As the world still vividly recalls the previous monkeypox (mpox) outbreak that impacted over 120 countries worldwide with more than 99,000 cases in 2022, we are now facing a second wave of infections from the monkeypox virus (MPXV), characterized by an exponential increase in cases. The current 2024 outbreak has already recorded more than 20,000 cases in Africa, marking a dramatic escalation compared to previous outbreaks. The predominance of the newly identified clade Ib variant, first detected in the Democratic Republic of the Congo (DRC) and now identified across multiple African nations and beyond, underscores its enhanced transmissibility and potential for international spread, evidenced by cases in Sweden and Thailand. The World Health Organization (WHO) declared on August 14, 2024, the current mpox outbreak a Public Health Emergency of International Concern (PHEIC), calling for heightened global public health measures. The ongoing pattern of unusual, frequent, and extensive outbreaks of mpox with potential global implications poses significant questions. This review addresses, in the format of 50 questions and answers, the 2024 mpox outbreak, detailing its characteristics, epidemiological data, and impact compared to previous outbreaks. It comprehensively explores critical questions related to MPXV virological characteristics, immunological response, clinical manifestations, epidemiology, diagnostics, and available treatments. The review also documents the significant and evolving challenges posed by the current mpox outbreak, highlighting its scale, spread, and public health response.
