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BACKGROUND: Acute respiratory infection (ARI), diarrheal disease (DD) and infective dermatitis (ID) are important causes of morbidity in children under five, in Northeast Brazil. Objectives: (a) to evaluate the morbidity of ARI, DD and ID; and (b) to determine their association with cellular immunity in poor urban children from Fortaleza, Brazil. MATERIALS AND METHODS: A prospective cohort study. At enrollment, multipuncture skin-tests (Multitest CMI) were performed and interpreted according to standard procedures. Children were followed for infectious diseases by weekly home visits. RESULTS: Seventy-one children aged 6 to 21 months were recruited in an ongoing cohort of newborns. A mean of 39 (6 to 63) home visits per child were made, which detected 184.5 symptomatic days per child-year of observation. ARI was present in 62% of the days of illness (6,378 out of 10,221), DD in 23% (2,296 days), ID in 6% (597) and other infections in 4% (373). Episodes per child-year were: 10 for ARI, 7 for DD and 1 for ID. Twelve (17%) out of 71 children were anergic. The incidences of ARI, DD and ID were similar in responsive versus anergic children. The mean duration of ID in anergy was 8.5 days, while it was 4.3 in the responsive group (P=0.007). Anergy was independent of age, sex and nutritional status. CONCLUSIONS: A high incidence of ARI and DD was found in these poor urban children. Skin-test responsiveness was not related to malnutrition, nor to morbidity due to ARI and DD, however anergic children had a longer duration of infective dermatitis.

Increased precipitation and temperature variability as well as extreme events related to climate change are predicted to affect the availability and quality of water globally. Already heavily burdened with diarrheal diseases due to poor access to water, sanitation and hygiene facilities, communities throughout the developing world lack the adaptive capacity to sufficiently respond to the additional adversity caused by climate change. Studies suggest that diarrhea rates are positively correlated with increased temperature, and show a complex relationship with precipitation. Although climate change will likely increase rates of diarrheal diseases on average, there is a poor mechanistic understanding of the underlying disease transmission processes and substantial uncertainty surrounding current estimates. This makes it difficult to recommend appropriate adaptation strategies. We review the relevant climate-related mechanisms behind transmission of diarrheal disease pathogens and argue that systems-based mechanistic approaches incorporating human, engineered and environmental components are urgently needed. We then review successful systems-based approaches used in other environmental health fields and detail one modeling framework to predict climate change impacts on diarrheal diseases and design adaptation strategies., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Clostridium difficile is a pathogen of rapidly increasing public health importance. An estimated quarter of a million Clostridium difficile infections (CDI) occur in the United States annually, at a resultant cost of 14,000 deaths and 1 billion dollars. Clostridium difficile related deaths have risen 400% over the last decade, and current standard antibiotic treatments are only 75 to 85% successful. Besides increasing the risk of antibiotic resistance and side effects, these treatments are very expensive. The most vulnerable population for Clostridium difficile is older adults, who make up approximately half of the cases, but account for 90% of the related deaths. Probiotics may have potential as adjunctive therapeutic agents for CDIs, however, current data is limited., Methods: This pilot study is a single-site, randomized, placebo-controlled, double-blind, phase two clinical trial. The trial primarily evaluates the effect of four weeks of probiotic therapy in addition to standard of care on Clostridium difficile diarrhea duration and recurrence. Secondary outcomes include effect on fecal cytokines, fecal lactoferrin, and Clostridium difficile toxin density in stool, as well as patient functional status., Discussion: This pilot study will determine the feasibility and effect size to conduct larger randomized controlled trials of probiotic interventions in patients with CDI, to determine the impact of probiotics on the symptoms of CDI. ClinicalTrials.gov Identifier: NCT01680874., (Published by Elsevier Inc.)

Introduction: Long-term care facilities (LTCF) residents have been estimated to have the highest incidence of diarrheal illness among adults living in the developed world. This study describes undiagnosed diarrhea, intestinal inflammation, and Clostridium difficile colonization in a LTC population and explores whether these are associated with functional decline, as defined by weight loss or a change in cognitive or ADL status., Methods: An observational study of a convenience sampling of residents in a 180-bed LTCF was obtained; evaluation of stool and medical records was done. Stool specimens were evaluated for consistency, gross blood, inflammation (via quantitative fecal lactoferrin, IBD-SCAN), and C difficile (via PCR for gdh). SPSS and STATA were used and significance was set at P < .05., Results: There were 46 stools collected; 13 of the subjects were male, 28 were older than 65 years, and 35 were prescribed 5 to 15 medications. Twenty-six of the 46 stools collected had elevated quantitative fecal lactoferrin levels. Although only 5 subjects were reported to have diarrhea (4 with elevated lactoferrin), 28 stool specimens were observed to be liquid or semi-solid (19 with elevated lactoferrin), and these liquid/ semisolid stools were significantly correlated with lactoferrin positivity (P = .017). In analysis of functional status, there was no statistically significant association between change in ADL (n = 17) or cognitive status (n = 5) and elevated lactoferrin. However, all 3 subjects who had significant weight loss had elevated lactoferrin, although the mean fecal lactoferrin was not statistically different from those without weight loss. Of the 2 samples with C difficile, both were liquid and, when compared with all other liquid stools (n = 22), the mean lactoferrin was statistically higher (134.1 versus 28.8 microg/mL, P = .008). These 2 subjects had neither weight loss nor change in cognitive status, but 1 had a change in ADL status., Discussion and Conclusions: Diarrhea in LTCF residents is underdiagnosed. Diarrhea and the presence of C difficile in the stool are associated with intestinal inflammation, as detected by fecal lactoferrin. With our small numbers, we were not able to identify a specific link; however, we were able to identify a correlation between weight loss and intestinal inflammation, but, with just 2 samples, not C difficile colonization. This relationship highlights the importance of larger studies to further examine the rate of diarrhea in LTCF; the effect of diarrhea and intestinal inflammation on weight loss; and the interaction of C difficile colonization with weight loss, malnutrition, and functional decline., (Copyright (c) 2010 American Medical Directors Association. Published by Elsevier Inc. All rights reserved.)

Objective: This study was undertaken to determine the relationship among cervical lactoferrin concentration, other cervical markers potentially related to infection, and spontaneous preterm birth., Study Design: Cervical lactoferrin concentrations obtained at 22 to 24 weeks' gestation among 121 women who had a spontaneous preterm birth <35 weeks' gestation were compared with cervical lactoferrin concentrations among 121 women matched for race, parity, and center who were delivered at >/=37 weeks' gestation. Results were compared against levels of cervical interleukin 6, fetal fibronectin, and sialidase, against cervical length according to ultrasonography, and according to the bacterial vaginosis Gram stain score., Results: Cervical lactoferrin concentrations ranged from not measurable (19% of the concentrations were below the threshold for this assay) to a titer of >/=1:64. There was no significant difference in the overall distributions of lactoferrin concentrations between the case patients and control subjects (P =.18). Only when the highest titers of lactoferrin were considered were there more women in the spontaneous preterm birth group (6/121 vs 0/121; P =.03). According to Spearman correlation analyses the cervical lactoferrin concentrations were strongly related to interleukin 6 concentration (r =.51; P =.0001), sialidase activity (r =.38; P =.0001), and bacterial vaginosis (r =.38; P =.0001), were weakly related to fetal fibronectin (r =. 16; P =.01), and were not related to cervical length. With the 90th percentile (a dilution of 1:32) used as a cutoff to establish a dichotomous variable, lactoferrin concentration had the following odds ratios and 95% confidence intervals for associations with other potential markers of infection: bacterial vaginosis odds ratio, 4.8 (95% confidence interval, 2.2-10.3); interleukin 6 concentration odds ratio, 2.8 (95% confidence interval, 1.2-6.5); sialidase activity odds ratio, 5. 5 (95% confidence interval, 2.2-13.7); fetal fibronectin concentration odds ratio, 0.6 (95% confidence interval, 0.2-2.0); chlamydiosis odds ratio, 2.3 (95% confidence interval, 0.8-6.9); and short cervix odds ratio, 0.5 (95% confidence interval, 0.2-1.4)., Conclusions: Lactoferrin found in the cervix correlated well with other markers of lower genital tract infection. High lactoferrin levels were associated with spontaneous preterm birth but had a very low predictive sensitivity.

Background: Endemic diarrhea and its associated malnutrition remain leading causes of childhood morbidity and mortality in developing countries. This study was undertaken to describe changes in the incidence of diarrhea and prevalence of malnutrition among children in an urban Brazilian shantytown from 1989 to 1996. A secondary purpose was to examine associations between malnutrition and increased incidence and duration of diarrhea., Methods: From August 1989 through December 1996 a dynamic birth cohort of 315 children was followed for surveillance of diarrhea and nutrition. Study homes were visited twice or thrice weekly to assess the occurrence of diarrhea. Length and weight of the subjects were measured quarterly. Poisson regression was used to test for associations between prior nutritional status and subsequent diarrhea during a quarter. Multiple regression was used to test for an association between nutritional status and episode duration., Results: Declines in both age-adjusted attack rates (6.0 episodes/child-year in study year 3 [1991] to 2.5 episodes per child-year in study year 8 [1996] and days of diarrhea per child-year (30.8 days/child-year in year 3 to 8.5 days/child-year in year 8) were correlated with yearly improvements in mean nutritional status (R2= 0.84, P < 0.05, for mean length-for-age with mean number of episodes/child-year [corrected]. Both length- and weight-for-age were significant predictors of diarrhea incidence, including persistent episodes (> or =14 d), but not duration., Conclusions: These results demonstrate marked changes over time in the diarrhea burden and nutritional status of children in this population and provide further evidence of a significant association between malnutrition and increased incidence of diarrhea.

Clinically, the ratio of lactulose/mannitol excretion in urine after administration of these non-metabolized sugars has been used to evaluate the extent of malabsorption and intestinal permeability disruption in several infections and nutritional diseases, including human immunodeficiency virus (HIV) infection. A range of methodologies have been reported to determine the lactulose/mannitol ratio, including enzymatic assay, gas-liquid chromatography (GC), thin-layer chromatography (TLC) and high-performance liquid chromatography (HPLC). Most published methods involve tedious sample preparations, rendering them unsuitable for routine or automated clinical laboratory testing. We describe in this paper a method in which weak anion-exchange high-performance liquid chromatography in conjunction with a pulsed amperometric detector was used. It requires very simple sample preparation and avoids interference by other components present in the urine. The linear range of determination for mannitol, lactulose and glucose are up to 10 nmol, in a single injection. The limits of detection are 8, 12, 47 and 52 pmol, respectively, for mannitol, glucose, lactose and lactulose. The separation and quantification using this method are highly reproducible, yielding standard errors of less than 2.5% for retention times and less than 3.5% for quantitation. The ratios of lactulose/mannitol recovery in controls and in HIV-infected subjects with and without diarrhea showed striking differences, which are in close agreement with the published results derived with similar HPLC methods.