Risk Factors for Death among Children Less than 5 Years Old Hospitalized with Diarrhea in Rural Western Kenya, 2005–2007: A Cohort Study

Background

Diarrhea is a leading cause of childhood morbidity and mortality in sub-Saharan Africa. Data on risk factors for mortality are limited. We conducted hospital-based surveillance to characterize the etiology of diarrhea and identify risk factors for death among children hospitalized with diarrhea in rural western Kenya.

Methods and Findings

We enrolled all children <5 years old, hospitalized with diarrhea (≥3 loose stools in 24 hours) at two district hospitals in Nyanza Province, western Kenya. Clinical and demographic information was collected. Stool specimens were tested for bacterial and viral pathogens. Bivariate and multivariable logistic regression analyses were carried out to identify risk factors for death. From May 23, 2005 to May 22, 2007, 1,146 children <5 years old were enrolled; 107 (9%) children died during hospitalization. Nontyphoidal Salmonella were identified in 10% (118), Campylobacter in 5% (57), and Shigella in 4% (42) of 1,137 stool samples; rotavirus was detected in 19% (196) of 1,021 stool samples. Among stools from children who died, nontyphoidal Salmonella were detected in 22%, Shigella in 11%, rotavirus in 9%, Campylobacter in 5%, and S. Typhi in <1%. In multivariable analysis, infants who died were more likely to have nontyphoidal Salmonella (adjusted odds ratio [aOR] = 6·8; 95% CI 3·1–14·9), and children <5 years to have Shigella (aOR = 5·5; 95% CI 2·2–14·0) identified than children who survived. Children who died were less likely to be infected with rotavirus (OR = 0·4; 95% CI 0·2–0·8). Further risk factors for death included being malnourished (aOR = 4·2; 95% CI 2·1–8·7); having oral thrush on physical exam (aOR = 2·3; 95% CI 1·4–3·8); having previously sought care at a hospital for the illness (aOR = 2·2; 95% CI 1·2–3·8); and being dehydrated as diagnosed at discharge/death (aOR = 2·5; 95% CI 1·5–4·1). A clinical diagnosis of malaria, and malaria parasites seen on blood smear, were not associated with increased risk of death. This study only captured in-hospital childhood deaths, and likely missed a substantial number of additional deaths that occurred at home.

Conclusion

Nontyphoidal Salmonella and Shigella are associated with mortality among rural Kenyan children with diarrhea who access a hospital. Improved prevention and treatment of diarrheal disease is necessary. Enhanced surveillance and simplified laboratory diagnostics in Africa may assist clinicians in appropriately treating potentially fatal diarrheal illness. Please see later in the article for the Editors'' Summary     

Fetuin-A triggers the secretion of a novel set of exosomes in detached tumor cells that mediate their adhesion and spreading

Our goal in this study was to define the mechanisms by which fetuin-A mediates the adhesion of tumor cells. The data show that in the absence of fetuin-A, detached tumor cells secrete exosomes that contain most of the known exosomal associated proteins but lack the capacity to mediate cellular adhesion. In the presence of fetuin-A, the cells secrete exosomes, which contain, in addition to the other exosomal proteins, fetuin-A, plasminogen and histones. These exosomes mediate adhesion and cell spreading. Plasminogen is a participant in this novel adhesion mechanism. The data suggest that these exosomes play a role in tumor progression.     

Haplotype analysis of the mitochondrial DNA d‐loop region reveals the maternal origin and historical dynamics among the indigenous goat populations in east and west of the Democratic Republic of Congo

This study aimed at assessing haplotype diversity and population dynamics of three Congolese indigenous goat populations that included Kasai goat (KG), small goat (SG), and dwarf goat (DG) of the Democratic Republic of Congo (DRC). The 1169 bp d‐loop region of mitochondrial DNA (mtDNA) was sequenced for 339 Congolese indigenous goats. The total length of sequences was used to generate the haplotypes and evaluate their diversities, whereas the hypervariable region (HVI, 453 bp) was analyzed to define the maternal variation and the demographic dynamic. A total of 568 segregating sites that generated 192 haplotypes were observed from the entire d‐loop region (1169 bp d‐loop). Phylogenetic analyses using reference haplotypes from the six globally defined goat mtDNA haplogroups showed that all the three Congolese indigenous goat populations studied clustered into the dominant haplogroup A, as revealed by the neighbor‐joining (NJ) tree and median‐joining (MJ) network. Nine haplotypes were shared between the studied goats and goat populations from Pakistan (1 haplotype), Kenya, Ethiopia and Algeria (1 haplotype), Zimbabwe (1 haplotype), Cameroon (3 haplotypes), and Mozambique (3 haplotypes). The population pairwise analysis (F_ST ) indicated a weak differentiation between the Congolese indigenous goat populations. Negative and significant (p‐value <.05) values for Fu''s Fs (−20.418) and Tajima''s (−2.189) tests showed the expansion in the history of the three Congolese indigenous goat populations. These results suggest a weak differentiation and a single maternal origin for the studied goats. This information will contribute to the improvement of the management strategies and long‐term conservation of indigenous goats in DRC.     

Status and distribution of mangrove forests of the world using earth observation satellite data

Aim Our scientific understanding of the extent and distribution of mangrove forests of the world is inadequate. The available global mangrove databases, compiled using disparate geospatial data sources and national statistics, need to be improved. Here, we mapped the status and distributions of global mangroves using recently available Global Land Survey (GLS) data and the Landsat archive. Methods We interpreted approximately 1000 Landsat scenes using hybrid supervised and unsupervised digital image classification techniques. Each image was normalized for variation in solar angle and earth–sun distance by converting the digital number values to the top‐of‐the‐atmosphere reflectance. Ground truth data and existing maps and databases were used to select training samples and also for iterative labelling. Results were validated using existing GIS data and the published literature to map ‘true mangroves’. Results The total area of mangroves in the year 2000 was 137,760 km² in 118 countries and territories in the tropical and subtropical regions of the world. Approximately 75% of world's mangroves are found in just 15 countries, and only 6.9% are protected under the existing protected areas network (IUCN I‐IV). Our study confirms earlier findings that the biogeographic distribution of mangroves is generally confined to the tropical and subtropical regions and the largest percentage of mangroves is found between 5° N and 5° S latitude. Main conclusions We report that the remaining area of mangrove forest in the world is less than previously thought. Our estimate is 12.3% smaller than the most recent estimate by the Food and Agriculture Organization (FAO) of the United Nations. We present the most comprehensive, globally consistent and highest resolution (30 m) global mangrove database ever created. We developed and used better mapping techniques and data sources and mapped mangroves with better spatial and thematic details than previous studies.     

Detachment of breast tumor cells induces rapid secretion of exosomes which subsequently mediate cellular adhesion and spreading

Exosomes are nano-vesicles secreted by a wide range of mammalian cell types. These vesicles are abundant in serum and other extracellular fluids and contain a large repertoire of proteins, mRNA and microRNA. Exosomes have been implicated in cell to cell communication, the transfer of infectious agents, and neurodegenerative diseases as well as tumor progression. However, the precise mechanisms by which they are internalized and/or secreted remain poorly understood. In order to follow their release and uptake in breast tumor cells in real time, cell-derived exosomes were tagged with green fluorescent protein (GFP)-CD63 while human serum exosomes were rhodamine isothiocynate-labeled. We show that detachment of adherent cells from various substrata induces a rapid and substantial secretion of exosomes, which then concentrate on the cell surfaces and mediate adhesion to various extracellular matrix proteins. We also demonstrate that disruption of lipid rafts with methyl-beta-cyclodextrin (MβCD) inhibits the internalization of exosomes and that annexins are essential for the exosomal uptake mechanisms. Taken together, these data suggest that cellular detachment is accompanied by significant release of exosomes while cellular adhesion and spreading are enhanced by rapid uptake and disposition of exosomes on the cell surface.     

Unusual pheromone receptor neuron responses in heliothine moth antennae derived from inter-species imaginal disc transplantation

Single-cell electrophysiological recordings were obtained from olfactory receptor neurons housed in sensilla trichodea along the adult antennae arising from transplantation of the antennal imaginal discs between larval male Helicoverpa zea and Heliothis virescens. The olfactory receptor neurons from the majority of type C sensilla sampled on transplanted antennae displayed response characteristics consistent with those of the species that donated the antennae. However, some of the sensilla type C sampled in either transplant type contained olfactory receptor neurons that responded in a manner typical of the recipient species or other neurons that have not previously been found in the type C sensilla of either species. The single-cell data help to explain behavioral results showing that some transplant males do fly upwind to both species' pheromone blends, an outcome not expected based on known antennal sensory phenotypes. Our results suggest that host tissue can influence antennal olfactory receptor neuron development, and further that because of a common phylogenetic ancestry the donor tissue has the genetic capability to produce a variety of sensillar and receptor types.     

Members of the cystatin superfamily interact with MMP-9 and protect it from autolytic degradation without affecting its gelatinolytic activities

Matrix metalloproteinases (MMPs), like other proteinases, can undergo autolytic degradation once activated in vivo. Whereas the activities of these enzymes are tightly regulated by tissue inhibitors of matrix metalloproteinases (TIMPs), it is not clear mechanistically how these enzymes are protected from autolysis in their active state. We previously reported that MMPs particularly MMP-9 and MMP-2 interact with the serum glycoprotein fetuin-A [Arch. Biochem. Biophys. (1995) 322, 250], a member of the cystatin superfamily. In the present analyses, we demonstrate that this interaction protects MMP-9 from autolytic degradation without interfering with its enzymatic activity, allowing it to efficiently digest gelatin. Our data demonstrate that MMP-9 binds to members of the cystatin family with K(diss) ranging from 25 to 58 nM for fetuin-A and 1.5-1.9 microM for cystatin C. The ability of fetuin-A to protect MMP-9 from autolysis requires a molar ratio of at least 8:1 (fetuin-A/MMP-9). More interestingly, our data show that the other members of the cystatin also have the ability to protect MMP-9 from autolysis, provided they are in molar excess relative to MMP-9. Taken together, our data suggest that cystatins, particularly fetuin-A, in any cellular compartment including the circulatory system, efficiently protect MMP-9 and possibly other MMPs from autolysis. This mechanism ensures the digestion of the preferred substrate for MMP-9 without sacrificing the enzyme in the process.