Suchergebnisse

The influence pre-exposure of mice to Vi capsular polysaccharide, purified from Salmonella enterica Serovar Typhi, on the subsequent immune response induced by a Vi-diphtheria toxoid (Vi-DT) conjugate was evaluated. Vi induced low anti Vi IgG titers with the dominant subclass being IgG3. The Vi-DT conjugate induced high titers of anti Vi IgG with the dominant subclass being IgG1 but with considerable quantities of IgG2a, IgG2b and IgG3. Priming of mice with Vi suppressed the response to a subsequent dose of conjugate and the suppression was overcome by a second dose of conjugate. Priming with conjugate prevented suppression of the anti Vi response and subsequent dosing with Vi raised titers back to previous levels but did not boost to new higher levels. The anti DT IgG response to one dose of conjugate was relatively strong and protracted and continued to rise for 12 weeks, compared to the response to one dose of DT which was poor and peaked at two weeks. The prolonged anti DT response was most likely due to the slow release of DT from the conjugate lattice as it degrades within the mouse resulting in a continuous stimulation of the immune response. The presence of increasing amounts of un-conjugated Vi, up to 50%, administered with the conjugate resulted in increasingly higher levels of both anti Vi and anti DT. Larger amounts of un-conjugated Vi inhibited the anti Vi response. These findings have implications for vaccine quality and a limit for un-conjugated polysaccharide should not exceed 50% and from a vaccine program perspective if the results presented here translate to humans then a Vi conjugate, once it becomes available, should replace Vi polysaccharide vaccines. (C) 2011 Elsevier Ltd. All rights reserved. ; This work was supported by grants from the Bill and Melinda Gates Foundation, UBS Optimus Foundation and from the governments of the Republic of Korea and Sweden (SIDA). ; OAIID:oai:osos.snu.ac.kr:snu2012-01/102/0000002410/4 ; SEQ:4 ; PERF_CD:SNU2012-01 ; EVAL_ITEM_CD:102 ; USER_ID:0000002410 ; ADJUST_YN:Y ; EMP_ID:A002014 ; DEPT_CD:458 ; CITE_RATE:3.766 ; FILENAME:Immune suppression induced by Vi capsular polysaccharide is overcome by.pdf ; DEPT_NM:화학생물공학부 ; EMAIL:thpark@snu.ac.kr ; SCOPUS_YN:Y ; CONFIRM:Y

OBJECTIVE: To estimate incidence of shigellosis in the Kaengkhoi district, Saraburi Province, Thailand. METHODS: Population-based surveillance of shigellosis based in treatment centres. The detected rates of treated shigellosis were corrected for the number of cases missed due to the low sensitivity of microbiological culture methods and participants' use of health-care providers not participating in the study. FINDINGS: The overall uncorrected incidence of shigellosis was 0.6/1000 population per year (95% confidence interval (CI) = 0.5-0.8). The unadjusted incidence of treated shigellosis was highest among children less than 5 years old (4/1000 children per year; 95% CI = 3-6) and significantly lower among people aged > 5 years (0.3/1000 population per year; 95% CI = 0.2-0.5; P < 0.001). Adjusting for cases likely to be missed as a result of culture and surveillance methods increased estimates approximately five times. The majority of Shigella isolates (122/146; 84%) were S. sonnei; the rest were S. flexneri. Of the 22 S. flexneri isolates, the three most frequently encountered serotypes were 2a (36%), 1b (23%) and 3b (28%). A total of 90-95% of S. sonnei and S. flexneri isolates were resistant to tetracycline and co-trimoxazole. In contrast to S. sonnei isolates, more than 90% of the S. flexneri isolates were also resistant to ampicillin and chloramphenicol (P < 0.0001). CONCLUSION: Estimates of incidence of Shigella infection in the community are 10-fold to 100-fold greater than those found from routine government surveillance. The high prevalence of Shigella strains resistant to multiple antibiotics adds urgency to the development of a vaccine to protect against shigellosis in this region of Thailand.

OBJECTIVE: To estimate incidence of shigellosis in the Kaengkhoi district, Saraburi Province, Thailand. METHODS: Population-based surveillance of shigellosis based in treatment centres. The detected rates of treated shigellosis were corrected for the number of cases missed due to the low sensitivity of microbiological culture methods and participants' use of health-care providers not participating in the study. FINDINGS: The overall uncorrected incidence of shigellosis was 0.6/1000 population per year (95% confidence interval (CI) = 0.5-0.8). The unadjusted incidence of treated shigellosis was highest among children less than 5 years old (4/1000 children per year; 95% CI = 3-6) and significantly lower among people aged > 5 years (0.3/1000 population per year; 95% CI = 0.2-0.5; P < 0.001). Adjusting for cases likely to be missed as a result of culture and surveillance methods increased estimates approximately five times. The majority of Shigella isolates (122/146; 84%) were S. sonnei; the rest were S. flexneri. Of the 22 S. flexneri isolates, the three most frequently encountered serotypes were 2a (36%), 1b (23%) and 3b (28%). A total of 90-95% of S. sonnei and S. flexneri isolates were resistant to tetracycline and co-trimoxazole. In contrast to S. sonnei isolates, more than 90% of the S. flexneri isolates were also resistant to ampicillin and chloramphenicol (P < 0.0001). CONCLUSION: Estimates of incidence of Shigella infection in the community are 10-fold to 100-fold greater than those found from routine government surveillance. The high prevalence of Shigella strains resistant to multiple antibiotics adds urgency to the development of a vaccine to protect against shigellosis in this region of Thailand.