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PRI’s MPV (Monkeypox) Situation Update – October 25

Oct 25, 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: 28,004 (10.24.2022). (full version). 
  • NY State: As of October 21 2022, a total of 3,712 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

  • Variations in low-complexity regions in monkeypox genome found to impact virus transmissibility (News Medical) The present study investigated whether LCR variations were mainly responsible for MPXV genome alterations and the unexpected MPXV 2022 outbreak epidemiology. Overall, the study findings showed that most of the MPXV genomic variability occurred in LCRs. Therefore, research emphasizing phenotypic MPXV differences should focus on LCR variations rather than SNP variations.

Articles by Category

Epi/Transmission/Mitigation

Oral lesions in patients with human monkeypox: a systematic scoping review (Ardila et al., Journal of Oral Pathology and Medicine)

In this systematic scoping review, researchers aimed to describe the clinical features and location of oral lesions in patients with human monkeypox (MP). The review was accomplished by implementing the PRISMA extension for scoping reviews. The analysis incorporated varied databases and the gray literature. The initial electronic exploration included 889 reports, of which 843 studies were eliminated. Reading the full text occasioned the omission of 27 additional investigations. In the end, 19 publications were included. These reports analyzed 1256 patients with MP, mostly described in Europe. Most of them were men who have sex with men. The study population consisted mainly of adults but children were also infected. The oral lesions of MP patients were observed in different parts of the oral mucosa, including lips and tongue, but mainly in the tonsils (15 cases). The oral lesions manifested as papules, vesicles, pustules, and ulcers. Erythema, edema, enanthema, and severe pain were also observed, accompanied by tonsillar enlargement. Sore throat was also reported. MP is accompanied by a significant number of systemic manifestations, mainly including multiple skin lesions throughout the body, as well as lymphadenopathy, fever, headache, myalgia, and fatigue, among others. The symptoms associated with MP were managed with different antiretroviral and antimicrobial therapies and medications to control pain and fever principally. Seventeen deaths were documented. In summary, most MP-associated oral lesions are seen in different parts of the oral mucosa, mainly in the tonsils manifested as papules, vesicles, pustules, and ulcers.

High monkeypox vaccine acceptance among male users of smartphone-based online gay-dating apps in Europe, 30 July to 12 August 2022 (Reyes-Urueña et al., Eurosurveillance)

In this survey study, researchers aimed to assess the acceptance of MPX vaccination among male adult users of smartphone-based online gay-dating apps in the World Health Organization (WHO) European Region. Among 32,902 individuals who answered the online survey, the median age was 38 years (interquartile range (IQR):  30–47). Most of the respondents were living in the Western and Mediterranean subregions of Europe. Overall, 11.5% (n = 3,780) of respondents were people living with HIV (PLWHIV) on antiretroviral therapy (ART), 0.4% (n = 123) were PLWHIV not on ART. Of those who were HIV-negative, 26.1% (7,210/27,585) among those who provided information reported using pre-exposure prophylaxis (PrEP) for HIV in the last 3 months. Almost a quarter of respondents (18.7%; n = 6,156) were diagnosed with a sexually transmitted infection (STI) in the last 12 months and 8.8% (n = 2,892) had engaged in chemsex (defined as having used mephedrone, GHB/GBL, ketamine or crystal methamphetamine during sex with other sexual partners) in the last 3 months. A total of 851 respondents (2.6%) reported that they had been diagnosed with MPX, whereas 13.5% (n = 4,449) knew someone who had been diagnosed with MPX. Overall, 26,980 (82.0%) respondents reported they would accept MPX vaccination. Vaccination acceptance was strongly associated with the belief that MPX is a ‘severe’ (aRR: 2.65; 90% CrI: 2.05–3.58) or ‘very severe’ (aRR: 2.78; 90% CrI: 2.12–3.81) disease, vs ‘not severe’ respectively. Being linked to healthcare was positively associated with vaccine acceptance:  PLWHIV on ART reported a slightly higher vaccine acceptance compared with HIV-negative individuals (88.2% vs 81.7%; aRR:  1.1; 90% CrI: 1.03–1.17); the association with vaccine acceptance was stronger among HIV-negative people on PrEP vs those not on PrEP (90.7% vs 78.2%; aRR:  1.19; 90% CrI: 1.12–1.28). Lastly, those considered to have higher risk sexual behaviors or who reported worry about being treated differently due to MPX were more likely to accept being vaccinated.

Monkeypox after Occupational Needlestick Injury from Pustule (Caldas et al., Emerging Infectious Diseases)

A healthy 29-year-old male physician in Portugal had a needlestick injury in the left index finger with a needle used to collect a fluid sample from a man who had a pustular rash, later confirmed to be monkeypox virus (MPXV). The physician punctured a pustule with the needle because he was unable to obtain material by swabbing it. He was wearing the recommended personal protective equipment; the gloves appeared intact to him, and there was no wound or bleeding. Four days later, a vesicle appeared on the pricked finger, and MPXV was identified in its fluid by PCR, showing a Ct of 28. No other lesions or symptoms developed during the next 5 days. PCR results for MPXV in the samples collected from the oropharynx and blood were negative on the seventh day after exposure. The case-patient was considered not eligible for PEP because he already had a lesion that contained MPXV. On the sixth day of illness, fever, chills, and malaise developed and lasted for ≈48 hours. The finger lesion became pustular and painful and showed surrounding erythema and swelling. A tender, indurated, erythematous and well-delimited linear streak from the left finger to the armpit appeared on the seventh day, without regional adenopathy. MPXV PCR was repeated in samples from the oropharynx and blood; again, results were negative. On the eighth day and for the next 3 days, vesicles developed on the scalp, neck, forearm, first finger from both hands and fifth left finger, scrotum, and ankle. A painless right cervical adenopathy also appeared. Despite the absence of leukocytosis or elevation of C-reactive protein level, a bacterial superinfection was assumed because of worsening of the inflammatory signs of the left index finger and of the arm lymphangia, and a course of 5 days of oral flucloxacillin was administered. The patient showed clinical improvement. Treatment with tecovirimat was discussed but considered unnecessary given the benign evolution. By the 18th day of illness, all skin lesions, except the one on the left index finger, had evolved through the pustular stage into crust. The index lesion became necrotic and was debrided on the 24th day of illness, showing a necrotic scab that had a diameter of 0.5 cm underneath the devitalized tissue. An MPXV PCR result was still positive in the crust and showed a Ct of 23, but viral culture was negative. The authors conclude that this case should remind HCWs about the need to report needlestick injuries and other exposures promptly, regardless of a self-notion of absence of risk.

Applicability and benefits of telemedicine in the monitoring of monkeypox close contacts (Seah et al., Journal of Telemedicine and Telecare)

Monkeypox is a zoonotic disease caused by the monkeypox virus and classically presents as a vesicular rash accompanied by fever and lymphadenopathy. Singapore reported the first imported case of monkeypox infection on 21 June 2022, the first local unlinked case on 6 July 2022, and the first local linked case on 5 August 2022. Telemedicine was used in the management of monkeypox close contacts to (1) screen for the development of signs and symptoms consistent with monkeypox infection, (2) assess for successful post-exposure prophylaxis via direct visualisation of vaccination site morphological progression, (3) detect serious reactions arising from post-exposure prophylaxis administration, and (4) evaluate for deterioration in mental health status during the 21-day quarantine period. A case series of 13 close contacts who received post-exposure prophylaxis in the form of the ACAM2000 live Vaccinia virus preparation is presented, illustrating the safe and efficacious application of telemedicine in the clinical follow-up of quarantined close contacts throughout the 21-day incubation period, and post-exposure prophylaxis monitoring. Inherent limitations included difficulties in the assessment of sensitive areas such as the peri-genital and peri-anal regions and video quality–related issues.

Screening for Monkeypox Infection in Asymptomatic High-Risk-Behaviour Men Having Sex with Men (MSM) (Pestel et al., Infectious Disease Reports)

Since the outbreak of monkeypox in formerly non-endemic countries, we have included a screening for monkeypox in our sexually transmitted diseases (STD) routine in patients with high-risk behavior, as it is mainly transmitted through close skin to mucous membrane contact with infected individuals. Methods: Between 16 June 2022 and 14 July 2022, we screened 53 MSM with high-risk behavior for monkeypox acquisition in an observational prospective cohort trial. We complemented the throat and anal swabs for chlamydia and gonococci with monkeypox using polymerase chain reaction (PCR). In addition, all patients participated in a questionnaire survey about their risk behavior and previous STD in their medical history. Results: None of the 53 participants had tested positive for the monkeypox virus. One patient was diagnosed with syphilis and one with an oral and anorectal chlamydia infection. Conclusions: STD screening in highrisk populations is a valuable tool to detect asymptomatic patients for chlamydia, gonococci, HIV, hepatitis B and C and syphilis. Based on our small cohort, monkeypox screening in asymptomatic MSM patients in areas of low prevalence does not seem to be an appropriate approach to deal with the ongoing outbreak. Therefore, we recommend to focus more on vaccinations, targeted nonstigmatizing information and behavior recommendation for risk populations, and to engage further investigations.

Observational Cohort Study of Evolving Epidemiologic, Clinical, and Virologic Features of Monkeypox in Southern France (Cassir et al., Emerging Infectious Diseases)

We enrolled 136 patients with laboratory-confirmed monkeypox during June 4-August 31, 2022, at the University Hospital Institute Méditerranée Infection in Marseille, France. The median patient age was 36 years (interquartile range 31-42 years). Of 136 patients, 125 (92%) were men who have sex with men, 15 (11%) reported previous smallpox vaccinations, and 21 (15.5%) were HIV-positive. The most frequent lesion locations were the genitals (68 patients, 53%), perianal region (65 patients, 49%), and oral/perioral area (22 patients, 17%). Lesion locations largely corresponded with the route of contamination. Most (68%) patients had isolated anal, genital, or oral lesions when they were first seen, including 56 (61%) who had >1 positive site without a visible lesion. Concurrent sexually transmitted infections were diagnosed in 19 (15%) patients, and 7 patients (5%) were asymptomatic. We recommend vaccination campaigns, intensified testing for sexually transmitted infections, and increased contact tracing to control the ongoing monkeypox outbreak.

Vaccine

Receipt of First and Second Doses of JYNNEOS Vaccine for Prevention of Monkeypox — United States, May 22–October 10, 2022 (Kriss et al., MMWR Early Release)

The U.S. Department of Health and Human Services (HHS) allocated 1.1 million vials of JYNNEOS vaccine from the Strategic National Stockpile, with doses allocated to jurisdictions based on case counts and estimated size of population at risk. However, initial vaccine supplies were severely constrained relative to vaccine demand during the expanding outbreak. Some jurisdictions with highest incidence responded by prioritizing first dose administration during May–July. The FDA emergency use authorization (EUA) of 0.1 mL dosing for intradermal administration of JYNNEOS for persons aged ≥18 years on August 9, 2022, substantially expanded available vaccine supply. The U.S. vaccination strategy focuses primarily on persons with known or presumed exposures to monkeypox or those at high risk for occupational exposure. Data on monkeypox vaccine doses administered and reported to CDC by U.S. jurisdictions were analyzed to assess vaccine administration and completion of the 2-dose series. A total of 931,155 doses of JYNNEOS vaccine were administered and reported to the CDC by 55 U.S. jurisdictions during May 22–October 10, 2022. Among persons who received ≥1 dose, 51.4% were non-Hispanic White (White), 22.5% were Hispanic or Latino (Hispanic), and 12.6% were non-Hispanic Black or African American (Black). The percentages of vaccine recipients who were Black (5.6%) and Hispanic (15.5%) during May 22–June 25 increased to 13.3% and 22.7%, respectively, during July 31–October 10. Among 496,888 persons who received a first dose and were eligible for a second dose during the study period, 57.6% received their second dose. Second dose receipt was highest among older adults, White persons, and those residing in the South U.S. Census Bureau Region. The authors conclude that tracking and addressing disparities in vaccination can reduce inequities, and equitable access to and acceptance of vaccine should be an essential factor in planning vaccination programs, events, and strategies.

Designing, characterization, and immune stimulation of a novel multi-epitopic peptide-based potential vaccine candidate against monkeypox virus through screening its whole genome encoded proteins: An immunoinformatics approach (Bhattacharya et al., Travel Medicine and Infectious Disease)

The current monkeypox virus (MPXV) spread in the non-epidemic regions raises global concern. Presently, the smallpox vaccine is used against monkeypox with several difficulties. Conversely, no next-generation vaccine is available against MPXV. Here, we proposed a novel multi-epitopic peptide-based in-silico potential vaccine candidate against the monkeypox virus. The multi-epitopic potential vaccine construct was developed from antigen screening through whole genome-encoded 176 proteins of MPXV. Afterward, ten common B and T cell epitopes (9-mer) having the highest antigenicity and high population coverage were chosen, and a vaccine construct was developed using peptide linkers. The vaccine was characterized through bioinformatics to understand antigenicity, non-allergenicity, physicochemical properties, and binding affinity to immune receptors (TLR4/MD2-complex). Finally, the immune system simulation of the vaccine was performed through immunoinformatics and machine learning approaches. The highest antigenic epitopes were used to design the vaccine. The docked complex of the vaccine and TLR4/MD2 had shown significant free binding energy (−98.37 kcal/mol) with a definite binding affinity. Likewise, the eigenvalue (2.428517e-05) from NMA analysis of this docked complex reflects greater flexibility, adequate molecular motion, and reduced protein deformability, and it can provoke a robust immune response. The designed vaccine has shown the required effectiveness against MPXV without any side effects, a significant milestone against the neglected disease.

Virology

Low levels of monkeypox virus neutralizing antibodies after MVA-BN vaccination in healthy individuals (Zaeck et al., Nature Medicine)

In July 2022, the ongoing monkeypox (MPX) outbreak was declared a public health emergency of international concern. Modified vaccinia virus Ankara-Bavarian Nordic (MVA-BN, also known as Imvamune, Jynneos, or Imvanex) is a 3rd generation smallpox vaccine that is authorized and in use as a vaccine against MPX. To date, there is no data demonstrating MPX virus (MPXV)-neutralizing antibodies in vaccinated individuals, or vaccine efficacy against MPX. Here, the researchers show that MPXV-neutralizing antibodies can be detected after MPXV infection and after historic smallpox vaccination. However, a 2-shot MVA-BN immunization series in non-primed individuals yields relatively low levels of MPXV-neutralizing antibodies. Dose-sparing of an MVA-based influenza vaccine leads to lower MPXV-neutralizing antibody levels, whereas a third vaccination with the same MVA-based vaccine significantly boosts the antibody response. As the role of MPXV-neutralizing antibodies as a correlate of protection against disease and transmissibility is currently unclear, the researchers conclude that cohort studies following vaccinated individuals are necessary to assess vaccine efficacy in at-risk populations.

Retrospective detection of monkeypox virus in the testes of nonhuman primate survivors (Liu et al., Nature Microbiology)

Close contact through sexual activity has been associated with the spread of monkeypox virus (MPXV) in the ongoing, global 2022 epidemic. However, it remains unclear whether MPXV replicates in the testes or is transmitted via semen to produce an active infection. We carried out a retrospective analysis of MPXV-infected crab-eating macaque archival tissue samples from acute and convalescent phases of infection of clade I or clade II MPXV using immunostaining and RNA in situ hybridization. We detected MPXV in interstitial cells and seminiferous tubules of testes as well as epididymal lumina, which are the sites of sperm production and maturation. We also detected inflammation and necrosis during the acute phase of the disease by histological analysis. Finally, we found that MPXV was cleared from most organs during convalescence, including healed skin lesions, but could be detected for up to 37 d post-exposure in the testes of convalescent macaques. Our findings highlight the potential for sexual transmission of MPXV in humans.

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