PRI’s MPV (Monkeypox) Situation Update – November 29

Nov 29, 2022 | News

Created by PRI for the NYC Health Department. Latest editions Tuesdays. While we use the language “MPV”, most sources do not, and readers will see the language fluctuate within the report. For questions and feedback, please email info@pri.nyc

Summary

Case Counts/Trends and Large Guidance/Response Changes (Limited by latest reporting)

  • GLOBAL: From 1 January through 13 November 2022, a cumulative total of 79 411 laboratory-confirmed cases of monkeypox and 50 deaths have been reported to WHO from 110 countries/territories/areas (hereafter ‘countries’[i]) in all six WHO Regions (Table 1). Since the last edition published on 2 November 2022, 2147 new cases (2.8% increase in total cases), and 14 new deaths have been reported. In the past seven days, 18 countries reported an increase in the weekly number of cases, with the highest increase reported in Brazil. Overall, 63 countries have not reported new cases for over 21 days, the maximum incubation period of the disease, five more countries since the last report. (WHO Sit Rep – Latest 11/16/2022 / Dashboard)
  • US: Total confirmed MPV cases: 29,288 (11.28.2022). (full version). 
  • NY State: As of November 14 2022, a total of 3,771 confirmed orthopoxvirus/monkeypox cases – a designation established by the Centers for Disease Control and Prevention (CDC). (NY Sit Rep and County List) 

US Updates/News

Global Updates/News

Articles by Category

Epi/Transmission/Mitigation

Public understanding and awareness of and response to monkeypox virus outbreak: A cross-sectional survey of the most affected communities in the United Kingdom during the 2022 public health emergency (Paparini et al., HIV Medicine)

The objective of this study was to examine the public response to public health and media messaging during the human monkeypox virus (MPXV) outbreak in the UK, focusing on at-risk communities. A co-produced, cross-sectional survey was administered in June and July 2022 using community social media channels and the Grindr dating app. Basic descriptive statistics, logistic regression, and odds ratio p values are presented. Of 1932 survey respondents, 1750 identified as men, 88 as women, and 64 as gender non-conforming. Sexual identity was described as gay/lesbian/queer (80%), bisexual (12%), heterosexual (4%), and pansexual (2%); 39% were aged <40 years; 71% self-identified as White, 3% as Black, 8% as Asian, 2%as LatinX, and 11% as ‘Mixed or Other’ heritage groups. In total, 85% were employed and 79% had completed higher education. A total of 7% of respondents identified themselves as living with HIV. Overall, 34% reported limited understanding of public health information, 52% considered themselves at risk, 61% agreed that people with MPXV should isolate for 21 days, 49% reported they would first attend a sexual health clinic if symptomatic, 86% reported they would accept a vaccine, and 59% believed that MPXV originated from animals. The most trusted sources of information were healthcare professionals (37%), official health agencies (29%), and mainstream media (12%). The authors conclude that vaccine acceptability was very high, yet the understanding and acceptance of public health information varied.

Understanding sexual transmission dynamics and transmission contexts of monkeypox virus: a mixed-methods study of the early outbreak in Belgium (May–June 2022) (Vanhamel et al., Sexually Transmitted Infections)

The available epidemiological and clinical evidence from the currently ongoing monkeypox (MPX) outbreak in non-endemic areas suggests an important factor of sexual transmission. However, limited information on the behaviour and experiences of individuals with an MPX infection has to date been provided. Here, the authors aimed to describe the initial phase of the MPX outbreak in Belgium, and to provide a more in-depth description of sexual behaviour and transmission contexts. They used routine national surveillance data of 139 confirmed MPX cases with date of symptom onset until 19 June 2022, complemented with 12 semistructured interviews conducted with a subsample of these cases. Sexualised environments, including large festivals and cruising venues for gay men, were the suspected exposure setting for the majority of the cases in the early outbreak phase. In-depth narratives of sexual behaviour support the hypothesis of MPX transmission through close physical contact during sex. Despite awareness of the ongoing MPX outbreak, low self-perceived risk of MPX acquisition and confusing initial signs and symptoms for other STIs or skin conditions delayed early detection of an MPX infection. In addition, they describe relevant contextual factors beyond individual behaviour, related to sexual networks, interpersonal interactions and health systems. Some of these factors may complicate early MPX detection and control efforts. These findings highlight the role of sexual contact and networks in the transmission of MPX during the early phase of the outbreak in Belgium. The authors recommend risk communication messages should consistently and transparently state the predominant sexual transmission potential of MPX virus, and prevention and control measures must be adapted to reflect multilevel factors contributing to MPX transmission risk.

Clinical and Epidemiological Features of Hospitalized and Ambulatory Patients with Human Monkeypox Infection: A Retrospective Observational Study in Portugal (Caria et al., Infectious Disease Reports)

This study aimed to characterize the clinical and epidemiological features of a cohort of patients with MPXV infection in a Portuguese hospital, admitted between 5 May and 26 July 2022. In this retrospective observational study, aggregate data of a case series on the presentation, clinical course, and outcomes of confirmed MPXV infections are reported. The study included 40 men and 1 woman, with a mean age of 37.2 years old; 92.7% identified as men who have sex with men, 90.2% had unprotected sex or sex with multiple or anonymous partners in the previous month, and 39.0% reported to have had sex with an MPXV-confirmed case; 59.5% had previously known human immunodeficiency virus (HIV) infection, all of whom were under antiretroviral therapy, and no patients had acquired immunodeficiency syndrome (AIDS) criteria. About a quarter of patients were observed only a week after symptom onset. All patients had skin or mucosal lesions and the anogenital region was the most frequent lesion site. There were no statistically significant clinical differences between HIV-positive and negative individuals. Four patients were admitted to the inpatient clinic, two of whom had proctitis with difficult-to-manage anal pain. There were no reported deaths. These findings suggest the sexual route as a relevant mode of transmission of MPXV and confirm the mostly benign presentation of this disease.

Monitoring monkeypox virus in saliva and air samples in Spain: a cross-sectional study (Hernaez et al., Lancet Microbe)

In this cross-sectional study, researchers aimed to assess the presence of monkeypox virus DNA and infectious virus in saliva samples and droplets and aerosols exhaled from patients infected with monkeypox virus. The study included patients with monkeypox confirmed by PCR who attended two health centers in Madrid, Spain. For each patient, the research team collected samples of saliva, exhaled droplets within a mask, and aerosols captured by air filtration through newly developed nanofiber filters. Between May 18 and July 15, 2022, 44 patients with symptomatic monkeypox attended two health centers in Madrid and were included in the study. All were cisgender men, with a median age of 35.0 years (IQR 11.3). They identified high loads of monkeypox virus DNA by qPCR in 35 (85%) of 41 saliva samples. Infectious monkeypox virus was recovered from 22 (67%) of 33 saliva samples positive for monkeypox virus DNA. They also found a significant association between the number of affected cutaneous areas or general symptoms and the viral load present in saliva samples. Droplets exhaled from patients with monkeypox, detected inside a mask, contained monkeypox virus DNA in 32 (71%) of 45 samples, with two of the 32 positive samples showing the presence of the infectious virus. Monkeypox virus DNA in aerosols, collected from the medical consultation room, were detected in 27 (64%) of 42 samples, despite patients wearing an FFP2 mask during the visit. Infectious virus was not recovered from aerosol samples. High levels of monkeypox virus DNA were identified in aerosols collected from a hospital isolation room housing a patient with monkeypox. Overall, the detection of high monkeypox viral loads in saliva and monkeypox DNA in respiratory excretions warrants further epidemiological studies to evaluate the potential relevance of the respiratory route of infection in the 2022 outbreak.

Diagnosis, treatment, and prevention of monkeypox in children: an experts’ consensus statement (Jiang et al., World Journal of Pediatrics)

Monkeypox is a zoonotic disease. Since the first human monkeypox case was detected in 1970, it has been prevalent in some countries in central and western Africa. Since May 2022, monkeypox cases have been reported in more than 96 non-endemic countries and regions worldwide. As of September 14, 2022, there have been more than 58,200 human monkeypox cases, and there is community transmission. The cessation of smallpox vaccination in 1980, which had some cross-protection with monkeypox, resulted in a general lack of immunity to monkeypox, which caused global concern and vigilance. As of September 14, 2022, there are four monkeypox cases in China, including three in Taiwan province and one in Hong Kong city. Previous foreign studies have shown that children are vulnerable to monkeypox and are also at high risk for severe disease or complications. In order to improve pediatricians’ understanding of monkeypox and achieve early detection, early diagnosis, early treatment, and early disposal, we have organized national authoritative experts in pediatric infection, respiratory, dermatology, critical care medicine, infectious diseases, and public health and others to formulate this expert consensus, on the basis of the latest “Clinical management and infection prevention and control for monkeypox” released by The World Health Organization, the “guidelines for diagnosis and treatment of monkeypox (version 2022)” issued by National Health Commission of the People’s Republic of China and other relevant documents. During the development of this consensus, multidisciplinary experts have repeatedly demonstrated the etiology, epidemiology, transmission, clinical manifestations, laboratory examinations, diagnosis, differential diagnosis, treatment, discharge criteria, prevention, disposal process, and key points of prevention and control of suspected and confirmed cases.

Smallpox vaccination discontinuation and monkeypox incidence in an African endemic region: a reanalysis on the relationship between the withdrawal of smallpox vaccine and subsequent morbidity (Mungmunpuntipantip et al., American Journal of Clinical and Experimental Immunology)

Background: Monkey pox has expanded across Europe as a result of the widespread outbreak, creating a severe public health risk. Monkey pox is an uncommon pox infection that has reappeared due to zoonosis. Monkey pox has spread over Europe and North America, posing a serious public health risk. The regular smallpox vaccine has been shown to be effective against monkeypox. The suspension of smallpox immunization is currently being debated due to the possibility of a connection with the current monkeypox outbreak. In clinical immunology, the link between a desire for smallpox vaccination, low population immunity, and a higher incidence of monkeypox is an intriguing topic. Methods: This is a descriptive analysis done in the past. The writers investigate the situation in West Africa in this research. The available data on monkeypox incidence in an African endemic area was reassessed. Results: Based on a recent analysis of epidemiological data from an endemic area, there is no indication of a yearly ongoing increase in monkeypox incidence following the discontinuation of the smallpox vaccine, and incidence varies. Conclusion: There is no evidence of an annual increase in monkeypox incidence following the withdrawal of smallpox immunization.

Vaccine

Single and 2-dose vaccinations with modified vaccinia Ankara-Bavarian Nordic® induce durable B cell memory responses comparable to replicating smallpox vaccines (Ilchmann et al., Journal of Infectious Diseases)

This article reports on two studies that were conducted to assess safety, immunogenicity, and boost response with Modified Vaccinia Ankara – Bavarian Nordic (MVA-BN) in healthy adults with and without prior smallpox vaccination. These studies were conducted from 2006-2009 at one European site. Participants naïve to smallpox vaccination were randomized to 1 dose MVA-BN (1×MVA, N = 181), 2 doses MVA-BN (2×MVA, N = 183), or placebo (N = 181). Participants with previous smallpox vaccination received 1 MVA-BN booster (HSPX+, N = 200). Subsets of the formerly naïve groups (∼75 each) received an MVA-BN booster 2 years later. Neutralizing antibody (nAb) geometric mean titers (GMTs) increased from 1.1 (baseline, both naïve groups) to 7.2 and 7.5 (Week 4, 1×MVA and 2×MVA, respectively), and further to 45.6 (Week 6, 2×MVA after second vaccination). In HSPX+, nAb GMT rapidly increased from 21.6 (baseline) to 175.1 (Week 2). At 2 years, GMTs for 1×MVA, 2×MVA, and HSPX+ were 1.1, 1.3, and 10.3, respectively. After boosting in the previously naïve groups, nAb GMTs increased rapidly in 2 weeks to 80.7 (1×MVA) and 125.3 (2×MVA), higher than after primary vaccination and comparable to boosted HSPX+ subjects. Six months after boosting, GMTs were 25.6 (1×MVA) and 49.3 (2×MVA). No safety concerns were identified. In summary, anamnestic responses without sustained high nAb titers support presence of durable immunological memory following MVA-BN immunization.

Comparison of Biological, Pharmacological Characteristics, Indications, Contraindications and Adverse Effects of JYNNEOS and ACAM2000 Monkeypox Vaccines (Meo et al., Vaccines)

Human monkeypox is an emerging viral zoonotic disease, that has caused highly distinctive, challenging and threatening problems worldwide. The US Food and Drug Administration (FDA) has given interim authorization for the JYNNEOS and ACAM2000 vaccines for the outbreak of monkeypox 2022. The present study aims to highlight the globally derived evidence about the biological and pharmacological features, indications, contraindications and adverse effects of JYNNEOS and ACAM2000 vaccines. Initially, 82 documents were selected and, finally, 14 fact sheets, documents and international organizations were included. The data were recorded from the World Health Organization (WHO), Centers for Disease Control and Prevention (CDC), Food and Drug Administration (FDA) USA, ISI-Web of Science, PubMed, EMBASE and Scopus. The data revealed that the JYNNEOS vaccine has been recommended to children, adults, females during pregnancy and people of all age groups with a dose of 0.5 mL, and the complete vaccination cost per person is about USD 115. It provides immunogenicity, and the mean titer of neutralizing antibodies was 153.5. However, the ACAM2000 vaccine is contraindicated in infants and pregnant females, and recommended to people over 18 years of age and older, with a single dose of 0.0025 mL, and a cost of about USD 139. ACAM2000 provides immunogenicity, and the mean titer of neutralizing antibodies was 79.3. The JYNNEOS vaccine has mild adverse effects including pain, redness, swelling or itching at the site of the vaccine shot, fever, fatigue, headache, nausea and muscle pain. However, the ACAM2000 vaccine can cause pain, redness, edema, headache, fever, fatigue, muscle pain, body ache, nausea, vomiting, diarrhea, shortness of breath and increased risk of myopericarditis and cardiomyopathy. The evidence supports the view that both vaccines are beneficial, but the overall impact of JYNNEOS is better than that of ACAM2000.

Treatment

Virtual screening and computational simulation analysis of antimicrobial photodynamic therapy using propolis-benzofuran A to control of Monkeypox (Pourhajibagher et al., Photodiagnosis and Photodynamic Therapy)

Monkeypox is a viral zoonotic disease and there are no available treatments that specifically target the monkeypox virus. Antimicrobial photodynamic therapy (aPDT) is a non-invasive approach that has been introduced as a targeted adjuvant treatment against various microbial infections. In this study, we used a computational strategy to investigate the potential of aPDT using propolis-benzofuran A against the Monkeypox virus. In this in silico study, the evaluation of drug-likeness, molecular properties, and bioactivity of propolis-benzofuran A was carried out using SwissADME. Pro-Tox II and OSIRIS servers were used to identify the organ toxicities and toxicological endpoints of propolis-benzofuran A. Molecular docking approach was employed to screen the potential binding modes of propolis-benzofuran A ligand with the Monkeypox virus A48R protein (PDB ID: 2V54). The results of the computational investigation revealed that propolis-benzofuran A obeyed all the criteria of Lipinski’s rule of five and exhibited drug-likeness. The photosensitizing agent tested was categorized as toxicity class-5 and was found to be non-hepatotoxic, non-carcinogenic, non-mutagenic, and non-cytotoxic. The docking studies employing a predicted three-dimensional model of Monkeypox virus A48R protein with propolis-benzofuran A ligand exhibited good binding affinity (-7.84 kcal/mol). The computational simulation revealed that propolis-benzofuran A had a strong binding affinity with the Monkeypox virus A48R protein. Hence, aPDT based on this natural photosensitizer can be proposed as an adjuvant treatment against the Monkeypox virus.

Virology

Inverted repeats in the monkeypox virus genome are hot spots for mutation (Dobrovolná et al., Journal of Medical Virology)

The current monkeypox virus (MPXV) strain differs from the strain arising in 2018 by 50+ single nucleotide polymorphisms (SNPs) and is mutating much faster than expected. The cytidine deaminase apolipoprotein B messenger RNA editing enzyme, catalytic subunit B (APOBEC3) was hypothesized to be driving this increased mutation. APOBEC has recently been identified to preferentially mutate cruciform DNA secondary structures formed by inverted repeats (IRs). IRs were recently identified as hot spots for mutation in severe acute respiratory syndrome coronavirus 2, and we aimed to identify whether IRs were also hot spots for mutation within MPXV genomes. We found that MPXV genomes were replete with IR sequences. Of the 50+ SNPs identified in the 2022 outbreak strain, 63.9% of these were found to have arisen within IR regions in the 2018 reference strain (MT903344.1). Notably, IR sequences found in the 2018 reference strain were significantly lost over time, with an average of 32.5% of these sequences being conserved in the 2022 MPXV genomes. This evidence was highly indicative that mutations were arising within IRs. This data provides further support to the hypothesis that APOBEC may be driving MPXV mutation and highlights the necessity for greater surveillance of IRs of MPXV genomes to detect new mutations.

Print Friendly, PDF & Email