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Tropical sprue (TS), once known to be a common cause of malabsorption syndrome (MAS) in India and other tropical countries, is believed to be uncommon currently in spite of contrary evidence. Several recent studies from India showed TS to be the commonest cause of sporadic MAS in Indian adults. TS is diagnosed in patients presenting with suggestive clinical presentation, which cannot be explained by another cause of MAS and investigations revealing malabsorption of two unrelated substances, abnormal small-intestinal mucosal histology, which responds to treatment with antibiotics such as tetracycline and folic acid. There is substantial overlap between TS and postinfectious irritable bowel syndrome. There have been several advances in epidemiology, pathogenesis, and diagnosis of TS, hitherto an enigmatic condition.

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Tropical sprue (TS) is a chronic diarrheal disease of unknown etiology characterized by malabsorption and small bowel mucosal abnormalities. TS affects residents of, and visitors to, endemic tropical regions. Rarely the disease may remain latent for several years, and to date, few cases of latent TS have been reported in Europe or North America. However, in our increasingly multicultural communities and in a 'global village' where travel is common, clinicians must maintain a high index of suspicion for TS in patients presenting with diarrhea and malabsorption who have traveled to endemic regions. TS may mimic common diarrheal diseases that are seen in developed nations, including celiac disease, Crohn's disease, bacterial overgrowth, and other infectious etiologies. Accordingly, once these more common etiologies have been ruled out, TS must be considered in patients presenting with diarrhea after travel to endemic regions. We present a unique Canadian case of latent TS, with a brief review of the diagnostic approach and treatment.

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Tropical sprue (TS) is a clinical entity of unknown etiology characterized by an acquired chronic diarrheal illness and malabsorption that affects indigenous inhabitants and expatriates, either long-term residents or short-term visitors, in the tropical countries. The exact pathogenetic sequence of TS remains incompletely characterized. Bacterial overgrowth, disturbed gut motility, and hormonal and histopathologic abnormalities contribute to the development of TS in a susceptible host. Treatment with tetracycline and folate is effective in some patients, although relapses after treatment are common. Research in the areas of microbial factors, pathogenesis, immunogenetics, and hormonal and immune regulation, using modern diagnostic techniques, may be able to settle some of the unanswered issues and open new venues for diagnosis, prevention, and treatment of tropical sprue.

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One of the important consequences of the infection-nutrition interaction is mediated by malabsorption associated with chronic inflammation in the intestine, enteritis. Studies made possible after development of the peroral intestinal biopsy technique in the 1950s indicated the wide prevalence of enteropathy, particularly in tropical developing countries with poor levels of sanitation. Some consider this so-called subclinical tropical malabsorption to be the base of an iceberg, whose tip is tropical sprue, a severe form of malabsorption leading to nutritional deficiency that had been reported in colonial expatriates in tropical countries for 200 y. Some of the first demonstrations of the prevalence of tropical enteritis in Asia were made in quest of the pathologic lesion of cholera, and further examination of the water and electrolyte, as well as nutrient, malabsorption in cholera led serendipitously to the discovery of the oral rehydration solution for the treatment of diarrheal disease.

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Aside from infectious intestinal diseases with known etiology, there is a group of gastrointestinal disorders mainly affecting the small intestine of individuals predominantly living in and less often visiting or returning from the Third World, usually the tropics, and ranging from asymptomatic structural and/or functional abnormalities of the gastrointestinal mucosa (subclinical enteropathy, SE) to a fully symptomatic condition highlighted by malabsorption of nutrients with associated nutritional deficiencies responsive to folate and broad spectrum antibiotic treatment (tropical sprue, TS). Mounting evidence supports an infectious cause in many instances. The exact nature of the infection, whether initiated and/or perpetuated by enterotoxigenic coliform bacteria, virus(es) or a combination of these, is not clear. Further studies, including those using molecular techniques, are needed in order to clarify various aspects of these widely prevalent disorders.

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Tropical sprue, a primary malabsorption syndrome affecting residents and visitors to several tropical regions, occurs in southern India in endemic and epidemic forms. The stomach, the small intestine and colon are affected and malabsorption results in nutrient deficiency. Enterocyte damage, the primary lesion in southern Indian tropical sprue, is the result of a persistent lesion of the stem cell compartment. This lesion occurs on a background of tropical enteropathy and the available evidence suggests that an immunity conferring agent may be responsible for initiating the damage.

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The sprue syndromes, tropical and nontropical sprue, were both described as disease entities in the 1880s and share similar morphological features with varying degrees of villus atrophy of the small intestinal mucosa, and both present clinically with malabsorption. Recent cell kinetic studies of the turnover of the intestinal epithelium in sprue have convincingly demonstrated that the flat mucosa is caused by increased efflux (cell death) with compensatory crypt hyperplasia. The pathogenetic insult in tropical sprue appears to be a persistent overgrowth of the small intestine by enteric pathogens after a bout of turista. The pathogenesis of nontropical sprue is determined by both genetic factors, demonstrated with a strong association with certain HLA haplotypes (B8, DR3, DR7 and DC3) and presumably also environmental events (virus infection?), which render the mucosa susceptible to gluten. The cause of the malabsorption syndrome is multifactorial and results from both intraluminal and cellular events. The digestion of proteins, carbohydrates, and lipids is compromised due to decreased pancreatic and biliary secretion. The absorption of the digestive products is also severely affected due to decreased activity of microvillus enzymes (dipeptidases and disaccharidases) and a presumed reduction in the number of transport carriers. The clinical presentation is identical and the distinction between tropical and nontropical sprue is based on the history (ie, exposure to a tropical environment) and the response to treatment. Tropical sprue is cured by treatment with tetracycline and folic acid, whereas nontropical sprue responds to a gluten-free diet. Nontropical sprue is associated with dermatitis herpetiformis by common genetic and morphological features, and the skin lesions in dermatitis herpetiformis are also responsive to a gluten-free diet. Finally, there appears to be an increased incidence of intestinal malignancies (lymphoma, adenocarcinoma) in nontropical sprue.

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Hypochlorhydria by compromising the defence mechanisms of the upper gastrointestinal tract predisposes to intestinal bacterial and parasitic infections. Achlorhydria predisposes to anaerobic colonization of the small intestine; colonization is far greater than in normal subjects even with partial neutralization of their gastric acidity after a meal. The best evidence for increased incidence of specific bacterial infection in the presence of achlorhydria relates to the nontyphoid salmonelloses. There is also strongly suggestive evidence in cholera. Among parasitic infections, the most impressive evidence relates to giardiasis and strongyloidiasis. In some instances, the infections themselves may also cause hypochlorhydria. Longitudinal studies are required. Whether patients receiving H2-receptor antagonists are unduly vulnerable to gastrointestinal infections is unclear. The importance of hypochlorhydria in 'Third World' populations, in whom gastrointestinal infections are extremely common, especially in infancy, is, at present, also impossible to evaluate.

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