coli. Understanding the aetiology of diarrhoea is important, particularly in high disease burden areas where risk factors need to be identified and vaccine development priorities established. Most of what is known about the relative importance of different diarrhoeagenic E. coli categories comes from small, snapshot studies or studies of traveller’s diarrhoea, analogous

to what Guerrant et al. [26] refer to as the ‘eyes of the hippopotamus’. Many high-burden developing countries lack cell culture facilities for the Gold Standard HEp-2 assay needed to delineate some pathotypes of diarrhoea-causing E. coli from commensals. Non-radioactive DNA probes and, more recently, PCR have been advocated as methodology that might be used to detect enterovirulent E. coli in developing countries [27, 28]. The vast majority of earlier studies that have not used HEp-2 adherence assays have defined DAEC as E. coli that hybridize to the selleck chemicals llc Adriamycin solubility dmso daaC probe. Of 30 Medline-indexed controlled studies that sought DAEC, we were able to identify only nine that have heretofore demonstrated an association of DAEC with diarrhoea. Girón et al. [29] used daaC probe hybridization and HEp-2 adherence and found that DAEC were associated with disease in Mayan children in Mexico. However that study had a very short duration (3 weeks) and focused on a small remote population (63

cases, 1300 total population), and therefore there are limits to the extent to which the data should be extrapolated. Cegielski et al. [30] found probe-positive, but not diffuse-adherent DAEC associated with chronic diarrhoea in HIV-positive and HIV-negative patients in another ADAM7 small study in Tanzania. A recent Brazilian study made a similar finding: probe-positive

DAEC were associated with paediatric diarrhoeal disease, particularly in older children [13]. A Bangladeshi study reported that DAEC identified by adherence assay were associated with persistent but not acute diarrhoea (p < 0.05)[31]. A number of other developing country studies published since that time, employing probe and adherence, adherence alone, or PCR-based detection have failed to find an association between detection of DAEC and disease [8, 10, 12], 32-35. In 1993, Levine et al. observed that a Chilean study, entirely reliant on the daaC probe, represented the “”strongest epidemiologic evidence so far to indicate that DAEC may indeed be pathogenic”"[36]. This large, controlled cohort study identified DAEC, based on daaC hybridization alone, in 16.6% of cases and 11.9% of controls (p = 0.0024). In that study, children aged 4-5 years had a relative risk of 2.1 for DAEC (overall relative risk was 1.4). Subsequent reports from studies using only the probe support the findings of that study [13, 37, 38]. For example, a 2005 US study found that DAEC identified by SLM862 probe were associated with diarrhoea (p < 0.05) but DAEC identified by HEp-2 adherence were not [38].