Observational analysis of the immunogenicity and safety of various types of spinal muscular atrophy vaccines.

BACKGROUND: This study aimed to evaluate the immunogenicity and safety of different types of poliovirus vaccines. METHODS: A randomized, blinded, single-center, parallel-controlled design was employed, and 360 infants aged ≥ 2 months were selected as study subjects. They were randomly assigned to bOPV group (oral Sabin vaccine) and sIPV group (Sabin strain inactivated polio vaccine), with 180 infants in each group. Adverse reaction events in the vaccinated subjects were recorded. The micro-neutralization test using cell culture was conducted to determine the geometric mean titer (GMT) of neutralizing antibodies against poliovirus types I, II, and III in different groups, and the seroconversion rates were calculated. RESULTS: Both groups exhibited a 100% seropositivity rate after booster immunization. The titers of neutralizing antibodies for the three types were predominantly distributed within the range of 1:128 to 1:512. The fold increase of type I antibodies differed markedly between the two groups (P < 0.05). Moreover, the fold increase of type II and type III antibodies for poliovirus differed slightly between the two groups (P > 0.05). The fourfold increase rate in sIPV group was drastically superior to that in bOPV group (P < 0.05). When comparing the post-immunization GMT levels of type I antibodies in individuals who completed the full course of spinal muscular atrophy vaccination, bOPV group showed greatly inferior levels to sIPV group (P < 0.05). For type II and type III antibodies, individuals in bOPV group demonstrated drastically superior post-immunization GMT levels to those in sIPV group (P < 0.05). The incidence of adverse reactions between the bOPV and sIPV groups differed slightly (P > 0.05). CONCLUSION: These findings indicated that both the oral vaccine and inactivated vaccine had good safety and immunogenicity in infants aged ≥ 2 months. The sIPV group generated higher levels of neutralizing antibodies in serum, particularly evident in the post-immunization GMT levels for types II and III.

Persistence of immunity following a single dose of inactivated poliovirus vaccine: a phase 4, open label, non-randomised clinical trial.

BACKGROUND: The polio eradication endgame required the withdrawal of Sabin type 2 from the oral poliovirus vaccine and introduction of one or more dose of inactivated poliovirus vaccine (IPV) into routine immunisation schedules. However, the duration of single-dose IPV immunity is unknown. We aimed to address this deficiency. METHODS: In this phase 4, open-label, non-randomised clinical trial, we assessed single-dose IPV immunity. Two groups of infants or children were screened: the first group had previously received IPV at 14 weeks of age or older (previous IPV group; age >2 years); the second had not previously received IPV (no previous IPV group; age 7-12 months). At enrolment, all participants received an IPV dose. Children in the no previous IPV group received a second IPV dose at day 30. Blood was collected three times in each group: on days 0, 7, and 30 in the previous IPV group and on days 0, 30, and 37 in the no previous IPV group. Poliovirus antibody was measured by microneutralisation assay. Immunity was defined as the presence of a detectable antibody or a rapid anamnestic response (ie, priming). We used the χ2 to compare proportions and the Mann-Whitney U test to assess continuous variables. To assess safety, vaccinees were observed for 30 min, caregivers for each participating child reported adverse events after each follow-up visit and were questioned during each follow-up visit regarding any adverse events during the intervening period. Adverse events were recorded and graded according to the severity of clinical symptoms. The study is registered with ClinicalTrials.gov, NCT03723837. FINDINGS: From Nov 18, 2018, to July 31, 2019, 502 participants enrolled in the study, 458 (255 [65%] boys and 203 [44%] girls) were included in the per protocol analysis: 234 (93%) in the previous IPV group and 224 (90%) in the no previous IPV group. In the previous IPV group, 28 months after one IPV dose 233 (>99%) of 234 children had persistence of poliovirus type 2 immunity (100 [43%] of 234 children were seropositive; 133 [99%] of 134 were seronegative and primed). In the no previous IPV group, 30 days after one IPV dose all 224 (100%) children who were type 2 poliovirus naive had seroconverted (223 [>99%] children) or were primed (one [<1%]). No adverse events were deemed attributable to study interventions. INTERPRETATION: A single IPV dose administered at 14 weeks of age or older is highly immunogenic and induces nearly universal type 2 immunity (seroconversion and priming), with immunity persisting for at least 28 months. The polio eradication initiative should prioritise first IPV dose administration to mitigate the paralytic burden caused by poliovirus type 2. FUNDING: WHO and Rotary International.

Severe immune thrombocytopenia following diphtheria, tetanus, pertussis and polio vaccination in a 36-year-old Caucasian woman: a case report.

BACKGROUND: Immune thrombocytopenia (ITP) is a rare autoimmune disorder characterized by low platelet counts and increased bleeding risk. The disease may be induced by other disorders, including malignancies, autoimmune diseases, infectious agents or drugs. However, ITP has also been described following vaccinations, such as the measles-mumps-rubella vaccination. In rare cases, ITP may occur in children who received a DTaP-IP (diphtheria, tetanus, acellular pertussis vaccine and inactivated poliovirus) vaccine. Hereinafter, we report the first well-documented cases of ITP in an adult patient in the temporal context of a DTaP-IP vaccination. CASE PRESENTATION: This case report attempts to capture the life-threatening picture of a 36-year-old otherwise healthy Caucasian woman with newly diagnosed severe immune thrombocytopenia in the temporal context of a DTaP-IP vaccination. Four days after receiving the vaccine, the women presented to her primary care physician with malaise, fever and recurrent epistaxis. Clinical examination revealed oral petechiae, ecchymoses, and non-palpable petechiae on both legs. The patient was immediately referred to a local hematology unit where she developed hematuria and an intestinal bleeding (WHO Bleeding Grade III) requiring multiple transfusions. After receiving oral corticosteroids and intravenous immunoglobulins, her platelets gradually recovered. Common causes of secondary ITP were ruled out by laboratory investigations, bone marrow and peripheral blood examinations. This raises the possibility of a (secondary) vaccination-associated thrombocytopenia. To the best of our knowledge, this is the first well-documented case of a DTaP-IP vaccination-related ITP in an adult patient in the English literature. CONCLUSION: Although a causal connection between both entities may not be established, we would like to raise awareness in clinicians that ITP following DTaP-IP vaccinations is potentially not limited to children, but may also occur in adults. Users of DTaP-IP booster vaccines should be alert of the possibility of such adverse reactions.

The moral dilemma of the polio eradication programme.

During the last five years, globally, cases of polio caused by vaccine viruses have outnumbered those of polio caused by natural (wild) polioviruses, posing a moral dilemma. Public health ethics should ensure the best interests of the community, with equity in sharing benefits and risks irrespective of socioeconomic disparities. Vaccine viruses in oral polio vaccine (OPV) cause vaccine-associated paralytic polio (VAPP), while paralytic polio is also caused by vaccine-derived polioviruses (VDPVs). By its policy of the use of OPV in low and middle-income countries, while rich countries use the safe inactivated polio vaccine (IPV), the Global Polio Eradication Programme has been responsible for social injustice. In 2017 and 2018, there were outbreaks of polio in Syria and Papua New Guinea due to circulating VDPVs, after many years of these countries remaining free of polio due to wild polioviruses. The only ethical way forward for global polio eradication is to replace OPV with IPV in all countries.

[A case of vaccine-associated paralytic poliomyelitis in an infant]. / Sluchai vaktsinoassotsiirovannogo paraliticheskogo poliomielita u rebenka.

AIM: To present the clinical history, vaccination status, features of the clinical picture, composition of the cerebrospinal fluid (CSF), results of laboratory and instrumental examinations of a patient with vaccine-associated paralytic poliomyelitis (VAPP). MATERIAL AND METHODS: In 2017, a child, aged 15 month, mistakenly vaccinated with the first dose of bivalent (types 1 & 3) polioviruses oral vaccine (OPV) was followed up. RESULTS AND CONCLUSION: Clinical parameters of VAPP in the recipient of OPV are considered. Clinical features of disease caused by wild poliovirus and VAPP are compared. The disease was characterized by sudden onset, recurrence, short (2-4 days) period of progression of paresis, persistent residual effects, CSF protein-cell dissociation. It is emphasized that the occurrence of VAPP cases reflects primarily immunization defects.

Introduction of Inactivated Poliovirus Vaccine and Impact on Vaccine-Associated Paralytic Poliomyelitis - Beijing, China, 2014-2016.

When included in a sequential polio vaccination schedule, inactivated polio vaccine (IPV) reduces the risk for vaccine-associated paralytic poliomyelitis (VAPP), a rare adverse event associated with receipt of oral poliovirus vaccine (OPV). During January 2014, the World Health Organization (WHO) recommended introduction of at least 1 IPV dose into routine immunization schedules in OPV-using countries (1). The Polio Eradication and Endgame Strategic Plan 2013-2018 recommended completion of IPV introduction in 2015 and globally synchronized withdrawal of OPV type 2 in 2016 (2). Introduction of 1 dose of IPV into Beijing's Expanded Program on Immunization (EPI) on December 5, 2014 represented China's first province-wide IPV introduction. Coverage with the first dose of polio vaccine was maintained from 96.2% to 96.9%, similar to coverage with the first dose of diphtheria and tetanus toxoids and pertussis vaccine (DTP) (96.5%-97.2%); the polio vaccine dropout rate (the percentage of children who received the first dose of polio vaccine but failed to complete the series) was 1.0% in 2015 and 0.4% in 2016. The use of 3 doses of private-sector IPV per child decreased from 18.1% in 2014, to 17.4% in 2015, and to 14.8% in 2016. No cases of VAPP were identified during 2014-2016. Successful introduction of IPV into the public sector EPI program was attributed to comprehensive planning, preparation, implementation, robust surveillance for adverse events after immunization (AEFI), and monitoring of vaccination coverage. This evaluation provided information that helped contribute to the expansion of IPV use in China and in other OPV-using countries.

[VACCINE-ASSOCIATED PARALYTIC POLIOMYELITIS IN RUSSIAN FEDERATION DURING THE PERIOD OF CHANGES IN VACCINATION SCHEDULE (2006-2013 yy.)].

The results of virologic testing of clinical materials and epidemiological analysis of vaccine-associated paralytic poliomyelitis (VAPP) cases obtained in 2006-2013 during AFP surveillance are presented. Among the 2976 cases of AFP 30 cases were VAPP. 15 cases were observed in OPV recipients, whereas 15 cases were observed in non-vaccinated contacts. The age of the patients varied from 4 months to 5.5 years (13.6 ± 12.4 months old). Children younger than 1 year constituted 63.3% of the group; boys were dominant (73.3%); 53.3% of children were vaccinated with OPV; the time period between receipt of OPV and onset of palsy was from 2 to 32 days (18.7 ± 8.2). Lower paraparesis was documented in 48.3% of patients; lower monoparesis in 37.9%; upper monoparesis, in 6.9%; tetraparesis with bulbar syndrome, in 6%. The majority of the patients (85.7%) had an unfavorable premorbid status. The violations of the humoral immunity were found in 73.9% cases: CVID (52.9%), hypogammaglobulinemia (41.2%); selective lgA deflciency (5.9%). In 70.6% cases damage to humoral immunity was combined with poor premorbid status. The most frequently observed (76%, p < 0.05) represented the single type of poliovirus--type 2 (44%) and type 3 (32%). All strains were of the vaccine origin, the divergence from the homotypic Sabin strains fell within the region of the gene encoding VPI protein, which did not exceed 0.5% of nucleotide substitutions except vaccine derived poliovirus type 2--multiple recombinant (type 2/type 3/ type 2/type 1) with the degree of the divergence of 1.44% isolated from 6-month old unvaccinated child (RUS08063034001). The frequency of the VAPP cases was a total of 1 case per 3.4 million doses of distributed OPV in 2006-2013; 2.2 cases per 1 million of newborns were observed. This frequency decreased after the introduction of the sequential scheme of vaccination (IPV, OPV) in 2008-2013 as compared with the period of exclusive use of OPV in 2006-2007: 1 case per 4.9 million doses, 1.4 cases per million newborns and 1 case per 1.9 million doses, 4.9 cases per 1 million newborns, respectively. The study has been financed from Russian Federation budget within the framework of the Program for eradication of poliomyelitis in the Russian Federation, WHO Polio eradication initiative, WHO's European Regional Bureau, Russian Foundation for Basic Research (project No. 15-15-00147).

Bcgitis and vaccine-derived poliovirus infection in a patient with a novel deletion in RAG1 binding site.

A girl who developed severe BCGitis and vaccine-derived poliovirus infection was discovered to have a novel deletion of RAG1. A neonatal screening program for SCID would identify affected infants at birth, before live vaccines are administered.

The effect of infliximab on antiviral antibody profiles in patients with rheumatoid arthritis.

The duration of humoral immunity in patients treated with immunosuppressive drugs is poorly defined. The objective of the study was to investigate the effect of infliximab on the levels of antiviral antibodies against poliomyelitis, rubella and measles in rheumatoid arthritis (RA) patients. Fifty-two consecutive RA patients being treated with 3 mg/kg infliximab were prospectively studied. The antiviral antibody profiles for measles, rubella and three serotypes of poliomyelitis were tested on the day of the first infusion of infliximab and 6 months later. The study group comprised 36 women and 16 men (mean age 54 years, range 33-81) with a mean disease duration of 15 +/- 9 years. Forty-two (81%) patients were being treated with methotrexate and 22 (42%) were receiving prednisone. All patients had baseline protective levels of antibodies against measles and the three strains of polio, while 48 (92%) patients had protective antibodies against rubella. No significant change in the levels of antiviral antibodies was observed after 6 months of treatment with infliximab: from 3.67 at baseline to 3.87 IU/ml for measles, 169.50-197.0 IU/ml for rubella. No change was noticed for the geometric mean concentrations of antibodies against strains of poliomyelitis: 366-478 IU/ml for the Mahoney polio strain, 906-845 IU/ml for the MEF strain and 175-196 IU/ml for the Sauket strain. Patients with longstanding RA conserve long-term immunity to common viruses despite the use of immunosuppressive drugs. Levels of antiviral antibodies against measles, rubella and polio remain stable under treatment with infliximab.

Vaccine-associated paralytic poliomyelitis: a case report of flaccid monoparesis after oral polio vaccine.

This report describes a case of acute flaccid paralysis after administration of oral polio vaccine (OPV). A 4 month-old male patient with the decreased movement of left lower extremity for 1 month was transferred to the Department of Pediatrics. He received OPV with DTaP at 2 months of age. Flaccid paralysis was detected 4 weeks after OPV immunization. Attempts to isolate Sabin-like viruses in the two stool and CSF samples failed because those specimens were collected more than 2 month after the onset of paralysis. Hypotonic monoparesis (GIV/V), hypotonia and atrophy on the left lower extremity, and ipsilateral claw foot persisted for more than 18 months, while we followed him with rehabilitation therapy. This is the first case of officially approved, recipient vaccine-associated paralytic poliomyelitis in Korea.

Neurological morbidity in vaccine-associated paralytic poliomyelitis in Brazil from 1989 up to 1995.

UNLABELLED: We collected 30 cases of vaccine associated paralytic poliomyelitis (VAPP) from 4081 cases of acute flaccid palsies cases notified from 1989 to 1995 to the Brazilian Ministry of Health. There were 30 VAPP cases with 56% of children younger than 1 year old, 56.7% of female. 46% of cases were reported in the Northeast. Ten P2 vaccine virus, 8 P3 and 2 P1 and associations amongst them were isolated. The clinical pattern in 60 days was: monoplegia (16), paraplegia (6), tetraplegia (5), hemiplegia (2) and triplegia (1). There was no strong relationship between fever, before or after the prodrome period, or the use of intramuscular medication to morbidity. CONCLUSION: if the anti-poliomyelitis strategy adopted in Brazil has lead to the eradication of the poliomyelitis with wild virus infection, the existence of a minimum risk of vaccine-associated poliomyelitis is a matter of concern because there will be a permanent neurological deficit.

Neurological morbidity in vaccine-associated paralytic poliomyelitis in Brazil: from 1989 up to 1995

Trinta casos de poliomielite associada à vacinação oral (Sabin) foram estudados a partir de 4081 notificações de paralisias agudas e flácidas feitas ao Ministério da Saúde no período de 1989 a 1995, com o objetivo de avaliar a gravidade do quadro neurológico. Dezesseis pacientes tiveram monoplegia, 6 paraplegia, 5 tetraplegia, 2 hemiplegia e 1 triplegia. Foram 56% em menores de 1 ano, 56,7% no sexo feminino, 46% dos casos provenientes do nordeste. Em 10 pacientes foi isolado o vírus vacinal P2, em oito o P3 e dois o P1. Os demais tinham associações de mais de um tipo de vírus. Febre antes ou após o período prodrômico e o uso de medicação intramuscular não se relacionaram a maior morbidade. A política antipoliomielite adotada no Brasil levou à erradicação da poliomielite pelo vírus selvagem com um risco mínimo do ponto de vista epidemiológico, porém ainda com custos individuais não desprezíveis.

Cost analysis of post-polio certification immunization policies.

OBJECTIVE: An analysis was conducted to estimate the costs of different potential post-polio certification immunization policies currently under consideration, with the objective of providing this information to policy-makers. METHODS: We analyzed three global policy options: continued use of oral poliovirus vaccine (OPV); OPV cessation with optional inactivated poliovirus vaccine (IPV); and OPV cessation with universal IPV. Assumptions were made on future immunization policy decisions taken by low-, middle-, and high-income countries. We estimated the financial costs of each immunization policy, the number of vaccine-associated paralytic poliomyelitis (VAPP) cases, and the global costs of maintaining an outbreak response capacity. The financial costs of each immunization policy were based on estimates of the cost of polio vaccine, its administration, and coverage projections. The costs of maintaining outbreak response capacity include those associated with developing and maintaining a vaccine stockpile in addition to laboratory and epidemiological surveillance. We used the period 2005-20 as the time frame for the analysis. FINDINGS: OPV cessation with optional IPV, at an estimated cost of US$ 20,412 million, was the least costly option. The global cost of outbreak response capacity was estimated to be US$ 1320 million during 2005-20. The policy option continued use of OPV resulted in the highest number of VAPP cases. OPV cessation with universal IPV had the highest financial costs, but it also had the least number of VAPP cases. Sensitivity analyses showed that global costs were sensitive to assumptions on the cost of the vaccine. Analysis also showed that if the price per dose of IPV was reduced to US$ 0.50 for low-income countries, the cost of OPV cessation with universal IPV would be the same as the costs of continued use of OPV. CONCLUSION: Projections on the vaccine price per dose and future coverage rates were major drivers of the global costs of post-certification polio immunization. The break-even price of switching to IPV compared with continuing with OPV immunizations is US$ 0.50 per dose of IPV. However, this doses not account for the cost of vaccine-derived poliovirus cases resulting from the continued use of OPV. In addition to financial costs, risk assessments related to the re-emergence of polio will be major determinants of policy decisions.

A developing country perspective on vaccine-associated paralytic poliomyelitis.

When the Expanded Programme on Immunization was established and oral poliovirus vaccine (OPV) was introduced for developing countries to use exclusively, national leaders of public health had no opportunity to make an informed choice between OPV and the inactivated poliovirus vaccine (IPV). Today, as progress is made towards the goal of global eradication of poliomyelitis attributable to wild polioviruses, all developing countries where OPV is used face the risk of vaccine-associated paralytic poliomyelitis (VAPP). Until recently, awareness of VAPP has been poor and quantitative risk analysis scanty but it is now well known that the continued use of OPV perpetuates the risk of VAPP. Discontinuation or declining immunization coverage of OPV will increase the risk of emergence of circulating vaccine-derived polioviruses (cVDPV) that re-acquire wild virus-like properties and may cause outbreaks of polio. To eliminate the risk of cVDPV, either very high immunization coverage must be maintained as long as OPV is in use, or IPV should replace OPV. Stopping OPV without first achieving high immunization coverage with IPV is unwise on account of the possibility of emergence of cVDPV. Increasing numbers of developed nations prefer IPV, and manufacturing capacities have not been scaled up, so its price remains prohibitively high and unaffordable by developing countries, where, in addition, large-scale field experience with IPV is lacking. Under these circumstances, a policy shift to increase the use of IPV in national immunization programmes in developing countries is a necessary first step; once IPV coverage reaches high levels (over 85%), the withdrawal of OPV may begin.

Vaccine associated paralytic poliomyelitis.

Vaccine Associated Paralytic Poliomyelitis (VAPP), although a known hazard with Oral Polio Vaccine (OPV), has not received adequate attention in India despite increasing use of OPV in repeated rounds of national immunization days. An analysis by National Polio Surveillance Project in 1999 suggested that incidence of VAPP is lower in India compared to that in the developed countries. However a re-analysis of the NPSP data suggests that the incidence in India is likely to be 1 in 1.5-2.0 million doses, which is higher than that reported elsewhere. Since 1999, the number of AFP cases in which the vaccine virus has been isolated, has progressively gone down, despite increasing number of OPV doses being administered in the national program. This contradictory phenomenon is difficult to explain unless either the doses being actually given are much less than those recorded or the vaccine being given is not potent. It is essential that the problem of VAPP is looked at in depth, and if it reveals that it is a significant problem then it would be imperative to gradually replace OPV by IPV in the national program. This article suggests a plan for gradual introduction of IPV in the national program, which will not only eliminate the problem of VAPP but also address other post polio eradication concerns.