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Nature Communications May 2024The Modified Vaccinia Ankara vaccine developed by Bavarian Nordic (MVA-BN) was widely deployed to prevent mpox during the 2022 global outbreak. This vaccine was... (Meta-Analysis)
Meta-Analysis
The Modified Vaccinia Ankara vaccine developed by Bavarian Nordic (MVA-BN) was widely deployed to prevent mpox during the 2022 global outbreak. This vaccine was initially approved for mpox based on its reported immunogenicity (from phase I/II trials) and effectiveness in animal models, rather than evidence of clinical efficacy. However, no validated correlate of protection after vaccination has been identified. Here we performed a systematic search and meta-analysis of the available data to test whether vaccinia-binding ELISA endpoint titer is predictive of vaccine effectiveness against mpox. We observe a significant correlation between vaccine effectiveness and vaccinia-binding antibody titers, consistent with the existing assumption that antibody levels may be a correlate of protection. Combining this data with analysis of antibody kinetics after vaccination, we predict the durability of protection after vaccination and the impact of dose spacing. We find that delaying the second dose of MVA-BN vaccination will provide more durable protection and may be optimal in an outbreak with limited vaccine stock. Although further work is required to validate this correlate, this study provides a quantitative evidence-based approach for using antibody measurements to predict the effectiveness of mpox vaccination.
Topics: Animals; Humans; Antibodies, Viral; Enzyme-Linked Immunosorbent Assay; Smallpox Vaccine; Vaccination; Vaccine Efficacy; Vaccinia; Monkeypox virus
PubMed: 38719852
DOI: 10.1038/s41467-024-48180-w -
The Lancet. Global Health Apr 2024Although mpox has been detected in paediatric populations in central and west Africa for decades, evidence synthesis on paediatric, maternal, and congenital mpox, and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Although mpox has been detected in paediatric populations in central and west Africa for decades, evidence synthesis on paediatric, maternal, and congenital mpox, and the use of vaccines and therapeutics in these groups, is lacking. A systematic review is therefore indicated to set the research agenda.
METHODS
We conducted a systematic review and meta-analysis, searching articles in Embase, Global Health, MEDLINE, CINAHL, Web of Science, Scopus, SciELO, and WHO databases from inception to April 17, 2023. We included studies reporting primary data on at least one case of confirmed, suspected, or probable paediatric, maternal, or congenital mpox in humans or the use of third-generation smallpox or mpox vaccines, targeted antivirals, or immune therapies in at least one case in our population of interest. We included clinical trials and observational studies in humans and excluded reviews, commentaries, and grey literature. A pooled estimate of the paediatric case fatality ratio was obtained using random-effects meta-analysis. This study is registered with PROSPERO (CRD420223336648).
FINDINGS
Of the 61 studies, 53 reported paediatric outcomes (n=2123 cases), seven reported maternal or congenital outcomes (n=32 cases), two reported vaccine safety (n=28 recipients), and three reported transmission during breastfeeding (n=4 cases). While a subset of seven observational studies (21 children and 12 pregnant individuals) reported uneventful treatment with tecovirimat, there were no randomised trials reporting safety or efficacy for any therapeutic agent. Among children, the commonest clinical features included rash (86 [100%] of 86), fever (63 [73%] of 86), and lymphadenopathy (40 [47%] of 86). Among pregnant individuals, rash was reported in 23 (100%) of 23; fever and lymphadenopathy were less common (six [26%] and three [13%] of 23, respectively). Most paediatric complications (12 [60%] of 20) arose from secondary bacterial infections. The pooled paediatric case fatality ratio was 11% (95% CI 4-20), I=75%. Data from 12 pregnancies showed half resulted in fetal death. Research on vaccine and immune globulin safety remains scarce for children and absent for pregnant individuals.
INTERPRETATION
Our review highlights critical knowledge gaps in the epidemiology, prevention, and treatment of mpox in children and pregnant individuals, especially those residing in endemic countries. Increased funding, international collaboration, and equitable research is needed to inform mpox control strategies tailored for at-risk communities in endemic countries.
FUNDING
None.
TRANSLATIONS
For the French, Spanish and Portuguese translations of the abstract see Supplementary Materials section.
Topics: Female; Pregnancy; Child; Humans; Mpox (monkeypox); Family; Exanthema; Lymphadenopathy; Vaccines
PubMed: 38401556
DOI: 10.1016/S2214-109X(23)00607-1 -
BMJ Open Gastroenterology Jan 2024Mpox is a viral infection caused by the monkeypox virus, a member of the Poxviridae family and Orthopoxvirus genus. Other well-known viruses of the Orthopoxvirus genus...
INTRODUCTION
Mpox is a viral infection caused by the monkeypox virus, a member of the Poxviridae family and Orthopoxvirus genus. Other well-known viruses of the Orthopoxvirus genus include the variola virus (smallpox), cowpox virus and vaccinia virus. Although there is a plethora of research regarding the dermatological and influenza-like symptoms of mpox, particularly following the 2022 mpox outbreak, more research is needed on the gastrointestinal (GI) effects.
OBJECTIVES
This systematic review is to outline the GI manifestations of the monkeypox virus.
METHODS
The authors conducted this systematic review using guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. A search was conducted through the PubMed, EMBASE and MEDLINE databases from January 1958 to June 2023. The authors selected English language papers that discussed the GI symptoms in mpox patients. A manual search was also conducted in the reference sections of these publications for other relevant papers.
RESULTS
33 papers involving 830 patients were selected for this review. The GI manifestations in mpox patients are proctitis, vomiting, diarrhoea, rectal pain, nausea, tenesmus, rectal bleeding and abdominal pain. Although various papers explored transmission routes, one paper established a direct connection between anal-receptive sex transmission route and the development of a GI complication (proctitis). Another study reported that the mode of transmission could potentially impact the occurrence of GI symptoms and severity of the disease. The reviewed papers did not discover a relation between the severity of dermatological and influenza-like symptoms and the GI manifestations mentioned.
CONCLUSION
This systematic review confirms that GI manifestations are observed in mpox patients. GI symptoms of mpox are crucial for gastroenterologists and other healthcare professionals to recognise in order to address patient discomfort and further understand the pathophysiology of the virus.
Topics: Humans; Gastrointestinal Hemorrhage; Mpox (monkeypox); Proctitis; Vomiting
PubMed: 38184298
DOI: 10.1136/bmjgast-2023-001266 -
Journal of Microbiology, Immunology,... Feb 2024Monkeypox is a viral zoonotic disease rarely found outside Africa. Monkeypox can be spread from person to person through close contact with an infected person, and the... (Review)
Review
Monkeypox is a viral zoonotic disease rarely found outside Africa. Monkeypox can be spread from person to person through close contact with an infected person, and the rate of transmission is not very high. In addition, monkeypox and variola virus are both pox viruses, and the spread of monkeypox virus was also controlled to some extent by the smallpox campaign, so monkeypox was not widely paid attention to. However, as smallpox vaccination is phased out in various countries or regions, people's resistance to orthopoxviruses is decreasing, especially among people who have not been vaccinated against smallpox. This has led to a significant increase in the frequency and geographical distribution of human monkeypox cases in recent years, and the monkeypox virus has become the orthopoxvirus that poses the greatest threat to public health. Since the last large-scale monkeypox infection was detected in 2022, the number of countries or territories affected has exceeded 100. Many confirmed and suspected cases of monkeypox have been found in individuals who have not travelled to affected areas, and the route of infection is not obvious, making this outbreak of monkeypox a cause for concern globally. The purpose of this systematic review is to further understand the pathophysiological and epidemiological characteristics of monkeypox, as well as existing prevention and treatment methods, with a view to providing evidence for the control of monkeypox.
Topics: Humans; Mpox (monkeypox); Smallpox; Monkeypox virus; Disease Outbreaks; Public Health
PubMed: 38177001
DOI: 10.1016/j.jmii.2023.12.006 -
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 -
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 -
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 -
Diagnostics (Basel, Switzerland) Feb 2023Monkeypox or Mpox is an infectious virus predominantly found in Africa. It has spread to many countries since its latest outbreak. Symptoms such as headaches, chills,... (Review)
Review
Monkeypox or Mpox is an infectious virus predominantly found in Africa. It has spread to many countries since its latest outbreak. Symptoms such as headaches, chills, and fever are observed in humans. Lumps and rashes also appear on the skin (similar to smallpox, measles, and chickenpox). Many artificial intelligence (AI) models have been developed for accurate and early diagnosis. In this work, we systematically reviewed recent studies that used AI for mpox-related research. After a literature search, 34 studies fulfilling prespecified criteria were selected with the following subject categories: diagnostic testing of mpox, epidemiological modeling of mpox infection spread, drug and vaccine discovery, and media risk management. In the beginning, mpox detection using AI and various modalities was described. Other applications of ML and DL in mitigating mpox were categorized later. The various machine and deep learning algorithms used in the studies and their performance were discussed. We believe that a state-of-the-art review will be a valuable resource for researchers and data scientists in developing measures to counter the mpox virus and its spread.
PubMed: 36899968
DOI: 10.3390/diagnostics13050824 -
Vaccines Jan 2023The most recent monkeypox (Mpox) outbreak is mostly affecting men who have sex with men (MSM) who participate in high-risk sexual behaviors, which is typically the case... (Review)
Review
The most recent monkeypox (Mpox) outbreak is mostly affecting men who have sex with men (MSM) who participate in high-risk sexual behaviors, which is typically the case among human immunodeficiency virus (HIV) carriers, according to clinical and epidemiological statistics. The objective of this research is to determine the epidemiological situation of HIV and smallpox co-infection. Until 1 October 2022, a thorough evaluation of the literature was conducted utilizing the databases PubMed, Embase, Scopus, and Web of Science. Studies were evaluated based on the criteria for selection. Fifty-three studies met the selection criteria. A total of 6345 confirmed cases of monkeypox were recorded, and 40.32% ( = 2558) of these cases also had HIV co-infection. In addition, 51.36% ( = 3259) of the men (91.44%; = 5802), whose ages ranged from 18 to 71 years, exhibited MSM-specific sexual behaviors. Co-infection with these two viruses can be especially dangerous because it can exacerbate the symptoms of both diseases and make them more difficult to treat. People with HIV are more vulnerable to certain infections, including monkeypox, because their immune systems are weakened. Therefore, it is important that they take measures to prevent infection, such as avoiding contact with infected animals, risky behaviors, and maintaining good hygiene.
PubMed: 36851124
DOI: 10.3390/vaccines11020246 -
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