An Epizootic of Lymphoplasmacytic Gastritis Attributed to Helicobacter pylori Infection in Cynomolgus Monkeys (Macaca fascicularis)

Abstract

Abstract. An epizootic of subclinical lymphoplasmacytic gastritis occurred in cynomolgus monkeys maintained at our research facility. Gastric pathology data and histologic sections of 63 adolescent monkeys (2.5-3.5 years old) sacrificed during the epizootic were reviewed. Localized to multifocal reddening of the gastric mucosa was noted grossly in 7 of 44 (16%) monkeys harboring Helicobacter pylori, but not in any of 19 monkeys in which these bacteria were not seen. Gastritis, characterized by accentuation of lymphoplasmacytic infiltrates in antral and to a lesser degree cardiac mucosa, occurred in 42 of 63 (67%) monkeys evaluated and in 42 of 44 (93%) monkeys in which H. pylori was observed microscopically. Two monkeys with H. pylori infection had infiltrate scores that overlapped with the upper limit of scores of H. pylori-negative animals. Coincident with accentuated infiltrates were gastric gland epithelial hyperplasia, reduction in mucin content of surface and gland epithelia, and comparatively minor infiltrates of neutrophils in superficial lamina propria and gastric glands. Antral mucosa thickness often exceeded 1.5 to 2 times normal. Antral mucosal erosions occurred in 7 of 44 (16%) monkeys with H. pylori. Argyrophilic bacteria morphologically consistent with H. pylori were present in antral and less commonly cardiac mucosal glands. Intensity of bacterial colonization correlated with lymphoplasmacytic infiltrates (r ϭ 0.754) and hyperplasia (r ϭ 0.700), although responses were quite variable. These bacteria were not detected in fundic mucosa except in instances where parietal cells were substantially depleted in glands coincident with localized increases in lamina propria inflammatory cell infiltrates. Helicobacter heilmannii-like organisms (HHLOs) were present in fundic glands of all 63 monkeys; colonization was often pronounced. Scores for fundic mucosal inflammation did not correlate with presence or intensity of colonization with HHLOs (r ϭ 0.005). Rather, fundic inflammation scores positively correlated with the antral inflammation scores (r ϭ 0.548). Bacteria morphologically, biochemically, and genetically consistent with H. pylori were cultured from gastric mucosal specimens confirming bacterial identification. These findings demonstrate that adolescent cynomolgus monkeys are susceptible to natural infection with H. pylori and develop many morphologic hallmarks of H. pylori-related gastritis in humans.Key words: Animal model; bacteria; gastritis; Gastrospirillum hominis; Helicobacter; Helicobacter heilmannii; Helicobacter pylori; monkey; nonhuman primate; spirochetes; stomach.Spirochetes or spiral-shaped bacteria have long been recognized as constituents of gastric microflora in various mammalian species. 8,29,36,48,55,61,62 38 Most Helicobacter species do not have strict host specificity. Rather, certain species have been isolated from multiple host species and experimental transmission among animal species has been shown. 19,22,31,37,41,52 Suspected zoonotic transmission has also been reported. ...

Helicobacter pylori invades the gastric mucosa and translocates to the gastric lymph nodes

“…The presence of large spiral-shaped Helicobacter organisms within the cytoplasm of parietal cells is a common finding in several animal species, such as rhesus monkeys, 45 cynomolgus monkeys, 46 rats, 47 cats, and dogs. 48 Electron microscopic observation indicates that these organisms in those animals reside within dilated intracellular canaliculi of parietal cells.…”

Distribution of collagen types I, III, and IV in gastric tissue of marmosets (Callithrix spp., Callitrichidae: Primates)

“…And because pathological conditions such as gastritis also occur among primate species (Dubois et al 1991, Khanolkar-Gaitonde et al 2000, Reindel et al 1999, this study was conducted to analyze the expression of collagen types I, III, and IV in the gastric tissue of marmosets (Callithrix sp. ).…”

Molecular characterization of Helicobacter pylori strains isolated from cynomolgus monkeys (M. fascicularis)

“…One of the animals (no. 1200), originated from the Phillipines and was among the 63 monkeys that were the subject of a previous report (Reindel et al, 1999). The other four animals (nos.…”

“…The health status of the monkeys was monitored routinely as described and none of the animals displayed signs of disease (Reindel et al, 1999). Following euthanasia, all animals were subjected to necropsy and specimens from the antro-pyloric mucosa were collected, cultured, isolated, and stored as described .…”

“…The natural reservoir for H. pylori is believed to be limited to humans, certain macaques (M. mulatta, M. fascicularis, and M. nemestrinae) (Dubois et al, 1995;Reindel et al, 1999;Suerbaum et al, 2002), and cats (Handt et al, 1994). …”