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Viruses Nov 2022The outbreak of monkeypox, coupled with the onslaught of the COVID-19 pandemic is a critical communicable disease. This study aimed to systematically identify and review... (Review)
Review
The outbreak of monkeypox, coupled with the onslaught of the COVID-19 pandemic is a critical communicable disease. This study aimed to systematically identify and review research done on preclinical studies focusing on the potential monkeypox treatment and immunization. The presented juxtaposition of efficacy of potential treatments and vaccination that had been tested in preclinical trials could serve as a useful primer of monkeypox virus. The literature identified using key terms such as monkeypox virus or management or vaccine stringed using Boolean operators was systematically reviewed. Pubmed, SCOPUS, Cochrane, and preprint databases were used, and screening was performed in accordance with PRISMA guidelines. A total of 467 results from registered databases and 116 from grey literature databases were screened. Of these results, 72 studies from registered databases and three grey literature studies underwent full-text screening for eligibility. In this systematic review, a total of 27 articles were eligible according to the inclusion criteria and were used. Tecovirimat, known as TPOXX or ST-246, is an antiviral drug indicated for smallpox infection whereas brincidofovir inhibits the viral DNA polymerase after incorporation into viral DNA. The ability of tecovirimat in providing protection to poxvirus-challenged animals from death had been demonstrated in a number of animal studies. Non-inferior with regard to immunogenicity was reported for the live smallpox/monkeypox vaccine compared with a single dose of a licensed live smallpox vaccine. The trial involving the live vaccine showed a geometric mean titre of vaccinia-neutralizing antibodies post two weeks of the second dose of the live smallpox/monkeypox vaccine. Of note, up to the third generation of smallpox vaccines-particularly JYNNEOS and Lc16m8-have been developed as preventive measures for MPXV infection and these vaccines had been demonstrated to have improved safety compared to the earlier generations.
Topics: Animals; Humans; Mpox (monkeypox); Smallpox Vaccine; Smallpox; Pandemics; COVID-19; Monkeypox virus; Variola virus; Vaccinia virus; Vaccines, Attenuated; COVID-19 Drug Treatment
PubMed: 36423105
DOI: 10.3390/v14112496 -
Immunity, Inflammation and Disease Nov 2022The recent outbreak of Human Monkeypox (MPXV) in nonendemic regions of the world is of great concern.
BACKGROUND
The recent outbreak of Human Monkeypox (MPXV) in nonendemic regions of the world is of great concern.
OBJECTIVE
We aimed to systematically analyze the current epidemiology, clinical presentation, and outcomes of the Monkeypox virus.
METHOD
Systematic literature was conducted in PubMed, Embase, Google Scholar, and Scopus using predefined MESH terms by using "AND" and "OR." The following search terms were used: Monkeypox [MeSH] OR "Monkeypox virus" [MeSH] OR "POX" OR "Monkeypox" AND "Outbreak" AND "Outcomes" from December 2019 till 14th June 2022 without restrictions of language.
RESULTS
A total of 1074 (99.90%) patients tested positive for Monkeypox virus through RT-PCR while 1 (0.09) patient was suspected. There was a gender difference with male predominance (54.23% vs. 45.48%) compared with female patients. Mean age (±SD) of patients was 20.66 ± 16.45 years. The major symptoms were rash (100%), fever (96%), and other important symptoms were upper respiratory symptoms (97%), headache (95%), vomiting (95%), oral ulcers (96%), conjunctivitis (96%) and lymphadenopathy (85%). The average mean duration of treatment was 5 days, while the mean hospitalization duration was 13.3 ± 6.37 days. The outcome of 20 patients was available, 19 of 20 patients recovered fully from monkeypox, however, 1 patient was not able to survive resulting in death.
CONCLUSION
The recent monkeypox virus outbreak has shown that the virus could transmit in ways that were not previously expected. Further research is needed to understand the possible outcomes and association with humans and their different organ systems.
Topics: Adolescent; Adult; Child; Child, Preschool; Female; Humans; Male; Young Adult; COVID-19; Disease Outbreaks; Mpox (monkeypox); Monkeypox virus; Prognosis
PubMed: 36301040
DOI: 10.1002/iid3.722 -
Journal of Infection and Chemotherapy :... Feb 2023Since May 2022, many human monkeypox cases have been reported from non-endemic countries. This systematic review aimed to evaluate and summarize the existing research on...
Since May 2022, many human monkeypox cases have been reported from non-endemic countries. This systematic review aimed to evaluate and summarize the existing research on the efficacy and safety of tecovirimat, brincidofovir, and cidofovir for patients with monkeypox. We searched studies that reported the efficacy and adverse events of tecovirimat, brincidofovir, or cidofovir for patients with human monkeypox in several databases including preprint servers. Only five studies were included. The efficacy and adverse events were assessed in only five and four patients, respectively. Regarding tecovirimat, all two patients recovered from monkeypox. One had no adverse event and the other has no description of an adverse event. Regarding brincidofovir, all three patients recovered from monkeypox but all of them had increased alanine transaminase, and one had nausea and abdominal discomfort. There was no study on treatment with cidofovir. Based on past studies and our results, tecovirimat might be the best choice due to ease of administration (oral drug), fewer side effects, and past treatment results for human monkeypox administration. However, very few studies were included in this scoping review. Therefore, further studies are needed to assess their efficacy and safety as possible treatments for human monkeypox.
Topics: Humans; Mpox (monkeypox); Cidofovir; Antiviral Agents; Benzamides
PubMed: 36283609
DOI: 10.1016/j.jiac.2022.10.009 -
Tropical Medicine & International... Nov 2022On 7th May 2022, human monkeypox was identified in the United Kingdom, a non-endemic zone, with subsequent multi-country outbreaks. About 6 weeks later, the European... (Review)
Review
BACKGROUND
On 7th May 2022, human monkeypox was identified in the United Kingdom, a non-endemic zone, with subsequent multi-country outbreaks. About 6 weeks later, the European Centre for Disease Prevention and Control reported 1158 confirmed cases in non-endemic countries scattered within the European Economic Area (EEA), and a total of 1882 cases confirmed worldwide, inclusive of the EEA. These numbers are expected to increase with high alert and amplified surveillance established in non-endemic regions. In light of a looming epidemic, current understanding of the virus, and identification of gaps in the literature remain critical hence warranting a scoping review of available literature.
METHODS
Literature searches were performed through PubMed, SCOPUS, ScienceDirect and Hinari to identify studies eligible for inclusion in accordance with PRISMA guidelines.
RESULTS
Seventy-seven articles were included in the review. Majority of the cases were from the Central African clade (n = 29,905) versus the West African clade (n = 252). 6/16 articles that reported vaccination status stated that none of the cases were vaccinated. In the remaining articles, approximately 80%-96% cases were unvaccinated. It was noted that 4%-21% of the vaccinated individuals got infected. The secondary attack rate ranged from 0% to 10.2%, while the calculated pooled estimated case fatality rate was 8.7%.
CONCLUSION
This scoping review provides an extensive look at our current understanding on monkeypox disease. Further studies are needed to better understand its risk factors, genetics and natural history, in order for public health strategists to generate prevention strategies and management decisions.
Topics: Humans; Mpox (monkeypox); Monkeypox virus; Disease Outbreaks; Public Health; Epidemics
PubMed: 36229989
DOI: 10.1111/tmi.13821 -
Journal of Medical Virology Jan 2023Improved diagnostic tests and accessibility are essential for controlling the outbreak of monkeypox. We describe a saliva-based polymerase chain reaction (PCR) assay for...
Improved diagnostic tests and accessibility are essential for controlling the outbreak of monkeypox. We describe a saliva-based polymerase chain reaction (PCR) assay for monkeypox virus, in vitro test performance, and clinical implementation of that assay in Los Angeles, San Francisco, and Palm Springs, CA. Finally, using prespecified search terms, we conducted a systematic rapid review of PubMed and Web of Science online databases of studies reporting the performance of oral pharyngeal or saliva-based tests for the monkeypox virus. The assay showed in silico inclusivity of 100% for 97 strains of monkeypox virus, with an analytic sensitivity of 250 copies/ml, and 100% agreement compared to known positive and negative specimens. Clinical testing identified 22 cases of monkeypox among 132 individuals (16.7%), of which 16 (72.7%) reported symptoms, 4 (18.2%) without a rash at the time of testing. Of an additional 18 patients with positive lesion tests, 16 (88.9%) had positive saliva tests. Our systematic review identified six studies; 100% of tests on oropharyngeal specimens from 23 patients agreed with the PCR test result of a lesion. Saliva-based PCR tests are potential tools for case identification, and further evaluation of the performance of such tests is warranted.
Topics: Humans; Monkeypox virus; Mpox (monkeypox); Saliva; Polymerase Chain Reaction; Disease Outbreaks
PubMed: 36183189
DOI: 10.1002/jmv.28191 -
BMJ Global Health Aug 2022Monkeypox (MPX) is an important human Orthopoxvirus infection. There has been an increase in MPX cases and outbreaks in endemic and non-endemic regions in recent...
BACKGROUND
Monkeypox (MPX) is an important human Orthopoxvirus infection. There has been an increase in MPX cases and outbreaks in endemic and non-endemic regions in recent decades. We appraised the availability, scope, quality and inclusivity of clinical management guidelines for MPX globally.
METHODS
For this systematic review, we searched six databases from inception until 14 October 2021, augmented by a grey literature search until 17 May 2022. MPX guidelines providing treatment and supportive care recommendations were included, with no exclusions for language. Two reviewers assessed the guidelines. Quality was assessed using the Appraisal of Guidelines for Research and Evaluation II tool.
RESULTS
Of 2026 records screened, 14 guidelines were included. Overall, most guidelines were of low-quality with a median score of 2 out of 7 (range: 1-7), lacked detail and covered a narrow range of topics. Most guidelines focused on adults, five (36%) provided some advice for children, three (21%) for pregnant women and three (21%) for people living with HIV. Treatment guidance was mostly limited to advice on antivirals; seven guidelines advised cidofovir (four specified for severe MPX only); 29% (4/14) tecovirimat, and 7% (1/14) brincidofovir. Only one guideline provided recommendations on supportive care and treatment of complications. All guidelines recommended vaccination as post-exposure prophylaxis (PEP). Three guidelines advised on vaccinia immune globulin as PEP for severe cases in people with immunosuppression.
CONCLUSION
Our results highlight a lack of evidence-based clinical management guidelines for MPX globally. There is a clear and urgent need for research into treatment and prophylaxis including for different risk populations. The current outbreak provides an opportunity to accelerate this research through coordinated high-quality studies. New evidence should be incorporated into globally accessible guidelines, to benefit patient and epidemic outcomes. A 'living guideline' framework is recommended.
PROSPERO REGISTRATION NUMBER
CRD42020167361.
Topics: Adult; Antiviral Agents; Child; Databases, Factual; Disease Outbreaks; Female; Humans; Mpox (monkeypox); Pregnancy
PubMed: 35973747
DOI: 10.1136/bmjgh-2022-009838 -
Annals of Clinical Microbiology and... Aug 2022A multicountry monkeypox disease (MPX) outbreak began in May 2022 in Europe, leading to the assessment as a potential Public Health Emergency of International Concern... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
A multicountry monkeypox disease (MPX) outbreak began in May 2022 in Europe, leading to the assessment as a potential Public Health Emergency of International Concern (PHEIC) on June 23, 2022. Some observational studies have partially characterised clinical features, hospitalisations, and deaths. However, no systematic reviews of this MPX outbreak have been published.
METHODS
We performed a systematic review with meta-analysis, using five databases to assess clinical features, hospitalisations, complications and deaths of MPX confirmed or probable cases. Observational studies, case reports and case series, were included. We performed a random-effects model meta-analysis to calculate the pooled prevalence and 95% confidence interval (95% CI). In addition, we carried out a subgroup analysis according to the continents and a sensitivity analysis excluding studies classified as having a high risk of bias.
RESULTS
A total of 19 articles were included, using only 12 articles in the quantitative synthesis (meta-analysis). For 1958 patients, rash (93%, 95% CI 80-100%), fever (72%, 95% CI 30-99%), pruritus (65%, 95% CI 47-81%), and lymphadenopathy (62%, 47-76%), were the most prevalent manifestations. Among the patients, 35% (95% CI 14-59%) were hospitalised. Some 4% (95% CI 1-9%) of hospitalised patients had fatal outcomes (case fatality rate, CFR).
CONCLUSION
MPX is spreading rapidly, with a third of hospitalised patients, but less than 5% with fatal outcomes. As this zoonotic virus spreads globally, countries must urgently prepare human resources, infrastructure and facilities to treat patients according to the emerging guidelines and the most reliable clinical information.
Topics: Disease Outbreaks; Europe; Fever; Hospitalization; Humans; Mpox (monkeypox)
PubMed: 35948973
DOI: 10.1186/s12941-022-00527-1 -
PLoS Neglected Tropical Diseases Feb 2022Monkeypox, 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... (Meta-Analysis)
Meta-Analysis
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.
Topics: Adolescent; Adult; Child; Child, Preschool; Democratic Republic of the Congo; Female; History, 20th Century; History, 21st Century; Humans; Male; Mpox (monkeypox); Monkeypox virus; Travel-Related Illness; Young Adult
PubMed: 35148313
DOI: 10.1371/journal.pntd.0010141 -
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 -
BMC Public Health Dec 2020Previous initiatives have aimed to document the history and legacy of the Smallpox Eradication Program (SEP) and the Global Polio Eradication Initiative (GPEI). In this...
A multi-pronged scoping review approach to understanding the evolving implementation of the Smallpox and Polio eradication programs: what can other Global Health initiatives learn?
BACKGROUND
Previous initiatives have aimed to document the history and legacy of the Smallpox Eradication Program (SEP) and the Global Polio Eradication Initiative (GPEI). In this multi-pronged scoping review, we explored the evolution and learning from SEP and GPEI implementation over time at global and country levels to inform other global health programs.
METHODS
Three related reviews of literature were conducted; we searched for documents on 1) the SEP and 2) GPEI via online database searches and also conducted global and national-level grey literature searches for documents related to the GPEI in seven purposively selected countries under the Synthesis and Translation of Research and Innovations from Polio Eradication (STRIPE) project. We included documents relevant to GPEI implementation. We conducted full text data analysis and captured data on Expert Recommendations for Implementing Change (ERIC) implementation strategies and principles, tools, outcomes, target audiences, and relevance to global health knowledge areas.
RESULTS
200 articles were included in the SEP scoping review, 1885 articles in the GPEI scoping review, and 963 documents in the grey literature review. M&E and engagement strategies were consistently translated from the SEP to GPEI; these evolved into newer approaches under the GPEI. Management strategies including setting up robust record systems also carried forward from SEP to GPEI; however, lessons around the need for operational flexibility in applying these strategies at national and sub-national levels did not. Similarly, strategies and lessons around conducting health systems readiness assessments prior to implementation were not carried forward from SEP to GPEI. Differences in the planning and communication strategies between the two programs included fidelity to implementation blueprints appeared to be higher under SEP, and independent monitoring boards and communication and media strategies were more prominent under GPEI.
CONCLUSIONS
Linear learning did not always occur between SEP and GPEI; several lessons were lost and had to be re-learned. Implementation and adaptation of strategies in global health programs should be well codified, including information on the contextual, time and stakeholders' issues that elicit adaptations. Such description can improve the systematic translation of knowledge, and gains in efficiency and effectiveness of future global health programs.
Topics: Communication; Disease Eradication; Global Health; Health Education; Humans; Immunization Programs; Poliomyelitis; Smallpox
PubMed: 33339517
DOI: 10.1186/s12889-020-09439-1