninety-nine adverse events were reported, 29 serious including two deaths; none were attributed to study vaccines.InterpretationGiven with the second mOPV1 dose, fIPV improved intestinal immunity but not humoral immunity. One mOPV1 dose induced higher humoral and intestinal immunity than bOPV.FundingU.S. Centers for Disease Control and Prevention.

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:BackgroundPostpartum 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.MethodsA 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.ResultsDue 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 misoprostolConclusionA 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.Trial registrationClinical trials.gov, Registry No. NCT00116480.

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Evaluation of vaccine derived poliovirus type 2 outbreak response options: A randomized controlled trial, Karachi, Pakistan.

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Evaluation of vaccine derived poliovirus type 2 outbreak response options: A randomized controlled trial, Karachi, Pakistan.

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