The infectious diseases impact statement: a mechanism for addressing emerging diseases.

The use of an Infectious Diseases Impact Statement (IDIS) is proposed for predictive assessments of local changes in infectious diseases arising from human-engineered activities. IDIS is intended to be analogous to an Environmental Impact Statement. The drafting of an IDIS for specific activities, particularly in developing nations, would provide a formal mechanism for examining potential changes in local health conditions, including infected and susceptible populations, diseases likely to fluctuate in response to development, existing control measures, and vectors likely to be affected by human activities. The resulting survey data could provide a rational basis and direction for development, surveillance, and prevention measures. An IDIS process that balances environmental alterations, local human health, and economic growth could substantially alter the nature of international development efforts and infectious disease outbreaks.

Emerging bacterial zoonotic and vector-borne diseases. Ecological and epidemiological factors.

Among the etiologic agents of emerging infectious diseases are several bacterial organisms that naturally reside in animal and arthropod hosts. The most compelling emerging bacterial zoonotic and vector-borne diseases in the United States are Lyme disease; a Southern erythema migrans-like illness; human monocytic ehrlichiosis; human granulocytic ehrlichiosis; a novel cat flea-associated typhus group rickettsiosis; bartonelloses of immunocompetent and immunocompromised persons, particularly with AIDS; and sylvatic plague. Some of these antimicrobial-treatable infections are life threatening. During the acute stage of illness when antimicrobial agents are most effective, the flulike clinical signs and symptoms and available laboratory tests frequently do not point to a particular diagnosis. Epidemiological factors determined by the ecology of the bacteria are often the most useful diagnostic clues. The recognition of these evolving problems emphasizes the need for development of better laboratory diagnostic methods, for surveillance for and tracking of disease, and for continued research into factors contributing to transmission of the organisms. The continual appearance of previously unidentified bacterial infections requires prospective national strategies for timely recognition of the syndrome, identification of the agent, establishment of criteria and methods for diagnosis, optimization of the treatment regimen, and determination of successful approaches to prevention and control.

Intestinal mucus gel and secretory antibody are barriers to Campylobacter jejuni adherence to INT 407 cells.

An in vitro mucus assay was developed to study the role of mucus gel and secretory immunoglobulin A (sIgA) in preventing attachment of Campylobacter jejuni to INT 407 cells. An overlay of rabbit small intestinal mucus was found to impede the attachment of C. jejuni to a monolayer of INT 407 cells. Mucus from rabbits previously colonized with C. jejuni was found to completely inhibit bacterial adherence to the underlying cells. Anti-Campylobacter sIgA was readily detected in mucus samples from previously exposed rabbits and was responsible for eliminating bacterial adherence to the INT 407 cells. This was shown by loss of inhibition after mucus absorption with Campylobacter cells. sIgA-containing mucus caused aggregation of the C. jejuni cells within the mucus layer of the assay system. Nonimmune mucus and sIgA alone were unable to cause bacterial aggregation, suggesting a cooperative role for mucus and sIgA. Antibodies responsible for adhesion inhibition were cross-reactive among several Campylobacter strains and were not directed solely against flagellar antigens.

Identification and characterization of two Campylobacter jejuni adhesins for cellular and mucous substrates.

Campylobacter jejuni is able to colonize the human intestinal mucosa and cause disease. For this reason, it was important to investigate mechanisms by which C. jejuni adheres to epithelial cells and intestinal mucus gel. All strains of C. jejuni used were able to adhere to INT 407 epithelial cells and mucus, but high adherence to one substrate did not necessarily indicate comparable adherence to the other. The adherence of C. jejuni to cells was inhibited partially by treating the bacterial cells with proteases or glutaraldehyde or by adding a certain carbohydrate (fucose or mannose) to the medium. The flagellum of C. jejuni was identified as a potential adhesin by comparing adherence of flagellated and aflagellated variants. Shearing of the bacterial cells to remove the flagella reduced bacterial adhesion, whereas immobilization of the flagellum with KCN increased adhesion. Purified flagella showed specific, fucose-resistant binding to epithelial cells but not to intestinal mucus. The presence of a second, nonproteinaceous adhesin was suggested because no single treatment of the bacteria completely inhibited adhesion. Lipopolysaccharide (LPS) was identified as another C. jejuni adhesin. [3H]LPS specifically bound to epithelial cells, and this phenomenon was inhibited by periodate oxidation of the LPS or glutaraldehyde fixation of the epithelial cells. LPS, unlike flagella, was fucose sensitive and inhibited binding of whole bacterial cells to INT 407 cells. LPS was also able to bind to intestinal mucus gel. These data indicate that both flagella and LPS are important in adhesion to the mucosal surface.

Identification and characterization of mouse small intestine mucosal receptors for Escherichia coli K-12(K88ab).

Adhesion of 3H-labeled Escherichia coli K-12(K88ab) to CD-1 mouse small intestine mucus and brush border preparations, immobilized on polystyrene, was studied. E. coli K12(K88ab) was shown to adhere readily to either crude mucus or brush border preparations, but not to bovine serum albumin. In contrast, the nearly isogenic E. coli K-12 strain, i.e., lacking the K88ab plasmid, did not bind well to either mucus, brush borders, or bovine serum albumin. The adhesion of E. coli K-12(K88ab) to both mucus and brush borders required pilus expression (i.e., growth at temperatures greater than 18 degrees C) and was inhibited by pretreatment of either mucus or brush borders with trypsin, pronase, or sodium metaperiodate and by the presence of D-galactosamine. Crude mucus was fractionated by gel filtration, and the proteins in receptor-containing fractions were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Separated proteins were Western blotted to nitrocellulose. Adhesion of 35SO4-labeled E. coli K-12(K88ab) and 35SO4-labeled E. coli K-12 to Western blots followed by autoradiography revealed two E. coli K-12(K88ab)-specific mucus receptor proteins (57 and 64 kilodaltons). Brush borders contained the same two receptor proteins present in mucus and an additional 91-kilodalton receptor protein.