Monkeypox: a global health emergency.

Over the past 2 years, the world has faced the impactful Coronavirus Disease-2019 (COVID-19) pandemic, with a visible shift in economy, medicine, and beyond. As of recent times, the emergence of the monkeypox (mpox) virus infections and the growing number of infected cases have raised panic and fear among people, not only due to its resemblance to the now eradicated smallpox virus, but also because another potential pandemic could have catastrophic consequences, globally. However, studies of the smallpox virus performed in the past and wisdom gained from the COVID-19 pandemic are the two most helpful tools for humanity that can prevent major outbreaks of the mpox virus, thus warding off another pandemic. Because smallpox and mpox are part of the same virus genus, the Orthopoxvirus genus, the structure and pathogenesis, as well as the transmission of both these two viruses are highly similar. Because of these similarities, antivirals and vaccines approved and licensed in the past for the smallpox virus are effective and could successfully treat and prevent an mpox virus infection. This review discusses the main components that outline this current global health issue raised by the mpox virus, by presenting it as a whole, and integrating aspects such as its structure, pathogenesis, clinical aspects, prevention, and treatment options, and how this ongoing phenomenon is being globally approached.

Serological responses to smallpox A33 antigen and monkeypox A35 antigen in healthy people and people living with HIV-1 from Guangzhou, China.

People are expected to have been previously vaccinated with a Vaccinia-based vaccine, as until 1980 smallpox vaccination was a standard protocol in China. It is unclear whether people with smallpox vaccine still have antibody against vaccinia virus (VACV) and cross-antibody against monkeypox virus (MPXV). Herein, we assessed the binding antibodies with antigen of VACV-A33 and MPXV-A35 in the general population and HIV-1 infected patients. Firstly, we detected VACV antibody with A33 protein to evaluate the efficiency of smallpox vaccination. The result show that 29% (23 of 79) of hospital staff (age ≥ 42 years) and 63% (60 of 95) of HIV-positive patients (age ≥ 42 years) from Guangzhou Eighth People's Hospital were able to bind A33. However, among the subjects below 42 years of age, 1.5% (3/198) of the hospital volunteer samples and 1% (1/104) of the samples from HIV patients were positive for antibodies against A33 antigen. Then, we assessed the specific cross-reactive antibodies against MPXV A35 protein. 24% (19 of 79) hospital staff (age〉 = 42 years) and 44% (42 of 95) of HIV-positive patients (age〉 = 42 years) were positive. 98% (194/198) of the hospital staff and 99% (103/104) of the HIV patients had no A35-binding antibodies. Further, we found significant sex differences for the reactivity to A35 antigen were observed in HIV population, but no significant sex differences in hospital staff. Further, we analyzed the positivity rate of anti-A35 antibody of men who have sex with men (MSM) and non-MSM in HIV patients (age〉 = 42years). We found that 47% of no-MSM population and 40% of MSM population were positive for A35 antigen, with no significant difference. Lastly, we found only 59 samples were positive for anti-A33 IgG and anti-A35 IgG in all participants. Together, we demonstrated A33 and A35 antigens binding antibodies were detected in HIV patients and general population who were older than 42 years, and cohort studies only provided data of serological detection to support early response to monkeypox outbreak.

Mpox (Formally Known as Monkeypox).

This article reviews Mpox, including its epidemiology, transmission, clinical presentation, diagnosis, prevention, and management and treatment of the virus. This article also investigates the current outbreak of Mpox in nonendemic countries, including the United States. It discusses the high prevalence of Mpox affecting the men who have sex with men community. It examines the social stigma related to disease outbreaks of the past and it provides strategies that should be implemented to prevent stigmatization of the men who have sex with men community with the present-day outbreak of Mpox.

Complement-dependent mpox-virus-neutralizing antibodies in infected and vaccinated individuals.

Mpox virus (MPXV) caused a multi-country outbreak in non-endemic areas in 2022. Following historic success of smallpox vaccination with vaccinia virus (VACV)-based vaccines, the third generation modified vaccinia Ankara (MVA)-based vaccine was used as prophylaxis for MPXV, but its effectiveness remains poorly characterized. Here, we applied two assays to quantify neutralizing antibodies (NAbs) in sera from control, MPXV-infected, or MVA-vaccinated individuals. Various levels of MVA NAbs were detected after infection, historic smallpox, or recent MVA vaccination. MPXV was minimally sensitive to neutralization. However, addition of complement enhanced detection of responsive individuals and NAb levels. Anti-MVA and -MPXV NAbs were observed in 94% and 82% of infected individuals, respectively, and 92% and 56% of MVA vaccinees, respectively. NAb titers were higher in individuals born before 1980, highlighting the impact of historic smallpox vaccination on humoral immunity. Altogether, our results indicate that MPXV neutralization is complement dependent and uncover mechanisms underlying vaccine effectiveness.

Monkeypox: another pandemic in the making?

Monkeypox is a zoonotic disease caused by the monkeypox virus, which is a member of the Poxviridae family of viruses. It is transmitted through direct or indirect contact with fluid secretions. Initial symptoms include fever, chills, headache, and malaise, followed by a maculopapular rash that starts on the face and progresses centrifugally. Polymerase chain reaction is the preferred laboratory test for the diagnosis, and management is mostly supportive. The clinical presentation of monkeypox is quite similar to that of another member of the Poxviridae family: smallpox, which wreaked havoc in the 20th century, before being eradicated with the help of the vaccinia virus vaccine in 1977. This vaccine protects not only against smallpox but also monkeypox; therefore, when use of this vaccine was discontinued, monkeypox had a new susceptible population to infect and way to proliferate and evolve. Initially the disease spread in Africa, but now the more evolved monkeypox is quickly spreading to other countries. On July 23, 2022, the World Health Organization declared this multicountry outbreak a public health emergency of international concern. Given its mutating ability and high transmissibility, we need to quickly devise measures to control this virus before it turns into a pandemic.

Anti-viral drug discovery against monkeypox and smallpox infection by natural curcumin derivatives: A Computational drug design approach.

Background: In the last couple of years, viral infections have been leading the globe, considered one of the most widespread and extremely damaging health problems and one of the leading causes of mortality in the modern period. Although several viral infections are discovered, such as SARS CoV-2, Langya Henipavirus, there have only been a limited number of discoveries of possible antiviral drug, and vaccine that have even received authorization for the protection of human health. Recently, another virial infection is infecting worldwide (Monkeypox, and Smallpox), which concerns pharmacists, biochemists, doctors, and healthcare providers about another epidemic. Also, currently no specific treatment is available against Monkeypox. This research gap encouraged us to develop a new molecule to fight against monkeypox and smallpox disease. So, firstly, fifty different curcumin derivatives were collected from natural sources, which are available in the PubChem database, to determine antiviral capabilities against Monkeypox and Smallpox. Material and method: Preliminarily, the molecular docking experiment of fifty different curcumin derivatives were conducted, and the majority of the substances produced the expected binding affinities. Then, twelve curcumin derivatives were picked up for further analysis based on the maximum docking score. After that, the density functional theory (DFT) was used to determine chemical characterizations such as the highest occupied molecular orbital (HOMO), lowest unoccupied molecular orbital (LUMO), softness, and hardness, etc. Results: The mentioned derivatives demonstrated docking scores greater than 6.80 kcal/mol, and the most significant binding affinity was at -8.90 kcal/mol, even though 12 molecules had higher binding scores (-8.00 kcal/mol to -8.9 kcal/mol), and better than the standard medications. The molecular dynamic simulation is described by root mean square deviation (RMSD) and root-mean-square fluctuation (RMSF), demonstrating that all the compounds might be stable in the physiological system. Conclusion: In conclusion, each derivative of curcumin has outstanding absorption, distribution, metabolism, excretion, and toxicity (ADMET) characteristics. Hence, we recommended the aforementioned curcumin derivatives as potential antiviral agents for the treatment of Monkeypox and Smallpox virus, and more in vivo investigations are warranted to substantiate our findings.

Comparison of human monkeypox, chickenpox and smallpox: a comprehensive review of pathology and dermatological manifestations.

Variola virus, the causing agent of smallpox, was eradicated in 1980s and today no new cases are reported. The first human infectious illness to be eliminated globally is variola. On the contrary to Variola, monkeypox, which is a zoonotic and variola-like disease, has nowadays turned to be a major health problem worldwide. VZV is a neurotropic virus and the cause of varicella (chickenpox) and herpes zoster (shingles), which is also a highly infectious disease, especially prevalent in children. These three skin diseases-monkeypox, smallpox, and chickenpox-are frequently mistaken with one another due to similar manifestations including fever, rash, myalgia, chills and headache, but they can all be distinguished by their distinctive symptoms. Although these rash-causing disorders might present different skin lesions; diagnostic tests can be extremely useful in their differentiation. We searched for these concepts on a search engine like Google Scholar, scanning the results for alternative words and phrases, and examined relevant abstracts or articles for alternative words. The clinical diagnosis of monkeypox infection is commonly made based on the occurrence pattern of its skin rash. It is possible in varicella to concurrently identify lesions in their various stages including macular, papular, vesicular, pustular, and crusts; however, monkeypox lesions are all in the same stage and evolve with the same rate. In this review, we have tried to provide a holistic and comprehensive comparison between these three skin infections with a focus on the newly epidemic monkeypox, bringing about the most recent knowledge about its features and its diagnosis.

Monkeypox (Mpox) requires continued surveillance, vaccines, therapeutics and mitigating strategies.

The widespread outbreak of the monkeypox virus (MPXV) recognized in 2022 poses new challenges for public healthcare systems worldwide. With more than 86,000 people infected, there is concern that MPXV may become endemic outside of its original geographical area leading to repeated human spillover infections or continue to be spread person-to-person. Fortunately, classical public health measures (e.g., isolation, contact tracing and quarantine) and vaccination have blunted the spread of the virus, but cases are continuing to be reported in 28 countries in March 2023. We describe here the vaccines and drugs available for the prevention and treatment of MPXV infections. However, although their efficacy against monkeypox (mpox) has been established in animal models, little is known about their efficacy in the current outbreak setting. The continuing opportunity for transmission raises concerns about the potential for evolution of the virus and for expansion beyond the current risk groups. The priorities for action are clear: 1) more data on the efficacy of vaccines and drugs in infected humans must be gathered; 2) global collaborations are necessary to ensure that government authorities work with the private sector in developed and low and middle income countries (LMICs) to provide the availability of treatments and vaccines, especially in historically endemic/enzootic areas; 3) diagnostic and surveillance capacity must be increased to identify areas and populations where the virus is present and may seed resurgence; 4) those at high risk of severe outcomes (e.g., immunocompromised, untreated HIV, pregnant women, and inflammatory skin conditions) must be informed of the risk of infection and be protected from community transmission of MPXV; 5) engagement with the hardest hit communities in a non-stigmatizing way is needed to increase the understanding and acceptance of public health measures; and 6) repositories of monkeypox clinical samples, including blood, fluids, tissues and lesion material must be established for researchers. This MPXV outbreak is a warning that pandemic preparedness plans need additional coordination and resources. We must prepare for continuing transmission, resurgence, and repeated spillovers of MPXV.

Outbreak of Monkeypox Virus Disease: An Update on Epidemiology, Pathophysiology and Available Treatment Options.

The monkeypox virus is a zoonotic illness with a tropical distribution in Africa, and around the world. The disease is spread through contact with infected animals or humans, and can also be spread from person to person through close contact with respiratory or bodily fluids. Fever, swollen lymph nodes, blisters, and crusted rashes characterize the disease. The incubation period is five to twenty-one days. It is difficult to distinguish the rash caused by infection from varicella and smallpox. Laboratory investigations are essential aspects of illness diagnosis and surveillance, and novel tests are required for more accurate and faster diagnosis. Antiviral drugs are being used to treat monkeypox. Scarring as well as other comorbidities, are prevalent in survivors, with the case mortality rate varying from1 to 11%. The virus was found in monkeys at a Danish research facility in 1958, from which the term 'monkeypox' is derived. The primary human case was found in a child in the Democratic Republic of the Congo (DRC) in 1970. The World Health Organisation (WHO) has recently declared monkeypox a public health emergency of international concern. This manuscript attempts to review the various aspects of monkeypox disease and its allopathic as well as alternative treatment options available and serves as a valuable resource for healthcare professionals, researchers, and the general public.

An APOBEC3 Mutational Signature in the Genomes of Human-Infecting Orthopoxviruses.

The ongoing worldwide monkeypox outbreak is caused by viral lineages (globally referred to as hMPXV1) that are related to but distinct from clade IIb MPXV viruses transmitted within Nigeria. Analysis of the genetic differences has indicated that APOBEC-mediated editing might be responsible for the unexpectedly high number of mutations observed in hMPXV1 genomes. Here, using 1,624 publicly available hMPXV1 sequences, we analyzed the mutations that accrued between 2017 and the emergence of the current predominant variant (B.1), as well as those that that have been accumulating during the 2022 outbreak. We confirmed an overwhelming prevalence of C-to-T and G-to-A mutations, with a sequence context (5'-TC-3') consistent with the preferences of several human APOBEC3 enzymes. We also found that mutations preferentially occur in highly expressed viral genes, although no transcriptional asymmetry was observed. A comparison of the mutation spectrum and context was also performed against the human-specific variola virus (VARV) and the zoonotic cowpox virus (CPXV), as well as fowlpox virus (FWPV). The results indicated that in VARV genomes, C-to-T and G-to-A changes were more common than the opposite substitutions, although the effect was less marked than for hMPXV1. Conversely, no preference toward C-to-T and G-to-A changes was observed in CPXV and FWPV. Consistently, the sequence context of C-to-T changes confirmed a preference for a T in the -1 position for VARV, but not for CPXV or FWPV. Overall, our results strongly support the view that, irrespective of the transmission route, orthopoxviruses infecting humans are edited by the host APOBEC3 enzymes. IMPORTANCE Analysis of the viral lineages responsible for the 2022 monkeypox outbreak suggested that APOBEC enzymes are driving hMPXV1 evolution. Using 1,624 public sequences, we analyzed the mutations that accumulated between 2017 and the emergence of the predominant variant and those that characterize the last outbreak. We found that the mutation spectrum of hMPXV1 has been dominated by TC-to-TT and GA-to-AA changes, consistent with the editing activity of human APOBEC3 proteins. We also found that mutations preferentially affect highly expressed viral genes, possibly because transcription exposes single-stranded DNA (ssDNA), a target of APOBEC3 editing. Notably, analysis of the human-specific variola virus (VARV) and the zoonotic cowpox virus (CPXV) indicated that in VARV genomes, TC-to-TT and GA-to-AA changes are likewise extremely frequent. Conversely, no preference toward TC-to-TT and GA-to-AA changes is observed in CPXV. These results suggest that APOBEC3 proteins have an impact on the evolution of different human-infecting orthopoxviruses.

Evidence synthesis of Chinese medicine for monkeypox: Suggestions from other contagious pox-like viral diseases.

Background: Monkeypox, a zoonotic disease caused by an Orthopoxvirus, presents an etiology similar to smallpox in humans. Currently, there are no licensed treatments for human monkeypox, so clear and urgent research on its prophylaxis and treatment is needed. Objective: The purpose of this study was to explore the evidence of Chinese medicine for contagious pox-like viral diseases and provide suggestions for the multi-country outbreak management of monkeypox. Methods: The review was registered on INPLASY (INPLASY202270013). Ancient classics in China and clinical trials involving randomized controlled trials , non-RCTs, and comparative observational studies of CM on the prevention and treatment of monkeypox, smallpox, measles, varicella, and rubella were retrieved from the Chinese Medical Code (fifth edition), Database of China Ancient Medicine, PubMed, the Cochrane Library, China National Knowledge Infrastructure, Chongqing VIP, Wanfang, Google Scholar, International Clinical Trial Registry Platform, and Chinese Clinical Trial Registry until 6 July 2022. Both quantitative and qualitative methods were applied to present the data collected. Results: The use of CM to control contagious pox-like viral diseases was traced back to ancient Chinese practice cited in Huangdi's Internal Classic, where the pathogen was recorded nearly two thousand years back. There were 85 articles (36 RCTs, eight non-RCTs, one cohort study, and 40 case series) that met the inclusion criteria, of which 39 studies were for measles, 38 for varicella, and eight for rubella. Compared with Western medicine for contagious pox-like viral diseases, CM combined with Western medicine showed significant improvements in fever clearance time (mean difference, -1.42 days; 95% CI, -1.89 to -0.95; 10 RCTs), rash/pox extinction time (MD, -1.71 days; 95% CI, -2.65 to -0.76; six RCTs), and rash/pox scab time (MD, -1.57 days; 95% CI, -1.94 to -1.19; five RCTs). When compared with Western medicine, CM alone could reduce the time of rash/pox extinction and fever clearance. Chinese herbal formulas, including modified Yinqiao powder, modified Xijiao Dihaung decoction, modified Qingjie Toubiao decoction, and modified Shengma Gegen decoction, were frequently applied to treat pox-like viral diseases and also showed significant effects in shortening the time of fever clearance, rash/pox extinction, and rash/pox scabs. Compared with Western medicine (placental globulin) or no intervention, eight non-randomized trials and observational studies on the prevention of contagious pox-like viral diseases showed a significant preventive effect of Leiji powder among high-risk populations. Conclusion: Based on historical records and clinical studies of CM in managing contagious pox-like viral diseases, some botanical drugs could be an alternative approach for treating and preventing human monkeypox. Prospective, rigorous clinical trials are urgently needed to confirm the potential preventive and treatment effect of Chinese herbal formulas. Systematic Review Registration: [https://inplasy.com/], identifier [INPLASY202270013].

Effect of prior immunisation with smallpox vaccine for protection against human monkeypox: 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.

Evaluating the Immunogenicity and Safety of a Smallpox Vaccine to Monkeypox in Healthy Japanese Adults: A Single-Arm Study.

Monkeypox (mpox) is an acute exanthematous disease caused by the monkeypox virus (MPXV). Since May 2022, patients with mpox have been reported worldwide, mainly in Europe and the Americas. In Japan, LC16"KMB," which is a smallpox vaccine derived from a dried cell culture, against mpox, has been approved. Although inoculation with a smallpox vaccine has been recommended to prevent MPXV infection, the immunogenicity of the smallpox vaccine against the MPXV is unclear, and information regarding postvaccination safety is scarce. We present the protocol for a single-arm open-label study to investigate the immunogenicity and safety of LC16"KMB" against the MPXV in healthy Japanese adults. The primary endpoint is the seroconversion rate of neutralizing antibodies against the MPXV on postvaccination day 28. The secondary endpoints are the seroconversion rates against the MPXV on postvaccination days 14 and 168; the seroconversion rates against the vaccinia virus on postvaccination days 14, 28, and 168; the incidence of mpox until day 168; and adverse and serious adverse events until postvaccination days 28 and 168. These results will pave the way for larger comparative studies using other smallpox vaccines to evaluate the test vaccine's safety and efficacy in preventing mpox.

Guidelines on epidemics in Mexico. Historical perspective.

A perspective of epidemics and pandemics in Mexico is offered, focusing on three time periods, namely, end of the 18th century, the 20th century, and the 21st century, in order to analyze how they were approached by health and government authorities, as well as the challenges they have represented. Historical documentary sources were consulted and, in current cases, participation in them was analyzed. Epidemiological and social historical methodologies were combined. The presence of epidemics in Mexico is a constant on its evolution, which highlights the need for the epidemiological surveillance system to be updated, the importance of being prepared to face an epidemic and to develop a contingency plan.

Se ofrece una perspectiva de las epidemias y pandemias en México en tres periodos: fines del siglo XVIII y siglos XX y XXI, con el fin de analizar cómo las autoridades sanitarias y gubernamentales abordaron estos problemas, así como los desafíos que han representado. Se consultaron fuentes históricas documentales y, en los casos actuales, la participación en ellos. Se combinó metodología epidemiológica e histórica social. La presencia de las epidemias en México es una constante, lo cual evidencia la necesidad de actualizar el sistema de vigilancia epidemiológica, de estar preparados para enfrentar una epidemia y de elaborar un plan de contingencia.

The outbreak of the monkeypox virus in the shadow of the pandemic.

The human monkeypox virus (MPXV) was first identified in 1959. Since then, the incidence of the disease has been sporadic. The endemic regions were identified in Africa's central and western areas. However, the infection started to spread in 2017 to non-endemic regions such as North and South America, Europe, and Asia. Since May 2022, the non-endemic areas reported 62,635 till 20th September 2022. Although the monkeypox virus has a mortality of ≥ 10%, it showed only 82 mortalities worldwide in 2022. The common symptoms include chills, fever, fatigue, and skin lesions, and the complications include secondary respiratory tract infections, encephalitis, blindness, and severe diarrhea. The factors responsible for spreading the virus include improper handling and consumption of infected bushmeat, unprotected sexual intercourse, contact with an infected person, no smallpox vaccination, improper hygiene, lower diagnostic capacity, and strong travel history from the endemic regions. The therapeutic strategy is symptom-based treatment and supportive care. Antivirals and vaccines such as Tecovirimat, Brincidofovir, Cidofovir, Imvamune, and ACAM2000 have shown promising results. The primary purpose of the review is to perform an epidemiological study and investigate the pathobiology, diagnosis, prevention, treatment, and some associated complications of the monkeypox virus in 2022.

Characteristics of confirmed mpox cases among clinical suspects: A prospective single-centre study in Belgium during the 2022 outbreak.

Background: The presentation of mpox clade IIb during the 2022 outbreak overlaps with a range of other diseases. Understanding the factors associated with mpox is important for clinical decision making. Methods: We described the characteristics of mpox patients who sought care at Belgian sexual health clinic. Furthermore we compared their characteristics to those of patients with a clinical suspicion of mpox but who tested negative on polymerase chain reaction. Results: Between May 23 and September 20, 2022, 155 patients were diagnosed with mpox, and 51 patients with suspected symptoms tested negative. All mpox patients self-identified as men and 148/155 (95.5%) as gay or bisexual MSM. Systemic symptoms were present in 116/155 (74.8%) patients. All but 10 patients (145/155, 93.5%) presented with skin lesions. Other manifestations were lymphadenopathy (72/155, 46.5%), proctitis (50/155, 32.3%), urethritis (12/155, 7.7%), tonsillitis (2/155, 1.3%). Complications involved bacterial skin infection (13/155, 8.4%) and penile oedema with or without paraphimosis (4/155, 2.6%). In multivariable logistic regression models, the presence of lymphadenopathy (OR 3.79 95% CI 1.44-11.49), skin lesions (OR 4.35 95% CI 1.15-17.57) and proctitis (OR 9.41 95% CI 2.72-47.07) were associated with the diagnosis of mpox. There were no associations with age, HIV status, childhood smallpox vaccination, number of sexual partners and international travel. Conclusions: The presence of proctitis, lymphadenopathies and skin lesions should increase clinical suspicion of mpox in patients with compatible symptoms.

Protective immunity rate against monkeypox: expectation for present and future in case that there is no smallpox vaccine booster.

OBJECTIVES: Monkeypox is now regarded as a major global public health concern. A common symptom of this disease is an acute febrile illness with skin sores. The likelihood of the virus spreading from person to person is increasing. The aim of the present study is to estimate the protective immunity rate against monkeypox. METHODS: Based on the current situation in Africa, the authors forecast the protective immunity rate against monkeypox for the present and future if a smallpox vaccination booster is not available. The clinical mathematical model was used. The primary data for analysis include data on the current serological rate against smallpox and data on the declining rate of smallpox immunity after the last vaccination. RESULTS: According to the current clinical modeling study, protective immunity to monkeypox is limited. The rate among people who have previously been immunized against smallpox is still higher than the general population rate. If the present monkeypox outbreak (2022) is not successfully controlled, there could be a severe public health danger, such as a pandemic. On a larger scale, in a few years, no immunity will be a concern. CONCLUSIONS: To suppress the current monkeypox outbreak, it may be necessary to research the use of a novel monkeypox immunization or a traditional smallpox vaccine.

Overview of the regulatory approval of tecovirimat intravenous formulation for treatment of smallpox: potential impact on smallpox outbreak response capabilities, and future tecovirimat development potential.

INTRODUCTION: Tecovirimat oral capsule formulation is approved in the US and Canada for treatment of smallpox and in the United Kingdom (UK) and European Union (EU) for treatment of multiple human orthopoxvirus diseases, including mpox. Smallpox is considered a serious threat, and there is currently an unprecedented global mpox outbreak. AREAS COVERED: A brief summary of the threat of smallpox, the threat of increasing mpox spread in endemic regions, and the unprecedented emergence of mpox into non-endemic regions is presented. The tecovirimat intravenous formulation clinical development program leading to USFDA approval for smallpox treatment is discussed. EXPERT OPINION: As of January 2023 tecovirimat is approved to treat mpox in the UK and EU. However, published clinical trial data evaluating tecovirimat efficacy and safety in mpox patients is pending. Increasing global prevalence of mpox highlights the potential benefits of a well-characterized, effective, and safe antiviral treatment for mpox infection. Ongoing trials in mpox patients may provide results supporting the use of tecovirimat to treat this disease. USFDA approval of tecovirimat for post-exposure prophylaxis in the event of a smallpox release, and the development of pediatric liquid formulations for patients under 13 kg, could provide additional public health benefits.

Possible Mpox Protection from Smallpox Vaccine-Generated Antibodies among Older Adults.

Smallpox vaccination may confer cross-protection to mpox. We evaluated vaccinia virus antibodies in 162 persons ≥50 years of age in Spain; 68.5% had detectable antibodies. Highest coverage (78%) was among persons 71-80 years of age. Low antibody levels in 31.5% of this population indicates that addressing their vaccination should be a priority.