UNASSIGNED: Vaccine-associated paralytic poliomyelitis (VAPP) is a rare adverse event of oral poliovirus vaccines (OPV), particularly affecting immunodeficient individuals.
UNASSIGNED: This study aimed to (1) Assess the association between OPV and VAPP using Vaccine Adverse Event Reporting System (VAERS) database (2) Outline patient characteristics and risk factors associated with the occurrence of VAPP in OPV recipients through a systematic review of case reports and case series. A disproportionality analysis was conducted using the data from VAERS, encompassing adverse events reported from 1990 till February 2023. Additionally, we conducted a systematic review of case reports and case series using PubMed, Scopus, and Embase databases.
UNASSIGNED: The VAERS data revealed 130 VAPP reports among 1,739,903 OPV linked adverse events, with year 2010 reporting the strongest association. The systematic review of 37 studies highlighted VAPP occurrence within 2 months to 4 years post-vaccination, typically with acute flaccid paralysis. Immunodeficiency and perianal abscess emerged as major risk factors. Out of the 37 included studies, 27 showed consistent causal association of VAPP with OPV using WHO-AEFI causality assessment tool.
UNASSIGNED: The study emphasized the seriousness of VAPP and highlights its association with OPV, identifying immunodeficiency as a prominent contributor to VAPP manifestation.

The introduction of anti-poliomyelitis vaccines has driven progress toward the global eradication of wild polioviruses, a millennium goal of the World Health Organization. With the vaccination campaigns carried out since 1964, in 2002 Italy was certified polio-free, considering that no cases had been recorded since 1983. Nevertheless, it is crucial to guarantee high level of immunization coverage also in low-endemicity countries, considering that sporadic polio cases can be recorded. To evaluate the presence of susceptible subjects in the population, seroepidemiological studies are key actions.
We conducted a systematic review of the relevant literature to evaluate the prevalence of anti-PV neutralizing antibodies in Italian population. Seven studies, selected among scientific articles available in MEDLINE/PubMed, ISI Web of Knowledge and Scopus and published from January 1, 2012, to November 15, 2022, were included.
The pooled prevalence of subjects without PV1 neutralizing antibodies was 6.4% (95%CI = 0.5-16.9), for PV2 it was 5.3% (95%CI = 0.4-14.2), and for PV3 it was 13.0% (95%CI = 4.0-25.7; I2 = 98.5%). Levels of neutralizing antibodies appears to decrease with increasing age; this decline is a proxy for the real risk factor, which is the time since the last vaccine dose.
Public health institutions must be aware of the risk of reintroduction of wild PV in polio-free countries and therefore they must keep high level of immunization in population and reinforce the active surveillance systems.

Delivering inactivated poliovirus vaccine (IPV) with oral poliovirus vaccine (OPV) in campaigns has been explored to accelerate the control of type 2 circulating vaccine-derived poliovirus (cVDPV) outbreaks. A review of scientific literature suggests that among populations with high prevalence of OPV failure, a booster with IPV after at least two doses of OPV may close remaining humoral and mucosal immunity gaps more effectively than an additional dose of trivalent OPV. However, IPV alone demonstrates minimal advantage on humoral immunity compared with monovalent and bivalent OPV, and cannot provide the intestinal immunity that prevents infection and spread to those individuals not previously exposed to live poliovirus of the same serotype (i.e. type 2 for children born after the switch from trivalent to bivalent OPV in April 2016). A review of operational data from polio campaigns shows that addition of IPV increases the cost and logistic complexity of campaigns. As a result, campaigns in response to an outbreak often target small areas. Large campaigns require a delay to ensure logistics are in place for IPV delivery, and may need implementation in phases that last several weeks. Challenges to delivery of injectable vaccines through house-to-house visits also increases the risk of missing the children who are more likely to benefit from IPV: those with difficult access to routine immunization and other health services. Based upon this information, the Strategic Advisory Group of Experts in immunization (SAGE) recommended in October 2020 the following strategies: provision of a second dose of IPV in routine immunization to reduce the risk and number of paralytic cases in countries at risk of importation or new emergences; and use of type 2 OPV in high-quality campaigns to interrupt transmission and avoid seeding new type 2 cVDPV outbreaks.

Vaccination is an effective strategy to reduce the burden of preventable illness. However, many clinical reports revealed that various vaccinations may associate with neurological disorders, mainly including autoimmune disease, febrile seizure, and vaccine-associated paralytic poliomyelitis (VAPP). Although more and more reports revealed that part of the above post-vaccine neurological disorders is not directly related to vaccination, it may be merely a coincidence. However, these reports may increase the hesitancy on vaccination for the public population and influence the coverage of vaccination. In this report, we described a child with acute flaccid paralysis possibly caused by a poliovirus vaccine. To provide feasible ways to realize or reduce the risk of neurological adverse events caused by vaccines, we further provide a mini-review of the literature of vaccination associated with neurological adverse events. This revealed that oral poliomyelitis vaccine use exclusively and type 2 serotype poliomyelitis vaccine virus were the risk factors for VAPP. The combination vaccine was associated with an increased risk of ADEM and FS following immunization when compared with the administration of vaccines separately. Even though cases have been reported that vaccination may be a trigger of anti-NMDARe and GBS, there is no direct evidence to prove that vaccination increased the risk of GBS and anti-NMDARe.

The eradication of wild and vaccine-derived poliovirus requires the global withdrawal of oral poliovirus vaccines (OPVs) and replacement with inactivated poliovirus vaccines (IPVs). The first phase of this effort was the withdrawal of the serotype 2 vaccine in April 2016, with a switch from trivalent OPVs to bivalent OPVs. The aim of our study was to produce comparative estimates of humoral and intestinal mucosal immunity associated with different routine immunisation schedules.
We did a random-effect meta-analysis with single proportions and a network meta-analysis in a Bayesian framework to synthesise direct and indirect data. We searched MEDLINE and the Cochrane Library Central Register of Controlled Trials for randomised controlled trials published from Jan 1, 1980, to Nov 1, 2018, comparing poliovirus immunisation schedules in a primary series. Only trials done outside western Europe or North America and without variation in age schedules (ie, age at administration of the vaccine) between study groups were included in the analyses, because trials in high-income settings differ in vaccine immunogenicity and schedules from other settings and to ensure consistency within the network of trials. Data were extracted directly from the published reports. We assessed seroconversion against poliovirus serotypes 1, 2, and 3, and intestinal immunity against serotype 2, measured by absence of shedding poliovirus after a challenge OPV dose.
We identified 437 unique studies; of them, 17 studies with a maximum of 8279 evaluable infants were eligible for assessment of humoral immunity, and eight studies with 4254 infants were eligible for intestinal immunity. For serotype 2, there was low between-trial heterogeneity in the data (τ=0·05, 95% credible interval [CrI] 0·009-0·15) and the risk ratio (RR) of seroconversion after three doses of bivalent OPVs was 0·14 (95% CrI 0·11-0·17) compared with three doses of trivalent OPVs. The addition of one or two full doses of an IPV after a bivalent OPV schedule increased the RR to 0·85 (0·75-1·0) and 1·1 (0·98-1·4). However, the addition of an IPV to bivalent OPV schedules did not significantly increase intestinal immunity (0·33, 0·18-0·61), compared with trivalent OPVs alone. For serotypes 1 and 3, there was susbstantial inconsistency and between-trial heterogeneity between direct and indirect effects, so we only present pooled estmates on seroconversion, which were at least 80% for serotype 1 and at least 88% for serotype 3 for all vaccine schedules.
For WHO\'s polio eradication programme, the addition of one IPV dose for all birth cohorts should be prioritised to protect against paralysis caused by type 2 poliovirus; however, this inclusion will not prevent transmission or circulation in areas with faecal-oral transmission.
UK Medical Research Council.

Oral vaccines underperform in low-income and middle-income countries compared with in high-income countries. Whether interventions can improve oral vaccine performance is uncertain.
We did a systematic review and meta-analysis of interventions designed to increase oral vaccine efficacy or immunogenicity. We searched Ovid-MEDLINE and Embase for trials published until Oct 23, 2017. Inclusion criteria for meta-analysis were two or more studies per intervention category and available seroconversion data. We did random-effects meta-analyses to produce summary relative risk (RR) estimates. This study is registered with PROSPERO (CRD42017060608).
Of 2843 studies identified, 87 were eligible for qualitative synthesis and 66 for meta-analysis. 22 different interventions were assessed for oral poliovirus vaccine (OPV), oral rotavirus vaccine (RVV), oral cholera vaccine (OCV), and oral typhoid vaccines. There was generally high heterogeneity. Seroconversion to RVV was significantly increased by delaying the first RVV dose by 4 weeks (RR 1·37, 95% CI 1·16-1·62) and OPV seroconversion was increased with monovalent or bivalent OPV compared with trivalent OPV (RR 1·51, 95% CI 1·20-1·91). There was some evidence that separating RVV and OPV increased RVV seroconversion (RR 1·21, 95% CI 1·00-1·47) and that higher vaccine inoculum improved OCV seroconversion (RR 1·12, 95% CI 1·00-1·26). There was no evidence of effect for anthelmintics, antibiotics, probiotics, zinc, vitamin A, withholding breastfeeding, extra doses, or vaccine buffering.
Most strategies did not improve oral vaccine performance. Delaying RVV and reducing OPV valence should be considered within immunisation programmes to reduce global enteric disease. New strategies to address the gap in oral vaccine efficacy are urgently required.
Wellcome Trust, Bill & Melinda Gates Foundation, UK Medical Research Council, and WHO Polio Research Committee.

In May 2016, countries using oral polio vaccine for routine immunization switched from trivalent oral poliovirus vaccine (tOPV) to bivalent type 1 and 3 OPV (bOPV). This was done in order to reduce risks from type 2 vaccine-derived polioviruses (VDPV2) and vaccine-associated paralytic poliomyelitis (VAPP) and to introduce ≥1 dose of inactivated poliovirus vaccine (IPV) to mitigate post-switch loss of type 2 immunity. We conducted a literature review of studies that assessed humoral and intestinal immunogenicity induced by the newly recommended schedules. Differences in seroconversion rates were closely associated with both timing of first IPV administration and number of doses administered. All studies demonstrated high levels of immunity for types 1 and 3 regardless of immunization schedule. When administered late in the primary series, a second dose of IPV closed the humoral immunity gap against polio type 2 associated with a single dose. IPV doses and administration schedules appear to have limited impact on type 2 excretion following challenge.

The emergence of vaccine-associated paralytic poliomyelitis has become an ongoing burden of poliomyelitis. During this special period from OPV to IPV-only immunization schedule, we did a meta-analysis to compare the immunogenicity of sequential IPV and OPV versus IPV alone in healthy infants.
This systematic review and meta-analysis was registered at international prospective register of systematic reviews (PROSPERO), and the number was CRD42017054889. We performed it as described.
Finally, 6 articles were qualified for our review. The results showed that seroconversion rates against all 3 serotype polioviruses were non-inferior and Geometric mean antibody titers (GMTs) were superior in sequential schedules compared with IPV-only schedule. Thus, the sequential vaccination schedules could induce a stronger immunogenicity.
To decrease vaccine-associated and vaccine-derived poliomyelitis, it is a reasonable option to select sequential schedules during this special transition from OPV to IPV-only immunization schedule, which coincides with the current WHO recommendations.

The use of oral poliovirus vaccine in a worldwide scale has led to a 99.9% decrease in annual incidence of wild-type poliomyelitis and the eradication of serotype 2 poliovirus. However, the emergence of vaccine-derived polioviruses (VDPVs) is endangering the eradication program. Patients with combined immunodeficiencies are at increased risk of both vaccine-associated poliomyelitis and prolonged asymptomatic infection with immunodeficiency-associated VDPVs (iVDPVs). Herein, we present a severe combined immunodeficiency patient with prolonged and asymptomatic iVDPV infection. He continued to shed poliovirus during immunoglobulin replacement therapy and cleared the infection following successful hematopoietic stem cell transplantation (HSCT). To explain the efficiency of HSCT in clearing the infection, we reviewed the literature for all reports of HSCT in iVDPV-excreting patients and discussed novel ideas about the role of different immune mechanisms, including cell-mediated interactions, in mounting immune responses against poliovirus infections. This study could provide further insights into the immune mechanisms contributing to the clearance of enteroviral infections.

Widespread administration of oral poliovirus vaccine (OPV) has decreased global incidence of poliomyelitis by ≈99.9%. However, the emergence of vaccine-derived polioviruses (VDPVs) is threatening polio-eradication program. Primary immunodeficiency (PID) patients are at higher risks of vaccine-associated paralytic poliomyelitis (VAPP) and prolonged excretion of immunodeficiency-associated VDPV (iVDPV). We searched Embase, Medline, Science direct, Scopus, Web of Science, and CDC and WHO databases by 30 September 2016, for all reports of iVDPV cases. Patient-level data were extracted form eligible studies. Data on immunization coverage and income-level of countries were extracted from WHO/UNICEF and the WORLD BANK databases, respectively. We assessed bivariate associations between immunological, clinical, and virological parameters, and exploited multivariable modeling to identify independent determinants of poliovirus evolution and patients\' outcomes. Study protocol was registered with PROSPERO (CRD42016052931). 4329 duplicate-removed titles were screened. A total of 107 iVDPV cases were identified from 68 eligible articles. The majority of cases were from higher income countries with high polio-immunization coverage. 74 (69.81%) patients developed VAPP. Combined immunodeficiency patients showed lower rates of VAPP (p < .001) and infection clearance (p = .02), compared to humoral immunodeficiency patients. The rate of poliovirus genomic evolution was higher at early stages of replication, decreasing over time until reaching a steady state. Independent of replication duration, higher extent (p = .04) and rates (p = .03) of genome divergence contributed to a less likelihood of virus clearance. PID type (p < .001), VAPP occurrence (p = .008), and income-level of country (p = .04) independently influenced patients\' survival. With the use of OPV, new iVDPVs will emerge independent of the rate of immunization coverage. Inherent features of PIDs contribute to the clinical course of iVDPV infection and virus evolution. This finding could shed further light on poliomyelitis pathogenesis and iVDPV evolution pattern. It also has implications for public health, the polio eradication effort and the development of effective antiviral interventions.