Gardia lamblia and Strongyloides stercoralis and tropical sprue (tropical malabsorption)
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Tropical sprue is a diagnosis about which we have to think when we are confronted to a patient back from overseas. We examined a young man back from Central African Republic where he got diarrhoea which keeps going on in France, with alteration of his general condition and stigmata of malabsorption. Taking advantage of such observation, the authors report on the present knowledge about that disease peculiar to tropical zone. Biological elements of malabsorption are associated to partial emaciation of villi of small intestine. As a matter of fact, diagnosis is made by elimination. Its pathogenesis remains unknown and is linked to some troubles of intestinal microbism of which exact causes has not been yet put into evidence. An easy treatment by tetracycline and folic acid is a true diagnosis test, as general condition is set up again, as well as villi intestinalis.
The existence of tropical sprue in Africa is controversial. In this paper we present 31 cases seen in Rhodesia over a 15 month period. They have the clinical features, small intestinal morphology, malabsorption pattern, and treatment response of tropical sprue. Other causes of malabsorption, and primary malnutrition, have been excluded. The severity of the clinical state and intestinal malabsorption distinguish these patients from those we have described with tropical enteropathy. The previous work on tropical sprue in Africa is reviewed and it is apparent that, when it has been adequately looked for, it has been found. It is clear that the question of tropical sprue in Africa must be re-examined and that it existence may have hitherto been concealed by the assumption that primary malnutrition is responsible for the high prevalence of deficiency states.
Fifteen of sixteen Caucasians with acute tropical sprue were founc to have numerous aerobic bacteria closely associated with the mucosal layer of the proximal jejunum. Four species of Enterobacteria were grown in eleven patients, and concentrations were higher in the mucosal patients than in the jejunal fluid. Only one of eight control cases with similar tropical exposure but without mucosal morphological abnormalities had any similar bacteria in the mucosal biopsy. In no case were Bacteroides isolated. Since clinical and biochemical improvement only occurred on treatment with tetracycline when enterobacteria were eliminated from the mucosa, it is suggested that these organisms may be responsible for persisting jejunal abnormalities in tropical sprue.
Ten patients with tropical sprue (TS) and 10 with irritable bowel syndrome (IBS) as controls were studied to characterize the immunocytes in the jejunal mucosa. IgA cells numbered 516,155 +/- 48,715 cells/mm3 in TS and 729,308 +/- 146,011/mm3 in the IBS patients. IgG cell counts were 28,885 +/- 8,081/mm3 in TS and 10,615 +/- 4,100/mm3 in IBS; IgM counts were 170,729 +/- 25,015/mm3 in TS and 169,253 +/- 45,353/mm3 in IBS. A positive correlation was present between IgM-bearing plasma cells and corresponding serum immunoglobulins (r = +0.71; p less than 0.05). No correlation was evident between the different immunocytes (IgA, IgG, and IgM) and the duration of illness, serum albumin, and tests for absorption of fat, B-12, and D-xylose (p greater than 0.05). The gut immunocytes expressed in absolute numbers were higher in our controls and TS patients than reported in Western populations.
Moderately severe tropical sprue was diagnosed in two American servicemen 15 and 19 months after return from Vietnam. Intestinal parasites were not demonstrated, and clinical, laboratory, and jejunal histological abnormalities returned to normal following treatment with tetracycline and folic acid in one patient and folic acid alone in the other. Neither patient was anemic, although one had hypersegmented polymorphonuclear leukocytes and both had macrocytosis and megaloblastic bone marrows. In each of these patients, diagnosis was delayed because of the failure to consider tropical sprue in the differential diagnosis of diarrhea and weight loss. The findings in these patients indicate that individuals from nonendemic areas who reside in Vietnam are at risk of developing overt tropical sprue.
Twenty-four patients have been found who appear to have endemic tropical sprue, with malabsorption on biochemical, radiological and histological grounds. Patients with the tropical sprue syndrome responded equally well clinically and biochemically to folate and tetracycline. Jejunal histology responded least well to treatment. It is suggested that as more Gastrointestinal Units are opened, especially in humid sea level areas in Africa, more cases of endemic tropical sprue will be found.
There is a lot of diversity in the observations on jejunal histology between light and discretion microscopy in tropical sprue. In order to compare the light and dissection microscopic appearances, a three-dimensional model of the villous pattern was constructed after a study of 350 serial sections of jejunal biopsy from a patient with tropical sprue. There was considerable variation in the morphological appearance of the villi in different sections. The changes seen varied from mild to partial villous atrophy. Broad synechia and bridge formation between adjoining villi due to fusion was frequently observed. It is postulated that the process of fusion of villi may be partly responsible for the development of features of partial villous atrophy seen in jejunal biopsies in tropical sprue. Normal jejunal pattern reported by some workers in patients with tropical sprue could possibly be due to inadequate sampling of the total biopsy piece.
The respective roles of reduced dietary intake and malabsorption in the pathogenesis of weight loss in persons with chronic tropical sprue have been evaluated . Dietary intake was found to be significantly (P less than 0.001) less in a group of 45 patients with tropical sprue, all of whom had anorexia due to deficiency of folate and/or vitamin B12, than in a group of 51 healthy Puerto Ricans. Weight loss was equally prominent in those patients with tropical sprue who had normal absorption of fat and protein as in those who had excessive fecal loss and reduced absorption of these nutrients. Treatment of five sprue patients with folic acid or vitamin B12 for 2 weeks resulted in improved appetite and increased in dietary intake with weight gain in the absence of significant improvement in intestinal absorption. Treatment with oral tetracycline for a similar period of time in five other patients was not associated with vitamin repletion, return of appetite or weight gain. These observations indicate that reduced dietary intake resulting from anorexia caused by vitamin deficiency is a significant, and sometimes the most important, factor in the pathogenesis of weight loss in persons with chronic tropical sprue.
Pteroylglutamic acid (PGA) absorption was assessed in ten untreated tropical sprue (TS) and eight control subjects utilizing a marker perfusion technique. Physiologic concentrations of the vitamin (25 ng/ml) dissolved in iso-osmotic solutions containing either mannitol of glucose at a concentration of 55.6 mM were perfused on each subject on two consecutive days. A statistically significant difference in PGA absorption between TS and control subjects was obtained only when glucose was present in the perfusate. Thus, unequivocal malabsorption of PGA is demonstrable in all subjects with TS when more refined techniques than the ones applied heretofore are utilized.
The intraluminal fate of orally administered radioactive vitamin B12 has been studied in control subjects with normal vitamin B12 absorption and those with vitamin B12 malabsorption due to tropical sprue. In control subjects 1 to 21% of the dose was bound to sedimentable material and 37 to 75% was bound to immunoreactive intrinsic factor. In subjects with vitamin B12 malabsorption due to tropical sprue, the results were identical with the control subjects. Bacteriological studies showed a statistically significant correlation between both the number of flora in the jejunum and the number of bacteroides in both the jejunum and ileum and vitamin B12 malabsorption. In patients with tropical sprue who have normal intrinsic factor secretion, the vitamin B12 absorptive defect is not due to binding of the vitamin to bacteria or to alteration to the intrinsic factor vitamin B12 complex in the intestinal lumen. The lesion appears to be one of the mucosal cell receptors or of the cells themselves, possibly caused by bacterial toxins.
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Cell-free broth filtrates of a strain of Klebsiella pneumoniae serotype 5 retained their capacity to induce fluid secretion in the rabbit ileal loop model after heating (100 C for 30 min), acid treatment (pH 4.4), and dialysis through viscose tubing. Sequential passage of an acetone precipitate of the broth filtrate through Diaflo membranes yielded an active fraction in the UM 2, but not the UM 10, retentate; this observation indicates that the molecular weight of the enterotoxin is in the range of 1,000-10,000. Klebsiella pneumoniae enterotoxin thus resembles the heat-stable enterotoxin of Escherichia coli in a number of respects.
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