低发病率环境中的Mpox-HIV合并感染：来自中国青海的流行病学见解

摘要(中文译文)

以中国青海省首例报告的猴痘（mpox）与HIV共感染病例为个案研究，本文探讨了低发病率地区猴痘-HIV共感染的流行病学特征和传播动力学，以及监测、诊断和应对方面的系统性缺口。旨在为全球类似低发病率地区的猴痘防控提供具有广泛适用性的见解。开展了一项回顾性流行病学调查，涉及病例A（青海省某医院于2025年6月24日报告的一例猴痘-HIV共感染患者）及其密切接触者。病例和密切接触者的定义依据世界卫生组织（WHO）标准、《（2022年版）》和《（2022年版）》予以适用。通过面对面现场流行病学调查，收集并分析患者的流行病学史、临床诊断、治疗信息及实验室检测结果。所有生物样本均由专业实验室人员在对猴痘病例进行现场流行病学调查期间，严格按照国家标准检测方法和实验室质量控制规范采集。患者及密切接触者均签署知情同意书，研究过程遵循《赫尔辛基宣言》的相关原则。病例A为一名男性HIV感染者，自述有男男性行为史。他于6月19日首次出现会阴部瘙痒。次日体温升至39.4 °C，服药后症状未见改善。他于6月23日至医院就诊，7月7日痊愈出院；总病程为18天。在症状出现前21天内，患者无国际或跨市旅行史，无天花疫苗接种史，无野生动物接触史。然而，他近期在男男性行为者（MSM）人群中经历过高风险暴露。6月24日，接诊医院采集鼻咽拭子标本进行猴痘病毒（MPXV）核酸检测，确诊为猴痘。6月27日，对患者静脉血标本进行基因测序，鉴定病毒为MPXV clade IIb。该序列进一步归属于MPXV clade IIb（原西非分支）内的C.1.1亚系，完整命名为B.1.3.1.1。共确定三名密切接触者，其MPXV核酸检测均为阴性。一名密切接触者MPXV IgG抗体检测阳性，提示既往暴露于MPXV。综合流行病学史、血清学结果及症状出现时间，提示高风险性接触是病例A最可能的暴露途径。症状出现时间与报告的高风险性暴露后7-14天的典型猴痘潜伏期一致。系统发育分析显示，与病例A序列亲缘关系最近的序列为EPI_ISL_19893388，由中国台湾提交。青海省既往报告的病例以输入性为主。然而，病例A无明确的国际旅行或省外旅行史，因此不符合输入性病例的典型流行病学特征。传播模式因此更符合特定社交或性网络内的本地传播。这一发现提示低发病率地区可能已存在隐匿性传播。通过对青海省首例报告的猴痘-HIV共感染病例的回顾性分析，本研究确定了三项关键发现。第一，研究结果提供了低发病率地区既往未被识别的暴露及可能存在隐匿性传播的证据。这些结果可为早期识别隐藏的社区传播和加强预警系统提供参考。与病例A序列亲缘关系最近的猴痘病毒序列由中国台湾提交。三名确定的密切接触者均未出现发热或皮疹等典型临床症状；然而，其中一人MPXV IgG抗体检测阳性。由于所有密切接触者均对病例A有高风险暴露，这一发现提示与该病例相关的本地高风险人群网络中可能存在既往未被识别的暴露。然而，仅凭血清学证据无法确定传播的确切来源、时间或方向。第二，本研究表明低发病率地区的猴痘监测主要依赖医疗机构被动报告，缺乏针对高风险人群的主动筛查机制。被动报告的有效性直接取决于个人就医意愿和识别症状的能力。病例A仅在典型皮疹出现后才就医并获得诊断；发热和乏力等早期症状未得到足够重视，患者未及时就医。这提示轻症、非典型或无症状感染者若不主动就医，可能被监测系统遗漏。这些发现为支持低发病率地区优化主动监测模式、从被动监测向更主动的防控策略转变提供了证据。第三，本研究凸显了猴痘流行病学中重要的血清学缺口，并强调了血清学检测在识别既往暴露和重建可能传播链方面的价值。部分感染者可能不出现典型皮疹或仅有轻微症状。此外，病毒核酸不可检测后，IgM和IgG抗体可能持续较长时间。因此，血清学标志物有助于识别既往暴露、无症状感染和隐匿性传播，从而弥补仅依赖病例报告和核酸检测所相关的监测盲区。总之，低发病率地区的猴痘防控应优先关注隐匿性传播风险。这需要加强高风险人群的主动筛查，减少对就医行为的过度依赖，并建立动态血清学监测系统，以提高对隐匿性传播的早期识别和控制能力。

Abstract

Using the first reported case of mpox and HIV co-infection in Qinghai Province, China, as a case study, this paper examines the epidemiological characteristics and transmission dynamics of mpox-HIV co-infection in low-incidence settings, as well as systemic gaps in surveillance, diagnosis, and response. It aims to generate broadly applicable insights for mpox prevention and control in similar low-incidence regions worldwide. A retrospective epidemiological investigation was conducted involving Case A, a patient with mpox-HIV co-infection reported by a hospital in Qinghai Province on 24 June 2025, and the patient's close contacts. Case and close-contact definitions were applied in accordance with World Health Organization (WHO) criteria, the (2022 Edition), and the (2022 Edition). Face-to-face, on-site epidemiological investigations were conducted to collect and analyse the patient's epidemiological history, clinical diagnosis, treatment information, and laboratory test results. All biological samples were collected by specialist laboratory personnel during the on-site epidemiological investigation of the mpox case, in strict accordance with national standard testing methods and laboratory quality-control protocols. Both the patient and close contacts signed informed consent forms, and the research process was conducted in accordance with the relevant principles of the Declaration of Helsinki. Case A was a male patient living with HIV who reported sex with men. He first developed perineal pruritus on 19 June. The following day, his temperature rose to 39.4 °C, and his symptoms did not improve after medication. He sought medical attention at a hospital on 23 June and was discharged on 7 July after full recovery; the total duration of illness was 18 days. During the 21 days before symptom onset, the patient had no history of international or out-of-city travel, no history of smallpox vaccination, and no history of contact with wild animals. He had, however, recently experienced high-risk exposure within the men who have sex with men (MSM) community. On 24 June, the admitting hospital collected a nasopharyngeal swab specimen for mpox virus (MPXV) nucleic acid testing, which confirmed a diagnosis of mpox. On 27 June, genetic sequencing was performed on a venous blood specimen from the patient, and the virus was identified as MPXV clade IIb. The sequence was further assigned to the C.1.1 sublineage, full designation B.1.3.1.1, within MPXV clade IIb, formerly known as the West African clade. A total of three close contacts were identified, all of whom tested negative for MPXV nucleic acid. One close contact tested positive for MPXV IgG antibodies, suggesting previous exposure to MPXV. Taken together, the epidemiological history, serological findings, and timing of symptom onset suggest that high-risk sexual contact was the most likely route of exposure for Case A. The onset of symptoms was consistent with the typical mpox incubation period of 7-14 days after the reported high-risk sexual exposure. Phylogenetic analysis showed that the sequence most closely related to that from Case A was EPI_ISL_19893388, submitted by Taiwan, China. Previously reported cases in Qinghai Province were predominantly imported. However, Case A had no clear history of international travel or travel outside the province and therefore did not meet the typical epidemiological profile of an imported case. The transmission pattern was therefore more consistent with local transmission within specific social or sexual networks. This finding suggests that silent transmission may already be occurring in low-incidence regions. Through a retrospective analysis of the first reported case of mpox-HIV co-infection in Qinghai Province, this study identified three key findings. First, the findings provide evidence of previously unrecognized exposure and possible silent transmission in a low-incidence region. These results may inform the early identification of hidden community transmission and the strengthening of early warning systems. The mpox virus sequence most closely related to that from Case A had been submitted from Taiwan, China. None of the three identified close contacts presented with typical clinical symptoms, such as fever or rash; however, one tested positive for MPXV IgG antibodies. Because all close contacts had high-risk exposure to Case A, this finding suggests the possibility of prior, unrecognized exposure within the local high-risk population network associated with the case. However, serological evidence alone cannot establish the exact source, timing, or direction of transmission. Second, this study shows that mpox surveillance in low-incidence areas relies primarily on passive reporting by healthcare institutions and lacks active screening mechanisms for high-risk populations. The effectiveness of passive reporting depends directly on individuals' willingness to seek medical care and their ability to recognize symptoms. Case A sought medical attention and was diagnosed only after the onset of a typical rash; earlier symptoms, such as fever and fatigue, did not receive sufficient attention, and the patient did not seek timely care. This suggests that individuals with mild, atypical, or asymptomatic infections may be missed by surveillance systems if they do not proactively seek medical attention. These findings provide evidence to support the optimization of active surveillance models in low-incidence areas and the transition from passive surveillance to more proactive prevention and control strategies. Third, this study highlights an important serological gap in mpox epidemiology and emphasizes the value of serological testing in identifying previous exposure and reconstructing possible transmission chains. Some infected individuals may not present with a typical rash or may have only mild symptoms. Moreover, after viral nucleic acid becomes undetectable, IgM and IgG antibodies may persist for an extended period. Serological markers can therefore help identify previous exposure, asymptomatic infection, and silent transmission, thereby addressing surveillance blind spots associated with reliance on case reports and nucleic acid testing alone. In summary, mpox prevention and control in low-incidence areas should priorities the risk of silent transmission. This requires strengthening proactive screening among high-risk groups, reducing over-reliance on healthcare-seeking behavior, and establishing dynamic serological surveillance systems to improve the early identification and control of silent transmission.

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