Clinical features and novel presentations of human monkeypox in a central London centre during the 2022 outbreak: descriptive case series.

OBJECTIVE: To characterise the clinical features of monkeypox infection in humans. DESIGN: Descriptive case series. SETTING: A regional high consequences infectious disease centre with associated primary and secondary care referrals, and affiliated sexual health centres in south London between May and July 2022. PARTICIPANTS: 197 patients with polymerase chain reaction confirmed monkeypox infection. RESULTS: The median age of participants was 38 years. All 197 participants were men, and 196 identified as gay, bisexual, or other men who have sex with men. All presented with mucocutaneous lesions, most commonly on the genitals (n=111 participants, 56.3%) or in the perianal area (n=82, 41.6%). 170 (86.3%) participants reported systemic illness. The most common systemic symptoms were fever (n=122, 61.9%), lymphadenopathy (114, 57.9%), and myalgia (n=62, 31.5%). 102/166 (61.5%) developed systemic features before the onset of mucocutaneous manifestations and 64 (38.5%) after (n=4 unknown). 27 (13.7%) presented exclusively with mucocutaneous manifestations without systemic features. 71 (36.0%) reported rectal pain, 33 (16.8%) sore throat, and 31 (15.7%) penile oedema. 27 (13.7%) had oral lesions and 9 (4.6%) had tonsillar signs. 70/195 (35.9%) participants had concomitant HIV infection. 56 (31.5%) of those screened for sexually transmitted infections had a concomitant sexually transmitted infection. Overall, 20 (10.2%) participants were admitted to hospital for the management of symptoms, most commonly rectal pain and penile swelling. CONCLUSIONS: These findings confirm the ongoing unprecedented community transmission of monkeypox virus among gay, bisexual, and other men who have sex with men seen in the UK and many other non-endemic countries. A variable temporal association was observed between mucocutaneous and systemic features, suggesting a new clinical course to the disease. New clinical presentations of monkeypox infection were identified, including rectal pain and penile oedema. These presentations should be included in public health messaging to aid early diagnosis and reduce onward transmission.

The Long and the Short of it: Gene and Environment Interactions During Early Cortical Development and Consequences for Long-Term Neurological Disease.

Cortical development is a complex amalgamation of proliferation, migration, differentiation, and circuit formation. These processes follow defined timescales and are controlled by a combination of intrinsic and extrinsic factors. It is currently unclear how robust and flexible these processes are and whether the developing brain has the capacity to recover from disruptions. What is clear is that there are a number of cognitive disorders or conditions that are elicited as a result of disrupted cortical development, although it may take a long time for the full pathophysiology of the conditions to be realized clinically. The critical window for the manifestation of a neurodevelopmental disorder is prolonged, and there is the potential for a complex interplay between genes and environment. While there have been extended investigations into the genetic basis of a number of neurological and mental disorders, limited definitive associations have been discovered. Many environmental factors, including inflammation and stress, have been linked to neurodevelopmental disorders, and it may be that a better understanding of the interplay between genes and environment will speed progress in this field. In particular, the development of the brain needs to be considered in the context of the whole materno-fetal unit as the degree of the metabolic, endocrine, or inflammatory responses, for example, will greatly influence the environment in which the brain develops. This review will emphasize the importance of extending neurodevelopmental studies to the contribution of the placenta, vasculature, cerebrospinal fluid, and to maternal and fetal immune response. These combined investigations are more likely to reveal genetic and environmental factors that influence the different stages of neuronal development and potentially lead to the better understanding of the etiology of neurological and mental disorders such as autism, epilepsy, cerebral palsy, and schizophrenia.