ETIOLOGY AND EPIDEMIOLOGY OF PERSISTENT DIARRHEA IN NORTHEASTERN BRAZIL - A HOSPITAL-BASED, PROSPECTIVE, CASE-CONTROL STUDY

With the improved therapy for acute diarrhea, persistent diarrhea (>14 days) is emerging as a major problem in developing countries. However, the etiologies and pathogenesis of persistent diarrhea remain poorly understood, We conducted a prospective case-control study in children <3 years old presenting to the hospital with persistent diarrhea in Fortaleza, Brazil. Over the study period (August 1988 to March 1991), 56 children seen with persistent diarrhea, 52 children seen with acute diarrhea, and 42 controls attending the same hospital/clinic for illnesses other than diarrhea were enrolled. A potential pathogen was found in 91% of children with persistent diarrhea and 90% of those with acute diarrhea versus 45% of controls (both p's < 0.01). Thirty-four percent of persistent (19/56) and 38% of acute (20/52) diarrhea cases versus 2% (1/42) of controls (both p's < 0.01) had multiple pathogens, Enteroaggregative Escherichia coli (EAggEC) were found in 68% (38/56) of children with persistent diarrhea versus 31% (13/42) of controls (p < 0.01) and in 46% (24/52) of those with acute diarrhea. Furthermore, when the EAggEC were subdivided into aggregative adherence (AA) gene probe positive (18/56; 32%) and negative (20/56; 36%), both subgroups were still significantly different from controls [6/42 (14%) and 7/42 (17%), respectively; both p's < 0.05], EAggEC were the sole pathogen in 17 of 56 (30%) of patients with persistent diarrhea [vs. 11/94 (11.7%) in those with acute diarrhea and controls; p < 0.01], and AA gene probe-positive EAggEC were the sole pathogen in 20% of children with persistent diarrhea, whereas only 6% of those with acute diarrhea and 7% of controls had AA probe-positive E, coli (persistent diarrhea vs. acute diarrhea and controls; p < 0.03) Cryptosporidia were found in 25% (14/56) of children with persistent diarrhea (vs, 5% of controls; p < 0.02). Of 32 children with persistent diarrhea who had quantitative small bowel cultures, 13 (41%) had greater than or equal to 10(4)/ml EAggEC (2 had AA probe-positive EAggEC) in the upper small bowel. Of 10 EAggEC isolated from the small bowel of seven patients with persistent diarrhea, 6 significantly colonized and caused diarrhea in the rabbit-reversible ileal tie model. Both AA gene probe-positive and AA gene probe-negative EAggEC and Cryptosporidium are important potential pathogens in young children with persistent diarrhea and warrant further study to improve our understanding of their pathogenesis and control.