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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 -
Cureus Jan 2023Monkeypox virus (MPOX) is a zoonotic disease in humans. It is similar genetically to its virus family member, smallpox. This virus has been studied since the 1970s. The... (Review)
Review
Monkeypox virus (MPOX) is a zoonotic disease in humans. It is similar genetically to its virus family member, smallpox. This virus has been studied since the 1970s. The virus remains endemic to the Congo and West African regions, but non-endemic spreads have been cited. The most recent non-endemic outbreak in the spring of 2022 amidst the current COVID-19 pandemic is of interest due to its impact on global medical, economic, and societal climates. This literature review aims to highlight the virology, clinical signs and symptoms, diagnosis, prevention, and treatment of MPOX and discuss the social implications of the recent 2022 outbreak. We hope this review can pinpoint important clinical pearls of the MPOX virus and its societal impacts to further promote important discussion of this virus and its disease.
PubMed: 36779102
DOI: 10.7759/cureus.33515 -
Vaccines Aug 2023Prevention of mpox has become an important public health interest. We aimed to evaluate the safety and immunogenicity of the Modified Vaccinia Ankara (MVA) vaccine. We... (Review)
Review
Prevention of mpox has become an important public health interest. We aimed to evaluate the safety and immunogenicity of the Modified Vaccinia Ankara (MVA) vaccine. We conducted a systematic review and meta-analysis of randomized-controlled trials (RCTs) comparing MVA versus no intervention, placebo, or another vaccine. Outcomes included safety and immunogenicity outcomes. We also performed a systematic review of RCTs evaluating various MVA regimens. Fifteen publications were included in the quantitative meta-analysis. All but one (ACAM2000) compared MVA with placebo. We found that cardiovascular adverse events following two MVA doses were significantly more common compared to placebo (relative risk [RR] 4.07, 95% confidence interval [CI] 1.10-15.10), though serious adverse events (SAEs) were not significantly different. Following a single MVA dose, no difference was demonstrated in any adverse event outcomes. Seroconversion rates were significantly higher compared with placebo after a single or two doses. None of the RCTs evaluated clinical effectiveness in preventing mpox. This meta-analysis provides reassuring results concerning the immunogenicity and safety of MVA. Further studies are needed to confirm the immunogenicity of a single dose and its clinical effectiveness. A single vaccine dose may be considered according to vaccine availability, with preference for two doses.
PubMed: 37766090
DOI: 10.3390/vaccines11091410 -
Cureus Sep 2023Human monkeypox virus (MPVX) infection represents an emerging zoonotic disease caused by an orthopoxvirus, resulting in a condition reminiscent of smallpox. More recent... (Review)
Review
Human monkeypox virus (MPVX) infection represents an emerging zoonotic disease caused by an orthopoxvirus, resulting in a condition reminiscent of smallpox. More recent developments have witnessed a notable surge in global MPVX outbreaks, eliciting significant concerns. We aimed to investigate the epidemiological factors of the emerging human monkeypox virus infection, including the number of suspected, confirmed, and fatal cases, as well as the risk factors for contracting monkeypox infection. We performed a systematic review of peer-reviewed literature by following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. An electronic database search (PubMed, Wiley Online Library, and Science Direct) was undertaken. For monkeypox-related studies, we included 25 peer-reviewed articles from 2018 and 2022, and data were extracted on the current evidence on the cases and the risk factors for MPVX infection, to develop public health advisories. Our reports show a rapid rise of MPVX cases in the highly endemic African regions after the 1970s, spread to other countries, and an increase in the median age from young children to young adults. The cessation of smallpox vaccination might have been one of the factors responsible for these findings. As of 2022, the genomic sequences of ten MPVX strains associated with the recent countrywide outbreak have been determined. While the West African Clade has been primarily implicated in the recent viral surge, data were insufficient to determine which mutation contributed to increased transmissibility. In the Democratic Republic of the Congo (DRC), sleeping on the floor was significantly associated with contracting MPVX, while eating or processing of animal foods was not a significant risk factor. In the United States, cleaning the cages and bedding of sick animals, touching infected animals, and daily exposure to sick animals were associated with an increased probability of contracting the MPVX infection. Recent global outbreaks and the rising incidence of MPVX infections among young adults in the endemic zones might be a result of the cessation of the smallpox vaccine. The increased risk associated with exposure to sick animals or sleeping on the floor suggests high infectivity from animal excretions. Increasing awareness, strict surveillance, and contact tracing can help contain global outbreaks. The ring vaccination approach for exposed individuals is another potential disease containment strategy. Future studies should investigate measures for rapid laboratory diagnosis, maintaining lab safety, and transmissibility.
PubMed: 37842498
DOI: 10.7759/cureus.45123 -
EClinicalMedicine Oct 2022Neuropsychiatric presentations of monkeypox (MPX) infection have not been well characterised, despite evidence of nervous system involvement associated with the related...
BACKGROUND
Neuropsychiatric presentations of monkeypox (MPX) infection have not been well characterised, despite evidence of nervous system involvement associated with the related smallpox infection.
METHODS
In this pre-registered (PROSPERO ID 336649) systematic review and meta-analysis, we searched MEDLINE, EMBASE, PsycINFO, AMED and the preprint server MedRxiv up to 31/05/2022. Any study design of humans infected with MPX that reported a neurological or psychiatric presentation was included. For eligible symptoms, we calculated a pooled prevalence using an inverse variance approach and corresponding 95% confidence intervals. The degree of variability that could be explained by between-study heterogeneity was assessed using the statistic. Risk of bias was assessed with the Newcastle Ottawa Scale and the Joanna Briggs Institute quality assessment tool.
FINDINGS
From 1705 unique studies, we extracted data on 19 eligible studies (1512 participants, 1031 with confirmed infection using CDC criteria or PCR testing) most of which were cohort studies and case series with no control groups. Study quality was generally moderate. Three clinical features were eligible for meta-analysis: seizure 2.7% (95% CI 0.7-10.2%, I 0%), confusion 2.4% (95% CI 1.1-5.2%, I 0%) and encephalitis 2.0% (95% 0.5-8.2%, I 55.8%). Other frequently reported symptoms included myalgia, headache and fatigue, where heterogeneity was too high for estimation of pooled prevalences, possibly as a result of differences in viral clades and study methodology.
INTERPRETATION
There is preliminary evidence for a range of neuropsychiatric presentations including severe neurological complications (encephalitis and seizure) and nonspecific neurological features (confusion, headache and myalgia). There is less evidence regarding the psychiatric presentations or sequelae of MPX. This may warrant surveillance within the current MPX outbreak, with prospective longitudinal studies evaluating the mid- to long-term sequelae of the virus. Robust methods to evaluate the potential causality of MPX with these clinical features are required. More evidence is necessary to explain heterogeneity in prevalence estimates.
FUNDING
UKRI/MRC (MR/V03605X/1), MRC-CSF (MR/V007181/1), MRC/AMED (MR/T028750/1) and the Wellcome Trust (102186/B/13/Z) and (102186/B/13/Z) and UCLH BRC.
PubMed: 36246957
DOI: 10.1016/j.eclinm.2022.101644 -
Orphanet Journal of Rare Diseases Aug 2021Osteomyelitis variolosa is a self-limiting disease triggered by variola virus that cannot be prevented or repaired. Smallpox has been eradicated for 40 years, and... (Review)
Review
BACKGROUND
Osteomyelitis variolosa is a self-limiting disease triggered by variola virus that cannot be prevented or repaired. Smallpox has been eradicated for 40 years, and complications that remain after smallpox has been cured have become a remarkable diagnostic challenge for contemporary physicians. In this systematic review, we searched PubMed (MEDLINE), Web of Science, and Google Scholar for cases on complications, diagnosis, and treatment for osteomyelitis variolosa between January 1980 and February 2021.
RESULTS
Ten papers and eleven finished cases, all patients from India, were included for comparison with the present case. In total, 100% of patients presented with bilateral elbow deformities, the ankle was the second most common site of lesion in 50%, and knee lesions accounted for 25% in this study. Flexion contracture, joint instability, secondary arthritis, and fracture are common complications of osteomyelitis variolosa, and most patients receive conservative treatment, while internal fixation has good results for combined fractures.
CONCLUSIONS
Although osteomyelitis variolosa is not a direct threat to the safety of patients, severe skeletal deformities can have a significant impact on quality of life. With advances in surgical techniques, clinicians are offering an increasing number of treatment options for patients with osteomyelitis variolosa. However, most importantly, smallpox has basically been removed from the historical arena, and for areas where smallpox was once endemic, physicians need to deepen the understanding of this disease again.
Topics: Humans; Joint Instability; Osteomyelitis; Quality of Life; Smallpox; Variola virus
PubMed: 34362412
DOI: 10.1186/s13023-021-01985-0 -
Iranian Journal of Microbiology Dec 2022The ongoing 2022 multicountry monkeypox epidemic has drawn worldwide attention. Human monkeypox is a virus that spreads from animals to humans. It is an endemic disease... (Review)
Review
The ongoing 2022 multicountry monkeypox epidemic has drawn worldwide attention. Human monkeypox is a virus that spreads from animals to humans. It is an endemic disease in the rain forests of Central and West Africa. However, the disease recently emerged in India, and also in United States through imported wild rodents from Africa, even though the world is still struggling to escape from the clutches of the COVID-19 pandemic. Monkeypox is one of the contagious zoonotic diseases caused by the monkeypox virus (MPXV), transmitted to humans by direct contact with an infected person or animal or contact with virus-contaminated material. Its lesions are similar to smallpox in humans with various medical complications including flu-like symptoms, fever, malaise, back pain, headache, and a characteristic rash. Public health experts around the world are very concerned about the rapid spread of the infection, which has intensified efforts to find the source and cause of this phenomenon. Several viral infections with epidemic potential threaten global health security. Early recognition of cases and timely intervention of potential transmission chains are necessary to contain further outbreaks. At this early stage of monkeypox outbreaks, the current review provides updated information on the current worldwide monkeypox outbreak status, disease aetiology, clinical presentation, therapy, and preventive measures worldwide. Our review will also provide useful information to health professionals and the general public.
PubMed: 36721435
DOI: 10.18502/ijm.v14i6.11252