Transmission dynamics of Monkeypox virus: a mathematical modelling approach

Monkeypox (MPX), similar to both smallpox and cowpox, is caused by the monkeypox virus (MPXV). It occurs mostly in remote Central and West African communities, close to tropical rain forests. It is caused by the monkeypox virus in the Poxviridae family, which belongs to the genus Orthopoxvirus. We develop and analyse a deterministic mathematical model for the monkeypox virus. Both local and global asymptotic stability conditions for disease-free and endemic equilibria are determined.
It is shown that the model undergo backward bifurcation, where the locally stable disease-free equilibrium co-exists with an endemic equilibrium. Furthermore, we determine conditions under which the disease-free equilibrium of the model is globally asymptotically stable. Finally, numerical simulations to demonstrate our findings and brief discussions are provided. The findings indicate that isolation of infected individuals in the human population helps to reduce disease transmission.

Monkeypox

Monkeypox virus was first isolated and identified in 1958 when monkeys shipped from Singapore to a Denmark research facility fell ill. However, the first confirmed human case was in 1970 when the virus was isolated from a child in the Democratic Republic of Congo suspected to have smallpox.
Coincident immunity to monkeypox virus was previously achieved with vaccinia vaccination; however, eradicating smallpox and subsequent lack of vaccination efforts paved the way for monkeypox to gain clinical relevance. Furthermore, because most cases of monkeypox occur in rural Africa, suspected underreporting may translate to an underestimation of the potential threat of this pathogen.

Family cluster of three cases of monkeypox imported from Nigeria to the United Kingdom

Most reported cases of human monkeypox occur in Central and West Africa, where the causing virus is endemic. We describe the identification and public health response to an imported case of West African monkeypox from Nigeria to the United Kingdom (UK) in May 2021. Secondary transmission from the index case occurred within the family to another adult and a toddler. Concurrent COVID-19-related control measures upon arrival and at the hospital, facilitated detection and limited the number of potential contacts.

Misinformation making a disease outbreak worse: outcomes compared for influenza, monkeypox, and norovirus

Health misinformation can exacerbate infectious disease outbreaks. Especially pernicious advice could be classified as “fake news”: manufactured with no respect for accuracy and often integrated with emotive or conspiracy-framed narratives. We built an agent-based model that simulated separate but linked circulating contagious disease and sharing of health advice (classified as useful or harmful). Such advice has potential to influence human risk-taking behavior and therefore the risk of acquiring infection, especially as people are more likely in observed social networks to share bad advice.
We test strategies proposed in the recent literature for countering misinformation. Reducing harmful advice from 50% to 40% of circulating information, or making at least 20% of the population unable to share or believe harmful advice, mitigated the influence of bad advice in the disease outbreak outcomes. How feasible it is to try to make people “immune” to misinformation or control the spread of harmful advice should be explored.

The genomic history of human monkeypox infections in the Central African Republic between 2001 and 2018

Monkeypox is an emerging infectious disease, which has a clinical presentation similar to smallpox. In the two past decades, Central Africa has seen an increase in the frequency of cases, with many monkeypox virus (MPXV) isolates detected in the Democratic Republic of Congo (DRC) and the Central African Republic (CAR). To date, no complete MPXV viral genome has been published from the human cases identified in the CAR. The objective of this study was to sequence the full genome of 10 MPXV isolates collected during the CAR epidemics between 2001 and 2018 in order to determine their phylogenetic relationships among MPXV lineages previously described in Central Africa and West Africa.
Our phylogenetic results indicate that the 10 CAR isolates belong to three lineages closely related to those found in DRC. The phylogenetic pattern shows that all of them emerged in the rainforest block of the Congo Basin. Since most human index cases in CAR occurred at the northern edge of western and eastern rainforests, transmissions from wild animals living in the rainforest is the most probable hypothesis.
In addition, molecular dating estimates suggest that periods of intense political instability resulting in population movements within the country often associated also with increased poverty may have led to more frequent contact with host wild animals. The CAR socio-economic situation, armed conflicts and ecological disturbances will likely incite populations to interact more and more with wild animals and thus increase the risk of zoonotic spillover.

Reemergence of Human Monkeypox and Declining Population Immunity in the Context of Urbanization

A monkeypox outbreak in Nigeria during 2017-2020 provides an illustrative case study for emerging zoonoses. We built a statistical model to simulate declining immunity from monkeypox at 2 levels: At the individual level, we used a constant rate of decline in immunity of 1.29% per year as smallpox vaccination rates fell. At the population level, the cohort of vaccinated residents decreased over time because of deaths and births. By 2016, only 10.1% of the total population in Nigeria was vaccinated against smallpox; the serologic immunity level was 25.7% among vaccinated persons and 2.6% in the overall population.
The substantial resurgence of monkeypox in Nigeria in 2017 appears to have been driven by a combination of population growth, accumulation of unvaccinated cohorts, and decline in smallpox vaccine immunity. The expanding unvaccinated population means that entire households, not just children, are now more susceptible to monkeypox, increasing risk of human-to-human transmission.

Pharmacokinetics and Efficacy of a Potential Smallpox Therapeutic, Brincidofovir, in a Lethal Monkeypox Virus Animal Model

Smallpox, caused by Variola virus (VARV), was eradicated in 1980; however, VARV bioterrorist threats still exist, necessitating readily available therapeutics. Current preparedness activities recognize the importance of oral antivirals and recommend therapeutics with different mechanisms of action. Monkeypox virus (MPXV) is closely related to VARV, causing a highly similar clinical human disease, and can be used as a surrogate for smallpox antiviral testing. The prairie dog MPXV model has been characterized and used to study the efficacy of antipoxvirus therapeutics, including recently approved TPOXX (tecovirimat). Brincidofovir (BCV; CMX001) has shown antiviral activity against double-stranded DNA viruses, including poxviruses.
To determine the exposure of BCV following oral administration to prairie dogs, a pharmacokinetics (PK) study was performed. Analysis of BCV plasma concentrations indicated variability, conceivably due to the outbred nature of the animals. To determine BCV efficacy in the MPXV prairie dog model, groups of animals were intranasally challenged with 9 × 105 plaque-forming units (PFU; 90% lethal dose [LD90]) of MPXV on inoculation day 0 (ID0). Animals were divided into groups based on the first day of BCV treatment relative to inoculation day (ID-1, ID0, or ID1). A trend in efficacy was noted dependent upon treatment initiation (57% on ID-1, 43% on ID0, and 29% on ID1) but was lower than demonstrated in other animal models. Analysis of the PK data indicated that BCV plasma exposure (maximum concentration [C max]) and the time of the last quantifiable concentration (AUClast) were lower than in other animal models administered the same doses, indicating that suboptimal BCV exposure may explain the lower protective effect on survival.

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Recombivirus Monkey Anti-monkeypox IgG ELISA kit, 96 tests, Quantitative

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Goat anti Monkey IgG

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Goat anti Monkey IgG + IgA + IgM (H + L) (biotin)

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Monkey Anti Alpha Fodrin IgG/IgA ELISA kit

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Goat anti Monkey IgG + IgA + IgM (H + L) (rhodamine)

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Goat anti Monkey IgG + IgA + IgM (H + L) (Texas Red)

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Goat Anti-Human IgG (Monkey Adsorbed), unlabeled

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Monkey Anti proteinase 3 antibody IgG ELISA kit

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IMPORTANCE Preparedness activities against highly transmissible viruses with high mortality rates have been highlighted during the ongoing coronavirus disease 2019 (COVID-19) pandemic. Smallpox, caused by variola virus (VARV) infection, is highly transmissible, with an estimated 30% mortality. Through an intensive vaccination campaign, smallpox was declared eradicated in 1980, and routine smallpox vaccination of individuals ceased. Today’s current population has little/no immunity against VARV. If smallpox were to reemerge, the worldwide results would be devastating.
Recent FDA approval of one smallpox antiviral (tecovirimat) was a successful step in biothreat preparedness; however, orthopoxviruses can become resistant to treatment, suggesting the need for multiple therapeutics. Our paper details the efficacy of the investigational smallpox drug brincidofovir in a monkeypox virus (MPXV) animal model. Since brincidofovir has not been tested in vivo against smallpox, studies with the related virus MPXV are critical in understanding whether it would be protective in the event of a smallpox outbreak.

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