| 摘要: | 背景
本研究探討帶狀疱疹與水痘，水痘疫苗之間的關連，以及帶狀疱疹與心血管疾病發生危險，肺結核發生危險相關聯之流行病學。
方法
本研究分三部分執行。一.從健保資料庫找出2000 - 2009年診斷帶狀疱疹與水痘病患，以卜瓦松迴歸分析或zero inflated Poisson (ZIP) regression model估計水痘 (或帶狀疱)與帶狀疱疹（或水痘），年度，季節，性別，溫度，日照的相關。二.從健保資料庫找出1998-2008年診斷帶狀疱疹和非帶狀疱疹世代，追蹤至2010年，計算此二世代心律不整和冠心病的發生率，並以Cox比例風險迴歸模型來評估風險比 (HR)及其95 %信賴區間 (CI)。三.從健保資料庫找出2000 - 2005年診斷帶狀疱疹和非帶狀疱疹世代，追蹤至2009年，計算二世代心肺結核的發生率，並以Cox比例風險迴歸模型來評估此風險比（HR）及其95％信賴區間。
結果
一.水痘和帶狀疱疹的相關
在施行水痘疫苗之後，水痘對帶狀疱疹發生的相關比起施行水痘疫苗之前每週增加約1.6 %，溫度的效應約增強18.5 ％，日照的效應約增強16.6 ％，女性較男性易得帶狀疱疹，水痘則無性別差異。帶狀疱疹對於水痘不管是施打疫苗前或疫苗後都是負面的影響，施打疫苗前，水痘的發生與日照有正相關，與溫度有負相關，在施打疫苗後則日照、溫度與水痘的發生無統計學上相關。
二.帶狀疱疹和心血管疾病的發生
帶狀疱疹和非帶狀疱疹世代相比，心律不整發生率高1.17倍 (每千人年13.2比11.3)，風險比為1.16倍 (p < 0.01)。冠心症發生率高1.16倍 (每千人年9.02比7.83)，風險比為1.11倍 (p < 0.01)。追蹤帶狀疱疹發病二年內，心律不整風險比為1.22倍 (95 % CI, 1.02-1.28)，冠心症風險比為1.22倍 (95 % CI, 1.02-1.28)，隨著追蹤時間增加，風險降低。從共病來看，有高血壓的病患，冠心症風險最高，風險比為2.16 ( 95% CI, 2.02 - 2.32)。
三.帶狀疱疹和肺結核的發生
帶狀疱疹世代的肺結核整體發生率為非帶狀疱疹世代的1.34倍 (4.87 vs. 3.64 per 1000 person-years)，以多變量Cox迴歸模型調整後的風險比為1.25 (95% CI, 1.10 - 1.43)。風險隨著年齡增加而增加，以年齡大於70歲和年齡小於50歲相比，風險比為6.47 (95 % CI, 5.27 - 7.99)，且風險男性大於女性，風險比為1.99 ( 95% CI, 1.76 - 2.25)。共病會增加肺結核的風險，在慢性阻塞性肺疾病或酗酒比無共病者增加3倍以上的發生率 (10.6 and 19.4 per 1000 person-years)。
結論
帶狀疱疹在施打水痘疫苗後增加發生的機會，且與季節性相比，溫度及紫外線與帶狀疱疹有較強的相關。水痘疫苗明顯降低水痘發生的機會，也降低水痘與溫度及紫外線的相關。帶狀?疹增加心血管發生的機會，但是效應低於傳統的高血壓，高血脂等危險因子。帶狀疱疹增加肺結核發生的機會，尤其是合併共病 (慢性阻塞性肺疾病，酗酒)的患者。
Background: Population studies on trends of varicella and herpes zoster (HZ) associated with varicella zoster vaccination, climate and cardiovascular complications and tuberculosis are limited.
Methods: This dissertation study consisted three parts of study. First, the Taiwan insurance claims data were used to investigate the chronological changes in incident varicella and HZ associated with varicella zoster vaccination from 2000 to 2009. Poisson regression was used to estimate the occurrence of varicella associated with the occurrence of HZ and vice versa by year, season, sex, temperature, and sunny hours.
Second, a HZ cohort and a non-HZ cohort were established to estimate cardiovascular incidences. The HZ cohort to non-HZ cohort incidence rate ratio and adjusted hazard ratio (HR) of the cardiovascular complications with 95% confidence interval (CI) were estimated.
Third, we used the claims data of Taiwan to identify 9441 patients with newly diagnosed HZ in 2000 - 2005, and a comparison cohort of 37764 persons without HZ, frequency matched by gender, age, and diagnosis year. Incidence rates of pulmonary tuberculosis for the 2 cohorts and the HZ cohort to the non-HZ cohort rate ratios were measured by the end of 2009. We further measured hazard ratio (HR) of pulmonary tuberculosis and 95 % confidence interval (CI) associated with HZ using the Cox proportional hazards regression model.
Results: A. The varicella incidence declined from 7.14 to 0.76 per 1,000 person-years in 2000 - 2009, whereas the HZ incidence increased from 4.04 to 6.24 per 1,000 person-years. Females tended to have a higher risk than men for HZ (p < 0.0001) but not varicella. The monthly mean varicella incidence was the lowest in September (160 cases) and the highest in January (425 cases), while the mean HZ incidence was lower in February (370 cases) and higher in August (470 cases). HZ was negatively associated with the incidence of varicella before and after the varicella zoster vaccination (p < 0.001), increased 1.6 % within one week post-vaccination. The effect of temperature on HZ was attenuated by 18.5 % (p < 0.0001) in association with vaccination. The varicella risk was positively associated with sun exposure hours, but negatively associated with temperature only before vaccination.
B. We identified 19,483 patients with HZ diagnosed in 1998-2008 and 77,932 subjects without HZ. Both cohorts were followed up until the end of 2010 to measure the incidence of arrhythmia and coronary artery disease (CAD). The incidence of arrhythmia was 1.17-fold greater in the HZ cohort than in the non-HZ cohort (13.2 vs. 11.3 per 1,000 person-years), with an adjusted HR of 1.16 (p < 0.01). The CAD incidence in the HZ cohort was 1.16-fold higher than that in the non-HZ cohort (9.02 vs. 7.83 per 1,000 person-years), with an adjusted HR of 1.11 (p < 0.01). During the follow-up years, adjusted HRs were 1.22 (95 % CI, 1.12-1.34) for arrhythmia and 1.14 (95 % CI, 1.02-1.28) for CAD within two years after HZ diagnosis. The risk measured for these disorders declined over time. The HR of CAD was the greatest in those with hypertension (2.16; 95 % CI, 2.02 - 2.32).
C. The overall incidence of pulmonary tuberculosis was 1.34-fold higher in the HZ cohort than in the comparison cohort (4.87 vs. 3.64 per 1000 person-years), with an adjusted HR of 1.25 (95 % CI, 1.10 - 1.43) in the multivariable Cox proportional hazards regression analysis. The adjusted HR increased with age to 6.47 (95 % CI, 5.27 - 7.99) for those aged > 70 years compared with those aged < 50 years. Men compare with women, had an adjusted HR of 1.99 (95 % CI, 1.76 - 2.25). Comorbidity enhanced the pulmonary tuberculosis risk, with the incidence increased for 3-fold or greater for HZ patients with COPD or alcoholism, compared with patients without the comorbidity (10.6 vs. 2.86 or 19.4 vs. 4.80 per 1000 person-years, respectively).
Conclusions: The varicella vaccination is effective in varicella prevention, but the incidence of HZ increases after vaccination. HZ has a stronger association with temperature and UV than with seasonality while the varicella risk associated with temperature and UV is diminished HZ potentially increases cardiovascular presentations, although less strong than traditional risk factors. Patients with HZ are at an elevated risk for pulmonary tuberculosis, particularly in those with comorbidities. |
