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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.

ObjectiveTo describe outcomes within different ethnic groups of a cohort of hospitalised patients with confirmed COVID-19 infection. To quantify and describe the impact of a number of prognostic factors, including frailty and inflammatory markers.SettingFive acute National Health Service Hospitals in east London.DesignProspectively defined observational study using registry data.Participants1737 patients aged 16 years or over admitted to hospital with confirmed COVID-19 infection between 1 January and 13 May 2020.Main outcome measuresThe primary outcome was 30-day mortality from time of first hospital admission with COVID-19 diagnosis during or prior to admission. Secondary outcomes were 90-day mortality, intensive care unit (ICU) admission, ICU and hospital length of stay and type and duration of organ support. Multivariable survival analyses were adjusted for potential confounders.Results1737 were included in our analysis of whom 511 had died by day 30 (29%). 538 (31%) were from Asian, 340 (20%) black and 707 (40%) white backgrounds. Compared with white patients, those from minority ethnic backgrounds were younger, with differing comorbidity profiles and less frailty. Asian and black patients were more likely to be admitted to ICU and to receive invasive ventilation (OR 1.54, (95% CI 1.06 to 2.23); p=0.023 and OR 1.80 (95% CI 1.20 to 2.71); p=0.005, respectively). After adjustment for age and sex, patients from Asian (HR 1.49 (95% CI 1.19 to 1.86); p<0.001) and black (HR 1.30 (95% CI 1.02 to 1.65); p=0.036) backgrounds were more likely to die. These findings persisted across a range of risk factor-adjusted analyses accounting for major comorbidities, obesity, smoking, frailty and ABO blood group.ConclusionsPatients from Asian and black backgrounds had higher mortality from COVID-19 infection despite controlling for all previously identified confounders and frailty. Higher rates of invasive ventilation indicate greater acute disease severity. Our analyses suggest that patients of Asian and black backgrounds suffered disproportionate rates of premature death from COVID-19.

Since May, 2022, a large global outbreak of human mpox (formerly known as monkeypox) has predominantly affected men who have sex with men. The strain responsible, Clade IIb, has mutated substantially from precursors originating from the 2017–18 outbreak in Nigeria. Immunity to smallpox, another orthopoxvirus, via previous infection or vaccination provides lifelong immunity. However, since the 2022 mpox outbreak, recent clusters were described in individuals with presumed immunity through recent infection or vaccination. We aim to describe the epidemiological and clinical characteristics of mpox in individuals with past infection or vaccination to improve the understanding of this disease in the setting of previous immunity. In this global case series, international collaborators from nine countries provided data on individuals with PCR-confirmed mpox after documented previous infection or vaccination between May 11, 2022, and June 30, 2023. We excluded cases that could not confirm vaccination status or cases with partial immunisation or any doses received before the current multi-national mpox outbreak (cutoff date May 1, 2022). Data were collected via a case report spreadsheet that reported on dates of infection and vaccination, route of immunisation, demographic characteristics, clinical findings, HIV status, concomitant sexually transmitted infections, and markers of disease severity (mpox severity score system). We describe case epidemiology, clinical course, and mpox severity scores; all analyses were descriptive. We report mpox infections in 37 gay and bisexual men who have sex with men: seven individuals had mpox reinfections, 29 individuals had mpox infections that occurred after two appropriately spaced Modified Vaccinia Ankara-Bavarian Nordic vaccine courses, and one individual had an infection that met the criteria for both reinfection and infection after vaccination. The median age of individuals was 36 years (IQR 30–45; range 21–58). Those with natural immunity after initial infection had a shorter disease course with less mucosal disease upon reinfection than with their initial infection. Infections post-vaccination were characterised by few lesions, little mucosal disease, and minimal analgesia requirements; two people received oral tecovirimat. Overall, there were no deaths, no bacterial superinfections, and all individuals were managed in the ambulatory clinic with one hospital admission for a necrotising neck lesion. The epidemiology of people with mpox reinfection or infection post-vaccination was similar to other published cohorts during the 2022 outbreak—predominantly young, sexually active gay and bisexual men who have sex with men. Clinical features and outcomes of repeat infection and infection after vaccination appear to be less clinically severe than those described in 2022 case literature. Specifically, compared with the 2022 case series, these individuals in the present study had fewer confluent lesions, less mucosal involvement, reduced analgesia requirement, and fewer admissions. Natural immunity and vaccine-induced immunity are not fully protective against mpox infection. However, in this small series both disease duration and severity appear to be reduced. None.

Human mpox, caused by the mpox virus, is a reemerging viral zoonosis that has gained global attention due to recent Clade IIb outbreaks outside of Africa, as well as ongoing Clade Ia and Ib outbreaks in the Democratic Republic of Congo (DRC) and surrounding regions. Since the start of these outbreaks in 2022, approximately 160,000 people have been affected across more than 100 countries. People with human immunodeficiency virus (HIV; hereafter referred to as PWH) have been disproportionately affected, accounting for approximately 50% of all cases. Mpox is typically a self-limiting illness causing smallpox-like symptoms lasting 2–4 weeks, which can cause significant pain and morbidity. People with uncontrolled or advanced HIV face an elevated risk of severe mpox, secondary complications, and worse outcomes. Vaccination with second- and third-generation vaccinia-based smallpox vaccines has emerged as an important tool in mpox prevention, alongside behavioural modification to mitigate risk. However, only the third-generation, live-attenuated, non-replicating vaccine, modified vaccinia Ankara (MVA-BN [Bavarian Nordic]), is approved for use in PWH. Real-world estimates suggest that two doses of MVA-BN administered as pre-exposure prophylaxis confers vaccine effectiveness in the range of 66–90%. Additionally, MVA-BN has been widely demonstrated to have an acceptable safety profile. This narrative review explores the changing epidemiology, clinical manifestations, and outcomes of mpox in PWH. We also summarise evidence from the Clade IIb outbreaks on the effectiveness and safety of MVA-BN among PWH. Despite progress in our understanding, knowledge gaps persist regarding vaccine performance in individuals with advanced immunosuppression. Furthermore, due to the emergent nature of outbreaks in the DRC and surrounding areas, limited information is available regarding implications for PWH in the context of Clade Ia and Ib. We aim to provide healthcare providers, community stakeholders, and researchers with a foundational understanding of mpox in PWH and the role of MVA-BN in mpox prevention among this group, while highlighting areas of uncertainty. These insights may be helpful in the planning of future research and to inform strategies for the prevention and management of mpox among PWH, particularly those with advanced or uncontrolled HIV.

Mechanisms underlying sex differences in the development and prognosis of many diseases remain largely elusive. Here, we systematically investigated sex differences in the genetic regulation of plasma proteome (>5800 protein targets) across two cohorts (30,307 females; 26,058 males). Plasma levels of two-thirds of protein targets differ significantly by sex. In contrast, genetic effects on protein targets are remarkably similar across sexes, with only 103 sex-differential protein quantitative loci (sd-pQTLs; for 2.9% and 0.3% of protein targets from antibody- and aptamer-based platforms, respectively). A third of those show evidence of sexual discordance, i.e., effects observed in one sex only ( n  = 30) or opposite effect directions ( n  = 1 for CDH15). Phenome-wide analyses of 365 outcomes in UK Biobank did not provide evidence that the identified sd-pQTLs accounted for sex-differential disease risk. Our results demonstrate similarities in the genetic regulation of protein levels by sex with important implications for genetically-guided drug target discovery and validation. Analysing proteogenomic data from two large cohorts reveals that genetic regulation of the plasma proteome is highly similar between biological sexes, despite large differences in plasma abundance, with key implications for genetically guided drug discovery.

Simplified treatment regimens for HIV-1 may have advantages. In this open-label, randomized, controlled trial, patients with HIV-1 infection who had not previously received antiretroviral therapy were given oral induction therapy, then treated with either monthly injections of long-acting cabotegravir and rilpivirine or standard treatment. At 48 weeks, similar viral suppression was observed with the two regimens.

Background Tecovirimat, an antiviral treatment for smallpox, was approved as a treatment for mpox by the European Medicines Agency in January 2022. Approval was granted under “exceptional circumstances” based on effectiveness found in pre-clinical challenge studies in animals and safety studies in humans showing minimal side effects. As clinical efficacy studies are still ongoing, there is currently limited information with regard to the acceptability of tecovirimat to treat mpox. The aim of this study is to understand prospective acceptability of use of tecovirimat as treatment for mpox. Methods A co-produced, qualitative, focus group study design was conducted with a theoretically informed sample of people from communities at higher risk and with experience of mpox illness. Thirteen participants took part: all self-identified as cisgender male, 1 self-identified as Black British, 1 as British Asian, 5 as White, 3 as White British, 3 as White Other. Inclusion criteria were as follows: experience of mpox illness; age 18 and over; living in the United Kingdom (UK); living in the UK during 2022 mpox outbreak. Focus groups were recorded, transcribed and thematically analysed using a combination inductive and deductive coding informed by the Treatment Acceptability Framework. Results Very few participants were aware of tecovirimat as a treatment option and none were offered it during their mpox illness. Key factors influencing acceptability found in this study were as follows: levels of trust in medicine; level of information; provider communication approach; quality of experience of mpox care. Marginalised communities at highest risk of mpox may have prior experience of structural discrimination which can greatly influence treatment acceptability. Conclusions This exploratory study suggest that offering tecovirimat (or comparable emergency-licensed treatments) to people with mpox is acceptable, although uptake will depend on knowledge of mpox treatment options, trust in medicine and medical professionals and provision of relevant information and choice. To increase acceptability of such treatments, clinicians should ensure patients are aware of mpox symptom management options, including pain relief; acknowledge and address patient concerns upfront and within the context of non-stigmatising care; and communicate offers in a consistent and supportive manner in line with locally approved eligibility criteria and protocols at the time.

Background During the mpox outbreak in 2022-2023, inequities in vaccine access and uptake were highlighted in several countries. We present an intersectionality-informed, equity-focused approach to understand how the intersection of several characteristics, practices, and circumstances created unique and specific barriers to accessing the mpox vaccine in the UK. Methods The study was co-produced with community co-researchers. Between April and July 2023, semi-structured in-depth interviews and focus group discussions were conducted online with 35 UK-based people of diverse ethnicity, sexual identity and orientation with risk factors for mpox. Interviews and focus groups were audio-recorded and transcribed. Transcripts and codes were analysed applying an equity lens focused on understanding how the intersection of demographics, practices and circumstances might lead to exclusion from the mpox vaccination public health campaign. Combining data from all participants, we designed four composite fictional personas who correspond to representative profiles of people that found themselves at the margins of the UK mpox vaccination campaign. Results The thirty-five participants were diverse in terms of gender (28 cisgender men, 7 transgender or non-binary) and ethnicity (including White, Black, Asian, Latino/x and Arab individuals). We identified six circumstances leading to the exclusion of the UK mpox vaccination campaign: i) not being connected to sexual health services or community organisations and advocates; ii) feeling that the vaccine criteria are too restrictive; iii) lacking trust in institution, often because of structural racism; iv) experiencing feasibility barriers; v) living outside of London; vi) being in a relationship with someone with more risk factors. Our four fictional personas combine these circumstances and represent the characteristics of someone on the margins, either geographically or socially. Conclusion Our findings highlight the need to design more inclusive vaccine campaigns during evolving public health emergencies that consider how the intersection of stigma, characteristics, practices, and circumstances might lead to exclusion and inhibit vaccine uptake. Our persona approach further highlights the need to consider whether shared barriers to engagement (which can span multiple identities and positionalities) require tailored solutions. Guidelines should be co-designed with affected communities and include stigma-reduction interventions to ensure equitable provision and access to vaccine programmes.

ObjectivesRacially minoritised communities (RMCs) were disproportionately affected by COVID-19, experiencing among the highest mortality rates of the UK’s pandemic. We sought to understand the priorities for action to address the impact of the COVID-19 pandemic on the health and well-being of RMCs in the ethnically diverse and socioeconomically unequal area of East London, located in the northeastern part of London, England.DesignProspective surveys and a consensus meeting following the established James Lind Alliance priority setting partnership (PSP) methodology, adapted for a specific geographic location and ethnic groups.SettingConducted in East London between 2021 and 2023.ParticipantsParticipants were individuals aged ≥18 years living and/or working in East London. Communities represented included Black African, Black Caribbean, Somali, South Asian and Bangladeshi.Outcome measurePeople were asked to submit suggestions for the priorities for action to address the impact of the COVID-19 pandemic. Return responses were reviewed and prioritised in a final workshop.Results816 suggestions were gathered from 187 responses to the initial survey. These were summarised into a longlist of 40 for the second survey, from which 243 respondents identified a shortlist of 26 priorities for discussion in a consensus meeting. The final top 10 priorities cover community-based support and spaces spanning education, social support, mental health and housing.ConclusionA systematic methodology was used to identify the priorities of RMCs in East London in the context of recovery from the COVID-19 pandemic. The breadth of the top 10 reflects how profound the effects of the pandemic have been among these communities. It also demonstrates the capacity of a PSP to articulate diverse community-driven priorities for a topic that was wider than healthcare. The findings could have applications in other disease areas that disproportionately affect RMCs.

Between May and November, 2022, global outbreaks of human monkeypox virus infection have been reported in more than 78 000 people worldwide, predominantly in men who have sex with men. We describe the epidemiological and clinical characteristics of monkeypox virus infection in cisgender (cis) and transgender (trans) women and non-binary individuals assigned female sex at birth to improve identification and understanding of risk factors. International collaborators in geographical locations with high numbers of diagnoses of monkeypox virus infection were approached and invited to contribute data on women and non-binary individuals with confirmed monkeypox virus infection. Contributing centres completed deidentified structured case-report spreadsheets, adapted and developed by participating clinicians, to include variables of interest relevant to women and non-binary individuals assigned female at birth. We describe the epidemiology and clinical course observed in the reported infections. Collaborators reported data for a total of 136 individuals with monkeypox virus infection who presented between May 11 and Oct 4, 2022, across 15 countries. Overall median age was 34 years (IQR 28–40; range 19–84). The cohort comprised 62 trans women, 69 cis women, and five non-binary individuals (who were, because of small numbers, grouped with cis women to form a category of people assigned female at birth for the purpose of comparison). 121 (89%) of 136 individuals reported sex with men. 37 (27%) of all individuals were living with HIV, with a higher proportion among trans women (31 [50%] of 62) than among cis women and non-binary individuals (six [8%] of 74). Sexual transmission was suspected in 55 (89%) trans women (with the remainder having an unknown route of transmission) and 45 (61%) cis women and non-binary individuals; non-sexual routes of transmission (including household and occupational exposures) were reported only in cis women and non-binary individuals. 25 (34%) of 74 cis women and non-binary individuals submitted to the case series were initially misdiagnosed. Overall, among individuals with available data, rash was described in 124 (93%) of 134 individuals and described as anogenital in 95 (74%) of 129 and as vesiculopustular in 105 (87%) of 121. Median number of lesions was ten (IQR 5-24; range 1–200). Mucosal lesions involving the vagina, anus, or oropharynx or eye occurred in 65 (55%) of 119 individuals with available data. Vaginal and anal sex were associated with lesions at those sites. Monkeypox virus DNA was detected by PCR from vaginal swab samples in all 14 samples tested. 17 (13%) individuals were hospitalised, predominantly for bacterial superinfection of lesions and pain management. 33 (24%) individuals were treated with tecovirimat and six (4%) received post-exposure vaccinations. No deaths were reported. The clinical features of monkeypox in women and non-binary individuals were similar to those described in men, including the presence of anal and genital lesions with prominent mucosal involvement. Anatomically, anogenital lesions were reflective of sexual practices: vulvovaginal lesions predominated in cis women and non-binary individuals and anorectal features predominated in trans women. The prevalence of HIV co-infection in the cohort was high. None.