(1.25%), were also detected during this study period. Twenty two percent of specimens showed mixed infections, 38 (24%) of the total samples remained untypeable for either VP7 or VP4, while only 4 (2.5%) of the samples were untypeable for both genes. Eleven specimens collected from Manipur were also genotyped and revealed a very high degree of genomic reassortment.Group A rotaviruses are the major cause of severe dehydrating gastroenteritis among human infants and young of a wide variety of mammalian and avian species (17), and it has been estimated that nearly a million deaths occur every year (9, 20), predominantly in developing countries.Fifteen G serotypes of rotaviruses (27) are recognized, depend on the molecular characterization of VP7 (glycosylated outer capsid protein). However, G1 to G4 are the most predominant genotypes in humans. Moreover, a number of unusual genotypes, G5, G8, and G9, have also been reported recently from various countries (8). Thirteen P serotypes (22) and 21 P genotypes are recognized on the basis of VP4 (protease-sensitive outer capsid protein), but the most common P serotypes infecting humans are P1A and P1B, corresponding to the P[8] and P[4] genotypes, respectively. Although the role of VP4 protein in protective immunity is not very well established, information on G and P typing is important for identifying unusual or new virus strains circulating in different populations (19).The first human rotavirus vaccine (a human-animal tetravalent vaccine) was licensed in the United States in 1998; however, the same vaccine has not been tried extensively in other countries. Due to strain diversity in different parts of the world, knowledge of molecular epidemiology and antigenic diversity of rotaviruses in circulation is imperative for the development of a suitable, efficacious vaccine to combat rotaviral diarrhea. Therefore, in this study we report the characterization of different G and P types of rotavirus strains circulating in a particular area of India.
A double-blind, randomized, controlled clinical trial was conducted on 80 malnourished children with acute dehydrating diarrhoea to evaluate the efficacy of oral supplementation of zinc as an adjunct therapy to oral rehydration solution (ORS). After decoding it was observed that 44 children received zinc sulphate (177 mg/kg/day in three divided doses equivalent to 40 mg elemental zinc) in a syrup form and 36 children received only syrup placebo. Clinical parameters and microbiological findings of stool samples were comparable in the two groups at the time of enrollment. All the children (100 per cent) in the zinc supplemented group and 32 (89 per cent) children in the placebo group recovered within 5 days of hospitalization (p = 0.04). The zinc supplemented group had a significantly shorter duration of diarrhoea (70.4 +/- 10.0 vs. 103.4 +/- 17.1 h; p = 0.0001), passed less liquid stool (1.5 +/- 0.7 vs. 2.4 +/- 0.7kg; p=0.0001), consumed less oral rehydration solution (2.5 +/- 1.0 vs. 3.6 +/- 0.8 litre; p = 0.0001) and other liquids (867.0 +/- 466.1 vs. 1354.7 +/- 675.6 ml; p = 0.0001) as compared to the placebo group. Our findings suggest that zinc supplementation as an adjunct therapy to ORS has beneficial effects on the clinical course of dehydrating acute diarrhoea.
Aims-To compare the clinical eYcacy of hypo-osmolar oral rehydration salt (ORS) solution (224 mmol/l) and standard ORS solution (311 mmol/l) in severely malnourished (marasmic) children having less than 60% Harvard standard weight for age with dehydrating acute watery diarrhoea. Methods-In a double blind, randomised, controlled trial, 64 children aged 6-48 months were randomly assigned standard (n = 32) or hypo-osmolar ORS (n = 32). Results-Stool output (52.3 v 96.6 g/kg/ day), duration of diarrhoea (41.5 v 66.4 hours), intake of ORS (111.5 v 168.9 ml/kg/ day), and fluid intake (214.6 v 278.3 ml/kg/ day) were significantly less in the hypoosmolar group than in the standard ORS group. Percentage of weight gain on recovery in the hypo-osmolar group was also significantly less (4.3 v 5.4% of admission weight) than in the standard ORS group. A total of 29 (91%) children in the standard ORS group and 32 (100%) children in the hypo-osmolar group recovered within five days of initiation of therapy. Mean serum sodium and potassium concentrations on recovery were within the normal range in both groups. Conclusion-Our findings suggest that hypo-osmolar ORS has beneficial eVects on the clinical course of dehydrating acute watery diarrhoea in severely malnourished (marasmic) children. Furthermore, children did not become hyponatraemic after receiving hypo-osmolar ORS. (Arch Dis Child 2001;84:237-240)
Antimicrobial peptides (AMPs) are integral components of the host innate immune system and functional throughout the plant and animal kingdoms. AMPs are short cationic molecules and lethal against a wide range of bacteria, viruses, fungi, yeast and protozoa due to their membranolytic effects on the negatively-charged microbial membranes. In addition, they exert multiple immunomodulatory roles like chemotaxis, modulation of cytokine and chemokine expression, leukocyte activation etc. Since AMPs suffer loss of microbicidal properties under serum and tissue environments, their capacity to modulate the immune system may predominates under the physiological conditions. Discovery of new antibiotics is lagging far behind the rapidly spreading drug resistance among the microorganisms. Both natural and synthetic AMPs have shown promise as 'next generation antibiotics' due to their unique mode of action, which minimises the chance of development of microbial resistance. In addition, they have therapeutic potential against non-infectious diseases like chronic inflammation and cancer. Many of the synthetic AMPs are currently undergoing clinical trials for the treatment of debilitating diseases, such as catheter-related infections, diabetic foot ulcers, chemotherapy-associated infections etc. Some of them have already entered the market as topical preparations. In this review, we synopsise the current literature of natural and synthetic AMPs in different infectious and inflammatory diseases of human microfloral habitats, especially the gastrointestinal, respiratory and genitourinary tracts and the skin. We also discuss the classification of AMPs, their mode action and antimicrobial spectrum, including the pathogen evasion mechanisms. In short, we tried to present the locus standi of AMPs in relation to human diseases and highlight the most promising synthetic peptides emerging from the clinical trials. Finally, we focused on the limitations and hurdles in terms of cost of production, bioavailability, pharmacokinetic stability and toxicity faced by commercial development and clinical use of the AMPs and strategies to overcome these hurdles.
One hundred and sixty-six shigellae strains, isolated from stool samples of paediatric patients (< 5 years old) at a Childrens' Hospital in Kolkata, India during the period of 1995-2000 were examined for serotyping, drug resistance pattern and plasmid profiles. Sh. flexneri (58 %) was found to be commonest isolate of total shigellae, followed by Sh. sonnei (28 %), Sh. boydii (9%) and Sh. dysenteriae (5%). This profile of species was in sharp contrast to the picture obtained before 1995, when Sh. dysenteriae 1 predominated over Sh. flexneri. In Sh. flexneri strains, Sh. flexneri 2a (35%) was the most prevalent serotype, following Sh. flexneri 3a (31%), Sh. flexneri 6 (14%), Sh. flexneri 2b (11%) and Sh. flexneri 4 (9%). Resistance patterns of the strains to 12 commonly used antimicrobial agents and minimum inhibitory concentrations (MICs) of the antibiotics were also tested. All strains were found uniformly susceptible to norfloxacin, but more than 90% strains were resistant to tetracycline, co-trimoxazole and 67% strains were resistant to ampicillin. Resistance to amoxicillin, chloramphenicol and nalidixic acid was found in 55% (range 45-74%), 46% (range 40-60%) and 29% (range 15-40%) strains respectively. Overall, shigellae strains showed statistically significant increase in resistance against tetracycline, nalidixic acid and furazolidone (P < 0.05) over the years of this study. This indicates decreased efficacy of furazolidone, cotrimoxazole and nalidixic acid for the empirical treatment of shigellosis in Kolkata. Although a few strains showed intermediate susceptibility to ciprofloxacin (4%) and cefotaxime (10%) by disk diffusion test, but the MICs of those antibiotics were within the normal limits. Almost 57% of the strains were resistant to four or more drugs with high MICs of the antibiotics. Plasmid profile analysis revealed presence of large plasmid of 220 kb in majority of the strains except in Sh. sonnei and a correlation between presence of smaller plasmids and shigellae serotypes. Hence this study reports epidemiological change of shigellae species in Kolkata, India with regard to serotypes and antibiotic resistance patterns.
Enteric fever, caused by Salmonella enterica, remains an unresolved public health problem in India and antimicrobial therapy is the main mode of treatment. The objective of this study was to characterize the Salmonella enterica isolates from Kolkata with respect to their antimicrobial resistance (AMR), virulence profiles and molecular subtypes. Salmonella enterica blood isolates were collected from clinically suspected enteric fever patients attending various hospitals in Kolkata, India from January 2009 to June 2013 and were tested for AMR profiles by standard protocols; for resistance gene transfer by conjugation; for resistance and virulence genes profiles by PCR; and for molecular subtypes by Pulsed Field Gel Electrophoresis (PFGE). A total of 77 Salmonella enterica serovar Typhi (S. Typhi) and 25 Salmonella enterica serovar Paratyphi A (S. Paratyphi A) from Kolkata were included in this study. Although multidrug resistance (resistance to chloramphenicol, ampicillin, co-trimoxazole) was decreasing in S. Typhi (18.2%) and absent in S. Paratyphi A, increased resistance to fluoroquinolone, the current drug of choice, caused growing concern for typhoid treatment. A single, non-conjugative non-IncHI1 plasmid of 180 kb was found in 71.4% multidrug resistant (MDR) S. Typhi; the remaining 28.6% isolates were without plasmid. Various AMR markers (bla TEM-1, catA, sul1, sul2, dfrA15, strA-strB) and class 1 integron with dfrA7 gene were detected in MDR S. Typhi by PCR and sequencing. Most of the study isolates were likely to be virulent due to the presence of virulence markers. Major diversity was not noticed among S. Typhi and S. Paratyphi A from Kolkata by PFGE. The observed association between AMR profiles and S. Typhi pulsotypes might be useful in controlling the spread of the organism by appropriate intervention. The study reiterated the importance of continuous monitoring of AMR and molecular subtypes of Salmonella isolates from endemic regions for better understanding of the disease epidemiology.
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