Epidemiologic Quantities for Monkeypox Virus Clade I from Historical Data with Implications for Current Outbreaks, Democratic Republic of the Congo.

We used published data from outbreak investigations of monkeypox virus clade I in the Democratic Republic of the Congo to estimate the distributions of critical epidemiological parameters. We estimated a mean incubation period of 9.9 days (95% credible interval [CrI] 8.5-11.5 days) and a mean generation time of 17.2 days (95% CrI 14.1-20.9 days) or 11.3 days (95% CrI 9.4-14.0 days), depending on the considered dataset. Presymptomatic transmission was limited. Those estimates suggest generally slower transmission dynamics in clade I than in clade IIb. The time-varying reproduction number for clade I in the Democratic Republic of the Congo was estimated to be below the epidemic threshold in the first half of 2024. However, in the South Kivu Province, where the newly identified subclade Ib has been associated with sustained human-to-human transmission, we estimated an effective reproduction number above the epidemic threshold (95% CrI 0.96-1.27).

Editorial: Reasons for Increasing Global Concerns for the Spread of Mpox.

On August 14, 2024, the Director General of the World Health Organization (WHO) declared that the increasing outbreaks of mpox (formerly monkeypox) should be regarded as an international public health emergency due to the growing number of cases in endemic and non-endemic geographical areas, and increasing disease severity. The latest update from the WHO and the alerts given regarding the status of mpox follows an upsurge in the incidence and severity of mpox in the Democratic Republic of the Congo (DRC) and an increasing number of African countries, with spread to other continents and countries This Editorial aims to provide an update on the current status of mpox and includes reasons for the increasing global concerns for the spread of the mpox virus (MPXV).

One Health Investigation into Mpox and Pets, United States.

Monkeypox virus (MPXV) is zoonotic and capable of infecting many mammal species. However, whether common companion animals are susceptible to MPXV infection is unclear. During July 2022-March 2023, we collected animal and environmental swab samples within homes of confirmed human mpox case-patients and tested for MPXV and human DNA by PCR. We also used ELISA for orthopoxvirus antibody detection. Overall, 12% (22/191) of animal and 25% (14/56) of environmental swab samples from 4 households, including samples from 4 dogs and 1 cat, were positive for MPXV DNA, but we did not detect viable MPXV or orthopoxvirus antibodies. Among MPXV PCR-positive swab samples, 82% from animals and 93% from environment amplified human DNA with a statistically significant correlation in observed cycle threshold values. Our findings demonstrate likely DNA contamination from the human mpox cases. Despite the high likelihood for exposure, we found no indications that companion animals were infected with MPXV.

Presumed Transmission of 2 Distinct Monkeypox Virus Variants from Central African Republic to Democratic Republic of the Congo.

We linked 4 mpox cases in South Ubangi, Democratic Republic of the Congo, to transboundary transmission from Central African Republic. Viral genome sequencing demonstrated that the monkeypox virus sequences belonged to distinct clusters of subclade Ia. This finding demonstrates the borderless nature of mpox and highlights the need for vigilant regional surveillance.

As Mpox Cases Surge in Africa, WHO Declares a Global Emergency-Here's What to Know.

This Medical News article discusses the World Health Organization's emergency declaration related to an mpox outbreak in Africa and the emergence of a new virus strain spread by sexual contact.

Role of Direct Sexual Contact in Human Transmission of Monkeypox Virus, Italy.

The 2022 global mpox outbreak was driven by human-to-human transmission, but modes of transmission by sexual relationship versus sexual contact remain unclear. We evaluated sexual transmission of mpox by using monkeypox virus (MPXV) G2R-mRNA as a marker of ongoing viral replication through in vitro experiments. We analyzed clinical samples of 15 MPXV-positive patients in Italy from different biological regions by using the setup method. The presence of MPXV DNA, MPXV G2R-mRNA, or both in all analyzed lesion swab samples, independent of viral load, confirmed a higher infectivity risk from skin lesions. Positivity for MPXV G2R-mRNA in nasopharyngeal swabs was associated with high MPXV load, whereas positive results for MPXV G2R-mRNA were obtained only in the 2 semen samples with the lowest MPXV loads. Our results suggest that close or skin-to-skin contact during sexual intercourse is the main route of sexual transmission and that semen is a minor driver of infection, regardless of MPXV load.

Estimating the relative importance of epidemiological and behavioural parameters for epidemic mpox transmission: a modelling study.

BACKGROUND: Many European countries experienced outbreaks of mpox in 2022, and there was an mpox outbreak in 2023 in the Democratic Republic of Congo. There were many apparent differences between these outbreaks and previous outbreaks of mpox; the recent outbreaks were observed in men who have sex with men after sexual encounters at common events, whereas earlier outbreaks were observed in a wider population with no identifiable link to sexual contacts. These apparent differences meant that data from previous outbreaks could not reliably be used to parametrise infectious disease models during the 2022 and 2023 mpox outbreaks, and modelling efforts were hampered by uncertainty around key transmission and immunity parameters. METHODS: We developed a stochastic, discrete-time metapopulation model for mpox that allowed for sexual and non-sexual transmission and the implementation of non-pharmaceutical interventions, specifically contact tracing and pre- and post-exposure vaccinations. We calibrated the model to case data from Berlin and used Sobol sensitivity analysis to identify parameters that mpox transmission is especially sensitive to. We also briefly analysed the sensitivity of the effectiveness of non-pharmaceutical interventions to various efficacy parameters. RESULTS: We found that variance in the transmission probabilities due to both sexual and non-sexual transmission had a large effect on mpox transmission in the model, as did the level of immunity to mpox conferred by a previous smallpox vaccination. Furthermore, variance in the number of pre-exposure vaccinations offered was the dominant contributor to variance in mpox dynamics in men who have sex with men. If pre-exposure vaccinations were not available, both the accuracy and timeliness of contact tracing had a large impact on mpox transmission in the model. CONCLUSIONS: Our results are valuable for guiding epidemiological studies for parameter ascertainment and identifying key factors for success of non-pharmaceutical interventions.

Global Mpox spread due to increased air travel.

Mpox is an emerging, infectious disease that has caused outbreaks in at least 91 countries from May to August 2022. We assessed the link between international air travel patterns and Mpox transmission risk, and the relationship between the translocation of Mpox and human mobility dynamics after travel restrictions due to the COVID-19 pandemic had been lifted. Our three novel observations were that: i) more people traveled internationally after the removal of travel restrictions in the summer of 2022 compared to pre-pandemic levels; ii) countries with a high concentration of global air travel have the most recorded Mpox cases; and iii) Mpox transmission includes a number of previously nonendemic regions. These results suggest that international airports should be a primary location for monitoring the risk of emerging communicable diseases. Findings highlight the need for global collaboration concerning proactive measures emphasizing realtime surveillance.

No evidence of mpox virus circulation in putative animal reservoirs in Gabon wildlife.

OBJECTIVES: Mpox is a neglected viral endemic tropical disease in Central and Western African countries transmitted to humans by an animal. However, the natural reservoir of the virus remains elusive. In this study, we looked for potential reservoirs of the mpox virus (MPXV) in Gabonese wildlife to prevent future outbreaks and enrich the literature with additional data on animal reservoirs. METHODS: DNA was extracted from the livers and spleens from 2549 animals (bats [859], bushmeats [356], rodents [1309], and shrews [25]) collected between 2012 and 2021. DNA was analyzed by real-time and conventional polymerase chain reaction, targeting the 14 kD protein and the rpo subunit RNA polymerase of orthopoxviruses. RESULTS: No MPXV DNA was detected despite the presence of potential host reservoirs such as Critcetomys, Crocidura, Praomys, and Atherurus africanus. This absence could be due to (i) the low number of animals collected for some species, (ii) the acute nature of mpox infection but also (iii) the lack of the potential reservoir Funisciurus anerythrus among collected animals, and (iv) the fact that the samplings are not included in the probable ecological niche of MPXV. CONCLUSION: Longitudinal studies including potential ecological niches of F. anerythrus and MPXV in Gabon may be useful to get more information on MPXV circulation.

Monkeypox: Past, Present, and Future.

Monkeypox (Mpox) is a zoonotic disease caused by a virus (monkeypox virus-MPV) belonging to the Poxviridae family. In humans, the disease has an incubation period of 5-21 days and then progresses in two phases, the prodromal phase and the rash phase. The prodromal phase is characterized by non-specific symptoms such as fever, muscle pain, malaise, lymphadenopathy, headache, and chills. Skin lesions appear in the rash phase of the disease. These lesions progress through different stages (macules, papules, vesicles, and pustules). In May 2022, WHO reported an outbreak of human Mpox in several countries which were previously Mpox-free. As per the CDC report of March 01, 2023, a total of 86,231 confirmed cases of Mpox and 105 deaths have been reported from 110 countries and territories across the globe. Notably, more than 90% of these countries were reporting Mpox for the first time. The phylogenetic analysis revealed that this outbreak was associated with the virus from the West African clade. However, most of the cases in this outbreak had no evidence of travel histories to MPV-endemic countries in Central or West Africa. This outbreak was primarily driven by the transmission of the virus via intimate contact in men who have sex with men (MSM). The changing epidemiology of Mpox raised concerns about the increasing spread of the disease in non-endemic countries and the urgent need to control and prevent it. In this chapter, we present all the documented cases of Mpox from 1970 to 2023 and discuss the past, present, and future of MPV.

Zoonotic and Zooanthroponotic Potential of Monkeypox.

The current multicounty outbreak of monkeypox virus (MPXV) posed an emerging and continued challenge to already strained public healthcare sector, around the globe. Since its first identification, monkeypox disease (mpox) remained enzootic in Central and West African countries where reports of human cases are sporadically described. Recent trends in mpox spread outside the Africa have highlighted increased incidence of spillover of the MPXV from animal to humans. While nature of established animal reservoirs remained undefined, several small mammals including rodents, carnivores, lagomorphs, insectivores, non-human primates, domestic/farm animals, and several species of wildlife are proposed to be carrier of the MPXV infection. There are established records of animal-to-human (zoonotic) spread of MPXV through close interaction of humans with animals by eating bushmeat, contracting bodily fluids or trading possibly infected animals. In contrast, there are reports and increasing possibilities of human-to-animal (zooanthroponotic) spread of the MPXV through petting and close interaction with pet owners and animal care workers. We describe here the rationales and molecular factors which predispose the spread of MPXV not only amongst humans but also from animals to humans. A range of continuing opportunities for the spread and evolution of MPXV are discussed to consider risks beyond the currently identified groups. With the possibility of MPXV establishing itself in animal reservoirs, continued and broad surveillance, investigation into unconventional transmissions, and exploration of spillover events are warranted.

Biological Characteristics and Pathogenesis of Monkeypox Virus: An Overview.

Although the smallpox virus has been eradicated worldwide, the World Health Organization (WHO) has issued a warning about the virus's potential to propagate globally. The WHO labeled monkeypox a world public health emergency in July 2022, requiring urgent prevention and treatment. The monkeypox virus is a part of the Poxviridae family, Orthopoxvirus genus, and is accountable for smallpox, which has killed over a million people in the past. Natural hosts of the virus include squirrels, Gambian rodents, chimpanzees, and other monkeys. The monkeypox virus has transmitted to humans through primary vectors (various animal species) and secondary vectors, including direct touch with lesions, breathing particles from body fluids, and infected bedding. The viral particles are ovoid or brick-shaped, 200-250 nm in diameter, contain a single double-stranded DNA molecule, and reproduce only in the cytoplasm of infected cells. Monkeypox causes fever, cold, muscle pains, headache, fatigue, and backache. The phylogenetic investigation distinguished between two genetic clades of monkeypox: the more pathogenic Congo Basin clade and the West Africa clade. In recent years, the geographical spread of the human monkeypox virus has accelerated despite a paucity of information regarding the disease's emergence, ecology, and epidemiology. Using lesion samples and polymerase chain reaction (PCR), the monkeypox virus was diagnosed. In the USA, the improved Ankara vaccine can now be used to protect people who are at a higher risk of getting monkeypox. Antivirals that we have now work well against smallpox and may stop the spread of monkeypox, but there is no particular therapy for monkeypox.

Molecular Virology of Orthopoxviruses with Special Reference to Monkeypox Virus.

Poxviruses are large (200-450 nm) and enveloped viruses carrying double-stranded DNA genome with an epidermal cell-specific adaptation. The genus Orthopoxvirus within Poxviridae family constitutes several medically and veterinary important viruses including variola (smallpox), vaccinia, monkeypox virus (MPXV), and cowpox. The monkeypox disease (mpox) has recently emerged as a public health emergency caused by MPXV. An increasing number of human cases of MPXV have been documented in non-endemic nations without any known history of contact with animals brought in from endemic and enzootic regions, nor have they involved travel to an area where the virus was typically prevalent. Here, we review the MPXV replication, virus pathobiology, mechanism of viral infection transmission, virus evasion the host innate immunity and antiviral therapies against Mpox. Moreover, preventive measures including vaccination were discussed and concluded that cross-protection against MPXV may be possible using antibodies that are directed against an Orthopoxvirus. Despite the lack of a specialised antiviral medication, several compounds such as Cidofovir and Ribavirin warrant consideration against mpox.

Monkeypox Outbreak 2022, from a Rare Disease to Global Health Emergence: Implications for Travellers.

Monkeypox (mpox), a zoonotic disease caused by the monkeypox virus (MPXV), poses a significant public health threat with the potential for global dissemination beyond its endemic regions in Central and West Africa. This study explores the multifaceted aspects of monkeypox, covering its epidemiology, genomics, travel-related spread, mass gathering implications, and economic consequences. Epidemiologically, mpox exhibits distinct patterns, with variations in age and gender susceptibility. Severe cases can arise in immunocompromised individuals, underscoring the importance of understanding the factors contributing to its transmission. Genomic analysis of MPXV highlights its evolutionary relationship with the variola virus and vaccinia virus. Different MPXV clades exhibit varying levels of virulence and transmission potential, with Clade I associated with higher mortality rates. Moreover, the role of recombination in MPXV evolution remains a subject of interest, with implications for understanding its genetic diversity. Travel and mass gatherings play a pivotal role in the spread of monkeypox. The ease of international travel and increasing globalization have led to outbreaks beyond African borders. The economic ramifications of mpox outbreaks extend beyond public health. Direct treatment costs, productivity losses, and resource-intensive control efforts can strain healthcare systems and economies. While vaccination and mitigation strategies have proven effective, the cost-effectiveness of routine vaccination in non-endemic countries remains a subject of debate. This study emphasizes the role of travel, mass gatherings, and genomics in its spread and underscores the economic impacts on affected regions. Enhancing surveillance, vaccination strategies, and public health measures are essential in controlling this emerging infectious disease.

Incubation Period and Serial Interval of Mpox in 2022 Global Outbreak Compared with Historical Estimates.

Understanding changes in the transmission dynamics of mpox requires comparing recent estimates of key epidemiologic parameters with historical data. We derived historical estimates for the incubation period and serial interval for mpox and contrasted them with pooled estimates from the 2022 outbreak. Our findings show the pooled mean infection-to-onset incubation period was 8.1 days for the 2022 outbreak and 8.2 days historically, indicating the incubation periods remained relatively consistent over time, despite a shift in the major mode of transmission. However, we estimated the onset-to-onset serial interval at 8.7 days using 2022 data, compared with 14.2 days using historical data. Although the reason for this shortening of the serial interval is unclear, it may be because of increased public health interventions or a shift in the mode of transmission. Recognizing such temporal shifts is essential for informed response strategies, and public health measures remain crucial for controlling mpox and similar future outbreaks.

Experimental inoculation of pigs with monkeypox virus results in productive infection and transmission to sentinels.

Monkeypox virus (MPXV) is a re-emerging zoonotic poxvirus responsible for producing skin lesions in humans. Endemic in sub-Saharan Africa, the 2022 outbreak with a clade IIb strain has resulted in ongoing sustained transmission of the virus worldwide. MPXV has a relatively wide host range, with infections reported in rodent and non-human primate species. However, the susceptibility of many domestic livestock species remains unknown. Here, we report on a susceptibility/transmission study in domestic pigs that were experimentally inoculated with a 2022 MPXV clade IIb isolate or served as sentinel contact control animals. Several principal-infected and sentinel contact control pigs developed minor lesions near the lips and nose starting at 12 through 18 days post-challenge (DPC). No virus was isolated and no viral DNA was detected from the lesions; however, MPXV antigen was detected by IHC in tissue from a pustule of a principal infected pig. Viral DNA and infectious virus were detected in nasal and oral swabs up to 14 DPC, with peak titers observed at 7 DPC. Viral DNA was also detected in nasal tissues or skin collected from two principal-infected animals at 7 DPC post-mortem. Furthermore, all principal-infected and sentinel control animals enrolled in the study seroconverted. In conclusion, we provide the first evidence that domestic pigs are susceptible to experimental MPXV infection and can transmit the virus to contact animals.

Reverse Zoonotic Transmission of SARS-CoV-2 and Monkeypox Virus: A Comprehensive Review.

Reverse zoonosis reveals the process of transmission of a pathogen through the human-animal interface and the spillback of the zoonotic pathogen. In this article, we methodically demonstrate various aspects of reverse zoonosis, with a comprehensive discussion of SARS-CoV-2 and MPXV reverse zoonosis. First, different components of reverse zoonosis, such as humans, different pathogens, and numerous animals (poultry, livestock, pets, wild animals, and zoo animals), have been demonstrated. Second, it explains the present status of reverse zoonosis with different pathogens during previous occurrences of various outbreaks, epidemics, and pandemics. Here, we present 25 examples from literature. Third, using several examples, we comprehensively illustrate the present status of the reverse zoonosis of SARS-CoV-2 and MPXV. Here, we have provided 17 examples of SARS-CoV-2 reverse zoonosis and two examples of MPXV reverse zoonosis. Fourth, we have described two significant aspects of reverse zoonosis: understanding the fundamental aspects of spillback and awareness. These two aspects are required to prevent reverse zoonosis from the current infection with two significant viruses. Finally, the One Health approach was discussed vividly, where we urge scientists from different areas to work collaboratively to solve the issue of reverse zoonosis.