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Investigation On Risk Factors And Follow-up Study Of SARS Patients

Posted on:2010-05-01Degree:DoctorType:Dissertation
Country:ChinaCandidate:F TangFull Text:PDF
GTID:1114360275462269Subject:Epidemiology and Health Statistics
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Severe acute respiratory syndrome (SARS) is an emerging infectious disease that caused a global epidemic in 2003. The clinical manifestations, laboratory findings, radiologic presentations, and outcomes of SARS for patients have been well described. Much of the epidemiology of the disease is still not fully understood.Healthcare workers (HCW) were at the highest risk of having the disease. Risk factors for infection in HCWs have been studied extensively, and a review on SARS infection and healthcare workers disclosed a number of risk and protective factors, however with conflicting results from different studies. To evaluate possible risk and protective factors associated with infection of SARS among the HCWs by means of a case control study. Fifty-one infected and 426 uninfected staff members were included. All participants were surveyed about risk behaviours and protective measures when attending to SARS patients. Univariate and multivariate logistic regression analyses were performed to identify the major risk and protective factors. Multivariate analysis confirmed the strong role of performing chest compression (adjusted OR 4.52, 95% confidence interval [CI] 1.08-18.81) and contact with patient secretion (adjusted OR 3.27, 95%CI 1.41-7.57). For the studied protective measures, wearing 16-layer cotton surgical mask, wearing 12-layer cotton surgical mask and wearing multiple layers of mask, taking prophylactic medicine, training activity and nose washing remained protective from SARS infection.The recent studies displayed the significant role of the genetic host factors in SARS infection. We conducted a case-control study to investigate the association between interleukin (IL)-12receptorβ1 (IL-12Rβ1) gene genetic polymorphisms and SARS in Chinese individuals. The genotypes of 4SNPs on IL-12Rβ1 gene, +705A/G, +1158T/C, +1196G/C and +1664C/T were determined by PCR-RFLP. Comparison between patients and close contacts showed that individuals with the +1664C/T (CT and TT) genotype had a 2.09-fold (95%CI 1.90–7.16) and 2.34-fold (95%CI 1.79–13.37) increased risk of developing SARS, respectively. For any of the other three polymorphisms, however, no significant difference can be detected in allele or genotype frequencies between patients and controls. Pairwise linkage disequilibrium (LD) analysis of the four SNPs showed strong LD among +705A/G, +1158T/C and +1196G/C SNPs (D, = 0.90–0.98) and modest LD value between +1664C/T and one of the other three SNPs (D, = 0.64–0.81), thus revealing two common haplotypes (A-T-G-C (705-1158-1196-1664) and G-C-C-T). The frequency of GCCT haplotype in SARS patients was significantly increased when compared to the control A group (ORs (95% CI) =2.31 (1.72–8.47).Maintenance of long-term antibody responses is critical for protective immunity against SARS re-infection. However, the duration of humoral immunity has not yet been defined clearly. We performed a longitudinal analysis of antibody titers specific for viral SARS-CoV in 44 subjects for a period of up to 4 years. In addition, possible factors that might influence the dynamic trend of antibodies were assessed. The ELISA results showed positive rates of IgG antibody were 85%, 80%, 63% and 32%, at month 12, 27, 40 and 50, respectively. The geometric mean titers (GMT) of IgG antibody were 1:31, 1:27, 1:13, and 1:6 respectively at four time points after the disease. Survival analysis disclosed a significant association between the antibody duration and steroid use and disease severity, which was further confirmed in survival analysis when using the time of antibody negativation as outcome variable.However, disappearance of anti-SARS antibodies does not necessarily indicate loss of protection. We then evaluated antigen-specific memory T-cell and B-cell response in 6-yr recovered SARS sample by means of ELISPOT. Possible factors that might influence the dynamic trend of antibodies and the memory cells count were assessed. The results showed with all the individuals observed in the present study had no detectable IgG antibody when 6 years after disease. Then by using ELISPOT method, we demonstrated a moderate SARS Ag-specific immunologic memory in the T cell, but not in the B cell in individuals whose anti-SARS antibody had disappeared. These data indicated that humoral immunological response and memory is short-lived after SARS infection. Humal memory T cell responses specific for SARS-CoV S proten could presist for 6 years in the absence of antigen, immunological response might provide long-term protection, however its ability in providing effective protection in case of SARS-CoV reexposure remained unclear.
Keywords/Search Tags:severe acute respiratory syndrome (SARS), risk factors, interleukin -12 receptorβ1, Case-control study, follow-up epidemiological study, antibody duration, anamnestic response
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