2015-2017台灣急性A型肝炎爆發流行期間A型肝炎疫苗接種在男男間性行為者之效果

Abstract

背景：自2015年起，急性A型肝炎於男男間性行為者之間再度爆發流行 。而台灣此次發生之大規模急性A型肝炎疫情，主要影響者為愛滋病毒感染之男男間性行為者。本研究旨在於台灣急性A型肝炎爆發流行期間，探討A型肝炎疫苗應用在群體層面上之效果。方法：因應急性A型肝炎爆發流行，台灣發起至少施打一劑A型肝炎疫苗的接種措施。我們先進行一項1:4的巢式病例對照研究以估算A型肝炎疫苗於愛滋病毒感染之男男間性行為者個人層面上之效果。再藉此進行一項針對男男間性行為者A型肝炎傳播之數理模型研究，根據其是否愛滋病毒感染分層，並將模型與台灣2015年6月至2017年12月間的疫情資料做校正，以評估A型肝炎疫苗接種措施於男男間性行為者群體層面上之效果。結果：於前瞻研究期間內，共收案1470位初始A肝抗體陰性之愛滋病毒感染者，其中共有55位為罹患急性A型肝炎之病例，其成功配對於220位未罹患急性A型肝炎之病例。於愛滋病毒感染之男男間性行為者，施打一劑及兩劑A型肝炎疫苗之個人層面預防效果分別為96.1%及97.8%。在數理模型與疫情資料做校正後，我們估算傳播係數為2.47 month-1，因此相對應的基礎再生數(R0)在愛滋病毒感染者及未感染者分別為8.2與4.1。當假設數理模型未進行A型肝炎疫苗的接種措施時，則疫情會在第21個月達到高峰，並共有7410位急性A型肝炎感染者；而當假設數理模型有進行A型肝炎疫苗的接種措施時，則疫情會在第14個月達到高峰，並共有1303位急性A型肝炎感染者。因此能估算出A型肝炎疫苗接種措施於男男間性行為者群體層面上之效果為82.4%。結論：於愛滋病毒感染之男男間性行為者施打A型肝炎疫苗，能有效的遏止急性A型肝炎爆發流行。

Background: Outbreaks of acute hepatitis A among men who have sex with men (MSM) have reemerged since 2015. We aimed to investigate the population-level effectiveness of the hepatitis A virus (HAV) vaccination campaign during a large outbreak mainly affecting HIV-positive MSM in Taiwan. Methods: In response to the outbreak, a vaccination campaign mainly for HIV-positive MSM was implemented with administration of at least 1 dose of HAV vaccine. The individual-level effectiveness of HAV vaccine among HIV-positive individuals was first ascertained by a nested case-control study. A mathematical model of HAV transmission was then developed among MSM to estimate population-level effectiveness of the vaccination campaign. The model was risk-structured according to the HIV status and calibrated with the epidemic curve of acute hepatitis A in Taiwan during June 2015 to December 2017. Findings: Among 1,470 initially HAV-seronegative HIV-positive individuals in a prospective cohort, 55 case patients of acute hepatitis A were matched to 220 controls. Single-dose and 2-dose HAV vaccination provided an individual-level protection of 96.1% and 97.8% among HIV-positive MSM vaccinees, respectively. With model fitting to the whole epidemic curve, we estimated a transmission rate of 2.47 month-1 for HAV. The corresponding reproduction number (R0) were 8.2 and 4.1 for HIV-positive and HIV-negative MSM, respectively. In the simulated counterfactual scenario without the HAV vaccination campaign, the outbreak would peak in month 21 with a total of 7,410 incident cases. With the vaccination campaign, the epidemic peaked in month 14 with 1,303 incident cases, resulting in a population-level effectiveness of 82.4% among all MSM. Interpretation: HAV vaccination for MSM is a highly effective strategy to curb the hepatitis A outbreak in this high-risk population.