Tropical/Environmental Enteropathy – David Brewster
Epidemiology of Coeliac Disease - Decker Butzner
Tropical Sprue in North Indian Children – Santosh Mittal

David Brewster. Northern Territory Clinical School, Darwin, Australia

There is considerable evidence from the developing world that apparently healthy individuals often have abnormalities of small bowel structure and function.¹ Instead of the usual finger-shaped villi seen on small bowel biopsy, affected individuals have leaves, ridges or convoluted villi with hypercellularity of the lamina propria. These changes were also associated with malabsorption and small bowel bacterial overgrowth in a number of studies.² Small intestinal malabsorption in asymptomatic residents of the developing world is often referred to as tropical enteropathy syndrome. It has been found to affect 30-50% of the population, including children, in almost all poor tropical areas studied. It is now clear that this syndrome is due to small intestinal mucosal damage from exposure to enteric pathogens in a contaminated environment. Since these changes in expatriates living in the tropics resolve after return to their home country, they are environmental rather than genetic.³ The increased intraepithelial lymphocyte count and raised serum globulin values suggest that they are due to recurrent gastrointestinal infections due to living in a contaminated environment with overexposure to enteric pathogens.⁴ This is highly relevant to Aboriginal children in northern Australia since the poor environmental health conditions in remote communities have already been documented.⁵

The result of dual sugar testing in post-infective tropical malabsorption in adults was a mean L/R ratio of 20 compared to 2.0 in controls with both increased lactulose and reduced L-rhamnose permeation.⁶ Young children are even more exposed to a contaminated environment than adults, so it is not surprising that the features of tropical enteropathy syndrome are acquired in early childhood in communities in the developing world.⁷ The biopsy changes of childhood tropical enteropathy are loss of villous height, crypt lengthening, and lymphocyte infiltration of the lamina propria.⁴⁴ Environmental contamination is a particular risk during the weaning period and in the tropical rainy season, affecting drinking water and foods such as cereal gruels and cow’s milk.⁸ Although there was controversy initially about the nutritional significance of subclinical malabsorption in children,⁹ more recent studies using intestinal permeability ratios in The Gambia have documented that this underlying small bowel damage accounts for over 40% of growth failure in weanlings.¹⁰ This raises the question as to the contribution of abnormal intestinal permeability or subclinical malabsorption in asymptomatic Aboriginal children to the high prevalence of growth retardation.

J. Decker Butzner. Department of Pediatrics, University of Calgary, Calgary, Alberta, CANADA

Coeliac disease occurs in genetically susceptible individuals who develop intolerance to the wheat storage protein, gluten, and to other similar proteins found in barley and rye. It occurs in 8 to 15% of 1^st degree relatives of patients with coeliac disease and has been associated with the selected major histocompatibillity complex genes, HLA-DR3 and DQ2. Infants with coeliac disease classically present with chronic diarrhoea, abdominal distension and failure to thrive; features identical to those of the postenteritis enteropathy syndrome that frequently occurs in infants from the tropical world. Coeliac disease is manifested by a small intestinal injury, characterised by villus blunting, crypt hyperplasia, and inflammation of the lamina propria. This injury appears indistinguishable from that observed in biopsies of infants with postenteritis enteropathy. Serum screening tests, including IgA-antiendomysial (IgA-EMA) and tissue transglutaminase (IgA-tTG) antibodies, have markedly improved diagnostic accuracy and demonstrated that coeliac disease is more common than previously suspected. Epidemiological studies carried out in Europe and more recently North America have documented a prevalence ranging from 1:130-1:500. It is reasonable to suspect a similar prevalence in populations of the rest of the world with similar HLA haplotypes and where wheat-type grains are food staples. Few studies have been conducted, but recent investigations from South America, North Africa, and Asia suggest coeliac is under diagnosed in susceptible populations. Tools are now available to conduct large epidemiological studies to determine the prevalence of coeliac disease and its contribution to the postenteritis enteropathy syndrome in the developing world. Funding to conduct these studies is urgently required.

S.K. Mittal, K. Rajeshwari, Sushil Srivastava, Veena Malhotra.* Departments of Pediatrics & Pathology*, MAMC & Associated L.N. Hospital & G.B. Pant Hospital, New Delhi-110002.

The first description of ‘Tropical Sprue’ in the English medical literature was made in the West Indies by Hillary in 1759 ¹ while the first report from India was in 1818. Baker was the first to recognise in 1957 that intestinal malabsorption due to tropical sprue was not confined to European or American expatriates living in the tropics, but rather was widespread among the indigenous population of South India^2,3 Tropical Sprue has also been subsequently recognised in other parts of India.^4-7 This clinical condition has been extensively studied in adults but has not yet been clearly defined in children.

There is still considerable controversy about the aetiology of tropical sprue. While much of the available evidence in adults suggests that sprue is an infectious disease⁸, with persistent contamination of the small bowel by enteric pathogens there is evidence that cannot easily be refuted suggesting that nutritional factors may play a predominant role.⁹ The etiological factors appear to be infection and poor nutrition and in many cases a combination of the two.

The original definition adult tropical sprue has now been considerably modified because of better understanding of its pathogenesis. The present accepted definition for tropical sprue is " A syndrome among persons in the tropics who have morphologic abnormalities of the small intestine associated with malabsorption of two or more unrelated substances for which no aetiology can be ascertained." ⁽¹⁰⁾ This definition however has drawbacks. The basis for accepting malabsorption of two substances and net three or one as a diagnostic criterion is not clear. The proposed criteria can be seen in symptomatic adults in tropical countries. ⁽¹¹⁾ The exact diagnostic criteria in children is still to be established. In the present study the clinical spectrum of chronic diarrhoea in children was studied with a view to define the incidence and problem of tropical sprue in children.

Methods: Children presenting to the paediatric gastroenterology wing of Maulana Azad Medical College with loose stools for more than 2 weeks duration or history of recurrent episodes of loose stools were subjected to a detailed clinical examination and diagnostic work up. Patients who had less than or equal to two visits in the follow up were excluded from the analysis.

Results: A total of 590 children registered at the paediatric gastroenterology clinic from January 1996 to June 2000 with various gastrointestinal complaints. Of these 162 (27.4%) had chronic diarrhoea as defined above. Seventy-four of these did not come for regular follow up and were dropped from the final analysis. After a complete clinical history, stool examination, Mantoux test, abdominal ultrasound, biochemical tests of liver function and small bowel biopsy where indicated the aetiology of chromic diarrhoea was established as shown in Table1. Thirty six patients who were diagnosed as tropical sprue had clinical evidence of malabsorption in the form of loose frothy bulky foul smelling stools, anaemia (mean Hb 8.3 g|dL), Vitamin A deficiency was seen in 5, Vitamin D deficiency in 7, 4 patients had both vitamin A & D deficiency & D-xylose test was abnormal in all.

In patients of tropical sprue duration of therapy ranged from 6-12 weeks (6 weeks, n = 23; 8 weeks, n = 10; 12 weeks, n = 2; 10 weeks, n = 1). The average weight gain was 1.28 kg at end of completion of therapy (mean 7 weeks, range 6 to 12 weeks) in patients of tropical sprue. In follow up all patients of tropical sprue were symptom free even after 6 months of completion of therapy. Repeat small bowel biopsy was done in 22 cases, in 16 the biopsy normalised, improvement but persistent biopsy changes were seen in 5 while in 1 case the biopsy findings had worsened despite marked clinical improvement. The comparative evaluation of these 36 cases of tropical sprue as compared to patients with coeliac disease is shown in table 2.

Discussion: Aside from infectious intestinal diseases with known aetiology, there is a group of gastrointestinal disorders mainly affecting the small intestine of individuals predominantly living in and less often visiting or returning usually from the tropics and ranging from asymptomatic structural and/or functional abnormalities of the gastro intestinal mucosa (subclinical enteropathy) to a fully symptomatic condition highlighted by malabsorption of nutrients with associated nutritional deficiencies responsive to folate and broad spectrum antibiotic treatment (tropical sprue)¹². Mounting evidence supports an infections cause in many instances. The exact nature of the infection whether initiated and / or perpetuated by enterotoxigenic coliform bacteria, virus (es) or a combination of these in not clear.

In the current study out of total of 106 cases of chronic diarrhoea, 36 patients (33.9%) had endemic tropical sprue. Coeliac disease and tropical sprue together constituted 50.94% (54/106) patients with chronic diarrhoea. It is plausible that the actual incidence might have been higher if the 56 patients with chromic diarrhoea who did not report for investigations and follow up were also recruited for further studies. Tropical sprue remains an ill-defined entity in paediatric patients. Previous studies about the incidence of tropical sprue among children with chronic diarrhoea has been reported to be 46.8%, while irritable bowel syndrome (10.6%), giardiasis (14.8%) coeliac disease (6.8%) and non-specific diarrhoea constituted 21.8% of cases. ⁽¹³⁾

Most of the published information about tropical sprue is pertaining to adults especially from southern India. It is perhaps prudent not to apply the diagnostic criteria established in adults to the paediatric population namely malabsorption of two substances. By using such stringent criteria for diagnosis, many cases of tropical sprue may not be picked up and the opportunity to treat a relatively benign condition is lost. In children in the tropics with chronic diarrhoea where a diagnosis is not evident after preliminary investigations and access to extensive investigative work up is not available, a trial of antibiotics with folate therapy is warranted before subjecting a child to a lifelong period of gluten withdrawal. It is unclear whether mere folate supplementation, might reverse the intestinal histology in such children with tropical sprue. A randomised double blind controlled trial may provide the answer. Another approach may be to supply folate only to these with demonstrable low serum folate levels. Till such time that a clear clinical consensus emerges about tropical sprue, a trial of antimicrobial therapy with folic acid may cure many children of chronic diarrhoea completely rather than subject them to diets devoid of gluten for a lifetime.

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