From pertussis to tuberculosis: what can be learned?

Following the introduction of whole-cell pertussis vaccines into the general population, the number of cases of Bordetella pertussis disease declined dramatically. As disease incidence declined, the public's concern for pertussis as a national health problem gradually waned. However, a shift in paradigm occurred, and various groups and the media began to voice their concerns regarding adverse events associated with whole-cell vaccines. These events provided an impetus for the expedited development of safer and as efficacious subunit acellular vaccines. Effective public health leadership, public advocacy, scientific ingenuity, and collaborative interactions between government, academia, and industry culminated in the licensure of acellular pertussis vaccines. In this article, emphasis is placed on conceptualizing how a national public health agenda was implemented that allowed better insight into various public health concerns related to the development and use of acellular pertussis vaccines, concerns that were eventually translated into concrete actions. Knowledge of the environment in which this occurred may play a major role in relating the pertussis experience to tuberculosis vaccine development.

Characterization of pneumococcal specific antibodies in healthy unvaccinated adults.

Unlike the elderly, healthy middle aged adults are at relatively low risk of acquiring serious pneumococcal disease. An explanation that has been proposed is that people in this age group have significant amounts of serum antibody (primarily IgG2) that react with any pneumococcal capsular polysaccharide serotypes. The level of antibody can be as high as several hundred micrograms per milliliter of blood for some serotypes. A significant component of this reactivity is directed toward the conserved C-polysaccharide depletion. Even after C-polysaccharide depletion, which is included as a routine part of the assay to determine antibody levels, resting antibody levels in a normal healthy adult population can vary widely. We have analyzed the reactivity of serum from 76 people to 16 pneumococcal capsular polysaccharide serotypes. The antibody reactivities to 13 of 16 serotypes are highly correlated with one another. Depletion of serum with C-polysaccharide and purified capsular polysaccharide inhibited antibody binding to type specific capsular polysaccharide. Cross-serotype inhibition of antibody binding was also observed. This indicates that there are materials contained within the pneumococcal polysaccharides that contribute to the cross-reactivity of serum antibodies in people that have not been vaccinated with the pneumococcal vaccine.

A controlled trial of two acellular vaccines and one whole-cell vaccine against pertussis. Progetto Pertosse Working Group.

BACKGROUND: Concern about both safety and efficacy has made the use of whole-cell pertussis vaccines controversial. In some European countries, including Italy, the rate of vaccination against pertussis is low. METHODS: We conducted a double-blind trial in Italy in which infants were randomly assigned to vaccination at two, four, and six months of age with an acellular pertussis vaccine together with diphtheria and tetanus toxoids (DTP); a DTP vaccine containing whole-cell pertussis (manufactured by Connaught Laboratories); or diphtheria and tetanus toxoids without pertussis (DT). The acellular DTP vaccine was either one containing filamentous hemagglutinin, pertactin, and pertussis toxin inactivated with formalin and glutaraldehyde (SmithKline Beecham) or one with filamentous hemagglutinin, pertactin, and genetically detoxified pertussis toxin (Chiron Biocine). Pertussis was defined as 21 days or more of paroxysmal cough, with infection confirmed by culture or serologic testing. RESULTS: The efficacy of each vaccine, given in three doses, against pertussis was determined for 14,751 children over an average of 17 months, with cases included in the analysis if cough began 30 days or more after the completion of immunization. For both of the acellular DTP vaccines, the efficacy was 84 percent (95 percent confidence intervals, 76 to 89 percent for Biocine DTP and 76 to 90 percent for SmithKline DTP), whereas the efficacy of the whole-cell DTP vaccine was only 36 percent (95 percent confidence interval, 14 to 52 percent). The antibody responses were greater to the acellular vaccines than to the whole-cell vaccine. Local and systemic adverse events were significantly more frequent after the administration of the whole-cell vaccine. For the acellular vaccines, the frequency of adverse events was similar to that in the control (DT) group. CONCLUSIONS: The two acellular DTP vaccines we studied were safe, immunogenic, and efficacious against pertussis, whereas the efficacy of the whole-cell DTP vaccine was unexpectedly low.

A strategy for the chemical synthesis of nanostructures.

Highly localized chemical catalysis was carried out on the surface groups of a self-assembled monolayer with a scanning probe device. With the use of a platinum-coated atomic force microscope tip, the terminal azide groups of the monolayer were catalytically hydrogenated with high spatial resolution. The newly created amino groups were then covalently modified to generate new surface structures. By varying the nature of the catalyst and the chemical composition of the surface, it may be possible to synthesize molecular assemblies not readily produced by existing microfabrication techniques.

Vaccine technologies: view to the future.

The development of vaccines to prevent infectious diseases has been one of the most important contributions of biomedical science. Recent advances in the basic sciences are now fueling the development of a new generation of vaccines that will be based on rational design approaches. Two factors are making this possible: an improved understanding of the microbial factors required for virulence and the nature of the immune response to infection. The status of new vaccine technologies is summarized here.

Health coverage for retirees: a timebomb.

Offering health-care plans to retired employees has become an increasingly expensive corporate benefit. The aging population, health-care inflation, and reduced medicare financing have forced many companies to modify their programs.

Mammography after needle aspiration of palpable breast masses.

Hematoma resulting from attempted aspiration of a palpable breast mass can cause incorrect mammographic interpretation by rendering irregular and indistinct the otherwise smooth and sharply defined margins characteristic of a benign lesion. In this study of recently aspirated breast masses, we found 17 benign lesions that demonstrated poorly defined, irregular margins on mammograms that suggested malignancy. All these false-positive interpretations occurred when aspiration preceded mammography by less than 2 weeks (17 of 47, 36 percent); no such diagnostic error occurred in the 31 cases when mammography was delayed for 2 weeks or more after aspiration. An appreciation of the frequency and natural history of postaspiration hematoma formation should either encourage physicians to request mammography before carrying out invasive procedures, or alternatively, to defer mammography until 2 weeks after aspiration, since mammography then should more clearly portray the benign characteristics of truly benign masses, thereby possibly obviating biopsy.

Inhibition of rat adenocarcinoma metastases by "Staphylococcus aureus" protein A.

Fischer F 344/CRBL female rats were injected intravenously with 10(6) syngeneic 13,762 adenocarcinoma cells, and daily doses of either 10 micrograms, 100 micrograms or 1 mg Staphylococcus aureus protein A were administered intraperitoneally on days 1 through 11. The animals were sacrificed on day 12, their lungs infused with Bouin's solution, and lung metastases counted. A significant reduction in the number of visible metastatic nodules was observed in the animals given 100 micrograms and 1 mg of Staphylococcus aureus protein A daily.