Wasting Marmoset Syndrome is a Malabsorption Process With Features Similar to Celiac Disease
Malabsorption is characterized by failure to digest or absorb fats, fat-soluble and other vitamins, proteins, carbohydrates, electrolytes, minerals, and water. Clinically the malabsorption disorders resemble each other more than they differ and the consequences affect many organ systems such as the alimentary tract, hematopoietic system, musculoskeletal system, nervous system, urinary tract, and endocrine system.
Wasting marmoset syndrome (WMS) is a major cause of morbidity and mortality of marmosets and tamarins in numerous colonies of different countries, including Brazil. The general features of WMS are diarrhea, weight loss, muscle atrophy, chronic colitis, anemia, alopecia, nephritis, parasitic or bacterial infection, progressive reluctance to move and paralysis of hind limbs, generalized weakness, and death. There are four hypotheses concerning the pathogenesis of WMS: nutritional problem due to incorrect diet (protein-calorie deficiency or food antigens), malabsorption (including pancreatic insufficiency due to Trichospirura leptostoma), infectious diseases (Campylobacter spp.), and behavioral alteration (inadequate adaptation to captivity). Although diarrhea and weight loss as a consequence of dysfunction of the small intestine is common in general practice, a panel of screening investigations may provide insight into the cause, and should distinguish malabsorption syndromes, including pancreatic exocrine insufficiency, giardiasis and reduced small intestinal absorptive surface area.
The main objective of this research is to demonstrate that WMS is a malabsorption process due impaired mucosal absorption.
Sick marmosets were selected based on general symptoms of WMS, which meant weight loss, diarrhea, anemia, or historic report of low body weight, anemia and diarrhea at least once during a year. The marmoset control group was formed based on good health of primates, with weight between 249 g and 497 g (median 345.8 g). All animals were kept in captivity for more than 6 months at the Mucky Association of Small Primates, Jundiaí, São Paulo State, Brazil. The diet and general management were similar to others colonies described in literature, and all animals were maintained on a TID feeding schedule.
The control group contained 21 marmosets, 19 adults (10 males and nine females) and two subadults (one male and one female). The group consisted of ten black-tufted-ear marmoset (Callithrix penicillate), two common marmoset (Callithrix jacchus), one Geoffroy’s tufted-ear marmoset (Callithrix geoffroyi), and eight hybrid marmosets (C. penicillate and C. jacchus). The WMS group was formed by 22 primates, 20 adults (11 males and nine females), and two subadults (one male and one female), which included 11 black-tufted-ear marmosets, one common marmoset, one Geoffroy’s tufted-ear marmoset, and nine hybrid marmosets. All 43 animals had a physical examination, clinical follow up (1 year) and appropriate treatment when necessary.
A panel of screening tests was selected to differentiate impaired intraluminal digestion from impaired mucosal absorption of nutrients.
Identical biologic material was collected and processed from all marmosets studied:
1. Feces were evaluated for form, color, odor, and fat content
2. Fecal trypsin
3. Fecal evaluation for parasites
4. Fecal Campylobacter spp. culture
5. Urinalysis and 5-hour urinary excretion for D-xylose absorption test
Clinically the sick marmosets showed weight loss, pallor of oral mucous membranes (anemia), intermittent diarrhea with or without improvement after antibiotic therapy, abdominal distention, weakness, muscle wasting, peripheral neuropathy, and 18 died.
The laboratory results of WMS group demonstrated normal feces to intermittent bulky, greasy, foul, yellow or gray feces, which had fat globules (steatorrhea), undigested starch granules, and rare muscle fibers. Feces also showed intermittent proteolytic activity (gelatin test). Ten sick and 6 healthy animals were diagnosed with the cyst form of Giardia spp. All sick marmosets with Giardia spp. infection were treated before the D-xylose absorption test was performed. No abnormalities were found in the control or WMS group on urinalysis. Eighteen animals of the WMS group had less than 10% (median 7.5%) urinary excretion of D-xylose, while 14 animals in the control group had excretion above 10% (median 15%). In statistical analysis there was a significant difference (p<0.05) between the control and WMS group in the D-xylose absorption test using Mann-Whitney Test, with p=0.0023.
A complete necropsy was performed on 18 animals that died due to WMS at the pathology department of FMVZ-USP. Gross examination revealed marked weight loss, muscle wasting, pallor of mucous membranes and organs, abdominal distention due to distention of intestinal loops, and secondary systemic bacterial infection or fungal infection in lungs, esophagus and intestine. Microscopically the small intestine had diffuse enteritis characterized by marked atrophy or total loss of villi, crypt hyperplasia, and moderate to markedly increased numbers of lymphocytes, plasma cells and macrophages in the lamina propria. None of the cases had Giardia spp. identified histologically.
The clinical, laboratory, gross, and histologic findings described in WMS cases indicated that WMS is a malabsorption process due to reduced small intestine surface area. In humans the major causes of malabsorption are celiac disease (CD), pancreatic insufficiency, giardiasis, cystic fibrosis, and Crohn’s disease. The classic signs of CD are weight loss, anemia, diarrhea, and weakness and the mainstay of diagnosis is a small-bowel mucosal biopsy. The characteristic histopathologic changes involve serious damage of villous architecture with decreased villous height to crypt depth, decreased epithelial cell height, hyperplasia of crypts, and increased lymphocytic infiltration of the mucosa. Similar changes were noted in the WMS animals in this study suggesting a similar pathogenesis. It is suggested that further study of WMS in marmosets involve maintaining symptomatic animals on a gluten-free diet and monitor for clinical remission.
We would like to thank Lívia Bótar and technical staff from Mucky Association of Small Primates for facilitating this research, Dr. José Luiz Catão Dias from Pathology Department of FMVZ-USP for encouraging this investigation. This work was supported financially by FAPESP with grants 00/04412-1, and the study is part of the PhD project of L.R.M. de Sá.