Comprehensive Vaccination Program Research Articles

Interplay of Carbohydrate and Carrier in Antibacterial Glycoconjugate Vaccines.

Bacterial infections are a serious health concern and are responsible for millions of illnesses and deaths each year in communities around the world. Vaccination is an important public health measure for reducing and eliminating this burden, and regions with comprehensive vaccination programs have achieved significant reductions in infection and mortality. This is often accomplished by immunization with bacteria-derived carbohydrates, typically in conjunction with other biomolecules, which induce immunological memory and durable protection against bacterial human pathogens. For many species, however, vaccines are currently unavailable or have suboptimal efficacy characterized by short-lived memory and incomplete protection, especially among at-risk populations. To address this challenge, new tools and techniques have emerged for engineering carbohydrates and conjugating them to carrier molecules in a tractable and scalable manner. Collectively, these approaches are yielding carbohydrate-based vaccine designs with increased immunogenicity and protective efficacy, thereby opening up new opportunities for this important class of antigens. In this chapter we detail the current understanding of how carbohydrates interact with the immune system to provide immunity; how glycoengineering, especially in the context of glycoconjugate vaccines, can be used to modify and enhance immune responses; and current trends and strategies being pursued for the rational design of next-generation glycosylated antibacterial vaccines. Graphical Abstract.

The Ilocos Norte Communities against Rabies Exposure Elimination Project in the Philippines: Epidemiological and Economic Aspects.

As canine rabies control in Africa and Asia transitions from research-led proof-of-concept studies to government-led programs for elimination, experience and evidence of their impact and costs must be shared for the benefit of future programs. The Ilocos Norte Communities against Rabies Exposure project was implemented in April 2012 by the provincial veterinary and health offices and supported by many other partners. It delivered a comprehensive dog vaccination program and increased awareness of the need for postexposure prophylaxis (PEP), aiming to eliminate human and animal rabies cases from Ilocos Norte by 2015. Prior to the intervention, confirmed rabies cases in dogs were between 19 and 50 per year (2008–2011). The primary outcome of the project was a reduction in rabies cases in both dogs and humans to 0 in 2014 and 2015, which has subsequently been maintained. Animal bite consultations increased significantly during the project. Economic data for the dog vaccination and PEP components of the project were collated for two sites: Laoag City (an urban setting) and Dingras Municipality (a rural setting) between 2012 and 2014. The average programmatic cost of vaccinating each dog was $4.54 in Laoag City and $8.65 in Dingras, and costs fell as the project reached more dogs. The average costs of providing PEP were $69.72 per patient and $49.02 per patient for the two sites, respectively, again falling as the project reached more people. External donor contributions contributed less than 20% of dog vaccination costs and less than 1% of PEP costs. The project demonstrated that rabies elimination can be achieved in a short period of time, with concerted effort across multiple sectors. A lack of clear dog population estimates hampered interpretation of some aspects of the programme. From 2016, the provincial government has assumed complete responsibility for the programme and must now continue the vaccination and surveillance efforts. Although safeguards are in place, reintroduction from surrounding areas remains a threat, and vigilance must be maintained.

Economic evaluation of universal newborn hepatitis B vaccination in China

ObjectiveTo estimate the long-term cost-effectiveness of universal newborn hepatitis B vaccination in China, an area of high endemicity. MethodA decision tree was used to describe perinatal hepatitis B virus (HBV) transmission, early infection and impact of vaccination. A Markov model based on 1-year cycles was used to simulate these impacts for the lifetime of a cohort of 10,000,000 infants born in 2002 in China. We compared both cost and health outcomes for two strategies: universal newborn vaccination comprising a timely birth dose (HepB1) with a three-dose vaccination (HepB3) compared with no vaccination. Univariate and probabilistic sensitivity analyses using Monte Carlo simulations were performed to test parameter uncertainty. ResultsOver the cohort's lifetime, 79,966 chronic infections, 37,553 cases of hepatocellular carcinoma (HCC) and 130,796 HBV related deaths would be prevented by universal infant vaccination. The prevalence of HBV infection is reduced by 76%. Over 743,000 life-years and 620,000 quality adjusted life years (QALYs) would be gained and there would be monetary benefits of more than 1 billion US dollars in medical care costs and lost productivity avoided. ConclusionThe newborn vaccination programme for Hepatitis B in China both gains QALYs and saves medical care costs. It is important to ensure that timely and comprehensive vaccination programmes continue.

Ecological Niche Modeling to Estimate the Distribution of Japanese Encephalitis Virus in Asia

Background Culex tritaeniorhynchus is the primary vector of Japanese encephalitis virus (JEV), a leading cause of encephalitis in Asia. JEV is transmitted in an enzootic cycle involving large wading birds as the reservoirs and swine as amplifying hosts. The development of a JEV vaccine reduced the number of JE cases in regions with comprehensive childhood vaccination programs, such as in Japan and the Republic of Korea. However, the lack of vaccine programs or insufficient coverage of populations in other endemic countries leaves many people susceptible to JEV. The aim of this study was to predict the distribution of Culex tritaeniorhynchus using ecological niche modeling.Methods/Principal FindingsAn ecological niche model was constructed using the Maxent program to map the areas with suitable environmental conditions for the Cx. tritaeniorhynchus vector. Program input consisted of environmental data (temperature, elevation, rainfall) and known locations of vector presence resulting from an extensive literature search and records from MosquitoMap. The statistically significant Maxent model of the estimated probability of Cx. tritaeniorhynchus presence showed that the mean temperatures of the wettest quarter had the greatest impact on the model. Further, the majority of human Japanese encephalitis (JE) cases were located in regions with higher estimated probability of Cx. tritaeniorhynchus presence.Conclusions/SignificanceOur ecological niche model of the estimated probability of Cx. tritaeniorhynchus presence provides a framework for better allocation of vector control resources, particularly in locations where JEV vaccinations are unavailable. Furthermore, this model provides estimates of vector probability that could improve vector surveillance programs and JE control efforts.

New approaches for influenza vaccination of healthcare workers

Vaccination of healthcare workers (HCWs) against influenza is an important component of infection control in healthcare settings but HCW vaccination rates remain low. Here we review current and emerging strategies for influenza vaccination of HCWs. Professional organizations have recommended annual influenza vaccination for HCWs since 1984, but HCW vaccination rates have improved minimally. Recent studies indicate that comprehensive influenza vaccination programs have failed to achieve adequate influenza vaccination rates for HCWs in spite of allocating substantial resources to HCW vaccination programs. Mandatory HCW influenza vaccination programs have been introduced and clearly outperform traditional comprehensive vaccination programs. Some argue that mandatory vaccination programs infringe on HCW autonomy, and introduction of mandatory vaccination programs can be controversial. Public reporting of institutional HCW influenza vaccination rates is another strategy to achieve high vaccination rates, as HCW influenza vaccination may be used in the future as a quality and safety metric. HCW influenza vaccination in the setting of a comprehensive infection control program is a core patient-safety practice. Mandatory HCW influenza vaccination and public reporting of HCW vaccination rates will complement one another in achieving substantial gains for HCW influenza vaccination programs.

Tetanus Immunity in Neonates in a Developed Country

Objective: In consideration of comprehensive and well-established vaccination programmes in industrialized countries, it is expected that immunity against tetanus among expectant mothers and their offspring is complete. Our study evaluated seroprotection against tetanus among newborns in Austria, who may gain passive immunity by transplacental transfer of maternal tetanus antibody. Methods: Cord blood samples from 99 deliveries were analyzed for antibody concentration against tetanus toxoid by standardized ELISA. Results: 85/99 (85.8%) individuals presented with levels of tetanus immunity having a protective antibody concentration ≧0.1 IU/ml. 9/99 (9.1%) samples showed low seropositivity, while in 5/99 (5.1%) samples no tetanus antibodies could be detected. The median antibody concentration was 0.95 IU/ml. Conclusions: Our data provide evidence for a lack of adequate tetanus immunity in 14.2% of newborns delivered in an Austrian University Hospital. This investigation is emphasizing the importance of stringent regimens concerning prenatal vaccination care, even in countries with generalized immunization programs. If indicated, maternal immunization during pregnancy should be initiated for protection of newborns.

Production of the 42-kDa fragment of Plasmodium falciparum merozoite surface protein 1, a leading malaria vaccine antigen, in Arabidopsis thaliana seeds

Malaria is widely associated with poverty, and a low-cost vaccine against malaria is highly desirable for implementing comprehensive vaccination programmes in developing countries. Production of malaria antigens in plants is a promising approach, but its development has been hindered by poor expression of the antigens in plant cells. In the present study, we targeted plant seeds as a low-cost vaccine production platform and successfully expressed the Plasmodium falciparum 42-kDa fragment of merozoite surface protein 1 (MSP1₄₂), a leading malaria vaccine candidate, at a high level in transgenic Arabidopsis seeds. We overcame hurdles of transcript and protein instabilities of MSP1₄₂ in plants by synthesizing a plant-optimized MSP1₄₂ cDNA and either targeting the recombinant protein to protein storage vacuoles or fusing it with a stable plant storage protein. An exceptional improvement in MSP1₄₂ expression, from an undetectable level to 5% of total extractable protein, was achieved with these combined strategies. Importantly, the plant-derived MSP1₄₂ maintains its natural antigenicity and can be recognized by immune sera from malaria-infected patients. Our results provide a strong basis for the development of a plant-based, low-cost malaria vaccine.

Health disparities in liver disease: Time to take notice and take action

Health disparities between various groups in the United States have received increasing attention over the past decade, and solving this problem has become a major public health priority. The Federally-sponsored Healthy People 2010, our nation’s health promotion and disease prevention initiative, calls to “eliminate health disparities, including differences that occur by gender, race or ethnicity, education or income, disability, geographic location, or sexual orientation” (1). These health disparity populations constitute a large proportion of patients with liver disease (2, 3), and evidence suggests that these populations are disproportionately affected by several common hepatic disorders that include viral hepatitis (4-7), non-alcoholic fatty liver disease (8, 9), and hepatocellular carcinoma (10-13). Health disparities, therefore, have special relevance to the field of hepatology. This policy statement aims to inform the hepatology community about the importance of health disparities in our field, provide a framework for approaching health disparities in research and clinical practice, and recommend ways the AASLD and its membership can work toward the reduction and elimination of health disparities in patients with liver disease.

Burden of cervical cancer in the United States, 1998-2003

Recent interest in human papillomavirus (HPV)-associated cancers and the availability of several years of data covering 83% of the US population prompted this descriptive assessment of cervical cancer incidence and mortality in the US during the years 1998 through 2003. This article provides a baseline for monitoring the impact of the HPV vaccine on the burden of cervical cancer over time. Data from 2 federal cancer surveillance programs, the Centers for Disease Control and Prevention (CDC)'s National Program of Cancer Registries and the National Cancer Institiute's Surveillance, Epidemiology, and End Results Program, were used to examine cervical cancer incidence by race, Hispanic ethnicity, histology, stage, and US census region. Data from the CDC's National Center for Health Statistics were used to examine cervical cancer mortality by race, Hispanic ethnicity, and US census region. The incidence rate of invasive cervical cancer was 8.9 per 100,000 women during 1998 through 2003. Greater than 70% of all cervical carcinomas were squamous cell type, and nearly 20% were adenocarcinomas. Cervical carcinoma incidence rates were increased for black women compared with white women and for Hispanic women compared with non-Hispanic women. Hispanic women had increased rates of adenocarcinomas compared with non-Hispanic women. The South had increased incidence and mortality rates compared with the Northeast. Disparities by race/ethnicity and region persist in the burden of cervical cancer in the US. Comprehensive screening and vaccination programs, as well as improved surveillance, will be essential if this burden is to be reduced in the future.

Epidemiology of Human Papillomavirus Infection and Cervical Cancer and Future Perspectives in Hong Kong, Singapore and Taiwan

Hong Kong, Singapore and Taiwan are three island states that are newly emerged affluent economic areas in Asia. The majority of the populations are ethnically Chinese with a total population of 6.98, 4.5 and 23 million, respectively. Cervical cancer has been declining over the last thirty years in all three states and is largely attributable to widespread opportunistic cervical cancer screening. The age-standardized incidence rates of cervical cancer are 9.6 per 100,000 women in Hong Kong in 2004, 10.6 per 100,000 women in Singapore in 2002 and 18.6 per 100,000 women in Taiwan in 2003. High prevalence of human papillomavirus (HPV) was observed in all three states. In cervical cancer, HPV 16 and 18 are the two most prevalent HPV types, but HPV 58 and 52 are also highly prevalent in these three states. Important epidemiological risk factors for invasive cervical cancer include smoking and age at sexual debut for women, although this is changing towards an earlier age. Of the three states, Taiwan was the first to have a comprehensive national screening programme in 1995 followed by Hong Kong in 2002 and Singapore in 2004. Women in these three states are well aware of cervical cancer and the preventative means by Pap smear screening, although their awareness and understanding of the role of HPV in cervical carcinogenesis is low. Prophylactic HPV vaccines have been licensed in the three states. Routine comprehensive public vaccination programme for adolescent girls has yet to be adopted by the governmental agency, despite an affirmative recommendation by medical professional bodies.

SENSORY HEARING LOSS IN CHILDREN WITH MUMPS WITH MUMPS INFECTION

Objective: Mumps infection is endemic in Iran and mumps parotiditis is a common disease in Iranian children. There has been a dramatic decrease in the worldwide incidence of mumps since the introduction and use in 1968 of the very effective and inexpensive mumps vaccine. In Iran probably due to a higher percentage of unvaccinated young persons Material& Methods: This descriptive case-series study was conducted in 94children, aged less than 14 years, hospitalized between 1999 and 2001, in the pediatric ward of the Hazrat Rasool Hospital in Tehran. All patients with documented mumps infection (specific mumps-IgM antibody) were evaluated twice for audiometeric function on the basis of diagnostic parameters for sensory neural hearing loss; the first evaluation was done on admission and the second three weeks later. 54 patients (age range 1-14y, mean age 4.83±3.93, male: female ratio30:24) were studied in two years. Results: The highest incidence of mumps was seen in winter (37%) and spring (28%) and the lowest in summer (13%). Specific IgM antibody for mumps virus was detected in 74 children. Comprehensive audiologic evaluation was done in 54 patients at admission and again 3 weeks later. SNHL was detected in 7.2% of patients; the 4.4% incidence of SNHL in this study was higher than in other studies in developed countries prior to comprehensive vaccination programs. Conclusion: Implementation of comprehensive vaccination programs in young Iranians could dramatically reduce the burden and costs imposed by the infection and its sequelae. Keywords: Mumps infection ;SNLH(sensorineural hearing loss);Mumps vaccination

The changing pattern of hepatitis B virus infection over the past three decades in Italy

By the end of 1970s, Italy was a country at medium endemic level of hepatitis B virus infection, with wide geographical differences; intrafamily transmission was the major mode by which infection spread; hepatitis B e antigen positivity and hepatitis Delta positivity were frequently detected in hepatitis B surface antigen chronic carriers; a high proportion of subjects with chronic liver disease resulted as hepatitis B surface antigen positive. Three decades apart, the picture was completely changed, as documented by several surveys. Nowadays, Italy is a country at very low endemic level of hepatitis B, without geographical differences; the infection is mostly sexually transmitted; hepatitis B e antigen positivity and hepatitis Delta positivity are rarely detected in hepatitis B surfaces antigen chronic carriers; a low proportion of subjects with chronic liver disease result hepatitis B surface antigen positive. These important changes may be due to both non-specific (i.e. improvement in socio-demographic features) and specific (i.e. a comprehensive vaccination program against hepatitis B) preventive measures.

Bioterrorism: the current threat

Bioterrorism is receiving ever more attention both in the popular press and in scientific publications. In the JRSM Beale1 has discussed responses to the threat, particularly the requirement for a comprehensive vaccination programme; he also noted the remarkable fact that the UK's Public Health Laboratory Service is to be broken up. The South and West Region of the RSM, at its inaugural academic meeting held at Britannia Royal Naval College Dartmouth in June, addressed the subject in more general terms under the title ‘Bioterrorism: the current threat’.

Economic evaluation of strategies for the control and management of influenza in Europe

We compared the cost-effectiveness of different strategies for the control and management of influenza for the elderly populations in three European countries (England and Wales, France, Germany). A “no intervention” scenario was compared with six control strategies: opportunistic vaccination (passive recruitment), comprehensive vaccination programmes (active recruitment), 4 weeks chemoprophylaxis course using neuraminidase inhibitors (NIs), 4 weeks chemoprophylaxis course using ion-channel inhibitors (ICIs), early treatment with NIs, and early treatment with ICIs. Vaccination strategies were the most cost-effective. Chemoprophylaxis strategies were highly expensive even under assumptions of optimal timing. Early treatment strategies with antivirals substantially increased demand for GP services and were more expensive than prevention through vaccination.

Foot-and-mouth disease and beyond: vaccine design, past, present and future.

The first experimental vaccines against foot-and-mouth disease were made in 1925 by Vallee, Carre and Rinjard using formaldehyde inactivation of tongue tissue from cattle infected with the virus. This method was essentially unaltered until the late 1940s when the important experiments by Frenkel in Holland showed that the quantities of virus required for vaccine production could be obtained from fragments of tongue epithelium incubated in vitro following infection with the virus. This major step made possible the comprehensive vaccination programmes which followed in Western Europe and which, in turn, resulted in the elimination of the disease from that part of the world by 1989. This spectacular success has led many to question whether other kinds of vaccine are required to control the disease worldwide. Such reservations ignore the danger to the environment associated with the growth of large amounts of virus. This can never be a zero-risk situation. Consequently, a vaccine which is not based on infectious virus as starting material has many attractions from safety considerations alone. In addition, a vaccine based on more fundamental considerations would not only be more aesthetically satisfying but could possibly provide an understanding at the molecular level of antigenic variation, still a problem in the control of the disease. The advances in our knowledge of the structure of the virus and the fragments which elicit a protective immune response now allow us to envisage a vaccine which does not require infectious virus and which protects against the multiple serotypes of the agent. Since antigenic variation is still a major problem in the control of the disease by vaccination, such a product would have important advantages over the current vaccines.

Hepatitis B and hepatitis delta virus infection in South America.

About 100,000 cases of acute hepatitis B virus (HBV) infection occur annually in South America. The overall prevalence of HBV infection in low risk populations ranges from 6.7% to 41%, while hepatitis B surface antigen (HBsAg) rates range from 0.4% to 13%. In high endemicity aboriginal or rural populations, perinatal transmission may play a major part in the spread of HBV. In urban populations, however, horizontal transmission, probably by sexual contact, is the predominant mode of spread, with higher rates of HBV positivity in lower socioeconomic groups. High risk populations such as health care workers and haemodialysis patients show higher rates of HBV infection than comparable populations elsewhere. The risk of posttransfusion hepatitis B remains high in some areas. Concomitant HBV infection may accelerate the chronic liver disease seen in decompensated hepatosplenic schistosomiasis. In the north, the prevalence of hepatitis delta virus (HDV) infection ranks among the highest in the world. In the south, the problem appears negligible although it is increasing within high risk urban communities. HDV superinfection has been the cause of large outbreaks of fulminant hepatitis. The cost of comprehensive or mass vaccination programmes remains unaffordable for most South American countries. Less expensive alternatives such as low dose intradermal schedules of immunisation have been used with success in selected adult subjects.

The elimination of indigenous measles, mumps, and rubella from Finland by a 12-year, two-dose vaccination program.

In the 1970s measles, mumps, and rubella were rampant in Finland, and rates of immunization were inadequate. In 1982 a comprehensive national vaccination program began in which two doses of a combined live-virus vaccine were used. Public health nurses at 1036 child health centers administered the vaccine to children at 14 to 18 months of age and again at 6 years, and also to selected groups of older children and young adults. Vaccination was voluntary and free of charge. In follow-up studies, we focused on rates of vaccination, reasons for noncompliance, adverse reactions, immunogenicity, persistence of antibody, and incidence of the three diseases. Since 1987, paired serum samples have been collected from all patients with suspected cases of measles, mumps, or rubella. Over a period of 12 years, 1.5 million of the 5 million people in Finland were vaccinated. Coverage now exceeds 95 percent. The vaccine was efficient and safe, even in those with a history of severe allergy. No deaths or persistent sequelae were attributable to vaccination. The most frequent complication requiring hospitalization was acute thrombocytopenic purpura, which occurred at a rate of 3.3 per 100,000 vaccinated persons. The 99 percent decrease in the incidence of the three diseases was accompanied by an increasing rate of false positive clinical diagnoses. In 655 vaccinated patients with clinically diagnosed disease, serologic studies confirmed the presence of measles in only 0.8 percent, mumps in 2.0 percent, and rubella in 1.2 percent. The few localized outbreaks were confined to patients in the partially vaccinated age groups. There are now fewer than 30 sporadic cases of each of the three diseases per year, and those are probably imported. Over a 12-year period, an immunization program using two doses of combined live-virus vaccine has eliminated indigenous measles, mumps, and rubella from Finland. Serologic studies show that most reported sporadic cases are now due to other causes, but a continued high rate of vaccination coverage is essential to prevent outbreaks resulting from exposure to imported disease.

European Union tries to control disease

The recent outbreaks of plague in India and diphtheria in eastern Europe and the spread of diseases such as hepatitis have convinced the European Commission that it should extend its existing programme to combat AIDS to cover other communicable diseases. The commission is proposing to spend 50m European currency units over the next five years, encouraging governments in the European Union to implement a comprehensive vaccination programme and improve early detection and screening. With 105 000 cases of AIDS reported in the 12 member states last March and possibly …

Role of Infectious Agents in Respiratory Disease

There is no question that disease prevention, rather than treatment, represents the single most significant advancement in the management of infectious diseases in companion animals. In particular, the introduction of sensitive, rapid in-clinic diagnostic test kits, new vaccines, and implementation of strict vaccination protocols has dramatically decreased the morbidity and mortality associated with viral infections in cats. However, neither the agents nor the disease they cause will be eradicated through the use of even the most comprehensive testing and vaccination programs alone. In 1908, W. T. Sedgwick wrote in his leading public health textbook that "the absence of dirt is not merely an esthetic adornment." Comments such as this, published by noted public health authorities at the turn of the century, marked the beginning of the health revolution in the United States. As the nineteenth century ended, mortality rates from infectious diseases among infants and young adults dramatically and abruptly plunged. The fact that personal hygiene was the hero of this revolution illustrates the importance of the fundamental rules of cleanliness in disease prevention that still apply today. Although basic to infection control, ignoring even the simplest concepts of cleanliness and hygiene in the environment of the multiple cat household can lead to diastrous consequences.

A comprehensive vaccination program as a preventive contribution in a large-scale chemical industry

The different vaccination programs in a large chemical company with 12,000 co-workers are discussed. On the one hand mass-vaccinations against influenza, tetanus, and polio are carried out; on the other hand attention is paid to special target groups (people on business trips, members of agro units who have to work several months in the tropics under bad hygienic conditions, laboratory personal which has daily contact with human blood, serum, urine, and faeces). On all this people special vaccinations are performed which are discussed in detail. Moreover great attention is paid on a regular and effective malaria prophylaxis in all co-workers travelling and working in the tropics.