Human Monkeypox Research

We report a fatal case of disseminated mpox infection that progressed over more than three months in an HIV-infected patient with acquired immunodeficiency syndrome (AIDS). Mucocutaneous, pleuropulmonary, central nervous system, and gastrointestinal involvement was documented. This course of disease resembles progressive vaccinia, a formerly reported disease caused by uncontrolled replication of smallpox vaccination orthopoxviruses in immunosuppressed patients. Severe small bowel involvement jeopardized normal oral tecovirimat and antiretroviral therapy absorption. This problem prompted the use of full parenteral antiretrovirals and endovenous cidofovir. Although a remarkable decrease in HIV viral load occurred in six days, mpox infection continued to progress, and the patient died of septic shock. This case offers new clinical insights on the presentation of severe disease in AIDS patients. Moreover, this case alerts for the need for prompt therapy initiation in patients at risk of ominous clinical progression. Full article

Mpox is a great public health concern worldwide currently; thus, a global primary epidemiological analysis of mpox and a phylogenetic analysis of currently circulating MPXV strains based on open-source data is necessary. A total of 83,419 confirmed cases with 72 deaths were reported from 7 May to 23 December 2022, representing an ongoing increasing trend. Mpox was largely restricted to being endemic in children in West Africa (WA) before 2022, and it mainly spread from animals to humans. Our analysis highlights that mpox has not only spread across regions within Africa but has also led to most infection events outside Africa. Currently, mpox has been dominated by human-to-human spread in 110 countries, with the majority of cases distributed in the non-endemic regions of Europe and North America. These data indicate that the geographic range, transmission route, vulnerable populations, and clinical manifestations of mpox have changed, which suggests that the niche of mpox has the potential to change. Remarkably, approximately 38,025 suspected mpox cases were recorded in West and Central Africa during 1970–2022, which implied that the epidemiology of mpox in the two regions remained cryptic, suggesting that strengthening the accuracy of molecular diagnosis on this continent is a priority. Moreover, 617 mpox genomes have been obtained from 12 different hosts; these data imply that the high host diversity may contribute to its ongoing circulation and global outbreak. Furthermore, a phylogenetic analysis of 175 MPXV genome sequences from 38 countries (regions) showed that the current global mpox outbreak was caused by multiple sub-clades in the clade IIb lineage. These data suggest that MPXV strains from the clade IIb lineage may play a predominated role in the spread of mpox worldwide, implying that the current mpox outbreak has a single infection source. However, further investigations into the origin of the new global mpox outbreak are necessary. Therefore, our analysis highlights that adjusted timely interventive measures and surveillance programs, especially using cheap and quick strategies such as wastewater monitoring the DNA of MPXV in Africa (WA), are important for uncovering this disease’s transmission source and chain, which will help curb its further spread. Full article

Due to the rapid evolution of the monkeypox virus, the means by which the monkeypox virus is spread is subject to change. Therefore, the present study aims to analyze the detection of the monkeypox virus according to the collection site of samples from confirmed monkeypox cases. A systematic literature review was performed using PubMed, Scopus, Web of Science, and Embase databases until 5 October 2022. A total of 1022 articles were retrieved using the search strategy. After removing duplicates (n = 566) and examining by title, abstract, and full text, 65 studies reporting monkeypox case reports were included with a detailed description of risk factors, sexually transmitted infections (STIs), site of monkeypox virus-positive specimens, location of skin lesions, and diagnostic test. A total of 4537 confirmed monkeypox cases have been reported, of which 98.72% of the cases were male with a mean age of 36 years, 95.72% had a sexual behavior of being men who have sex with men, and 28.1% had human immunodeficiency virus (HIV). The most frequent locations of lesions in patients diagnosed with monkeypox were: 42.85% on the genitalia and 37.1% in the perianal region. All confirmed monkeypox cases were diagnosed by reverse transcriptase polymerase chain reaction (RT-PCR), and the most frequent locations of samples collected for diagnosis that tested positive for monkeypox virus were: 91.85% from skin lesions, 20.81% from the oropharynx, 3.19% from blood, and 2.43% from seminal fluid. The disease course of the cases with monkeypox was asynchronous, with no severe complications, and most patients did not report specific treatment but simply followed a symptomatic treatment. Full article

The recent outbreak of Monkeypox virus requires the development of a vaccine specifically directed against this virus as quickly as possible. We propose here a new strategy based on a two-step analysis combining (i) the search for binding domains of viral proteins to gangliosides present in lipid rafts of host cells, and (ii) B epitope predictions. Based on previous studies of HIV and SARS-CoV-2 proteins, we show that the Monkeypox virus cell surface-binding protein E8L possesses a ganglioside-binding motif consisting of several subsites forming a ring structure. The binding of the E8L protein to a cluster of gangliosides GM1 mimicking a lipid raft domain is driven by both shape and electrostatic surface potential complementarities. An induced-fit mechanism unmasks selected amino acid side chains of the motif without significantly affecting the secondary structure of the protein. The ganglioside-binding motif overlaps three potential linear B epitopes that are well exposed on the unbound E8L surface that faces the host cell membrane. This situation is ideal for generating neutralizing antibodies. We thus suggest using these three sequences derived from the E8L protein as immunogens in a vaccine formulation (recombinant protein, synthetic peptides or genetically based) specific for Monkeypox virus. This lipid raft/ganglioside-based strategy could be used for developing therapeutic and vaccine responses to future virus outbreaks, in parallel to existing solutions. Full article

During the COVID-19 pandemic, the increase in reports of human monkeypox virus infection cases spreading in many countries outside Africa is a major cause for concern. Therefore, this study aimed to explore the evidence of antiviral pharmacotherapy available for the treatment of adult patients with monkeypox. A scoping review of the literature was conducted using PubMed, Scopus, Web of Science, Embase, and CENTRAL databases until 12 September 2022. The key search terms used were “monkeypox” and “treatment”. A total of 1927 articles were retrieved using the search strategy. After removing duplicates (n = 1007) and examining by title, abstract, and full text, 11 studies reporting case reports of monkeypox with antiviral treatment were included, detailing the number of monkeypox cases, clinical manifestations, number of participants with antiviral treatment, history of sexually transmitted diseases, method of diagnosis, location of skin lesions, drugs used in antiviral treatment, route of administration, and outcome. A total of 1281 confirmed cases of monkeypox have been reported, of which 65 monkeypox cases had antiviral treatment distributed most frequently in the United States (n = 30), the United Kingdom (n = 6), and Spain (n = 6). Of the total cases, 1269 (99.1%) were male with an age range of 18 to 76 years, and 1226 (95.7%) had a sexual behavior of being men who have sex with men. All confirmed cases of monkeypox were diagnosed by reverse transcriptase polymerase chain reaction (RT-PCR). The most frequent clinical manifestations were skin lesions, fever, lymphadenopathy, headache, fatigue, and myalgia. The most frequent locations of the lesions were perianal, genital, facial, and upper and lower extremities. The most commonly used drugs for antiviral treatment of monkeypox were: tecovirimat, cidofovir, and brincidofovir. All patients had a complete recovery. According to current evidence, the efficacy and safety of antiviral drugs against monkeypox is of low quality and scarce. Full article

Background. The clinical and epidemiological data of the recent outbreak of monkeypox (MPX) differ from previous reports. One difference is the epidemiological profile; the disease mainly affects a subgroup of MSM (men who have sex with men) with high-risk sexual behaviors, frequently persons living with human immunodeficiency virus (PLHIV). Methods. In this observational analysis, all patients with PCR (polymerase chain reaction)-confirmed MPX attending an Infectious Diseases and Tropical Medicine Unit in Gran Canaria (Spain) between May and July 2022 were considered. Results. In total, 42 men were included; 88% were identified as MSM, with a median age of 40 years. Only 43% were born in Spain. All the patients had systemic symptoms and skin lesions. The distribution of lesions was more frequent in the genital/anal region, and the involvement of hands and feet was less common. Fever and lymphadenopathies were less frequent than in other series. Other unusual manifestations were proctitis, pharyngitis and penile–scrotal edema. Half of the patients had other associated infections (mainly STIs, sexually transmitted infections), and 60% of the monkeypox patients had PLHIV (People Living with HIV). When comparing the clinical characteristics between HIV-positive and -negative patients, we found three main differences: (i) a higher frequency of perioral lesions, (ii) a higher frequency of pharyngitis and (iii) a higher number of sexually transmitted infections in HIV-positive patients. Conclusions. The clinical findings in this outbreak of MPX had great variability in presentation. Several clinical differences were found in PLHIV-coinfected patients. Full article

The current monkeypox epidemic is most prevalent among men who have sex with men (MSM). PrEP users and MSM with HIV (MSMHIV) are considered at highest risk of monkeypox infection in The Netherlands, and are being targeted for monkeypox vaccination. Together with the epidemiological evidence, perceived concern and risk are also relevant for decision making about health behaviour, e.g., vaccination uptake. It is thus timely to examine which subpopulations among MSM consider themselves to be most at risk and are most concerned about monkeypox. This study aimed to help determine if the current measures to curb the epidemic are successfully targeted or not in The Netherlands. We conducted an online survey among 394 MSM living in The Netherlands. We first calculated the prevalence and standardised prevalence ratio (SPR) of high perceived monkeypox concern/risk by PrEP-use and HIV status. We then conducted two multivariable logistic regression analyses to investigate perceived monkeypox concern/risk and their potential socio-demographic/behavioural/health/psycho-social determinants. Among the included MSM, 52% showed high perceived concern about and 30% showed high perceived risk of monkeypox infection. PrEP users (SPR = 0.83) showed a significantly lower chance of perceived concern; in addition, MSMHIV (SPR = 2.09) were found to have a significantly higher chance of perceiving high risk of monkeypox infection. In the multivariable logistic analyses, non-PrEP users (aOR = 2.55) were more likely to perceive higher concern, while MSM who were retired (aOR = 0.23) and who had had chemsex recently (aOR = 0.63) were less likely to perceive higher concern. MSMHIV (aOR = 4.29) and MSM who had an unknown/undisclosed HIV status (aOR = 6.07), who had attended private sex parties (aOR = 2.10), and who knew people who have/had monkeypox (aOR = 2.10) were more likely to perceive a higher risk for monkeypox infection. We found that high perceived risk (aOR = 2.97) and high perceived concern (aOR = 3.13) were correlated with each other. In sum, only one-third of MSM living in The Netherlands considered themselves at high risk of monkeypox infection, and only half of them reported high concern. We identified a potential discrepancy between “actual risk” and perceived risk of and concern about monkeypox among MSM in this early stage of the monkeypox epidemic in The Netherlands, especially among PrEP users and MSMHIV. More refined public health communication strategies may be needed to improve the understanding and knowledge of the “actual risk” of monkeypox infections among MSM sub-populations, to facilitate health behaviour uptake. Full article

Rapid diagnosis is key to containing viral outbreaks. However, for the current monkeypox outbreak the major deterrent to rapid testing is the requirement for higher biocontainment of potentially infectious monkeypox virus specimens. The current CDC guidelines require the DNA extraction process before PCR amplification to be performed under biosafety level 3 unless vaccinated personnel are performing assays. This increases the turn-around time and makes certain laboratories insufficiently equipped to handle specimens from patients with suspected monkeypox infection. We investigated the ability of five commercially available lysis buffers and heat for inactivation of monkeypox virus. We also optimized the use of monkeypox virus in Hologic^® Panther Specimen Lysis Buffer for detection of virus in the Panther Fusion^® Open Access System using published generic and clade specific monkeypox virus primers and probes. Full article

Background: Human monkeypox was a neglected zoonotic disease considered endemic to rainforests of rural parts of Central and Western Africa, until a global outbreak in May 2022. Methods: This review describes the epidemiological characteristics of human monkeypox. Results: Since the first confirmed case in the United Kingdom on 13 May 2022, and up until 19 September, more than 62,000 cases of human monkeypox were reported in 104 countries in the world (among them 97 countries where the monkeypox virus was not endemic). Up to today, 20 persons have died in this global outbreak. This outbreak predominantly affects men self-identifying as gay or bisexual or other men who have sex with men, and for now, there is no sign of continuous transmission of the disease in other populations. Today, the monkeypox outbreak is increasing alarmingly in many countries and presents a new challenge and a large issue for public health worldwide. The World Health Organization declared the global monkeypox outbreak a public health emergency of international concern on 24 July 2022. Before this outbreak, health professionals in many countries had a knowledge gap and a lack of experience in the management of monkeypox. Conclusions: Advances in the comprehension of the epidemiology of human monkeypox are necessary for effective prevention and outbreak response. Full article