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BMJ Global Health Nov 2023Recent outbreaks of mpox are characterised by changes in the natural history of the disease, the demographic and clinical characteristics of the cases, and widening...
INTRODUCTION
Recent outbreaks of mpox are characterised by changes in the natural history of the disease, the demographic and clinical characteristics of the cases, and widening geographical distribution. We investigated the role of HIV and other sexually transmitted infections (STIs) coinfection among cases in the re-emergence of mpox to inform national and global response.
METHODS
We conducted a national descriptive and case-control study on cases in the 2017-2019 Nigerian mpox outbreak. Mpox cases were age, sex and geographical area matched each with two randomly selected controls from a representative national HIV/AIDS survey. Logistic regression was used to investigate the association between HIV infection and the risk of mpox acquisition and death.
RESULTS
Among 204 suspected mpox cases, 86 were confirmed (median age 31 years (IQR 27-38 years), mostly males (61 cases, 70.9%). Three-fifths of mpox cases had serological evidence of one or more STIs with 27.9% (24/86) coinfected with HIV. The case fatality rate was 9.4% (8/86) and 20.8% (5/24) overall and in HIV positive cases respectively. Mpox cases were more likely to have HIV coinfection compared with an age, gender and geography-matched control group drawn from the general population (OR 45 (95% CI 6.1 to 333.5, p=0.002) and when compared with non mpox rash cases (7.29 (95% CI 2.6 to 20.5, p<0.0001)). HIV coinfection and young age were associated with mortality among mpox cases (aOR 13.66 (95% CI 1.88 to 98.95, p=0.010) and aOR 0.90 (0.82-0.97, p=0.008), respectively).
CONCLUSION
HIV infection was associated with a higher risk of contracting and dying from mpox. Children are also at high risk of death. STIs in mpox cases may be suggestive of high-risk sexual behaviours among these individuals.
Topics: Adult; Female; Humans; Male; Case-Control Studies; Coinfection; HIV Infections; Mpox (monkeypox); Nigeria
PubMed: 38035733
DOI: 10.1136/bmjgh-2023-013126 -
The Lancet. Infectious Diseases Sep 2023In response to a national mpox (formerly known as monkeypox) outbreak in England, children exposed to a confirmed mpox case were offered modified vaccinia Ankara-Bavaria...
Early evaluation of the safety, reactogenicity, and immune response after a single dose of modified vaccinia Ankara-Bavaria Nordic vaccine against mpox in children: a national outbreak response.
BACKGROUND
In response to a national mpox (formerly known as monkeypox) outbreak in England, children exposed to a confirmed mpox case were offered modified vaccinia Ankara-Bavaria Nordic (MVA-BN), a third-generation smallpox vaccine, for post-exposure prophylaxis. We aimed to assess the safety and reactogenicity and humoral and cellular immune response, following the first reported use of MVA-BN in children.
METHODS
This is an assessment of children receiving MVA-BN for post-exposure prophylaxis in response to a national mpox outbreak in England. All children receiving MVA-BN were asked to complete a post-vaccination questionnaire online and provide a blood sample 1 month and 3 months after vaccination. Outcome measures for the questionnaire included reactogenicity and adverse events after vaccination. Blood samples were tested for humoural, cellular, and cytokine responses and compared with unvaccinated paediatric controls who had never been exposed to mpox.
FINDINGS
Between June 1 and Nov 30, 2022, 87 children had one MVA-BN dose and none developed any serious adverse events or developed mpox disease after vaccination. Post-vaccination reactogenicity questionnaires were completed by 45 (52%) of 87 children. Their median age was 5 years (IQR 5-9), 25 (56%) of 45 were male, and 22 (49%) of 45 were White. 16 (36%) reported no symptoms, 18 (40%) reported local reaction only, and 11 (24%) reported systemic symptoms with or without local reactions. Seven (8%) of 87 children provided a first blood sample a median of 6 weeks (IQR 6·0-6·5) after vaccination and five (6%) provided a second blood sample at a median of 15 weeks (14-15). All children had poxvirus IgG antibodies with titres well above the assay cutoff of OD 0·1926 with mean absorbances of 1·380 at six weeks and 0·9826 at 15 weeks post-vaccination. Assessment of reactivity to 27 recombinant vaccina virus and monkeypox virus proteins showed humoral antigen recognition, primarily to monkeypox virus antigens B6, B2, and vaccina virus antigen B5, with waning of humoral responses observed between the two timepoints. All children had a robust T-cell response to whole modified vaccinia Ankara virus and a select pool of conserved pan-Poxviridae peptides. A balanced CD4 and CD8 T-cell response was evident at 6 weeks, which was retained at 15 weeks after vaccination.
INTERPRETATION
A single dose of MVA-BN for post-exposure prophylaxis was well-tolerated in children and induced robust antibody and cellular immune responses up to 15 weeks after vaccination. Larger studies are needed to fully assess the safety, immunogenicity, and effectiveness of MVA-BN in children. Our findings, however, support its on-going use to prevent mpox in children as part of an emergency public health response.
FUNDING
UK Health Security Agency.
Topics: Humans; Male; Child; Child, Preschool; Female; Vaccinia; Mpox (monkeypox); Vaccinia virus; Smallpox Vaccine; Immunity, Cellular; Antigens, Viral; Disease Outbreaks; Antibodies, Viral
PubMed: 37336224
DOI: 10.1016/S1473-3099(23)00270-0 -
Virulence Dec 2023
Topics: Humans; Mpox (monkeypox); Measles; Vaccination; Immunity, Herd
PubMed: 36602152
DOI: 10.1080/21505594.2022.2154424 -
Medicine Sep 2023The last few decades have witnessed an appalling rise in several emerging and re-emerging viral and zoonotic outbreaks. Amongst those emerging zoonosis, one of the...
BACKGROUND
The last few decades have witnessed an appalling rise in several emerging and re-emerging viral and zoonotic outbreaks. Amongst those emerging zoonosis, one of the diseases which is gaining popularity these days and has been declared as public health emergency of international concern by the world health organization, is human monkeypox virus (HMPX). Proper understanding of the clinical spectrum of the disease is of paramount importance for early diagnosis and treatment. In this review, we aimed to study and quantify the neurological manifestations of HMPX virus infection.
METHODS
Any study, released prior to April 13, 2023, that reported neurological manifestations in patients infected by HMPX virus were reviewed systematically on PubMed, Scopus, Google Scholar, and Cochrane Library using the PRISMA (Preferred Reporting Items for Systematic review and Meta-Analysis) statement.
RESULTS
Our systematic review included data from 22 eligible studies: 10 cohort studies, 3 cross sectional studies, one retrospective study, 5 case series, and 2 case reports. The most commonly reported neurological manifestations of HMPX were headache (48.84%), myalgia (27.50%), fatigue (17.73%), and photophobia (4.43%). Uncommonly, HMPX can also present with visual deficit (0.57%), seizure (0.34%), encephalitis (0.8%), dizziness (0.34%), encephalomyelitis (0.23%), coma (0.11%), and transverse myelitis (0.11%).
DISCUSSIONS
Monkeypox virus usually presents with self-limiting painful rash, lymphadenitis, and fever, complications like secondary skin infection, eye problems and pneumonia can be life threatening, carrying a case fatality rate of 1% to 10%. Neurological manifestations are not uncommon and can further add-on to morbidity and mortality.
Topics: Humans; Coinfection; Cross-Sectional Studies; Mpox (monkeypox); Monkeypox virus; Public Health; Retrospective Studies
PubMed: 37657009
DOI: 10.1097/MD.0000000000034664 -
BMC Veterinary Research Oct 2023Sheep and goat pox (SGP) caused by sheep poxvirus (SPV) and goat poxvirus (GPV) respectively; are transboundary and World Organisation for Animal Health...
BACKGROUND
Sheep and goat pox (SGP) caused by sheep poxvirus (SPV) and goat poxvirus (GPV) respectively; are transboundary and World Organisation for Animal Health (WOAH)-notifiable viral diseases. There is barely any coherent information about the distribution and prevalence of SGP for Uganda. We therefore conducted this study to describe the temporal and spatial distribution of SGP suspected outbreaks in Uganda for the period 2011-2020 as well as serologically confirm presence of SGP antibodies in suspected SGP outbreaks reported in 2021-2022.
RESULTS
Thirty-seven [37] SGP outbreaks were reported across the country during the study period. North-eastern region [that comprises of Karamoja region] had the highest number of outbreaks [n = 17, 45%]; followed by Central [n = 9, 2.4%], Northern [n = 8, 2.2%] and Western region [n = 3, 0.08%]. Reports from district veterinary personnel indicate that the prevalence of; and mortality rate and case fatality rate associated with SGP were 0.06%, 0.02% and 32% respectively. There was a steady increase in the number of reported SGP outbreaks [x̄ = 4] over the study period. Seropositivity of SGPV antibodies in outbreak sheep and goats that were investigated during the study period [2021-2022] was [n = 41, 27%, 95 CI;] CONCLUSION: Our analyses of SGPV passive and active reports indicate that SGP is present in Uganda with a decade long average of four outbreaks per annum. During this period, about a third of all SGPV-clinically infected animals died. SPG is therefore a major constraint to small ruminant health and productivity in Uganda. Introduction of animals from infected herds and breach in farm biosecurity were the most important predictors of SGP outbreaks. In addition to the already existing SGP commercial vaccines, small ruminant screening for SGPV before introducing them to naïve herds and ensuring on farm biosecurity should be part of the SGP control tool pack for Ugandan small ruminant farmers.
Topics: Sheep; Animals; Uganda; Goat Diseases; Sheep Diseases; Poxviridae Infections; Capripoxvirus; Goats; Disease Outbreaks; Spatio-Temporal Analysis
PubMed: 37891597
DOI: 10.1186/s12917-023-03788-w -
Annals of Internal Medicine Aug 2023
Topics: Humans; Virus Shedding; Mpox (monkeypox); Antiviral Agents; Immunocompromised Host; Benzamides
PubMed: 37487213
DOI: 10.7326/L23-0131 -
Clinical Infectious Diseases : An... Nov 2023
Topics: Humans; Monkeypox virus; Mpox (monkeypox); Smallpox Vaccine; Vaccinia virus; Antibodies, Neutralizing
PubMed: 37417243
DOI: 10.1093/cid/ciad414 -
Travel Medicine and Infectious Disease 2023Monkeypox (Mpox) is a transmissible infection induced by the Monkeypox virus (a double-stranded DNA virus), recognised under the family orthopoxvirus genus. Monkeypox,... (Review)
Review
Monkeypox (Mpox) is a transmissible infection induced by the Monkeypox virus (a double-stranded DNA virus), recognised under the family orthopoxvirus genus. Monkeypox, like endemic diseases, is a substantial concern worldwide; thus, comprehending the pathogenesis and mutagenesis of amino acids is indispensable to combat the infection. According to the World Health Organization's report, about 89 thousand cases with 160 mortalities have been reported from 114 countries worldwide. The conventional orthopoxvirus vaccines developed on live attenuated viruses exempted any clinical validation from combating monkeypox due to inadequate immunogenicity, toxicity, instability, and multiple doses. Therefore, novel drug delivery systems come into the conception with high biological and mechanical characteristics to address the resurgence of Global Monkeypox. The edges of metallic biomaterials, novel molecules, and vaccine development in targeted therapy increase the modulation of the immune response and blockage of host-virus interaction, with enhanced stability for the antigens. Thus, this review strives to comprehend the viral cell pathogenesis concerning amino acid mutagenesis and current epidemiological standards of the Monkeypox disease across the globe. Furthermore, the review also recapitulates the various clinical challenges, current therapies, and progressive nanomedicine utilisation in the Monkeypox outbreak reinforced by various clinical trial reports. The contemporary challenges of novel drug delivery systems in Monkeypox treatment cannot be overlooked, and thus, authors have outlined the future strategies to develop successful nanomedicine to combat monkeypox. Future pandemics are inevitable but can be satisfactorily handled if we comprehend the crises, innovate, and develop cutting-edge technologies, especially by delving into frontiers like nanotechnology.
Topics: Humans; Mpox (monkeypox); Disease Outbreaks; Drug Delivery Systems; Endemic Diseases; Monkeypox virus; Orthopoxvirus
PubMed: 37633474
DOI: 10.1016/j.tmaid.2023.102636 -
MBio Feb 2024Vaccinia virus assembly in the cytoplasm of infected cells involves the formation of a biconcave viral core inside the maturing viral particle. The boundary of the core...
Vaccinia virus assembly in the cytoplasm of infected cells involves the formation of a biconcave viral core inside the maturing viral particle. The boundary of the core is defined by a pseudohexagonal palisade layer, composed of trimers projecting from an inner wall. To understand the assembly of this complex core architecture, we obtained a subnanometer structure of the palisade trimer by cryo-electron tomography and subtomogram averaging of purified intact virions. Using AlphaFold2 structure predictions, we determined that the palisade is formed from trimers of the proteolytically processed form of the viral protein A10. In addition, we found that each A10 protomer associates with an α-helix (residues 24-66) of A4. Cellular localization assays outside the context of infection demonstrate that the A4 N-terminus is necessary and sufficient to interact with A10. The interaction between A4 and A10 provides insights into how the palisade layer might become tightly associated with the viral membrane during virion maturation. Reconstruction of the palisade layer reveals that, despite local hexagonal ordering, the A10/A4 trimers are widely spaced, suggesting that additional components organize the lattice. This spacing would, however, allow the adoption of the characteristic biconcave shape of the viral core. Finally, we also found that the palisade incorporates multiple copies of a hexameric portal structure. We suggest that these portals are formed by E6, a viral protein that is essential for virion assembly and required to release viral mRNA from the core early in infection.IMPORTANCEPoxviruses such as variola virus (smallpox) and monkeypox cause diseases in humans. Other poxviruses, including vaccinia and modified vaccinia Ankara, are used as vaccine vectors. Given their importance, a greater structural understanding of poxvirus virions is needed. We now performed cryo-electron tomography of purified intact vaccinia virions to study the structure of the palisade, a protein lattice that defines the viral core boundary. We identified the main viral proteins that form the palisade and their interaction surfaces and provided new insights into the organization of the viral core.
Topics: Humans; Vaccinia virus; Vaccinia; Virus Assembly; Virion; Viral Proteins; Piperidones; Benzeneacetamides
PubMed: 38171004
DOI: 10.1128/mbio.03134-23 -
Cell Mar 2024The World Health Organization declared mpox a public health emergency of international concern in July 2022. To investigate global mpox transmission and population-level...
The World Health Organization declared mpox a public health emergency of international concern in July 2022. To investigate global mpox transmission and population-level changes associated with controlling spread, we built phylogeographic and phylodynamic models to analyze MPXV genomes from five global regions together with air traffic and epidemiological data. Our models reveal community transmission prior to detection, changes in case reporting throughout the epidemic, and a large degree of transmission heterogeneity. We find that viral introductions played a limited role in prolonging spread after initial dissemination, suggesting that travel bans would have had only a minor impact. We find that mpox transmission in North America began declining before more than 10% of high-risk individuals in the USA had vaccine-induced immunity. Our findings highlight the importance of broader routine specimen screening surveillance for emerging infectious diseases and of joint integration of genomic and epidemiological information for early outbreak control.
Topics: Humans; Communicable Diseases, Emerging; Disease Outbreaks; Epidemics; Mpox (monkeypox); Public Health; Monkeypox virus
PubMed: 38428425
DOI: 10.1016/j.cell.2024.02.003