PRI’s MPV (Monkeypox) Situation Update – November 15

Nov 15, 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 30 October 2022, a cumulative total of 77 264 laboratory-confirmed cases of monkeypox and 36 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 19 October 2022, 3827 new cases (5.2% increase in total cases), and seven new deaths have been reported. In the past seven days, 15 countries reported an increase in the weekly number of cases, with the highest increase reported in Nigeria. Overall, 58 countries have not reported new cases for over 21 days, the maximum incubation period of the disease, nine more countries since the last report. (WHO Sit Rep – Latest 11/2/2022 / Dashboard)
  • US: Total confirmed MPV cases: 28,947 (11.14.2022). (full version). 
  • NY State: As of November 7 2022, a total of 3,758 confirmed orthopoxvirus/monkeypox cases – a designation established by the Centers for Disease Control and Prevention (CDC). (NY Sit Rep and County List) 
  • CDC: Black, Hispanic MSM most affected by monkeypox (CIDRAP) New, updated epidemiologic information about the US monkeypox outbreak appears today in Morbidity and Mortality Weekly Report, showing that 70% of the 26,384 US monkeypox case-patients confirmed to have the virus between May 17 and Oct 6 reported recent male-to-male sexual contact.

US Updates/News

Global Updates/News

  • WHO/Europe providing monkeypox diagnosis support to countries that need it most (WHO) To help meet this need and to ensure their support is targeted, WHO/Europe identified 18 priority Member States and territories (Albania, Armenia, Azerbaijan, Belarus, Bosnia and Herzegovina, Georgia, Kazakhstan, Kosovo*, Kyrgyzstan, Montenegro, North Macedonia, Republic of Moldova, Serbia, Tajikistan, Turkmenistan, Türkiye, Ukraine and Uzbekistan) that either lacked diagnostic capacity, or the supplies needed to provide an adequate response to the outbreak.

Articles by Category

Epi/Transmission/Mitigation

Contact Tracing and Exposure Investigation in Response to the First Case of Monkeypox Virus Infection in the United States During the 2022 Global Monkeypox Outbreak (Shenoy et al., Annals of Internal Medicine)

The objective of this study was to escribe the contact tracing, exposure identification, risk stratification, administration of postexposure prophylaxis (PEP), and exposure period monitoring for contacts of the index patient, including evaluation of persons who developed symptoms possibly consistent with MPXV infection. The study was conducted at multiple health care facilities and community settings in Massachusetts among persons identified as contacts of the index patient. Epidemiologic and clinical data collected through standard surveillance procedures at each facility and then aggregated and analyzed. There were 37 community and 129 health care contacts identified, with 4 at high risk, 49 at intermediate risk, and 113 at low or uncertain risk. Fifteen health care contacts developed symptoms during the monitoring period. Three met criteria for MPXV testing, with negative results. Two community contacts developed symptoms. Neither met criteria for MPXV testing, and neither showed disease progression consistent with monkeypox. Among 4 persons with high-risk exposures offered PEP, 3 elected to receive PEP. Among 10 HCP with intermediate-risk exposures for which PEP was offered as part of informed clinical decision making, 2 elected to receive PEP. No transmissions were identified at the conclusion of the 21-day monitoring period, despite the delay in recognition of monkeypox in the index patient. The authors conclude that in a contact tracing investigation involving 166 community and health care contacts of a patient with monkeypox, no secondary cases were identified.

Global monkeypox case hospitalisation rates: A rapid systematic review and meta-analysis (DeWitt et al., Lancet eClinical Medicine)

This rapid systematic review and meta-analysis aimed to estimate the case hospitalisation rate and case fatality rate from monkeypox (MPX) infections where hospital care is available. Researchers systematically searched PubMed, Embase, the Lancet Preprints, and MedRxiv for studies published between Jan 1, 1950 and Aug 2, 2022. They included documents which contained both the number of cases and associated hospitalisations of MPX infections. Of the 259 unique documents identified, 19 studies were eligible for inclusion. Included studies represented 7553 reported cases among which there were 555 hospitalizations. Of the 7540 cases for which outcomes were available, there were 15 recorded deaths. The median age of cases was 35 years (interquartile range 28–38, n = 2010) and primarily male (7339/7489, 98%) in studies where age or sex were available. Combined case hospitalisation rate (CHR) was estimated to be 14.1% (95% credible interval, 7.5–25.0, I2 97.4%), with a high degree of heterogeneity. Further analysis by outbreak period indicates CHRs of 49.8% (28.2–74.0, I2 81.4%), 21.7% (7.2–52.1, I2 57.7%), and 5.8% (3.2–9.4, I2 92.4%) during the pre-2017, 2017–2021, and 2022 outbreaks, respectively, again with high levels of heterogeneity. Lastly, the case fatality rate was estimated to be 0.03% (0.0–0.44, I2 99.9%), with evidence of large heterogeneity between the studies.

The changing epidemiology of human monkeypox-A potential threat? A systematic review (Bunge et al., PLOS Neglected Tropical Diseases)

Researchers conducted a systematic review of peer-reviewed and grey literature on how monkeypox epidemiology has evolved, with particular emphasis on the number of confirmed, probable, and/or possible cases, age at presentation, mortality, and geographical spread. They identified 48 peer-reviewed articles and 18 grey literature sources for data extraction. The number of human monkeypox cases has been on the rise since the 1970s, with the most dramatic increases occurring in the DRC. The median age at presentation has increased from 4 (1970s) to 21 years (2010–2019). There was an overall case fatality rate of 8.7%, with a significant difference between clades—Central African 10.6% (95% CI: 8.4%– 13.3%) vs. West African 3.6% (95% CI: 1.7%– 6.8%). Since 2003, import- and travel-related spread outside of Africa has occasionally resulted in outbreaks. Interactions/activities with infected animals or individuals are risk behaviors associated with acquiring monkeypox. This review shows an escalation of monkeypox cases, especially in the highly endemic DRC, a spread to other countries, and a growing median age from young children to young adults. These findings may be related to the cessation of smallpox vaccination, which provided some cross-protection against monkeypox, leading to increased human-to-human transmission. The appearance of outbreaks beyond Africa highlights the global relevance of the disease. Increased surveillance and detection of monkeypox cases are essential tools for understanding the continuously changing epidemiology of this resurging disease.

Evaluation of 11 commercially available PCR kits for the detection of monkeypox virus DNA, Berlin, July to September 2022 (Michel et al., Eurosurveillance)

To evaluate ready-to-use kits for monkeypox virus (MPXV) diagnostics, researchers established an 18-specimen panel using DNA from cultured viruses and characterized it using the diagnostic workflow of the German Consultant Laboratory for poxviruses. The panel included DNA from MPXV Clade I, Clade IIa and Clade IIb, other orthopoxvirus (OPV) and varicella zoster virus (VZV). All samples were analyzed in duplicate. The team compared 11 kits (A to L) as outlined in Table 3 in the article. For the 2012 Clade II MPXV isolate, most kits showed Cq values in the expected range, indicating good analytical sensitivity down to at least Cq = 36, reflecting approximately 5 genome equivalents (ge) per reaction (rxn). Only kit F failed to detect this dilution. For the highest dilution (Cq = 38, reflecting < 1 ge/rxn), two kits and two generic reference PCRs for OPV and MPXV failed to detect both replicates; six kits detected one of two replicates; three kits and the Clade II-specific reference PCR detected both replicates, indicating high analytical sensitivity. The team also assessed Clade I MPXV detection: kit K failed to detect one duplicate of the sample with Cq = 32, while three kits failed to detect one duplicate of the lowest concentration (Cq = 35). The team also assessed specificity using vaccinia virus (VACV), cowpox virus (CPXV) and VZV DNA. As expected, none of the kits detected VZV.  According to the manuals, all kits were designed to be specific for MPXV DNA, excluding other OPV, except for kits B and K which are generic for OPV. Results confirm that the OPV kits B and K also detect VACV and CPXV DNA with Cq values similar to those of the OPV reference PCR for the same samples whereas the MPXV-specific kits do not, with two exceptions: kits F and I unexpectedly detected VACV and CPXV DNA, indicating non-specific interactions. Both kits F and I resulted in similar Cq values, with Cq value shifts of ca six to seven cycles for VACV and 11–12 cycles for CPXV, indicating better, but still inefficient, binding to VACV DNA than to CPXV DNA. In summary, analytical sensitivity of the kits was generally high, detecting down to less than ca 5 ge/rxn (Cq = 36), and the limited specificity assessment showed that most assays were specific for MPXV or OPV, as per their intended design.

Epidemiologic Features of the Monkeypox Outbreak and the Public Health Response — United States, May 17–October 6, 2022 (Kava et al., MMWR)

On May 17, 2022, the Massachusetts Department of Health announced the first suspected case of monkeypox associated with the global outbreak in a U.S. resident. On May 23, 2022, CDC launched an emergency response. CDC’s emergency response focused on surveillance, laboratory testing, medical countermeasures, and education. Medical countermeasures included rollout of a national JYNNEOS vaccination strategy, Food and Drug Administration (FDA) issuance of an emergency use authorization to allow for intradermal administration of JYNNEOS, and use of tecovirimat for patients with, or at risk for, severe monkeypox. During May 17–October 6, 2022, a total of 26,384 probable and confirmed U.S. monkeypox cases were reported to CDC. Daily case counts peaked during mid-to-late August. Among 25,001 of 25,569 (98%) cases in adults with information on gender identity, 23,683 (95%) occurred in cisgender men. Among 13,997 cisgender men with information on recent sexual or close intimate contact, 10,440 (75%) reported male-to-male sexual contact (MMSC) ≤21 days preceding symptom onset. Among 21,211 (80%) cases in persons with information on race and ethnicity, 6,879 (32%), 6,628 (31%), and 6,330 (30%) occurred in non-Hispanic Black or African American (Black), Hispanic or Latino (Hispanic), and non-Hispanic White (White) persons, respectively. Among 5,017 (20%) cases in adults with information on HIV infection status, 2,876 (57%) had HIV infection. The authors conclude that prevention efforts, including vaccination, should be prioritized among persons at highest risk within groups most affected by the monkeypox outbreak, including gay, bisexual, and other men who have sex with men (MSM); transgender, nonbinary, and gender-diverse persons; racial and ethnic minority groups; and persons who are immunocompromised, including persons with advanced HIV infection or newly diagnosed HIV infection.

Knowledge, attitudes, and practices towards monkeypox during the 2022 outbreak: An online cross-sectional survey among clinicians in Ohio, USA (Bates et al., Journal of Infection and Public Health)

Controlling monkeypox effectively requires clinicians have knowledge of monkeypox, attitudes supporting of controlling it, and intentions to adopt practices to address it. Little is known, however, about levels of knowledge, attitudes, and practices (KAPs) in clinician populations in Ohio, United States. A cross-sectional, internet-based questionnaire assessed knowledge related to monkeypox, attitudes toward ability to control monkeypox and the threat of monkeypox, and prior relevant practices of having received a smallpox vaccine or having knowledge of monkeypox before 2022, intentions to adopt preventive practices, and demographics. Frequency reporting was used to assess overall knowledge and attitudes. Binary logistic regression was sued to predict which KAPs were associated with behavioral intentions. A total of 197 clinicians participated. No demographic factor was associated with KAPs. Clinicians had relatively poor levels of knowledge. Participants expressed mixed attitudes about eventual control of monkeypox and about threat posed by monkeypox. About one in four participants reported previous knowledge of monkeypox, and about 40% had received a smallpox vaccine Clinicians reported insufficient levels of intention to adopt preventive practices. Binary regression analysis suggests only perceptions of the threat of monkeypox to public health were associated with intentions to vaccinate self or others. Educational interventions with clinicians should address inadequate knowledge to support correct diagnosis and treatment. Efforts to enhance the perception of threat of monkeypox to public health may support adherence to preventive recommendations.

Treatment

Tecovirimat is effective against human monkeypox virus in vitro at nanomolar concentrations (Frenois-Veyrat et al., Nature Microbiology)

To assess the activity of tecovirimat on the 2022 monkeypox virus (MPXV) strain, researchers performed dose response studies on Vero cells. Tecovirimat completely abolished MPXV replication (measured by plaque reduction assay of plaque forming units (p.f.u.)) at 100 nM, with a 50% inhibitory concentration (IC50) of 12.7 nM. Researchers also used a VACV ANCHOR-GFP infection model, in which virus infection and propagation can be visualized in living cells, and found a comparable IC50 (6 to 8.6 nM). Cidofovir in vitro IC50 for MPXV lineage B.1 in Vero cells was 30 μM, indicating 3,000-fold lower potency than that of tecovirimat. In summary, FDA-approved tecovirimat (ST-246) is efficacious against this isolate in vitro at nanomolar concentrations, whereas cidofovir is only effective at micromolar concentrations. These results support the use of tecovirimat in the clinical response to the 2022 MPXV outbreak, in particular for immunosuppressed patients. Of note, tecovirimat is not recommended for pregnant women due to the lack of safety data. Clinical trials in humans will be needed to further establish the efficacy of tecovirimat in vivo.

Prevention and Treatment of Monkeypox: A Systematic Review of Preclinical Studies (Sudarmaji et al., Viruses)

The outbreak of monkeypox, coupled with the onslaught of the COVID-19 pandemic is a critical communicable disease. This study aimed to systematically identify and review research done on preclinical studies focusing on the potential monkeypox treatment and immunization. The presented juxtaposition of efficacy of potential treatments and vaccination that had been tested in preclinical trials could serve as a useful primer of monkeypox virus. The literature identified using key terms such as monkeypox virus or management or vaccine stringed using Boolean operators was systematically reviewed. Pubmed, SCOPUS, Cochrane, and preprint databases were used, and screening was performed in accordance with PRISMA guidelines. A total of 467 results from registered databases and 116 from grey literature databases were screened. Of these results, 72 studies from registered databases and three grey literature studies underwent full-text screening for eligibility. In this systematic review, a total of 27 articles were eligible according to the inclusion criteria and were used. Tecovirimat, known as TPOXX or ST-246, is an antiviral drug indicated for smallpox infection whereas brincidofovir inhibits the viral DNA polymerase after incorporation into viral DNA. The ability of tecovirimat in providing protection to poxvirus-challenged animals from death had been demonstrated in a number of animal studies. Non-inferior with regard to immunogenicity was reported for the live smallpox/monkeypox vaccine compared with a single dose of a licensed live smallpox vaccine. The trial involving the live vaccine showed a geometric mean titre of vaccinia-neutralizing antibodies post two weeks of the second dose of the live smallpox/monkeypox vaccine. Of note, up to the third generation of smallpox vaccines—particularly JYNNEOS and Lc16m8—have been developed as preventive measures for MPXV infection and these vaccines had been demonstrated to have improved safety compared to the earlier generations.

Antiviral Treatment against Monkeypox: A Scoping Review (Ortiz-Saavedra et al., Tropical Medicine and Infectious Disease)

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.

Vaccine

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

This study aims to estimate the global prevalence of vaccination acceptance against monkeypox. They 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. The authors conclude that despite the high prevalence of monkeypox vaccination acceptance in the LGBTI community found in the study, vaccination acceptance from healthcare workers and the general population are lower.