Diarrhoeal Diseases (Updated February 2009)
Campylobacter
Disease Burden
Campylobacter jejuni ranks as one of the most common bacterial causes of diarrhoea in both industrialized and developing countries, with an estimated 400 million cases worldwide (1.5 million cases in the USA alone) [46] . It also represents the second cause of travellers' diarrhoea and enteric disease in military populations after enterotoxigenic Escherichia coli (ETEC). In developing countries, infection is nearly universal in early childhood [47] . It also is an important cause of foodborne illness in young children, including less than 1 year-old infants [48] . Perhaps of greater concern is its reported association with life-threatening cases of Guillain-Barré syndrome (GBS).
Campylobacters are frequent commensals in the intestinal tract of animals - mostly birds - and, as such, are frequently implicated in food-borne diarrhoeal illness [49] [50] . Transmission generally occurs through consumption of contaminated water, raw milk or undercooked meat, especially poultry meat and meat products. Not washing one's hands and not cleaning kitchen utensils after carving a raw chicken carcass are major risk factors. Transmission also can occur through contaminated recreational waters. Asymptomatic excretion of the pathogen by immune individuals seems to be frequent. Antibiotic resistance is a growing concern.
Vaccine
Immunity to Campylobacter appears to be strain-specific and complex, and the antigens conferring immunity are not well understood [51] . No vaccine is available at the moment. Uncertainty regarding the mechanism of GBS is another obstacle to Campylobacter vaccine development [52] . A candidate vaccine consisting of heat- and formalin-killed whole bacteria combined with LT as a mucosal adjuvant has been developed by the Navy Medical Research Institute (USA) [53] and shown to provide 87% protection against intestinal colonization in a small number of volunteers challenged post vaccination with a pathogenic Campylobacter strain. Current studies have focussed on the use of flagellin [54] or flagella-secreted protein FspA1 as candidate vaccines to be administered by the nasal route with attenuated LT R192G as an adjuvant. Vaccination of mice with FspA1 resulted in 64% protection against C jejuni challenge [55] . The major outer membrane protein (MOMP) from C jejuni might be another promising candidate for a subunit vaccine, especially when made into proteoliposomes [56] .
An oral live multivalent vaccine expressing antigens from Campylobacter, Shigellas and ETEC is also currently being developed as a travellers’ diarrhoea vaccine (see Shigella vaccines below).