How poliomyelitis is to be eradicated completely

In 1988 the World Health Assembly resolved to eradicate poliomyelitis globally by the year 2000. The work continues. The problem arose how to quit the system of mass immunization with oral poliovirus vaccine (OPV) without trouble and to achieve the disappearance of polioviruses worldwide. After the cessation of the OPV use a certain number of vaccine viruses may remain that will circulate among the ever growing number of nonimmune population. Live enterovirus vaccines prepared from nonpathogenic serotypes of ECHO virus are proposed for application to stop the circulation of vaccine poliovirus. These vaccines will make it possible to eliminate the remaining vaccine viruses from circulation and to complete the process of worldwide poliomyelitis eradication.     

Characterization of the immune status of patients with vaccine-associated poliomyelitis

Specific humoral immunity, total immune status and typing of HLA antigens, class 1, in loci A and B were studied in children with vaccine-associated paralytic poliomyelitis (VAPP). The immune status investigation revealed that changes in the content of serum immunoglobulins were most frequent. Out of 8 examined children, 5 children had IgA deficiency and 1 child had total variable immunodeficiency. In one case disturbances in cell-mediated immunity prevailed. Tissue typing revealed the presence of HLA A2 and B44 in 5 out of 6 examined children, which considerably exceeded their average occurrence among the Belorussian population. In spite of frequent detection of immunological disturbances in VAPP patients, out of 38 serologically examined children 36 (95%) were found to have virus-neutralizing serum antibodies to poliovirus, which was indicative of the capacity of their immune system for response to the administration of vaccine virus. To minimize the risk of VAPP in children and to achieve the goal of poliomyelitis eradication the combined immunization scheme consisting of 1-3 vaccinations with inactivated poliovaccine with subsequent administration of oral vaccine prepared from attenuated Sabin viruses is regarded as most promising.     

Immunity to diphtheria and tetanus in some of the administrative territories of the RSFSR

The article deals with the state of immunity to diphtheria and tetanus among the adult population in some administrative regions of the RSFSR. Of the children and adults covered by the survey, 91.3-96.7% were found to have protective antibody titers against diphtheria and 98.7-100%, against tetanus. An essential drop in the level of immunity to diphtheria in persons over 18 years of age was revealed: 71.7% of them were nonimmune, which correlated with the high morbidity rate among these persons. At the same time the percentage of adults nonimmune to tetanus was considerably lower than that of adults nonimmune to diphtheria, reaching only 27.1%. The state of immunity to tetanus in adults was found to depend on the seasons.     

Strain-specific antibodies as an indicator of the circulation of wild poliomyelitis viruses and their role in the formation of collective immunity in the population

Essential differences in the intensity of collective immunity to poliomyelitis in the donors of Moscow and Kaluga were established. To find out the nature of high characteristics of collective immunity to poliovirus, types 1 and 2, in the donors of Kaluga, strain-specific antibodies to wild and vaccine polioviruses were studied. In a considerable number of donors strain-specific antibodies to poliovirus, types 1 and 2, were detected. This made it possible to presume a sufficiently wide circulation of these viruses among the population of the city in the middle of the 20th century and, as a consequence, high level of collective immunity appeared. Strain-specific antibodies to poliovirus of type 3 were rarely detected. This made it possible to suggest that the circulation of viruses of this type among the population was limited. Immunity to viruses of this type was due only to immunization. For this reason the characteristics of collective immunity in the donors of Moscow and Kaluga coincided. The detection of strain-specific antibodies to poliomyelitis virus allowed to retrospectively form the opinion of the spread and time of the circulation of wild poliomyelitis viruses in the population.     

POLIOMYELITIS VACCINE—Epidemiologic Observations on the Safety and Effectiveness in California in 1955

During the past year California has participated with other states in a nationwide field evaluation of the safety and effectiveness of poliomyelitis vaccine. Among 227,000 children who received Cutter vaccine, and the household contracts of these children, the incidence of poliomyelitis was higher during the early postvaccinal period than in comparable age groups of the population at large. Among 238,000 children who received poliomyelitis vaccine made by other manufacturers early in 1955 no increase in poliomyelitis was observed in the inoculated children or their household contacts.Subsequent observation on over 500,000 additional children vaccinated in California alone since September 1955 with vaccine that was made under revised safety standards has uncovered no evidence of unsafe vaccine. In children who received a single inoculation of vaccine prior to the onset of the poliomyelitis season in 1955 the incidence of paralytic poliomyelitis was about 60 per cent less than in unvaccinated children. Among those who received two inoculations an 85 per cent reduction was observed. The average reduction in paralytic poliomyelitis for the entire vaccinated group was approximately 75 per cent. Data thus far on children vaccinated since September 1955 with poliomyelitis vaccine made by methods now approved indicate that a similar overall effectiveness is still being maintained.     

Paralytic poliomyelitis in Russian Federation in 1998-2005

From 1998 through 2005 3,294 cases of acute flaccid paralysis (AFP) including 93 cases with clinical picture of poliomyelitis were registered in Russian Federation. From the latter cases 91 were classified as vaccine-associated paralytic poliomyelitis (VAPP): 66 were VAPP cases in oral poliomyelitis vaccine (OPV) recipients and 25--VAPP cases in contacts. VAPP rate was 1 case per 1.6 million of distributed OPV doses, 1 case per 2.2 million doses for OPV recipients, and 1 case per 186,000 doses for recipients of 1st OPV dose in children aged < 1 year. Majority of VAPP cases in recipients occurred after 1st dose (89.4%) and in contacts--in non-vaccinated children (76%). Mean interval between OPV administration and onset of VAPP in recipients was 21 days. Children aged < 1 year were predominant among VAPP cases (92.4% among recipient VAPP cases, and 80% among contact VAPP cases). Majority of the patients had unfavorable health status including defects of immunity. Most of poliovirus strains isolated from VAPP cases belonged to type 3 (52.9%) whereas to type 2 and 1--29.8% and 17.4% of strains respectively. All VAPP cases were associated with vaccine-derived polioviruses. A highly diverged poliovirus type 1 (2.65% of nucleotide substitutions in VP1 region) was isolated from patient with contact VAPP. Formation of poliovirus-neutralizing serum antibodies in children with VAPP including persons with immunodeficiency reflects the ability of the organism to produce specific antiviral immune response.     

Passive immunity modulates genetic reassortment between rotaviruses in mixedly infected mice.

Genetic reassortment between simian rotavirus SA11 and rhesus rotavirus (RRV) occurs with high frequency following mixed infection of nonimmune suckling mice (J. L. Gombold and R. F. Ramig, J. Virol. 57:110-116, 1986). We examined the effects of passively acquired homotypic or heterotypic immunity on reassortment in vivo. Passively immune suckling mice obtained from dams immune to either serotype 3 simian rotavirus (SA11) or serotype 6 bovine rotavirus (NCDV) were infected orally with either SA11 or RRV or a mixture of SA11 and RRV (both serotype 3 viruses). At various times postinfection, signs of disease were noted and the intestines of individual mice were removed and homogenized for titration of infectious virus and isolation of progeny plaques. Electrophoresis of genomic RNA was used to identify reassortants among the viral progeny isolated from infected animals. No reassortants (less than 0.45%) were detected among 224 clones examined from mixedly infected, homotypically immune mice. Twenty-nine reassortants (10.66%) were identified among 272 progeny clones from mixedly infected, heterotypically immune mice. Thus, reassortment was reduced more than 50-fold by homotypic immunity and approximately threefold by heterotypic immunity compared with prior data obtained from mixed infections of nonimmune mice. In addition, reassortment between SA11 and RRV in nonimmune mice was shown to be dependent on the virus dose. Taken together, these results suggest that immune responses may modulate the frequency of reassortment by reducing the effective multiplicity of infection (by neutralization or other immune mechanisms), thereby preventing efficient mixed infection of enterocytes.     

Characteristics of the distribution of the markers of hepatitis B vir us infection among the healthy population of the Tadzhik SSR and Azerbaijan SSR

A total of 708 healthy persons in Tajikistan and 576 healthy persons in Azerbaijan, these groups comprising persons of both sexes and different age groups, were examined by the method of double gel immunodiffusion (the gel precipitation test) and by the passive hemagglutination test for the presence of the markers of hepatitis B virus (HBV) infection (HBsAg and HBeAg) and antibodies to them. This investigation showed that, in accordance with the level of hepatitis B morbidity, HBsAg was significantly more often detected among the population in Tajikistan (7.2%) than in Azerbaijan (2.8%). In both republics HBV carriers occurred most frequently among children aged 1-4 years (4.0% in Azerbaijan and 13.9% in Tajikistan), and among men more frequently than among women. In accordance with different intensity of the spread of HBV infection in the territories under comparison, differences in the age structure of the immune population were noted: in Tajikistan the formation of the immune layer occurred most frequently among younger age groups and in Azerbaijan, among senior adult age groups. The presence of a considerable percentage of persons with HBe-antigenemia (14.3-14.9% as determined by the gel precipitation test) among HBV carriers, observed in Tajikistan and in Azerbaijan, indicates that some of them have undetected chronic hepatitis B.     

Comparative biochemical studies of type 3 poliovirus

A study of the biochemistry of type 3 poliovirus strains which involves the examination of the virus-coded polypeptides in infected cells and the preparation of oligonucleotide maps is reported. The polypeptide patterns were shown to be a relatively stable property of virus strains and distinguished Sabin vaccine strains from wild strains of poliovirus type 3. This approach may be of value in deciding the origin (vaccine or nonvaccine) of field isolates of poliovirus. Oligonucleotide maps were found to be sensitive indicators of differences among strains and appear to form a basis for determining genetic relationships among strains. The nucleotide maps of two viruses isolated from human cases of paralytic poliomyelitis temporally associated with the administration of attenuated vaccine suggested a vaccine origin for the strain. In one case the nucleotide map was indistinguishable from that of the vaccine strain.     

In vitro study of macrophage barrier function in mice vaccinated against tick-borne encephalitis and infection with flaviviruses of varying virulence

Tick-borne encephalitis (TBE) and Langat viruses were shown to be equally capable of multiplication in mouse peritoneal macrophages (PM) in vitro. The reproduction dynamics of TBE virus proved to be the same in PM of mice both highly sensitive and relatively less sensitive to TBE virus. The preliminary immunization of PM donors with commercial inactivated or experimental concentrated TBE virus vaccine produced no effect on the capacity of the virus for multiplication in PM. These facts indicate the absence of correlation between the capacity of the viruses under study for multiplication in PM in vitro and their virulence in vivo, as well as the insignificant role of circulating macrophages in the realization of the barrier function in an immune or nonimmune body.     

Distribution of antibodies to poliovirus in the children of a large industrial city

The results of prolonged dynamic observations on the state of herd immunity against poliomyelitis virus in an industrial city are given. The survey covered 1304 children. The data thus obtained, when synchronized according to years, seasons, the age of the surveyed children and the methods used in the survey, indicated that in every age group 20-30% of children had no antibodies to group I poliomyelitis virus and 30% of children had no antibodies to group III poliomyelitis virus. The geometrical mean of antibody titers to different types of the virus fluctuated from 1.8 to 4.6 log2, the lowest value being obtained for the titer of antibodies to type III poliomyelitis virus. During the whole period of immunological control (1974-1978) no mass circulation of poliomyelitis virus and no outbreaks of poliomyelitis were registered despite the fact that a considerable proportion of children having no antibodies to one or several types of the virus was constantly present among the most susceptible part of children.     

Diphtheria in the Maritime Territory

The results of the analysis of the present epidemiological situation in diphtheria in the Maritime Territory are presented. The data on absolute and intensive characteristics, death rate due to this infection, the vaccination status of diphtheria patients, as well as the results of the study of the level and intensity of antidiphtheria immunity in the healthy population of the territory. The study revealed that the defects of collective antidiphtheria immunity correlated with morbidity rate among adults and children. Adults aged 40-50 years and children aged 6-7 years were regarded as risk groups; among them the highest proportion of nonimmune persons and the highest diphtheria morbidity rate were registered. Stabilization achieved by the present moment was the result of the mass immunization of the adult population, ensuring the necessary coverage (92%) of vaccination in 1995.     

Human T-cell immunity against the emerging and re-emerging viruses

Over the past decade, we have seen an alarming number of high-profile outbreaks of newly emerging and re-emerging viruses. Recent outbreaks of avian influenza viruses, Middle East respiratory syndrome coronaviruses, Zika virus and Ebola virus present great threats to global health. Considering the pivotal role of host T-cell immunity in the alleviation of symptoms and the clearance of viruses in patients, there are three issues to be primarily concerned about T-cell immunity when a new virus emerges: first, does the population possess pre-existing T-cells against the new virus through previous infections of genetically relevant viruses; second, does a proper immune response arise in the patients to provide protection through an immunopathogenic effect; lastly, how long can the virus-specific immune memory persist. Herein, we summarize the current updates on the characteristics of human T-cell immunological responses against recently emerged or re-emerged viruses, and emphasize the necessity for timely investigation on the T-cell features of these viral diseases, which may provide beneficial recommendations for clinical diagnosis and vaccine development.     

Seroepidemiological characterization of virus hepatitis in the Republic of Armenia

The survey of the population immunological structure with respect to parenteral hepatitis showed awide circulation of hepatitis B (HB) and hepatitis C (HC) viruses among the adult population of Armenia. During the 5 year period of observation the number of persons having antibodies to HC virus increased 2.7-fold. High occurrence of antibodies to HBsAg of HB virus among the healthy population in 2002 (12.0%) in comparison with 1997 (5.4%) reflected a decreased infection rate with HB virus as well. Antibodies to hepatitis A (HA) virus were isolated, on the average, in 64 % of persons. Simultaneously with a decrease in the proportion of HA cases an increased number of HC patients was registered. No circulation of hepatitis E virus was detected. A high percentage of hepatitis cases of mixed etiology was established, as well as an increased number of combined parenteral hepatitis cases was registered (57.1%).     

The level of postvaccinal immunity to diphtheria, tetanus and poliomyelitis in relation to the number of inoculations]

The work was aimed at the comparative study of the intensity of immunity to diphtheria, tetanus and poliomyelitis, depending on the number of injections of adsorbed diphtheria-pertussis-tetanus (DPT) vaccine and poliomyelitis vaccine, for the purpose of finding out the possibility of reducing the antigenic load given to children without diminishing the intensity of immunity. To determine the level of immunity to diphtheria and tetanus, 1900 children under school age were serologically studied by the micromethod in the passive hemagglutination test. The intensity of immunity to poliomyelitis virus was studied in 333 children by means of the neutralization test. The immunogenic properties of the diphtheria component of adsorbed DPT vaccine were found to be less pronounced than those of the tetanus component of the vaccine, which made it impossible to reduce the antigenic load by decreasing the number of vaccinations against diphtheria. The results of the study of postvaccinal immunity to poliomyelitis suggest that during the first and second year of life the course of vaccination against poliomyelitis may be reduced to 3 injections.     

Antigenic Analysis of Polioviruses Isolated from a Child with Agammaglobulinemia and Paralytic Poliomyelitis after Sabin Vaccine Administration

A 3-year-old boy with agammaglobulinemia developed paralytic poliomyelitis on day 553 after being fed poliovaccine. Non-vaccine-like type 2 polioviruses were isolated from 22 stools obtained within 684 days after the onset of illness. Antigenic variations were observed among these viruses. The non-vaccine-like virus isolated 1 week after the onset of paralysis differed in virulence from the Sabin type 2 vaccine strain in the neurovirulence test in monkeys, and did not have the same antigenic character as the wild virulent strains. Another virus isolated on day 348 before the onset of illness was also classified as non-vaccine-like. However, the Sabin type 2 strain was shown to be homologous with this strain by the McBride test. Some Sabin-like particles were found in this stock virus. We may conclude that the non-vaccine-like virus isolates were derived from Sabin vaccine by antigenic variation that occurred during long-term multiplication in the intestinal tract.     

Recent mumps outbreaks in vaccinated populations: no evidence of immune escape

Recently, numerous large-scale mumps outbreaks have occurred in vaccinated populations. Clinical isolates sequenced from these outbreaks have invariably been of genotypes distinct from those of vaccine viruses, raising concern that certain mumps virus strains may escape vaccine-induced immunity. To investigate this concern, sera obtained from children 6 weeks after receipt of measles, mumps, and rubella (MMR) vaccine were tested for the ability to neutralize a carefully selected group of genetically diverse mumps virus strains. Although the geometric mean neutralizing antibody titer of the sera was lower against some virus strains than others, all viruses were readily neutralized, arguing against immune escape.     

Indicators of immunity in children vaccinated with live poliomyelitis vaccine]

Serological examination of 1057 children, residents of Leningrad, vaccinated with poliomyelitis vaccine at the appropriate calendar dates according to the scheme, showed the presence of antibodies to the polioviruses in 81.5-99.1% of the cases. There were more serologically negative children against the virus type III, and much less--against the virus type II. The value of the mean geometrical titres somewhat decreased with the advance of the children's age and the time lapse after the vaccination and revaccination. The greatest antibody titres determined were against the poliovirus type II, and the least--against type III. No antibodies against the viruses of types I and III were revealed in case of deficiency against the poliovirus type II. The number of children with the absence of antibodies against the poliovirus of all the types was insignificant.