Academic journal article Journal of Health Population and Nutrition

Differential Host Immune Responses to Epidemic and Endemic Strains of Shigella Dysenteriae Type 1

Academic journal article Journal of Health Population and Nutrition

Differential Host Immune Responses to Epidemic and Endemic Strains of Shigella Dysenteriae Type 1

Article excerpt

INTRODUCTION

Shigellosis is a global public-health problem. According to the recent report of the World Health Organization on the worldwide burden of shigellosis, 90 million cases of diarrhoea due to Shigella occur annually mostly in developing countries, and an estimated 108,000 deaths per year are attributed to Shigella infections (http://www. who.int/vaccine_research/diseases/diarrhoeal/en/ index6.html # vaccine). Currently, no licensed vaccines against Shigella infection exist (1).

Four species of Shigella are responsible for causing bacillary dysentery: Shigella dysenteriae, S. flexneri, S. sonnei, and S. boydii. Of the four species, S. dysenteriae type 1 produces the most severe form of disease with a high mortality rate in young children, elderly people, and the malnourished and can be associated with various complications (1,2). Since the 1960s, S. dysenteriae type 1 is known to be an important cause of epidemic dysentery in Latin America, Africa, and Asia, including Bangladesh (1,3-6). Epidemic shigellosis largely depends on drug resistance (7), variation in Shiga toxin (8), or other unknown causes. Studies on differences between epidemic and circulating endemic strains of Shigella are scarce. In one study, the plasmid profile of Shigella spp. isolated during an outbreak was shown to be different from that of endemic isolates (9). Another study reported that, during sporadic and outbreak incidences of shigellosis, epidemic variants had the most stable plasmids (10). To understand the transmission dynamics of Vibrio cholerae during epidemics, Merrel et al. showed that increased infectivity of V. cholerae was associated with variable expression level of various genes (11). However, till date, no studies on comparison between host immune responses to epidemic and endemic Shigella isolates have been conducted.

Studies to understand the differences in the host immune response to epidemic and endemic Shigella strains may eventually aid in designing alternative treatment strategies during epidemics and vaccine development. Therefore, we aimed to assess the immune responses evoked by epidemic and endemic strains of S. dysenteriae type 1 by studying phagocytic response and oxidative burst of neutrophils and monocytes, serum and LL-37-mediated killing of these strains. The difference in immunogenicity of these strains was also evaluated by Western blot analysis of the whole-cell antigens.

MATERIALS AND METHODS

S. dysenteriae type 1 strains

The epidemic strain T2218 was collected during a dysentery epidemic in Teknaf, a coastal area in Bangladesh, that caused high mortality among children aged less than one year (12). Endemic S. dysenteriae type 1 strains isolated from S. dysentetiae type 1-infected adult patients (n=8) admitted to the Dhaka Hospital of icddr,b enrolled in a previous study (13) were used in the present study. Patients were empirically treated with pivmecillinam.

Table 1 shows the different strains that were used for various immunological assays. Serum and strain from the same source (patient or immunized rabbit) were designated as homologous while serum and strain isolated from different sources (patient or immunized rabbit) were designated as heterologous strain or heterologous serum. The bacterial cultures were stored at -80 °C in Trypticase Soy Broth (TSB) (Difco, Spartus, MD) with 15% glycerol. Before using in immunological assays, isolates were confirmed by biochemical reactions, agglutination with specific antiserum, and Séreny test.

Blood and serum samples

Patients with shigellosis were followed for one month, and blood samples were collected at different intervals after the onset of diarrhoea (3-5, 14- 16, and 30-35 days) (13). For convenience, these follow-up days were referred to as days after admission (day 1, 11, and 30). Blood samples obtained from healthy adults (laboratory staff, n=15, aged 24-30 years) at icddr,b were from Shigella-endemic area and from healthy Swedish adults (n=5, aged 21-56 years) as Shigella non-endemic area (13). …

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