Case of Poliomyelitis Caused by Significantly Diverged Derivative of the Poliovirus Type 3 Vaccine Sabin Strain Circulating in the Orphanage.

Significantly divergent polioviruses (VDPV) derived from the oral poliovirus vaccine (OPV) from Sabin strains, like wild polioviruses, are capable of prolonged transmission and neuropathology. This is mainly shown for VDPV type 2. Here we describe a molecular-epidemiological investigation of a case of VDPV type 3 circulation leading to paralytic poliomyelitis in a child in an orphanage, where OPV has not been used. Samples of feces and blood serum from the patient and 52 contacts from the same orphanage were collected twice and investigated. The complete genome sequencing was performed for five polioviruses isolated from the patient and three contact children. The level of divergence of the genomes of the isolates corresponded to approximately 9-10 months of evolution. The presence of 61 common substitutions in all isolates indicated a common intermediate progenitor. The possibility of VDPV3 transmission from the excretor to susceptible recipients (unvaccinated against polio or vaccinated with inactivated poliovirus vaccine, IPV) with subsequent circulation in a closed children's group was demonstrated. The study of the blood sera of orphanage residents at least twice vaccinated with IPV revealed the absence of neutralizing antibodies against at least two poliovirus serotypes in almost 20% of children. Therefore, a complete rejection of OPV vaccination can lead to a critical decrease in collective immunity level. The development of new poliovirus vaccines that create mucosal immunity for the adequate replacement of OPV from Sabin strains is necessary.

Immunity status against poliomyelitis in young migrants: a seroprevalence study.

BACKGROUND AND AIM OF THE WORK: Recent seroprevalence studies in different population groups have shown low antibody titers against poliomyelitis, especially in young adults. This, together with the reduction of vaccination rates, could favor the reintroduction of poliovirus in long-time polio-free countries. Within the Surveillance system of acute flaccid paralysis, a prevalence study was conducted to estimate the immunological status associated with poliomyelitis in young migrants. METHODS: Local Health Authority collected serum samples in young migrants, without vaccination documentation. Antibodies levels were assessed with a long incubation neutralization assay. Subjects were stratified by age and by WHO region. Seroprotection was defined by a titer equal or above 1:8 and titers > 1:2 were log-transformed and evaluated as geometric mean titers (GMTs). RESULTS: From January 2004 to August 2017, 1138 blood samples were collected. Mean age was 13.3 years with no differences between WHO regions. The percentage of antibody titers below 1:8 was 6.0% versus poliovirus 1 (PV1), 7.7% versus poliovirus 2 (PV2) and 15% versus poliovirus 3 (PV3). The GMTs were 45.5, 29.5 and 20 towards PV1, PV2 and PV3 respectively. In each WHO region, the GMTs towards PV3 were consistently the lowest, and the Europeans showed the lowest GMTs both towards PV2 and PV3 (27.5 and 15.3 respectively). GMTs decreased with age. CONCLUSION: The low GMTs and the clear tendency to decrease with increasing age of the subjects, especially against to PV1, confirm the framework of attention that polio is receiving at national and international level.

Evaluation of antigenic differences between wild and Sabin vaccine strains of poliovirus using the pseudovirus neutralization test.

In the endgame of global polio eradication, serosurveillance is essential to monitor each country's vulnerability to poliomyelitis outbreaks. Previously, we developed pseudovirus poliovirus (PV) neutralization test (pPNT) with type 1, 2, and 3 PV pseudovirus (PVpv), which possess a luciferase-encoding PV replicon in the capsids of wild-type strains (PVpv[WT]), showing that pPNT with type 2 and 3 PVpv(WT) but not type 1 shows high correlation with the conventional PV neutralization test (cPNT) performed with vaccine strains. Here, we analyse the antigenicity of PVpv(WT) and PVpv with capsid proteins of Sabin vaccine strains (PVpv[Sabin]) in human serum. Type 2 and 3 PVpv(WT) and PVpv(Sabin) show similar antigenicity in the analysed set of human sera in contrast to type 1 PVpv. The levels of PVpv(Sabin) infection (%), including about 70% of PVpv infection (%) measured in the presence of human serum diluted to the cPNT titre, serve as the optimal threshold values for pPNT (5% for type 1 and 2, 10% for type 3) to show high correlation with cPNT results. Our results suggest that pPNT with PVpv(Sabin) could serve as an alternative to cPNT and provide a rationale for pPNT threshold values.

Immunoglobulins and virus antibody titers: of past needs, current requirements, and future options.

BACKGROUND: Immunoglobulins (Igs) have been in clinical use for almost 70 years, and early on were also used in conjunction with exposure to the measles virus or polio virus. The US regulations that describe functional Ig lot release thus require the demonstration of minimum antibody titers against these two viruses, although the use of vaccines has now dramatically reduced their incidence. The lower clinical importance of these viruses raises the question of whether other virus antibodies might be more informative for patients with immunodeficiency. STUDY DESIGN AND METHODS: A literature survey was conducted to identify viruses of potential clinical concern for people with immunodeficiency. The viruses selected have stable seroepidemiology and associated functional antibody assays. As a result, neutralizing antibody titers to human adenovirus 5 (HAdV5), respiratory syncytial virus (RSV) serotypes A and B, and human parainfluenza virus 3 (hPIV3) were determined in Ig lots produced from plasma collected in either the United States or the European Union. RESULTS: The virus antibody titers measured were high and consistent among the Ig lots tested. Use of either US- or EU-derived plasma as starting material resulted in equivalent virus antibody titers, with the exception of RSV serotype B, for which a lower titer was seen in EU plasma-derived Ig lots. CONCLUSION: With the significant decline in measles virus and polio virus circulation, and even their potential eradication, measurement of antibody titers against other viruses in Ig products may be more informative for functional lot release testing.

Epidemiological serosurvey of poliovirus in Guangdong, China: A cross-sectional study.

A cross-sectional study for poliovirus seroprevalence in Guangdong was carried out in 2014, just before a change in polio vaccine commenced in 2015. The aim of the study was to test whether polio immunity level was high enough to satisfy the polio vaccine switch. A total of 6339 people were tested for poliovirus neutralization antibodies (NA). Overall NA seropositivity for PV1, PV2 and PV3 were 95.2%, 94.9% and 88.7%, and the respective geometric mean titer (GMT) were 82.9, 55.8, and 26.3, respectively. There were statistically significant differences in the positive rates and GMT of the 3 serotypes and PV3 had relatively lower positive rates and GMT. The highest seropositivity and GMT were observed in the 1-9 year-old age group. The positive rates of NA and GMT for PV1, PV2 and PV3 in the western region of Guangdong were lower than those of other three regions. The results of this study showed that the population of Guangdong province had a high polio immunity level, a stable base for a polio vaccine switch.

Standardized Methods for Detection of Poliovirus Antibodies.

Testing for neutralizing antibodies against polioviruses has been an established gold standard for assessing individual protection from disease, population immunity, vaccine efficacy studies, and other vaccine clinical trials. Detecting poliovirus specific IgM and IgA in sera and mucosal specimens has been proposed for evaluating the status of population mucosal immunity. More recently, there has been a renewed interest in using dried blood spot cards as a medium for sample collection to enhance surveillance of poliovirus immunity. Here, we describe the modified poliovirus microneutralization assay, poliovirus capture IgM and IgA ELISA assays, and dried blood spot polio serology procedures for the detection of antibodies against poliovirus serotypes 1, 2, and 3.

[Collective immunity against poliomyelitis among the population of several regions of Russia].

The goal of this work was to estimate the collective immunity against poliomyelitis among the population of 8 regions and republics of Russia. The rates of the collective immunity against poliomyelitis allow the polio vaccination quality to be estimated and the population protection rate to be simultaneously demonstrated. A total of 8 regions (2138 people) were tested. The antibodies to the polioviruses of 1-3 types were determined against the vaccine Sabin strains in the neutralization test in the RD cell line. As a result, we found that vaccination against poliomyelitis in all observed regions was maintained at the required high level. Thus, the number of people with antibodies to the polio in most regions and age groups approximates or reaches 100%, while GMT is also high. This work demonstrated the necessity of the continuation of vaccination against poliomyelitis and control over collective immunity.

Zinc supplementation fails to increase the immunogenicity of oral poliovirus vaccine: a randomized controlled trial.

BACKGROUND: Polio eradication remains a challenge in Pakistan and the causes for the failure to eradicate poliomyelitis are complex. Undernutrition and micronutrient deficiencies, especially zinc deficiency, are major public health problems in Pakistan and could potentially affect the response to enteric vaccines, including oral poliovirus vaccine (OPV). OBJECTIVE: To assess the impact of zinc supplementation among infants on immune response to oral poliovirus vaccine (OPV). METHODS: A double-blind, randomized placebo-controlled trial was conducted in newborns (aged 0-14 days). Subjects were assigned to either receive 10mg of zinc or placebo supplementation daily for 18 weeks. Both groups received OPV doses at birth, at 6 weeks, 10 weeks and 14 weeks. Data was collected on prior immunization status, diarrheal episodes, breastfeeding practices and anthropometric measurements at recruitment and at 6 and 18 weeks. Blood samples were similarly collected to determine the antibody response to OPV and for micronutrient analysis. Logistic regression was used to determine the relationship between seroconversion and zinc status. RESULTS: Overall, 404 subjects were recruited. At recruitment, seropositivity was already high for poliovirus (PV) serotype 1 (zinc: 91.1%; control: 90.5%) and PV2 (90.0%; 92.7%), with lower estimates for PV3 (70.0%; 64.8%). By week 18, the proportion of subjects with measured zinc levels in the normal range (i.e. ≥60 µg/dL) was significantly greater in the intervention group compared to the control group (71.9%; 27.4%; p<0.001). No significant difference in seroconversion was demonstrated between the groups for PV1, PV2, or PV3. CONCLUSIONS: There was no effect of zinc supplementation on OPV immunogenicity. These conclusions were confirmed when restricting the analysis to those with measured higher zinc levels.

Sero-survey of polio antibodies during wild poliovirus outbreak in southern Xinjiang Uygur Autonomous Region, China.

BACKGROUND: After being polio free for more than 10 years, an outbreak following importation of wild poliovirus (WPV) was confirmed in Xinjiang Uygur Autonomous Region, China, in 2011. METHODS: A cross-sectional study was conducted prior to supplementary immunization activities (SIAs), immediately after the confirmation of the WPV outbreak. In selected prefectures, participants aged ≤ 60 years old who visited hospitals at county-level or above to have their blood drawn for reasons not related to the study, were invited to participate in our study. Antibody titers ≥ 8 were considered positive. RESULTS: Among the 2,611 participants enrolled, 2,253 (86.3%), 2,283 (87.4%), and 1,989 (76.2%) were seropositive to P1, P2 and P3 respectively, and 1744 (66.8%) participants were seropositive to all the three serotypes. Lower antibody seropositivities and geometric mean titers were observed in children <1 year of age and in adults aged 15-39 years. CONCLUSION: Serosurveys to estimate population immunity in districts at high risk of polio importation might be useful to gauge underlying population immunity gaps to polio and possibly to guide preparedness and response planning. Consideration should be given to older children and adults during polio risk assessment planning and outbreak response.

Novel hollow microneedle technology for depth-controlled microinjection-mediated dermal vaccination: a study with polio vaccine in rats.

PURPOSE: The aim of the study was to develop a cheap and fast method to produce hollow microneedles and an applicator for injecting vaccines into the skin at a pre-defined depth and test the applicability of the system for dermal polio vaccination. METHODS: Hollow microneedles were produced by hydrofluoric acid etching of fused silica capillaries. An electromagnetic applicator was developed to control the insertion speed (1-3 m/s), depth (0-1,000 µm), and angle (10°-90°). Hollow microneedles with an inner diameter of 20 µm were evaluated in ex vivo human skin and subsequently used to immunize rats with inactivated poliovirus vaccine (IPV) by an intradermal microinjection of 9 µL at a depth of 300 µm and an insertion speed of 1 m/s. Rat sera were tested for IPV-specific IgG and virus-neutralizing antibodies. RESULTS: Microneedles produced from fused silica capillaries were successfully inserted into the skin to a chosen depth, without clogging or breakage of the needles. Intradermal microinjection of IPV induced immune responses comparable to those elicited by conventional intramuscular immunization. CONCLUSIONS: We successfully developed a hollow microneedle technology for dermal vaccination that enables fundamental research on factors, such as insertion depth and volume, and insertion angle, on the immune response.

[State of collective immunity against poliomyelitis in some regions of Russia].

AIM: Study the state of collective immunity against poliomyelitis in 7 regions of Russia in the last 3 years. MATERIALS AND METHODS: 2579 sera were studied for antibodies against poliomyelitis virus. Antibodies (AT) against 3 types of viruses were determined in neutralization reaction in RD cell culture, the state of collective immunity in the examined individuals was evaluated by the percent of individuals with AT against a type of poliovirus and geometric mean AT titer. The circulation of wild polioviruses was judged by the presence of strain specific AT against wild and vaccine viruses in the examined children (311 sera were studied). RESULTS: The indicators of collective immunity against poliomyelitis in both select examined regions and select age groups were generally high. The data obtained allow to make a conclusion that the quality of vaccine prophylaxis in the examined regions is good. Introduction of wild poliovirus type 1 from Tajikistan in 2010 caused disease in 7 residents of Russia whereas an epidemic that had affected more than 700 individuals emerged in Tajikistan. CONCLUSION: The studies carried out confirmed the necessity to continue qualitative poliomyelitis vaccine prophylaxis in the country despite the lack of circulation of wild polioviruses that can be introduced at any time.

[Monitoring of implementation of international programs of poliomyelitis eradication and measles and rubella elimination in the Republic of Belarus].

AIM: Monitoring of implementation of international programs of poliomyelitis eradication, and measles and rubella elimination in the Republic of Belarus based on results of molecular-epidemiologic studies of 2009 - 2010. MATERIALS AND METHODS: 271 viral agents isolated from children with acute flaccid paralysis syndrome, other diseases, healthy children and from sewage water within the framework of poliomyelitis control implementation were identified by serological and molecular methods. Blood sera of 528 patients with fever and rash were examined for the presence of IgM to measles and rubella virus, 418 - for the presence of IgM to parvovirus B19 and parvovirus DNA. Blood sera of 33 pregnant women and 64 children with signs of intrauterine infection were studied for IgM and IgG antibodies to rubella virus. Measles virus was isolated, N-gene sequence and phylogenetic analysis carried out. RESULTS: The studies performed confirmed that indigenous wild polioviruses in the country do not circulate, imported wild or vaccine-related polioviruses were also not detected. Measles and rubella morbidity in the Republic of Belarus was less than 1 in 1 000 000. 2 cases of rubella (2009) and 1 case of measles (2010) was detected during adequate control level: the rate of detection of patients with fever and rash, in whom measles and rubella diagnosis was excluded by the results of laboratory examination, was more than 2 in 100 000 of the population. The etiologic agent in more than 20% of diseases with fever and rash was parvovirus B19. A single case of measles was caused by genotype D8 virus imported from India. CONCLUSION: The data obtained give evidence to conformance of the poliomyelitis, measles, rubella, innate rubella syndrome control implemented in the Republic of Belarus to WHO recommendations; maintenance of status of country as free from poliomyelitis and achievement of main criteria of elimination of both measles and rubella by 2010.

Combined Haemophilus Influenzae type B-Neisseria meningitidis serogroup C vaccine is immunogenic and well tolerated in preterm infants when coadministered with other routinely recommended vaccines.

BACKGROUND: Preterm infants are at greater risk of morbidity from vaccine-preventable diseases. Therefore, their responses to vaccination are of particular interest. METHODS: In this open, controlled, Spanish multicenter study, we assessed immunogenicity and safety following primary vaccination of 163 preterm infants (n = 56, <31 weeks' gestation; n = 107, 31-36 weeks' gestation) and 150 full-term infants (>36 weeks' gestation), with Haemophilus Influenzae type B (Hib)-MenC-TT, DTaP(diphtheria-tetanus-acellular pertussis vaccine)-HepB-IPV, and PCV7 at 2 to 4-6 months of age followed by booster vaccination at 16 to 18 months of age. Serum bactericidal activity (rabbit complement) against MenC, and antibodies to Hib and hepatitis b (anti-HBs) were determined. Local/general symptoms were assessed after each vaccination via diary cards. Serious adverse events were recorded throughout the study. RESULTS: There were no statistically significant differences between preterm and full-term infants in either Hib or MenC seroprotection rates or geometric mean concentrations at 1 month postdose 3, before or 1 month postbooster. Postdose 3, >99% of participants had seroprotective anti-HBs antibody concentrations. Anti-HBs geometric mean concentrations was significantly lower in the <31-week group compared with other groups and this difference persisted until 16 to 18 months of age. Hib-MenC-TT vaccine was well tolerated at all ages. There was one death caused by meningococcal serogroup-B sepsis (full term). No serious adverse events were assessed by the investigator as being vaccine related. CONCLUSIONS: Hib-MenC-TT vaccine had a similar immunogenicity and safety profile in preterm and full-term infants. These results demonstrate that preterm infants can be safely vaccinated with Hib-MenC-TT at the recommended chronologic age without impacting the responses to the Hib and MenC antigens.

Body composition assessment in Taiwanese individuals with poliomyelitis.

OBJECTIVES: To measure the changes in the total and regional body fat mass, and assess the clinical usefulness of the body mass index (BMI) in detecting overweight subjects with sequelae of poliomyelitis. DESIGN: Prospective, cross-sectional study. SETTING: General community. PARTICIPANTS: Subjects with poliomyelitis (n=17; age range, 42-57y; mean, 47y; 12 men, 5 women) and able-bodied people (n=17) matched by sex, age, body weight, and body height participated in the study. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Total and regional body composition was measured with dual-energy x-ray absorptiometry. Clinical characteristics such as blood pressure, serum biochemical studies, and habitual behaviors (daily cigarette smoking, alcohol consumption, and exercise regimen) of all participants were evaluated. RESULTS: Compared with able-bodied controls, subjects with poliomyelitis had a 50% greater total body fat mass, significant increases in the regional fat mass in every part of the body, and had the greatest increase of fat mass in the thorax. Nearly all the subjects (94%) with poliomyelitis were obese according to standards of body composition. However, one third of them had a BMI value of less than 25.0kg/m(2). CONCLUSIONS: People with poliomyelitis have a higher prevalence of obesity and a significant increase in total and regional fat mass. Current BMI underestimates the total body fat mass percentage compared with the control; therefore, a population-specific BMI should be used to address the prevalence of obesity in postpolio survivors.

[Immunity to poliovirus after vaccination of children with type 1 diabetes mellitus and rheumatic diseases].

AIM: To assess immunization coverage against poliomyelitis and level of immunity postvaccination in children with type 1 diabetes mellitus (DM1) and rheumatic diseases. MATERIALS AND METHODS: Vaccination status of 299 children with DM1 and 136 children with rheumatic diseases was determined. Serologic test using neutralization reaction was performed in 31 children with DM1 and 29 children with rheumatic diseases. Three hundred and eighty healthy children aged 3-14 years were included in the control group. All children previously received oral poliovirus vaccine. RESULTS: During postimmunization period decompensations of main disease in children with DM1 and rheumatic diseases were not observed. There were no seronegative children to all poliovirus types revealed. Proportion of children with DM1 and rheumatic diseases seronegative to two serotypes was 12.9% and 13.8% respectively. Proportion of children with DM1 seropositive to all 3 serotypes was 54.8% that is lower than in general population (p<0.01), whereas in children with rheumatic diseases this proportion was 75.8%. In children with DM1 real proportion of immune subjects was normal--94.9% and 82.0% for pqliovirus types 1 and 2 respectively, whereas the same proportion for poliovirus type 3 was 49.7%. In children with rheumatic diseases real proportion of immune subjects was normal for poliovirus types 1 and 2, and was 72.4% for poliovirus type 3. CONCLUSION: Algorithms of examination of patientswith DM1 and rheumatic diseases, which allow to purposefully perform serologic evaluation as well as recommendations about additional immunization against poliomyelitis, were developed.

[Analysis on poliomyelitis neutralizing antibody in healthy population on border areas of Guangxi Zhuang Autonomous Region].

OBJECTIVE: To understand the antibody level of poliomyelitis in healthy population on border districts of Guangxi Zhuang Autonomous Region. METHODS: The surveillance of poliomyelitis neutralizing antibody was conducted from a selected randomly stratified sample of 902 border residents who aged from 1- to 59-years-old. RESULTS: The positive rate and geometric mean titer (GMT) of poliomyelitis neutralizing antibody type I, II and III were 93.90%, 97.67%, 92.02% and 1:53.22, 1:66.51, 1:20.01 respectively. CONCLUSION: A higher level of immunity against poliovirus in healthy population has been established on border areas.

[Analysis of polio antibody levels in healthy population in Beijing in 2007].

OBJECTIVE: To investigate the poliomyelitis antibody level in healthy people in Beijing. METHODS: 10 age groups (0, 1 to 4, 5 to 9, 10 to 14, 15 to 19, 20 to 24, 25 to 29, 30 to 34, 35 to 39, and > or = 40) were sampled by the Multi-stage stratified sampling method in 7 districts in Beijing, and 1552 sera from healthy population were collected. The poliomyelitis antibody was determined with microcell neutralization method. RESULTS: The neutralized antibody-positive rate for polio I, II, III were 97.04%, 97.29% and 91.04% respectively, the geometric mean titers (GMT) were 1:70.05, 1:54.60, and 1:31.83 respectively. A trend of decreasing was observed in the GMTs with increasing age and years after immunization. There were no significant differences in antibody levels between different gender, residents or regions. The results of multiple-factors analysis showed that the GMTs were significantly associated with age and the years after immunization. CONCLUSION: A stable immunization barrier has been established in healthy population in Beijing.

[Surveillance on poliomyelitis neutralization antibody level in the border areas in Jilin province].

OBJECTIVE: This project is designed for understand poliomyelitis (Polio) neutralization antibody level in the the border areas in Jilin province. METHOD: 263 serum samples were collected from age groups of under 1-year-old, 1-2, 3-4, 5-6, 7-14, 15-19 and above 20-years-old. Microplate neutralization test was used to determine antibody level. RESULT: Positive rates of neutralization antibody against Polio type I, II, III were 94.98%, 94.59%, 92.28%. The geometric mean titre of Polio type I, II, III were 1:40.53, 1:29.68, 1:20.71 respectively,which was decreased with the age increasing. CONCLUSION: The population especially the population under 15-years-old lived in places that near the border in Jilin province had good immunity barriar against poliomyelitis.

Circulating vaccine derived polio viruses and their impact on global polio eradication.

Poliomyelitis vaccination via live Oral Polio Vaccine (OPV) suffers from the inherent problem of reversion: the vaccine may, upon replication in the human gut, mutate back to virulence and transmissibility resulting in circulating vaccine derived polio viruses (cVDPVs). We formulate a general mathematical model to assess the impact of cVDPVs on prospects for polio eradication. We find that for OPV coverage levels below a certain threshold, cVDPVs have a small impact in comparison to the expected endemic level of the disease in the absence of reversion. Above this threshold, the model predicts a small but significant endemic level of the disease, even where standard models predict eradication. In light of this, we consider and analyze three alternative eradication strategies involving a transition from continuous OPV vaccination to either continuous Inactivated Polio Vaccine (IPV), pulsed OPV vaccination, or a one-time IPV pulse vaccination. Stochastic modeling shows continuous IPV vaccination is effective at achieving eradication for moderate coverage levels, while pulsed OPV is effective if higher coverage levels are maintained. The one-time pulse IPV method may also be a viable strategy, especially in terms of the number of vaccinations required and time to eradication, provided that a sufficiently large pulse is practically feasible. More investigation is needed regarding the frequency of revertant virus infection resulting directly from vaccination, the ability of IPV to induce gut immunity, and the potential role of spatial transmission dynamics in eradication efforts.