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Historically, human mpox was predominantly a zoonotic disease occurring more frequently in rural children in Africa and characterized by a largely self-limiting febrile centrifugal monomorphic rash illness. However, the 2022 mpox global outbreak has shown that the disease is changing in many ways, including sustained human-to-human transmission via sexual contact, novel clinical presentations, and adverse associations between mpox and advanced HIV. The aim of this paper is to review the traditional and emerging clinical aspects of human mpox and provide updated information on the clinical course and outcome of the disease. We searched electronic databases including PubMed and Google Scholar and identified relevant published literature on mpox. The clinical presentation of human mpox is influenced by the route of infectious exposure, the strain and dose of the infecting virus, and the host immune system. Exposure to the virus can result in sub-clinical or clinical diseases of variable severity. Infections caused by clade I viral strains are more severe than class IIa and IIb strains, which are associated with a milder febrile rash illness, and with anogenital skin lesions in clade IIb infections. Most cases of mpox recover entirely within 2–4 weeks after onset of illness and a few develop skin-related sequelae. Overall, people with advanced HIV infection, children <5 years of age, and pregnant women may present with more severe disease and higher case fatalities. The continued endemicity of the classical mpox in Africa, the emergence of a new clinical form of the disease during the 2022 global outbreak, and the adverse associations between advanced HIV and mpox have implications for the surveillance, clinical diagnosis, and management of human mpox. [ABSTRACT FROM AUTHOR]

Monkeypox is a zoonotic illness caused by the monkeypox virus, an Orthopoxvirus in the same genus as the variola, vaccinia, and cowpox viruses. Since the detection of the first human case in the Democratic Republic of the Congo in 1970, the disease has caused sporadic infections and outbreaks, mainly restricted to some countries in west and central Africa. In July, 2022, WHO declared monkeypox a Public Health Emergency of International Concern, on account of the unprecedented global spread of the disease outside previously endemic countries in Africa and the need for global solidarity to address this previously neglected disease. The 2022 outbreak has been primarily associated with close intimate contact (including sexual activity) and most cases have been diagnosed among men who have sex with men, who often present with novel epidemiological and clinical characteristics. In the 2022 outbreak, the incubation period ranges from 7 days to 10 days and most patients present with a systemic illness that includes fever and myalgia and a characteristic rash, with papules that evolve to vesicles, pustules, and crusts in the genital, anal, or oral regions and often involve the mucosa. Complications that require medical treatment (eg, antiviral therapy, antibacterials, and pain control) occur in up to 40% of patients and include rectal pain, odynophagia, penile oedema, and skin and anorectal abscesses. Most patients have a self-limited illness; between 1% and 13% require hospital admission (for treatment or isolation), and the case-fatality rate is less than 0·1%. A diagnosis can be made through the presence of Orthopoxvirus DNA in PCRs from lesion swabs or body fluids. Patients with severe manifestations and people at risk of severe disease (eg, immunosuppressed people) could benefit from antiviral treatment (eg, tecovirimat). The current strategy for post-exposure prophylaxis or pre-exposure prophylaxis for people at high risk is vaccination with the non-replicating modified vaccinia Ankara. Antiviral treatment and vaccines are not yet available in endemic countries in Africa. [ABSTRACT FROM AUTHOR]

On August 14, 2024, following a regional declaration by the Africa Centres for Disease Control and Prevention, the World Health Organization declared mpox a Public Health Emergency of International Concern, marking the second such declaration in two years. A series of outbreaks involving the more virulent clade I virus (compared to clade II, which caused a global outbreak in 2022), has now spread in 13 African countries, exposing the inadequacies of the public health infrastructure in these settings. There was significant investment during the 2022 global outbreak, but these efforts failed to address vaccine access and treatment in the Global South. Regulatory delays, unequal access to vaccines, and a lack of compassionate use treatments for severe cases have resulted in preventable cases and deaths, especially among vulnerable populations such as pregnant women, children, and the immunocompromised. The current outbreak also underscores critical knowledge gaps in our understanding of mpox, including its transmission, pathogenesis, and viral evolution. We join intensified calls for global solidarity and action to control mpox, emphasizing immediate containment measures and long-term local and international investment in African public health systems, to prevent future epidemics.

Competing Interests: We declare no competing interests.

Competing Interests: JBN is supported by the US National Institutes of Health (grant numbers NIH/FIC 1R25TW011217-01, NIH/FIC 1D43TW010937-01A1, NIH/FIC D43TW011827-01A1, NIH/FIC 1R21TW011706-0, and NIH/NIAID 5U01AI096299-13). FN and AZ are codirectors of the Pan-African Network on Emerging and Re-Emerging Infections funded by the European and Developing Countries Clinical Trials Partnership (EDCTP) within the EU Horizon 2020 Framework Programme. FN and AZ also acknowledge support from the EDCTP Central Africa Clinical Research Network. AZ is a UK National Institute for Health Research senior investigator, and a Mahathir Science Award and EU-EDCTP Pascoal Mocumbi Prize laureate. JJM-T holds National Institutes of Health National Institute of Allergy and Infectious Diseases grants (number 75N91019D00024-P00001-759102000025-5). JK is supported by grant funding from the Canadian Institutes of Health Research and International Development Research Centre (grant numbers MRR-184813 and PPE-185821). ELM is supported by the US National Institutes of Health (grant number 1R01AI182082-01). All other authors declare no competing interests. We thank John L Johnson for critical review and helpful advice. The views and conclusions in this Personal View are those of the authors and do not necessarily represent the views of their institutions.

Data on mpox in pregnancy are currently limited. Historically, only 65 cases in pregnancy have been reported globally since mpox was discovered in 1958. This includes 59 cases in the current outbreak. Vertical transmission was confirmed in one patient. Pregnant women are at high risk of severe disease owing to immunological and hormonal changes that increase susceptibility to infections in pregnancy. African women appear to be at higher risk of mpox infection and adverse outcomes in pregnancy for epidemiological and immunologic reasons, in addition to the background high rates of adverse feto-maternal outcomes in the region. This risk is potentially heightened during the COVID-19 pandemic due to the possibility of mpox virus exportation/importation as a result of the lifting of movement restrictions and trans-border travels between countries affected by the current outbreak. Furthermore, coinfection with mpox and COVID-19 in pregnancy is possible, and the clinical features of both conditions may overlap. Challenges of diagnosis and management of mpox in pregnancy in Africa include patients concealing their travel history from healthcare providers and absconding from/evading isolation after diagnosis, shortage of personal protective equipment and polymerase chain reaction testing facilities for diagnosis, vaccine hesitancy/resistance, and poor disease notification systems. There is a need for local, regional and global support to strengthen the capacity of African countries to address these challenges and potentially reduce the disease burden among pregnant women in the continent., (© 2023 International Federation of Gynecology and Obstetrics.)