Campylobacter fetus subspecies (ssp.) jejuni has been recently recognized to cause diarrheal disease in man. To assess its importance as an enteric pathogen, we prospectively studied 514 patients with diarrhea. Campylobacter fetus ssp. jejuni was isolated from the feces of 26 patients (5%) and seven of 11 of their symptomatic household contacts. This organism was isolated from the feces of only one of 18 asymptomatic household contacts and not at all from 157 other healthy persons. Seventeen of 20 patients from whom C. fetus ssp. jejuni was isolated from fecal culture showed at least a fourfold rise in specific IgG titers. Review of 35 cases of campylobacter enteritis identified a typical clinical syndrome with acute onset of diarrhea, abdominal pain, fever, and constitutional symptoms. Stool examination revealed blood in 60% and polymorphonuclear leukocytes in 78% of patients. Epidemiologic investigation strongly suggested an external source for the infection in 22 of 35 patients.

Many studies have shown that lactoferrin and transferrin have antimicrobial activity against gram-negative bacteria, but a mechanism of action has not been defined. We hypothesized that the iron-binding proteins could affect the gram-negative outer membrane in a manner similar to that of the chelator EDTA. The ability of lactoferrin and transferrin to release radiolabeled lipopolysaccharide (LPS) from a UDP-galactose epimerasedeficient Escherichia coli mutant and from wild-type Salmonella typhimurium strains was tested. Initial studies in barbital-acetate buffer showed that EDTA and lactoferrin cause significant release of LPS from all three strains. Further studies found that LPS release was blocked by iron saturation of lactoferrin, occurred between pH 6 and 7.5, was comparable for bacterial concentrations from 104 to 107 CFU/mI, and increased with increasing lactoferrin concentrations. Studies using Hanks balanced salt solution lacking calcium and magnesium showed that transferrin also could cause LPS release. Additionally, both lactoferrin and transferrin increased the antibacterial effect of a subinhibitory concentration of rifampin, a drug excluded by the bacterial outer membrane. This work demonstrates that these iron-binding proteins damage the gram-negative outer membrane and alter bacterial outer membrane permeability.

The disappearance of NmA carriage among both vaccinated and unvaccinated populations is consistent with a vaccine-induced herd immunity effect.

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The PsA-TT vaccine elicited a stronger response to group A antibody than the PsACWY vaccine. (Funded by the Meningitis Vaccine Project through a grant from the Bill and Melinda Gates Foundation; Controlled-Trials.com numbers, ISRCTN78147026 and ISRCTN87739946.).