Porcine epidemic diarrhea virus (PEDV) is the predominant cause of severe entero-pathogenic diarrhea in swine. The lack of effective therapeutical treatment underlines the importance of research for new antivirals. In this study, we identified Q7R, which actively inhibited PEDV replication with a 50% inhibitory concentration (IC(50)) of 0.014 microg/mL. The 50% cytotoxicity concentration (CC(50)) of Q7R was over 100 microg/mL and the derived therapeutic index was 7142. Several structural analogues of Q7R, quercetin, apigenin, luteolin and catechin, also showed moderate anti-PEDV activity. Antiviral drugs and natural compounds revealed ribavirin, interferon-alpha, coumarin and tannic acid have relative weaker efficacy compared to Q7R. Q7R did not directly interact with or inactivate PEDV particles and affect the initial stage of PEDV infection by interfering of PEDV replication. Also, the effectiveness of Q7R against the other two viruses (TGEV, PRCV) was lower compared to PEDV. Q7R could be considered as a lead compound for development of anti-PEDV drugs to may be used to during the early stage of PEDV replication and the structure-activity data of Q7R may usefully guideline to design other related antiviral agents.

Porcine epidemic diarrhea virus (PEDV) is the predominant cause of severe entero-pathogenic diarrhea in swine. The lack of effective therapeutical treatment underlines the importance of research for new antivirals. In this study, we identified Q7R, which actively inhibited PEDV replication with a 50% inhibitory concentration (IC(50)) of 0.014 microg/mL. The 50% cytotoxicity concentration (CC(50)) of Q7R was over 100 microg/mL and the derived therapeutic index was 7142. Several structural analogues of Q7R, quercetin, apigenin, luteolin and catechin, also showed moderate anti-PEDV activity. Antiviral drugs and natural compounds revealed ribavirin, interferon-alpha, coumarin and tannic acid have relative weaker efficacy compared to Q7R. Q7R did not directly interact with or inactivate PEDV particles and affect the initial stage of PEDV infection by interfering of PEDV replication. Also, the effectiveness of Q7R against the other two viruses (TGEV, PRCV) was lower compared to PEDV. Q7R could be considered as a lead compound for development of anti-PEDV drugs to may be used to during the early stage of PEDV replication and the structure-activity data of Q7R may usefully guideline to design other related antiviral agents.

BACKGROUND:Although it is recognized that diarrhoea commonly complicates enteral nutrition, the causes remain unknown.

AIM:To identify factors associated with diarrhoea in patients receiving enteral nutrition with specific attention to formula composition.

METHODS:Medical histories of in-patients receiving enteral nutrition were identified by ICD-10-AM coding and randomly selected from the year 2003 to 2008. Clinical and demographic data were extracted. Formulas were classified according to osmolality, fibre and FODMAP (fermentable oligo-, di- and mono-saccharides and polyols) content.

RESULTS:Formula FODMAP levels ranged from 10.6 to 36.5 g/day. Of 160 patients receiving enteral nutrition, 61% had diarrhoea. Univariate analysis showed diarrhoea was associated with length of stay>21 days (OR 4.2), enteral nutrition duration>11 days (OR 4.0) and antibiotic use (OR 2.1). After adjusting for influencing variables through a logistic regression model, a greater than five-fold reduction in risk of developing diarrhoea was seen in patients initiated on Isosource 1.5 (P = 0.029; estimated OR 0.18). The only characteristic unique to this formula was its FODMAP content, being 47-71% lower than any other formula.

CONCLUSIONS:Length of stay and enteral nutrition duration independently predicted diarrhoea development, while being initiated on a lower FODMAP formula reduced the likelihood of diarrhoea. As retrospective evaluation does not support a cause-effect relationship, an interventional study investigating FODMAPs in enteral formula is indicated.

OBJECTIVES: To describe breastfeeding practices and investigate the influence of exclusive breastfeeding in early infancy on the risk of infant deaths, especially those attributable to respiratory infections (ARI) and diarrhea. METHODS: A prospective observational study was conducted on a birth cohort of 1677 infants who were born in slum areas of Dhaka in Bangladesh and followed from birth to 12 months of age. After enrollment at birth, the infants were visited 5 more times by 12 months of age. Verbal autopsy, based on a structured questionnaire, was used to assign a cause to the 180 reported deaths. Proportional hazards regression models were used to estimate the effect of breastfeeding practices, introduced as a time-varying variable, after accounting for other variables, including birth weight. Overall neonatal, postneonatal and infant mortality, and mortality attributable to ARI and diarrhea were measured. RESULTS: The proportion of infants who were breastfed exclusively was only 6% at enrollment, increasing to 53% at 1 month and then gradually declining to 5% at 6 months of age. Predominant breastfeeding declined from 66% at enrollment to 4% at 12 months of age. Very few infants were not breastfed, whereas the proportion of partially breastfed infants increased with age. Breastfeeding practices did not differ between low and normal birth weight infants at any age. The overall infant mortality rate was 114 deaths per 1000 live births. Compared with exclusive breastfeeding in the first few months of life, partial or no breastfeeding was associated with a 2.23-fold higher risk of infant deaths resulting from all causes and 2.40- and 3.94-fold higher risk of deaths attributable to ARI and diarrhea, respectively. CONCLUSION: The important role of appropriate breastfeeding practices in the survival of infants is clear from this analysis. The reduction of ARI deaths underscores the broad-based beneficial effect of exclusive breastfeeding in prevention of infectious diseases beyond its role in reducing exposure to contaminated food, which may have contributed to the strong protection against diarrhea deaths.

Eight adult female patients suffering from abdominal pain and chronic diarrhea which was often incapacitating and frequently nocturnal, had dramatic relief on a gluten-free diet and return of symptoms after gluten challenge. Previous nonspecific measures and a milk-free diet were ineffective. Multiple jejunal biopsies showed minor, but significant changes in cellularity which returned to normal on the gluten-free diet. Apart from a slight increase in jejunal cellularity, no immunological abnormalities were found after gluten challenge. Steatorrhea or other biochemical defects, common in celiac disease, were not found. It was concluded that these patients had a gluten-sensitive diarrhea, but had no evidence of celiac disease.

OBJECTIVE:To investigate whether the finding in a previous study that homeopathic medicines decrease the duration of acute diarrhea in children could be replicated in a different study population.

DESIGN:Randomized, double-blind, placebo-controlled trial.

SETTING:Private, charitable health clinic in Kathmandu, Nepal.

SUBJECTS:A consecutive sample of 126 children, 6 months to 5 years of age, who presented during April through June, 1994, with more than three unformed stools in the previous 24 hours.

INTERVENTION:Children received either an individualized homeopathic medicine or placebo, to be taken one dose after each unformed stool for 5 days. Parents recorded daily stools on diary cards, and health workers made home visits daily to monitor children.

OUTCOME MEASURES:Predefined measures were based on the previous study: (1) duration of diarrhea, defined as the time until there were fewer than three unformed stools per day, for two consecutive days, and (2) Average number of stools per day for each group.

RESULTS:Of the 126 children initially enrolled, 116 completed treatment. The mean number of stools per day over the entire 5-day treatment period was 3.2 for the treatment group and 4.5 for the placebo group (P = 0.023). A Kaplan-Meier survival analysis of the duration of diarrhea, which included data from all patient visits, showed an 18.4% greater probability that a child would be free of diarrhea by day 5 under homeopathic treatment (P = 0.036).

CONCLUSIONS:These results are consistent with the finding from the previous study that individualized homeopathic treatment decreases the duration of diarrhea and number of stools in children with acute childhood diarrhea.

BACKGROUND:Previous studies have shown a positive treatment effect of individualized homeopathic treatment for acute childhood diarrhea, but sample sizes were small and results were just at or near the level of statistical significance. Because all three studies followed the same basic study design, the combined data from these three studies were analyzed to obtain greater statistical power.

METHODS:Three double blind clinical trials of diarrhea in 242 children ages 6 months to 5 years were analyzed as 1 group. Children were randomized to receive either an individualized homeopathic medicine or placebo to be taken as a single dose after each unformed stool for 5 days. Parents recorded daily stools on diary cards, and health workers made home visits daily to monitor children. The duration of diarrhea was defined as the time until there were less than 3 unformed stools per day for 2 consecutive days. A metaanalysis of the effect-size difference of the three studies was also conducted.

RESULTS:Combined analysis shows a duration of diarrhea of 3.3 days in the homeopathy group compared with 4.1 in the placebo group (P = 0.008). The metaanalysis shows a consistent effect-size difference of approximately 0.66 day (P = 0.008).

CONCLUSIONS:The results from these studies confirm that individualized homeopathic treatment decreases the duration of acute childhood diarrhea and suggest that larger sample sizes be used in future homeopathic research to ensure adequate statistical power. Homeopathy should be considered for use as an adjunct to oral rehydration for this illness.

The persistent diarrhoea-malnutrition syndrome (PDM) remains a leading cause of morbidity and mortality in hospitals in resource-poor countries. In view of the benefits of elemental or oligomeric feeds in inflammatory bowel diseases, we performed a randomized controlled trial of an exclusive diet of amino acid-based elemental feed (AAF) compared with standard nutritional rehabilitation (based on skimmed milk and then soya) for PDM. Treatment was given for 4 weeks in the malnutrition ward of the University Teaching Hospital, Lusaka, in a single-blind study. Intestinal and systemic infections were treated with routine therapies. The main outcome measures were weight gain, recovery from diarrhoea, and mortality. Two hundred children (106 HIV seropositive, 90 HIV seronegative) were randomized; 155 children completed therapy, 39 died, and six were lost to follow-up. At randomization, they were severely malnourished: median baseline weight-for-age z-score was -4.0 (interquartile range, IQR -4.4, -3.5); 9 per cent were underweight, 23 per cent had marasmus, 47 per cent had kwashiorkor, and 21 per cent had marasmic-kwashiorkor. Weight gain was greater in the AAF group (median gain in weight-for-age z-score was 1.23, IQR 0.89-1.57) compared with the control group (0.87, IQR 0.47-1.25; p=0.002), although calorie intakes were higher in the control group. The increase in haemoglobin concentration was also greater in the AAF group (0.8 g/dl, IQR 0-1.8) than in the control group (0.3, IQR -0.6, -1.6; p=0.04). Diarrhoea frequency and global recovery scores improved equally in both treatment groups and mortality did not differ. A diet of reduced molecular complexity was associated with significantly improved weight gain.

Osteogenesis imperfecta (OI) is a genetic disease, with a connective tissue alteration, consisting in the presence of multiple spontaneous fractures or after minimal traumatism. Its association with other metabolic processes is rarely described. We present the clinical case of a female adult patient of 43 years. From her infancy, she has had multiple fractures, needing several surgical interventions, and she was diagnosed of OI type 2 at adolescence age. Due mainly to difficulties in walking remaining in wheel-chair in the last three years, she was overweight with morbid obesity (BMI = 45.4) and had a type-II DM associated. She suffered from recurrent abdominal pain and chronic diarrhea and was diagnosed of celiac disease (CD) with increased intraepithelial duodenal infiltration, being classified as lymphocytic enteritis, Marsh I type. She was put on a gluten-free diet (GFD), having lost 6 kg of weight after 6 months, with a good control of DM-II and presenting a significant clinical improvement. It is rewarding to search the presence of two coincidental metabolic diseases associated to OI, specially CD, because of the dramatic clinical benefit in the general found after putting on a GFD.

OBJECTIVES:To assess the usefulness of a new class of antibodies, the anti-deamidated gliadin peptides, in the diagnostic approach to children less than 2 years with suspected celiac disease.

PATIENTS AND METHODS:We investigated 40 children (median age: 16.8 months; age range: 4-24 months), with symptoms and signs of chronic enteropathy and high serum levels of conventional anti-gliadin antibodies, but normal values of anti-transglutaminase and anti-endomysial antibodies; all underwent measurement of anti-deamidated gliadin peptides serum levels, upper gastrointestinal endoscopy with biopsies and HLA typing; 40 subjects served as controls.

RESULTS:In 29 patients (group A) serum levels of anti-deamidated gliadin peptides were normal and duodenal histology showed a spectrum of abnormalities ranging from mucosal inflammatory infiltrates to villous damage (in almost all cases compatible with Marsh 1-to-2 lesions). All improved on a cow's and soy milk free diet containing gluten. In 11 patients (group B) there were high serum levels of anti-deamidated gliadin peptides and histology showed features suggestive of celiac disease (Marsh 2-to-3 lesions) in all; furthermore, human leucocyte antigen typing was consistent with a celiac disease genetic pattern in all. Group B patients significantly improved on a gluten free diet containing cow's and soy milk proteins. None of the control group was anti-deamidated gliadin peptides positive.

CONCLUSIONS:In children younger than 2 years with signs of chronic enteropathy and normal values of classical serum markers of celiac disease, the latter can be predicted by high serum levels of anti-deamidated gliadin peptides.

OBJECTIVE:Acute diarrhea is the leading cause of pediatric morbidity and mortality worldwide. Oral rehydration treatment can prevent death from dehydration, but does not reduce the duration of individual episodes. Homeopathic treatment for acute diarrhea is used in many parts of the world. This study was performed to determine whether homeopathy is useful in the treatment of acute childhood diarrhea.

METHODOLOGY:A randomized double-blind clinical trial comparing homeopathic medicine with placebo in the treatment of acute childhood diarrhea was conducted in León, Nicaragua, in July 1991. Eighty-one children aged 6 months to 5 years of age were included in the study. An individualized homeopathic medicine was prescribed for each child and daily follow-up was performed for 5 days. Standard treatment with oral rehydration treatment was also given.

RESULTS:The treatment group had a statistically significant (P<.05) decrease in duration of diarrhea, defined as the number of days until there were less than three unformed stools daily for 2 consecutive days. There was also a significant difference (P<.05) in the number of stools per day between the two groups after 72 hours of treatment.

CONCLUSIONS:The statistically significant decrease in the duration of diarrhea in the treatment group suggests that homeopathic treatment might be useful in acute childhood diarrhea. Further study of this treatment deserves consideration.

BACKGROUND:Previous analyses derived the relative risk (RR) of dying as a result of low weight-for-age and calculated the proportion of child deaths worldwide attributable to underweight.

OBJECTIVES:The objectives were to examine whether the risk of dying because of underweight varies by cause of death and to estimate the fraction of deaths by cause attributable to underweight.

DESIGN:Data were obtained from investigators of 10 cohort studies with both weight-for-age category (<-3 SDs, -3 to<-2 SDs, -2 to<-1 SD, and>-1 SD) and cause of death information. All 10 studies contributed information on weight-for-age and risk of diarrhea, pneumonia, and all-cause mortality; however, only 6 studies contributed information on deaths because of measles, and only 3 studies contributed information on deaths because of malaria or fever. With use of weighted random effects models, we related the log mortality rate by cause and anthropometric status in each study to derive cause-specific RRs of dying because of undernutrition. Prevalences of each weight-for-age category were obtained from analyses of 310 national nutrition surveys. With use of the RR and prevalence information, we then calculated the fraction of deaths by cause attributable to undernutrition.

RESULTS:The RR of mortality because of low weight-for-age was elevated for each cause of death and for all-cause mortality. Overall, 52.5% of all deaths in young children were attributable to undernutrition, varying from 44.8% for deaths because of measles to 60.7% for deaths because of diarrhea.

CONCLUSION:A significant proportion of deaths in young children worldwide is attributable to low weight-for-age, and efforts to reduce malnutrition should be a policy priority.