Immune structure of the population in some regions of the USSR with respect to Legionella pneumophila

For the first time in the USSR the structure of the immunity of different population groups to L. pneumophila was studied. Antibodies to L. pneumophila were detected in the passive hemagglutination test with the use of erythrocyte diagnosticum prepared at the Gamaleya Research Institute of Epidemiology and Microbiology (Moscow). The survey covered the total number of 2,902 persons in differ nt regions of the USSR, among them 2,430 adults and 472 children. Among the healthy adult population antibodies to L. pneumophila were detected, on the average, in 5.9% of persons. The highest number of persons with antibodies in diagnostic titers was detected among the population of the Baltic Republics (15.9%) and Kazakhstan (10.2%). The survey revealed an essential difference in the number of children aged 3-7 years, found to have antibodies to L. pneumophila, in the Brest region of the Byelorussian SSR (31.4%) and in the Turkmen SSR (1.3%). The high risk groups exposed to L. pneumophila infection were found to include narcological patients with the changed reactivity of the body and healthy adults professionally employed in earth-moving works.     

A calendar of prophylactic inoculations in wide practical use

The validity of immunizations, made in due time in children aged up to 7 years in accordance with the approved immunization schedule, is analyzed in this work. The content of antibodies to diphtheria, tetanus and poliomyelitis antigens in children immunized in accordance with the old and new schedules has been studied. This study has revealed that the injection of adsorbed DPT vaccine to children aged 3-4 months induces fully valid immune response to all antigens under study. The level of measles and parotitis antibodies after the injections of measles and parotitis vaccines, introduced separately and simultaneously, has been measured. The simultaneous administration of these preparations did not decrease the levels of immunity to parotitis and measles.     

Total immunization of children against influenza decreases morbidity in a number of diseases among elderly persons during influenza epidemic

Immunization of children aged 3-6 years in kindergartens and school children aged 7-17 years against influenza with inactivated influenza vaccine was carried out in two districts of the Moscow region. The comparison of morbidity in influenza-like diseases among the immunized children with that among nonimmunized children in control districts revealed that the effectiveness of immunization was 60.9% in kindergartens and 68.8% in schools. The analysis of morbidity in a number of diseases among 158,451 elderly persons not immunized against influenza demonstrated that, in comparison with the control districts, in those districts where mass immunization of children was carried out morbidity in influenza-like diseases among elderly persons was 3.4 times lower and, out of other 10 diseases under study, morbidity in 8 diseases was 1.5-2.6 times lower. As indicated by the data obtained in this study, total anti-influenza immunization of children in organized groups not only essentially decreased influenza morbidity among children, but also greatly decreased morbidity in influenza and a number of diseases, appearing as complications of influenza infection, among nonimmunized elderly persons during influenza epidemic.     

Retrospective analysis of a local cessation of vaccination against poliomyelitis: a possible scenario for the future

The global eradication of poliomyelitis will require substantial changes in immunization practices. One of the proposed scenarios includes cessation of vaccination with live oral poliovirus vaccine (OPV) and the creation of an OPV stockpile for emergency response in case of the reintroduction of poliovirus into circulation. We describe here a retrospective analysis of the cessation of OPV usage in a region of the Byelorussian Republic of the former Soviet Union in 1963 to 1966. During this period, a widespread circulation and evolution of independent lineages of vaccine-derived polioviruses took place in the region. Some of these lineages appeared to originate from OPV given to 40 children in the community during this period of essentially no vaccinations. The data demonstrate very high risks associated with both the local cessation of OPV vaccination and the proposed use of OPV to control a possible reemergence of poliovirus in the postvaccination period. The high transmissibility of OPV-derived viruses in nonimmune population, documented here, and the known existence of long-term OPV excretors should be also considered in assessing risks of the synchronized global cessation of OPV usage.     

The reactogenicity and immunological efficacy of a Klebsiella vaccine in donors

Klebsiella vaccine, when injected subcutaneously to donors, proved to be faintly reactogenic and safe. The injection of the vaccine had no effect on changes in the morphological composition of peripheral blood and on liver function. In persons with the initially low content of IgG an increase in this characteristic was observed after immunization. No changes in the synthesis of IgE occurred in healthy donors under the influence of immunization. The vaccine was shown to be immunogenic when introduced according to immunization schedules comprising 3 and 5 injections, the titer of Klebsiella antibodies increasing 3- to 5-fold.     

Prevention of mumps in preschool institutions using a live mumps vaccine made from strain L-3

The effectiveness of the emergency vaccinal prophylaxis of epidemic parotitis was studied in 19 children's day-care centers. As revealed in this study, the immunological effectiveness of vaccination did not depend on the age of vaccinees, but sharply decreased if live parotitis vaccine contained less than 10,000 HADU50 per immunization dose. After a single administration of the vaccine 91.1 +/- 0.98% of children were found to produce mumps antibodies. The immunization of children with live parotitis vaccine prepared from strain l-3 immediately after the first case of parotitis had been registered proved to be a highly effective measure. The coefficient of epidemiological effectiveness was 96.4%.     

Method for immunization against tuberculosis using BCG-M vaccine--a preparation with a reduced antigenic load

Experimental and clinical investigations on the possibility of reducing the antigenic content of the vaccine intended for the immunization of newborn infants have been made. Experiments on guinea pigs and white mice have demonstrated that the reduced dose of the preparation, twice as low by weight (0.025 mg), produces the same level of protection against tuberculosis as the full dose (0.5 mg). A new preparation with reduced antigenic content, vaccine BCG-M, has been developed, the technical specifications for this preparation have been approved, and its serial production has been allowed. Clinical tests have revealed that the use of the new preparation makes it possible to decrease the occurrence of unusual postvaccinal reactions and complications (lymphadenitis, ulceration) 3-fold and at the same time to increase the coverage of infants by primary immunization against tuberculosis by 7-8% annually. Since January 1986 this vaccine has been introduced into medical practice.     

Will Dengue Vaccines Be Used in the Public Sector and if so,How? Findings from an 8-country Survey of Policymakers and Opinion Leaders

Background

A face-to-face survey of 158 policymakers and other influential professionals was conducted in eight dengue-endemic countries in Asia (India, Sri Lanka, Thailand, Vietnam) and Latin America (Brazil, Colombia, Mexico, Nicaragua) to provide an indication of the potential demand for dengue vaccination in endemic countries, and to anticipate their research and other requirements in order to make decisions about the introduction of dengue vaccines. The study took place in anticipation of the licensure of the first dengue vaccine in the next several years.

Methods/Principal Findings

Semi-structured interviews were conducted on an individual or small group basis with government health officials, research scientists, medical association officers, vaccine producers, local-level health authorities, and others considered to have a role in influencing decisions about dengue control and vaccines. Most informants across countries considered dengue a priority disease and expressed interest in the public sector use of dengue vaccines, with a major driver being the political pressure from the public and the medical community to control the disease. There was interest in a vaccine that protects children as young as possible and that can fit into existing childhood immunization schedules. Dengue vaccination in most countries surveyed will likely be targeted to high-risk areas and begin with routine immunization of infants and young children, followed by catch-up campaigns for older age groups, as funding permits. Key data requirements for decision-making were additional local dengue surveillance data, vaccine cost-effectiveness estimates, post-marketing safety surveillance data and, in some countries vaccine safety and immunogenicity data in the local population.

Conclusions/Significance

The lookout for the public sector use of dengue vaccines in the eight countries appears quite favorable. Major determinants of whether and when countries will introduce dengue vaccines include whether WHO recommends the vaccines, their price, the availability of external financing for lower income countries, and whether they can be incorporated into countries'' routine immunization schedules.     

Background of recent JE vaccine issues

In Japan, more than 5,000 patients were reported in 1950, and there have been less than 10 cases annually since 1992. However, Japanese encephalitis virus caused of Japanese encephalitis (JE) are still existed highly and widely in the country, reported by National Institute of Infectious Diseases with serological examination among domestic pig population. JE immunization had been provided to children as category 1 routine immunization in Japan. However, the Ministry of Health, Labor and Welfare (HOHLW) decided not to recommend JE immunization to children as a routine immunization at May 2005. Major reason on this decision was that the Minter of MOHLW certified to pay loss of medical costs for the case of ADEM (acute disseminated encephalomyelopathy) after JE immunization, recognized as adverse events with JE vaccine, although MOHLW stated that the strict scientific evidence was unknown. MOHLW stated also that it is expected Vero cell derived JE vaccine should be replaced with the present mouse brain derived JE vaccine as the next generation, to be able to avoid theoretical possibility of neurological adverse events associated with JE vaccine. Small but increasing number of requests recently to be certified as health injuries on ADEM cases associated with JE immunization is also another reason for MOHLLW's decision. Further, fifth doses of JE vaccine given to children at 14-15 years old as a routine immunization was decided to be discontinued by MOHLW at July 2005, considering present epidemiological situation on JE and JE immunization status in Japan, although four doses has been recommended continuously as routine. The background details on JE vaccine issues decided by MOHLW in 2005 were reviewed on this paper.     

Experience with vaccine prophylaxis of hepatitis B among different groups of children

The immunological activity of different vaccines against hepatitis B was evaluated in the Hepatological Center organized on the basis of the Infectious Hospital in Tula. Newborn infants were immunized with the use of the following vaccines: Engerix B (Belgium), Combiotech (Russia), Euvax B (Aventis Pastèur, South Korea). Altogether, after the full course of immunization anti-HBs were detected in 76 children out of 81 (in 93.8%). Vaccine Engerix B, when introduced according to the schedule 0-1-2-12 months, exhibited high immunogenic properties in a group of infants born of women with persistent HBs-antigenemia. Anti-HBs at a concentration exceeding 1000 I.U./I could be detected in 84.6%. In another group of children immunized according to the schedule 0-1-6 months first with vaccine Combiotech at the age of 0 and 1 month, then (at the age of 6 months) with vaccine Euvax, the presence of postvaccinal anti HBs at protective concentration was registered in all children. After immunization against hepatitis B with the use of all above-mentioned vaccines introduced according to both schedules high immunological activity and safety of immunization were noted.     

The control of viral diseases in the developing countries with the use of existing vaccines]

In developing countries, every year about 70 million measles cases occur with 1.5 million deaths, over 200,000 children contract paralytic poliomyelitis, 50 million people get infected with viral B hepatitis causing over 1 million deaths, and several thousand people perish because of yellow fever according to WHO data. At the present time, there are 12 vaccines against viruses: vaccines against German measles and mumps in addition to the above. The universal immunization program (UIP) of WHO targets measles and polio. In 1989, a WHO resolution envisioned a 90% immunization coverage by the year 2000. Measles vaccination is recommended for children aged 9-23 months, since most children have maternal antibodies during the first 3-13 months of age. The Edmonston-Zagreb vaccine provided seroconversion of 92, 96, and 98% for 18 months vs. the 66, 76, and 91% rate of the Schwarz vaccine. In the US, measles incidence increased from 1497 cases in 1983 to 6382 cases in 1988 to over 14,000 cases in 1989, prompting second vaccination in children of school age. The highest incidence of polio was registered in Southeast Asia, although it declined from 1 case/100,000 population in 1975 to .5/100,000 in 1988. Oral poliomyelitis vaccine (OPV) provides protection: there is only 1 case/2.5 million vaccinations. Hepatitis B has infected over 2 billion people. About 300 million are carriers, with a prevalence of 20% in African, Asian, and Pacific region populations. Plasmatic and bioengineered recombinant vaccine type have been used in 30 million people. The first dose is given postnatally, the second at 1-2 months of age, and the 3rd at 1 year of age. Yellow fever vaccine was 50 years old in 1988, yet during 1986-1988 there were 5395 cases with 3172 deaths in Africa and South America. Vaccination provides 90-95% seroconversion, and periodic follow-up vaccinations under UIP could eradicate these infections and their etiologic agents.     

Vaccines for control of fertility.

Major developments in birth control vaccines are on the horizon. The human chorionic gonadotropin (hCG) vaccine has entered phase II clinical trials after successful completion of phase I studies at 5 centers in India and 4 centers abroad. It is the most advanced vaccine of its type in the world. The trials are being conducted on women of proven fertility who are sexually active. The available results indicate the efficiency of the vaccine to prevent pregnancy in women at or above titres of 50 ng/ml. A vaccine inducing antibodies against gonadotropin releasing hormone (GnRH) has been approved in India for trials in postpartum women, to determine whether immunization can help prolong lactational amenorrhea. The GnRH vaccine is also in clinical trial in prostate cancer patients at 2 centers in India and in Austria and the Dominican Republic. The follicle stimulating hormone (FSH) vaccine is about to enter phase I clinical trial after completing experimental and toxicological studies. A vaccine against FSH has been developed for human males employing ovine FSH (oFSH) as an immunogen. oFSH adsorbed on alum induces antibodies reactive with human FSH in bonnet monkeys. Immunization leads to oligospermia with resultant impairment of fertilization potential. No reduction in testosterone levels has been reported. Research is in progress to identify antigens on spermatozoa, which could serve as vaccine candidates. PH-20, a protein located on the inner acrosomal membrane of capacitated sperms, has been reported to have 100% contraceptive efficacy in both sexes of guinea pigs in active immunization studies. cDNA probes of PH-20 cross-react with genomic DNAs of mouse, rat, hamster, and human. The sperm antigen, lactate dehydrogenase C4 (LDH-C4), is a glycolytic enzyme. Active immunization with LDH-C4 suppressed fertility in mice, rabbits, and baboons. SP-10, which is a testis-specific human sperm protein, is also a promising candidate.     

Immunoprophylaxis of respiratory syncytial virus: global experience

Respiratory syncytial virus (RSV) infects nearly all children by age 2 years, and it causes considerable illness and death in certain high-risk pediatric populations. Historically, treatment for RSV has been symptomatic, and developing a safe and effective vaccine has been a challenge. Therefore, research efforts have turned to passive immunization as the best option to control RSV. Palivizumab, a genetically engineered humanized monoclonal antibody, has been shown to reduce RSV-related hospitalizations significantly, with few adverse effects. It was approved for use in high-risk children in the USA in 1998 and in Europe in 1999; it is now approved for use in more than 45 countries. The efficacy and safety of palivizumab continue to be supported by both clinical trial and outcomes data.     

Reactions to and immunogenic properties of the combined vaccine Bubo-M for immunization of children against diphtheria, tetanus and viral hepatitis B

Bubo-M, the first Russian combined vaccine, was found to have low reactogenicity. The difference between the number of postvaccinal reactions in the group of children immunized with Bubo-M (25.9%) and those in the group of children who had been simultaneously injected into different sites of the body with ADS-M toxoid (adsorbed DT toxoid with reduced antigen content) and hepatitis B vaccine (26.7%) was not statistically significant. Following immunization a considerable increase in the level of diphtheria and tetanus antibodies (p < 0.005) was observed in all children (100%), the level of HBs antibodies in the group of children immunized with Bubo-M (the geometric mean titer: 13,721 IU/l) essentially exceeding that observed in the control group injected with ADS-M toxoid and hepatitis B vaccine (the geometric mean of the titer: 2,441 IU/l). Bubo-M was duly registered and allowed for industrial production and medical use.     

A cultured concentrated inactivated vaccine against tick-borne encephalitis studied during the immunization of children and adolescents

The word deals with the results obtained in the study of the reactogenicity and immunological activity of concentrated and inactivated tissue-culture tick-borne encephalitis vaccine, manufactured by the Chumakov Institute of Poliomyelitis and Viral Encephalitides, in the immunization of children and adolescents. The vaccine proved to be moderately reactogenic and exhibited pronounced immunological activity. In 91.5% of the immunized children the fourfold increase of the antibody level was observed. On the basis of the data obtained in this study the tick-borne encephalitis vaccine was recommended for use in medical practice for the prophylaxis of tick-borne encephalitis among children and adolescents.     

Assessment of the prophylactic effectiveness of an inactivated influenza vaccine by immunizing schoolchildren in the springtime

To evaluate the prophylactic effectiveness of influenza inactivated chromatographic vaccine, limited epidemiological observations were made on school children aged 11-14 years in Leningrad, in the autumn of 1981 and the spring of 1982. For immunization, made in a single administration, the vaccine composed of A (H3N2) + +A (H1N1) and containing 3.0-3.4 micrograms of hemagglutinin of each component per 0.2 ml of the preparation was used. Altogether 6928 schoolchildren were under observation; of these, 3686 children were immunized and 3242 children received placebo. The results of questioning and the analysis of morbidity rate among the schoolchildren, both immunized and receiving placebo, showed the safety and low reactogenicity of the vaccine irrespective of the time of the immunization campaign. The immunogenic potency of the preparation, as indicated by all observation results, proved to be higher in spring, than in autumn. The data thus obtained indicate that children immunized in spring were better protected and retained a higher level of protection within 12 months after immunization. The shift of the time of the immunization campaign from autumn to spring increased the immune layer in the groups of children by 16.5%. In 10 months after spring immunization the morbidity rate in influenza and acute respiratory diseases among the vaccinees was found to decrease 1.7 times.     

Experience of the People's Republic of Bulgaria in controlling diphtheria, tetanus and whooping cough

The analysis of the morbidity and mortality rates in diphtheria, tetanus and pertussis in Bulgaria after the introduction of the compulsory mass immunization of children with combined DPT vaccine is presented. These data indicate that morbidity in diphtheria, tetanus and pertussis has sharply decreased. Favorable results with respect to these three diseases are the consequence of the complete coverage of the child population by immunization with the vaccine whose quality has been steadily improving for the last 20 years. A higher purity of toxoids has been achieved, and at present it exceeds the latest WHO requirements. Pertussis vaccine is produced with the use of strains whose serological characteristics correspond to those of the pertussis strains circulating in the country. The study of the reactogenicity of DPT vaccine, carried out over the period of 20 years, has shown that the vaccine has low reactogenicity.     

Immunological effectiveness of a dried group-A meningococcal polysaccharide vaccine

The immunological effectiveness of dried group A meningococcal polysaccharide vaccine, developed at the Gabrichevsky Research Institute of Epidemiology and Microbiology, Moscow, for children aged 5-14 years was studied. The intensiveness of the immune response of children to 0.5 ml of the vaccine introduced in a single injection was evaluated by a rise in the level of agglutinating antibodies to group A meningococcal polysaccharide in the sera of the vaccinees 3-4 weeks after immunization with the following optimum doses: 25 micrograms for children aged 5-8 years, 50 micrograms for children aged 9-13 years and 75 micrograms for children aged 14 years and over. The vaccine was shown to be highly immunogenic. Antibodies to group A meningococcal polysaccharide were identified as IgM. These antibodies in a titer of 1:40 and higher could be detected in 90% of the vaccinated children in the younger age group, 7 months after immunization.     

The dynamics of the T-lymphocyte subpopulations and the peroxidase activity of the neutrophils in children immunized with a live mumps vaccine

The amount of T-helpers and T-suppressors and the T-helper/T-suppressor ratio were determined in 30 practically healthy children aged 1.5-2 years, immunized with live parotitis vaccine prepared from strain -3. One immunization dose of the vaccine contained 7,950 HADU50. In all children peroxidase activity in the cytoplasm of neutrophils was studied. This investigation revealed that in all examined children the formation of immune response to immunization with live parotitis vaccine was accompanied by the development of an imbalance of immunoregulatory T-cell subpopulations and by functional changes in neutrophils, characterized by the inhibition of peroxidase activity. The changes revealed in this study were most pronounced in children with a high level of antibody formation.     

Study of combined vaccination against yellow fever and measles in infants from six to nine months

A study has been carried out in the Ivory Coast to assess the efficacy of a combined vaccine against yellow fever and measles relative to that of each vaccine administered separately. Healthy children aged six to nine months were recruited and divided into two age groups: less than seven months (group I) and more than eight months (group II). In each group, they were randomly assigned to receive either yellow fever vaccine only (A), measles vaccine only (B), or the combined vaccine (C). The serological responses to measles and yellow fever were assessed in 219 initially seronegative children 45 days after immunization. More than 90% of the children developed yellow fever haemagglutination inhibiting antibodies. Neither age nor combination with measles vaccine influenced the responses to yellow fever vaccine. Measles haemagglutinational inhibiting antibodies were found in 97% of the children and the seroconversion rate was influenced neither by age nor by combination with yellow fever vaccine. Younger infants had lower titres of measles antibody. No particular adverse reactions were notified during the follow up. This study shows that combined yellow fever and measles vaccines are immunogenic in infants from the age of six months. Controlling yellow fever in endemic areas and the prevention of measles in young infants may greatly benefit by this combination.