Pharmaceutical and immunological evaluation of mucoadhesive nanoparticles based delivery system(s) administered intranasally.

Tri-methyl chitosan synthesis accompanies polymer chain scission, which may affect the carrier and adjuvant properties of the polymer. The main objective of this study was to synthesize the tri-methylated chitosan using mild (TMC-M) and conventional (TMC) method and compare their efficacy as nasal vaccine delivery vehicle. During in vitro studies TMC-M nanoparticles showed the lowest nasal clearance rate when compared with chitosan (CS) and TMC nanoparticles. The immunogenicity of nanoparticles based delivery system(s) was assessed by measuring anti-HBsAg antibody titer in mice serum and secretions after intranasal administration. The alum based HBsAg vaccine injected subcutaneously was used as positive control. Results indicated that alum based HBsAg induced strong humoral but negligible mucosal immunity. However, TMC-M nanoparticles induced stronger immune response at both of the fronts as compared to generated by CS or TMC nanoparticles. Present study demonstrates that TMC-M can be a better carrier adjuvant for nasal subunit vaccines.

Candida colonization and candidemia in a pediatric intensive care unit.

OBJECTIVE: To evaluate role of Candida colonization in development of candidemia and to identify risk factors associated with Candida colonization and candidemia in children treated for severe sepsis or septic shock in a pediatric intensive care unit (PICU) for >5 days. DESIGN: Prospective observational. SETTING: PICU of a tertiary care teaching hospital. SUBJECTS: Of 186 children, aged 1 month to 14 yrs, consecutively admitted to PICU for severe sepsis or septic shock, 65 patients having a stay of >5 days. INTERVENTIONS: Clinical and demographic data at admission and variables likely to influence Candida colonization were recorded. Oropharyngeal, rectal, and skin (groin) swabs were taken on days 0, 2, 5, and 7 of admission. Blood for fungal culture (two samples 48 hrs apart) was obtained if a patient developed signs of sepsis. The yeast growth was identified by conventional methods. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated, and multivariate logistic regression analysis was conducted. MEASUREMENTS AND MAIN RESULTS: Colonization by Candida species occurred in 45 (69%) patients. Oropharyngeal (52%) and rectal (43%) colonization was more common than skin (34%) colonization. The colonizing species were C. tropicalis (34.2%), C. parapsilosis (28.8%), C. albicans (14.4%), and others. Use of central venous catheters was the only independent predictor of colonization on multivariate logistic regression (OR 4.1; 95% CI 1.01-17.1). Twenty (30.2%) patients developed candidemia; 18 (90%) of them were colonized, 15 (75%) with the same Candida species. Independent predictors of candidemia on multivariate stepwise logistic regression analysis were presence of colonization (OR 5.1; 95% CI 1.01-25.6, p = .048) and Pediatric Risk of Mortality score (OR 1.3; 95% CI 1.02-1.6, p = .034). CONCLUSIONS: Monitoring for colonization with Candida species in children undergoing treatment for severe sepsis or sepsis shock in PICU for >5 days may offer opportunity for early intervention for prevention of candidemia.

Enterotoxigenic Escherichia coli causing cholerogenic syndrome during an interepidemic period of cholera in North India.

A study was undertaken to look for heat-labile enterotoxin producing Escherichia coli (LT-ETEC) in patients with acute watery diarrhea resembling cholera in Chandigarh in North India. Two periods were selected, an interepidemic (2001) and an epidemic (2002) period. Heat-labile enterotoxin (LT) was detected using reverse passive latex agglutination test. LT-ETEC strains were serotyped and antimicrobial susceptibility was studied. LT-ETEC was detected in 16 of 21 stool samples during 2001. Other organisms isolated included Vibrio cholerae O1 Ogawa and Aeromonas hydrophila in 2 and 3 patients, respectively. During the epidemic period, 4 of 17 samples tested positive for LT-ETEC, whereas V. cholerae, Shigella, and Salmonella were isolated in 91, 2, and 1 patient, respectively. Similar features such as acute watery diarrhea and dehydration were common to patients examined in the interepidemic period and those examined during the cholera epidemic. The serotypes isolated were O15 (8), O63 (2), O148 (2), and O158 (2), and the remaining strains were untypable. More than 50% of patients were adults. Antimicrobial susceptibility was as follows: amoxycillin (3/20), nalidixic acid (6/20), trimethoprim (5/20), chloramphenicol (8/20), amikacin (19/20), gentamicin (13/20), cefotaxime (15/20), and ciprofloxacin (10/20). High fluoroquinolone resistance in ETEC may be a serious cause of concern for travelers visiting this region, and thus thereis a need to monitor drug resistance in this pathogen.

Mannan antigen detection in the diagnosis of patients with invasive candidiasis.

BACKGROUND & OBJECTIVES: With the increase in the incidence of invasive candidiasis (IC) in recent years, there is a need to improve the sensitivity of diagnosis. A conventional technique like blood culture is positive in nearly 50 per cent of cases. To improve the diagnostic efficiency in invasive candidiasis mannan antigen detection holds promise. Hence mannan antigen detection was evaluated in patients with suspected invasive candidiasis in the Paediatric Intensive Care Unit (PICU). METHODS: A prospective study, involving 186 consecutive patients admitted to the PICU of the Advanced Paediatric Center at the Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh between March 1999 and November 1999 were followed up for possible invasive candidiasis. Sixty five children clinically suspected to have sepsis and at risk for developing IC and or who stayed in the hospital more than 5 days were further evaluated for the diagnosis of IC by collecting two blood culture samples 48 h apart and by mannan antigen and anti-mannan antibody detection. Both antigen and antibody were detected by in-house standardized techniques: antibody by whole cell agglutination (WCA) and antigen by sandwich enzyme linked immunosorbent assay (ELISA). RESULTS: Twenty of 65 patients (30.7%) were positive by blood culture. Mannan antigen was positive in all 20 patients and significant anti-mannan antibody titre (> or = 128) was present in 12 (60%) patients. Mannan antigen was detected in 15 more patients, who were negative for isolation of Candida from blood. Twelve of these patients had febrile episode not responding to antibacterial therapy but responding to fluconazole/itraconazole therapy indicating that the patients possibly had IC. Mannan concentration was also found to be significantly higher in the patients with Candida isolated from blood. INTERPRETATION & CONCLUSION: Thus, the present study confirms the earlier claim that mannan antigen detection possibly improves the diagnostic efficiency of IC.