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Chronic diarrhea is a common disorder in tropical regions, affecting residents, visitors, and even expatriates. It may stem from a myriad of infectious, inflammatory, and even malignant causes. In patients in whom no etiology has been found, tropical sprue (TS) is an important diagnosis to consider. We report the case of a 60-year-old man originally from Guatemala, presenting with chronic diarrhea and megaloblastic anemia due to severe vitamin B12 deficiency. Biopsies of the small bowel revealed partial villous atrophy and inflammatory infiltrate with the participation of eosinophils. The diagnosis of TS was established after exclusion of other causes of malabsorption syndrome. This is a disease of unknown etiology with complex and multifactorial pathophysiology, with an important component of intestinal dysbiosis. Antibiotics and vitamin supplementation are the pillars of therapy. Awareness of this disorder is essential in preventing delayed diagnosis and subsequent morbidity.

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Our current understanding of tropical sprue is that it is a malabsorption syndrome that responds to treatment with folic acid and a broad spectra antibiotic. This realization came only after countless years of research by legions of investigators. Twenty-seven individual studies on various aspects of tropical sprue were published in the Puerto Rico Journal of Public Health and Tropical Medicine from 1925 to 1949. This article summarizes significant findings, presented chronologically, and speculates on the direction of future investigations into tropical sprue.

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The Indian Neurogastroenterology and Motility Association (INMA), earlier named the Indian Motility and Functional Diseases Association developed this evidence-based practice guidelines for the management of irritable bowel syndrome (IBS). A modified Delphi process was used to develop this consensus containing 28 statements, which were concerning diagnostic criteria, epidemiology, etiopathogenesis and comorbidities, investigations, lifestyle modifications and treatments. Owing to the Coronavirus disease-19 (COVID-19) pandemic, lockdowns and mobility restrictions, web-based meetings and electronic voting were the major tools used to develop this consensus. A statement was regarded as accepted when the sum of "completely accepted" and "accepted with minor reservation" voted responses were 80% or higher. Finally, the consensus was achieved on all 28 statements. The consensus team members are of the view that this work may find use in teaching, patient care, and research on IBS in India and other nations.

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Environmental enteric dysfunction (EED) is characterized by malabsorption and diarrhea that result in irreversible deficits in physical and intellectual growth. We sought to define the expression of transport and tight junction proteins by quantitative analysis of duodenal biopsies from patients with EED. Biopsies from Pakistani children with confirmed EED diagnoses were compared to those from age-matched North American healthy controls, patients with celiac disease, and patients with nonceliac disease with villous atrophy or intraepithelial lymphocytosis. Expression of brush border digestive and transport proteins and paracellular (tight junction) proteins was assessed by quantitative multiplex immunofluorescence microscopy. EED was characterized by partial villous atrophy and marked intraepithelial lymphocytosis. Epithelial proliferation and enteroendocrine, tuft, and Paneth cell numbers were unchanged, but there was significant goblet cell expansion in EED biopsies. Expression of proteins involved in nutrient and water absorption and that of the basolateral Cl- transport protein NKCC1 were also increased in EED. Finally, the barrier-forming tight junction protein claudin-4 (CLDN4) was significantly upregulated in EED, particularly within villous enterocytes. In contrast, expression of CFTR, CLDN2, CLDN15, JAM-A, occludin, ZO-1, and E-cadherin was unchanged. Upregulation of a barrier-forming tight junction protein and brush border and basolateral membrane proteins that support nutrient and water transport in EED is paradoxical, as their increased expression would be expected to be correlated with increased intestinal barrier function and enhanced absorption, respectively. These data suggest that EED activates adaptive intestinal epithelial responses to enhance nutrient absorption but that these changes are insufficient to restore health.

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Celiac disease is an autoimmune disorder characterized by a broad spectrum of histological damage to the intestinal mucosa. Comprehension and understanding of the association between anti-tissue transglutaminase (anti-tTG) antibody levels and the histological severity of celiac disease are not well established, prompting the need for meta-analysis. This study aims to offer insights into the diagnostic abilities of anti-tTG antibody levels in determining the histological severity of celiac disease by providing quantitative evidence based on a diverse range of studies. An extensive search was conducted across four electronic research databases to identify primary research articles reporting serum anti-tTG antibody levels in correlation with different Marsh grades, signifying the histological severity of celiac disease. The software tool RevMan 5.4 (the Cochrane Collaboration, London, UK) was used to compile standardized mean differences (SMD) alongside their respective confidence intervals. A total of 13 studies were included in the meta-analysis, with a patient pool of 2505 patients. Marsh grade I and II were found to have higher anti-tTG antibody levels compared to those with grade 0 (SMD 1.50; 95% CI: 1.12, 1.87; p-value <0.00001). Antibody levels were higher in Marsh grade IIIa when compared to both grade 0 (SMD 0.97; 95% CI: 0.67, 1.28; p-value <0.00001) and grade ≤2 (SMD 0.61; 95% CI: 0.44, 0.79; p-value <0.00001). Patients with Marsh IIIb also reported greater anti-tTG levels compared to grade 0 (SMD 1.48; 95% CI: 0.99, 1.96; p-value <0.00001) and grade ≤2 (SMD 0.98; 95% CI: 0.79, 1.18; p-value <0.00001). Likewise, Marsh grade ≥IIIc reported high levels of anti-tTG antibodies in comparison with grade 0 (SMD 1.06; 95% CI: 0.72, 1.39; p-value <0.00001) and grade ≤2 (SMD 1.18; 95% CI: 1.02, 1.34; p-value <0.00001). Our meta-analysis revealed a consistent, robust correlation between anti-tTG antibody levels and the histological severity of celiac disease, with a clear trend of increasing antibody levels corresponding to the severity of mucosal damage. Large-scale primary research initiatives are needed to reach definitive conclusions.

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Following acute gastroenteritis (AGE) due to bacteria, viruses, or protozoa, a subset of patients develop new onset Rome criteria positive irritable bowel syndrome (IBS), called postinfection IBS (PI-IBS). The pooled prevalence of PI-IBS following AGE was 11.5%. PI-IBS is the best natural model that suggests that a subset of patients with IBS may have an organic basis. Several factors are associated with a greater risk of development of PI-IBS following AGE including female sex, younger age, smoking, severity of AGE, abdominal pain, bleeding per rectum, treatment with antibiotics, anxiety, depression, somatization, neuroticism, recent adverse life events, hypochondriasis, extroversion, negative illness beliefs, history of stress, sleep disturbance, and family history of functional gastrointestinal disorders (FGIDs), currently called disorder of gut-brain interaction. Most patients with PI-IBS present with either diarrhea-predominant IBS or the mixed subtype of IBS, and overlap with other FGIDs, such as functional dyspepsia is common. The drugs used to treat non-constipation IBS may also be useful in PI-IBS treatment. Since randomized controlled trials on the efficacy of drugs to treat PI-IBS are rare, more studies are needed on this issue.

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Tropical sprue (TS) is a post-infective disease of the small bowel characterized by a malabsorption syndrome affecting tropics inhabitants and visitors. Diagnosis of TS remains challenging since it can be confused with common diarrheal diseases, especially in non-endemic areas. We report a Tunisian case of latent TS. A 58-year-old male with a history of chronic watery diarrhea, was admitted to the intensive care unit for confusion which was related to a severe metabolic acidosis. Despite the neurological improvement after hydro-electrolytic resuscitation and acid-base disorders correction, the patient continued to have three to five loose stools daily. A nutritional assessment showed a malabsorption syndrome: iron, Vitamin B12and folate deficiencies; normochromic normocytic anemia and hypoalbuminemia. Gastrointestinal endoscopy showed duodenal villous atrophy and biopsy confirmed subtotal villous atrophy with increased intraepithelial lymphocytosis and a thickened hyalonalized sub-epithelial basal lamina. Celiac disease was evoked, however the patient did not improve on a gluten-free diet and the celiac serology was negative. On re-interviewing, we discovered that the patient had spent two months in India three years prior. Given the travel history, clinico-biological and histological data TS was highly considered and a good response to a five-month antibiotic course combined to nutritional supplementation supported this diagnosis. Clinico-biological, endoscopic and histological findings were overlapping between TS and other malabsorption diseases, explaining diagnosis difficulties. TS should be systematically discussed in tropics visitors presenting with chronic diarrhea. Improvement after micronutrient and vitamin deficiencies replacement combined to a prolonged antibiotic course supports the diagnosis of TS.

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Introduction Megaloblastic anemia is one of the common causes of anemia in India. Duodenal biopsies are routinely performed in the investigation of megaloblastic anemia. The present study was undertaken to analyze the value of duodenal biopsy in megaloblastic anemia and to correlate endoscopic findings with biopsy. As a secondary aim, the study has also analyzed the hematological profile and vitamin B 12 and folate status of these patients. Materials and Methods All the cases of megaloblastic anemia with bone marrow studies diagnosed at PSG Institute of Medical Sciences and Research during the two year period from January 2016 to December 2017 were retrieved. Clinical and laboratory findings (serum vitamin B 12 and folate levels) and endoscopic findings were retrieved from hospital records of the patients. Duodenal biopsies of these patients reported in the histopathology department were retrieved and reviewed. Statistical analysis was done using SPSS software 20.0. Results There were 93 cases of megaloblastic anemia diagnosed on bone marrow biopsies. Tropical sprue was diagnosed in 49.5% of cases, followed by intraepithelial lymphocytosis (17.2%), peptic duodenitis (17.2%), and no significant pathology in 16% of cases. Pancytopenia was present in 54.8% of cases. Isolated vitamin B 12 deficiency including low levels was present in 48.38% and folate deficiency was seen in 4.3% cases; 34.48% cases had both vitamin B 12 and folate deficiency. Conclusion The incidence of tropical sprue in megaloblastic anemia is 49.5% in the study. Duodenal biopsy is valuable in the work up of megaloblastic anemia, irrespective of the endoscopic changes in identifying the etiology.

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PURPOSE OF REVIEW: Review recent developments pertaining to the epidemiology, molecular pathogenesis, and sequelae of enterotoxigenic Escherichia coli (ETEC) infections in addition to discussion of challenges for vaccinology. RECENT FINDINGS: ETEC are a major cause of diarrheal illness in resource poor areas of the world where they contribute to unacceptable morbidity and continued mortality particularly among young children; yet, precise epidemiologic estimates of their contribution to death and chronic disease have been difficult to obtain. Although most pathogenesis studies, and consequently vaccine development have focused intensively on canonical antigens, more recently identified molecules unique to the ETEC pathovar may inform our understanding of ETEC virulence, and the approach to broadly protective vaccines. ETEC undeniably continue to have a substantial impact on global health; however, further studies are needed to clarify the true impact of these infections, particularly in regions where access to care may be limited. Likewise, our present understanding of the relationship of ETEC infection to non-diarrheal sequelae is presently limited, and additional effort will be required to achieve a mechanistic understanding of these diseases and to fulfill Koch's postulates on a molecular level. Precise elucidation of the role played by novel virulence factors, the global burden of acute illness, and the contribution of these pathogens and/or their toxins to non-diarrheal morbidity remain important imperatives.

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Celiac disease features duodenal intraepithelial lymphocytosis with or without villous atrophy. Lymphocytosis without villous atrophy will be proven to represent celiac disease in 10% to 20% of cases. The differential diagnosis is broad: Helicobacter pylori gastritis, NSAID injury and bacterial overgrowth are considerations. Lymphocytosis with villous atrophy is very likely to be celiac disease, but there are mimics to consider, including collagenous sprue, tropical sprue, drug injury, and common variable immunodeficiency. Histologic clues to a diagnosis other than celiac disease include paucity of plasma cells, excess of neutrophils, granulomas, and relative paucity of intraepithelial lymphocytes.

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PURPOSE OF REVIEW: The term 'tropical enteropathy' originated in observations in the 1960s that small intestinal morphology and function differed in the tropics from the norms found in temperate climates. It was subsequently shown that this enteropathy is more closely related to environmental conditions than latitude, and it was re-labelled 'environmental enteropathy'. It is now recognised that environmental enteropathy (also now called environmental enteric dysfunction) has implications for the health and linear growth of children in low- and middle-income countries, and it may underlie poor responses to oral vaccination in these countries. The purpose of this review is to define and clarify this enteropathy despite the confusing terminology it has attracted and to contrast it with other enteropathic states. RECENT FINDINGS: Recent work has begun to demonstrate the nature of the mucosal lesion and the relationship with microbial translocation which is currently thought to link a failure of mucosal barrier function and the cascade of systemic inflammation which inhibits growth. The evidence is still correlative rather than definitive, but derives some additional support from animal models. There are some common features between environmental enteropathy and other enteropathies, but there are important differences also. The mechanism of the link between enteropathy and vaccine failure is not understood, and neither is it clear how the more severe form of enteropathy, which we refer to as malnutrition enteropathy, is driven by nutrient depletion and intestinal infection. Tropical enteropathies form a group of disorders which include environmental and nutritional enteropathies. The long-term health implications of these disorders for health in low-income countries are just being explored, but the scale of their effects is very large, with millions of people affected.

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Gut microbiota is the largest organ of the human body. Although growth of bacteria more than 105 colony forming unit (CFU) per milliliter in culture of upper gut aspirate is used to diagnosis small intestinal bacterial overgrowth (SIBO), 103 CFU or more is being considered to suggest the diagnosis, particularly if colonic type bacteria are present in the upper gut. Although neither very sensitive nor specific, hydrogen breath tests are widely used to diagnose SIBO. Rifaximin is the best treatment for SIBO due to its broad spectrum, lack of systemic absorption, and safety profile.

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Malabsorption syndrome (MAS) is a common condition in India. In Indian adults, tropical sprue and celiac disease are leading causes of MAS. Sometimes, the diagnosis of MAS may pose a challenge due to the varied signs and symptoms. We present a case of MAS in a young female, whose presenting symptoms were mainly neurological. She was successfully treated under regular follow-up for the past 6 years without any symptoms.

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BACKGROUND: Previous studies have linked an increase in functional and pathological gastrointestinal (GI) disorders following antecedent infectious gastroenteritis (IGE), yet studies of other chronic GI disorders such as tropical sprue (TS) and intestinal malabsorption (IM) are lacking. This study was performed to evaluate the association between documented IGE and the risk of TS and IM using a matched case-control study. METHODS: The odds of IGE (exposure) among subjects with TS and IM were compared to the odds of exposure in matched controls. Data were obtained from the Defense Medical Surveillance System. Incidence was estimated based on the number of active duty military personnel, and conditional logistic regression models were used to evaluate the relationship between IGE and TS/IM while adjusting for potential confounders. RESULTS: The overall incidence of TS and IM was 0.24 and 1.98 per 100,000 person-years, respectively. After adjusting for important covariates, prior IGE was associated with an increase in the odds of TS (odds ratio (OR) 36.64) and IM (OR 3.93) (p < 0.001). Other covariates demonstrating an increased risk were being of Caucasian race, having greater than high school education, and service in military branches other than the Army. CONCLUSION: Overall, this study demonstrates the first significant estimates that a case of antecedent IGE is associated with an increased risk of TS and IM in an active duty military population. Ultimately, acquisition of TS or IM has the potential to decrease operational efficiency, which may have a significant impact on deployed military missions.

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Tropical sprue (TS) is a malabsorption syndrome of presumed infectious aetiology that affects residents of (or visitors to) the tropics. The histological changes of TS are similar to those of coeliac disease, with increased intraepithelial lymphocytes being central to both. Unlike in coeliac disease, however, a completely flat small bowel biopsy is uncommon in TS. TS typically involves the terminal ileum, whereas coeliac disease does not. Small intestinal bacterial overgrowth (SIBO) has been defined as an increase in number and/or a change in the type of bacteria in the upper gut. Conditions that predispose to SIBO are largely those that decrease or interfere with small bowel motility. The mucosal histology is variable, and may include modest villous blunting accompanied by increased lamina propria and epithelial inflammation. Autoimmune enteropathy (AE) is a family of rare diseases that share common themes such as immunodeficiency states and autoantibodies. AE cases typically have marked villous atrophy similar to that in fully developed coeliac disease, but they lack the intense surface epithelial lymphocytosis. Apoptosis and lymphocyte infiltration at the base of the crypts, crypt abscesses and cryptitis are also seen. Patients with anti-goblet cell antibodies can have a lack of goblet cells, endocrine cells, and Paneth cells.

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In the late nineteenth and early twentieth centuries, British physicians led the way in tropical medicine research. Several years later scientific advances had slowed, and Fairley's numerous contributions were thus most welcome. Neil Hamilton Fairley was born of Scottish parents at Victoria, Australia. After qualification at Melbourne, he joined the Australian Army Medical Service (AAMS) and after several minor research projects, made valuable contributions to the understanding of tropical sprue at Bombay (now Mumbai), India. However, Fairley's major researches were carried out during World War II (1939-45). Together with J S K Boyd he demonstrated the great value of sulphaguanidine in bacillary dysentery. Working in northern Australia and the south-Pacific region, he both contributed to elucidation of the Plasmodium vivax life-cycle, and more importantly demonstrated the value of alternative anti-malarial compounds to quinine (which was not readily available). Back in London after the war, Fairley briefly occupied the Wellcome Chair of Tropical Medicine, strongly supported London's clinical tropical medicine, and was subsequently knighted in 1950.

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