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 F ortaleza, Brazil. Over the study period (August 1988 to March 1991), 5 6 children seen with persistent diarrhea, 52 children seen with acute diarrhea, and 42 controls attending the same hospital/clinic for illne sses other than diarrhea were enrolled. A potential pathogen was found in 91% of children with persistent diarrhea and 90% of those with acu te diarrhea versus 45% of controls (both p's < 0.01). Thirty-four perc ent of persistent (19/56) and 38% of acute (20/52) diarrhea cases vers us 2% (1/42) of controls (both p's < 0.01) had multiple pathogens, Ent eroaggregative 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, wh en the EAggEC were subdivided into aggregative adherence (AA) gene pro be positive (18/56; 32%) and negative (20/56; 36%), both subgroups wer e still significantly different from controls [6/42 (14%) and 7/42 (17 %), respectively; both p's < 0.05], EAggEC were the sole pathogen in 1 7 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 prob e-positive EAggEC were the sole pathogen in 20% of children with persi stent 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 < 0.0 2). 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 EAgg EC isolated from the small bowel of seven patients with persistent dia rrhea, 6 significantly colonized and caused diarrhea in the rabbit-rev ersible 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.