Glucose Malabsorption and Intestinal Histopathology in Trichinella spiralis-Infected Guinea Pigs

Abstract

Intestinal nmalabsorption of glucose was induced in guinea pigs experimentally infected with Trichinella spiralis. In vitro and in vivo studies, carried out over a 28-day infection period, showed that the capacity of the small intestine to absorb glucose was significantly reduced in animals infected with 10,000 but not 5,000 larvae. Impaired absorption was first detected in the anterior three-quarters of the intestine on day 3 and for the fourth quarter on day 14 postinfection. The first and second quarters were capable of normal glucose uptake on day 14, whereas uptake in the third quarter remained impaired. On days 21 and 28 malabsorption was observed only in the fourth quarter. Impaired glucose uptake was associated with histopathology of the small intestine similar to that reported for humans with malabsorption syndromes. A loss of normal villous pattern, aberrant epithelial cells, and inflammation of the lamina propria were observed during the course of infection. Chronologically, these alterations occurred in the anterior half of the intestine during early infection and later extended into the posterior intestine. Localization of adult T. spiralis in the small intestine was studied to determine if a relationship could be established between histopathology and the distribution of worms in the gut. There was a shift in the relative distribution of worms from the anterior to posterior end of the small intestine as infection time progressed. Only a small fraction of a dose of 10,000 larvae could be recovered from the small intestine following infection. Eight to 10% of the infective dose was recovered at various times during the 1st week, 1.8% on day 14, 0.2% on day 21, and only rarely were worms recovered on day 28. These findings have significance in revealing previously unknown components in the pathogenesis of trichinosis and in providing a rational basis for explaining, in part, weight loss and diarrhea in guinea pigs with this disease. Guinea pigs infected with Trichinella spiralis are unable to gain weight at a normal rate. Although most of this weight loss can be attributed to reduced food and water consumption, some loss cannot be so explained and may be due to pathologic processes associated with the intestinal and extraintestinal phases of trichinosis (Castro and Olson, 1967). The effect of T. spiralis on the normal physiologic processes of the guinea pig small intestine is not known. Possibly infection with this parasite could lead to impaired intestinal absorption, which in turn may contribute to a reduction in weight. Weight loss and diarrhea are two of the most common signs of intestinal malabsorption (Johnson, 1965) and were observed in the T. spiralis-infected guinea pig (Castro and Olson, Received for publication 12 August 1966. * This investigation was supported in part by research grant AI-02732 from the NIAID, NIH, PHS; The James W. McLaughlin Fellowship Fund for the Study of Infection and Immunity; and research grant AM-05778 from the NIAMD, NIH, PHS. t Present address: Department of Zoology, University of Massachusetts, Amherst, Massachusetts 01002. 1967). Rats infected with T. spiralis or Nippostrongylus brasiliensis also fail to gain weight normally and are often diarrheic (Pambuccian and Cironeanu, 1962; Symons and Fairbairn, 1962). These same signs have been observed, along with malabsorption, in clinical nematode infections of man, e.g., hookworm disease (Sheehy et al., 1962) and strongyloidiasis (Stemmermann and Nakasone, 1960). In exp rimental studies Rogers (1942) reported a fall in the intestinal calcium assimilation in rats 4 to 8 days following infection with T. spiralis. Rats infected with N. brasiliensis show malabsorption of Na+, Cl-, water, and glucose (Symons and Fairbairn, 1962), and impaired digestion of protein (Symons, 1960) and maltose (Symons, 1966) in heavily infected regions of the gut. In view of the various reports above it was postulated that malabsorption accompanies the intestinal phase of trichinosis in the guinea pig. The absorptive activity of the small intestine of this host, as reflected by its ability to absorb D-glucose, was studied in order to test this hypothesis. Experiments were performed to obtain information on (a) the effect of trichinosis on the in vitro and in vivo move-