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Basu S.,Indian National Institute of Cholera and Enteric Diseases
European Journal of Clinical Microbiology and Infectious Diseases | Year: 2014

Colonization of the neonatal gut takes place immediately after birth. Bacteria that get colonized are considered to be “normal” flora derived principally from the mother and the immediate environment. However, for some neonates, the colonization of the gut, particularly with potential pathogens, may lead to subsequent infections or sepsis. The immune system and the gut barrier in neonates is vulnerable, with decreased acid secretion, low levels of protective mucous, and decreased motility, particularly in those who are premature and of low birth weight. This makes the neonatal gut especially prone to colonization with aerobic Gram-negative bacilli (GNB). And these GNB may later, under circumstances favorable to them, cause disease in the neonates. In developing countries, it is the GNB that cause the majority of the infections. In addition, the use of antibiotics in the neonatal intensive care unit also triggers colonization with antibiotic-resistant bacteria. This review discusses various aspects of neonatal gut colonization, neonatal sepsis, and tries to gather support to understand the connection between the gut and subsequent sepsis in neonates. © 2014, Springer-Verlag Berlin Heidelberg.

Safa A.,City University of Hong Kong | Nair G.B.,Indian National Institute of Cholera and Enteric Diseases | Kong R.Y.C.,City University of Hong Kong
Trends in Microbiology | Year: 2010

Vibrio cholerae typically contains a prophage that carries the genes encoding the cholera toxin, which is responsible for the major clinical symptoms of the disease. In recent years, new pathogenic variants of V. cholerae have emerged and spread throughout many Asian and African countries. These variants display a mixture of phenotypic and genotypic traits from the two main biotypes (known as 'classical' and 'El Tor'), suggesting that they are genetic hybrids. Classical and El Tor biotypes have been the most epidemiologically successful cholera strains during the past century, and it is believed that the new variants (which we call here 'atypical El Tor') are likely to develop successfully in a manner similar to these biotypes. Here, we describe recent advances in our understanding of the epidemiology and evolution of the atypical El Tor strains. © 2009 Elsevier Ltd. All rights reserved.

Ghosh A.,Cleveland Clinic | Chawla-Sarkar M.,Indian National Institute of Cholera and Enteric Diseases | Stuehr D.J.,Cleveland Clinic
FASEB Journal | Year: 2011

Maturation of NOS enzymes requires that they incorporate heme to become active, but how this cellular process occurs is unclear. We investigated a role for chaperone heat shock protein 90 (hsp90) in enabling heme insertion into the cytokine-inducible mouse NOS. We used macrophage cell line RAW 264.7 and human embryonic kidney HEK293T cells and studied insertion of native heme during iNOS expression and insertion of exogenous heme into preformed apo-iNOS. Pulldown experiments showed that the hsp90-iNOS complex was present in cells, but the extent of their association was inversely related to iNOS heme content. Hsp90 was primarily associated with apo-iNOS monomer and was associated 11-fold less with heme-containing iNOS monomer or dimer in cells. Kinetic studies showed that hsp90 dissociation occurred coincident with cellular heme insertion into apo-iNOS (0.8 h-1). The hsp90 inhibitor radicicol or coexpression of an ATPase-defective hsp90 blocked heme insertion into apo-iNOS by 90 and 75%, respectively. The ATPase activity of hsp90 was not required for complex formation with iNOS but was essential for heme insertion to occur. We conclude that hsp90 plays a primary role in maturation of iNOS protein by interacting with the apoenzyme in cells and then driving heme insertion in an ATP-dependent manner. © FASEB.

Patil S.R.,Network for Engineering and Economics Research and Management NEERMAN | Patil S.R.,University of California at Berkeley | Arnold B.F.,University of California at Berkeley | Salvatore A.L.,Stanford University | And 4 more authors.
PLoS Medicine | Year: 2015

Background: Poor sanitation is thought to be a major cause of enteric infections among young children. However, there are no previously published randomized trials to measure the health impacts of large-scale sanitation programs. India’s Total Sanitation Campaign (TSC) is one such program that seeks to end the practice of open defecation by changing social norms and behaviors, and providing technical support and financial subsidies. The objective of this study was to measure the effect of the TSC implemented with capacity building support from the World Bank’s Water and Sanitation Program in Madhya Pradesh on availability of individual household latrines (IHLs), defecation behaviors, and child health (diarrhea, highly credible gastrointestinal illness [HCGI], parasitic infections, anemia, growth). Methods and Findings: We conducted a cluster-randomized, controlled trial in 80 rural villages. Field staff collected baseline measures of sanitation conditions, behaviors, and child health (May–July 2009), and revisited households 21 months later (February–April 2011) after the program was delivered. The study enrolled a random sample of 5,209 children ,5 years old from 3,039 households that had at least one child ,24 months at the beginning of the study. A random subsample of 1,150 children ,24 months at enrollment were tested for soil transmitted helminth and protozoan infections in stool. The randomization successfully balanced intervention and control groups, and we estimated differences between groups in an intention to treat analysis. The intervention increased percentage of households in a village with improved sanitation facilities as defined by the WHO/UNICEF Joint Monitoring Programme by an average of 19% (95% CI for difference: 12%–26%; group means: 22% control versus 41% intervention), decreased open defecation among adults by an average of 10% (95% CI for difference: 4%–15%; group means: 73% intervention versus 84% control). However, the intervention did not improve child health measured in terms of multiple health outcomes (diarrhea, HCGI, helminth infections, anemia, growth). Limitations of the study included a relatively short follow-up period following implementation, evidence for contamination in ten of the 40 control villages, and bias possible in self-reported outcomes for diarrhea, HCGI, and open defecation behaviors. Conclusions: The intervention led to modest increases in availability of IHLs and even more modest reductions in open defecation. These improvements were insufficient to improve child health outcomes (diarrhea, HCGI, parasite infection, anemia, growth). The results underscore the difficulty of achieving adequately large improvements in sanitation levels to deliver expected health benefits within large-scale rural sanitation programs. © 2014 World Bank.

Dutta S.,Indian National Institute of Cholera and Enteric Diseases
eLife | Year: 2013

It has long been assumed that resistance to antibiotics reduces the fitness of disease-causing bacteria, but experiments on Salmonella Typhi, the bacteria that causes Typhoid fever, are now challenging this view. © Dellas et al.

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