G AS'l'BOENTEROLOGY Copyright 1966 by The Williams & Wilkins Co. Vol. 50, No.3 Printed in U.S.A. INTESTINAL MALABSORPTION AND HELMINTHIC AND PROTOZOAN INFECTIONS OF THE SMALL INTESTINE EMIL KOTCHER, Sc.D., MARIO MIRANDA G., M.D., RODRIGO ESQUIVEL R., M.Q.C., ANTONIO PENA-CHAVARRIA, M.D., D.P.H., DONALD L. DONOHUGH, M.D., M.P.H. & T.M., CESAR BALDIZ6N L., M.D., ALBERTO ACOSTA G., M.D., AND JOSE LE6N Apuy A., M.D. Louisiana State University, International Center for Medical Research and Training, University of Costa Rica, School of Medicine, Hospital San Juan de Dios, San Jose, Costa Rica One of the chief functions of the human small intestine is the absorption of digested nutrients. Data presented by Borgstrom et au show that lipids derived from ingested fat as well as carbohydrates are absorbed chiefly in the distal part of the duodenum and proximal part of the jejunum. In view of these data, it is not unreasonable to assume that any condition, or organism, which produced alterations in the mucosa of the small intestine might thereby interfere with its absorptive function. This investigation was carried out to assess the role of parasites of the small intestine in bringing about changes in the mucosa which might result in a malabsorption syndrome. Although over a dozen protozoa and helminths parasitize man's small intestine, four were chosen for study because of the availability of patients infected with these parasites in Costa Rica. The four parasitic infections are strongyloidiasis, regarded by Frye 2 as the most important nematode infection of the small bowel, hookworm infection, ascariasis, and Received August 18, 1965. Accepted Novem- per high power field. ber 23, 1965. Address requests for reprints to: Dr. Emil Kotcher, Parasitology Section, International Center for Medical Research and Training, Apartado 5140, San Jose, Costa Rica. This investigation was supported in part by Research Grant AM-08683 from the National Institute of Allergy and Infectious Diseases, United States Public Health Service, by Research Grant TW00148 from the Office of International Research of the National Institutes of Health, and in part by a research grant from Merck Sharp & Dohme Research Laboratories. 366 giardiasis. The tissue alterations produced by each of these parasites vary depending upon the numbers present, perhaps the strains involved, and the condition of the host. By collecting clinical, pathological, and biochemical data, it is possible to determine whether or not the parasite-induced pathology is sufficient to reduce the absorptive ability of the mucosa to a point where a malabsorption syndrome exists. Materials and Methods Patients with strongyloidiasis, hookworm infection, ascariasis, and giardiasis were selected for study. Patients with single infections were sought but such individuals were not always available as one or more of these parasites as well as Trichuris trichiura were also present in many cases. The severity of these infections varied considerably although the most severe infections, as determined by egg or larval counts of diluted feces (Stoll technique), were chosen for study. One patient had almost 300,000 Strongyloides larvae per gram of feces. Another patient had over 83,000 hookworm eggs per gram of feces. The Giardia infections were graded 1 to 4, the latter having over 50 cysts Two types of biochemical tests were used to evaluate intestinal absorption. The method of Van de Kamer et al." was used in determining fat absorption. D-Xylose urine values were used to determine carbohydrate absorption using a 5-g oral dose and a 5-hr excretion time (Santini et al.'). The Carey capsule was used to obtain mucosal biopsies of the duodenum or jejunum before treatment for the parasites and, when possible, after treatment. Patients with normal fecal fat and D-xylose values, who were not infected with parasites and who were obviously in
March 1966 PARASITES AND INTESTINAL MALABSORPTION 367 good nutritional status, were also biopsied for comparative purposes. The biopsies were oriented for sectioning so that the villi were cut longitudinally. The sections were stained with hematoxylin and eosin. Thirty-seven duodenal and jejunal biopsies were obtained from 35 patients. Procedure When suitably infected individuals were found, an attempt was made to pursue the following procedure: 1. Before specific treatment for the parasite, feces was collected for fecal fat determinations for 5 days, urine was collected for 2 days for D xylose determinations, and a mucosal biopsy was obtained. 2. Specific chemotherapy: (a) Strongyloidiasis was treated with thiabendazole, 50 mg per kg body weight in one dose. (b) Hookworm infection was treated with tetrachlorethylene, 3 g per adult in one dose. (c) Giardiasis was treated with quinacrine, 0.1 g, three times daily, for 5 days. (d) Ascariasis and trichuriasis were not treated. 3. A 2-week period was allowed for repair of intestinal mucosa; this period was spent in the hospital or at home. 4. The feces were re-examined for evidence of eradication of the parasites 2 weeks or more after treatment. 5. Post-treatment biochemical tests were carried out for a 5-day period and a mucosal biopsy was obtained for comparison. A series of uninfected individuals was studied similarly as controls. Results Figure 1 shows fecal fat values for three series of individuals. The data grouped in series 1 of the figure consist of values obtained on hospitalized patients with and without a variety of intestinal parasites. The control patients represent individuals who did not have any intestinal parasites and without any gastrointestinal disorder. The fecal fat values of these patients were all within the limits accepted as normal, except for one Strongyloides-infected individual who had hepatitis with jaundice, and one hookworm patient whose values were only slightly greater than normal. While the average values of the control individuals clustered in the lower end of the normal value range, some of the patients had values below the normal range, indicating a higher percentage of fat absorption. In an effort to determine whether fat absorption would be improved after eradication of the parasites by chemotherapy, a series of patients was studied before and after treatment (series 2). Figure 1 shows the results on such patients (indicated by separate geometric figures) who were infected with either Strongyloides or Giardia. It will be observed that the fecal fat values (averages of three to five daily fecal specimens from each patient) were all within normal limits. Before and after biopsy data were obtained on two of these patients. Figure 2 (A.M.Q., before treatment) shows a biopsy of the jejunal mucosa with Strongyloides adults in a heavily infected patient. This patient had 290,000 Strongyloides larvae in a gram of feces in one of the examinations. The villi can be seen to be stunted and fused, with hemorrhage in the lamina propria. About 3 months before this biopsy was taken the patient began to vomit three or four times a day and had diarrhea (as many as eight movements per day) with gas and abdominal pain. The patient was treated for Strongyloides with thiabendazole and sent home cured of her infection. About 7 weeks later, a second jejunal biopsy was performed (fig. 3). There was no evidence of parasites and the mucosa was normal. Her stool specimens were negative for intestinal parasites. The pretreatment fecal fat values in this patient were within normal limits (average of 4.38 g for four stool specimens). The n-xylose test was also normal (1.11 g). The post-treatment fecal fat values (average of 1.62 g for four stool specimens) and n-xylose test (2.5 g) were normal and indicated relatively improved absorptive ability of the mucosa. Other individuals in the series studied (series 3 with individuals of each series identified with different geometric figures) were adult male prisoners. The series consisted of a group of uninfected controls and a series of men all infected with Strongyloides stercoralis of varying intensity, and some having additionally hookworm, Ascaris or Trichuris, or both. The infected
368 KOTCHER ET AL. Vol. 50, No.3 8 7 r X X I:l I:l CIl 4 a: '" z.....j 3 <l (.) IL '" 2 I a: 0 z I Itt, z <l a: l-, a I " A (22) " I B C 0 (20) (10) (8) Sarie, I I:l A 0 i A() + 0 X j() 0 " 8 0. 0 6., X 0.. 8 E F G Pre, Post. F-r. Post. Pre. Post. (S) (II) (4) (9) H K Series 2 Series 3 FIG. 1. Series 1: A = Controls (22), uninfected patients; B = patients with hookworm and Trichuris (20); C = patients with hookworm, Ascaris, and Trichuris (0); D = patients with hookworm, Ascaris, and Strongyloides (eight); E = patients with hookworm and Strongyloides (six); F = patients with Strongyloides (11); G = patients with Giardia (four). Series 2: Six patients with Strongyloides and three patients with Giardia, showing their pre- and post-treatment fecal fat values. Series 3: H = Controls, uninfected (six), showing their fecal fat values, pre- and post-treatment with thiabendazole; K = prisoners (11), all infected with Strongyloides, and some with hookworm, Ascaris, Trichuris, and Giardia, pre- and post-treatment with thiabendazole. individuals were treated with thiabendazole to eradicate the Strongyloides. The fecal fat values, consisting of five daily observations with the diet supplemented with 100 g of fat per day, were within normal limits in both controls and infected men. In the control group, four of the men had fecal fat values that were very close in the two sets of observations. One man had fecal fat values significantly lower in the second set of observations. In the infected prisoners, four men had essentially the same fecal fat values before and after treatment; four men had higher values (by 1 g or more) after treatment; and two men had lower values (by 1 g or
March 1966 PARASITES AND INTESTINAL MALABSORPTION 369 FIG. 2. Pretreatment jejunal biopsy of patient A. M. Q., 13 July 1964, showing two adult Strongyloides stercoralis in the mucosa with stunted and fused villi, and hemorrhage of the lamina propria. FIG. 3. Post-treatment jejunal biopsy of patient A. M. Q., 31 August 1964, 7 weeks later, showing return of villi to normal structure. more) after treatment. On the basis of these data it is not possible to state that there was an appreciable improvement in the absorption of fat following treatment for the eradication of Strongyloides. A series of infected adult hospital patients were studied for carbohydrate absorption using the 5-g D-xylose test. These patients were infected in varying intensity with Strongyloides, hookworm, Ascaris,
370 KOTCHER ET AL. Vol. 50, No.3 3 - rn a:: '" C!I!!: 2. rn III :::;) 'i J a:: 0 z III rn IL 0 9 III >- x C!I ". I Z a '" a:: '- I 0 Controll Hookworm Hookworm Hookworm Trichuris Ascarll Alcarll. SlronVll. Trlchurll (7) (2) (2) (4) 121 FIG. 4. D-Xylose excretion values of hospital patients (5-g oral dose and 5-hr urine specimen. Giardia, and Trichuris. The 5-hr urine values obtained for the majority of patients fell within the range of values reported for normal, uninfected individuals (fig. 4). In three of these patients, all infected with Strongyloides, the values were slightly below normal in two, and somewhat lower in the third. Discussion In recent years, several investigators have studied the problem of intestinal parasitism and the malabsorption syndrome. Palumbo et a1. 5 studied giardiasis in relation to this syndrome and found no conclusive evidence to support such a relationship. The data presented here on giardiasis patients support the conclusions of Palumbo and his coworkers. Sheehy et a1. 6 presented clinical, pathological, and biochemical data in support of a malabsorption syndrome in Puerto Rican patients with severe hookworm disease (patients with up to 19,000 eggs per gram of fecal solids). Abdalla et au studied Egyptian patients with ancylostomiasis and found these patients had fecal fat and D xylose values that were within normal limits. Layrisse et al. 8 studied Venezuelan patients with heavy hookworm infections and also found the fecal fat, D-xylose, and other biochemical test values within normal limits. The Venezuelan investigators believed that etiological factors other than hookworm were present in the Puerto Rican patients. They point out that sprue is common in Puerto Rico, whereas it is a rarity in Venezuela. The results of the cur-
March 1966 PARASITES AND INTESTINAL MALABSORPTION 371 rent investigation support the findings of both the Egyptian and Venezuelan reports inasmuch as the fecal fat and n-xylose values are within normal limits for our Costa Rican patients with hookworm. Alcorn and Kotcher9 reported a malabsorption syndrome secondary to severe chronic strongyloidiasis in two patients who were autopsied. Both of these patients had progressive weight loss, and at autopsy had extensive mucosal destruction of the distal stomach and proximal small intestine caused by Strongyloides. Unfortunately biochemical data (fecal fat values, n-xylose tests, etc.) were not available for these patients. The strongyloidiasis patients in the present series have biochemical values which indicate that their absorption of fats and carbohydrates is within normal limits. These values are normal even for patients with heavy infections (up to 290,000 larvae per gram of feces) and with evidence of pathological changes in their duodenal and jejunal mucosa obtained by biopsy. After eradicative treatment for their Strongyloides infection the majority of these patients had fecal fat values lower than their pretreatment tests, indicating improvement of their ability to absorb fat. Sheehy et a1. 6 reported such improvement in their hookworm patients after treatment. It is obvious, however, that while these parasites of the small intestine may indeed embarrass the absorptive ability of the mucosa, the tissue changes they produce, even with what appears to be severe infection, are not so great as to reduce the absorptive ability to such levels as exist in sprue and other malabsorptive conditions. The tissue damage produced by these parasites is generally localized as petechiae, occasionally as larger ulcers, and rarely as extensive mucosal damage. The alterations produced by these parasites appear to be largely mechanical due to their migratory habits. Unless tremendously large numbers of helminth or protozoan parasites are present, it appears there is a sufficient reserve of normal mucosal surface to maintain the absorptive ability of the intestine within limits accepted as normal by biochemical tests. Summary A series of patients with various parasites of the small intestine was studied for evidence of intestinal malabsorption using clinical, pathological and biochemical tests. There was no evidence to support a malabsorption syndrome in cases of giardiasis, strongyloidiasis, and hookworm infection. REFERENCES 1. Borgstrom, B., A. Dahlquist, G. Lundh, and J. Sjovall. 1957. Studies of intestinal digestion and absorption in the human. J. Clin. Invest. 36: 1521-1536. 2. Frye, W. W. 1963. Parasitism of the small bowel. J. A. M. A. 183: 368--370. 3. Van de Kamer, J. H., H. ten Bokkel Huinink, and H. A. Weijers. 1949. Rapid method for determination of fat in feces. J. BioI. Chem. 177: 347-355. 4. Santini, R., Jr., T. W. Sheehy, and J. Martinez. 1961. The xylose tolerance test using a five-gram dose. Gastroenterology 40: 772-774. 5. Palumbo, P. J., H. H. Scudamore, and J. H. Thompson, Jr. 1962. Relationship of infestation with Giardia Lamblia to intestinal malabsorption syndromes. Proc. Mayo Clin. 37: 589-598. 6. Sheehy, T. W., W. H. Meroney, R. S. Cox, and J. E. Soler. 1962. Hookworm disease and malabsorption. Gastroenterology 42: 148--156. 7. Abdalla, A., N. Gad-EI Mawla, A. EI-Rooby, M. Shaker, and N. Galil. 1963. Studies on the malabsorption syndrome among Egyptians. 1. Fecal fat and n-xylose absorption tests in pellagra and ancylostomiasis. J. Egypt. Med. Ass. 46: 544--552. 8. Layrisse, M., N. Blumenfeld, L. Carbonell, J. Desenne, and M. Roche. 1964. Intestinal absorption tests and biopsy of the jejunum in subjects with heavy hookworm infection. Amer. J. Trop. Med. 13: 297-305. 9. Alcorn, M. 0., Jr., and E. Kotcher. 1961. Secondary malabsorption syndrome produced by chronic strongyloidiasis. Southern Med. J. 54: 193-197.