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PRI’s MPV (Monkeypox) Situation Update – November 1

Nov 1, 2022 | News

Created by PRI for the NYC Health Department. Latest editions Tuesdays and Thursdays. 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 16 October 2022, a cumulative total of 73 437 laboratory-confirmed cases of monkeypox and 29 deaths have been reported to WHO from 109 countries/territories/areas (hereafter ‘countries’[i]) in all six WHO Regions (Table 1). Since the last edition published on 5 October 2022, 4537 new cases (6.6% increase in total cases), and four new deaths have been reported. In the past seven days, 17 countries reported an increase in the weekly number of cases, with the highest increase (7.7%) reported in Peru. Three new countries Mozambique (n=1,) San Marino (n=1), and Vietnam (n=1) reported its first cases in the past seven days. Overall, 49 countries have not reported new cases for over 21 days, the maximum incubation period of the disease; 10 more countries since the last report. (WHO Sit Rep – Latest 10/19/2022 / Dashboard)
  • US: Total confirmed MPV cases: 28,302 (10.28.2022). (full version). 
  • NY State: As of October 28 2022, a total of 3,735 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

  • In Africa’s monkeypox outbreak, sickness and death go undetected (Reuters) The Africa CDC says that Congo has had more than 4,000 suspected and confirmed cases and 154 deaths this year, based in part on health authority data. That is far lower than the 27,000-odd cases recorded in the United States and 7,000 in Spain. African nations with outbreaks include Ghana, where there are about 600 suspected and confirmed cases, and Nigeria, where there are nearly 2,000.

Articles by Category

Epi/Transmission/Mitigation

Public sentiment on the global outbreak of monkeypox: an unsupervised machine learning analysis of 352,182 twitter posts (Ng et al., Public Health)

In this exploratory analysis, researchers aimed to study the public’s sentiments on the current monkeypox outbreaks via an unsupervised machine learning analysis of social media posts on Twitter. The research team extracted original tweets containing the terms ‘monkeypox’, ‘monkey pox’ or ‘monkey_pox’ and posted them in the English language from 6 May 2022 (first case detected in the United Kingdom) to 23 July 2022 (when World Health Organization declared Monkeypox to be a global health emergency). Based on topic modelling and thematic analysis of a total of 352,182 Twitter posts, they derived five topics clustered into three major themes related to the public discourse on the ongoing outbreaks. These include concerns of safety, stigmatization of minority communities, and a general lack of faith in public institutions. The public sentiments underscore growing (and existing) partisanship, personal health worries in relation to the evolving situation, as well as concerns of the media’s portrayal of lesbian, gay, bisexual, transgender and queer and minority communities, which might further stigmatize these groups. In summary, this study highlighted important societal issues, including misinformation, political mistrust and anti-gay stigma that should be sensitively considered when designing public health policies to contain the ongoing outbreaks.

Severe Monkeypox in Hospitalized Patients — United States, August 10–October 10, 2022 (Miller et al., MMWR Early Release)

As of October 21, 2022, a total of 27,884 monkeypox cases (confirmed and probable) have been reported in the United States. Gay, bisexual, and other men who have sex with men have constituted most cases, and persons with HIV infection and those from racial and ethnic minority groups have been disproportionately affected. During previous monkeypox outbreaks, severe manifestations of disease and poor outcomes have been reported among persons with HIV infection, particularly those with AIDS. This report summarizes findings from CDC clinical consultations provided for 57 patients aged ≥18 years who were hospitalized with severe manifestations of monkeypox during August 10–October 10, 2022 and highlights three clinically representative cases. Overall, 47 (82%) patients had HIV infection, four (9%) of whom were receiving antiretroviral therapy (ART) before monkeypox diagnosis. Most patients were male (95%) and 68% were non-Hispanic Black (Black). Overall, 17 (30%) patients received intensive care unit (ICU)–level care, and 12 (21%) have died. As of this report, monkeypox was a cause of death or contributing factor in five of these deaths; six deaths remain under investigation to determine whether monkeypox was a causal or contributing factor; and in one death, monkeypox was not a cause or contributing factor. The authors recommend that health care providers and public health professionals should be aware that severe morbidity and mortality associated with monkeypox have been observed during the current outbreak in the United States, particularly among highly immunocompromised persons. Providers should test all sexually active patients with suspected monkeypox for HIV at the time of monkeypox testing unless a patient is already known to have HIV infection. Providers should consider early commencement and extended duration of monkeypox-directed therapy in highly immunocompromised patients with suspected or laboratory-diagnosed monkeypox.

Monkeypox (Gessain et al., NEJM Review Article)

Here, the authors discuss the history, virology, clinical features (both in historically endemic areas and nonendemic areas), epidemiologic features, vaccination, and treatment of monkeypox virus. The authors conclude that the gradual decline in immunity to smallpox may partly explain an increase in the incidence of monkeypox in some regions where the disease is endemic. However, the current epidemic reminds the global infectious disease community that viral emergence is a permanent phenomenon without boundaries and is often unpredictable in its nature, target, and magnitude. This current outbreak in 2022 illustrates how a disease affecting one region of the world can have a strong effect on areas where it is not endemic, with different target populations and new clinical presentations. To thwart the continuation of the current monkeypox epidemic, both in the African areas where it is endemic and in newly affected regions, the authors indicate that priorities are clear: first, increase awareness and education of populations, especially at-risk groups, to prevent infection and reduce transmission and spread; second, develop rapid, sensitive point-of-care detection tests to improve diagnosis and, consequently, prevention; and third, evaluate the effectiveness of existing treatments, vaccines, and vaccination strategies and improve efforts to make vaccination and treatment available to all affected groups and regions.

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)

Monkeypox, a neglected and re‐emergent zoonotic disease caused by monkeypox virus (MPXV) infection, has been endemic in Central and Western Africa for decades. More recently, an outbreak has spread to a global level, occurring in sites with no previous reported cases and being clustered among men who have sex with men, suggesting new modes of transmission. There is an urgent need for research for a better understanding of the genomic evolution and changing epidemiology of the Orthopoxvirus group. Our work 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. Our findings suggest the sexual route as a relevant mode of transmission of MPXV and confirm the mostly benign presentation of this disease.

Vaccine

A Health Equity Approach for Implementation of JYNNEOS Vaccination at Large, Community-Based LGBTQIA+ Events — Georgia, August 27–September 5, 2022 (Millman et al., MMWR)

The Georgia Department of Public Health (DPH) requested CDC support for a vaccine pilot and received an additional allocation of 5,500 doses of JYNNEOS vaccine for administration at events leading up to and throughout a Black gay Pride festival in Atlanta, a multiday event held Labor Day weekend (September 2–5, 2022). The event celebrates lesbian, gay, bisexual, transgender, queer or questioning, intersex, asexual, and other (LGBTQIA+) communities of color and hosts more than 125,000 attendees each year. Vaccination events held before the festival (August 27–September 1) were located at local health department clinics and at venues acceptable and convenient for Black MSM, such as familiar large event spaces, bars, and clubs. During the festival (September 2–5), vaccine events were held during the day and after hours at health department clinics and at bars and clubs via mobile vans to increase broad reach and access. Georgia DPH staff members used social media, community-based organizations, and field outreach to promote vaccination events. Vaccines were administered by Georgia DPH, partner organizations, and local health departments. Patient demographic data were collected at the time of vaccination. During August 27–September 5, a total of 4,282 JYNNEOS vaccine doses (78% of the additional allocation) were administered. Two thirds (2,874) of doses were administered before the festival and one third (1,408) during the event. Overall, 2,886 (67%) doses were administered at 22 routine vaccination events at health department clinics, 702 (16%) doses at 20 mobile, community pop-up events, and 694 (16%) doses at one fixed location (a Georgia DPH-sponsored mass vaccination event). Among vaccine recipients, 93% were male, 55% were aged 30–49 years, 48% were Black, and 8% were Hispanic (Table). The proportion of Black persons receiving vaccine was higher during the festival (53%) than before the event (46%), but the proportion of Hispanic recipients was similar (7% versus 8%). Nearly one third (31%) of records were missing data on state of residence. The authors conclude that vaccinating communities disproportionately affected by the monkeypox outbreak is important in stopping spread of Monkeypox virus and ending the outbreak. A community-based approach by a coalition of festival organizers, government entities, and LGBTQIA+ community advocates was successful at improving equitable monkeypox vaccination.

Acceptance towards Monkeypox Vaccination: A Systematic Review and Meta-Analysis (Ulloque-Badaracco et al., Pathogens)

Vaccination it is considered a vital strategy in order to mitigate monkeypox by protecting from severe disease and helping in reduction of hospitalisations. In this sense, this study aims to estimate the global prevalence of vaccination acceptance against monkeypox. We conducted a systematic review with a comprehensive search strategy for the following databases: PubMed, Scopus and Web of Science. A random-effect model meta-analysis was carried out using observational studies assessing the intention of vaccines against monkeypox from multiple continents. The quality assessment was developed using the Newcastle-Ottawa Scale adapted for cross-sectional studies. In addition, a subgroup analysis by study location and population and a sensitivity analysis was developed.Eleven cross-sectional studies were included. A total of 8045 participants were included. The pooled prevalence of monkeypox vaccination acceptance in all participants was 56.0% (95%CI: 42.0–70.0%). In the subgroup analysis of monkeypox vaccine acceptance according to continents, the prevalence of
vaccine acceptance was 50.0% (95%CI: 24.0–76.0%) in Asian countries and 70.0% (95%CI: 55.0–84.0%) in European countries. The prevalence of vaccine acceptance was 43.0% (95%CI: 35.0–50.0%) in the general population, 63.0% (95%CI: 42.0–70.0%) in healthcare workers, and 84.0% (95%CI: 83.0–86.0%) in the LGBTI community. Despite the high prevalence of monkeypox vaccination acceptance in the LGBTI community found in our study, vaccination acceptance from healthcare workers and the general population are lower. Governments could use these results for planning, developing or promoting vaccination strategies and public health policies focused on these populations.

A severe monkeypox infection in a patient with an advanced HIV infection treated with Tecovirimat: clinical and virological outcome (Viguier et al., International Journal of Infectious Diseases)

A 28-year-old immunocompromised patient living with HIV/AIDS became infected with monkeypox virus. His clinical condition deteriorated for 37 days, with fever, skin lesions and diarrhea before going to the infectious diseases department, where his severe, protracted infection was treated with Tecovirimat for 14 days. He rapidly improved, the skin lesions decreased, as did the monkeypox virus loads, with no adverse events. This case indicates that Tecovirimat might be effective for treating immunocompromised patients infected with monkeypox virus.

Virology

ORF-Interrupting Mutations in Monkeypox Virus Genomes from Washington and Ohio, 2022 (Sereewit et al., Viruses)

Monkeypox virus, the causative agent of the 2022 monkeypox outbreak, is a doublestranded DNA virus in the Orthopoxvirus genus of the Poxviridae family. Genes in terminal regions of Orthopoxvirus genomes mostly code for host-pathogen interaction proteins and are prone to selective pressure and modification events. Using viral whole genome sequencing, we identified twenty-five total clinical samples with ORF-disrupting mutations, including twenty samples encoding nonsense mutations in MPXVgp001/191 (OPG001), MPXVgp004/188 (OPG015), MPXVgp010 (OPG023), MPXVgp030 (OPG042), MPXVgp159 (OPG0178), or MPXVgp161 (OPG181). Additional mutations include a frameshift leading to an alternative C-terminus in MPXVgp010 (OPG023) and an insertion in an adenine homopolymer at the beginning of the annotated ORF for MPXVgp153 (OPG151), encoding a subunit of the RNA polymerase, suggesting the virus may instead use the start codon that encodes Met9 as annotated. Finally, we detected three samples with large (>900 bp) deletions. These included a 913 bp deletion that truncates the C-terminus of MPXVgp010 (OPG023); a 4205 bp deletion that eliminates MPXVgp012 (OPG025), MPXVgp013 (OPG027), and MPXVgp014 (OPG029) and truncates MPXVgp011 (OPG024; D8L) and MPXVgp015 (OPG030); and a 6881 bp deletion that truncates MPXVgp182 (OPG210) and eliminates putative ORFs MPXVgp184, MPXVgp185 (OPG005), and MPXVgp186, as well as MPXVgp187 (OPG016), and MPXVgp188 (OPG015) from the 3’ ITR only. MPXVgp182 encodes the monkeypox specific, highly immunogenic surface glycoprotein B21R which has been proposed as a serological target. Overall, we find greater than one-tenth of our sequenced MPXV isolates have at least one gene inactivating mutation and these genes together comprised greater than one-tenth of annotated MPXV genes. Our findings highlight non-essential genes in monkeypox virus that may be evolving as a result of selective pressure in humans, as well as the limitations of targeting them for therapeutics and diagnostic testing.

Immunoinformatics-Aided Design of a Peptide Based Multiepitope Vaccine Targeting Glycoproteins and Membrane Proteins against Monkeypox Virus (Akhtar et al., Viruses)

Monkeypox is a self-limiting zoonotic viral disease and causes smallpox-like symptoms. The disease has a case fatality ratio of 3–6% and, recently, a multi-country outbreak of the disease has occurred. The currently available vaccines that have provided immunization against monkeypox are classified as live attenuated vaccinia virus-based vaccines, which pose challenges of safety and efficacy in chronic infections. In this study, we have used an immunoinformatics-aided design of a multi-epitope vaccine (MEV) candidate by targeting monkeypox virus (MPXV) glycoproteins and membrane proteins. From these proteins, seven epitopes (two T-helper cell epitopes, four Tcytotoxic cell epitopes and one linear B cell epitopes) were finally selected and predicted as antigenic, non-allergic, interferon-γ activating and non-toxic. These epitopes were linked to adjuvants to design a non-allergic and antigenic candidate MPXV MEV. Further, molecular docking and molecular dynamics simulations predicted stable interactions between predicted MEV and human receptor TLR5. Finally, the immune-simulation analysis showed that the candidate MPXV-MEV could elicit a human immune response. The results obtained from these in silico experiments are promising but require further validation through additional in vivo experiments.

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