Unnoticed Entry, Noticed Transmission: Epidemiological Insights into China's First clade Ib MPXV cluster

The mpox outbreak caused by clade Ib monkeypox virus (MPXV) spread rapidly in Central and East Africa and led the World Health Organization to declare the outbreak a Public Health Emergency of International Concern (PHEIC). In response, China implemented enhanced surveillance measures; nevertheless, an ostensibly asymptomatic returning traveler with repeatedly negative screening tests initiated China's first documented clade Ib mpox transmission cluster.

We conducted a comprehensive epidemiological, clinical, environmental, and genomic investigation to characterize the transmission pattern and inform public health response strategies. Quantitative PCR, serological testing and whole-genome sequencing were performed on human and environmental samples to confirm infection and assess viral contamination.

Four epidemiologically linked individuals were identified, including one imported index case, two first-generation confirmed cases resulting from unprotected heterosexual contact with the index case, and one suspected second-generation case associated with intimate contact (overnight co-sleeping). No fever was documented during clinical assessment or follow-up; two cases presented with rash, and one had inguinal lymphadenopathy. Whole-genome sequencing confirmed infection with clade Ib MPXV. All 158 throat swabs collected from general (non-sexual) contacts tested negative. Among 314 environmental samples, 25 of 62 samples collected from case residences were MPXV qPCR-positive, whereas all 252 samples from public settings were negative.

These findings demonstrate that clade Ib mpox transmission can occur from an apparently asymptomatic returning traveler despite repeated negative entry screening, underscoring the limitations of symptom-based or entry-point screening alone and the need for enhanced, risk-based surveillance, diagnostic testing, and targeted prevention strategies.