Monkeypox

Monkeypox, a vesiculo-pustular rash illness, was initially discovered to cause human infection in 1970 through the World Health Organization (WHO)-sponsored efforts of the Commission to Certify Smallpox Eradication in Western Africa and the Congo Basin. The virus had been discovered to cause a nonhuman primate rash illness in 1958, and was thus named monkeypox. The causative agents of monkeypox and smallpox diseases both are species of Orthopoxvirus. Orthopoxvirus monkeypox, when it infects humans as an epizootic, produces a similar clinical picture to that of ordinary human smallpox. Since 1970, extensive epidemiology, virology, ecology and public health research has enabled better characterization of monkeypox virus and the associated human disease. This work reviews the progress in this body of research, and reviews studies of this "newly" emerging zoonotic disease.

Human monkeypox is an emerging viral zoonotic disease, which is caused by monkey pox virus. The disease occurs mostly in the rain forests of central and western Africa. People living in or near the forested areas may have indirect or low-level exposure, possibly leading to subclinical infection. However, the disease recently emerged in the United States in imported wild rodents from Africa. Monkeypox has a clinical presentation like ordinary forms of smallpox, including flulike symptoms, fever, malaise, back pain, headache, and characteristic rash. In view of the eradication of smallpox, such symptoms in a monkepox endemic region should be carefully diagnosed. Primarily, monkey pox transmission to humans is believed to occur through direct contact with infected animals or possibly by ingestion of inadequately cooked flesh. Infection by inoculation through contact with cutaneous or mucosal lesions on the animal, especially when the skin barrier is compromised secondary to bites, scra...

At the onset of the 2003 US monkeypox outbreak, virologic data were unavailable regarding which animal species were involved with virus importation and/or subsequent transmission to humans and whether there was a risk for establishment of zoonotic monkeypox in North America. Similarly, it was unclear which specimens would be best for virus testing. Monkeypox DNA was detected in at least 33 animals, and virus was cultured from 22. Virus-positive animals included three African species associated with the importation event (giant pouched rats, Cricetomys spp.; rope squirrels, Funisciuris sp.; and dormice, Graphiuris sp.). Virologic evidence from North American prairie dogs (Cynomys sp.) was concordant with their suspected roles as vectors for human monkeypox. Multiple tissues were found suitable for DNA detection and/or virus isolation. These data extend the potential host range for monkeypox virus infection and supports concern regarding the potential for establishment in novel reserv...

Human monkeypox is an emerging viral zoonotic disease, which is caused by monkey pox virus. The disease occurs mostly in the rain forests of central and western Africa. People living in or near the forested areas may have indirect or low-level exposure, possibly leading to subclinical infection. However, the disease recently emerged in the United States in imported wild rodents from Africa. Monkeypox has a clinical presentation like ordinary forms of smallpox, including flulike symptoms, fever, malaise, back pain, headache, and characteristic rash. In view of the eradication of smallpox, such symptoms in a monkepox endemic region should be carefully diagnosed. Primarily, monkey pox transmission to humans is believed to occur through direct contact with infected animals or possibly by ingestion of inadequately cooked flesh. Infection by inoculation through contact with cutaneous or mucosal lesions on the animal, especially when the skin barrier is compromised secondary to bites, scra...

This report describes the first reported outbreak of human monkeypox in the Republic of Congo. Eleven confirmed and probable monkeypox cases were observed during this outbreak, all were less than 18 years old, and most resided on the grounds of the Government Hospital in Impfondo. Molecular, virologic, and serologic, and diagnostic assays were used to detect evidence of monkeypox (or orthopox) virus infection in individuals with striking dermatologic and other clinical manifestations. The majority of cases in this outbreak experienced significant, symptomatic illnesses; there was one death, possibly involving secondary complications, and one instance of profound sequelae. Up to six sequential transmissions of monkeypox virus from person to person are hypothesized to have occurred, making this the longest uninterrupted chain of human monkeypox fully documented to date. The pattern of sustained human-to-human transmission observed during this outbreak may influence our current percept...

At the onset of the 2003 US monkeypox outbreak, virologic data were unavailable regarding which animal species were involved with virus importation and/or subsequent transmission to humans and whether there was a risk for establishment of zoonotic monkeypox in North America. Similarly, it was unclear which specimens would be best for virus testing. Monkeypox DNA was detected in at least 33 animals, and virus was cultured from 22. Virus-positive animals included three African species associated with the importation event (giant pouched rats, Cricetomys spp.; rope squirrels, Funisciuris sp.; and dormice, Graphiuris sp.). Virologic evidence from North American prairie dogs (Cynomys sp.) was concordant with their suspected roles as vectors for human monkeypox. Multiple tissues were found suitable for DNA detection and/or virus isolation. These data extend the potential host range for monkeypox virus infection and supports concern regarding the potential for establishment in novel reserv...

The current 'pandemic' is approached through the lens of (mainly) the concept of Homo sacer, elaborated on by Giorgio Agamben (1998). Taking the work of Michel Foucault on the 'disciplinary society' and 'bio-politics' further, and drawing on the role played by the principle of homo sacer in antiquity, Agamben uncovers the disconcerting extent to which this principle has become generalised in contemporary societies. In antiquity the principle of 'sacred man/human' was invoked in cases where someone was exempted from ritual sacrifice, but simultaneously seen as 'bare life', and therefore as being fit for execution. Agamben argues that the sphere of 'sacred life' has grown immensely since ancient times in so far as the modern state arrogates to itself the right to wield biopolitical power over 'bare life' in a manner analogous to ancient practices, and finds in the concentration camp the contemporary paradigm of this phenomenon. Arguing that today we witness a further downward step in the treatment of humans as 'bare life', these concepts are employed as heuristic for bringing into focus current practices under the aegis of the Covid-19 'pandemic'. In particular, the spotlight falls on those areas where burgeoning 'bare life' practices can be detected, namely 'origin of the virus', 'lethal vaccines', 'engineered economic collapse', 'chemtrails' and 'what (to expect) next'. In the light of emerging evidence it is argued that these practices take the notion of homo sacer, 'bare life' and its concomitant biopolitical and pharma-political practices to unprecedented, virtually incomprehensible levels of depravity.

Monkeypox virus (MPXV), a zoonotic orthopoxvirus (OPX), is endemic in the Democratic Republic of Congo (DRC). Currently, diagnostic assays for human monkeypox (MPX) focus on real-time quantitative polymerase chain reaction (PCR) assays, which are typically performed in sophisticated laboratory settings. Herein, we evaluated the accuracy and utility of a multiplex MPX assay using the GeneXpert platform, a portable rapid diagnostic device that may serve as a point-of-care test to diagnose infections in endemic areas. The multiplex MPX/OPX assay includes a MPX-specific PCR test, OPX-generic PCR test, and an internal control PCR test. In total, 164 diagnostic specimens (50 crusts and 114 vesicular swabs) were collected from suspected MPX cases in Tshuapa Province, DRC, under national surveillance guidelines. The specimens were tested with the GeneXpert MPX/OPX assay and an OPX PCR assay at the Institut National de Recherche Biomedicale (INRB) in Kinshasa. Aliquots of each specimen were ...

Monkeypox (MPXV) and cowpox (CPXV) are emerging agents that cause severe human infections on an intermittent basis, and variola virus (VARV) has potential for use as an agent of bioterror. Vaccinia immune globulin (VIG) has been used therapeutically to treat severe orthopoxvirus infections but is in short supply. We generated a large panel of orthopoxvirus-specific human monoclonal antibodies (Abs) from immune subjects to investigate the molecular basis of broadly neutralizing antibody responses for diverse orthopoxviruses. Detailed analysis revealed the principal neutralizing antibody specificities that are cross-reactive for VACV, CPXV, MPXV, and VARV and that are determinants of protection in murine challenge models. Optimal protection following respiratory or systemic infection required a mixture of Abs that targeted several membrane proteins, including proteins on enveloped and mature virion forms of virus. This work reveals orthopoxvirus targets for human Abs that mediate cros...

A monkeypox outbreak occurred in the United States in 2003. Patient's sera were sent to the Centers for Disease Control and Prevention as a part of outbreak response measures. Clinical and epidemiologic information was abstracted from the case investigation forms. Serum ...

Since its emergence in early 2020 and up until the end of May 2022, the coronavirus SARS-CoV-2 has caused more than 524 million COVID-19 cases globally, with 6.2 million deaths (∼1.2%, case fatality rate, CFR) [1,2]. Today, the risk for concurrent pandemics or the onset of future pandemics is inevitable. In fact, the history of mankind has been shaped by infectious diseases acting as independent forces of societal transformation. Zoonotic viruses represent the greatest threat impacting global health, including not only coronaviruses like the Middle East Respiratory Syndrome (MERS-CoV) [3] but also haemorrhagic fever viruses, hantaviruses, arenaviruses, arboviruses [4], and zoonotic influenza viruses [[5], [6], [7], [8]]. In addition, re-emerging conditions are also a cause of concern, particularly those comprising multiple zoonotic viruses originating from both Africa and Asia.

Background Ecological niche modeling is a method for estimation of species distributions based on certain ecological parameters. Thus far, empirical determination of significant differences between independently generated distribution maps for a single species (maps which are created through equivalent processes, but with different ecological input parameters), has been challenging. Results We describe a method for comparing model outcomes, which allows a statistical evaluation of whether the strength of prediction and breadth of predicted areas is measurably different between projected distributions. To create ecological niche models for statistical comparison, we utilized GARP (Genetic Algorithm for Rule-Set Production) software to generate ecological niche models of human monkeypox in Africa. We created several models, keeping constant the case location input records for each model but varying the ecological input data. In order to assess the relative importance of each ecologica...

The recent apparent increase in human monkeypox cases across a wide geographic area, the potential for further spread, and the lack of reliable surveillance have raised the level of concern for this emerging zoonosis. In November 2017, the World Health Organization (WHO), in collaboration with CDC, hosted an informal consultation on monkeypox with researchers, global health partners, ministries of health, and orthopoxvirus experts to review and discuss human monkeypox in African countries where cases have been recently detected and also identify components of surveillance and response that need improvement. Endemic human monkeypox has been reported from more countries in the past decade than during the previous 40 years. Since 2016, confirmed cases of monkeypox have occurred in Central African Republic, Democratic Republic of the Congo, Liberia, Nigeria, Republic of the Congo, and Sierra Leone and in captive chimpanzees in Cameroon. Many countries with endemic monkeypox lack recent ...

Monkeypox virus is a zoonotic orthopoxvirus (OPX) of west and central sub-Saharan Africa. We conducted a cross-sectional serosurvey in Likouala region, Republic of Congo to assess exposure to OPX. Whole blood was collected using Nobuto blood filter strips (NBFS). Titers of IgM and IgG to OPX were assessed using an enzyme-linked immunosorbent assay. Demographic and clinical characteristics were compared with serostatus using the chi-square test or Fisher's exact test. Multivariate logistic regression was performed to evaluate factors for independent association with serostatus. A total of 994 specimens were analyzed; the overall seroprevalence for OPX IgM was 1.7%. Age < 25 years reduced the likelihood of OPX exposure, and persons living in Ngangania village had independently higher odds (odds ratio = 33.5, 95% confidence interval = 7.2-166). Blood collection for serosurveys using NBFS is feasible and practical. Adult activities such as hunting and carcass preparation may play...

During 2012, 2013 and 2015, we collected small mammals within 25 km of the town of Boende in Tshuapa Province, the Democratic Republic of the Congo. The prevalence of monkeypox virus (MPXV) in this area is unknown; however, cases of human infection were previously confirmed near these collection sites. Samples were collected from 353 mammals (rodents, shrews, pangolins, elephant shrews, a potamogale, and a hyrax). Some rodents and shrews were captured from houses where human monkeypox cases have recently been identified, but most were trapped in forests and agricultural areas near villages. Real-time PCR and ELISA were used to assess evidence of MPXV infection and other Orthopoxvirus (OPXV) infections in these small mammals. Seven (2.0%) of these animal samples were found to be anti-orthopoxvirus immunoglobulin G (IgG) antibody positive (six rodents: two Funisciurus spp.; one Graphiurus lorraineus; one Cricetomys emini; one Heliosciurus sp.; one Oenomys hypoxanthus, and one elephant...

Following the U.S. monkeypox outbreak of 2003, blood specimens and clinical and epidemiologic data were collected from cases, defined by standard definition, and household contacts of cases to evaluate the role of preexisting (smallpox vaccine-derived) and acquired immunity in susceptibility to monkeypox disease and clinical outcomes. Orthopoxvirus-specific immunoglobulin G (IgG), IgM, CD4, CD8, and B-cell responses were measured at ∼7 to 14 weeks and 1 year postexposure. Associations between immune responses, smallpox vaccination, and epidemiologic and clinical data were assessed. Participants were categorized into four groups: (i) vaccinated cases, (ii) unvaccinated cases, (iii) vaccinated contacts, and (iv) unvaccinated contacts. Cases, regardless of vaccination status, were positive for orthopoxvirus-specific IgM, IgG, CD4, CD8, and B-cell responses. Antiorthopoxvirus immune responses consistent with infection were observed in some contacts who did not develop monkeypox. Vaccina...

Monkeypox is a zoonotic disease endemic to central and western Africa, where it is a major public health concern. Although Monkeypox virus (MPXV) and monkeypox disease in humans have been well characterized, little is known about its natural history, or its maintenance in animal populations of sylvatic reservoir(s). In 2003, several species of rodents imported from Ghana were involved in a monkeypox outbreak in the United States with individuals of three African rodent genera (Cricetomys, Graphiurus, Funisciurus) shown to be infected with MPXV. Here, we examine the course of MPXV infection in Cricetomys gambianus (pouched Gambian rats) and this rodent species' competence as a host for the virus. We obtained ten Gambian rats from an introduced colony in Grassy Key, Florida and infected eight of these via scarification with a challenge dose of 4X104 plaque forming units (pfu) from either of the two primary clades of MPXV: Congo Basin (C-MPXV: n = 4) or West African (W-MPXV: n = 4)...

Since the eradication of smallpox and the cessation of routine childhood vaccination for smallpox, the proportion of the world's population susceptible to infection with orthopoxviruses, such as variola virus (the causative agent of smallpox) and monkeypox virus, has grown substantially. In the United States, the only vaccines for smallpox licensed by the Food and Drug Administration (FDA) have been live virus vaccines. Unfortunately, a substantial number of people cannot receive live virus vaccines due to contraindications. Furthermore, no antiviral drugs have been fully approved by the FDA for the prevention or treatment of orthopoxvirus infection. Here, we show the inhibitory effect of one new antiviral compound, ST-246, on the in vitro growth properties of six variola virus strains and seven monkeypox virus strains. We performed multiple assays to monitor the cytopathic effect and to evaluate the reduction of viral progeny production and release in the presence of the compou...

During 2012, 2013 and 2015, we collected small mammals within 25 km of the town of Boende in Tshuapa Province, the Democratic Republic of the Congo. The prevalence of monkeypox virus (MPXV) in this area is unknown; however, cases of human infection were previously confirmed near these collection sites. Samples were collected from 353 mammals (rodents, shrews, pangolins, elephant shrews, a potamogale, and a hyrax). Some rodents and shrews were captured from houses where human monkeypox cases have recently been identified, but most were trapped in forests and agricultural areas near villages. Real-time PCR and ELISA were used to assess evidence of MPXV infection and other Orthopoxvirus (OPXV) infections in these small mammals. Seven (2.0%) of these animal samples were found to be anti-orthopoxvirus immunoglobulin G (IgG) antibody positive (six rodents: two Funisciurus spp.; one Graphiurus lorraineus; one Cricetomys emini; one Heliosciurus sp.; one Oenomys hypoxanthus, and one elephant...

Monkeypox virus is a zoonotic orthopoxvirus (OPX) of west and central sub-Saharan Africa. We conducted a cross-sectional serosurvey in Likouala region, Republic of Congo to assess exposure to OPX. Whole blood was collected using Nobuto blood filter strips (NBFS). Titers of IgM and IgG to OPX were assessed using an enzyme-linked immunosorbent assay. Demographic and clinical characteristics were compared with serostatus using the chi-square test or Fisher's exact test. Multivariate logistic regression was performed to evaluate factors for independent association with serostatus. A total of 994 specimens were analyzed; the overall seroprevalence for OPX IgM was 1.7%. Age < 25 years reduced the likelihood of OPX exposure, and persons living in Ngangania village had independently higher odds (odds ratio = 33.5, 95% confidence interval = 7.2-166). Blood collection for serosurveys using NBFS is feasible and practical. Adult activities such as hunting and carcass preparation may play...

Monkeypox virus (MPXV), a zoonotic orthopoxvirus (OPX), is endemic in the Democratic Republic of Congo (DRC). Currently, diagnostic assays for human monkeypox (MPX) focus on real-time quantitative polymerase chain reaction (PCR) assays, which are typically performed in sophisticated laboratory settings. Herein, we evaluated the accuracy and utility of a multiplex MPX assay using the GeneXpert platform, a portable rapid diagnostic device that may serve as a point-of-care test to diagnose infections in endemic areas. The multiplex MPX/OPX assay includes a MPX-specific PCR test, OPX-generic PCR test, and an internal control PCR test. In total, 164 diagnostic specimens (50 crusts and 114 vesicular swabs) were collected from suspected MPX cases in Tshuapa Province, DRC, under national surveillance guidelines. The specimens were tested with the GeneXpert MPX/OPX assay and an OPX PCR assay at the Institut National de Recherche Biomedicale (INRB) in Kinshasa. Aliquots of each specimen were ...