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Dhaka, Bangladesh

Leung D.T.,University of Utah | Das S.K.,Center for Nutrition and Food Security | Malek M.A.,Center for Nutrition and Food Security | Faruque A.S.G.,Center for Nutrition and Food Security | And 3 more authors.
American Journal of Tropical Medicine and Hygiene

Respiratory and gastrointestinal infections are the top killers of children worldwide, and their co-occurrence is reported but not well understood. Our aim was to determine the risk factors for concurrent presentation of diarrhea and pneumonia (DP) in a resource-limited setting in Bangladesh. We used data from the Diarrheal Disease Surveillance System of the icddr,b Dhaka Hospital to identify children < 60 months of age with diarrhea and concurrent pneumonia, defined as a history of cough, an abnormal lung examination, and tachypnea. For the years 1996-2007, out of total 14,628 diarrheal patients surveyed, there were 607 (4%) patients who satisfied criteria for pneumonia. Those with DP had a higher mortality rate (4% versus 0.05%, odds ratio [OR] = 86, 95% confidence interval [CI] = 26-286) and a longer hospital stay (mean 84 versus 26 hours, difference 58 hours, 95% CI = 52-64 hours) than those with diarrhea (D) only. In multivariable logistic regression comparing cases (N = 607) with controls matched for month and year of admission at a ratio of 1:3 (N = 1,808), we found that DP was associated with younger age, male gender, severe acute malnutrition (SAM), less maternal education, lower family income, and lack of current breast-feeding history. Copyright © 2015 by The American Society of Tropical Medicine and Hygiene. Source

Seed K.D.,Howard Hughes Medical Institute | Faruque S.M.,International Center for Diarrhoeal Disease Research | Mekalanos J.J.,Harvard University | Calderwood S.B.,Harvard University | And 2 more authors.
PLoS Pathogens

The Vibrio cholerae lipopolysaccharide O1 antigen is a major target of bacteriophages and the human immune system and is of critical importance for vaccine design. We used an O1-specific lytic bacteriophage as a tool to probe the capacity of V. cholerae to alter its O1 antigen and identified a novel mechanism by which this organism can modulate O antigen expression and exhibit intra-strain heterogeneity. We identified two phase variable genes required for O1 antigen biosynthesis, manA and wbeL. manA resides outside of the previously recognized O1 antigen biosynthetic locus, and encodes for a phosphomannose isomerase critical for the initial step in O1 antigen biosynthesis. We determined that manA and wbeL phase variants are attenuated for virulence, providing functional evidence to further support the critical role of the O1 antigen for infectivity. We provide the first report of phase variation modulating O1 antigen expression in V. cholerae, and show that the maintenance of these phase variable loci is an important means by which this facultative pathogen can generate the diverse subpopulations of cells needed for infecting the host intestinal tract and for escaping predation by an O1-specific phage. © 2012 Seed et al. Source

Khan W.A.,Center for Vaccine science | Griffiths J.K.,Tufts University | Bennish M.L.,Mpilonhle

Objective:To determine the clinical manifestations and outcome of shigellosis among children infected with different species of Shigella.Methods:We identified all patients <15 years infected with Shigella admitted to the icddr, b Dhaka hospital during one year. Study staff reviewed admission records and repeated the physical examinations and history of patients daily.Results:Of 792 children with shigellosis 63% were infected with S. flexneri, 20% with S. dysenteriae type 1, 10% with S. boydii, 4% with S. sonnei, and 3% with S. dysenteriae types 2-10. Children infected with S. dysenteriae type 1, when compared to children infected with other species, were significantly (P<0.05) more likely to have severe gastrointestinal manifestations: grossly bloody stools (78% vs. 33%), more stools in the 24 h before admission (median 25 vs. 11), and rectal prolapse (52% vs. 15%) - and extra-intestinal manifestations - leukemoid reaction (22% vs. 2%), hemolytic-uremic syndrome (8% vs. 1%), severe hyponatremia (58% vs. 26%) and neurologic abnormalities (24% vs. 16%). The overall fatality rate was 10% and did not differ significantly by species. In a multiple regression analysis young age, malnutrition, hyponatremia, lesser stool frequency, documented seizure, and unconsciousness were predictive of death.Conclusions:Both severe intestinal disease and extra-intestinal manifestations of shigellosis occur with infection by any of the four species of Shigella, but are most common with S. dysenteriae type 1. Among these inpatient children, the risk of death was high with infection of any of the four Shigella species. © 2013 Khan et al. Source

Fleckenstein J.,University of Washington | Fleckenstein J.,Veterans Affairs Medical Center | Sheikh A.,University of Washington | Qadri F.,Center for Vaccine science
Expert Review of Vaccines

Enterotoxigenic Escherichia coli (ETEC) are the most common bacterial pathogens causing diarrhea in developing countries where they lead to hundreds of thousands of deaths, mostly in children. These organisms are a leading cause of diarrheal illness in travelers to endemic countries. ETEC pathogenesis, and consequently vaccine approaches, have largely focused on plasmid-encoded enterotoxins or fimbrial colonization factors. To date these approaches have not yielded a broadly protective vaccine. However, recent studies suggest that ETEC pathogenesis is more complex than previously appreciated and involves additional plasmid and chromosomally encoded virulence molecules that can be targeted in vaccines. Here, we review recent novel antigen discovery efforts, potential contribution of these proteins to the molecular pathogenesis of ETEC and protective immunity, and the potential implications for development of next generation vaccines for important pathogens. These proteins may help to improve the effectiveness of future vaccines by making them simpler and possibly broadly protective because of their conserved nature. © 2014 Informa UK, Ltd. Source

Ahmad S.M.,Center for Vaccine science | Hossain M.I.,Center for Nutrition and Food Security | Bergman P.,Karolinska University Hospital | Kabir Y.,University of Dhaka | Raqib R.,Center for Vaccine science

Because of limited impact on infant morbidity, mortality, and vitamin A status, the new guideline of the World Health Organization (WHO) does not recommend postpartum vitamin A supplementation (VAS) as a public health intervention in developing countries. However, breast milk contains numerous immune-protective components that are important for infant immune development, and several of these components are regulated by vitamin A. Methods/design: Postpartum women are being enrolled within 3 days (d) of delivery at a maternity clinic located in a slum area of Dhaka city and randomized to one of four postpartum VAS regimens (32/group, total 128). The regimens are as follows: Group 1: 200,000 IU VAS at <3 d and placebo at 6 weeks postpartum; Group 2: placebo at <3 d and 200,000 IU VAS at 6 weeks postpartum; Group 3: 200,000 IU VAS, both at <3 d and 6 weeks postpartum; Group 4: placebo, both at <3 d and 6 weeks postpartum. Breast milk samples at <3 d (before supplementation) and 4 months postpartum will be used to measure vitamin A and bioactive compounds. Infant blood samples at 2 and 4 months of age will be used to measure vitamin A, as well as innate and vaccine-specific immune responses. Dietary, anthropometric, and morbidity data are also being collected. Discussion: This is the first placebo-controlled randomized clinical trial of postnatal vitamin A supplementation to investigate the key bioactive compounds in breast milk, important for infant immunity, in relation to dose and time point of postpartum supplementation and whether such maternal supplementation improves infant immune status during the critical period of early infancy. Trial registration: ClinicalTrials.gov: NCT02043223, 5 December 2013. © Ahmad et al.; licensee BioMed Central. Source

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