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.     

Qualification of long-stored samples of serum banks for seroepidemiological studies.

Serum samples were tested for antibodies against polio virus and measles virus from two serum banks after having been stored under different conditions for several years. The results are compared with those ones obtained immediately after sampling. Despite of small increases of antibody-negative samples and of small decreases of the titres the suitability of the samples stored could be shown. Special attention should be given to the establishment, e.g. in the framework of Expanded Programme on Immunization of the World Health Organization and in order to study new pathogens unknown to date, and the technical preconditions for that should be planed.     

The cluster method in conducting epidemiological research

The Expanded Programme on Immunization (EPI) whose goal is to reduce morbidity and mortality by providing children with immunizations against diphtheria, pertussis, tetanus, poliomyelitis, measles, and tuberculosis continually faces the problem of documenting immunization coverage rates. Therefore the EPI seeks simple, effective, and inexpensive methods of evaluation which could be implemented in different countries. An example of such a method is a simplified cluster sampling technique of estimation of immunization coverage through the examination of 210 children, selected randomly as 30 groups of 7 children each. In 1978-1984 more than 1000 immunization coverage surveys were performed all over the world, mainly in developing countries. In a modified way this method is also used to collect data on morbidity and mortality of certain EPI target diseases as well as diarrhoeal diseases.     

中山市2011年健康儿童脊髓灰质炎、麻疹和乙型肝炎抗体水平监测

目的了解中山市1~14岁健康儿童脊髓灰质炎(脊灰)病毒、麻疹病毒和乙型肝炎(乙肝)病毒抗体水平状况,为维持无脊灰、消除麻疹和控制乙肝提供依据。方法采用多阶段整群抽样方法,随机选择220名1~14岁健康儿童抽取静脉血,采用ELISA法检测麻疹病毒抗体Ig G、乙肝病毒表面抗原和抗体;用中和试验检测脊灰(Ⅰ、Ⅱ、Ⅲ)型病毒中和抗体。结果脊灰、麻疹和乙肝病毒抗体阳性率分别为91.36%、93.18%和66.36%,脊灰病毒Ⅰ、Ⅱ、Ⅲ型和麻疹病毒抗体几何平均滴度(GMT)分别为1∶215.90、1∶119.05、1∶31.40和1∶1 254.45;乙肝病毒表面抗原阳性率为1.36%。结论中山市1~14岁健康儿童对脊灰病毒具有较高的免疫水平,已形成对脊灰病毒有效的免疫屏障;乙肝得到有效控制;但麻疹未能形成有效的免疫屏障。     

Poliomyelitis and vaccination strategy in Russian Federation in post-certification period

Immunization schedules implemented in various countries by using poliovirus vaccines are presented. Approaches to prevent development of vaccine associated paralytic poliomyelitis and risk groups for this infection are discussed. In recent years poliomyelitis morbidity situation in the European region has become more complex, with the example of poliomyelitis outbreak in Tajikistan in 2010. The resulting problem of protection of Russian against emergence and spread of poliomyelitis caused by wild type virus is discussed.     

The contribution of vaccination to global health: past,present and future

Vaccination has made an enormous contribution to global health. Two major infections, smallpox and rinderpest, have been eradicated. Global coverage of vaccination against many important infectious diseases of childhood has been enhanced dramatically since the creation of WHO''s Expanded Programme of Immunization in 1974 and of the Global Alliance for Vaccination and Immunization in 2000. Polio has almost been eradicated and success in controlling measles makes this infection another potential target for eradication. Despite these successes, approximately 6.6 million children still die each year and about a half of these deaths are caused by infections, including pneumonia and diarrhoea, which could be prevented by vaccination. Enhanced deployment of recently developed pneumococcal conjugate and rotavirus vaccines should, therefore, result in a further decline in childhood mortality. Development of vaccines against more complex infections, such as malaria, tuberculosis and HIV, has been challenging and achievements so far have been modest. Final success against these infections may require combination vaccinations, each component stimulating a different arm of the immune system. In the longer term, vaccines are likely to be used to prevent or modulate the course of some non-infectious diseases. Progress has already been made with therapeutic cancer vaccines and future potential targets include addiction, diabetes, hypertension and Alzheimer''s disease.     

Vaccines and future global health needs

Increased international support for both research into new vaccines and their deployment in developing countries has been evident over the past decade. In particular, the GAVI Alliance has had a major impact in increasing uptake of the six common infant vaccines as well as those against hepatitis B and yellow fever. It further aims to introduce pneumococcal and rotavirus vaccines in the near future and several others, including those against human papillomavirus, meningococcal disease, rubella and typhoid not long after that. In addition, there is advanced research into vaccines against malaria, HIV/AIDS and tuberculosis. By 2030, we may have about 20 vaccines that need to be used in the developing world. Finding the requisite funds to achieve this will pose a major problem. A second and urgent question is how to complete the job of global polio eradication. The new strategic plan calls for completion by 2013, but both pre-eradication and post-eradication challenges remain. Vaccines will eventually become available beyond the field of infectious diseases. Much interesting work is being done in both autoimmunity and cancer. Cutting across disease groupings, there are issues in methods of delivery and new adjuvant formulations.     

Monkey viral pathology in the Sukhum colony and modeling human viral infections

The data characterizing spontaneous infections of Old World monkeys: measles, poliomyelitis, hepatitis A (HPA), encephalomyocarditis, coronavirus infection, simian hemorrhagic fever (SHF), are presented. The experimental infections were reproduced with the isolated pathogens. On these models, pathogenesis and epidemiology of these diseases were studied. The efficiency of poliomyelitis, measles and HPA vaccines is shown. The priority of data on the discovery of earlier unknown disease—SHF and “Sukhumi” virus—are emphasized. Several important pathogenic mechanisms common for various hemorrhagic fevers were studied on experimental SHF of macaques. This model is uniquely safe and adequate for the assessment of therapy of hemorrhagic fevers dangerous for humans.     

Mechanism of Injury-Provoked Poliomyelitis

Skeletal muscle injury is known to predispose its sufferers to neurological complications of concurrent poliovirus infections. This phenomenon, labeled “provocation poliomyelitis,” continues to cause numerous cases of childhood paralysis due to the administration of unnecessary injections to children in areas where poliovirus is endemic. Recently, it has been reported that intramuscular injections may also increase the likelihood of vaccine-associated paralytic poliomyelitis in recipients of live attenuated poliovirus vaccines. We have studied this important risk factor for paralytic polio in an animal system for poliomyelitis and have determined the pathogenic mechanism linking intramuscular injections and provocation poliomyelitis. Skeletal muscle injury induces retrograde axonal transport of poliovirus and thereby facilitates viral invasion of the central nervous system and the progression of spinal cord damage. The pathogenic mechanism of provocation poliomyelitis may differ from that of polio acquired in the absence of predisposing factors.     

Protection against yellow fever in monkeys by immunization with yellow fever virus nonstructural protein NS1.

Immunization of monkeys with yellow fever virus-specified nonstructural protein NS1 resulted in protection against fatal hepatitis as well as marked reduction in the magnitude of viremia after subcutaneous challenge with yellow fever virus. The results may be relevant to the design of possible subunit or recombinant flavivirus vaccines.     

Prospects for new viral vaccines

Animal virology has made outstanding contributions to preventive medicine by the development of vaccines for the control of infectious disease in man and animals. Cost-benefit analysis indicates substantial savings in health care costs from the control of diseases such as smallpox, poliomyelitis, yellow fever and measels. Areas for further development include vaccines for influenza (living, attenuated virus), the herpes group (varicella: cytomegalovirus), respiratory syncytial virus, rotavirus and hepatitis A, B, and non A/non B. The general options for vaccine formulation are discussed with particular emphasis on approaches with the use of viral genetics to 'tailor make' vaccine viruses with defined growth potential in laboratory systems, low pathogenicity, and defined antigens. Current progress with the development of an inactivated hepatitis B vaccine is reviewed as a case study in vaccine development. The impact of recent experiments in cloning hepatitis B virus DNA in E. coli on the production of a purified viral polypeptide vaccine is assessed.     

消灭脊髓灰质炎行动现状分析及免疫策略建议

脊髓灰质炎曾在全球广泛流行和传播,严重危害儿童健康。自1988年世界卫生大会发起全球消灭脊髓灰质炎行动倡议以来,全球脊髓灰质炎防控工作取得显著进展,但消灭脊髓灰质炎工作仍面临重重挑战。在目前维持无脊髓灰质炎状态下,我国面临的主要问题是疫苗相关麻痹型脊髓灰质炎(vaccine associated paralytic poliomyelitis, VAPP)病例和脊髓灰质炎疫苗衍生病毒(vaccine-derived poliovirus,VDPV)病例的发生。为此,通过回顾消灭脊髓灰质炎工作取得的进展,总结不同国家或地区在消灭脊髓灰质炎过程中所采用的防控策略,尤其是不同国家或地区的脊髓灰质炎疫苗使用经验,分析消灭脊髓灰质炎最后阶段面临的挑战,进而提出应对策略和建议,即科学评价防控措施、适时调整脊髓灰质炎免疫策略、努力消除接种犹豫并提高疫苗接种率,这对早日实现根除脊髓灰质炎的目标是非常有必要的。     

Global measles elimination

Measles remains a leading vaccine-preventable cause of child mortality worldwide, particularly in sub-Saharan Africa where almost half of the estimated 454,000 measles deaths in 2004 occurred. However, great progress in measles control has been made in resource-poor countries through accelerated measles-control efforts. The global elimination of measles has been debated since measles vaccines were first licensed in the 1960's, and this debate is likely to be renewed if polio virus is eradicated. This review discusses the pathogenesis of measles and the likelihood of the worldwide elimination of this disease.     

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.     

The poliomyelitis story: a scientific hegira

There is evidence that paralytic poliomyelitis occurred in ancient times, but it was not recognized as a distinct disease until the eighteenth century and did not come into prominence until the late nineteenth century when epidemics began to appear. Outbreaks of increasing size were reported first in the Scandinavian countries, then in the United States and elsewhere, to the surprise and consternation of the medical profession. Poliovirus was first isolated in 1908, but many years of intensive research were required before the epidemiology and pathogenesis of the disease were sufficiently understood to allow preventive measures to be devised. The road to eventual success was complicated by controversies, setbacks, and tragedies, played out and influenced by many powerful personalities. Today there are two effective vaccines. The disease has been virtually eliminated in countries where they have been used extensively, yet in the developing areas of the world recent "lameness surveys" indicate that the incidence of paralytic poliomyelitis is as high as it was during the peak years in the United States in the early 1950s. The challenge now is to use the available vaccines to extend control to the developing countries and eventually to achieve elimination of the disease worldwide.     

Is poliomyelitis a serious problem in developing countries?--lameness in Ghanaian schools.

A postal survey of lameness in schools throughout Ghana showed an estimated prevalence of lameness attributable to poliomyetitis of 5-8 per 1000 school-aged children and an estimated mean annual incidence of paralytic poliomyelitis of 23 per 100 000 population. Official reported incidence rates range from 0-1 to 2-1 per 100 000 population, indicating that at least 90% of cases are not reported. No evidence of epidemics was found to account for these high rates. These suggest that mean annual incidence rates in tropical endemic countries have always been as great, if not greater, than those experienced by temperate countries during epidemic periods in the twentieth century and that the total number of cases of paralytic poliomyelitis occurring in the world each year has been reduced by only 25% since the advent of polio vaccine. Immunisation against poliomyelitis must have a high priority in Ghana and other tropical countries where the disease is endemic.     

Gates,GAVI, the glorious global funds and more: all you ever wanted to know

Global immunization programmes have achieved some remarkable successes. In 1977, Frank Fenner's Commission declared smallpox to have been eradicated by an 11-year-long intensive campaign. The Expanded Programme on Immunization encompassed six important childhood vaccines and reached over three-quarters of the world's children. Polio eradication has gone remarkably well, with only 10 out of 200 countries reporting residual cases. But amidst all the good news, there is also bad news. Coverage is variable; infrastructure is crumbling; and newer vaccines are not being incorporated in many country programmes. The Bill and Melinda Gates Foundation has introduced a new dynamic here. From their initial gift of $100 million in December 1998, their commitment to date is US$1.5 billion - and rising. At the centre is a Global Children's Vaccine Fund which permitted the launch, in January 2000, of the Global Alliance for Vaccines and Immunization. This is targeted to the 74 poorest countries of the world and is designed to improve vaccination infrastructure, to purchase newer vaccines and to support research and development. Even before we know how successful this programme will be, it has had its imitators. The Global Fund to Fight AIDS, TB and Malaria borrowed many concepts from GAVI. The Global Alliance for Improved Nutrition announced in May 2002 does so as well, and is heavily supported by Gates. Highly effective parasite control programmes antedate all this but will be much strengthened. However, we still face a sizeable budgetary gap both for research and for bringing the best advances to all people who need them.     

No evidence for prolonged excretion of polioviruses in persons with residual paralytic poliomyelitis in Ethiopia, Pakistan and Guatemala.

Persons who have developed acute flaccid paralysis following infection with wild-type polioviruses or vaccine-associated paralytic poliomyelitis usually excrete polioviruses for only a few weeks. However, some patients with paralytic poliomyelitis have had prolonged excretion of polioviruses for periods of up to 10 years after onset of disease. Most prolonged excretors have been identified in industrialized countries. We studied 348 patients 2-28 years old in Ethiopia, Pakistan and Guatemala with residual paralytic poliomyelitis to determine if they had IgA or IgG deficiency or persistent poliomyelitis excretion at least 1 year after onset of disease. None of the 348 affected individuals had IgG deficiency or persistent poliovirus excretion. One child had borderline low serum IgA concentration. Since we did not study children under 2 years of age, persons born with IgG deficiency disorders may have died in developing countries where replacement immunoglobulin therapy is not readily available. Nevertheless, persistent poliovirus excretion among persons 2 years of age and older with residual paralytic poliomyelitis is uncommon in developing countries.     

Production of hepatitis B surface antigen in recombinant plant systems: an update

There is a growing interest to develop oral vaccines for infectious diseases, as it is the most convenient and effective way to attain mucosal immunity. Hepatitis B continues to be a major infectious disease in many developing countries despite the availability of recombinant vaccine. On a global scenario, Hepatitis B Virus infection is probably the single most prevalent cause of persistent viraemia in humans. There are about 350 million chronic carriers of HBV, which is about 5% of the total world population. It is estimated that 75-100 million of them will die of liver cirrhosis and/or hepatocellular carcinoma. Progress in plant genetic engineering has enabled the transfer of useful genes for desirable traits. The recent trend is to use this technique to exploit plants as biofactories for the production of therapeutic proteins including vaccines. Rapid progress has been made in this area to develop plant-based vaccines for hepatitis B. This review describes the expression, characterization, and immunogenicity studies of hepatitis B vaccines produced in recombinant plant systems and their implications for developing a plant-based vaccine.     

Enteroviruses in the XX and XXI centuries

The modern view of the role of enteroviruses in the eradication of poliomyelitis is presented. Enteroviruses were discovered in the XX century. In the 1950s they caused great epidemics of poliomyelitis and serous meningitis in many countries of the world. The introduction of oral poliomyelitis vaccine (OPV) into medical practice made it possible to eliminate the epidemics of poliomyelitis in a short time. Poliomyelitis morbidity was reduced to sporadic cases and in a number of regions disappeared. OPV produced non-specific influence also on the epidemics of serous meningitis, as well as on a case incidence. The eradication of poliomyelitis viruses and the cessation of immunization with OPV will not result in eradication of paralytic diseases. Paralytogenic viruses of 20 serotypes circulate in nature, and some of these viruses are capable of causing the outbreaks of severe paralytic diseases. The authors propose either to retain immunization with OVP as tour immunizations with monovaccine of type 2, or to create new live enterovirus vaccines on the basis of avirulent enterovirus strains.