The first local case of mpox caused by an imported case in the Chinese mainland

Highlights

• •We report the first local case of monkeypox (mpox) in the Chinese mainland.
• •Secondary infection was observed in the current case caused by sexual contact in the men who have sex with men (MSM) population.
• •The monkeypox virus (MPXV) of current cases belonged to the B.1.3 branch of the West African lineage.

Abstract

Monkeypox (mpox) is a zoonotic disease caused by the mpox virus (MPXV) that has been primarily limited to Central and West African nations since its discovery. The recent spread of the West African lineage of MPXV in historically unaffected countries has raised concerns for global public health. Despite a significant decrease in global mpox cases, there is still a risk of a global resurgence. This study reports the first local case of mpox caused by an imported case in the Chinese mainland. Polymerase chain reaction (PCR) diagnosed the two cases, and the viral genomes were obtained by next-generation sequencing. Genomic analysis revealed that the two strains shared an identical genome sequence and belonged to the B.1.3 branch of the West African lineage, which is the first local case of mpox caused by an imported case in the Chinese mainland, highlighting the potential threat of mpox in China and the immediate need for adequate surveillance measures.

1. Introduction

Monkeypox (mpox), a zoonotic disease caused by the mpox virus (MPXV), was first reported in the 1970s in the Democratic Republic of the Congo and is primarily limited to Central and West African nations [1], [2]. However, the spread of the West African lineage of MPXV in historically unaffected countries has raised concerns for global public health. From January 1, 2022, to June 5, 2023, a cumulative total of 87,929 cases of mpox, including 146 deaths in 111 countries or areas, have been reported to the World Health Organization (WHO) [1], [3], which has been the first time that multiple nonepidemic countries or areas worldwide have simultaneously reported numerous cases of mpox, which poses new challenges to the prevention and control of the mpox epidemics. On May 11, 2023, based on the current epidemic situation, the WHO declared that the mpox global health emergency had ended. However, as of June 5, 2023, 15 of the 111 countries affected in the past year reported new mpox cases within the last 21 days. Recently, the Western Pacific Region and the South-East Asia Region reported an increase in mpox cases, indicating that local transmission is ongoing in some countries or areas and poses a challenge to preventing and controlling mpox in China [3]. There was only one imported case, reported on September 16, 2022 [4], and no local cases have been reported in the Chinese mainland since the recent global spread of mpox. Here, we report the first local case of mpox caused by an imported case in the Chinese mainland.

2. Materials and methods

2.1. Epidemiological investigation

An epidemiological investigation of the two cases was conducted to collect demographic information, overseas travel history, the date of onset, and medical treatment course. Individuals in close contact with the mpox cases were identified and managed according to the National Technical Guidelines for Mpox Control (2022 edition) of China. The possible infection source and transmission route were investigated according to the available epidemiological data.

2.2. Real-time polymerase chain reaction

Oropharyngeal swabs, blood, and skin lesion swabs were collected for MPXV detection assays. Viral DNA was extracted using a commercial kit (Qiagen, Dusseldorf, Germany). Then, MPXV DNA was detected using the primers and probes targeting the F3L gene on the ABI 7500 system (Applied Biosystems, Carlsbad, CA, USA), according to the manufacturer’s protocol.

2.3. Next-generation sequencing

The amplicon sequencing method was used for generating MPXV genomes. Viral DNA was amplified by multiplex polymerase chain reaction (PCR) (Beijing Microfuture Ltd., Beijing, China). PCR products were purified with AMpure XP Beads (Beckman, Brea, CA, USA) and quantified using Qubit 3.0 (Thermo Fisher Scientific, Waltham, MA, USA). Then, the sequencing libraries were prepared with the Nextera XT Library Prep Kit and sequenced using the Illumina MiniSeq platform (Illumina, San Diego, CA, USA). Consensus sequences were extracted from each mapping and assembly for each sample.

3. Results

3.1. Case presentation

Patient 1 was a 30-year-old male who suffered from inguinal lymphadenopathy, had papules on the left inguinal on May 26, 2023, and had a fever with no cough or sore throat on May 27. The patient sought medical attention due to an aggravation of pus-filled skin pustules on May 29 and was thus considered a suspected case of mpox on May 31. Physical examination showed that pustular rashes had erupted on the face and perineum. Epidemiological investigation revealed that Patient 1 had no history of traveling abroad within one month before the onset of symptoms but had sexual contact with Patient 2 on May 7 and May 14, respectively. Patient 2 was subsequently investigated and sampled for MPXV detection. An epidemiological investigation showed that Patient 2 was a 26-year-old male who had had sexual contact with others abroad and returned to Beijing on April 19, 2023. Patient 2 developed fatigue, lethargy, and a sore throat on May 10 and reported a fever, fatigue, and sore throat on May 26. Patient 2 developed a perianal abscess on May 30 and went to the hospital on June 2. The specimens, including the oropharyngeal and perianal swabs, were sampled for MPXV detection on June 2 (Fig. 1).

Fig. 1.

Timeline of the onset, diagnosis, and clinical outcomes of two cases of monkeypox (mpox). Abbreviation: MPXV, monkeypox virus.

3.2. Real-time PCR test for MPXV

Clinical samples, including a skin lesion swab, an oropharyngeal swab, and a blood sample, were collected from Patient 1 on May 31, 2023, and primarily screened for MPXV nucleic acid using real-time PCR in the Beijing Center for Disease Prevention and Control (Beijing CDC). The specimens tested positive for MPXV nucleic acid and were positive in reconfirmation tests performed by the National Institute for Viral Disease Control and Prevention (IVDC), China CDC. Oropharyngeal and perianal swabs were collected from Patient 2 on June 2, and the perianal swab tested positive for MPXV nucleic acid (Table 1).

Table 1.

Detection of monkeypox virus (MPXV) by real-time polymerase chain reaction (PCR).

Case	Specimen collection date	Specimen	Result	Ct value
Patient 1	May 31, 2023	Oropharyngeal swab	Positive	26.3
	May 31, 2023	Skin lesion swab	Positive	16.5
	May 31, 2023	Blood	Positive	35.2
Patient 2	June 02, 2023	Oropharyngeal swab	Negative	NA
	June 02, 2023	Perianal swab	Positive	15.5

Note: NA = not available.

3.3. Genomic analysis

Viral genomes were obtained from the two patients by next-generation sequencing (NGS). The result showed that the viruses belonged to the B.1.3 branch of the West African lineage. The two genomes were clustered into the same clade with strains from Japan and were highly homologous to the strain collected on April 28, 2023 (GISAID ID: EPI_ISL_17692269). Genomic analysis revealed that the two viruses from the two patients shared an identical genome sequence. There were 80 nucleotide substitutions on both genomes compared with the reference human MPXV genome (Accession number: NC_063383.1).

4. Discussion

This study reports the first local case of mpox in the Chinese mainland. In the past year, 87,929 laboratory-confirmed cases of mpox were identified worldwide. In China, as of June 14, 2023, Taiwan and Hong Kong reported 162 and 7 confirmed cases of mpox, respectively. Both regions have reported cases imported from overseas that have subsequently caused local cases or even outbreaks. Chongqing Municipality reported the first imported case of mpox in the Chinese mainland on September 16, but no local cases have been reported until now [4]. Significantly, the Western Pacific Region and the South-East Asia Region have reported increased mpox cases recently [3], [5], suggesting that local transmission is still ongoing, increasing the risk of the mpox virus being imported into China. In the present study, both epidemiological investigations and NGS assays indicated that the first local case of mpox in the Chinese mainland was a secondary case of overseas infection.

The MPXV that caused the current global outbreak is classified as a Clade IIb strain and phylogenetically distinct from prior endemic strains (Clades I or IIa) [6]. Recent research revealed that G > A or C > T transitions might be caused by deaminase editing by the apolipoprotein B mRNA editing enzyme catalytic polypeptide 3G (APOBEC3) [7], which indicates that microevolution within the current widespread strains most likely reflects viral adaptability to humans and community dissemination. Clade IIb has recently evolved into branches consisting of A.1, A.1.1, B.1.1, B.1.2, B.1.3, etcetera., indicating the genetic diversity and ongoing evolution of the current prevalent MPXV strains. The virus identified in the present study belonged to branch B.1.3, prevalent in Europe, North America, and Asian countries such as Japan. These two strains were highly homologous to the strain collected from Japan. However, epidemiological data showed that Patient 2 returned from a South-East Asian country other than Japan, which suggests that branch B.1.3 might be prevalent in the region and is highly genetically related. Since recent global genomic monitoring of mpox virus and data sharing were insufficient, the genomic surveillance of MPXV still needs to be strengthened.

Evidence showed person-to-person transmission occurring in specific communities through close contact, primarily among men who have sex with men (MSM), during the 2022 mpox outbreak [8]. The first local case of mpox reported in this study is also a member of the MSM population, indicating that close contact with specific populations remains the main transmission route of the disease. Previous studies estimated that the Chinese mainland has an MSM population size of 12 million [9], spotlighting the potential transmission in this community. Therefore, personalized care measures such as health education, voluntary counseling, and testing should be developed for this population. Notably, mpox can also be transmitted through the air or close contact with contaminated objects [10]. Overemphasizing the sexual transmission of mpox among specific populations may ignore the necessary control measures for other transmission routes and mislead the public about mpox. More knowledge of the transmission routes of mpox may lead to earlier identification of the spillover of new cases into other groups [10].

In conclusion, we reported the first local case of mpox caused by an imported case in the Chinese mainland. The prevalence of mpox is a fixed threat to both China and the world in the future. There is an urgent need to develop proper and practical education, surveillance, and intervention measures.

Ethics statement

As a public health response to an emerging infectious disease outbreak, written informed consent could be waived. Data and sample collection procedures were in accordance with the Technical Guidelines for Mpox Control (2022 edition) approved by the National Health Commission of the People’s Republic of China.