Monkeypox Virus: WHO's Second Public Health Emergency of International Concern Within 2 Years

An upsurge of monkeypox disease (mpox) cases with clade I virus in Central Africa led WHO to declare a Public Health Emergency of International Concern for a second time shortly after the worldwide clade II mpox epidemic in 2022/3 among homosexual men. In the Democratic Republic of Congo (DRC), the annual incidence of clade I mpox, transmitted mostly from animal sources to children, increased 20-fold between 1980 and 2007; 60,000 mpox cases occurred between 2010 and 2023. The incidence again doubled between 2023 and 2024, showing a case fatality rate of 3.3%. A new clade Ib virus was detected in 2024 in eastern DRC where mostly adults were infected by heterosexual contact. Ib was recently introduced and showed a mutation spectrum of human-to-human transmission. Asymptomatic mpox infections, the release of infectious virus before symptom onset in a subgroup of cases, and superspreaders complicate containment measures during the 2022 epidemic. Isolation of cases until two consecutive negative PCR tests was recommended but necessitates cheap and rapid diagnostic tests which are in development. Sexual behavioural changes during the 2022 epidemic have contributed more to the curbing of the epidemic than vaccination. The smallpox vaccine Dryvax protected children exposed to clade I mpox in DRC in the 1980s. The attenuated third-generation smallpox Modified Vaccinia Ankara (MVA) vaccines and derivatives showed robust protection against clade IIb mpox during the 2022/3 epidemic in various study formats. Vaccine efficacy exceeding 75% was reported after two doses. mRNA in lipid-nanoparticle encoding surface proteins from extracellular enveloped and intracellular mature virions of monkeypox virus (MPXV) induced humoral and cellular immune responses that protected macaques against mpox disease with clade I and II viruses better than MVA. Only mixtures of monoclonal antibodies protected mice from mpox. The antiviral tecovirimat showed no efficacy in two clinical trials against clade I and II mpox.