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Measles epidemics in Kerman City, Iran.

In early 1990 an outbreak of measles occurred in Kerman City (population 257,284), Iran. Overall 745 cases were identified, four of whom died (case fatality ratio was 5.4 per thousand). Illness was limited, primarily, to children below 15 years of age: 166 (22.3%) cases were in children under five years, 573 (77%) in those aged between five and 14 years and six (0.8%) were above 15 years of age. The age of the cases ranged from 5 months to 35 years. The age-specific attack rates were 3.9, 1.8, 7.3 and 2.8 per 1,000 for children under 1, 1-4, 5-9 and 10-14 years of age respectively. Overall 14 (1.9%) children with measles were hospitalized for severe complications which consisted mainly of pneumonia, otitis and gastroenteritis. Based on 745 cases with available immunization records, vaccine efficacy was calculated at 88% indicating a slight problem with the cold chain or vaccine. The outbreak was primarily related to low immunization coverage during the last 10 years and indicates the need to improve vaccine coverage with the AIK-C existing vaccine. It also highlights the urgent need for an effective single-dose measles vaccine (Edmondson-Zagreb) for children below nine months of age.

Adolescent↗

GAVI, the first steps: lessons for the Global Fund.

The Global Alliance for Vaccines and Immunization (GAVI) is seen as a model for the new Global Fund to Fight AIDS, Tuberculosis and Malaria, to be launched early in 2002. We did an assessment in four African countries to report the experiences of ministries of health and their partners in applying to GAVI for funds to strengthen health systems and for new vaccines. Countries welcomed the introduction of hepatitis B vaccine, safe injection equipment, and the financial support to strengthen immunisation programmes. All reported that the pace of the application process was too rapid. District visits revealed low staffing levels, insufficient transport and fuel, poorly functioning cold chains, and infrequent supervision. Information systems were unreliable, which will be an obstacle to GAVI when monitoring and rewarding improvements in immunisation coverage. Also, the high cost of expensive new vaccines will be difficult to sustain if GAVI funding stops at the end of its 5 year commitment. Our study suggests that applications for support and planning for AIDS, tuberculosis, and malaria control under the new Global Fund, will be more complex and demanding on already over-stretched ministries of health. Further, the rapid onset of activities, coupled with uncertainty about the time-scale of donor commitment, could be problematic. A limited and carefully assessed set of initial activities, focusing on where and how to strengthen existing country systems, is more likely to be successful and could provide useful models for scaling-up to larger programmes in different contexts.

Acquired Immunodeficiency Syndrome↗

Aspects of emergency vaccination against foot-and-mouth disease.

Emergency vaccination is one of several measures which may be deployed to control outbreaks of foot-and-mouth disease. It can be a valuable adjunct to the application of the essential zoosanitary controls which must include rapid diagnosis, tracing, movement control and disinfection and which may also include slaughter of infected and in-contact animals and their safe disposal. Criteria which determine the successful application of emergency vaccination include access to vaccine(s) that (i) contain virus strain(s) of sufficient antigenic relatedness to the outbreak strain(s) (ii) are of the required type of vaccine formulation (iii) have acceptable innocuity and potency (iv) have appropriate availability, including quantity and immediacy of supply and (v) meet considerations of cost. Contingency planning should include provision for emergency vaccination and must address the complex decisions of not only when, where, and how to apply vaccine but also its economic consequences. Computer modelling may be a useful aid to cost benefit and decision support systems in this context. Planning must be detailed and regularly reviewed and should ensure, (i) that the legal and financial aspects are catered for (ii) that any contractual supply agreements are in place (iii) that information is collected and its currency maintained on the species, numbers and whereabouts of susceptible livestock (iv) that vaccination teams are formed and trained (v) that the vaccine cold chain is established and maintained (vi) that supplies of vaccination equipment are held in readiness and (vii) that briefing materials are available to inform the various stakeholders on relevant aspects of emergency vaccination. Knowledge concerning the characteristics and performance of emergency vaccines is summarised and areas identified for further research.

Animals↗

DNA vaccination in the avian.

Inoculation of naked DNA represents a novel approach to vaccine and immune therapeutic development. DNA vaccines or genetic immunization offers several advantages over the conventional vaccines for specific immune activation. Although a large number of vaccines have been made and are being used in the poultry industry, there have been no major advances in vaccine technology for this animal industry sector for decades. The potential advantages of DNA vaccines, such as over coming maternal immunity, in ovo delivery and absence of requirement for a cold-chain, combined with immunological efficacy make this new vaccine technology very attractive for the poultry industry. This review lists all of the published reports of experimental DNA vaccines developed for use in poultry and focuses on the trends, potentials and remaining barriers in the development of this new revolution in poultry vaccinology.

Animals↗

Bacterial ghosts as vaccine candidates for veterinary applications.

The application of new strategies to develop effective vaccines is essential in modern veterinary medicine. The bacterial ghost system is a novel vaccine delivery system endowed with intrinsic adjuvant properties. Bacterial ghosts are nonliving Gram-negative bacterial cell envelopes devoid of cytoplasmic contents while maintaining their cellular morphology and native surface antigenic structures including bioadhesive properties. They are produced by PhiX174 protein E-mediated lysis of Gram-negative bacteria. The intrinsic adjuvant properties of bacterial ghost preparations enhance immune responses against envelope bound antigens, including T-cell activation and mucosal immunity. Since native and foreign antigens can be expressed in the envelope complex of ghosts before E-mediated lysis, multiple antigens of various origins can be presented to the immune system simultaneously. The advantages of bacterial ghosts include the simplicity of the production method, safety, independence from the cold chain, and versatility as a combination vaccine.

Animals↗

[Analysis of the management of the vaccination campaign in 1996-1997 against meningococcus C in Galicia].

This paper describes the process to design and plan a vaccination campaign against group C N. Meningitidis developed in the Autonomous Community of Galicia between December 9, 1996 and January 31, 1997. We also analyse the results of this process in terms of management results, vaccine coverage and preliminary estimates of effectiveness. A Work group was established, made up of professionals in charge of different intervention areas. A person was designated in charge of the whole campaign and a follow-up and information system was created. The work plan consisted of daily meetings for follow-up, co-ordination and task distribution; and periodical meetings with primary health care and peripheral public health coordinators. Strategies of implantation--in order to make sure the campaign accessibility and acceptability; of budget and of communication with health workers, inhabitants and mass media were developed. Up to 100 tasks were identified to develop the technical information and logistic activities: mailings, meetings, leaflets, ...; purchasing of 584.980 doses of vaccine, supplying to 715 vaccination points (1040 deliveries); problem solving and intervention recording. A vaccination coverage of 85% was achieved, with notification of 8 adverse reactions and 6 errors in the administration of the vaccine (34 children affected). The strategy chosen for the design and planning of the campaign has proven to be effective and valid and sufficient to achieve the final goals, in due time and without problems of misinformation, shortage of vaccine or lack of participation of professionals or people. Mistakes due to incorrect administration of the vaccine, management problems, rupture of the cold chain or recording failures were minimal and accidental.

Health Education↗

Protection of cattle against rinderpest by intranasal immunisation with a dry powder tissue culture vaccine.

Dry powder tissue culture rinderpest vaccine containing 10(2.5) TCID(50) of virus per dose administered intranasally to cattle induced high titre circulating antibody responses and protection against challenge with a virulent strain of rinderpest virus. A reduction in the dose of virus to 10(1.1) TCID(50) resulted in a failure to elicit detectable antibody responses and a lack of protection. Intranasal powder vaccine offers several advantages over conventional needle-administered aqueous rinderpest vaccine, including greater stability in the absence of a cold chain, reduced risk of 'needle transfer' of other microbial agents present in the vaccinated herd and lower cost.

Administration, Intranasal↗

Infant and adolescent hepatitis B immunization up to 1999: a global overview.

This article presents a global overview of hepatitis B infant and adolescent immunization programmes. The 108 reported universal infant or adolescent immunization programmes and 87 reported national infant coverage rates fit a pattern, explained by hepatitis B endemicity, prosperity, policy emphasis, and immunization programme strength. Most East and Southeast Asian, Pacific, and Middle Eastern countries have intermediate to highly endemic hepatitis B. Most have achieved 65-100% coverage. South and Central Asia and sub-Saharan Africa have intermediate to high endemicity, with some countries having hepatitis B immunization programmes. Some Southern and Eastern European countries, with intermediate endemicity, have high coverage. Low endemic Northern European countries vaccinate higher risk groups; some have universal infant or adolescent programmes. Caribbean and Latin American countries have varying endemicity, and most started programmes. Low endemic North American countries have universal vaccination programmes. Universal immunization strategies have greatly reduced incidence and prevalence, and are cost-effective for many countries, but many have difficulties affording this vaccine. Globally, most infants are not being immunized against hepatitis B virus infection. Increasing coverage, and decreasing the numbers of people diseased and dying from this virus, may require delivering heat-stable vaccine beyond cold chains, creative financing to reduce prices, and multivalent vaccines.

Adolescent↗

Frequency and causes of vaccine wastage.

UNLABELLED: Assessing the frequency of vaccine wastage and the relative magnitude of its various causes may help to target efforts to reduce these losses and to husband funds for increasingly expensive vaccines. METHODS: As a preliminary overview of wastage in the United States, 64 public-sector state and local health department immunization programs were polled in 1998 and 1999 for wastage recording practices. Actual wastage data were collected from a non-random subset of five states. Data on returns of wasted vaccine to manufacturers were analyzed from routine national biologics surveillance and from an ad-hoc survey. Excise tax credit requests for such returns between 1994 and 1999 were reviewed. RESULTS: Rates of wastage among the five states ranged from about 1 to 5% in 1998, with an overall rate of 2.6% among 57 immunization programs in 1999. Categories of wastage used by the health departments varied widely, with overlapping classifications. The major causes appeared to be refrigeration (cold chain) lapses, followed by expiration. Overall rates of vaccine returns varied up to 8% by manufacturer, and from 1 to 50% by vaccine type, with higher return rates generally found for lesser-used vaccines. CONCLUSIONS: If these wastage estimates of 1-5% applied nationally, in 1998 there would have been approximately US dollars 6-31 million worth of unused vaccine in the public sector alone. The two most common forms of wastage reveal the potential value of developing vaccines with improved heat stability and longer shelf lives. We propose six main classifications of vaccine wastage for use in routine monitoring and reporting.

Humans↗

Enhanced immunogenicity of a hepatitis B virus peptide vaccine using oligosaccharide ester derivative microparticles.

Controlled release microspheres can overcome many of the disadvantages of multiple vaccine delivery such as rate of uptake and cost of administration. Proteins and peptides are difficult to administer using conventional polymers owing to protein degradation, premature release and stability. Here we report the successful development of room temperature stable, controlled release formulations using oligosaccharide ester derivatives (OEDs) of trehalose and a synthetic peptide analogue of hepatitis B surface antigen. Employing a range of different OED preparations, we have optimised the immunogenicity of the peptide formulation such that mice injected with a single preparation of microspheres consisting of trehalose octaacetate (TR101; Group G) produce high titre anti-hepatitis B (anti-HBs) surface antigen antibodies. The kinetics of the immune response could be manipulated with different peptide/OED formulations and correlated with the OED composition of the microspheres. Our data demonstrate the considerable potential of OED microspheres as novel delivery systems for vaccines. The ability to induce strong immune responses, without the requirement for multiple doses or cold-chain storage, could radically improve vaccination programmes in developing countries.

Animals↗

Priming of measles virus-specific humoral- and cellular-immune responses in macaques by DNA vaccination.

Although the currently used live attenuated measles vaccines are safe and effective, they are dependent on cold chain maintenance and are often ineffective in young infants due to interference by maternal antibody. Therefore, besides vector-based vaccines, different new generation non-replicating candidate measles vaccines are being considered, including nucleic acid vaccines. We have vaccinated cynomolgus macaques transdermally with DNA plasmids encoding measles virus (MV) proteins. Following two vaccinations, low serum antibody responses were detected. Wild-type measles virus challenge 1 year after vaccination showed reduced viraemia in some animals. However, accelerated humoral- and cellular-immune responses were observed in all vaccinated macaques, demonstrating successful priming by the DNA vaccines.

Animals↗

Immunogenicity of a recombinant lumpy skin disease virus (neethling vaccine strain) expressing the rabies virus glycoprotein in cattle.

Rabies virus (RV) readily infects cattle and causes a fatal neurological disease. A stable vaccine, which does not require the maintenance of a cold chain and that is administered once to elicit lifelong immunity to rabies would be advantageous. The present study describes the construction of a live recombinant lumpy skin disease virus (LSDV) vaccine, expressing the glycoprotein of rabies virus (RG) and assessment of its ability to generate a humoral and cellular immune response against rabies virus in cattle. Cattle inoculated with the recombinant virus (rLSDV-RG) developed humoral immunity that was demonstrated in ELISA and neutralisation assays to RV. High titres of up to 1513IU/ml of RV neutralising antibodies were induced. In addition, peripheral blood mononuclear cells from rLSDV-RG-immunised animals demonstrated the ability to proliferate in response to stimulation with inactivated RV, whereas the animal vaccinated with wild type LSDV did not. This recombinant vaccine candidate thus has the potential to be used in ruminants as a cost-effective vaccine against both lumpy skin disease (LSD) and rabies.

Animals↗

Safety, tolerability and humoral immune responses after intramuscular administration of a malaria DNA vaccine to healthy adult volunteers.

DNA-based vaccines are considered to be potentially revolutionary due to their ease of production, low cost, long shelf life, lack of requirement for a cold chain and ability to induce good T-cell responses. Twenty healthy adult volunteers were enrolled in a Phase I safety and tolerability clinical study of a DNA vaccine encoding a malaria antigen. Volunteers received 3 intramuscular injections of one of four different dosages (20, 100, 500 and 2500 microg) of the Plasmodium falciparum circumsporozoite protein (PfCSP) plasmid DNA at monthly intervals and were followed for up to twelve months. Local reactogenicity and systemic symptoms were few and mild. There were no severe or serious adverse events, clinically significant biochemical or hematologic changes, or detectable anti-dsDNA antibodies. Despite induction of excellent CTL responses, intramuscular DNA vaccination via needle injection failed to induce detectable antigen-specific antibodies in any of the volunteers.

Adult↗

Immunisation against East Coast fever by the infection and treatment method: evaluation of the use of ice baths for field delivery and appraisal of an acid formulation of long-acting tetracycline.

Immunisation by the infection and treatment method using the Katete strain is currently the most efficient prophylactic technique to control East Coast fever (ECF) in the endemic areas of the Eastern Province of Zambia. The maintenance of the cold chain in liquid nitrogen up to the time of inoculation and the cost of the reference long-acting oxytetracycline (Terramycin LA, Pfizer) are the main drawbacks of the method. The work presented in this paper aims at reducing the cost of immunisation against ECF by using an ice bath for the field delivery and a cheaper long-acting oxytetracycline formulation as chemotherapeutic agent. In experimental conditions, the results from 40 calves immunised after various periods of storage on ice ranging from 4 to 32 h indicate that deferred immunisation performed with a stabilate kept on ice for up to 6h after thawing has an efficiency of 90%. Moreover, sporozoites kept on ice were still surviving 32 h after thawing. In a field trial, 91 calves were inoculated with a stabilate kept for 3.5-5.5 h after thawing and dilution whereas 86 calves were immunised using the standard method. Clinical and parasitological reactions to immunisation were monitored as well as the seroconversion. In the field trial, the deferred immunisation was more efficient than the standard method. The acid formulation of oxytetracycline that was tested was found as suitable as the reference alkaline formulation for the chemotherapeutic control of the Katete strain in ECF immunisation. One indoor trial was carried out on 10 animals and a field trial involved 93 calves.

Animals↗

[Environmental risk factors in Crohn's disease and ulcerative colitis (excluding tobacco and appendicectomy)].

A rapid increase in the incidence of Crohn's disease and ulcerative colitis in developed countries, the occurrence of Crohn's disease in spouses, and a lack of complete concordance in monozygotic twins are strong arguments for the role of environmental factors in inflammatory bowel disease (IBD). Research in the field of environmental factors in IBD is based upon epidemiological (geographical and case-control), clinical and experimental studies. The role of two environmental factors has clearly been established in IBD. Smoking is a risk factor for Crohn's disease and a protective factor for ulcerative colitis; appendectomy is a protective factor for ulcerative colitis. Many other environmental factors for IBD have been investigated, including infectious agents, diet, drugs, stress and social status. They are detailed in the present review. Among them, atypical Mycobacteria, oral contraceptives and antibiotics could play a role in Crohn's disease. To date, three hypotheses associate environmental factors with the pathophysiology of IBD (loss of tolerance of intestinal immune system towards commensal bacterial flora): the hygiene, infection and cold chain hypotheses. Much work remains to be done to identify risk factors for IBD. Research identifying environmental factors that might cause a predisposition to IBD is useful. It may lead to disease prevention in subjects who are genetically predisposed and disease improvement in patients.

Adolescent↗

Maintaining and enhancing vaccine immunogenicity.

This contribution highlights factors involved with maintaining and enhancing antigen delivery or immunogenicity. Areas discussed include the cold chain, adjuvants, recombinant vectors for antigen delivery, routes for antigen delivery, and edible plant vaccines. It is doubtless that the technological understanding that underlies these advances is about to revolutionize vaccinology in the near future.

Adjuvants, Immunologic↗

Epidemiologic and clinical features of measles and rubella in a rural area in China.

BACKGROUND: Changes in the epidemiologic and clinical features of measles have resulted in diagnostic difficulties in distinguishing between measles and other rash and fever illnesses such as rubella. The objectives of this article are to report the true morbidity and epidemiologic and clinical features of measles and rubella, provide objective diagnostic indicators for distinguishing between the 2 diseases, and provide a time-efficient scientific basis for accurately evaluating the effectiveness of immunization with the measles vaccine and regulating the control strategies for measles in the rural areas of China in the cold chain era. METHODS: From 1992 to 2002, patients with measles and rubella were recorded and reported routinely in the rural disease surveillance spots of Jingzhou District, Hubei Province, by collecting their sera and testing for measles and rubella IgM and IgG antibodies. RESULTS: Over the 11-year study period, 146 cases of measles were reported in the disease surveillance spots. The annual incidence of measles was highest in 1999 (118.8/100,000 population). The incidence of measles in the 4-6 and 7-15 year old age groups were higher than in other age groups. During 5 outbreaks of measles, a total of 128 cases were reported, accounting for 87.7% of the total number of measles cases. A total of 566 rubella cases were reported, with 3 epidemic peaks (in 1992, 1997 and 2002). The incidence of rubella in the 4-6 and 7-15 year old age groups were higher than in other age groups. There were 13 outbreaks of rubella, with 547 cases being reported, accounting for 96.6% of the total number of rubella cases. Accuracy of the clinical diagnosis of measles was 40%, while it was 100% for rubella. The proportions of patients who had a moderate to high fever (> or = 38.6 degrees C) in the measles group (89.5%) and the combined infection (both measles and rubella) group (90%) were significantly higher than that of the rubella group (30.6%). The proportions of patients whose prodromal stage lasted > or = 3 days in the former 2 groups (68.4% and 95%, respectively) were significantly higher than that of the rubella group (16.7%). The proportions of patients whose exanthema lasted > or = 4 days in the former 2 groups (78.9% and 75%, respectively) were significantly higher than that of the rubella group (26.9%). CONCLUSION: Measles and rubella are 2 common communicable diseases in the children of Jingzhou District, with outbreaks being the main epidemic form. Some clinical features such as temperature, duration of the prodromal stage and exanthema are different in measles and rubella, and they can be useful in distinguishing between the 2 diseases. Accuracy in the clinical diagnosis of measles should be improved by enhancing serologic testing for measles and rubella, and by identifying patients' specific clinical characteristics.

Adolescent↗

DNA-antiviral vaccines: new developments and approaches--a review.

Current vaccines can be divided into "live," "recombinant" and "killed" vaccines. Live vaccines are traditionally composed of attenuated viruses or bacteria, selected for their reduced pathogenicity. Recombinant vaccines, driven by a viral or bacterial vector express foreign antigens, or only recombinant proteins injected as antigen. Killed vaccines consist of inactivated whole pathogens. But all these traditional vaccines have some disadvantages: Attenuated live vaccine are able to undergo mutation and as mutated viruses or bacteria can now provoke the diseases against which the vaccine should protect the organism. A further disadvantage of live vaccines is the possibility of shedding which is a real problem especially in veterinary medicine. Clearly, there is a need for better vaccines to protect against diseases without the disadvantages associated with vaccines presently in use. Modern vaccines might be characterized as safe, no risk of reversion to pathogenicity, and they should be stable without the necessity of a "cold chain." Production should be simple, standardized and inexpensive. Vaccine development has now been improved by the ability to use direct inoculations of plasmid DNA encoding viral or bacterial proteins. One of the major benefits of DNA-vaccines, variously termed "DNA-, genetic- or nucleic acid-immunization," is the endogenous synthesis of the encoded protein. Therefore DNA vaccines mimic natural infection and provoke both strong humoral and cellular immune response. This review summarizes new developments and approaches of DNA vaccination and explains the construction of expression plasmids as well as possible mechanisms of immune responses.

Animals↗