MPV Principal Scientific Advisor Report – November 22

Nov 22, 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: 29,133 (11.18.2022). (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

  • Study describes monkeypox in women; CDC warns of Tpoxx resistance (CIDRAP) The study, published yesterday in The Lancet, was performed by the same UK-based group that produced a study of male patients earlier this year. The current case study looks at 136 case-patients with monkeypox virus infection diagnosed between May 11 and Oct 4, 2022, across 15 countries.

Global Updates/News

  • Preparing for epidemics now and in the future (News Medical) The World Health Organization (WHO) recently conducted a virtual press conference on global health emergencies on November 16, 2022. Margaret Harris hosted the conference at WHO Headquarters in Geneva. In addition, a broad panel of technical experts was present online and offline for discussion.

Articles by Category

Epi/Transmission/Mitigation

Evaluating the accuracy of self-collected swabs for the diagnosis of monkeypox (Ubals et al., Clinical Infectious Diseases)

Researchers conducted a prospective diagnostic accuracy evaluation in individuals with suspected monkeypox in three centres in Spain. All patients presenting to participating centres with lesions suggestive of monkeypox and compatible symptoms were invited to participate. Patients who required hospital admission were not included in the study. At the baseline visit, a physician collected clinical samples, including lesion, oropharyngeal, and rectal swabs as appropriate (study day 0, physician-collected samples). Participants were provided with home testing kit materials, which included an instruction sheet and devices for self-collection (i.e., Dacron-tipped swabs, pre-labelled swab containers, and a mailing envelope); they were trained for self-collection of samples and asked to self-collect swabs from the same skin lesions, the oropharynx, and the rectum the following day (study day 1, self-collected samples). All samples were analysed for the detection of monkeypox virus DNA by quantitative polymerase chain reaction (qPCR). 50 patients were enrolled, of which 49 individuals had a skin lesion swab collected (all of which were positive), 38 had a oropharyngeal swab collected (26 [68%] were positive), and 11 had a rectal swab collected (9 [82%] were positive). The highest overall agreement was observed in lesional skin swabs (98% agreement), where only one individual tested negative in the physiciancollected swab and positive in the self-collected. For oropharyngeal and rectal specimens, the overall agreement was 79% (30/38, kappa 0.49) and 90% (9/10. kappa 0.6), respectively. They found no significant differences in CT values between physician- and self-collected skin lesion and oropharyngeal specimens.In conclusion, the researchers found that the performance of self-collected samples was similar to that of physician-collected samples, suggesting that self-sampling is a reliable and feasible strategy for diagnosing monkeypox.

Immunological signature in human cases of monkeypox infection in 2022 outbreak: an observational study (Agrati et al., The Lancet Infectious Diseases)

17 patients with laboratory-confirmed monkeypox admitted at the Lazzaro Spallanzani National Institute for Infectious Diseases, from May 19, to July 7, 2022, were tested for differentiation and activation profile of CD4 and CD8 T (expression of CD38, PD-1, and CD57 assessed by flow cytometry), frequency of pox-specific T cells (by standard interferon-γ ELISpot), and release of interleukin (IL)-1β, IL-6, IL-8, and tumour necrosis factor (TNF) in plasma (by ELISA). All patients were tested 10–12 days after symptoms onset. In a subgroup of nine patients with a laboratory-confirmed monkeypox, the kinetics of the immune response were analysed longitudinally according to timing from symptoms onset and compared with ten healthy donors. Among the 17 patients, ten were HIV negative and seven HIV positive, all with good viro-immunological status. On days 0–3 from symptom onset, patients with laboratory-confirmed monkeypox were characterised by a statistically significant reduction in CD4+ T cells (p=0·0011) and a concurrent increase of CD8+ T cells (p=0·0057) compared with healthy donors. A lower proportion of naive (CD45RA+CD27+) CD4+ T cells was observed in six (67%) of nine patients and a concomitant higher proportion of effector memory (CD45RA-CD27-) CD4+ T cells in all patients; this skewed immune profile tended to normalise over time. A similar differentiated profile was also observed in CD8+ T cells with a consistent expansion of terminally differentiated CD8+ T cells. Patients with monkeypox had a higher proportion of CD4+CD38+ and CD38+CD8+ T-cells than healthy donors, which normalised after 12–20 days from symptom onset. The expression of PD-1 and CD57 on CD4+ and CD8+ T-cells showed kinetics similar to that observed for CD38. Furthermore, the inflammatory cytokines (IL-1β, IL-6, IL-8, and TNF) were higher in patients with monkeypox than in healthy donors and, although they decreased over time, they remained elevated after recovery. Almost all patients (15 [94%] of 16) developed a pox-specific Th1 response. No differences in immune cells profile were observed between patients with and without HIV, whereas paucysimptomatic patients (without systemic symptoms, with less than five skin lesions, and no other mucosal localisation of monkeypox) showed a less perturbed immune profile early after symptom onset. In summary, the data showed the immunological signature of monkeypox virus infection, characterised by an early expansion of activated effector CD4+ and CD8+ T cells that persisted over time. Almost all patients, even regardless of HIV infection, developed a poxvirus-specific Th1 cell response.

Human Monkeypox in People With HIV: Transmission, Clinical Features, and Outcome (Vivancos-Gallego et al., Open Forum Infectious Diseases)

In this analysis, the authors = review the epidemiological and clinical characteristics of all consecutive individuals with confirmed MPXV infection who attended the HIV Clinic, University Hospital Ramón y Cajal, in Madrid, between May 16 (the first patient diagnosed) and June 23 (last patient included in this report). The information collected in the clinical records constitutes the basis of the study. During the study period, 25 PWH usually followed at the clinic were diagnosed with MPXV, representing a prevalence of at least 8.5 cases per 1000 population. All cases were identified as West African clade. All patients were MSM with a median age of 39.5 years. All were receiving antiretroviral treatment, had undetectable plasma viral loads, and their median CD4 count was 630 cells/mm3. Most patients (76%) presented with prodromic symptoms, mainly consisting of fever, general malaise, and pharyngitis. Lymphadenopathy was a prominent finding in 84% of the patients. Proctitis was present in 52% of the patients, in most cases (76%) with no other concomitant sexually transmitted infections. Symptoms were predominantly local, including perianal pain, tenesmus, and rectal bleeding. Skin lesions, presented in all patients, progressed from macules to a pustular appearance with an umbilicated necrotic center and an erythematous halo. The genital and perianal areas were involved in 56% of cases. MPXV DNA was detected in all patients, usually in >1 clinical specimen. Swabs from cutaneous lesions were positive in all but 2 patients, who were diagnosed by rectal samples. Of interest, MPXV was found in rectal swabs from 9 of 10 (90%) patients with proctitis. No treatment with tecovirimat was given to any of the patients. Smallpox vaccination was confirmed in 5 of 14 cases (36%). None of the patients required hospitalization, and resolution was complete, with a median duration of symptoms of 8 days. In summary, proctitis was the predominant finding in 52% of persons, and MPXV DNA was detected in rectal swabs from 90%. Proctitis and demonstration of MPXV in rectal swabs support the sexual transmission of MPXV.

Monkeypox Virus Infection in 22-Year-Old Woman after Sexual Intercourse, New York, USA (Zayat et al., Emerging Infectious Diseases)

Here, the authors report monkeypox virus infection in a 22-year-old woman with no remarkable medical history who sought care at the Kings County Hospital Center (Brooklyn, NY, USA) emergency department with numerous painful vulvar and intravaginal lesions. The patient reported a sexual encounter with 1 male partner 2.5 weeks before. She reported that they had vaginal sex and noted that her partner had a few “dark bumps” on his penis that resembled ingrown hairs. It was unknown if this partner had any sexually transmitted infections. Two weeks after the encounter, the patient experienced onset of myalgias, fatigue, and fever. Two days after the onset of fever, she first noticed 3 mildly painful flesh-colored bumps, which progressed the following day and became white in color and more numerous. The lesions prompted the patient to go to the emergency department at an outside hospital. At arrival, the patient was febrile to 100.7° F. She underwent screening for sexually transmitted infections, including testing for monkeypox. She was discharged home with prescriptions of lidocaine, bacitracin, and ibuprofen as needed for pain while laboratory results were pending. While waiting for the test results, the patient was informed by her male partner that he had tested positive for monkeypox virus earlier that day. The patient was admitted to the hospital and began a 14-day course of tecovirimat (600 mg every 12 h) with accompanying isolation precautions. All results of laboratory tests were negative except for a positive PCR result for monkeypox virus. The patient continued inpatient treatment with tecovirimat and was discharged on hospital day 3 without experiencing any other complications. Approximately 10 days after the onset of lesions, the patient reported in a follow-up telehealth visit that the lesions were decreasing in size and scabbing over and that the pain had greatly subsided.

Human monkeypox virus infection in women and non-binary individuals during the 2022 outbreaks: a global case series (Thornhill et al., The Lancet)

Here, researchers report a cohort from 15 countries of women and non-binary individuals with human monkeypox virus infection, with the aim of describing the epidemiological associations and clinical outcomes. International collaborators in geographical locations with high numbers of diagnoses were approached and invited to contribute data on this population. Data was reported for a total of 136 individuals with monkeypox virus infection who presented between May 11 and Oct 4, 2022. Overall median age was 34 years (IQR 28–40; range 19–84). The cohort comprised 62 trans women, 69 cis women, and five non-binary individuals (who were, because of small numbers, grouped with cis women to form a category of people assigned female at birth for the purpose of comparison). 121 (89%) of 136 individuals reported sex with men. 37 (27%) of all individuals were living with HIV, with a higher proportion among trans women (31 [50%] of 62) than among cis women and non-binary individuals (six [8%] of 74). Sexual transmission was suspected in 55 (89%) trans women (with the remainder having an unknown route of transmission) and 45 (61%) cis women and non-binary individuals; non-sexual routes of transmission (including household and occupational exposures) were reported only in cis women and non-binary individuals. 25 (34%) of 74 cis women and non-binary individuals submitted to the case series were initially misdiagnosed. Overall, among individuals with available data, rash was described in 124 (93%) of 134 individuals and described as anogenital in 95 (74%) of 129 and as vesiculopustular in 105 (87%) of 121. Mucosal lesions involving the vagina, anus, or oropharynx or eye occurred in 65 (55%) of 119 individuals with available data. Vaginal and anal sex were associated with lesions at those sites. Monkeypox virus DNA was detected by PCR from vaginal swab samples in all 14 samples tested. 17 (13%) individuals were hospitalized, predominantly for bacterial superinfection of lesions and pain management. 33 (24%) individuals were treated with tecovirimat and six (4%) received post-exposure vaccinations. No deaths were reported. In summary, clinical features of monkeypox in women and non-binary individuals were similar to those described in men, including the presence of anal and genital lesions with prominent mucosal involvement.

Human monkeypox virus infection in women and non-binary individuals during the 2022 outbreaks: a global case series (Thornhill et al., The Lancet)

Between May and November, 2022, global outbreaks of human monkeypox virus infection have been reported in more than 78 000 people worldwide, predominantly in men who have sex with men. We describe the epidemiological and clinical characteristics of monkeypox virus infection in cisgender (cis) and transgender (trans) women and non-binary individuals assigned female sex at birth to improve identification and understanding of risk factors. International collaborators in geographical locations with high numbers of diagnoses of monkeypox virus infection were approached and invited to contribute data on women and non-binary individuals with confirmed monkeypox virus infection. Contributing centres completed deidentified structured case-report spreadsheets, adapted and developed by participating clinicians, to include variables of interest relevant to women and non-binary individuals assigned female at birth. We describe the epidemiology and clinical course observed in the reported infections. Collaborators reported data for a total of 136 individuals with monkeypox virus infection who presented between May 11 and Oct 4, 2022, across 15 countries. Overall median age was 34 years (IQR 28–40; range 19–84). The cohort comprised 62 trans women, 69 cis women, and five non-binary individuals (who were, because of small numbers, grouped with cis women to form a category of people assigned female at birth for the purpose of comparison). 121 (89%) of 136 individuals reported sex with men. 37 (27%) of all individuals were living with HIV, with a higher proportion among trans women (31 [50%] of 62) than among cis women and non-binary individuals (six [8%] of 74). Sexual transmission was suspected in 55 (89%) trans women (with the remainder having an unknown route of transmission) and 45 (61%) cis women and non-binary individuals; non-sexual routes of transmission (including household and occupational exposures) were reported only in cis women and non-binary individuals. 25 (34%) of 74 cis women and non-binary individuals submitted to the case series were initially misdiagnosed. Overall, among individuals with available data, rash was described in 124 (93%) of 134 individuals and described as anogenital in 95 (74%) of 129 and as vesiculopustular in 105 (87%) of 121. Median number of lesions was ten (IQR 5-24; range 1–200). Mucosal lesions involving the vagina, anus, or oropharynx or eye occurred in 65 (55%) of 119 individuals with available data. Vaginal and anal sex were associated with lesions at those sites. Monkeypox virus DNA was detected by PCR from vaginal swab samples in all 14 samples tested. 17 (13%) individuals were hospitalised, predominantly for bacterial superinfection of lesions and pain management. 33 (24%) individuals were treated with tecovirimat and six (4%) received post-exposure vaccinations. No deaths were reported. The clinical features of monkeypox in women and non-binary individuals were similar to those described in men, including the presence of anal and genital lesions with prominent mucosal involvement. Anatomically, anogenital lesions were reflective of sexual practices: vulvovaginal lesions predominated in cis women and non-binary individuals and anorectal features predominated in trans women. The prevalence of HIV co-infection in the cohort was high.

MonkeyPox2022Tweets: A Large-Scale Twitter Dataset on the 2022 Monkeypox Outbreak, Findings from Analysis of Tweets, and Open Research Questions (Thakur, Infectious Disease Reports)

The mining of Tweets to develop datasets on recent issues, global challenges, pandemics, virus outbreaks, emerging technologies, and trending matters has been of significant interest to the scientific community in the recent past, as such datasets serve as a rich data resource for the investigation of different research questions. Furthermore, the virus outbreaks of the past, such as COVID-19, Ebola, Zika virus, and flu, just to name a few, were associated with various works related to the analysis of the multimodal components of Tweets to infer the different characteristics of conversations on Twitter related to these respective outbreaks. The ongoing outbreak of the monkeypox virus, declared a Global Public Health Emergency (GPHE) by the World Health Organization (WHO), has resulted in a surge of conversations about this outbreak on Twitter, which is resulting in the generation of tremendous amounts of Big Data. There has been no prior work in this field thus far that has focused on mining such conversations to develop a Twitter dataset. Furthermore, no prior work has focused on performing a comprehensive analysis of Tweets about this ongoing outbreak. To address these challenges, this work makes three scientific contributions to this field. First, it presents an open-access dataset of 556,427 Tweets about monkeypox that have been posted on Twitter since the first detected case of this outbreak. A comparative study is also presented that compares this dataset with 36 prior works in this field that focused on the development of Twitter datasets to further uphold the novelty, relevance, and usefulness of this dataset. Second, the paper reports the results of a comprehensive analysis of the Tweets of this dataset. This analysis presents several novel findings; for instance, out of all the 34 languages supported by Twitter, English has been the most used language to post Tweets about monkeypox, about 40,000 Tweets related to monkeypox were posted on the day WHO declared monkeypox as a GPHE, a total of 5470 distinct hashtags have been used on Twitter about this outbreak out of which #monkeypox is the most used hashtag, and Twitter for iPhone has been the leading source of Tweets about the outbreak. The sentiment analysis of the Tweets was also performed, and the results show that despite a lot of discussions, debate, opinions, information, and misinformation, on Twitter on various topics in this regard, such as monkeypox and the LGBTQI+ community, monkeypox and COVID-19, vaccines for monkeypox, etc., “neutral” sentiment was present in most of the Tweets. It was followed by “negative” and “positive” sentiments, respectively. Finally, to support research and development in this field, the paper presents a list of 50 open research questions related to the outbreak in the areas of Big Data, Data Mining, Natural Language Processing, and Machine Learning that may be investigated based on this dataset.

Virology

A Vaccine Strategy Based on the Identification of an Annular Ganglioside Binding Motif in Monkeypox Virus Protein E8L (Fantini et al., Viruses)

The recent outbreak of Monkeypox virus requires the development of a vaccine specifically directed against this virus as quickly as possible. We propose here a new strategy based on a two step analysis combining (i) the search for binding domains of viral proteins to gangliosides present in lipid rafts of host cells, and (ii) B epitope predictions. Based on previous studies of HIV and SARS-CoV-2 proteins, we show that the Monkeypox virus cell surface-binding protein E8L possesses a ganglioside-binding motif consisting of several subsites forming a ring structure. The binding of the E8L protein to a cluster of gangliosides GM1 mimicking a lipid raft domain is driven by both shape and electrostatic surface potential complementarities. An induced-fit mechanism unmasks selected amino acid side chains of the motif without significantly affecting the secondary structure of the protein. The ganglioside-binding motif overlaps three potential linear B epitopes that are well exposed on the unbound E8L surface that faces the host cell membrane. This situation is ideal for generating neutralizing antibodies. We thus suggest using these three sequences derived from the E8L protein as immunogens in a vaccine formulation (recombinant protein, synthetic peptides or genetically based) specific for Monkeypox virus. This lipid raft/ganglioside-based strategy could be used for developing therapeutic and vaccine responses to future virus outbreaks, in parallel to existing solutions.

Monkeypox and Pregnancy: Latest Updates (Cuérel et al., Viruses)

Monkeypox virus (MPXV) has emerged as a threatening zoonosis. Its spread around the world has been growing fast over the last 2 years, particularly in 2022. The reasons for this sudden spread are probably multifactorial. The R0 values of the two MPXV clades are rather low, and a massive pandemic is considered unlikely, although the increase in the number of single-nucleotide polymorphisms found in the 2022 MPXV strain could indicate an accelerated human adaptation. Very little is known about the risks of an infection during pregnancy for both the mother and the fetus. Further observations must be made to create clear, adapted, evidence-based guidelines. This article summarizes the current knowledge about MPXV infections and similar pregnancy virus infections.

Diagnosis of Monkeypox infection: validation of two diagnostic kits for viral detection using RT-PCR (Elbaz et al., Journal of Virological Methods)

Monkeypox virus, a zoonotic Orthopox DNA virus was rarely reported outside of African regions until April 2022. Since then, thousands of cases have been reported worldwide. In order to cope with the increasing need for laboratory diagnosis, the availability of reliable commercial PCR assays is of paramount importance. In this study we compared the diagnostic performance of two commercial real-time (RT)-PCR assays, the Novaplex™ MPXV Assay and the Bio-Speedy® Monkeypox Virus qPCR Kit, for the detection of Monkeypox virus (MPXV) DNA from 154 human samples. These assays were compared to a recently published in-house assay that included a general MPXV target (G2T) and a West African specific target (genericWA). All assays demonstrated 100% specificity. While sensitivity of the Novpalex assay was 100% the sensitivity of the other assays was lower; 94% for the Bio-speedy assay and G2R assay and 88% for the genericWA assay. The sensitivity differences between the methods manifested almost entirely in those pharyngeal samples in which the Ct values were high (≥35). The Novaplex™ MPXV Assay showed higher Ct values compared with the other methods with a median of 27.1 compared with the Bio-Speedy assay (median 15.8, p<0.001), the G2R assay (median 23.5, p<0.001) and the genericWA assay (median 23.6, p<0.001). For all 4 methods, the Ct values were higher in samples taken from oropharynx compared with samples from rectal and pustule swabs.

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