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Frontiers in Public Health 2023Monkeypox (mpox), a zoonotic viral infection, poses a global threat that is being acknowledged at the national and international levels. This systematic review aims to...
BACKGROUND
Monkeypox (mpox), a zoonotic viral infection, poses a global threat that is being acknowledged at the national and international levels. This systematic review aims to identify and characterize interventional clinical trials for mpox.
METHOD
All interventional clinical trials registered at ClinicalTrials.gov for mpox were searched up to January 6, 2023. We described the characteristics of interventional clinical trials, and drug interventions (including drugs and vaccines).
RESULTS
As of January 6, 2023, there were 10 clinical trials in the ClinicalTrials.gov registry that met our criteria. Most of the interventional clinical trials were focused on the treatment ( = 4, 40%) and prevention ( = 4, 40%) of mpox. From the 10 trials, 50% used random treatment allocation, and six (60%) chose the parallel assignment intervention model. All 10 studies were blinded, and six were open-label blinded. The largest proportion of the clinical trials ( = 4, 40%) were registered in Europe, followed by America ( = 3, 30%) and Africa and others ( = 3, 30%). The JYNNEOS vaccine (40%), followed by Tecovirimat (30%) were the most frequently studied drugs used against mpox.
CONCLUSION
A limited number of clinical trials have been registered on ClinicalTrials.gov since the first case of mpox was reported. Therefore, there is an urgent need to conduct large-scale randomized clinical trials to assess the safety and efficacy of the drugs and vaccines being used against the mpox virus.
Topics: Humans; Mpox (monkeypox); Africa; Benzamides; Databases, Factual; Europe
PubMed: 36969617
DOI: 10.3389/fpubh.2023.1144325 -
The Cochrane Database of Systematic... Mar 2023Mpox was declared a Public Health Emergency of International Concern (PHEIC) by the World Health Organization (WHO) on 23 July 2022, following the identification of... (Review)
Review
BACKGROUND
Mpox was declared a Public Health Emergency of International Concern (PHEIC) by the World Health Organization (WHO) on 23 July 2022, following the identification of thousands of cases in several non-endemic countries in previous months. There are currently no licenced therapeutics for treating mpox; however, some medications may be authorized for use in an outbreak. The efficacy and safety of possible therapeutic options has not been studied in humans with mpox. There is a need to investigate the evidence on safety and effectiveness of treatments for mpox in humans; should any therapeutic option be efficacious and safe, it may be approved for use around the world.
OBJECTIVES
There are two parts to this Cochrane Review: a review of evidence from randomized controlled trials (RCTs), and a narrative review of safety data from non-randomized studies. Randomized controlled trials review To systematically review the existing evidence on the effectiveness of therapeutics for mpox infection in humans compared to: a) another different therapeutic for mpox, or b) placebo, or c) supportive care, defined as the treatment of physical and psychological symptoms arising from the disease. Non-randomized studies review To assess the safety of therapeutics for mpox infection from non-randomized studies (NRS).
SEARCH METHODS
Randomized controlled trials review We searched the following databases up to 25 January 2023: MEDLINE (OVID), Embase (OVID), Biosis previews (Web of Science), CAB Abstracts (Web of science), and Cochrane CENTRAL (Issue 1 2023). We conducted a search of trial registries (Clinicaltrials.gov and International Clinical Trials Registry Platform (ICTRP)) on 25 January 2023. There were no date or language limits placed on the search. We undertook a call to experts in the field for relevant studies or ongoing trials to be considered for inclusion in the review. Non-randomized studies review We searched the following databases on 22 September 2022: Cochrane Central Register of Controlled Trials (CENTRAL; Issue 9 of 12, 2022), published in the Cochrane Library; MEDLINE (Ovid); Embase (Ovid); and Scopus (Elsevier). We also searched the WHO International Clinical Trials Registry Platform and ClinicalTrials.gov for trials in progress.
SELECTION CRITERIA
For the RCT review and the narrative review, any therapeutic for the treatment of mpox in humans was eligible for inclusion, including tecovirimat, brincidofovir, cidofovir, NIOCH-14, immunomodulators, and vaccine immune globulin. Randomized controlled trials review Studies were eligible for the main review if they were of randomized controlled design and investigated the effectiveness or safety of therapeutics in human mpox infection. Non-randomized studies review Studies were eligible for inclusion in the review of non-randomized studies if they were of non-randomized design and contained data concerning the safety of any therapeutic in human mpox infection.
DATA COLLECTION AND ANALYSIS
Randomized controlled trials review Two review authors independently applied study inclusion criteria to identify eligible studies. If we had identified any eligible studies, we planned to assess the risk of bias, and report results with 95% confidence intervals (CI). The critical outcomes were serious adverse events, development of disease-related complications, admission to hospital for non-hospitalized participants, pain as judged by any visual or numerical pain scale, level of virus detected in clinical samples, time to healing of all skin lesions, and mortality. We planned to perform subgroup analysis to explore whether the effect of the therapeutic on the planned outcomes was modified by disease severity and days from symptom onset to therapeutic administration. We also intended to explore the following subgroups of absolute effects: immunosuppression, age, and pre-existing skin disease. Non-randomized studies review One review author applied study inclusion criteria to identify eligible studies and extracted data. Studies of a non-randomized design containing data on the safety of therapeutics could not be meta-analyzed due to the absence of a comparator; we summarized these data narratively in an appendix.
MAIN RESULTS
Randomized controlled trials review We did not identify any completed RCTs investigating the effectiveness of therapeutics for treating mpox for the main review. We identified five ongoing trials that plan to assess the effectiveness of one therapeutic option, tecovirimat, for treating mpox in adults and children. One of these ongoing trials intends to include populations with, or at greater risk of, severe disease, which will allow an assessment of safety in more vulnerable populations. Non-randomized studies review Three non-randomized studies met the inclusion criteria for the narrative review, concerning data on the safety of therapeutics in mpox. Very low-certainty evidence from non-randomized studies of small numbers of people indicates no serious safety signals emerging for the use of tecovirimat in people with mpox infection, but a possible safety signal for brincidofovir. All three participants who received brincidofovir had raised alanine aminotransferase (ALT), but not bilirubin, suggesting mild liver injury. No study reported severe drug-induced liver injury with brincidofovir.
AUTHORS' CONCLUSIONS
Randomized controlled trials review This review found no evidence from randomized controlled trials concerning the efficacy and safety of therapeutics in humans with mpox. Non-randomized studies review Very low-certainty evidence from non-randomized studies indicates no serious safety signals emerging for the use of tecovirimat in people with mpox infection. In contrast, very low-certainty evidence raises a safety signal that brincidofovir may cause liver injury. This is also suggested by indirect evidence from brincidofovir use in smallpox. This warrants further investigation and monitoring. This Cochrane Review will be updated as new evidence becomes available to assist policymakers, health professionals, and consumers in making appropriate decisions for the treatment of mpox.
Topics: Adult; Child; Humans; Mpox (monkeypox); Organophosphonates; Immunoglobulins
PubMed: 36916727
DOI: 10.1002/14651858.CD015769 -
Vaccine Apr 2023As the primary public health strategy for controlling the 2022 Mpox outbreak, it is critical to evaluate the impact of Mpox vaccination campaigns for transgender people...
Uptake of Mpox vaccination among transgender people and gay, bisexual and other men who have sex with men among sexually-transmitted infection clinic clients in Vancouver, British Columbia.
OBJECTIVES
As the primary public health strategy for controlling the 2022 Mpox outbreak, it is critical to evaluate the impact of Mpox vaccination campaigns for transgender people and gay, bisexual and other men who have sex with men (T/GBM). We measured vaccine uptake and associated factors among T/GBM clients of an urban STI clinic in British Columbia (BC).
METHODS
We conducted a cross-sectional online survey between August 8-22, 2022 of clients who had attended the STI clinic, 5-7 weeks following the first-dose Mpox vaccination campaign in BC. We drew on a systematic review of factors associated with vaccine uptake to develop survey questions, and measured vaccine uptake among vaccine-eligible T/GBM.
RESULTS
Overall, 51% of T/GBM had received the first dose of the vaccine. The sample (331 participants) was majority White and university educated, identified as a man and gay, 10% had trans experience, and 68% met eligibility criteria for vaccination. Among vaccine-eligible participants identifying as T/GBM, 66% had been vaccinated; being unvaccinated was more common among participants identifying as bisexual or heteroflexible/mostly straight, and who spent less time with other T/GBM. Eligible yet unvaccinated participants had lower perceived susceptibility, and reported fewer cues to action (e.g., fewer saw information promoting the vaccine), and increased constraints to vaccine access; vaccine barriers related to accessing clinics and privacy were common. The majority (85%) of those eligible and unvaccinated at time of survey were willing to receive the vaccine.
CONCLUSION
In this sample of STI clinic clients, vaccine uptake among eligible T/GBM was high in the initial weeks following a Mpox vaccination campaign. However, uptake was patterned on social gradients with lower uptake among T/GBM who may be less effectively engaged by available promotion channels. We recommend early, intentional and diverse engagement of T/GBM populations in Mpox and other targeted vaccination programs.
Topics: Male; Humans; Sexual and Gender Minorities; Homosexuality, Male; British Columbia; Smallpox Vaccine; Transgender Persons; Cross-Sectional Studies; Mpox (monkeypox); Vaccination; Sexually Transmitted Diseases; HIV Infections
PubMed: 36894397
DOI: 10.1016/j.vaccine.2023.02.075 -
International Journal of Environmental... Feb 2023According to the World Health Organization, 83,339 laboratory-confirmed cases, including 72 deaths, of mpox (formerly known as monkeypox), have been reported from 110... (Meta-Analysis)
Meta-Analysis Review
According to the World Health Organization, 83,339 laboratory-confirmed cases, including 72 deaths, of mpox (formerly known as monkeypox), have been reported from 110 locations globally as of 20 December 2022, making the disease a public health concern. Most of the cases (56,171, 67.4%) were reported from countries in North America. Limited data on vaccine effectiveness in the current mpox outbreak are available. However, the modified vaccinia virus (smallpox vaccine) has been predicted to prevent or reduce the severity of the mpox infection. The present study of systematic review and meta-analysis aimed to evaluate the modified vaccinia vaccine's safety and efficacy on mpox by using reported randomized clinical trials. Following guidelines from the Cochrane Collaboration and PRISMA, multiple databases including PubMed, PLOS ONE, Google Scholar, British Medical Journal, and the U. S. National Library of Medicine were searched. Out of 13,294 research articles initially identified, 187 were screened after removing duplicates. Following the inclusion and exclusion criteria, the meta-analysis included ten studies with 7430 patients. Three researchers independently assessed the risk of bias in the included study. The pooled results suggest that the vaccinia-exposed group had fewer side effects when compared to the vaccinia naïve group (odds ratio: 1.66; 95% CI: 1.07-2.57; = 0.03). Overall, the modified vaccinia has proven safe and effective in both vaccinia naïve and previously exposed groups, with higher efficacy in the previously exposed groups.
Topics: Humans; Smallpox Vaccine; Vaccinia; Mpox (monkeypox); Vaccinia virus; Laboratories; Smallpox
PubMed: 36833653
DOI: 10.3390/ijerph20042963 -
International Journal of Public Health 2023We aimed to evaluate global epidemiological features of human monkeypox (mpox) cases and their associations with social-economic level and international travel... (Review)
Review
Global Epidemiological Features of Human Monkeypox Cases and Their Associations With Social-Economic Level and International Travel Arrivals: A Systematic Review and Ecological Study.
We aimed to evaluate global epidemiological features of human monkeypox (mpox) cases and their associations with social-economic level and international travel arrivals. We estimated the pooled value by random-effects models. Then, we conducted an ecological study to evaluate the relationship of confirmed cases with social-economic indices and international travel arrivals using correlation analyses. The average age (2022: 35.52, 95% CI [28.09, 42.94] vs. before 2022: 18.38, 95% CI [14.74, 22.02]) and comorbidity rate (2022: 15.7%, 95% CI [8.9%, 22.4%] vs. before 2022: 14.9%, 95% CI [8.5%, 21.3%]) of mpox cases in the 2022 human mpox outbreak were significantly higher than those of cases before 2022. During the 2022 mpox outbreak, the proportion of men who have sex with men (MSM) was high (79.8%, 95% CI [65.5%, 94.2%]). The number of confirmed mpox cases in 2022 significantly correlated with high social-economic levels and international travel arrivals (all < 0.05). Our findings highlighted the importance of early surveillance and timely detection in high-risk populations, including older people, MSM, and travelers, which is crucial to curb the wide transmission of mpox.
Topics: Male; Humans; Aged; Homosexuality, Male; Mpox (monkeypox); Sexual and Gender Minorities; Disease Outbreaks
PubMed: 36743344
DOI: 10.3389/ijph.2023.1605426 -
The Journal of Infectious Diseases Aug 2023This study aims to comparatively analyze clinical features, treatment, and patient outcomes between the previous and the 2022 mpox (monkeypox) outbreaks. (Meta-Analysis)
Meta-Analysis
BACKGROUND
This study aims to comparatively analyze clinical features, treatment, and patient outcomes between the previous and the 2022 mpox (monkeypox) outbreaks.
METHODS
Five bibliographic databases were searched for studies reporting clinical features, management, and patient outcomes of mpox. Systematic review and meta-analysis were performed.
RESULTS
In total, 73 studies were included in the systematic review, of which 33 studies were subjected to meta-analysis. Previous outbreaks substantially affected children, whereas the 2022 outbreak primarily affected male adults, of which 94.66% (95% confidence interval [CI], 88.03-98.95) were men who have sex with men. Furthermore, 72.47% (95% CI, 51.04-89.71) reported high-risk sexual activity and the overall human immunodeficiency virus (HIV) prevalence was 37.65% (95% CI, 30.09-45.50). Skin lesions remain the typical symptom; however, their anatomic distribution differed. Systemic manifestations were common, but rectal pain was unique to the 2022 outbreak. The estimated overall fatality during past outbreaks in Africa was 4.61% (95% CI, 2.39%-7.35%), whereas 6.34% (95% CI, 3.35%-10.10%) of patients from the 2022 outbreak required hospitalization. Antiviral treatment, in particular tecovirimat, has been prescribed for a subset of patients, but the efficacy remains inconclusive.
CONCLUSIONS
These findings are important for better understanding the disease and guiding adequate response to mpox outbreaks.
Topics: Adult; Child; Humans; Male; Female; Homosexuality, Male; Mpox (monkeypox); Sexual and Gender Minorities; Antiviral Agents; Disease Outbreaks; Pelvic Pain
PubMed: 36735342
DOI: 10.1093/infdis/jiad034 -
Current Problems in Cardiology May 2023Monkeypox virus has emerged in different parts of the world with varying clinical symptoms and outcomes. To date, only a few studies have reported cardiac manifestations... (Review)
Review
Monkeypox virus has emerged in different parts of the world with varying clinical symptoms and outcomes. To date, only a few studies have reported cardiac manifestations among monkeypox-infected patients. We aim to systematically evaluate the symptoms, imaging findings, management, and outcomes among monkeypox-induced myocarditis patients. We conducted a systematic literature search in PubMed, Embase, and Scopus from inception till 5th January 2023 by using predefined MESH terms and "AND" and "OR." The following search terms were used: "monkeypox virus" AND "myocarditis." A total of 6 studies with 9 monkeypox-induced myocarditis patients were included in this analysis. The mean age of patients was 33.6 years, with all being male patients. The most common symptoms were fever (89%) and chest pain (100%). Electrocardiogram findings showed 44% of patients had ST-elevation, and 22% had sinus tachycardia. The echocardiographic findings show a mean ejection fraction of 52.14%, while 57% of patients had preserved ejection fraction, and 67% had normal wall motion. Cardiac magnetic resonance findings show 40% of patients had late gadolinium enhancement, and 40% had edema. Management of patients was primarily supportive (33%), and 33% of patients were administered Beta blockers and ACE inhibitors. Overall all patients survived with a good prognosis. Our study's findings show that all cases were reported among male patients with the most common symptoms of chest pain. The overall prognosis was good, with no mortality reported. Infected patients complaining of chest pain should not be ignored, and proper investigation of myocarditis must be considered.
Topics: Humans; Male; Adult; Female; Myocarditis; Contrast Media; Mpox (monkeypox); Gadolinium; Chest Pain
PubMed: 36716982
DOI: 10.1016/j.cpcardiol.2023.101611 -
F1000Research 2022Monkeypox has been declared as a Public Health Emergency of International Concern (PHEIC) by the WHO Director General (WHO-DG). Most of the G20 nations have reported...
Monkeypox has been declared as a Public Health Emergency of International Concern (PHEIC) by the WHO Director General (WHO-DG). Most of the G20 nations have reported Monkeypox outbreak. Policies developed and implemented in G20 countries for the prevention and control of monkeypox preparedness and response have global consequences. This rapid review aimed to map the monkeypox prevention and control policies planned and implemented in G20 nations in line with temporary recommendations issued by the WHO-DG. We mapped monkeypox prevention and control policies in G20 nations based on the WHO-DG recommendations. Medline (through PubMed), Scopus, and ProQuest Health and Medical Complete were searched to understand G20 preventative, diagnostic, and therapeutic policies. We also performed an extensive gray literature search through the Ministry of Health websites and newspaper through Google. The documents/ studies that had an information on prevention, control and management guidelines/policies and published through journal, news articles and health ministry websites of G20 nations on monkeypox were included. We excluded the editorials, opinion, and perspective papers and studies published prior to May 6, 2022. We obtained 671 articles with 10 articles included in the review. Additionally, we identified 55 documents from the gray literature. We included national guidelines of the 18 countries on the control, prevention, and management of monkeypox. National guidelines were compared with the WHO guidelines in terms of implementing coordinated response, engaging and protecting communities, surveillance and public health measures and international travel, clinical management and infection, prevention and control (IPC) measures and medical countermeasures research. Depending on the availability of resources, some recommendations are followed by nations while others are not. Coordinated response among states is key to contain the transmission of monkeypox. To bring a coordinated response, G20 nations are following temporary recommendations that are context specific to their nation.
Topics: Humans; Mpox (monkeypox); Policy; Public Health; Disease Outbreaks
PubMed: 36545374
DOI: 10.12688/f1000research.125893.1 -
Comparative Immunology, Microbiology... Jan 2023Monkeypox was designated as an emerging illness in 2018 by the World Health Organization Research and Development Blueprint, necessitating expedited research,...
BACKGROUND
Monkeypox was designated as an emerging illness in 2018 by the World Health Organization Research and Development Blueprint, necessitating expedited research, development, and public health action. In this review, we aim to shed the light on the imported cases of monkeypox in attempt to prevent the further spread of the disease. Methodology An electronic search in the relevant database (Web of Science, PubMed Medline, PubMed Central, Google scholar, and Embase) was conducted to identify eligible articles. In addition to searching the grey literature, manual searching was carried out using the reference chain approach.
RESULTS
A total of 1886 articles were retrieved using the search strategy with 21 studies included in the systematic review. A total of 113 cases of imported monkeypox were confirmed worldwide. Nineteen patients mentioned a travel history from Nigeria, thirty-eight infected cases had travel destinations from Europe, fifty-four cases traveled from European countries such as; Spain, France, and the Netherlands, one case from Portugal, and another one from the United Kingdom (UK). All reported clades of the virus were West African clade. Nine studies showed the source of infection was sexual contact, especially with male partners. Six studies mentioned the cause of infection was contact with an individual with monkeypox symptoms. Two studies considered cases due to acquired nosocomial infection. Ingestion of barbecued bushmeat was the source of infection in three studies and rodent carcasses were the source of infection in the other two studies.
CONCLUSION
The development of functioning surveillance systems and point-of-entry screening is essential for worldwide health security. This necessitates ongoing training of front-line health professionals to ensure that imported monkeypox is properly diagnosed and managed. In addition, implementing effective health communication about monkeypox prevention and control is mandatory to help individuals to make informed decisions to protect their own and their communities' health.
Topics: Animals; Male; Europe; Mpox (monkeypox); Nigeria; Public Health; Rodentia; Travel
PubMed: 36521366
DOI: 10.1016/j.cimid.2022.101923 -
International Journal of Infectious... Feb 2023Human monkeypox virus (MPXV) infection is a recently declared public health emergency of international concern by the World Health Organization. Besides, there is scant...
OBJECTIVES
Human monkeypox virus (MPXV) infection is a recently declared public health emergency of international concern by the World Health Organization. Besides, there is scant literature available on the use of antivirals in MPXV infection. This systematic review compiles all evidence of various antivirals used on their efficacy and safety and summarizes their mechanisms of action.
METHODS
A review was done of all original studies mentioning individual patient data on the use of antivirals in patients with MPXV infection.
RESULTS
Of the total 487 non-duplicate studies, 18 studies with 71 individuals were included. Tecovirimat was used in 61 individuals, followed by cidofovir in seven and brincidofovir (BCV) in three individuals. Topical trifluridine was used in four ophthalmic cases in addition to tecovirimat. Of the total, 59 (83.1%) were reported to have complete resolution of symptoms; one was experiencing waxing and waning of symptoms, only one (1.8%) had died, and the others were having a resolution of symptoms. The death was thought unrelated to tecovirimat. Elevated hepatic panels were reported among all individuals treated with BCV (leading to treatment discontinuation) and five treated with tecovirimat.
CONCLUSION
Tecovirimat is the most used and has proven beneficial in several aggravating cases. No major safety concerns were detected upon its use. Topical trifluridine was used as an adjuvant treatment option along with tecovirimat. BCV and cidofovir were seldom used, with the latter often being used due to the unavailability of tecovirimat. BCV was associated with treatment discontinuation due to adverse events.
Topics: Humans; Antiviral Agents; Benzamides; Cidofovir; Disease Outbreaks; Isoindoles; Mpox (monkeypox); Monkeypox virus; Trifluridine
PubMed: 36470502
DOI: 10.1016/j.ijid.2022.11.040