PRI’s MPV (Monkeypox) Situation Update – November 9

Nov 8, 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: 28,709 (11.7.2022). (full version). 
  • NY State: As of October 31 2022, a total of 3,743 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 may spread before symptoms start, study suggests (CNN) “The thing is with poxviruses in general, you tend to see transmission once symptoms develop,” said Hanage, who was not involved in the study. “For several months now, there’s been a concern, or sort of the increasing realization, that if you’re talking about transmission in sexual networks, if there’s any type of contact where pre-symptomatic transmission would be possible, that’s it.”

Global Updates/News

Articles by Category

Epi/Transmission/Mitigation

Transmission dynamics of monkeypox in the United Kingdom: contact tracing study (Ward et al., BMJ)

This contact tracing study, linking data on case-contact pairs and on probable exposure dates, used case questionnaires from the UK Health Security Agency (UKHSA). 2746 people with PCR confirmed monkeypox virus in the UK between 6 May and 1 August 2022 were included. Main outcome measures included the incubation period and serial interval of a monkeypox infection using two bayesian time delay models—one corrected for interval censoring (ICC—interval censoring corrected) and one corrected for interval censoring, right truncation, and epidemic phase bias (ICRTC—interval censoring right truncation corrected).  The mean age of participants was 37.8 years and 95% reported being gay, bisexual, and other men who have sex with men (1160 out of 1213 reporting). The mean incubation period was estimated to be 7.6 days (95% credible interval 6.5 to 9.9) using the ICC model and 7.8 days (6.6 to 9.2) using the ICRTC model. The estimated mean serial interval was 8.0 days (95% credible interval 6.5 to 9.8) using the ICC model and 9.5 days (7.4 to 12.3) using the ICRTC model. Although the mean serial interval was longer than the incubation period for both models, short serial intervals were more common than short incubation periods, with the 25th centile and the median of the serial interval shorter than the incubation period. For the ICC and ICRTC models, the corresponding estimates ranged from 1.8 days (95% credible interval 1.5 to 1.8) to 1.6 days (1.4 to 1.6) shorter at the 25th centile and 1.6 days (1.5 to 1.7) to 0.8 days (0.3 to 1.2) shorter at the median. 10 out of 13 linked patients had documented pre-symptomatic transmission. Doubling times of cases declined from 9.07 days (95% confidence interval 12.63 to 7.08) on the 6 May, when the first case of monkeypox was reported in the UK, to a halving time of 29 days (95% confidence interval 38.02 to 23.44) on 1 August. In summary, analysis of the instantaneous growth rate of monkeypox incidence indicates that the epidemic peaked in the UK as of 9 July and then started to decline. Short serial intervals were more common than short incubation periods suggesting considerable pre-symptomatic transmission, which was validated through linked patient level records. For patients who could be linked through personally identifiable data, four days was the maximum time that transmission was detected before symptoms manifested. An isolation period of 16 to 23 days would be required to detect 95% of people with a potential infection. The 95th centile of the serial interval was between 23 and 41 days, suggesting long infectious periods.

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)

In this case report, the authors report on a 28-year-old MSM with no past medical history who developed a profuse pustular rash and asthenia and was diagnosed with monkeypox infection via NAAT on pastule, saliva, and nasopharyngeal samples. He reported a single sexual partner and contact with a monkeypox-infected patient in Spain in early July 2022. He had fever and inguinal lymphadenopathies, without severe anorectal pain, soft-tissue superinfection, or signs of myocarditis, encephalitis, respiratory or digestive involvement. He was not screened for sexually transmitted infections (STI) at that time and was asked to isolate himself at home with supportive care only. He was admitted to hospital on 24 August with a temperature of 40.5°C and a pulse of 140/min, but no sign of sepsis. Examination revealed about 25 painful, inflammatory crusted lesions with a diameter of 2-3 cm scattered over his face, scalp, trunk, limbs, and anal margins, associated with scalp cellulitis. Diagnostic workup revealed an advanced HIV-1/AIDS infection with a plasma virus load of 5.8 log10 copies/ml and a CD4+ T cell count of 63/μl (5%). Screening for opportunistic infections, viral hepatitis A, B and C, gonorrhea, chlamydiosis and in stools enteropathogens and protozoal infections were negative, except for latent syphilis.  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 Oral Tecovirimat 600 mg twice daily for 14 days. He rapidly improved, the skin lesions decreased, as did the monkeypox virus loads, with no adverse events. The authors conclude that this case indicates that Tecovirimat might be effective for treating immunocompromised patients infected with monkeypox virus.

Epidemiologic and Clinical Features of Children and Adolescents Aged <18 Years with Monkeypox — United States, May 17–September 24, 2022 (Hennessee et al., CDC MMWR)

In this report, researchers present data on the epidemiologic and clinical characteristics of monkeypox in persons aged ≤12 years (children) and adolescents during the ongoing 2022 monkeypox in the U.S. During May 17–September 24, 2022, a total of 25,038 monkeypox cases were reported in the U.S., primarily among adult gay, bisexual, and other men who have sex with men. During this period, CDC and U.S. jurisdictional health departments identified Monkeypox virus (MPXV) infections in 83 persons aged <18 years, accounting for 0.3% of reported cases. Among 28 children aged 0–12 years with monkeypox, 64% were boys, and most had direct skin-to-skin contact with an adult with monkeypox who was caring for the child in a household setting. Among 55 adolescents aged 13–17 years, most were male (89%), and male-to-male sexual contact was the most common presumed exposure route (66%). Most children and adolescents with monkeypox were non-Hispanic Black or African American (Black) (47%) or Hispanic or Latino (Hispanic) (35%). Most (89%) were not hospitalized, none received intensive care unit (ICU)–level care, and none died. Authors conclude that monkeypox in children and adolescents remains rare in the United States. Ensuring equitable access to monkeypox vaccination, testing, and treatment is a critical public health priority. Furthermore, they suggest that vaccination for adolescents with risk factors and provision of prevention information for persons with monkeypox caring for children might prevent additional infections.

Transmission dynamics of monkeypox in the United Kingdom: contact tracing study (Ward et al., BMJ)

Objective: To analyse the transmission dynamics of the monkeypox outbreak in the UK, declared a Public Health Emergency of International Concern in July 2022. Design: Contact tracing study, linking data on case-contact pairs and on probable exposure dates. Setting: Case questionnaires from the UK Health Security Agency (UKHSA), United Kingdom. Participants: 2746 people with polymerase chain reaction confirmed monkeypox virus in the UK between 6 May and 1 August 2022. Main outcome measures: The incubation period and serial interval of a monkeypox infection using two bayesian time delay models—one corrected for interval censoring (ICC—interval censoring corrected) and one corrected for interval censoring, right truncation, and epidemic phase bias (ICRTC—interval censoring right truncation corrected). Growth rates of cases by reporting date, when monkeypox virus was confirmed and reported to UKHSA, were estimated using generalised additive models. Results: The mean age of participants was 37.8 years and 95% reported being gay, bisexual, and other men who have sex with men (1160 out of 1213 reporting). The mean incubation period was estimated to be 7.6 days (95% credible interval 6.5 to 9.9) using the ICC model and 7.8 days (6.6 to 9.2) using the ICRTC model. The estimated mean serial interval was 8.0 days (95% credible interval 6.5 to 9.8) using the ICC model and 9.5 days (7.4 to 12.3) using the ICRTC model. Although the mean serial interval was longer than the incubation period for both models, short serial intervals were more common than short incubation periods, with the 25th centile and the median of the serial interval shorter than the incubation period. For the ICC and ICRTC models, the corresponding estimates ranged from 1.8 days (95% credible interval 1.5 to 1.8) to 1.6 days (1.4 to 1.6) shorter at the 25th centile and 1.6 days (1.5 to 1.7) to 0.8 days (0.3 to 1.2) shorter at the median. 10 out of 13 linked patients had documented pre-symptomatic transmission. Doubling times of cases declined from 9.07 days (95% confidence interval 12.63 to 7.08) on the 6 May, when the first case of monkeypox was reported in the UK, to a halving time of 29 days (95% confidence interval 38.02 to 23.44) on 1 August. Conclusions: Analysis of the instantaneous growth rate of monkeypox incidence indicates that the epidemic peaked in the UK as of 9 July and then started to decline. Short serial intervals were more common than short incubation periods suggesting considerable pre-symptomatic transmission, which was validated through linked patient level records. For patients who could be linked through personally identifiable data, four days was the maximum time that transmission was detected before symptoms manifested. An isolation period of 16 to 23 days would be required to detect 95% of people with a potential infection. The 95th centile of the serial interval was between 23 and 41 days, suggesting long infectious periods.

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

Estimates of the case hospitalization rate and case fatality rate when hospital care is available for monkeypox (MPX) infections have not been well defined. This rapid systematic review and meta-analysis aimed to estimate the case hospitalisation rate and case fatality rate where hospital care is available. We systematically searched PubMed, Embase, the Lancet Preprints, and MedRxiv for studies published between Jan 1, 1950 and Aug 2, 2022. We included documents which contained both the number of cases and associated hospitalisations of MPX infections. From eligible studies we extracted the country, the year of the study, the study design type, the clade of MPX, the participant characteristics, transmission type, any treatments used, number of cases (including suspected, probable, or laboratory confirmed diagnosis), number of hospitalizations, hospitalized patient outcomes, and case definition. Case hospitalization rate (CHR) was defined as the proportion of cases that were admitted to hospital care while case fatality rate (CFR) was defined as the proportion of cases that died. CHR and CFR were analysed in a fully Bayesian meta-analytic framework using random effects models, including sub-group analysis with heterogeneity assessed using I2. 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 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. CFR was estimated to be 0.03% (0.0–0.44, I2 99.9%), with evidence of large heterogeneity between the studies. There is limited data for MPX hospitalization rates in countries where MPX has been traditionally non-endemic until the current outbreak. Due to substantial heterogeneity, caution is needed when interpreting these findings. Health care organizations should be cognizant of the potential increase in healthcare utilization. Rapid identification of infection and use of appropriate therapies such as antivirals play a role reducing the CHR and associated CFR.

Vaccine

Design of a novel multiple epitope-based vaccine: an immunoinformatics approach to combat monkeypox (Hayat et al., Journal of Biomolecular Structure and Dynamics)

Monkeypox virus is an infectious agent that causes fever, Pneumonitis encephalitis, rash, lymphadenopathy and bacterial infection. The current outbreak of monkeypox has reawakened the global health concern. In the current situation of increasing viral infection, no vaccine or drug is available for monkeypox. Thus, there is an urgent need for viable vaccine development to prevent viral transmission by boosting human immunity. Herein, using immunoinformatics approaches, a multi-epitope vaccine was constructed for the Monkeypox virus. In this connection, B-Cell and T-cell epitopes were identified and joined with the help of adjutants and linkers. The vaccine construct was selected based on promising vaccine candidates and immunogenic potential. Further epitopes were selected based on antigenicity score, non-allergenicity and good immunological properties. Molecular docking reveals strong interactions between TLR-9 and the predicted vaccine construct. Finally, molecular dynamics simulations were performed to evaluate the stability and compactness of the constructed vaccine. The MD simulation results demonstrated the significant stability of the polypeptide vaccine construct. The predicted vaccine represented good stability, expression, immunostimulatory capabilities and significant solubility. Design vaccine was verified as efficient in different computer-based immune response investigations. Additionally, the constructed vaccine also represents a good population coverage in computer base analysis.

Virology

In vitro and in vivo efficacy of Tecovirimat against a recently emerged 2022 Monkeypox virus isolate (Warner et al., Science Translational Medicine)

The recent emergence of the monkeypox virus (MPXV) in non-endemic countries has been designated a Public Health Emergency of International Concern by the World Health Organization. There are currently no approved treatments for MPXV infection in the United States or Canada. The antiviral drug tecovirimat (commonly called TPOXX), previously approved for smallpox treatment, is currently being deployed for treatment of MPXV infections where available based on previously accrued data. Here, researchers tested the efficacy of TPOXX both in vitro and in vivo against a clade 2 Canadian 2022 isolate of MPXV isolated during the current outbreak. TPOXX prevented MPXV replication in vitro with an effective concentration in the nanomolar range. In order to evaluate TPOXX efficacy in vivo, they first characterized the CAST/EiJ mouse model with the same 2022 Canadian isolate. Interestingly, unlike previous descriptions of this model, the Canadian isolate was not lethal in CAST/EiJ mice, though it replicated efficiently in the respiratory tract following intranasal infection. Subsequent experiments demonstrated that daily oral TPOXX treatment dramatically reduced viral titers in the tissues one and two weeks following infection. The researchers conclude that these data indicate that TPOXX is highly effective against currently circulating MPXV strains and could be an important contributor to curbing the ongoing outbreak.

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. researhcers 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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