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Tecovirimat is available for the treatment of mpox (formerly known as monkeypox) in Europe and the United States, on the basis of findings from efficacy studies in animals and safety evaluations in healthy humans. Evidence from randomized, controlled trials of safety and efficacy in patients with mpox is lacking. We conducted a double-blind, randomized, placebo-controlled trial of tecovirimat in patients with mpox in the Democratic Republic of Congo (DRC). Patients with at least one mpox skin lesion and positive polymerase-chain-reaction results for clade I MPXV were assigned in a 1:1 ratio to receive tecovirimat or placebo. All patients received supportive care. The primary end point was resolution of mpox lesions, measured in number of days after randomization. Safety was also assessed. From October 7, 2022, through July 9, 2024, a total of 597 patients underwent randomization - 295 to receive tecovirimat and 302 to receive placebo. The median time from randomization to lesion resolution was 7 days with tecovirimat and 8 days with placebo; the competing-risks hazard ratio for lesion resolution was 1.13 (95% confidence interval [CI], 0.97 to 1.31; P = 0.14). Results were similar whether patients began the trial regimen within 7 days after the reported onset of symptoms (competing-risks hazard ratio, 1.16; 95% CI, 0.98 to 1.37) or more than 7 days after onset (competing-risks hazard ratio, 1.00; 95% CI, 0.71 to 1.40). Overall mortality was 1.7%, which was lower than the case fatality rate of 4.6% reported in the DRC in 2023. At 14 days, the percentages of patients who had blood, lesion, and oropharyngeal samples negative for MPXV by PCR were similar in the two groups. Adverse events occurred in 72.9% of the patients in the tecovirimat group and 70.5% of those in the placebo group, and serious adverse events were reported in 5.1% and 5.0%, respectively. Tecovirimat did not reduce the number of days to lesion resolution in patients with mpox caused by clade I MPXV. No safety concerns were identified. (Funded by the National Institute of Allergy and Infectious Diseases and others; PALM007 ClinicalTrials.gov number, NCT05559099.).

There are no FDA-approved antiviral agents to treat infection with variola virus, the cause of smallpox. In this report, the efficacy of tecovirimat, a new antiviral agent, is shown in monkey and rabbit models, with supporting human pharmacokinetic data.

Monkeypox, a zoonotic disease caused by an orthopoxvirus, results in a smallpox-like disease in humans. Since monkeypox in humans was initially diagnosed in 1970 in the Democratic Republic of the Congo (DRC), it has spread to other regions of Africa (primarily West and Central), and cases outside Africa have emerged in recent years. We conducted a systematic review of peer-reviewed and grey literature on how monkeypox epidemiology has evolved, with particular emphasis on the number of confirmed, probable, and/or possible cases, age at presentation, mortality, and geographical spread. The review is registered with PROSPERO (CRD42020208269). We identified 48 peer-reviewed articles and 18 grey literature sources for data extraction. The number of human monkeypox cases has been on the rise since the 1970s, with the most dramatic increases occurring in the DRC. The median age at presentation has increased from 4 (1970s) to 21 years (2010–2019). There was an overall case fatality rate of 8.7%, with a significant difference between clades—Central African 10.6% (95% CI: 8.4%– 13.3%) vs. West African 3.6% (95% CI: 1.7%– 6.8%). Since 2003, import- and travel-related spread outside of Africa has occasionally resulted in outbreaks. Interactions/activities with infected animals or individuals are risk behaviors associated with acquiring monkeypox. Our review shows an escalation of monkeypox cases, especially in the highly endemic DRC, a spread to other countries, and a growing median age from young children to young adults. These findings may be related to the cessation of smallpox vaccination, which provided some cross-protection against monkeypox, leading to increased human-to-human transmission. The appearance of outbreaks beyond Africa highlights the global relevance of the disease. Increased surveillance and detection of monkeypox cases are essential tools for understanding the continuously changing epidemiology of this resurging disease.

For decades after the identification of mpox in humans in the Democratic Republic of Congo (DRC) in 1970, the disease was largely confined to the rural areas of Central and West Africa and thus did not garner broad attention. On August 13, 2024, mpox was declared a Public Health Emergency of Continental Security (PHECS) by the Africa Centers for Disease Control and Prevention (Africa CDC), a notice that was followed the next day by a declaration of a Public Health Emergency of International Concern (PHEIC) by the World Health Organization. In this study we analyzed all mpox cases and deaths, based on clinical or laboratory diagnosis, that were reported to the Africa CDC from January 1, 2022, to October 30, 2024, to identify temporal variations, geographic distributions, and epidemiologic trends. From January 1, 2022, to August 18, 2024, a total of 45,652 mpox cases were clinically diagnosed and laboratory-confirmed in 12 African countries. These cases resulted in 1492 deaths (case fatality rate, 3.3%). From 2022 to 2024, weekly laboratory-confirmed mpox cases increased by a factor of 2.8 (from 176 to 489 cases), whereas all weekly reported cases (including those with a clinical diagnosis) increased by a factor of 4.3 (from 669 to 2900 cases). The DRC, which had reported approximately 88% of mpox cases in Africa in 2024, had 19,513 cases before the emergency declaration, with a case fatality rate of 3.1% - a weekly average of 591 cases as compared with 281 in 2023. In 2024, six African countries reported their first imported mpox infections, with Burundi also reporting local transmission. The high mpox disease burden in Africa, especially in the DRC - with a rising number of cases, high case fatality rate, and high degree of spread to other previously mpox-free African countries - is cause for increased international concern. Case detection, contact tracing, public health measures, and affordable vaccines are needed to implement interventions in the DRC to reduce the risk of global spread of the virus.

[...]ensuring equitable access to tests, treatments, and vaccines for all individuals, and focusing priorities in the epidemic area, are crucial for the public to prevent a global mpox epidemic. 2 Second, considering the poor availability of mpox vaccine, high mortality rates, and household transmission for children, it is recommended that family members seek medical care immediately and avoid contact with children if they have been in DR Congo or its neighboring countries in the last 21 days and develop suspected symptoms. 6 It is also necessary to avoid indirect contact with children (eg through contaminated clothing and furniture) to reduce the risk of household transmission. [...]environmental surveillance signals for early detection of clade I within nations might be useful. The low availability of point-of-care tests commonly means that the quick and early diagnosis of clade I mpox is potentially reliant on clinical information. 8 Precise clinical assessment tools (ie, visual assessment for lesions and robust biological indicators) to diagnose clade I and predict severe outcomes in the early stages are required to inform clinical, public health, and research priorities. 8 Last, but most importantly, in response to the aforementioned issues, international cooperation should be strengthened.

DR Congo has the highest global burden of mpox, a disease caused by infection with the monkeypox virus. The incidence has risen since 1980, but recent analyses of epidemiological trends are lacking. We aimed to describe trends in suspected and confirmed mpox cases in DR Congo using epidemiological and laboratory mpox surveillance data collected from 2010 to 2023, and provide insights that can better inform the targeting and monitoring of control strategies. We analysed aggregated national epidemiological surveillance data and individual-level laboratory data from 2010 to 2023. We calculated incidence based on suspected cases, case-fatality ratios, and percentage of laboratory-confirmed cases and assessed geospatial trends. Demographic and seasonal trends were investigated using generalised additive mixed models. Between Jan 1, 2010, and Dec 31, 2023, a total of 60 967 suspected cases and 1798 suspected deaths from mpox were reported in DR Congo (case-fatality ratio 2·9%). The number of reporting provinces increased from 18 of 26 provinces in 2010 to 24 of 26 provinces in 2023. The annual incidence increased from 2·97 per 100 000 in 2010 to 11·46 per 100 000 in 2023. The highest incidence (46·38 per 100 000) and case-fatality ratio (6·0%) were observed in children younger than 5 years. Incidence was higher in rural compared with urban areas. PCR testing was performed for 7438 suspected cases (12·2%), with 4248 (57·1%) of 7438 samples testing positive. Median age of confirmed cases (13·0 years [IQR 6·0–25·0]) remained stable, although the 95th percentile of age increased over time. The incidence and geographical distribution of suspected mpox cases have increased substantially since 2010. Improvements in surveillance and decentralised testing are essential to monitor mpox trends and direct interventions effectively, to address the public health emergency declarations issued in August, 2024. Belgian Directorate-General Development Cooperation and Humanitarian Aid; European and Developing Countries Clinical Trials Partnership; Research Foundation–Flanders; European Civil Protection and Humanitarian Aid Operations; Department of Economy, Science, and Innovation of the Flemish Government; Canadian Institutes of Health Research; and the International Development Research Centre.

Symptoms of severe disease differ from those seen during past outbreaks, causing researchers to re-evaluate their assumptions. Symptoms of severe disease differ from those seen during past outbreaks, causing researchers to re-evaluate their assumptions.

Monkeypox is a viral zoonotic disease on the rise across endemic habitats. Despite the growing importance of monkeypox virus, our knowledge on its host spectrum and sylvatic maintenance is limited. Here, we describe the recent repeated emergence of monkeypox virus in a wild, human-habituated western chimpanzee ( Pan troglodytes verus , hereafter chimpanzee) population from Taï National Park, Ivory Coast. Through daily monitoring, we show that further to causing its typical exanthematous syndrome, monkeypox can present itself as a severe respiratory disease without a diffuse rash. By analysing 949 non-invasively collected samples, we identify the circulation of at least two distinct monkeypox virus lineages and document the shedding of infectious particles in faeces and flies, suggesting that they could mediate indirect transmission. We also show that the carnivorous component of the Taï chimpanzees’ diet, mainly consisting of the sympatric monkeys they regularly hunt, did not change nor shift towards rodent consumption (the presumed reservoir) before the outbreaks, suggesting that the sudden emergence of monkeypox virus in this population is probably due to changes in the ecology of the virus itself. Using long-term mortality surveillance data from Taï National Park, we provide evidence of little to no prior viral activity over at least two decades. We conclude that great ape sentinel systems devoted to the longitudinal collection of behavioural and health data can help clarify the epidemiology and clinical presentation of zoonotic pathogens. Monkeypox is caused by an emerging zoonotic virus. This study describes a detailed investigation into monkeypox outbreaks in chimpanzees through non-invasive environmental sampling, virus genomics, pathology, behavioural ecology and dietary metabarcoding.

The authors have called for this form of mpox be added to the World Health Organization and US Center for Disease Control (CDC) lists of severe infections considered particularly dangerous to people with advanced HIV disease. WHO declared mpox a public health emergency of international concern in July 2022, and by the beginning of February 2023 more than 85 000 cases have been confirmed across 110 countries, with 93 deaths reported.2 While mpox cases are generally mild and people tend to recover within weeks, mortality varies depending on the type. Lead author Chloe Orkin, professor of HIV medicine at Queen Mary University of London and director of the Share Collaborative, said, “Currently, there is a list of 14 infections which behave differently and are particularly dangerous to immunosuppressed people with advanced HIV infection.

Background Limited data is available regarding the severity and mortality of Mpox in individuals with immunocompromised conditions. Therefore, we performed this meta-analysis to understand the impact of HIV- or non-HIV-associated immunosuppression on the severity of Mpox requiring hospitalization and mortality. Methods A thorough literature search was performed from 2022 up to January 2024. The results were presented as odds ratios (ORs). We only included patients who required hospitalization for severity rather than isolation. Results A total of 34 studies were included in this analysis. Our analysis did not find a significant difference in the hospitalization risk between HIV-positive individuals and those who were HIV-negative (OR = 1.03; P  = 0.85; 7 studies; CD4 count of fewer than 200 cells/µL was less than 0.5% across all studies). Patients with a CD4 count lower than 200 cells/µL or an unsuppressed RNA viral load (> 200 copies/ml) had a significantly higher hospitalization risk (OR = 5.3, P  < 0.001) and (OR = 3, P  < 0.001), respectively. Most of the reported deaths were reported in patients with HIV with CD4 counts below 200 cells/µL, with some fatal cases occurring in non-HIV immunosuppressed patients, particularly organ transplant recipients. Based on the autopsy findings, Mpox was confirmed in multiple organs, particularly the digestive tract, lung, and testes. Furthermore, some studies documented cases of death that were suspected to be related to hemophagocytic lymphohistiocytosis (HLH) and immune reconstitution inflammatory syndrome (IRIS). Most of the death reports showed concomitant non-Mpox infections at the time of hospitalization and death Conclusions Our finding shows that Mpox acts as an opportunistic pathogen in immunocompromised individuals. These individuals should be prioritized for early care and closely monitored for signs of deteriorating clinical conditions. Clinical manifestations and autopsy findings strongly suggest Mpox dissemination to multiple organs, particularly the digestive tract, and lungs. However, the presence of concomitant non-Mpox infections complicates the assessment of the attribution of Mpox to death. Caution should be exercised when interpreting data suggesting poorer outcomes in individuals with non-HIV immunosuppression, as current evidence is scarce and further research is needed.