中文摘要

背景：生殖器疱疹是我国重点监测和防控的五种性病之一，从2004年开始，我国对生殖器疱疹实行网络直报，2005年起报告数据趋于稳定，但其近年的流行趋势、时空分布特征、疾病负担尚不清楚。

       目的：阐明我国生殖器疱疹的流行趋势；探索生殖器疱疹的空间分布格局与聚集模式，明确热点地区，探测时空聚集区；估计全国生殖器疱疹的发病与患病负担；抽样调查与估计生殖器疱疹的直接医疗费用，为精准防控与优化医疗卫生资源配置提供依据。

       方法：通过中国疾病预防控制信息系统传染病报告信息管理系统收集2005-2023年31个省（自治区、直辖市）生殖器疱疹报告病例及发病率数据，使用Joinpoint回归模型，计算平均年度变化百分比（average annual percent change, AAPC），分析我国生殖器疱疹报告发病率的流行趋势；以县（区）为单位，建立各县（区）生殖器疱疹报告病例的地理信息系统数据库，使用ArcGIS和GeoDa软件进行全局空间趋势分析，拟合发病率投影曲线，进一步使用空间自相关分析，计算Moran指数、G系数等；应用SaTScan软件进行时空扫描分析，使用Poisson分布模型，计算LLR值，识别时空聚集区。应用Meta分析方法估计15-49岁人群的HSV-2感染率，参考WHO的方法估计生殖器疱疹发病与患病负担；根据地理区域的分布和可行性选择省份调查生殖器疱疹患者的直接医疗费用，估计全国15-49岁生殖器疱疹患者的年直接医疗费用。

       结果：2005-2023年全国生殖器疱疹报告发病率由0.35/10万增长至2.00/10万，报告发病率上升趋势有统计学意义（AAPC=8.99%, 95%CI: 5.60%~12.50%, P<0.001）；全国生殖器疱疹报告发病率整体表现为“东高西低，南高北低”的空间分布格局，从西北向东南方向逐渐增高；报告发病率呈显著的空间正自相关（Moran’s I =0.16~0.51，均P<0.001），进一步计算全局G系数表明，报告发病率整体呈高值聚集的分布模式［Z(G)=18.55~42.05，均 P<0.001］；热点地区数量呈增长趋势，由2005年的49个增加到2023年的232个，主要分布于浙江省、福建省、广东省和重庆市等；时空扫描分析共探测到75个有统计学意义的时空聚集区，主要分布于浙江省和福建省（2008-2011年）、广东省（2011-2014年）以及重庆市和贵州省（2020-2023年）。

从1990年到2023年间共检索文献3558篇，最终纳入分析139篇（176个独立数据点），Meta分析结果显示，2018-2023年我国15-49岁普通人群、MSM、FSW以及皮肤性病门诊患者人群的HSV-2合并感染率分别为7.31%（95%CI: 4.75%~11.09%）、13.51%（95%CI: 9.44%~18.96%）、43.23%（95%CI: 32.54%~ 54.59%）以及32.48%（95%CI: 24.39%~41.77%）。估计我国15-49岁全人群生殖器疱疹年发病数约为36.53万（95%CI: 27.04万~49.07万），年发病率约56.53/10万（95%CI: 41.84/10万~75.93/10万），患病数约1 438万（95%CI: 1 061万~1 939万），患病率约为2.23%（95%CI: 1.64%~3.00%）。

共收集10个省（自治区、直辖市）21家医疗机构413例生殖器疱疹病例的费用数据M（Q₁, Q₃），平均每例生殖器疱疹病例的直接医疗费用为174.59（79.30, 309.41）元，估计2018-2023年间每年全国生殖器疱疹病例的直接医疗费用约为32.30（95%CI: 20.52~50.33）亿元。

结论：2005-2023年我国生殖器疱疹报告发病率总体呈上升趋势；空间上整体呈现“东高西低，南高北低”的空间分布格局；聚集模式表现为高值聚集分布模式；高-高聚集区以及热点地区主要分布在东南沿海及西南地区；时空聚集区逐渐从东南沿海地区转变至西南地区，呈现出明显的动态变化趋势；生殖器疱疹的发病和患病负担较为严重，直接医疗费用较高。

Abstract

       Background: Genital herpes is one of the five sexually transmitted diseases that are mainly monitored and controlled in China. Since 2004, China has implemented the direct reporting network for genital herpes, and the reported data have tended to be stable since 2005, but its epidemic trend, spatiotemporal characteristics, and disease burden are still unclear.

       Objectives: To determine the report incidence trend of genital herpes; to explore the spatial distribution pattern and aggregation pattern of genital herpes, identify the hot spots, and detect the spatiotemporal aggregation area; to estimate the incidence and prevalence burden of genital herpes in the country; to calculate direct medical costs of genital herpes to provide a basis for accurate prevention and control and optimization of medical and health resource allocation.

Methods: The data of reported cases of genital herpes were collected from 31 provinces (autonomous regions and municipalities) between 2005 to 2023 through the National Notifiable Infectious Disease Reporting System of China Information System for Disease Control and Prevention. The Joinpoint regression model was used to calculate the average annual percent change(AAPC) to analyze the trend of genital herpes in China. The geographic information system database of reported genital herpes cases in each county was established, and ArcGIS and GeoDa software were used to analyze the global spatial trend, and further used spatial autocorrelation analysis to calculate the Moran’s I and G coefficients. SaTScan was used to conduct space-time scan analysis and Poisson distribution model was used, and then calculated the LLR and identified the spatiotemporal gathering area. A meta-analysis was conducted to estimate the prevalence of HSV-2 infection among low-risk populations, MSM, FSWS, and patients in the dermatology clinics aged 15-49 years. The burden of incidence and prevalence of genital herpes were estimated according to the methods of WHO. According to the geographical distribution and feasibility, provinces were selected to investigate the direct medical expenditure of genital herpes patients, and the annual direct medical costs of genital herpes patients aged 15-49 years in China was estimated.

Results: From 2005 to 2023, the reported incidence rate of genital herpes in China increased from 0.35/100 000 to 2.00/100 000. The Joinpoint regression analysis results showed that the reported incidence rate was increasing (AAPC=8.99%, 95%CI: 5.60%-12.50%, P<0.001). The overall spatial distribution pattern of the reported incidence of genital herpes in China was "high in the east and low in the west, high in the south and low in the north". The reported incidence had a significant positive spatial autocorrelation (Moran's I = 0.16-0.51, all P<0.001). Further analysis of global G coefficient showed that the reported incidence had a distribution pattern of high-value clustering [Z(G)=18.55-42.05, all P<0.001]. The number of hot spots increased from 49 in 2005 to 232 in 2023, mainly distributed in Zhejiang, Fujian, Guangdong and Chongqing. A total of 75 significant spatiotemporal clusters were detected by space-time scan analysis, mainly distributed in Zhejiang and Fujian (2008-2011), Guangdong (2011-2014), Chongqing and Guizhou (2020-2023).

A total of 3558 articles were retrieved from 1990 to 2023, and 139 articles (176 independent data points) were included in the final analysis. Meta-analysis showed that the HSV-2 infection rate among low-risk population, MSM, FSW and patients in the dermatology clinics aged 15-49 years was 7.31% (95%CI: 4.75%-11.09%), 13.51% (95%CI: 9.44%-18.96%), 43.23% (95%CI: 32.54%-54.59%) and 32.48% (95%CI: 24.39%-41.77%), respectively. It is estimated that annual number of cases was 365 300 (95%CI: 270 400-490 700), the annual incidence rate was 56.53/100 000 (95%CI: 41.84/100 000-75.93/100 000), and there were 14.38 million  (95%CI: 10.61 million-19.39 million) people would be infected with genital herpes from 2018 to 2023, with a prevalence of 2.23% (95%CI: 1.64%-3.00%).

This study investigated the cost data of 413 genital herpes cases in 21 medical institutions in 10 provinces (autonomous regions and municipalities). The results showed that the average direct medical cost per genital herpes case M (Q₁, Q₃) was 174.59 (79.30, 309.41) yuan. It was estimated that the direct medical costs for genital herpes cases in China each year from 2018 to 2023 was approximately 3.230 (95%CI: 2.052-5.033) billion yuan.

Conclusions: The reported incidence of genital herpes in China generally shows an upward trend from 2005 to 2023. The overall spatial distribution pattern of the reported incidence was "high in the east and low in the west, high in the south and low in the north". The clustering pattern showed a high-value clustering distribution pattern. The high-high clustering areas and hot spots were mainly distributed in the southeast and southwest areas. The spatiotemporal clustering areas gradually changed from the southeast to the southwest area, showing an obvious dynamic trend. The incidence and prevalence burden of genital herpes are serious, and the direct medical costs are high.