On May 6, 2022, the UK High Consequence Infectious Diseases (HCID) network was alerted to a confirmed case of monkeypox in an individual who had recently returned from West Africa. Over the following week, six additional cases were identified, none of which had any epidemiological link to West Africa. This marked a critical turning point in understanding the dynamics of the outbreak, as it suggested local transmission within the United Kingdom. By July 12, 2022, the total number of confirmed monkeypox cases in the UK had risen to 1,735. The vast majority of these cases, approximately 96%, occurred in gay, bisexual, or other men who have sex with men (GBMSM), and 79% of cases were concentrated in London.
The outbreak extended beyond the UK, with cases reported in non-endemic countries across Europe and the Americas. Spain and Germany recorded the highest case counts outside the UK, highlighting the virus’s ability to spread internationally in regions historically unaffected by monkeypox. The rapid rise in cases, combined with the geographic spread, raised concerns about the virus’s transmission pathways and its implications for public health on a global scale.
Overview of the Monkeypox Virus
Monkeypox is caused by an orthopoxvirus closely related to the smallpox virus. It was first identified in 1958 among primates kept in captivity for research purposes. Although the exact reservoir of the virus remains unknown, rodents are widely suspected to play a significant role in its transmission. The first documented human cases of monkeypox were reported in 1970 in the Democratic Republic of Congo, where a smallpox-like illness was investigated in regions previously thought to be free of variola (smallpox virus).
Two genetically distinct clades of the monkeypox virus have been identified: the Central African (Congo Basin) clade and the West African clade. The Central African clade is associated with higher mortality rates and more severe disease presentations, whereas the West African clade, which was implicated in the 2022 outbreak, generally causes milder illness with lower fatality rates.
Previously, monkeypox has been endemic to regions of the Congo Basin and West Africa. Outbreaks in these areas have typically been linked to zoonotic transmission through handling or consuming infected wild game animals. Human-to-human transmission, while less common, has occurred primarily through close physical contact with infected individuals or their bodily fluids. Transmission via respiratory droplets and contaminated objects (fomites) has also been documented, further highlighting the virus’s potential for spread under specific conditions.
Transmission and Clinical Presentation
The incubation period for monkeypox is approximately 12 days, with a range of 5 to 24 days. Classical presentations of monkeypox involve two distinct phases. The prodromal phase is characterised by fever, malaise, headache, lymphadenopathy, and sweats. This is followed by the eruption phase, during which skin lesions appear. These lesions evolve through predictable stages, beginning as macules, progressing to papules, vesicles, pustules, and finally crusting over before desquamation (shedding of the scabs). Historically, these lesions appear simultaneously and progress sequentially, typically affecting the face, palms, soles, and mucous membranes. Notably, lesions on the face have been observed in 95% of cases, while lesions on the palms and soles occur in approximately 75% of patients.
However, the 2022 outbreak indicated significant deviations from these historical patterns. In many cases, lesions were localised to the genital, perianal, and tonsillar regions. Additionally, solitary lesions and polymorphic rashes, where lesions appear at different stages simultaneously, were observed. These atypical presentations posed diagnostic challenges, as they could easily be mistaken for other conditions, such as syphilis, lymphogranuloma venereum, or herpes simplex virus infections. In some patients, systemic symptoms like fever and lymphadenopathy occurred after the appearance of skin lesions rather than preceding them, contradicting the traditional understanding of the disease progression.
The predominant routes of transmission during the 2022 outbreak included close physical contact with lesions, exposure to respiratory droplets during prolonged face-to-face interactions, and contact with contaminated objects. Sexual contact was a significant factor in the outbreak, with 96% of patients reporting recent sexual activity. Notably, only 25% of patients had known contact with someone diagnosed with monkeypox, suggesting a high likelihood of asymptomatic or minimally symptomatic transmission.
Historical Context of Monkeypox Outbreaks
Before the 2022 outbreak, monkeypox was largely confined to endemic regions in Central and West Africa. Outbreaks in these areas have typically been small, involving between 23 and 88 cases. Zoonotic transmission through handling or consuming wild game animals has been the primary route of infection, followed by limited human-to-human transmission within households.
The first significant outbreak outside Africa occurred in 2003 in the United States, involving 11 individuals who were exposed to infected prairie dogs. These animals had been housed alongside a Gambian giant rat, which was presumed to be the original source of the virus. Since 2018, sporadic cases of travel-associated monkeypox have been reported in the UK, the United States, Singapore, and Israel. These cases have typically involved individuals returning from endemic regions, with minimal onward transmission.
The 2022 outbreak marked a significant departure from this pattern, as it involved sustained community transmission within non-endemic countries. This shift highlighted the need for updated public health strategies to address the unique challenges posed by the outbreak.
Clinical Observations from the 2022 Outbreak
Data from a cohort of 197 patients managed at a South London HCID centre showed important insights into the clinical characteristics of the 2022 outbreak. Unlike previous outbreaks, which predominantly affected children, the UK cohort consisted exclusively of adult men, with 99.5% identifying as GBMSM. Only one patient in this group had recently travelled to an endemic region, providing further evidence of autochthonous (local) transmission within the UK.
Penile swelling and rectal pain emerged as common symptoms in this cohort, with both conditions frequently necessitating hospital admission for symptom management. Other notable findings included abscesses and solitary lesions, which were not typically associated with monkeypox in earlier reports. These atypical presentations often delayed diagnosis, as they could mimic other conditions such as bacterial tonsillitis or ingrown hairs.
Approximately 31.5% of patients screened for sexually transmitted infections (STIs) were found to have co-infections, most commonly with Neisseria gonorrhoeae and Chlamydia trachomatis. These co-infections may have exacerbated symptoms, particularly rectal pain and swelling. In patients who tested negative for monkeypox, alternative diagnoses included syphilis, herpes simplex virus, varicella zoster virus, N. gonorrhoeae, and C. trachomatis. These findings highlight the importance of comprehensive STI screening in patients presenting with suspected monkeypox to ensure accurate diagnosis and appropriate treatment.
Implications for Public Health and Policy
The 2022 outbreak has significant implications for public health and policy. First and foremost, the rapid community spread of the virus emphasised the need for robust contact tracing and isolation measures. However, the observation that only a quarter of patients had known contact with confirmed cases suggests that current contact tracing methods may be insufficient to capture all transmission pathways. Public health messaging must also be updated to reflect the atypical symptoms observed in this outbreak, such as penile swelling, rectal pain, and solitary lesions.
Healthcare providers, particularly those in primary care, sexual health clinics, and emergency departments, must be trained to recognise these atypical presentations. Early diagnosis is critical not only for preventing further transmission but also for managing symptoms effectively and reducing the risk of complications. The need for resource allocation to manage hospital admissions for symptom control also highlights the importance of preparing healthcare systems for future outbreaks.
The emergence of atypical transmission pathways, including the potential for asymptomatic spread, has major implications for infection control. Public health authorities must consider revising diagnostic criteria to account for these findings. For example, the current UK Health Security Agency definition of a probable monkeypox case requires the presence of typical systemic symptoms in addition to cutaneous lesions and epidemiological risk. However, 14% of patients in the South London cohort did not meet these criteria, suggesting that the definition may need to be broadened.
Challenges and Limitations
The 2022 outbreak also indicated several challenges and limitations in the current understanding of monkeypox. Retrospective analyses of clinical data are inherently limited by variability in documentation and the lack of standardised data collection criteria. Furthermore, the geographically restricted nature of some studies may not fully capture the diversity of presentations seen in other regions.
Another significant challenge is the potential for underdiagnosis and misdiagnosis, particularly in cases with atypical symptoms or co-infections. Misdiagnosed cases not only delay appropriate treatment but also increase the risk of further transmission. Addressing these challenges will require ongoing surveillance, research, and collaboration between healthcare providers and public health authorities.
Conclusion
The 2022 monkeypox outbreak represents a pivotal moment in the understanding of this historically neglected disease. The shift in transmission dynamics, clinical presentations, and affected populations highlights the need for adaptive public health strategies and enhanced awareness among healthcare providers. By learning from this outbreak, healthcare systems can better prepare for and respond to emerging infectious diseases, ultimately reducing their impact on public health and society as a whole.
Reference
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