Adverse drug reaction profile of third-generation smallpox vaccines used in France during the 2022 monkeypox epidemic.

Due to the start of the monkeypox epidemic in 2022, we retrospectively analyzed the adverse drug reactions (ADRs) reported in France after monkeypox vaccinations with the third-generation smallpox vaccine. Ninety-eight cases, representing 172 ADRs, were reported. ADRs were mostly expected reactogenicity reactions occurring within days after the first dose of vaccine and having a quick favorable outcome. Unexpected facial palsy and vaccination failure are discussed.

Vaccines for Mpox - An Unmet Global Need.

In 1970, the first case of mpox (formerly known as monkeypox) was documented in an infant in Equateur Province, Democratic Republic of Congo (DRC).1 Infections with clade I monkeypox virus (MPXV) are endemic in the rainforest regions of central Africa and result from both zoonotic and human-to-human transmission. The cessation of smallpox vaccination in 1980 because of the eradication of smallpox has led to an increase in the number of individuals who are orthopox immune naïve and is felt to be responsible for a recent increase in mpox cases in the DRC. Comparisons of active surveillance in Sankuru Province from 2005 through 2007 revealed a 20-fold increase in the incidence of mpox compared with the 1980s, with a 5-fold-lower incidence among those with a smallpox vaccination scar.2.

Monkeypox: An outbreak of a rare viral disease.

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.

Tracing the journey of poxviruses: insights from history.

The historical significance of the poxviruses is profound, largely due to the enduring impact left by smallpox virus across many centuries. The elimination of smallpox is a remarkable accomplishment in the history of science and medicine, with centuries of devoted efforts resulting in the development and widespread administration of smallpox vaccines. This review provides insight into the pivotal historical events involving medically significant poxviruses. Understanding the remarkable saga of combatting smallpox is crucial, serving as a guidepost for potential future encounters with poxvirus infections. There is a continual need for vigilant observation of poxvirus evolution and spillover from animals to humans, considering the expansive range of susceptible hosts. The recent occurrence of monkeypox cases in non-endemic countries stands as a stark reminder of the ease with which infections can be disseminated through international travel and trade. This backdrop encourages introspection about our journey and the current status of poxvirus research.

Human mpox: global trends, molecular epidemiology and options for vaccination.

The eradication of smallpox and the cessation of vaccination have led to the growth of the susceptible human population to poxviruses. This has led to the increasing detection of zoonotic orthopoxviruses. Among those viruses, monkeypox virus (MPV) is the most commonly detected in Western and Central African regions. Since 2022, MPV is causing local transmission in newly affected countries all over the world. While the virus causing the current outbreak remains part of clade II (historically referred to as West African clade), it has a significant number of mutations as compared to other clade II sequences and is therefore referred to as clade IIb. It remains unclear whether those mutations may have caused a change in the virus phenotype. Vaccine effectiveness data show evidence of a high cross-protection of vaccines designed to prevent smallpox against mpox. These vaccines therefore represent a great opportunity to control human-to-human transmission, provided that their availability has short time-frames and that mistakes from the recent past (vaccine inequity) will not be reiterated.

Lest we forget: Odunbaku Oguntona Sapara William (1895-1935) beyond the demystification of deity.

Oguntola Odunbaku Sapara Williams (born Alexander Johnson Williams, 1861-1935) was a Fellow of the Royal Institute of Public Health. This paper attempts to highlight the effort of an African doctor to fight disease outbreaks during the African colonial era. His uninterrupted 32 years career as a colonial medical officer in one of the British colonies in West Africa, provided superintendence for the eradication of smallpox as a result of this, he was credited with the demystification of metaphysical involvement in the smallpox epidemic and thus eradication of smallpox in the Lagos colony. He also provided leadership for the control of bubonic plague, and tuberculosis epidemics and pioneered initiatives to reduce maternal and infant mortality by vaccination, enactment of public health law, environmental sanitation, and health education in Southwest Nigeria.

Poc (Pox), a term for various infectious diseases in the history of public health and epidemiology: the dreaded Smallpox, the almost unknown Alastrim and the Mpox.

Introduction: In 2022, the appearance of cases of Mpox outside the countries where the disease is endemic, and of some cases of human-to-human transmission, alerted the scientific community to a virus that is closely related to the smallpox virus. Mpox is a zoonosis and can be transmitted to humans. Following the eradication of smallpox in 1980 and the subsequent cessation of smallpox vaccination, it is emerging as the most important Orthopoxvirus in terms of public health impact. Methods: In outlining the current situation of Mpox in the world, the authors frame the virus responsible within a broader reflection on the Orthopoxvirus family, focusing particular attention on the Variola virus, which formerly caused millions of deaths. Discussion: Since Edward Jenner initiated the practice of vaccination, a progressive and careful vaccination campaign has led to the eradication not only of human smallpox but also of a minor form, called Alastrim, which was caused by the same virus. The mode of transmission of Mpox has been debated. At first, it seemed that the disease mainly, though not exclusively, affected men who had sex with other men. This conviction has been partially revised and the WHO recently changed the name of the disease from Monkeypox to Mpox, thereby alleviating the stigma involved. Conclusion: The recent human cases of Mpox have prompted greater surveillance and research into the biology of MPXV and other closely related poxviruses. Studies have focused on the natural history of the virus, its transmission, pathogenesis, host interactions and evolution, and on the development of drugs and vaccines to prevent its spread.

Emergence of mpox in the post-smallpox era-a narrative review on mpox epidemiology.

BACKGROUND: The 2022 mpox outbreak drew global attention to this neglected pathogen. While most of the world was taken by surprise, some countries have seen this pathogen emerge and become endemic several decades prior to this epidemic. OBJECTIVES: This narrative review provides an overview of mpox epidemiology since its discovery through the 2022 global outbreak. SOURCES: We searched PubMed for relevant literature about mpox epidemiology and transmission through 28 February 2023. CONTENT: The emergence of human mpox is intertwined with the eradication of smallpox and the cessation of the global smallpox vaccination campaign. The first human clade I and II monkeypox virus (MPXV) infections were reported as zoonoses in Central and West Africa, respectively, around 1970 with sporadic infections reported throughout the rest of the decade. Over the next five decades, Clade I MPXV was more common and caused outbreaks of increasing size and frequency, mainly in the Democratic Republic of the Congo. Clade II MPXV was rarely observed, until its re-emergence and ongoing transmission in Nigeria, since 2017. Both clades showed a shift from zoonotic to human-to-human transmission, with potential transmission through sexual contact being observed in Nigeria. In 2022, clade II MPXV caused a large human outbreak which to date has caused over 86,000 cases in 110 countries, with strong evidence of transmission during sexual contact. By February 2023, the global epidemic has waned in most countries, but endemic regions continue to suffer from mpox. IMPLICATIONS: The changing epidemiology of mpox demonstrates how neglected zoonosis turned into a global health threat within a few decades. Thus, mpox pathophysiology and transmission dynamics need to be further investigated, and preventive and therapeutic interventions need to be evaluated. Outbreak response systems need to be strengthened and sustained in endemic regions to reduce the global threat of mpox.

Epidemiologic and Clinical Features of Mpox in Adults Aged >50 Years - United States, May 2022-May 2023.

During May 2022-May 2023, approximately 30,000 mpox cases were reported in the United States, predominantly among young adult men. Persons aged >50 years might experience more severe mpox disease because of a higher prevalence of comorbidities. Conversely, they could have residual protection from childhood smallpox vaccination against monkeypox virus infection and severe mpox, as has been suggested by investigation of some previous mpox outbreaks. To examine the characteristics of mpox cases among adults aged >50 years, analysts compared mpox epidemiology and clinical outcomes among all adults aged ≥18 years, by age group. Further, outcomes were compared among adults aged >50 years by JYNNEOS vaccination status. During May 10, 2022-May 17, 2023, among 29,984 adults with probable or confirmed mpox reported to CDC, 2,909 (9.7%) were aged >50 years, 96.3% of whom were cisgender men. Compared with adults aged 18-50 years, adults aged >50 years had higher prevalences of immunocompromising conditions (p<0.001) and HIV infection (p<0.001). Among adults with mpox aged >50 years, 27.6% had received JYNNEOS vaccination; this group had lower prevalences of constitutional symptoms (p<0.001), pruritus (p<0.001), and hospitalization (p = 0.002) compared with those who had not received JYNNEOS vaccine. Currently recommended JYNNEOS vaccination among all adults at risk for mpox should be encouraged, irrespective of childhood smallpox vaccination status.

Pandemic potential of poxviruses: From an ancient killer causing smallpox to the surge of monkeypox.

Smallpox caused by the variola virus (VARV) was one of the greatest infectious killers of mankind. Historical records trace back smallpox for at least a millennium while phylogenetic analysis dated the ancestor of VARV circulating in the 20th century into the 19th century. The discrepancy was solved by the detection of distinct VARV sequences first in 17th-century mummies and then in human skeletons dated to the 7th century. The historical records noted marked variability in VARV virulence which scientists tentatively associated with gene losses occurring when broad-host poxviruses narrow their host range to a single host. VARV split from camel and gerbil poxviruses and had no animal reservoir, a prerequisite for its eradication led by WHO. The search for residual pockets of VARV led to the discovery of the monkeypox virus (MPXV); followed by the detection of endemic smallpox-like monkeypox (mpox) disease in Africa. Mpox is caused by less virulent clade 2 MPXV in West Africa and more virulent clade 1 MPXV in Central Africa. Exported clade 2 mpox cases associated with the pet animal trade were observed in 2003 in the USA. In 2022 a world-wide mpox epidemic infecting more than 80,000 people was noted, peaking in August 2022 although waning rapidly. The cases displayed particular epidemiological characteristics affecting nearly exclusively young men having sex with men (MSM). In contrast, mpox in Africa mostly affects children by non-sexual transmission routes possibly from uncharacterized animal reservoirs. While African children show a classical smallpox picture, MSM mpox cases show few mostly anogenital lesions, low-hospitalization rates and 140 fatal cases worldwide. MPXV strains from North America and Europe are closely related, derived from clade 2 African MPXV. Distinct transmission mechanisms are more likely causes for the epidemiological and clinical differences between endemic African cases and the 2022 epidemic cases than viral traits.

Kaspar Hauser, the Child of Europe: Are smallpox vaccination scars the clue to a 2-century-old mystery?

We have explored the 19th century mystery of the identity of Kaspar Hauser, the so-called Child of Europe, from the perspective of the smallpox vaccination. We have highlighted the improbability that he was secretly inoculated based on the vaccination policies and methodologies applied at the time. This consideration allows for a reflection on the whole case and the importance of vaccination scars in ascertaining immunization against one of humanity's deadliest killers, especially given the recent monkeypox outbreak.

[Mpox, 40 years after smallpox eradication]. / Mpox, 40 ans après l'éradication de la variole humaine.

In 2022, mpox - a neglected tropical zoonosis - emerged to the world stage. From 1980, the disease was periodically noted, with increasing frequency, in endemic regions of Africa. In 2017, a large outbreak in Nigeria marks a turning point in the evolution of mpox and seems to be at the origin of the 2022 pandemic. The factors for mpox emergence are complex and include loss of cross-protection conferred by smallpox vaccination, increased exposure to the animal reservoir, and increased human-to-human transmission due to behavioral factors. While the current epidemic seems under control, an evolution towards a more transmissible or more virulent virus is not excluded. The 2022 pandemic is an opportunity to initiate and strengthen mpox surveillance, prevention and care management among all affected populations.

En 2022, le mpox ­ une zoonose tropicale négligée ­ a émergé sur la scène mondiale. Depuis 1980, la maladie a été notifiée avec une fréquence croissante dans les régions endémiques d'Afrique. En 2017, une large épidémie au Nigeria marque un tournant dans l'évolution du mpox et semble à l'origine de la pandémie 2022. Les facteurs d'émergence du mpox sont complexes et incluent la perte de la protection croisée conférée par la vaccination antivariolique, une exposition accrue au réservoir animal et une augmentation de la transmission interhumaine due à des facteurs comportementaux. Alors que l'épidémie actuelle semble sous contrôle, une évolution vers un virus plus transmissible ou plus virulent n'est pas exclue. La pandémie 2022 est une opportunité pour initier et renforcer la surveillance, la prévention et la prise en charge clinique du mpox auprès de toutes les populations affectées.

[Research progress on the effectiveness of smallpox vaccination against mpox virus infection].

With the expansion of mpox virus infection from endemic to a global epidemic in 2022, the WHO declared that the mpox event constituted a Public Health Emergency of International Concern. Due to the high degree of gene sequence similarity among orthopox viruses and cross-reactive antibodies induced by orthoviruses, smallpox vaccination may affect the immune response induced by mpox virus infection. The analysis of the protective effects of smallpox vaccination against mpox virus infection will help define the focus of prevention and control. In this review, we clarify the protection of the smallpox vaccine against mpox virus infection by analyzing the correlation between smallpox vaccination, immune response status, and clinical data and providing evidence for the prevention, control, and strategies of mpox epidemics.

Mpox neglect and the smallpox niche: a problem for Africa, a problem for the world.

Mpox (formerly known as monkeypox) is a zoonotic viral disease endemic in parts of Africa. In May, 2022, the world was alerted to circulation of monkeypox virus in many high-income countries outside of Africa. Continued spread resulted in a WHO declaration of a Public Health Emergency of International Concern. Although there has been much attention on the global outbreak, most of the focus has been on high-income countries outside of Africa, despite the fact that monkeypox virus has been causing disease in parts of Africa for at least 50 years. Furthermore, the long-term consequences of this event, especially the risk that mpox fills the niche vacated through smallpox eradication, have not been sufficiently considered. The heart of the problem is the historical neglect of mpox in Africa where the disease is endemic, and the actual and potential consequences if this neglect is left uncorrected.

Vacunas frente a la viruela del mono (monkeypox) / Vaccines against monkeypox

El virus de la viruela de los monos es un virus que presenta un 90% de homología genómica con el humano (smallpox), pero se trasmite de forma natural entre diferentes reservorios animales salvajes y es considerado una zoonosis. A lo largo del siglo XX se desarrollaron diferentes vacunas basadas en el poxvirus vaccinia que fueron utilizadas para la vacunación frente a la viruela humana. Tras la erradicación de la viruela humana estas vacunas dejaron de utilizarse. Las vacunas actuales frente a la viruela de los monos se clasifican por la OMS como replicativas (ACAM2000), mínimamente replicativas (LC16m8) y no replicativas (MVA-BN), siendo esta última la utilizada en la actualidad. La epidemia extraafricana de viruela de los monos de 2022ha puesto en evidencia la falta de vacunas de eficacia demostrada y de baja reactogenicidad. Se considera que la utilización de esta vacuna en el brote actual puede desempeñar un papel en la prevención o atenuación de la enfermedad como profilaxis preexposición en contactos estrechos de casos confirmados. (AU)

The monkeypox virus is a virus that has 90% genomic homology with the human (smallpox), but it is naturally transmitted between different wild animal reservoirs and is considered a zoonosis. Throughout the 20th century, different vaccines based on the vaccinia poxvirus were developed and used for vaccination against smallpox. After the eradication of smallpox, these vaccines were no longer used. Current vaccines against monkeypox virus are classified by the WHO as replicative (ACAM2000), minimally replicative (LC16m8) and non-replicative (MVA-BN), the latter being the one currently used. The 2022 extra-African monkeypox virus epidemic has highlighted the lack of vaccines with proven efficacy and low reactogenicity. It is considered that the use of this vaccine in the current outbreak may play a role in the prevention or attenuation of the disease as pre-exposure prophylaxis in close contacts of confirmed cases. (AU)

Effect of prior immunisation with smallpox vaccine for protection against human Mpox: A systematic review.

Monkeypox is an emerging threat to humans since a new outbreak in May 2022. It is hypothesised that increasing the immunologically naive population after the cessation of the smallpox vaccination campaign in the 1980s is one of the leading causes of it. A literature search was conducted using different electronic databases including MEDLINE (through PubMed), SCOPUS, Web of Science, Cochrane library, and EMBASE for relevant studies. After duplication removal, abstract and title screening, and full-text screening were done, the data were extracted, tabulated, and analysed. The risk of bias was assessed following the Risk of Bias Assessment tool for Non-randomised Studies. We found a total of 1068 relevant articles and finally, we included 6 articles including 2083 participants. The studies suggested that smallpox is 80.7% efficacious to prevent human monkeypox and the immunity provided by prior smallpox vaccination is long-lasting. Moreover, the smallpox vaccination decreases the risk of human monkeypox by 5.2-folds. Two cross-sectional studies based on the Democratic Republic of the Congo (DRC) including a total of around 1800 monkeypox cases found that unvaccinated participants had 2.73 and 9.64-fold increased risk of monkeypox compared to the vaccinated participants. Other studies in USA and Spain also demonstrated that unvaccinated people were more prone to develop monkeypox than vaccinated people. Furthermore, monkeypox incidence has increased by 20 folds, 30 years after the cessation of the smallpox vaccination campaign in DRC. Evidence-based preventive and therapeutic agents are still not available for human monkeypox. Further study should be done to explore the role of the smallpox vaccine in preventing human monkeypox.

[Vaccines against monkeypox]. / Vacunas frente a la viruela del mono (monkeypox).

The monkeypox virus is a virus that has 90% genomic homology with the human (smallpox), but it is naturally transmitted between different wild animal reservoirs and is considered a zoonosis. Throughout the 20th century, different vaccines based on the vaccinia poxvirus were developed and used for vaccination against smallpox. After the eradication of smallpox, these vaccines were no longer used. Current vaccines against monkeypox virus are classified by the WHO as replicative (ACAM2000), minimally replicative (LC16m8) and non-replicative (MVA-BN), the latter being the one currently used. The 2022 extra-African monkeypox virus epidemic has highlighted the lack of vaccines with proven efficacy and low reactogenicity. It is considered that the use of this vaccine in the current outbreak may play a role in the prevention or attenuation of the disease as pre-exposure prophylaxis in close contacts of confirmed cases.

Analysis of variola virus molecular evolution suggests an old origin of the virus consistent with historical records.

Archaeovirology efforts provided a rich portrait of the evolutionary history of variola virus (VARV, the cause of smallpox), which was characterized by lineage extinctions and a relatively recent origin of the virus as a human pathogen (~1700 years ago, ya). This contrasts with historical records suggesting the presence of smallpox as early as 3500 ya. By performing an analysis of ancestry components in modern, historic, and ancient genomes, we unveil the progressive drifting of VARV lineages from a common ancestral population and we show that a small proportion of Viking Age ancestry persisted until the 18th century. After the split of the P-I and P-II lineages, the former experienced a severe bottleneck. With respect to the emergence of VARV as a human pathogen, we revise time estimates by accounting for the time-dependent rate phenomenon. We thus estimate that VARV emerged earlier than 3800 ya, supporting its presence in ancient societies, as pockmarked Egyptian mummies suggest.

Lessons From a House on Fire-From Smallpox to Polio.

Global burden of disease morbidity and mortality has shifted dramatically in the last 30 years from infectious to non-communicable diseases, leading to major improvements in global child survival and enhanced life expectancy for all age groups. Vaccination efforts worldwide have been key to this achievement, but with a reduction in vaccine preventable diseases, anti-vaccine sentiments have concurrently increased. Eradication of smallpox in 1977 is a testament to vaccination impacts on human health. Despite this historic success, recent increases in infectious disease outbreaks, such as polio and measles, especially among poorly vaccinated populations, have underscored the risks of resurgence of diseases once thought eliminated in the United States and elsewhere. Engaging governments, community leaders, and the public will be critical to continuing the advancement of global health through elimination of vaccine preventable diseases.

Re-emerging human monkeypox: A major public-health debacle.

A multicountry outbreak of the monkeypox virus has gained global attention. As of May 25, 250 confirmed human monkeypox cases have been reported globally. Monkeypox is caused by the Monkeypox virus, which belongs to the Orthopoxvirus genus and Poxviridae family. Monkeypox is often a self-limiting infection, with symptoms lasting 2-4 weeks with the case fatality ratio around 3%-6%. Monkeypox is transmitted to humans by direct contact with an infected person or animal or contact with virus-contaminated material. Human monkeypox infections may lead to various medical complications such as fever, rash, and lymphadenopathies. Pneumonitis, encephalitis, sight-threatening keratitis, and subsequent bacterial infections are all possible complications of monkeypox. An antiviral agent developed to treat smallpox has also been approved for use in the treatment of monkeypox in the United States. Vaccines used in the smallpox eradication program also provided immunity to monkeypox. Newer vaccines have been developed, one of which has been approved for monkeypox prevention. In this study, we provide information about the recent outbreaks of human monkeypox, epidemiology, transmission pattern, possible diagnosis techniques, therapeutics, and available preventive strategies.