Immune Response of Bangladeshi Children With Acute Diarrhea Who Subsequently Have Persistent Diarrhea Tasnim Azim, *Laila N. Islam, Mohammed S. Sarker, Shaikh M. Ahmad, Jena D. Hamadani, Shah M. Faruque, and Mohammed A. Salam International Centre for Diarrhoeal Disease Research, Bangladesh, Mohakhali, Dhaka, Bangladesh; *Department of Biochemistry, University of Dhaka, Dhaka, Bangladesh ABSTRACT Background: Because altered immune responses may be a risk factor for persistent diarrhea, various aspects of the immune response were examined to elucidate the underlying immune mechanisms that may be involved in the development of per- sistent diarrhea. Methods: Children (7–12 months of age) with watery diarrhea for 6 to 8 days from the Dhaka Hospital of the Interna- tional Centre for Diarrheal Disease Research, Bangladesh (ICDDR,B), were enrolled. Children were classified as having acute diarrhea (AD) or persistent diarrhea (PD) if diarrhea re- solved within 14 days or persisted for more than 14 days, respectively. Uninfected control children (n  13), from the Nutrition Follow-Up Unit of ICDDR,B were also enrolled. Of the 123 children with diarrhea who were enrolled, 85 had AD and 38 had PD. Comparisons were performed for clinical fea- tures, nutritional status (weight for age, plasma transferrin, and serum albumin levels), and immune responses: neutrophil func- tion; peripheral blood mononuclear cell function, delayed-type hypersensitivity (DTH) responses, plasma levels of immuno- globulins, tumor necrosis factor-, and interferon-. Univariate analyses were conducted to assess differences among the three groups of children and between children with AD and PD. Logistic regression was performed to determine risk factors for PD. Results: There were no differences in clinical features and nutritional status among the groups of children studied. More children in whom PD developed had a negative DTH response to tuberculin than those with AD (P  0.021). Also, a negative DTH response to tuberculin was a significant risk factor for PD (odds ratio [OR]  3.8, 95% confidence interval [CI]  1.5– 9.9). Conclusions: Children with acute diarrhea with a negative DTH response to tuberculin are more likely to have develop- ment of persistent diarrhea. JPGN 31:528–535, 2000. Key Words: Delayed-type hypersensitivity—Immune response— Malnutrition—Persistent diarrhea. © 2000 Lippincott Williams & Wilkins, Inc. Acute diarrhea (AD) is usually self-limiting, but in some individuals diarrhea persists for 14 days or more and is defined as persistent diarrhea (PD) (1). In devel- oping countries, 30% to 50% of deaths from diarrhea are due to PD (2). Although the cause of PD is not well understood, several risk factors have been identified and include malnutrition (3), decreased breast-feeding (3,4), infection with enteroaggregative Escherichia coli (EAggEC) (5), concomitant signs of chest infection (3), and decreased cell-mediated immunity (6–8). More re- cently, it has been shown that in children with AD in whom PD subsequently developed there were increased numbers of peripheral blood CD8 + T cells and a lower CD4 + T-cell response to stimulants than in children who did not have PD (9). With specific diarrheal pathogens, such as rotavirus (RV), we recently found that plasma levels of interferon- (IFN) but not tumor necrosis fac- tor- (TNF) or interleukin (IL)-10, at 6 to 8 days of diarrhea were higher in children who subsequently had PD than in children who recovered without PD (10). The role of these risk factors is not clear, but they may be interlinked. It has been suggested that PD may not be related to specific biologic factors only but to a series of factors that are biologic, social, and environmental (11). However, because most analyses for risk factors for PD have been conducted in children with similar social and environmental backgrounds, biologic factors may play a key role. Therefore, a better understanding of the under- lying biologic factors is required for the prevention and management of PD. In this study, we examined various aspects of the im- mune response to assess whether they affect the duration of diarrhea in children with acute watery diarrhea. We compared responses in three groups of children: those with a history of diarrhea for 6 to 8 days who recovered Received April 19, 2000; accepted August 31, 2000. Address correspondence and reprint requests to Tasnim Azim, Labo- ratory Sciences Division, ICDDR,B, GPO Box 128, Dhaka 1000, Ban- gladesh. (e-mail tasnim@icddrb.org). Journal of Pediatric Gastroenterology and Nutrition 31:528–535 © November 2000 Lippincott Williams & Wilkins, Inc., Philadelphia 528