Role of Shigella flexneri 2a 34 kDa outer membrane protein in induction of protective immune response.

Emergence of Shigella vaccine is in great need in developing countries. In this paper we have shown that 34 kDa Shigella flexneri 2a outer membrane protein has a role in eliciting immune responses. When injected parentarally this protein gives significant protection against challenge with virulent Shigella flexneri 2a. Macrophages activated with the 34 kDa protein resulted in the dose dependent production of nitric oxide, the highly reactive free radical responsible for killing of invading bacterial pathogen. Also, treatment of murine peritoneal macrophages with the 34 kDa protein showed dose dependent increase in the production of tumor necrosis factor-alpha and interleukin-12. However, there was no dose dependent increase in interleukin-10 production. These data indicated that the 34 kDa outer membrane protein has the ability to modulate the protective immune response against the invading bacterial pathogen, mainly through TH1 mediated pathway. So, the 34 kDa outer mebrane protein can be one of the major components for developing subunit vaccine against shigellosis.

Protective efficacy of oral immunization with heat-killed Shigella flexneri 2a in animal model: study of cross protection, immune response and antigenic recognition.

Oral immunization of rabbits with four doses of 10(11) heat-killed Shigella flexneri 2a showed 100% protection against challenge with virulent S. flexneri 2a. After orally immunizing Guinea pigs with four doses of heat-killed S. flexneri 2a 100% protection could be shown against ocular challenge with the same virulent S. flexneri 2a strain but this conferred no protection against challenge with Shigella dysenteriae type 1. In enzyme-linked immunosorbent assay (ELISA) and immunoblot experiments both whole cell lysate-envelope (WCL-E) fraction and outer membrane proteins (OMPs) were recognized by the antisera. Though protective mechanism in shigellosis is not established with certainty, outer membrane proteins (specially 38, 34, 23 and 20kDa proteins) may be the major antigens in the induction of protective immune responses as indicated by this observation.

Risk factors for development of dehydration in young children with acute watery diarrhoea: a case-control study.

In a case-control study to understand the risk factors for development of life-threatening dehydration, a total of 379 children comprising 243 cases (moderate or severe dehydration) and 136 controls (non or mild dehydration) up to 2 years of age suffering from acute watery diarrhoea were studied. By univariate analysis, the presence of vibrios in stool, withdrawal of breast feeding during diarrhoea, not giving fluids, including oral rehydration solution (ORS), during diarrhoea, frequent purging ( > 8/day), vomiting ( > 2/day) and undernutrition were identified as risk factors. However, by multivariate analysis after controlling for confounders, withdrawal of breast feeding during diarrhoea (odds ratio (OR) = 6.8, p < 0.00001) and not giving ORS during diarrhoea (OR = 2.1, p < 0.006) were identified as significant risk factors. The confounding variables which also contributed significantly to increasing the risk were age ( < or = 12 months; OR = 2.7, p = 0.001), frequent purging ( > 8/day; OR = 4.1, p < 0.00001), vomiting ( > 2/day; OR = 2.4, p = 0.001) and severe undernutrition (%median < or = 60 weight-for-age of Indian Academy of Paediatrics classification; OR = 3.1, p = 0.001). We feel that these findings will be useful for Global and National Diarrhoeal Diseases Control Programmes for formulating intervention strategies for preventing death due to diarrhoeal dehydration.