The Puerto Rico Journal of Public Health and Tropical Medicine (1925-1949): Coverage of Tropical Sprue.

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.

Acute myocardial infarction in a young adult with hyperhomocysteinaemia secondary to tropical sprue.

Coronary heart disease and its complications remain the most common cause of morbidity and mortality throughout the world. In addition, its incidence among adults <45 years of age has also been steadily increasing in the past few decades. Besides the typical aetiology such as coronary artery abnormalities or autoimmune disorders, increasing rates can be attributed to escalating trends of obesity, type 2 diabetes mellitus, and illicit abuse of drugs such as cocaine and amphetamines in the younger population.1 Every cardiovascular event in a young adult must be thoroughly investigated as the aetiology is typically unconventional. Our case reports a young man who developed an acute inferior wall myocardial infarction (IWMI) in the setting of hyperhomocysteinaemia secondary to vitamin B12-folate deficiency itself due to tropical sprue.

Malabsorption Spectrums in India.

Among the causes of malabsorption, tropical sprue is one of the leading cause.Several reports indicating that celiac disease, now being recognised more frequently. MATERIAL: 94 patients, aged more than 12 years, presenting with Chronic diarrhoea and malabsorption syndrome were analyzed by clinical presentation, endoscopic and histopathological examination.The spectrum of disease in these patients and features differentiating celiac disease and tropical sprue are reported here. OBSERVATION: Most common cause was Celiac Disease (65%), followed by Tropical Sprue (21%), common variable immunodeficiency (2%), lymphangiectasia (1%), idiopathic (3%). Patients with celiac disease were younger,having anemia, scalloping of folds,moderate or severe villous atrophy, crypt hyperplasia, diffuse epithelial damage. Patients with tropical sprue were older and more often normal duodenal epithelium. CONCLUSION: Malabsorption, a disease which is often missed and not recognised by clinicians. A meticulous search for diagnosis is required.

Supplementation With Lactoferrin and Lysozyme Ameliorates Environmental Enteric Dysfunction: A Double-Blind, Randomized, Placebo-Controlled Trial.

INTRODUCTION: Environmental enteric dysfunction (EED) predisposes children throughout the developing world to high rates of systemic exposure to enteric pathogens and stunting. Effective interventions that treat or prevent EED may help children achieve their full physical and cognitive potential. The objective of this study is to test whether 2 components of breast milk would improve a biomarker of EED and linear growth during the second year of life. METHODS: A prospective, randomized, double-blind, placebo-controlled clinical trial among children aged 12-23 months was conducted in rural Malawi. The experimental group received a daily supplement of 1.5 g of lactoferrin and 0.2 g of lysozyme for 16 weeks. The primary outcome was an improvement in EED, as measured by the change in the percentage of ingested lactulose excreted into the urine (Δ%L). RESULTS: Among 214 children who completed the study, there was a significant difference in Δ%L between the control and experimental groups over 8 weeks (an increase of 0.23% vs 0.14%, respectively; P = 0.04). However, this relative improvement was not as strongly sustained over the full 16 weeks of the study (an increase of 0.16% vs 0.11%, respectively; P = 0.17). No difference in linear growth over this short period was observed. The experimental intervention group had significantly lower rates of hospitalization and the development of acute malnutrition during the course of the study (2.5% vs 10.3%, relative risk 0.25; P < 0.02). DISCUSSION: Supplementation with lactoferrin and lysozyme in a population of agrarian children during the second year of life has a beneficial effect on gut health. This intervention also protected against hospitalization and the development of acute malnutrition, a finding with a significant clinical and public health importance. This finding should be pursued in larger studies with longer follow-up and optimized dosing.

Clinical, endoscopic, and histological differentiation between celiac disease and tropical sprue: A systematic review.

BACKGROUND AND AIM: While the prevalence of celiac disease (CD) is increasing globally, the prevalence of tropical sprue (TS) is declining. Still, there are certain regions in the world where both patients with CD and TS exist and differentiation between them is a challenging task. We conducted a systematic review of the literature to find out differentiating clinical, endoscopic, and histological characteristics between CD and TS. METHODS: Medline, PubMed, and EMBASE databases were searched for keywords: celiac disease, coeliac, celiac, tropical sprue, sprue, clinical presentation, endoscopy, and histology. Studies published between August 1960 and January 2018 were reviewed. Out of 1063 articles available, 12 articles were included in the final analysis. RESULTS: Between the patients with CD and TS, there was no difference in the prevalence and duration of chronic diarrhea, abdominal distension, weight loss, extent of abnormal fecal fat content, and density of intestinal inflammation. The following features were more common in CD: short stature, vomiting/dyspepsia, endoscopic scalloping/attenuation of duodenal folds, histological high modified Marsh changes, crescendo type of IELosis, surface epithelial denudation, surface mucosal flattening, thickening of subepithelial basement membrane and celiac seropositivity; while those in TS include anemia, abnormal urinary D-xylose test, endoscopic either normal duodenal folds or mild attenuation, histologically decrescendo type of IELosis, low modified Marsh changes, patchy mucosal changes, and mucosal eosinophilia. CONCLUSIONS: Both patients with CD and TS have overlapping clinical, endoscopic, and histological characteristics, and there is no single diagnostic feature for differentiating CD from TS except for celiac specific serological tests.

Practical Approach to the Flattened Duodenal Biopsy.

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.

Epidemiological and clinical perspectives on irritable bowel syndrome in India, Bangladesh and Malaysia: A review.

Irritable bowel syndrome (IBS) is a chronic gastrointestinal disorder, common in clinic and in the community. It has a significant impact on both society and patients' quality of life. The epidemiology, clinical presentation, and management of IBS may vary in different geographical regions due to differences in diet, gastrointestinal infection, socio-cultural and psycho-social factors, religious and illness beliefs, symptom perception and reporting. Although previous reviews and consensus reports on IBS in Asia have been published, Asia is quite diverse socio-demographically. In this context, India, Bangladesh and Malaysia share some similarities, including: (1) large proportion of the population living in rural areas; (2) rapid development and associated lifestyle changes in urban areas; and (3) dietary, cultural and religious practices. The present review explores the clinical and epidemiological data on IBS from these three major nations in South and South-East Asia. In-depth review of the literature revealed important differences between IBS in the East, as revealed by studies from these three countries, and the West; these include a predominantly rural profile, differences in bowel habit and symptom profile, raising concern with regards to diagnostic criteria and subtyping of IBS, higher dietary fiber consumption, frequent lactose malabsorption, parasitosis, and possible overlap between post-infectious IBS and tropical sprue. Moreover, the current perception on difference in prevalence of the disorder in these countries, as compared to the West, might be related to variation in survey methods.

Lactoferrin and lysozyme to reduce environmental enteric dysfunction and stunting in Malawian children: study protocol for a randomized controlled trial.

BACKGROUND: Chronic childhood malnutrition, as manifested by stunted linear growth, remains a persistent barrier to optimal child growth and societal development. Environmental enteric dysfunction (EED) is a significant underlying factor in the causal pathway to stunting, delayed cognitive development, and ultimately morbidity and mortality. Effective therapies against EED and stunting are lacking and further clinical trials are warranted to effectively identify and operationalize interventions. METHODS/DESIGN: A prospective randomized placebo-controlled parallel-group randomized controlled trial will be conducted to determine if a daily supplement of lactoferrin and lysozyme, two important proteins found in breast milk, can decrease the burden of EED and stunting in rural Malawian children aged 12-23 months old. The intervention and control groups will have a sample size of 86 subjects each. All field and laboratory researchers will be blinded to the assigned intervention group, as will the subjects and their caregivers. The percentage of ingested lactulose excreted in the urine (Δ%L) after 4 h will be used as the biomarker for EED and linear growth as the measure of chronic malnutrition (stunting). The primary outcomes of interest will be change in Δ%L from baseline to 8 weeks and to 16 weeks. Intention-to-treat analyses will be used. DISCUSSION: A rigorous clinical trial design will be used to assess the biologically plausible use of lactoferrin and lysozyme as dietary supplements for children at high risk for EED. If proven effective, these safe proteins may serve to markedly reduce the burden of childhood malnutrition and improve survival. TRIAL REGISTRATION: Clinicaltrials.gov, NCT02925026 . Registered on 4 October 2016.

Post-infectious IBS, tropical sprue and small intestinal bacterial overgrowth: the missing link.

Evidence is emerging that IBS, a hitherto enigmatic disorder thought to be predominantly related to psychological factors, has a microorganic basis in a subset of patients with the disease. Post-infectious IBS (PI-IBS), commonly of the diarrhoea-predominant subtype (defined as new development of IBS following acute infectious diarrhoea), is one such condition known to occur in up to 10-30% individuals after acute gastroenteritis. However, following acute infectious gastroenteritis, patients can also develop post-infectious malabsorption syndrome (PI-MAS), popularly known as tropical sprue. As no study on PI-IBS has rigorously excluded tropical sprue by appropriate investigations, including small intestinal biopsy, the frequency of tropical sprue among patients with PI-IBS is not known. Small intestinal bacterial overgrowth (SIBO) has been suggested to be associated with IBS in general, and in particular diarrhoea-predominant IBS, including PI-IBS. SIBO is also known to be associated with tropical sprue. As both IBS, particularly the subset probably associated with SIBO, and tropical sprue improve with antibiotic treatment, we provide evidence and an explanatory model to support a link among these disorders.

Prevalence and Characteristics of Duodenal Villous Atrophy in Renal Transplant Patients Presenting With Persistent Diarrhea in a Developing Country.

OBJECTIVES: Persistent diarrhea is a common complication after solid-organ transplant, including kidney transplant. Data on duodenal villous atrophy as a cause of persistent diarrhea in renal transplant recipients are scarce. MATERIALS AND METHODS: We conducted a prospective analysis of 207 patients who received renal transplants from 2009 to 2012 with persistent diarrhea and who underwent upper gastrointestinal endoscopy and duodenal biopsies. Duodenal biopsies were examined for duodenal villous atrophy. Age, sex, transplant duration, and drugs were compared between patients with and without duodenal villous atrophy. After exclusion of known causes of duodenal villous atrophy, a 3-month course of antibiotics was given and outcomes were analyzed. RESULTS: Of 207 renal transplant recipients, 104 patients (49.8%) displayed duodenal villous atrophy. Of these, 92 (88.5%) were male patients. The mean age of patients with duodenal villous atrophy was 34.9 ± 10.3 years. The mean onset of persistent diarrhea in DVA-positive patients posttransplant was 2.16 ± 0.8 years. Celiac disease serology was positive in 18 (17.3) patients. Giardiasis was demonstrated in 11 patients (10.7%), whereas immunoproliferative small intestinal disease was shown in 7 patients (6.8%). The remaining 68 patients (65.38%) received antibiotics, with 50 recipients (74.6%) showing complete response, although 13 of these patients (26%) relapsed. Among the remaining 18 patients (26.47%), 9 (50%) had other causes and 9 (50%) had no cause found. Isoniazid prophylaxis showed statistically significant negative association with duodenal villous atrophy. CONCLUSIONS: Duodenal villous atrophy is highly prevalent in renal transplant recipients irrespective of age, sex, and posttransplant duration. We found tropical sprue, giardiasis, immunoproliferative small intestinal disease, and celiac disease to be important causes of duodenal villous atrophy. Therefore, duodenal biopsy is recommended in renal transplant recipients with persistent diarrhea.

Spectrum of chronic small bowel diarrhea with malabsorption in Indian subcontinent: is the trend really changing?

BACKGROUND/AIMS: This study aimed to document the recent etiological spectrum of chronic diarrhea with malabsorption and also to compare features that differentiate tropical sprue from parasitic infections, the two most common etiologies of malabsorption in the tropics. METHODS: We analyzed 203 consecutive patients with malabsorption. The etiological spectrum and factors that differentiated tropical sprue from parasitic infections were analyzed. RESULTS: The most common etiology was tropical sprue (n=98, 48.3%) followed by parasitic infections (n=25, 12.3%) and tuberculosis (n=22, 10.8%). Other causes were immunodeficiency (n=15, 7.3%; 12 with human immunodeficiency virus and 3 with hypogammaglobulinemia), celiac disease (n=11, 5.4%), Crohn's disease (n=11, 5.4%), small intestinal bacterial overgrowth (n=11, 5.4%), hyperthyroidism (n=4, 1.9%), diabetic diarrhea (n=4, 1.9%), systemic lupus erythematosus (n=3, 1.4%), metastatic carcinoid (n=1, 0.5%) and Burkitt's lymphoma (n=1, 0.5%). On multivariate analysis, features that best differentiated tropical sprue from parasitic infections were larger stool volume (P=0.009), severe weight loss (P=0.02), knuckle hyperpigmentation (P=0.008), low serum B12 levels (P=0.05), high mean corpuscular volume (P=0.003), reduced height or scalloping of the duodenal folds on endoscopy (P=0.003) and villous atrophy on histology (P=0.04). Presence of upper gastrointestinal (GI) symptoms like bloating, nausea and vomiting predicted parasitic infections (P=0.01). CONCLUSIONS: Tropical sprue and parasitic infections still dominate the spectrum of malabsorption in India. Severe symptoms and florid malabsorption indicate tropical sprue while the presence of upper GI symptoms indicates parasitic infections.

Infectious Gastroenteritis as a Risk Factor for Tropical Sprue and Malabsorption: A Case-Control Study.

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.

Chronic infections of the small intestine.

PURPOSE OF REVIEW: Chronic infections of the small intestine cause significant morbidity and mortality globally. This review focuses on the recent advances in the field of our understanding of selected intestinal infections. RECENT FINDINGS: Primary and secondary immunodeficiency increase the susceptibility to many chronic intestinal infections. Endoscopy and intestinal biopsies are central to establishing a diagnosis of these conditions. Tuberculosis (TB) remains a major global health challenge. Emerging therapeutic agents to counteract multidrug-resistant strains have shown clinical efficacy, but concerns regarding mortality remain. PCR-based diagnostic TB tests have the potential to reduce diagnostic delays, but remain to be validated for intestinal infections. Adjunctive diagnostic imaging modalities can differentiate infections from Crohn's disease with increasing accuracy. Whipple's disease remains rare, but there have been substantial advances in our understanding of the causative organism Tropheryma whipplei. Extended treatment with broad-spectrum antibiotics is effective in most cases. The narrow therapeutic window and limited armamentarium for treating invasive filamentous fungal infections contribute to their significant morbidity and high rates of mortality. SUMMARY: The speed and accuracy of diagnosing chronic intestinal infections have improved with recent imaging and laboratory methodologies. Significant research opportunities remain for clinicians and scientists to improve the diagnostic accuracy and clinical outcomes of chronic intestinal infections.

The biopsy pathology of non-coeliac enteropathy.

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.