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Sixteen patients with tropical sprue were treated with either sulfaguanidine or sulfasuxidine for 6 months. There was disappearance of clinical symptoms and weight gain in all patients. The xylose absorption became normal in 12 and improved significantly in 4. Steatorrhea was present in 9 out of 12 patients and reverted to normal in the 6 patients who had the study performed after therapy. The jejunal biopsy improved considerably in 15 patients, but in none did it return to normal. The hemoglobin increased in all patients and 15 had over 13 g per 100 ml at the end of therapy. The bone marrow megaloblastosis reverted to normoblastic in 12 patients and remained with mild deficiency changes in 4. The serum folic acid remained subnormal in 7 out of 16 patients. The serum vitamin B12 was abnormal in 10 patients initially and became normal in 9. The hematological response was delayed in most patients and a rise in hemoglobin occurred during the 4th to 8th week in 6 patients who were carefully observed for the hematological response. The successful use of poorly absorbed sulfonamides in the treatment of tropical sprue adds another antimicrobial agent to those already known to be effective in this condition. Furthermore, it limits the antibacterial action to the lumen of the gastrointestinal tract of surface epithelium and provides indirect evidence as to the location of the probable infectious etiological agent in tropical sprue.

Coliform bacteria were isolated by either aerobic or anaerobic culture techniques from aspirates of the proximal small intestine of 4 of 5 Haitians with tropical sprue, but not from any of 10 well nourished Haitians who had milder gastrointestinal complaints and abnormalities. Klebsiella (Klebsiella pneumoniae and Klebsiella ozaenae) was cultured from the jejunal aspirates of 2 sprue patients and Escherichiae coli from the other 2. Fifteen colonies of coliform bacteria cultured from each aspirate were specifically identified by their biotype. In three instances, every colony in each aspirate was the same; In three instances, every colony in each aspirate was the same; in the fourth aspirate, two biotypes of E. coli were present, one of which grew under both aerobic and anaerobic culture conditions and another which grew only under anaerobic conditions on initial isolation. A randomly selected strain of each of the five coliform biotypes isolated was examined for enterotoxigenicity by determining the effect of variously prepared cell-free preparations on water transport in the rat jejunum using standard marker perfusion techniques. Every strain tested was toxigenic; one produced only a heat-stable toxin, one produced a heat-labile toxin only, and three elaborated both forms of enterotoxin. These observations indicate that most Haitians with tropical sprue have colonization of the proximal small intestine by a specific strain of enterotoxigenic coliform bacteria, but such is not the case among Haitians who have milder intestinal abnormalities.

Changes in the world political situation, the rapidity of transportation, and the availability of effective therapy have altered the pattern of sprue in persons going to the tropics. Gone, for the most part, are the days when expatriates liver for years in tropical areas, progressed on the full-blown pattern of debilitating disease when they acquired sprue, and then were never totally cured either by return home or by the then-available forms of therapy. Today, visitors to the tropics usually return home by jet aircraft within weeks or months after acquiring the disease, and thus they present just with manifestations of small bowel disease in the absence of nutritional deficiencies. In this circumstance, the differential diagnosis usually lies between sprue and giardiasis. Both of these disorders are caused by chronic contamination of the small bowel by enteric pathogens, and both can be cured by specific therapy directed at eradicating these organisms. In contrast to the situation in travelers, sprue among the indigenous population of the tropics remains largely unchanged: a chronic debilitating disorder that represents a significant contributory factor to the pathogenesis of morbidity and malnutrition in some areas.

The flat mucosal lesion of the small intestine is not pathognomonic of gluten-sensitive enteropathy (GSE). Frequently, the definitive diagnosis of this condition can only be established after three intestinal biopsies are performed: an initial one to show a flat mucosal lesion, one after a gluten-free diet to show morphological recovery, and one after a gluten challenge to show morphological deterioration. We used an organ culture model of GSE to determine the usefulness of this technique in establishing a diagnosis of GSE on the basis of the initial biopsy. Seventy-five patients with diarrhea, and/or malabsorption were evaluated prospectively; 40 had a flat mucosal lesion of variable degree; of these 26 were ultimately determined to have gluten-sensitive enteropathy by the above criteria. A rise in alkaline phosphatase activity of intestinal tissue from 22 of these 26 patients was inhibited when the tissue was cultured in gluten-containing medium as compared to enzyme activities of cultures in a gluten-free medium (108 +/- 69 versus 206 +/- 96, mean +/- SD, P less than 0.001). Mean enzyme values in the similarly cultured intestinal tissue from 13 of 14 patients ultimately shown not to have GSE were not affected by gluten (224 +/- 94 versus 201 +/- 109, P greater than 0.4). Examination of the data by stepwise discriminant analysis provided a function which correctly classified 35 of the 40 patients (88%). The false-positive and false-negative rate for establishing the diagnosis of GSE was 7% (1 of 14) and 15% (4 of 26), respectively. All patients with normal biopsies were classified correctly. The model can be used to establish prospectively the definitive diagnosis of GSE, obviate the need for additional diagnostic biopsies, and allow for the prompt pursuit of alternative diagnoses when gluten sensitivity is not shown.

The absorption of seven amino acids from an equimolar mixture containing each of the eight essential amino acids in a concentration of 20 mM was evaluated using a marker perfusion technique in 9 patients with untreated tropical sprue and in 6 healthy Puerto Rican control subjects. The rate of absorption of from two to six of the amino acids tested was lower in 7 of the patients than in the control subjects. The absorption of isoleucine, leucine, valine, and threonine was significantly lower in the group of sprue patients than in the control subjects. Treatment of 4 patients with oral tetracycline for 2 weeks was associated with return of amino acid absorption to normal in the 3 persons who had improved intestinal function, as tested by other parameters. More prolonged treatment was required for normalization of amino acid absorption in the 4th patient. These observations indicate that the absorption of certain essential amino acids is reduced in some patients with untreated tropical sprue.

The ultrastructure of the jejunal mucosa obtained by peroral biopsy from 7 control subjects and 12 patients with tropical sprue was studied. Compared with biopsies from control subjects in temperature zones, southern Indian control subjects showed minimal increase in lysosomes in surface epithelial cells, an occasional dark-staining degenerating epithelial cell in the upper two-thirds of villi, and an increase in cellular infiltration of surface epithelium and lamina propria. The jejunal epithelial cells of tropical sprue patients had abnormal microvilli, marked increase in lysosomes, increase in intracellular fat, and degenerative changes in rough endoplasmic reticulum and mitochondria. Two types of degenerating epithelial cells, designated pale and dark based on their staining quality, were seen in the villi. Pale staining degenerating cells were also seen in the crypts. The basement membrane region showed an amorphous deposit with many collagen fibers and fat droplets. The epithelial layer and lamina propria showed increased cellular infiltration. In one biopsy from a patient with sprue, particles of possible viral origin were seen.