Influenza vaccine and pneumonia mortality in a nursing home population.

The effectiveness of immunization against influenza in elderly persons is uncertain. A retrospective cohort study in a New York City nursing home examined the occurrence of pneumonia and its related mortality over three consecutive influenza seasons (Nov 1 through April 30, 1979 to 1980, 1980 to 1981, and 1981 to 1982). Nearly one half of approximately 450 residents (mean age, 84 years) accepted immunization each year. The vaccinated and unvaccinated groups were similar. The attack rate of pneumonia did not differ significantly between the vaccinated and unvaccinated groups in any of the three influenza seasons. When influenza was occurring in the community (1979 to 1980 and 1980 to 1981), however, the risk of death from pneumonia in the unvaccinated group was three-fold higher than in the vaccinated group (60% vs 18% and 73% vs 25%, respectively). In a year when influenza was specifically sought and not found in the facility (1981 to 1982), however, vaccination did not affect pneumonia-related mortality. This study also suggests that estimates of mortality due to pneumonia should include deaths that occur up to 60 days after onset of pneumonia; shorter follow-up may overestimate the protective effect of vaccination.

Influenza: status and prospects for its prevention, therapy, and control.

This article describes current knowledge of the molecular properties of orthomyxoviruses, their epidemiology, and approaches to the control of influenza. The host's response to infection, approaches to prevent infection through vaccination, and the use of antiviral agents to treat or prevent this important infection are covered.

Fungal infections: a growing threat.

THE EMERGENCE OF newly identified fungal pathogens and the reemergence of previously uncommon fungal diseases is primarily related to increases in the numbers of susceptible persons: people with HIV infection, bone marrow and organ transplant recipients, cancer patients being treated with chemotherapy, critically ill persons, and very low birth weight ( < or = 1500 g) infants. These immunocompromised populations are at risk for infection not only with opportunistic pathogens (for example, Pneumocystis, Candida, Cryptococcus, Trichosporon, Malassezia, Aspergillus, Penicillium marneffei, and numerous other moulds or yeasts) but also with fungal pathogens that usually infect otherwise healthy persons not previously exposed to endemic fungi (for example, Coccidioides immitis, Histoplasma capsulatum, and Blastomyces dermatitidis) and Sporothrix schenckii. Morbidity, mortality, and health care costs associated with fungal infections are high. Addressing the emergence of fungal diseases will require increased surveillance coupled with the availability of rapid, noninvasive diagnostic tests; monitoring the development of resistance to antifungal agents; and research focused on the understanding, prevention, and control of fungal infections.

The United States research strategy on pertussis.

Wide-scale use of whole-cell vaccines has fed to good control of pertussis disease in the United States; however, this control has been achieved at the cost of common and uncommon adverse events of known frequencies. Agencies of the U.S. Public Health Service actively stimulated the development of new pertussis vaccines by directly supporting basic and applied research and increasing interactions with industry and with health authorities in other countries. This international cooperation resulted in a better understanding of the pathogenesis of pertussis and in the final development and clinical testing of several candidate acellular pertussis vaccines.

Biotechnology and research: promise and problems.

Biotechnology has expanded greatly during the last two decades. This expansion is due to worldwide investment in basic biomedical research. The new knowledge generated by this investment has led to a bounty of potential applications for improvement of health, which are being explored for commercial purposes by the biotechnology industry. Private investment is thus ever present in development of these biotechnological products. All these factors raise important questions, including increasing concerns about intellectual property and conflict of interest. As this expansion continues, the established processes of peer review should be strengthened.

Immunization programs and human immunodeficiency virus.

The emergence of human immunodeficiency virus (HIV) in epidemic form has implications for immunization programs. Infection with HIV, which is capable of infecting cells of the immune system and which can remain latent for many years, results in profound and progressive immunosuppression. As a consequence, vaccines may not elicit a protective response from HIV-infected individuals. Stimulation of the immune system may also be a cofactor for the progression of infection to AIDS, since stimulated lymphocytes are needed for the replication of HIV. HIV-positive individuals may also react differently to vaccines than do uninfected persons. The standard vaccines in use today are extremely safe. The possibility that the excellent safety profile of vaccines may be altered in HIV-positive patients must be considered. Since this virus can be transmitted through exposure to blood and blood products, mass immunization programs must take steps to minimize the possibility of accidental transmission of infection during a mass vaccination program. Finally, the problems and prospect for the testing and use of vaccines to prevent HIV are discussed.

From the National Institute of Allergy and Infectious Diseases: Summary of a workshop on disease mechanisms and prospects for prevention of Reye's syndrome.

The workshop participants identified several areas that are worthy of investigation. A better understanding of the populations at risk is necessary. First, the geographic distribution of cases is poorly understood, and efforts should be made to determine whether the apparent clustering of cases in the states bordering the Great Lakes is real or reflects better reporting and identification of cases in these states than in other regions. Second, reports of cases among siblings or relatives suggests either an underlying metabolic risk factor or the possibility of a common environmental risk factor. Further studies of carnitine metabolism would be appropriate in this regard. Third, epidemiologic experience with Reye's syndrome suggests that clusters of cases may occur more frequently when new influenza A or B viruses become epidemic. This pattern was observed most clearly in 1978 during the epidemic of A/USSR/77 (H1N1) influenza virus infection. Additional suggestive evidence was obtained during the epidemic of A/Asian/57 (H2N2) influenza in 1957-1958 [20] and that of B/Hong Kong/72 influenza in 1973-1974. This feature suggests that first infections with these viruses are more likely than reinfections to produce the rare sequela of Reye's syndrome. Fourth, the reported association of Reye's syndrome with the use of acetylsalicylate in the treatment of the antecedent illness requires further study. In this situation the potential risk factor has been recognized as a mitochondrial toxin capable of uncoupling oxidative phosphorylation. Finally, the question of a toxic product produced as a consequence of the prodromal infection or present coincident with the infection remains unresolved.(ABSTRACT TRUNCATED AT 250 WORDS)

The neglected global tuberculosis problem: a report of the 1992 World Congress on Tuberculosis.

Tuberculosis is the single leading cause of death from any single infectious agent. A world congress on tuberculosis was held to highlight the problem and to discuss recent scientific advances and global strategies for prevention and control. About one-third of the world population is latently infected with Mycobacterium tuberculosis. Over 8 million new cases and nearly 3 million deaths occur each year. The situation is deteriorating due, in part, to the human immunodeficiency virus pandemic and shifts in the age distribution of the population. Resistance to antituberculosis drugs has also emerged as an important obstacle to control. Tuberculosis control programs in many developing and some industrialized countries have inadequate resources to combat the problem. Despite these trends, successful strategies and programs have been developed that, if implemented, would likely significantly reduce morbidity and mortality. Furthermore, recent research findings suggest that technologic advances will soon lead to improved methods for prevention and control.

The promise of new technologies.

Efforts to provide the benefits of immunization to the world's children have reached an important crossroad. While remarkable progress has been achieved in successfully administering six important childhood vaccines (diphtheria, tetanus, polio, pertussis, measles, and tuberculosis), the benefits of new vaccines, such as hepatitis B and Haemophilus influenzae type B glycoconjugate vaccines, have not been realized except in the most developed countries. The three reasons often cited to explain this problem include poor access to immunization services, the evolution of complex primary immunization schedules, and the additional expense associated with new vaccines, potentially depleting scarce resources. The establishment of the Children's Vaccine Initiative is an organized effort to improve immunization by both technological and organizational innovation. Simplification of the vaccination process can be achieved by developing new combination vaccines or reducing the number of immunizations with vaccines that stimulate protective immune responses. Improvements in the organization of efforts to immunize children will also enhance the prospects of protecting the world's children from infectious diseases. To achieve the goals articulated in the Declaration of New York, the issues of transition from the old to the new vaccines must be addressed. Research on vaccines and technological innovation at all levels will be required to achieve these goals.

From the National Institute of Allergy and Infectious Diseases of the National Institutes of Health, the Center for Disease Control, and the Bureau of Biologics of the Food and Drug Administration. Summary of clinical trials of influenza vaccines--II.

These studies indicate that the high-risk and normal pediatric populations can be safely and effectively immunized with a two-dose regimen of the influenza A/New Jersey/76 virus vaccine. In addition, the studies have demonstrated important differences between split-product and whole-virus vaccines in the pediatric age group. Furthermore, reactogenicity from the whole-virus vaccine administered in the schedules employed was acceptable after the first dose and negligible after the second dose. More detailed examination of the data will undoubtedly yield additional information of importance to current and future use of inactivated influenza vaccines in children.

Public health implications of emerging vaccine technologies.

The field of public health and medicine stands to benefit immensely from the emerging vaccine technologies and improved application of existing technologies. Technological advances may promote: (1) greater flexibility and simplicity in the design and operation of immunization campaigns or ongoing prevention programs, including reduction in number of vaccine doses, cold chain elimination, slow-release/prolonged antigenic stimulation, reduced cost and hazard and increased ease of administration through noninvasive, oral delivery systems, greater population levels of immunization and health; (2) the development of documents by FDA, WHO, and other regulatory authorities and groups, to assist the manufacturer in the appropriate manufacturing, preclinical, and clinical development of these new vaccines; (3) a greater array of vaccines to protect the civilian and military populations; (4) increased vaccine potency; (5) vaccines eliciting mucosal immunity, cytotoxic T cells, and/or neutralizing antibody. At the end of the 20th century there remain many unconquered pathogens and noninfectious indications for which medical science suggests that vaccines could be effective. New technologies may provide the best hope to address this wide array of public health needs.

Summary of clinical trials of inactivated influenza vaccine - 1978.

This report summarizes the clinical trials of the A/USSR/77 (H1N1) influenza vaccines performed in 1978. A total of 2,091 subjects participated in these trials. The results of these clinical trials indicated that two doses of H1N1 viral antigen were necessary to produce serum titers of hemagglutinin-inhibiting (HAI) antibody of greater than 1:40 in 80% or more of the test subjects younger than 25 years of age, who were unlikely to have experienced natural infection during the earlier period of prevalence of H1N1 virus (1947-1957). Only one dose of the A/Texas/77 (H3N2) or B/Hong Kong/72 antigen was necessary to stimulate equivalent titers of HAI antibody in serum. Thus, previous natural exposure to H1N1 viruses primed individuals 26 years of age or older to respond to H1N1 antigens. No major differences in antigenicity were noted between whole-virus and split-virus vaccines. No differences in reaction indexes measuring systemic reactions were noted when vaccine types were compared. Only one vaccine was associated with a reaction index appreciably higher than that of placebo. The relatively uniform antibody responses observed were attributed to the newer methods of vaccine standardization introduced after the clinical trials in 1976. No cases of vaccine-related neurological problems, including Guillain-Barré syndrome, were found during these trials. Vaccines containing 7-21 micrograms of each viral antigen were antigenic and were well tolerated.