PRI’s MPV (Monkeypox) Situation Update – October 18

Oct 18, 2022 | News

Created by PRI for the NYC Health Department. Latest editions Tuesday 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 2 October 2022, 68 900 laboratory-confirmed cases of monkeypox and 25 deaths have been reported to WHO from 106 countries/territories/areas(hereafter ‘countries’[i]) in all six WHO Regions(Table 1). Since the last edition published on 21 September 2022, 7147 new cases (11.6% increase in total cases), and three new deaths have been reported. In the past seven days, 26 countries reported an increase in the weekly number of cases, with the highest increase (44.4%) reported in Nigeria. One new country, Egypt, reported its first case in the past seven days(27 September). Overall, 39 countries have not reported new cases for over 21 days, the maximum incubation period of the disease. (WHO Sit Rep – Latest 10/5/2022 / Dashboard)
  • US: Total confirmed MPV cases: 27,468 (10.17.2022). (full version). 
  • NY State: As of October 14 2022, a total of 3,683 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

  • Monkeypox cases in the U.S. are way down — can the virus be eliminated? (NPR) Monkeypox cases have declined since a peak in early August – from 440 cases a day, down to 60 – and they’re the lowest they’ve been since June. The virus has continued to circulate almost entirely within gay and queer sexual networks. And vaccine supply is plentiful, even outstripping the current demand.
  • GLAAD examines impact of HIV, COVID, & MPV in new report (Los Angeles Blade) On October 6, in a TIME Magazine exclusive, GLAAD released “Invisible People,” a first-of-its-kind report detailing the disruption caused by COVID-19 in the lives of people living with HIV. The 23-page report combines a comprehensive analysis of peer-reviewed scientific literature, qualitative interviews of people living with HIV, affected communities, and community-based organizations (CBOs) serving these populations.

Global Updates/News

  • With no monkeypox vaccine at home, frustrated Mexicans go abroad (Reuters) As monkeypox continues to impact gay and bisexual men in dozens of countries around the world, at-risk Mexicans are going abroad for vaccines they say their government has not bothered to make available at home. Mexico ranks ninth globally in total cases, according to the World Health Organization, but officials have not announced plans to acquire vaccines even as other Latin American countries receive shipments.

Articles by Category

Epi/Transmission/Mitigation

Monkeypox virus infection in HIV-1-coinfected patients previously vaccinated against smallpox: a series of 4 cases from Portugal (Brazão et al., Journal of the European Academy of Dermatology and V report

In this case report, authors describe four cases of a 58-year-old, a 50-year-old, a 49-year-old, and a 48-year-old men, who presented to a hospital dermatology department in Lisbon, Portugal with umbilicated lesions, fever, asthenia, and myalgias, which had developed in the previous three days. In the previous week, patients reported unprotected oral and anal sex with several male partners. Their past medical history was relevant for treated syphilis and Human Immunodeficiency Virus (HIV) infection, under treatment with Highly Active Antiretroviral Therapy (HAART). All patients had received anti-vaccinia virus vaccination during infancy. Physical examination revealed umbilicated papules and vesicles with an erythematous rim. Three patients had localized lesions (perioral, perianal, orgenital area), and one patient had disseminated disease (over thirty lesions). All had palpable regional lymphadenopathies. Infectious serologies were consistent with treated syphilis and negative for Hepatitis B and C. Three patients had negative HIV viral load and normal CD4+ lymphocyte count (those with localized disease), and one patient had detectable viral load and low CD4+ count (the one with disseminated   disease). Polymerase Chain Reaction of the skin lesions identified monkeypox virus. The patients were treated with supportive care and advised to self-isolate. The skin lesions resolved within three to four weeks. In summary, although there is evidence that smallpox vaccination during childhood gives partial protection against monkeypox virus, people may lose their immunity over time, especially those with HIV infection (even if treated with HAART). Dosing smallpox antibodies in previously vaccinated individuals (particularly the risk groups) could help distinguish the patients in need of vaccination in the setting of this outbreak.

Neonatal Monkeypox Virus Infection (Ramnarayan et al., NEJM Correspondance)

Here the authors report a case of perinatally acquired monkeypox virus infection and adenovirus coinfection in a 10-day-old infant. After the infant’s uneventful birth in late April 2022, a rash developed on day 9 of life. The rash was initially vesicular, starting on the palms and soles and subsequently spreading to the face and trunk, and gradually became pustular. Nine days before the birth, the infant’s father had had a febrile illness, followed by a widespread rash; the rash resolved before the infant’s birth. Four days after the infant’s delivery, a similar rash developed in the mother. The family had no history of travel to Africa or of contact with any travelers. The infant was transferred to the regional pediatric intensive care unit on day 15 of life owing to evolving hypoxemic respiratory failure. A number of diagnoses (neonatal varicella, herpes simplex virus infection and others) were considered. The presence of axillary lymphadenopathy, the nature of the skin lesions, and the atypical timeline of intrafamilial infection aroused concern regarding human monkeypox. PCR testing of blood, urine, vesicular-fluid, and throat-swab samples obtained from the infant and mother led to a diagnosis of monkeypox virus infection (clade IIb). Adenovirus was also identified in the infant’s respiratory secretions and blood. The infant’s condition worsened, and invasive ventilation was initiated. A 2-week course of enteral tecovirimat (at a dose of 50 mg twice a day) was commenced in combination with intravenous cidofovir. After 4 weeks in intensive care, including 14 days of invasive ventilation, the infant recovered and was discharged home. The authors conclude that reports of neonatal monkeypox virus infection are rare.3 This was a case of neonatal monkeypox virus infection after peripartum transmission within a family cluster; transplacental transmission could not be ruled out. Because this was a single case, it is not possible to attribute the clinical illness to either pathogen (monkeypox virus or adenovirus) directly, nor is it possible to attribute the improvement in the infant’s clinical condition to the use of tecovirimat or cidofovir.

Bibliometric analysis of human monkeypox research from 1975 to 2022 and novel prevention and control strategies (Lin et al., Frontiers Public Health)

This study aimed to evaluate the research hotspots and future development trends of human monkeypox by a bibliometric analysis, to analyze the preventive and control measures of various countries in response to human monkeypox outbreaks. The Web of Science Core Collection database was searched for all monkeypox related literature published from 1975 to 2022, and the search strategy was “TS = monkeypox.” From 1975 to 2022, a total of 1,068 monkeypox research papers were included, of which American researchers published 663 papers, and it was also the country that participated in the most international cooperation. Centers for Disease Control Prevention USA is the most prolific institution and a leader in research collaborations. The Journal of Virology has the largest number of published papers on monkeypox. In addition, Damon Inger K has made significant contributions to monkeypox research, with both the most published and the most citation. A total of 2,847 keywords were identified, four top topics were obtained through cluster analysis: (1) human monkeypox epidemiology and species research. (2) human monkeypox virus vaccine and experimental research. (3) human monkeypox disease diagnosis and treatment studies. (4) human monkeypox disease prevention and immunization studies. To curb the spread, regions or countries have developed and implemented detailed managements. The prevention and control measures focus on the isolation of suspected or confirmed patients, the investigation and tracking of the source of the disease, the disposal of pollutants, vaccination and the protection of health workers. In summary, the number of human monkeypox literature has grown since 2003. Infection, vaccine and efficacy were the top topic over the past 47 years while the contact tracing, testing, surveillance and vaccination have been the major concerns since the human monkeypox outbreak in May 2022. The treatment and management of human monkeypox deserves further attention.

Symptomatology, prognosis, and clinical findings of Monkeypox infected patients during COVID‐19 era: A systematic‐review (Jaiswal et al., Immunity, Inflammation and Disease)

The recent outbreak of Human Monkeypox (MPXV) in nonendemic regions of the world is of great concern. We aimed to systematically analyze the current epidemiology, clinical presentation, and outcomes of the Monkeypox virus. Systematic literature was conducted in PubMed, Embase, Google Scholar, and Scopus using predefined MESH terms by using “AND” and “OR.” The following search terms were used: Monkeypox [MeSH] OR “Monkeypox virus” [MeSH] OR “POX” OR “Monkeypox” AND “Outbreak” AND “Outcomes” from December 2019 till 14th June 2022 without restrictions of language. A total of 1074 (99.90%) patients tested positive for Monkeypox virus through RT‐PCR while 1 (0.09) patient was suspected. There was a gender difference with male predominance (54.23% vs. 45.48%) compared with female patients. Mean age (±SD) of patients was 20.66 ± 16.45 years. The major symptoms were rash (100%), fever (96%), and other important symptoms were upper respiratory symptoms (97%), headache (95%), vomiting (95%), oral ulcers (96%), conjunctivitis (96%) and lymphadenopathy (85%). The average mean duration of treatment was 5 days, while the mean hospitalization duration was 13.3 ± 6.37 days. The outcome of 20 patients was available, 19 of 20 patients recovered fully from monkeypox, however, 1 patient was not able to survive resulting in death. The recent monkeypox virus outbreak has shown that the virus could transmit in ways that were not previously expected. Further research is needed to understand the possible outcomes and association with humans and their different organ systems.

Artificial intelligence (AI) in Monkeypox infection prevention (Patel et al., Journal of Bimolecular Structure and Dynamics)

Monkeypox is a possible public health concern that requires appropriate attention in order to prevent the spread of the disease. Currently, artificial intelligence (AI) is making a significant impact on precision medicine, reshaping and integrating the large amount of data derived from multiomics analyses and revolutionizing the deep-learning strategies. There has been a significant progress in the use of AI to detect, screen, diagnose, and classify diseases, characterize virus genomes, assess biomarkers for prognostic and predictive purposes, and develop follow-up strategies. Hence, it is possible to use AI for the identification of disease clusters, cases monitoring, forecasting the future outbreak, determining mortality risk, diagnosing, managing, and identifying patterns for studying disease trends. AI may also be utilized to assist gene therapy and other therapies that we are not currently able to use in healthcare. It is possible to combine pharmacology and gene therapy with regenerative medicine with the help of AI. It will directly benefit the public in overcoming fear and panic of health risks. Therefore, AI can be an effective weapon to fight against Monkeypox infection, and may prove to be an invaluable future tool in improving the clinical management of patients.

Perceived Monkeypox Concern and Risk among Men Who Have Sex with Men: Evidence and Perspectives from The Netherlands (Wang et al., Tropical Medicine and Infectious Disease)

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

Integrated Analgesic Care in the Current Human Monkeypox Outbreak: Perspectives on an Integrated and Holistic Approach Combining Old Allies with Innovative Technologies (Hans et al., Medicina)

Monkeypox (MPX) is a zoonotic infection caused by an orthopoxvirus that is endemic to Central and Western Africa. The MPX virus is a part of the same family of viruses as the variola virus, which causes smallpox. Since May 2022, there has been a global increase in the incidence of MPX infections in multiple countries where the illness is not usually prevalent. A growing number of publications have emphasized on the need for increased awareness among all health professionals for the rapid recognition and diagnosis of this disease and for proper public health measures. However, atypical presentations and occurrence of uncommon symptoms receive less than the desired attention. More specifically, MPX infection related nociceptive symptoms are currently underexposed. Nevertheless, reports from the current outbreak have revealed that (severe) pain is one of the major causes for distress and even hospitalization in these patients. As for all serious pain conditions, an integrated, multidisciplinary, and holistic approach is indicated. This approach should be multimodal and include non-pharmacological therapies alongside pharmacological approaches. Health care professionals should be aware of available alternatives when first choice analgesic therapies fail. Protocols for identification of pain type and prolonged monitoring of clinical status should be implemented to improve patient well-being during acute infection, but also prevent chronic nociceptive syndromes.

Virology

Monkeypox Virus Detection in Different Clinical Specimen Types (Hasso et al., Emerging Infectious Diseases)

Here, the authors investigated detection of MPXV among different clinical specimen types. This retrospective study was conducted on patient specimens submitted to Public Health Ontario’s laboratory, the reference microbiology laboratory in Ontario and MPXV testing location, during the initial weeks of the provincial surge (May‒June 2022). All specimens were collected from symptomatic patients with suspected monkeypox infection. They tested 1,063 specimens from 372 patients (mean age 33.8 years, range >1–88 years); 71.2% were male. MPXV was detected in 81 (21.8%) patients, all adult males who had a mean age of 38 years (range 19–65 years). Specimen positivity rate was 23.4% (249/1,063); 2.8% (29/1,063) of all specimens tested had indeterminate results. Among specimens submitted from the 81 MPXV-positive patients, skin lesions displayed the highest positivity rate (177/213, 83.1%), followed by oropharyngeal (31/46, 67.4%), nasal or NP (20/36, 55.6%), blood (29/67, 43.3%) and urine (6/21, 28.6%) (Table). MPXV was also detected in 2/5 semen specimens and 1/1 saliva specimen submitted from known MPXV-positive patients. Across all positive specimens, the MPXV GR2-G target mean Ct (26.2) was 2.7 lower than that of the OPXV assay (29.9), and the clade II target mean Ct (26.3) was 2.6 times lower. The MPXV assay also had lower Ct values than the OPXV assay across all specimen types (Table), indicating higher analytical sensitivity. Skin lesion specimens were detected multiple cycles earlier, indicative of higher viral loads. Oropharyngeal samples had the second lowest Ct means. Among 78 monkeypox confirmed case-patients with skin and NP or throat swab specimens submitted for testing, 72/78 (92.3%) had >1 positive skin specimen and 38/78 (48.7%) had >1 positive NP or throat swab specimens. MPXV was only detected in skin specimens in 34/78 (43.6%) patients. All patients with a positive blood specimen had >1 other positive specimen type. Among 15 monkeypox confirmed case-patients who had both NP and throat swab specimens submitted, 8 had concordant (53.3%) positive and 2 (13.3%) had concordant negative results. One case-patient had a negative NP swab and positive throat swab specimens, and 4 discordant case-patients had 1 sample type indeterminate and the other negative. In summary, MPXV was detected in specimens from multiple sites. Skin lesions most often tested positive, as observed in 92.3% of laboratory confirmed case-patients who had >1 skin specimens tested. This finding indicates that this is the most clinically relevant specimen when skin lesions are available.

Mutations in the monkeypox virus replication complex: Potential contributing factors to the 2022 outbreak (Kannan et al., Journal of Autoimmunity)

Attributes contributing to the current monkeypox virus (MPXV) outbreak remain unknown. It has been established that mutations in viral proteins may alter phenotype and pathogenicity. To assess if mutations in the MPXV DNA replication complex (RC) contribute to the outbreak, we conducted a temporal analysis of available MPXV sequences to identify mutations, generated a DNA replication complex (RC) using structures of related viral and eukaryotic proteins, and structure prediction method AlphaFold. Ten mutations within the RC were identified and mapped onto the RC to infer role of mutations. Two mutations in F8L (RC catalytic subunit), and two in G9R (a processivity factor) were ∼100% prevalent in the 2022 sequences. F8L mutation L108F emerged in 2022, whereas W411L emerged in 2018, and persisted in 2022. L108 is topologically located to enhance DNA binding affinity of F8L. Therefore, mutation L108F can change the fidelity, sensitivity to nucleoside inhibitors, and processivity of F8L. Surface exposed W411L likely affects the binding of regulatory factor(s). G9R mutations S30L and D88 N in G9R emerged in 2022, and may impact the interaction of G9R with E4R (uracil DNA glycosylase). The remaining six mutations that appeared in 2001, reverted to the first (1965 Rotterdam) isolate. Two nucleoside inhibitors brincidofovir and cidofovir have been approved for MPXV treatment. Cidofovir resistance in vaccinia virus is achieved by A314T and A684V mutations. Both A314 and A684 are conserved in MPXV. Therefore, resistance to these drugs in MPXV may arise through similar mechanisms.

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