scholarly journals Isolation of an Intertypic Poliovirus Capsid Recombinant from a Child with Vaccine-Associated Paralytic Poliomyelitis

2002 ◽  
Vol 76 (21) ◽  
pp. 10921-10928 ◽  
Author(s):  
Javier Martín ◽  
Elena Samoilovich ◽  
Glynis Dunn ◽  
Angie Lackenby ◽  
Esphir Feldman ◽  
...  

ABSTRACT The isolation of a capsid intertypic poliovirus recombinant from a child with vaccine-associated paralytic poliomyelitis is described. Virus 31043 had a Sabin-derived type 3-type 2-type 1 recombinant genome with a 5′-end crossover point within the capsid coding region. The result was a poliovirus chimera containing the entire coding sequence for antigenic site 3a derived from the Sabin type 2 strain. The recombinant virus showed altered antigenic properties but did not acquire type 2 antigenic characteristics. The significance of the presence in nature of such poliovirus chimeras and the consequences for the current efforts to detect potentially dangerous vaccine-derived poliovirus strains are discussed in the context of the global polio eradication initiative.

2000 ◽  
Vol 74 (18) ◽  
pp. 8434-8443 ◽  
Author(s):  
Sophie Guillot ◽  
Valérie Caro ◽  
Nancy Cuervo ◽  
Ekaterina Korotkova ◽  
Mariana Combiescu ◽  
...  

ABSTRACT In a previous study of poliovirus vaccine-derived strains isolated from patients with vaccine-associated paralytic poliomyelitis (VAPP) (9, 11), we reported that a high proportion (over 50%) of viruses had a recombinant genome. Most were intertypic vaccine/vaccine recombinants. However, some had restriction fragment length polymorphism (RFLP) profiles different from those of poliovirus vaccine strains. We demonstrate here that five such recombinants, of 88 VAPP strains examined, carried sequences of wild (nonvaccine) origin. To identify the parental wild donor of these sequences, we used RFLP profiles and nucleotide sequencing to look for similarity in the 3D polymerase-coding region of 61 wild, cocirculating poliovirus isolates (43 type 1, 16 type 2, and 2 type 3 isolates). In only one case was the donor identified, and it was a wild type 1 poliovirus. For the other four vaccine/wild recombinants, the wild parent could not be identified. The possibility that the wild sequences were of a non-poliovirus-enterovirus origin could not be excluded. Another vaccine/wild recombinant, isolated in Belarus from a VAPP case, indicated that the poliovirus vaccine/wild recombination is not an isolated phenomenon. We also found wild polioviruses (2 of 15) carrying vaccine-derived sequences in the 3′ moiety of their genome. All these results suggest that genetic exchanges with wild poliovirus and perhaps with nonpoliovirus enteroviruses, are also a natural means of evolution for poliovirus vaccine strains.


1967 ◽  
Vol 65 (1) ◽  
pp. 77-84 ◽  
Author(s):  
Yvonne E. Cossart

Strains of poliovirus were obtained from 13 of the 18 persons in England and Wales with paralytic episodes after administration of oral vaccine in 1962. They have been studied using three marker tests: the R.C.T.40 test, intratypic serodifferentiation and inhibition by dextran sulphate. For comparison a number of strains from subjects with non-paralytic vaccine-associated reactions and from patients with paralytic poliomyelitis not related to vaccine were also tested.Of the eight patients excreting type 1 strains seven came from South Wales where an outbreak was in progress. They all resemble naturally occurring strains from the outbreak in growing at 39·3° but not at 39·8° C.Only one subject excreted type 2 virus which was of vaccine type.The type 3 strains included a series from a family group where a range of results from vaccine to the wild range was obtained. Three other patients with vaccineassociated paralysis excreted type 3 strains with the characteristic of naturally occurring strains.


1978 ◽  
Vol 80 (1) ◽  
pp. 155-167 ◽  
Author(s):  
J. W. G. Smith ◽  
P. J. Wherry

SUMMARYPoliomyelitis continued to be a rare disease in England and Wales in the period 1969–75. Only 31 paralytic and 44 cases of possible non-paralytic poliomyelitis were recorded during the 7 years.Of the 31 paralytic cases approximately one third were vaccine-associated; 3 were patients who had recently received oral poliovaccine and 7 had been in contact with a vaccinated person. Five of these 7 patients were parents of recently vaccinated children. The rate of vaccine-associated poliomyelitis was estimated in recipients to be 0·2 and in contacts 0·4 per million doses of vaccine given.Marker test results were reported on 555 strains of poliomyelitis virus isolated during 1969–75, using the reproductive capacity temperature test. Forty-eight (8·6%) resembled wild virus in this property, 15 strains being type 1, 8 type 2 and 25 type 3. Most of these isolations of apparently wild virus were from excreters with no symptoms of poliomyelitis, although 3 of the 15 type 1 strains were from patients with paralytic poliomyelitis and 3 from possible cases of non-paralytic poliomyelitis. None of the 8 apparently wild type 2 viruses was from a case of paralytic illness and only 1 of the 39 type 3 strains.Eleven of the 31 paralytic cases were in patients in whom the infection was likely to have been acquired abroad.


2008 ◽  
Vol 82 (18) ◽  
pp. 9179-9190 ◽  
Author(s):  
John K. Odoom ◽  
Zaira Yunus ◽  
Glynis Dunn ◽  
Philip D. Minor ◽  
Javier Martín

ABSTRACT The evolution of the Sabin strain of type 1 poliovirus in a hypogammaglobulinemia patient for a period of 649 days is described. Twelve poliovirus isolates from sequential stool samples encompassing days 21 to 649 after vaccination with Sabin 1 were characterized in terms of their antigenic properties, virulence in transgenic mice, sensitivity for growth at high temperatures, and differences in nucleotide sequence from the Sabin 1 strain. Poliovirus isolates from the immunodeficient patient evolved gradually toward non-temperature-sensitive and neurovirulent phenotypes, accumulating mutations at key nucleotide positions that correlated with the observed reversion to biological properties typical of wild polioviruses. Analysis of plaque-purified viruses from stool samples revealed complex genetic and evolutionary relationships between the poliovirus strains. The generation of various coevolving genetic lineages incorporating different mutations was observed at early stages of virus excretion. The main driving force for genetic diversity appeared to be the selection of mutations at attenuation sites, particularly in the 5′ noncoding region and the VP1 BC loop. Recombination between virus strains from the two main lineages was observed between days 63 and 88. Genetic heterogeneity among plaque-purified viruses at each time point seemed to decrease with time, and only viruses belonging to a unique genotypic lineage were seen from day 105 after vaccination. The relevance of vaccine-derived poliovirus strains for disease surveillance and future polio immunization policies is discussed in the context of the Global Polio Eradication Initiative.


1952 ◽  
Vol 96 (1) ◽  
pp. 35-53 ◽  
Author(s):  
Jordi Casals ◽  
Peter K. Olitsky ◽  
Albert B. Sabin

Sera from 81 patients with a diagnosis of paralytic or non-paralytic poliomyelitis, and from 159 individuals of similar age groups giving no history of the disease, were tested with a high titered, complement-fixing poliomyelitis antigen of Type 2 (Lansing-like). The antigen consisted of brain tissue from newborn mice injected with the MEF1 strain of virus as previously adapted to these animals. The presence or absence of Type 2 neutralizing antibody in the sera under test was found not to affect the complement fixation. Positive reactions were obtained with 57 per cent of the sera deriving from non-paralytic patients and in 70 per cent from paralytics, when the specimens were tested at a dilution of 1:16. The complement-fixing antibody was often present in highest titer as early as 24 hours after the onset of poliomyelitis, and in almost all instances within 7 days. In about half of the patients a 4-fold or greater drop in titer occurred within 3 months, with little or no change in the others. The incidence of titers of 1:16 or higher with the control sera varied with the season of the year at which they were procured, 3 per cent of the winter samples proving positive and 13 per cent of the summer. The tests of sera from the group of patients from whom poliomyelitis virus was recovered, disclosed no significant differences between those having the paralytic and those having the non-paralytic disease. Type 1 (Brunhilde-like) strains of virus were recovered from many of the patients yielding positive tests, although they presented no evidence of previous or concurrent infection with Type 2 virus. This finding shows that Type 1 virus can give rise in patients to Type 2 complement-fixing antibody. The application of these data to the serologic diagnosis of poliomyelitis infection in man will of necessity be limited until information is obtained on the development, persistence, and significance of complement-fixation reactions with antigens deriving from Type 1 and Type 3 poliomyelitis strains.


2002 ◽  
Vol 76 (11) ◽  
pp. 5339-5349 ◽  
Author(s):  
Javier Martín ◽  
Philip D. Minor

ABSTRACT CHAT and Cox type 1 live-attenuated poliovirus strains were developed in the 1950s to be used as vaccines for humans. This paper describes their characterization with respect to virulence, sensitivity for growth at high temperatures, and complete nucleotide and amino acid sequences. The results are compared to those for their common parental wild virus, the Mahoney strain, and to those for two other poliovirus strains derived from Mahoney, the Sabin 1 vaccine strain and the mouse-adapted LS-a virus. Analysis of four isolates from cases of vaccine-associated paralytic poliomyelitis related to the CHAT vaccine revealed genetic and phenotypic properties of the CHAT strain following replication in the human gut. CHAT-VAPP strain 134 contained a genome highly evolved from that of CHAT (1.1% nucleotide differences), suggesting long-term circulation of a vaccine-derived strain in the human population. The molecular mechanisms of attenuation and evolution of poliovirus in humans are discussed in the context of the global polio eradication initiative.


Author(s):  
A.M. Satarkulova

The assessment and dynamic control over students’ status is a very important task. It allows timely detection of prenosological status prior to pathology and health maintenance in students. The objective of the paper is to assess the adaptive abilities of the body, to analyze changes in heart rate variability indicators in students with various types of autonomic regulation, to identify prenosological status and precursory pathological symptoms. Materials and Methods. The study enrolled 302 students from India, aged 21.54±1.43. Programming complex «Psychophysiologist» was used to register the main HRV parameters within 5 minutes. Health status was evaluated according to the index of functional changes and the scale of functional states. Results. N.I. Shlyk (2009) distinguished two groups of students with different types of autonomic regulation: type 1 (53 %) with moderate and type 2 (5 %) with marked characteristics of central regulation profile, type 3 (35 %) with moderate and type 4 (7 %) with marked characteristics of autonomous regulation profile. Main parameters of HRV and adaptation potential were defined for each student.All the parameters characterized functional and health status. Conclusions. It was shown that 82 % of trial subjects (type 1), 53 % (type 2), 94 % (type 3) and 95 % (type 4) demonstrated satisfactory adaptation and their physiological processes were at an optimal level. 18 % of students (type 1) demonstrated reduced adaptive abilities of the body. Moreover, they were under moderate stress. 47 % of subjects (type 2) were also under a significant stress, which was proven by excessively high SI, low SDNN and TP, and an increased index of functional changes. 5 % of students (type 4) revealed dysfunctional characteristics in the heart rhythm, peculiar to pathology. Keywords: foreign students, heart rate variability, types of autonomic regulation, adaptation potential, functional status. Оценка состояния студентов и динамический контроль за ним является важной задачей, поскольку позволяет своевременно выявлять у студентов донозологические состояния, предшествующие патологии, и способствовать сохранению здоровья. Цель. Оценка адаптивных возможностей организма, анализ изменений показателей вариабельности сердечного ритма у студентов с различными типами вегетативной регуляции, выявление донозологических состояний и ранних признаков патологии. Материалы и методы. В исследовании участвовало 302 студента в возрасте 21,54+1,43 года из Индии. Регистрировались основные параметры ВСР в течение 5 мин с использованием программно-аппаратного комплекса «Психофизиолог». Состояние и уровень здоровья оценивались по индексу функциональных изменений и шкале функциональных состояний. Результаты. По способу, предложенному Н.И. Шлык, выделены группы студентов с различными типами вегетативной регуляции: I (53 %) и II типы (5 %) – с умеренным и выраженным преобладанием центрального контура регуляции соответственно, III (35 %) и IV типы (7 %) – с умеренным и выраженным преобладанием автономного контура регуляции соответственно. У каждого из студентов определены основные параметры ВСР и адаптационного потенциала, характеризующие функциональное состояние и уровень здоровья. Выводы. Показано, что для 82 % обследуемых с I типом, 53 % со II типом, 94 % c III типом и 95 % с IV типом регуляции характерно состояние удовлетворительной адаптации, физиологические процессы сохраняются на оптимальном уровне. В группе студентов I типа у 18 % студентов адаптивные возможности организма снижены, выявлено состояние умеренного напряжения. У 47 % обследуемых II типа также зафиксировано состояние резко выраженного напряжения, индикатором которого является чрезмерно высокое значение SI, низкие величины SDNN и ТP, повышенное значение индекса функциональных изменений. В группе студентов с IV типом у 5 % учащихсяв регуляции ритма сердца выявлены дисфункциональные признаки, характерные для патологии. Ключевые слова: иностранные студенты, вариабельность сердечного ритма, типы вегетативной регуляции, адаптационный потенциал, функциональное состояние.


1954 ◽  
Vol 32 (1) ◽  
pp. 119-125
Author(s):  
W. Wood ◽  
Eina M. Clark ◽  
F. T. Shimada ◽  
A. J. Rhodes

Studies on the basic immunology of poliomyelitis in Canadian Eskimos have been continued. Some 87 sera collected from Eskimos at Pangnirtung, Baffin Island, have been examined for the presence of Type 1 and Type 3 poliomyelitis antibody by quantitative tests in tissue cultures. The same sera were previously examined for Type 2 antibody by quantitative tests in mice. The results of the three determinations are now presented together for comparison. These sera came from Eskimos aged 2 to 72 years of age. None of the Eskimos showed any evidence of paralysis. Examination of the medical records did not suggest that any paralytic disease had been present in this part of Baffin Island. Very few of the sera showed the presence of poliomyelitis antibody; thus, Type 1 antibody was demonstrated in the sera of 8%, Type 2 antibody in the sera of 9%, and Type 3 antibody in the sera of 14%. No significant number of Eskimos below the age of 45 years had acquired poliomyelitis antibody. The antibody titers mostly ranged between 10−1.0 and 10−2.0, and were significantly lower than the titers customarily found in recently paralyzed cases. These findings suggest that poliomyelitis infection occurred in Pangnirtung Eskimos many years before the date on which the samples were taken (1951). These results point to the worldwide prevalence of the three types of poliomyelitis virus.


2021 ◽  
Vol 47 (02) ◽  
pp. 192-200
Author(s):  
James S. O'Donnell

AbstractThe biological mechanisms involved in the pathogenesis of type 2 and type 3 von Willebrand disease (VWD) have been studied extensively. In contrast, although accounting for the majority of VWD cases, the pathobiology underlying partial quantitative VWD has remained somewhat elusive. However, important insights have been attained following several recent cohort studies that have investigated mechanisms in patients with type 1 VWD and low von Willebrand factor (VWF), respectively. These studies have demonstrated that reduced plasma VWF levels may result from either (1) decreased VWF biosynthesis and/or secretion in endothelial cells and (2) pathological increased VWF clearance. In addition, it has become clear that some patients with only mild to moderate reductions in plasma VWF levels in the 30 to 50 IU/dL range may have significant bleeding phenotypes. Importantly in these low VWF patients, bleeding risk fails to correlate with plasma VWF levels and inheritance is typically independent of the VWF gene. Although plasma VWF levels may increase to > 50 IU/dL with progressive aging or pregnancy in these subjects, emerging data suggest that this apparent normalization in VWF levels does not necessarily equate to a complete correction in bleeding phenotype in patients with partial quantitative VWD. In this review, these recent advances in our understanding of quantitative VWD pathogenesis are discussed. Furthermore, the translational implications of these emerging findings are considered, particularly with respect to designing personalized treatment plans for VWD patients undergoing elective procedures.


2021 ◽  
Author(s):  
Hui Xu ◽  
Lei Chen ◽  
Wansuo Duan

AbstractThe optimally growing initial errors (OGEs) of El Niño events are found in the Community Earth System Model (CESM) by the conditional nonlinear optimal perturbation (CNOP) method. Based on the characteristics of low-dimensional attractors for ENSO (El Niño Southern Oscillation) systems, we apply singular vector decomposition (SVD) to reduce the dimensions of optimization problems and calculate the CNOP in a truncated phase space by the differential evolution (DE) algorithm. In the CESM, we obtain three types of OGEs of El Niño events with different intensities and diversities and call them type-1, type-2 and type-3 initial errors. Among them, the type-1 initial error is characterized by negative SSTA errors in the equatorial Pacific accompanied by a negative west–east slope of subsurface temperature from the subsurface to the surface in the equatorial central-eastern Pacific. The type-2 initial error is similar to the type-1 initial error but with the opposite sign. The type-3 initial error behaves as a basin-wide dipolar pattern of tropical sea temperature errors from the sea surface to the subsurface, with positive errors in the upper layers of the equatorial eastern Pacific and negative errors in the lower layers of the equatorial western Pacific. For the type-1 (type-2) initial error, the negative (positive) temperature errors in the eastern equatorial Pacific develop locally into a mature La Niña (El Niño)-like mode. For the type-3 initial error, the negative errors in the lower layers of the western equatorial Pacific propagate eastward with Kelvin waves and are intensified in the eastern equatorial Pacific. Although the type-1 and type-3 initial errors have different spatial patterns and dynamic growing mechanisms, both cause El Niño events to be underpredicted as neutral states or La Niña events. However, the type-2 initial error makes a moderate El Niño event to be predicted as an extremely strong event.


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