News & Events

PRI’s MPV (Monkeypox) Situation Update – August 30

Aug 30, 2022 | News

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: During the week of 15 to 21 August, the number of cases reported in the Region of the Americas shows a continuing steep rise, confirming trends seen over the last several weeks. Globally, after four consecutive weeks of increase, the number of MPV cases reported declined by 21% overall during the same week (n=5907 cases) as compared to the previous week (n=7477 cases). This decrease may reflect early signs of a declining case count in the European region, which would need to be subsequently confirmed. (WHO Sit Rep – Latest 8/24/2022 / Dashboard )
  • US: Total confirmed MPV cases: 18,101 (8.29.2022). (full version). 
  • NY State: As of August 29 2022, a total of 3,197 confirmed orthopoxvirus/monkeypox cases – a designation established by the Centers for Disease Control and Prevention (CDC). (NY Sit Rep and County List)
  • U.S. monkeypox cases may be peaking, experts say (Reuters) Since late May, the United States has recorded nearly 17,000 monkeypox cases. The outbreak, which so far has reached 80 countries outside of Africa, where the virus is endemic, is largely being transmitted among gay and bisexual men.

US Updates/News

  • A Risky Monkeypox Vaccine Is Looking Better All the Time (Atlantic) Now that the administration has asked that every dose of Jynneos be split into five and delivered a different way, between the layers of the skin, the party line has changed. But this new strategy of intradermal dosing “is a gamble,” says Caitlin Rivers, an epidemiologist at Johns Hopkins, and its weaknesses are already beginning to show. 
  • Biden admin strikes $11 million deal to fund monkeypox vaccine production (Axios) The Department of Health and Human Services’ Biomedical Advanced Research and Development Authority (BARDA) will provide $11 million to help GRAM buy additional equipment, as well as recruit and train new personnel, to help accelerate the packaging of the vaccine vials, per an HHS press release.

Global Updates/News

  • WHO: Monkeypox cases drop 21%, reversing month-long increase (AP News) The number of monkeypox cases reported globally dropped 21% in the last week, reversing a month-long trend of rising infections and signaling that Europe’s outbreak may be starting to decline, the World Health Organization said Thursday. The U.N. health agency reported 5,907 new weekly cases and said two countries, Iran and Indonesia, reported their first cases. To date, more than 45,000 monkeypox cases have been reported in 98 countries since late April.
  • Mexico, Cuba report rare deaths of two patients with monkeypox (Reuters) Mexico and Cuba have reported the deaths of two people who had tested positive for monkeypox, although neither country attributed the fatalities to the viral disease. The reports follow monkeypox-related deaths reported in Brazil and Ecuador in the past month, but fatalities remain extremely rare in the current outbreak.
  • Perceptions of monkeypox from those most at risk: men who have sex with men having multiple sexual partners (WHO) With the outbreak being declared a Public Health Emergency of International Concern at the end of July, the important thing right now is to focus on bringing this outbreak to an end, as Dr Hans Henri P. Kluge, WHO Regional Director for Europe highlighted in his 26 July statement: “the responsibility for stopping this outbreak is necessarily a joint responsibility, shared among health institutions and authorities, governments, affected communities and individuals themselves”.   

Official Guidance Sources

Articles by Category

Epi/Transmission/Mitigation

Human monkeypox outbreak: global prevalence and biological, epidemiological and clinical characteristics – observational analysis between 1970-2022 (Meo et al., European Review for Medical and Pharmacological Sciences)

This study is aimed at exploring the global epidemiological, biological and clinical characteristics of monkeypox from 1970 to July 1, 2022. Information about the monkeypox outbreak and its epidemiological and biological characteristics was obtained from the World Health Organization (WHO), Centers for Disease Control and Prevention (CDC) reports, Pub-Med, and Web of Science. Initially, these two leading international health organizations, and 10 documents were identified; after reviewing, they included WHO and CDC, and six documents in the analysis. Worldwide, from 1970 to July 1, 2022, the total number of confirmed and suspected cases of human monkeypox disease in endemic and non-endemic nations was 46,915. In endemic regions, the number of confirmed cases has been 2,805 and suspected cases have been 38,327, with a total number of 41,132. However, from May 7, 2022, to July 1, 2022, 5,783 monkeypox cases have been found in 52 non-endemic nations in Europe, the UK, the USA, Australia and the Middle East. The majority of cases have been found in the United Kingdom (1,235), Germany (1,054), Spain (800), France (498), United States (459), Portugal (402), Netherlands (288), Canada (287), Italy (192), Belgium (117), Switzerland (91), Israel (42), Ireland (39), Austria (37), Sweden (28), Brazil (21), and Denmark (20). The clinical presentation of monkeypox disease is mild symptoms, including headache, lymphadenopathy, body aches, severe weakness, and acute onset of fever above 38.5°C. A skin rash initiates as macules or papules, progresses to pustules and vesicles, ulcers, and ultimately transitions to crusted scabs. In a short period of about two months, the monkeypox cases swiftly spread in 52 non-endemic countries with an increased percentage worldwide. In conclusion, the geographic pattern of monkeypox disease spread is rapidly shifting from endemic to non-endemic regions. It now involves not only Africa but also Europe, the USA, the UK, Australia and the Middle East. The clinical characteristics of monkeypox infection are mostly mild symptoms, including headache, lymphadenopathy, body aches, severe weakness, and acute onset of fever above 38.5 degrees Centigrade. A skin rash originates as macules or papules, progresses to pustules and vesicles, ulcers, and eventually to crusted scabs.

Monkeypox: A clinical update for paediatricians (Huang et al., Journal of Pediatrics and Child Health)

Monkeypox disease is spread from animals to humans through infected lesions or fluids; human–human transmission occurs through fomites, droplets or direct contact. Illness is usually self-limiting, but severe disease can occur in specific groups – particularly children, and people who are immunocompromised or pregnant. Clinical presentation may include fever, lymphadenopathy and skin rash, but the rash may occur without other symptoms. Complications can include secondary bacterial infection of skin lesions, vision loss from corneal involvement, pneumonia, sepsis and encephalitis. Diagnosis of monkeypox requires consideration of epidemiological, clinical and laboratory findings, with sensitive history-taking, to elicit close contacts, critical. Supportive management is usually sufficient, but treatment options (where required) include antivirals and vaccinia immune globulin. A paucity of safety data for relevant antivirals may limit their use. There are two types of monkeypox vaccines: a replication-competent vaccinia vaccine, the use of which is logistically and clinically complex, and a replication-deficient modified vaccinia Ankara virus vaccine. Preparedness of health systems for addressing the current outbreak is constrained by historic underfunding for research, and compounded by stigma and discrimination against cases and affected communities. Key challenges in halting transmission include improving vaccine equity and countering discrimination against men who have sex with men to aid diagnosis and treatment.

Strategies Adopted by Gay, Bisexual, and Other Men Who Have Sex with Men to Prevent Monkeypox virus Transmission — United States, August 2022 (Delaney et al., MMWR)

The multipronged response to monkeypox has included expanding access to monkeypox vaccine and developing messaging for gay, bisexual, and other men who have sex with men (MSM) seeking to reduce their chances for acquiring monkeypox. During August 5–15, 2022, a monkeypox-specific follow-up survey was completed by a convenience sample of 824 MSM who responded to the annual American Men’s Internet Survey (AMIS). Overall, 48% of respondents reported reducing their number of sex partners, 50% reported reducing one-time sexual encounters, and 50% reported reducing sex with partners met on dating apps or at sex venues since learning about the monkeypox outbreak. Nearly one in five respondents reported receiving ≥1 dose of vaccine to prevent monkeypox. Receipt of vaccine was highest among Hispanic or Latino (Hispanic) men (27.1%) and lowest among non-Hispanic Black or African American (Black) men (11.5%); 17.7% of non-Hispanic White (White) men and 24.2% of men of other race or ethnicity received vaccine. Receipt of vaccine was higher in urban (27.8%) and suburban (14.5%) areas than in other areas (5.7%–7.0%). These data suggest that MSM are taking steps to protect themselves and their partners from monkeypox. It is important that federal, state, and local public health programs continue to deliver tailored, respectful harm reduction messages that do not create stigma to diverse communities of MSM. Vaccine programs should prioritize efforts to maximize equitable access to vaccines to prevent monkeypox.

Modeling the Impact of Sexual Networks in the Transmission of Monkeypox virus Among Gay, Bisexual, and Other Men Who Have Sex With Men — United States, 2022 (Spicknall et al., CDC MMWR)

Survey data suggest that gay, bisexual, and other men who have sex with men (MSM) have taken steps to protect themselves and their partners from monkeypox, including reducing one-time sexual partnerships. To gain a better understanding, CDC simulated dynamic network models representing the sexual behavior between MSM. The modeling indicated that men with more than one partner in the preceding 3 weeks had 1.8–6.9 times the risk for acquiring monkeypox as did men with only one partner. Although one-time partnerships represented <3% of the total daily partnerships and 16% of the sex between men on any given day, they accounted for approximately 50% of MPXV transmission. In this model, a 40% decrease in one-time partnerships yielded a 20%–31% reduction in the percentage of MSM infected and a delay in the spread of the outbreak. A decrease in one-time partnerships not only decreased the final percentage of MSM infected, but it also increased the number of days needed to reach a given level of infection in the population, allowing more time for vaccination efforts to reach susceptible persons. If decreasing one-time partnerships were combined with additional mitigation measures such as vaccination or shorter time from symptom onset to testing and treatment, this effect would be higher. Reductions in one-time partnerships, a change in behavior already being reported by MSM, might significantly reduce MPXV transmission.

Monkeypox virus from neurological complications to neuroinvasive properties: current status and future perspectives (Sepehrinezhad et al., Journal of Neurology)

Cases of monkeypox (MPV) are sharply rising around the world. While most efforts are being focused on the management of the first symptoms of monkeypox, such as cutaneous lesions and flu-like symptoms, the effect of the monkeypox virus (MPXV) on multiple organs still remains unclear. Recently, several neurological manifestations, such as headache, myalgia, malaise, fatigue, altered consciousness, agitation, anorexia, nausea, and vomiting, have been reported in patients with MPV. In addition, data from experimental studies have indicated that MPXV can gain access to the central nervous system (CNS) through the olfactory epithelium and infected circulatory monocytes/macrophages as two probable neuroinvasive mechanisms. Therefore, there are growing concerns about the long-term effect of MPXV on the CNS and subsequent neurological complications. This paper highlights the importance of the neuroinvasive potential of MPXV, coupled with neurological manifestations.

Treatment

A Glance at the Development and Patent Literature of Tecovirimat: The First-in-Class Therapy for Emerging Monkeypox Outbreak (Almehmadi et al., Viruses)

Monkeypox disease (MPX) is currently considered a global threat after COVID-19. European Medicines Agency (EMA) approved Tecovirimat in capsule dosage form (200 mg) as the first treatment for MPX in January 2022. This article highlights Tecovirimat’s development and patent literature review and is believed to benefit the scientists working on developing MPX treatments. The literature for Tecovirimat was gathered from the website of SIGA Technologies (developer of Tecovirimat), regulatory agencies (EMA, United States Food and Drug Administration (USFDA), and Health Canada), PubMed, and freely accessible clinical/patent databases. Tecovirimat was first recognized as an anti-orthopoxvirus molecule in 2002 and developed by SIGA Technologies. The USFDA and Health Canada have also recently approved Tecovirimat to treat smallpox in 2018 and 2021, respectively. The efficacy of Tecovirimat was verified in infected non-human primates (monkeys) and rabbits under the USFDA’s Animal Rule. Most clinical studies have been done on Tecovirimat’s safety and pharmacokinetic parameters. The patent literature has revealed inventions related to the capsule, injection, suspension, crystalline forms, amorphous form, and drug combinations (Tecovirimat + cidofovir) and process for preparing Tecovirimat. The authors foresee the off-label use of Tecovirimat in the USA and Canada for MPX and other orthopoxvirus infections. The authors also trust that there is immense scope for developing new Tecovirimat-based treatments (new drug combinations with other antivirals) for orthopoxvirus and other viral diseases. Drug interaction studies and drug resistance studies on Tecovirimat are also recommended. Tecovirimat is believed to handle the current MPX outbreak and is a new hope of biosecurity against smallpox or orthopoxvirus-related bioterrorism attack.

Vaccine

Maximizing the impact of limited vaccine supply under different epidemic conditions: a two-city monkeypox modelling analysis (Knight et al., medRxiv)

In this modelling study, researchers sought to explore optimal monkeypox vaccine allocation between two linked transmission networks over a short-term time horizon, across a range of epidemic conditions. The team constructed a deterministic compartmental susceptible, vaccinated, exposed, infectious, recovered (SVEIR) model of monkeypox transmission. They parameterized the model to reflect two representative, weakly connected gay and bisexual men who have sex with men (MSM) sexual networks (cities) in Ontario. They simulated roll-out of 5000 vaccine doses over 15 days, starting 60 days after epidemic seeding with 10 imported cases. Within this model, they varied: the relative city (network) sizes, epidemic potentials (R0), between-city mixing, and distribution of imported/seed cases between cities. Under the modelling assumptions, the team found that a fixed supply of vaccines could generally avert more infections over short-term time horizons when prioritized to: a larger transmission network, a network with more initial infections, and/or a network with greater R0. Greater between-city mixing decreased the influence of initial seed cases, and increased the influence of city R0 on optimal allocation. Under mixed conditions (e.g. fewer seed cases but greater R0), optimal allocation saw doses shared between cities, suggesting that proximity-based and risk-based vaccine prioritization can work in combination to minimize transmission. In summary, these findings suggest that prioritization of limited vaccine supply based on network-level risk factors can help minimize transmission during an emerging epidemic.

Repositioning potentials of smallpox vaccines and antiviral agents in monkeypox outbreak:A rapid review on comparative benefits and risks (Islam et al., Health Science Reports)

Monkeypox is spreading new worries around the world before the end of the Covid‐19 epidemic. Covid‐19 was a new type of virus that scientists had no idea about before the disease spread. Monkeypox is not a new disease. The disease was first reported in 1958.1 In 1970, the first case of human monkeypox was reported in a central African country named the Democratic Republic of the Congo.1 Afterward, monkeypox infections have been reported in several countries in West and Central Africa.2 However, the prevalence of the disease outside Africa was not so high before May 2022. Since January 1, 2022 to June 15, 2022, a total of 2103 confirmed cases of monkeypox and one death have been reported from 42 European, American, and nonendemic countries.3 Monkeypox virus is a poxvirus that belongs to the Orthopoxvirus genus of the Poxviridae family.4 The initial symptoms of monkeypox infection include a high fever, headache, backache, swollen lymph nodes, and chickenpox‐like rash.4 Most monkeypox symptoms are mild and patients recover within 2–4 weeks. The case fatality historically varies from 3% to 6% depending on the source of the monkeypox virus and the condition of the patients.5 Moreover, evidence‐based proven therapeutic intervention for monkeypox infection is still absent. However, there are similarities between the monkeypox virus, variola virus (smallpox virus), and vaccinia virus (a component of orthopoxvirus vaccines). Therefore, smallpox vaccines and drugs are assumed to be effective in monkeypox infection. Moreover, we have seen drug repurposing and authorization for Covid‐19 therapy.6,7 The healthcare authorities in many countries have started to offer or stockpile smallpox vaccines and drugs to control monkeypox outbreak. Here, we aimed to review and discuss the repurposing potentials of smallpox vaccines and drugs in monkeypox outbreaks based on their comparative benefits and risks. To do this, we searched Google Scholar and PubMed for relevant information for this rapid review. We found many articles have suggested the use of smallpox vaccines and antiviral drugs in monkeypox outbreak according to their study findings.

Virology

Rapid Amplicon Nanopore Sequencing (RANS) for the Differential Diagnosis of Monkeypox Virus and Other Vesicle-Forming Pathogens (Israeli et al., Viruses)

This study aimed to provide a rapid genetic-based diagnostic tool for accurate and specific identification of monkeypox virus (MPXV) and additional related vesicle-forming pathogens. Researchers initially assembled a list of 14 relevant viral pathogens, causing infectious diseases associated with vesicles, prone to be misdiagnosed as MPX. Next, they developed an approach that they termed rapid amplicon nanopore sequencing (RANS). The RANS approach uses diagnostic regions that harbor high homology in their boundaries and internal diagnostic single nucleotide polymorphisms (SNPs) that, when sequenced, aid the discrimination of each pathogen within a group. During a multiplex PCR amplification, a dA tail and a 5′-phosphonate were simultaneously added, thus making the PCR product ligation ready for nanopore sequencing. Following rapid sequencing (a few minutes), the reads were compared to a reference database and the nearest strain was identified. They first tested the approach using samples of known viruses cultured in cell lines. All the samples were identified correctly and swiftly. Next, they examined a variety of clinical samples from the 2022 MPX outbreak. The RANS approach identified correctly all the PCR-positive MPXV samples and mapped them to strains that were sequenced during the 2022 outbreak. For the subset of samples that were negative for MPXV by PCR, they obtained definite results, identifying other vesicle-forming viruses: Human herpesvirus 3, Human herpesvirus 2, and Molluscum contagiosum virus. This work was a proof-of-concept study, demonstrating the potential of the RANS approach for rapid and discriminatory identification of a panel of closely related pathogens. The simplicity and affordability of the approach makes it straightforward to implement in any genetics lab. Moreover, other differential diagnostics panels might benefit from the implementation of the RANS approach into their diagnostics pipelines. 

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