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PRI’s MPV (Monkeypox) Situation Update – September 20

Sep 20, 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: From 1 January through 4 September 2022, 52 996 laboratory-confirmed cases of monkeypox and 18 deaths have been reported to WHO from 102 countries/territories/areas in all six WHO Regions (Table 1). Since the last edition of this report published on 24 August 2022, 11 332 new cases (27% increase) and six new deaths were reported; and six new countries reported cases. In the past seven days, 25 countries reported an increase in the weekly number of cases, with the highest increase reported in Colombia, and one country, South Sudan, reported its first case (29 August 2022). There are 27 countries that have not reported new cases for over 21 days, the maximum incubation period of the disease. (WHO Sit Rep – Latest 9/7/2022 / Dashboard)
  • US: Total confirmed MPV cases: 23,499 (9.16.2022). (full version). 
  • NY State: As of September 19 2022, a total of 3,702 confirmed orthopoxvirus/monkeypox cases – a designation established by the Centers for Disease Control and Prevention (CDC). (NY Sit Rep and County List)
  • In two recently published viewpoint articles, authors Gregg Gonsalves and Carlos Rodriquez-Diaz et al. interrogate the global and U.S. response to the 2022 monkeypox outbreak and discuss the unheeded lessons from the COVID-19 and HIV epidemics.

US Updates/News

  • CDC opening applications for Monkeypox Vaccine Equity Pilot Program (CDC) This new pilot program is intended to reach populations that may face barriers to monkeypox vaccination, which may include differences in language, location of vaccination sites, vaccine hesitancy, mistrust of government, lack of access to on-line scheduling technology, accessibility/disability issues, immigration status, and stigma.

Global Updates/News

  • Mainland China reports first imported monkeypox case (Reuters) The Chinese city of Chongqing reported one case of the monkeypox virus infection on Friday in an individual who arrived from abroad, marking mainland China’s first known monkeypox infection amid the recent global outbreak of the virus.

Official Guidance Sources

Articles by Category

Epi/Transmission/Mitigation

Containing monkeypox on a college campus: a model-based analysis (Savinkina et al., medRxiv)

In this model-based analysis, researchers developed a stochastic dynamic transmission model of Monkeypox Virus (hMPXV) to simulate potential spread of hMPXV on a university campus. The model simulated transitions between susceptible, pre-symptomatic (non-infectious), symptomatic (infectious), and recovered states. The team explored the impact of varying levels of detection and isolation of cases as well as additional containment scenarios, one considering quarantine of contacts of detected cases and the other considering vaccination of contacts of detected cases. The following assumptions were made in the model: average time from infection to symptom onset: 7.6 days; time from symptom development to recovery: 21 days; basic reproductive number (R0): 1.4; quarantine period: 14 days on average; and vaccination is 80% effective in those who were not yet infected and 40% effective at preventing symptomatic illness among those already infected. In the absence of any diagnosis or isolation, the model predicted a growing outbreak and up to 300 cumulative cases (~5% of the student population) within 100 days. Additionally, Vaccination of known contacts was a useful strategy alongside isolation and detection and could prevent 50% of additional cases. Lastly, quarantine of known contacts provided little incremental benefit when 50% of cases were detected and isolated.

Wastewater Surveillance for Monkeypox Virus in Nine California Communities (Wolfe et al., medRxiv)

In this article, authors describe results from the rapid establishment of wastewater surveillance in selected regions in California within a month of the first reported case of monkeypox in the United States. PCR assays targeting genomic DNA from the monkeypox virus (MPXV) were deployed in an ongoing wastewater surveillance program in California. MPXV DNA concentrations were measured daily in settled solids samples from nine wastewater plants. Results over a four-week period were validated across different MPXV assays, compared using influent and solids samples, and correlated using non-parametric methods (Kendall’s tau) with the number of monkeypox cases reported from each sewershed. MPXV DNA was detected at all nine sites between June 19 and August 1, 2022; 5 of 9 sites detected MPXV DNA prior to or within a day of the first case identified in the source sewershed. At the four sites with >10 positive detections, they observed a positive, statistically significant correlation (p <0.001) between MPXV DNA in wastewater solids and incidence rate of reported cases. These findings suggest wastewater can be used to effectively detect the introduction of MPXV and monitor its circulation in the community to inform public health and clinical response.

Assessment of Knowledge on Human Monkeypox Virus among General Population in Bangladesh: A Nationwide Cross-sectional Study (Nath et al., medRxiv)

In this cross-sectional observational study, researchers aimed to determine the public awareness level about monkeypox among the general community in Bangladesh to provide information regarding future measures. From May to June 2022, a nationwide survey was conducted from Bangladesh’s eight administrative divisions. Among the total of 1,711 respondents to the questionnaire, about 66.6% of the respondents (N=1139) were aware of monkeypox. Among those that were aware of monkeypox, almost two-thirds of the (66.6%) respondents had insufficient knowledge about the transmission pathways (0.71± 0.73), vaccination (0.09±0.27), and the signs and symptoms of monkeypox (1.91±1.50). The majority of participants were unable to select the treatment of monkeypox (0.22±0.59). The factors affecting the knowledge level of monkeypox were educational status and occupation (p<0.001). In summary, authors concluded that general community had a minimal understanding of the spread of monkeypox and its prevention. They recommended additional research be conducted on its epidemiology, ecology, and biology in endemic regions so that it can be comprehended and prevented.

Epidemiological Trends of Human Monkeypox Cases in Northern, Southern, Western, and Eastern Regions in Europe: A Cross-Sectional Study (Meo et al., Journal of Tropical Medicine)

In this cross-sectional study, researchers aimed to analyze the prevalence and epidemiological trends of a human monkeypox outbreak in various regions in Europe. The data about the monkeypox outbreak in European countries were recorded by WHO and CDC reports. The period prevalence-based data were recorded from Jan 1, 2022, to July 7, 2022, and analyzed, and epidemiological trends were established in four different European regions and various countries. In Europe, the human monkeypox rapidly spread in all the four subregions and involved 30 European countries, infecting 6077 people. The rising number of monkeypox cases is identified in Western Europe, 2599 (42.76%); Southern Europe, 1932 (31.79%); Northern Europe, 1487 (24.46%); and Eastern Europe, 59 (0.97%). In Western Europe, significant cases are found in Germany (1304), France (604), the Netherlands (352), Belgium (168), and Switzerland (131). In Northern Europe, it is found in the United Kingdom (1351), Ireland (44), Sweden (28), and Denmark (26); in Southern Europe, it is found in Spain (1256), Portugal (415), and Italy (233). However, a smaller number of cases are found in Eastern European states, Hungary (22), Poland (13), and Romania (12). The results further revealed that the number of monkeypox cases per million people in Northern Europe was 14.40%; Southern Europe, 13.49%; Western Europe, 13.26%; and Eastern Europe, 0.70%. The highest monkeypox cases per million population are found in Portugal, 40.70; Gibraltar, 29.68; Spain, 26.86; the United Kingdom, 19.90; Malta, 18.12; the Netherlands, 20.54; Germany, 15.56; Switzerland, 15.14; Belgium, 14.50; France, 9.27; and Ireland, 8.90. In summary, in a short period, the monkeypox cases swiftly spread in 30 non-endemic European countries and involved all four European regions. Authors recommend that healthcare authorities make timely decisions to control the outbreak of human monkeypox disease, as the world cannot afford the global burden of human monkeypox outbreak as another potential pandemic.

The clinical manifestations and severity of the 2022 monkeypox outbreak among 4080 patients (Reda et al., Travel Medicine and Infectious Disease)

In this study, researchers aimed to conduct a systematic review and meta-analysis to estimate the clinical characteristics and severity of the current monkeypox (MPX) outbreak based on evidence from large studies. PRISMA guidelines were followed and studies that recruited >10 MPX patients and reported outcomes associated with the current outbreak (i.e., clinical features of MPX, hospitalization, intensive care unit admission (ICU), and mortality rates) were included. Out of 4231 citations, the team found 14 papers that recruited 4080 MPV cases. 11 studies (N = 3488) reported the prevalence of HIV in their MPX populations to be 11.6% (405/3488). The most common clinical features of MPX were rash 70% (95%CI: 32–92), lymphadenopathy 62% (95%CI: 55–69), and fever 62% (95%CI: 58–65). Only 7% (95%CI: 5–9) of MPX cases required hospitalization. However, all studies recorded no mortality or ICU admission events regarding all the included MPV cases. The reported hospitalization rate in the current study is remarkably lower than that reported in a recently published meta-analysis (Benites-Zapata et al.); 35% in the different MPX outbreaks. However, the authors demonstrated that the hospitalization rate is 1:6 between European and African patients. When reviewing the literature, they found some reports of MPX deaths. In this context, Sah et al. estimated a case fatality rate of 0.01% in non-endemic areas, compared to 1.81% in endemic regions in 2022. These rates are remarkably lower than the previously estimated ones from previous outbreaks, 4.6% (95%CI: 2.1–8.6%) for the West African clade (Clade II) and 10.6% (95%CI: 8.4–13.3%) for the Central African or Congo basin one (Clade I). These findings indicate that the current outbreak is significantly milder than previous outbreaks, which might be attributed to the quality of care offered to MPX cases as most patients in the current outbreak were located in high-income countries and were young. According to some case reports, the reported mortality rates in some patients might be attributed to the atypical presentation of MPX.

Monkeypox viral disease outbreak in non-endemic countries in 2022: What clinicians and healthcare professionals need to know (Onchonga, Saudi Pharmaceutical Journal)

An outbreak of monkeypox Viral Disease in non-endemic countries in May 2022 is increasingly spreading. Clinicians and other healthcare professionals need to understand the aetiology and characteristics of the monkeypox pathogen and illness. By familializing themselves with these characteristics, they can map out the outbreak and roll out necessary public health mitigation measures to curb the spread. This short communication presents a summarized message regarding the aetiology, mode of transmission, clinical features, risk factors, diagnosis, treatment, and prevention of monkeypox viral disease. Considerations for surveillance and reporting have also been highlighted. There is a possibility of increased cases of monkeypox viral disease upsurges compared to cases being reported currently across the countries affected. There is also a possibility of new cases being reported in countries that have not reported any case so far. In this regard, all patients with suspected monkeypox viral disease should be investigated and if confirmed, they should be isolated until their lesions have been encased, the scab has fallen off and a new layer of skin has formed underneath (Centre for Disease Prevention, 2022). 

Atypical presentation of sexuallly-transmitted monkeypox lesions (Guillermo Perez-Martin et al., Infectious Diseases)

The literature on monkeypox lesions describes an exanthema that is usually monomorphic with a centrifugal distribution (13,14). Given that the lesions appear in some areas and then spread to other regions of the body, cases of patients with lesions at different stages in different locations have been already published. The MPX cases described by Pittman et al. in Western and Central Africa (1981 to 1986), presented a sequential progression of the lesions in the same body region (15). More recently, Hammerschlag et al. presented a case with penile lesions at crust stage, papular pustules on lower limbs, and vesicular-state lesions and crusts on the upper limbs and trunk (1)4. Therefore, there is some evidence that lesions can evolve sequentially in parallel, at different stages on different locations after they appear. In our case, the lesions unexpectedly developed at different stages in the same body region, presenting simultaneous vesicular, pustular and crusted lesions. Palmore et al. indicated that clinical presentations in this epidemic have frequently been atypical, simulating other sexually transmitted diseases, and the characteristic prodromic fever of MPX has been absent or very mild (1)6. The same occurred in our case, who did not present febrile prodromes and began the disease with adenopathy and skin lesions. If MPX is not immediately diagnosed, it may have a torpid course without early treatment or be transmitted to other people. Since primary care physicians are often the first healthcare professional to come in contact with the patient, it is important for them to be aware that both the initial presentation and the subsequent evolution of the lesions may be different from those described in the literature. A comprehensive epidemiological survey is highly recommended, as it would help in the diagnosis of atypical lesions (16).

Monkeypox associated acute arthritis (Fonti et al., The Lancet)

A 31-year-old HIV-positive man presented to the hospital on June 30, 2022, with a vesicular rash (figure A), perianal lesions, swollen inguinal lymph nodes, and arthralgia of the right knee. Under antiretroviral therapy, the HIV viral load was below the limit of detection, and his CD4+ T-cell count was 802 cells per μL. Given the rising number of monkeypox cases in Europe at that time and the patient’s history of unprotected sexual contact with a man 1 week before symptom onset, an infection with monkeypox virus was suspected. Specimens from two different skin lesions yielded a positive PCR result (cycle threshold values of 20 and 21) for monkeypox virus. The patient was discharged and self-isolated. 11 days later a follow-up examination was scheduled, the rash and lymphadenopathy had completely resolved, but a marked swelling of the right knee was noted (figure B). Arthrocentesis was performed, resulting in aspiration of 60 mL of cloudy synovial fluid. Analysis of the synovial fluid showed a cell count of 16 127 cells per μL with 88·5% mononuclear cells (lymphocytes) and 11·5% neutrophil granulocytes. The synovial fluid PCR yielded a positive result for monkeypox virus (cycle threshold value of 27). Laboratory test results were unremarkable apart from a slightly elevated C-reactive protein of 18 mg/L.

Vaccine

Single and 2-dose vaccinations with MVA-BN® induce durable B cell memory responses in healthy volunteers that are comparable to older generation replicating smallpox vaccines COVID-19 (Ilchmann et al., medRxiv)

In this article, authors describe a set of clinical studies conducted to assess the safety, immunogenicity, and durability of MVA-BN in a mixed population, comprised of younger individuals

who had never been immunized against smallpox and older individuals who were vaccinated against smallpox in the distant past using live-replicating vaccinia vaccines. Participants were randomized to receive, 4 weeks apart: 2 placebo vaccinations (PBO group, N =181); 1 MVA-BN vaccination followed by placebo (1×MVA group, N =181); or 2 MVA-BN vaccinations (2×MVA group, N = 183). In addition, participants with a history of smallpox vaccination received 1 MVA-BN booster (HSPX+ group, N = 200). The 1×MVA and 2×MVA groups responded with increases in neutralizing antibody (nAb) GMTs at Week 2 (5.1 and 4.8, respectively) that further increased at Week 4 (7.2 and 7.5). Two weeks after the second primary vaccination in the 2×MVA group (at Week 6), nAb GMT peaked (45.6) before stabilizing 2 weeks thereafter (at Week 8) (34.0). In the HSPX+ group, a rapid anamnestic response was observed with a peak nAb GMT at Week 2 (175.1) that was much larger than the peak responses in either of the primary vaccination (1× or 2×MVA) dose groups of smallpox vaccine-naïve subjects. Persistence of nAbs relative to baseline was observed at 6 months in all groups (highest in HSPX+), with a return to near baseline nAb levels 2 years later. Subsets of ∼75 participants each, who received primary vaccinations in the 1×MVA and 2×MVA groups, were administered an MVA-BN booster 2 years later. Both booster dose (BD) groups exhibited rapid anamnestic responses with nAb GMTs that peaked 2 weeks post-booster (80.7 and 125.3). These post-booster titers in the 1×MVA and 2×MVA groups were higher than those observed at any timepoint following primary vaccination, were comparable to HSPX+ subjects who had been administered a booster, and remained elevated at 6 months post-booster (25.6 and 49.3). The observed anamnestic responses, in the absence of sustained detectable nAbs, support the presence of durable immunological memory following MVA-BN immunization. No safety concerns were identified, and the most common adverse event following the 2-year MVA-BN booster was injection site erythema in 82.2% of participants.

Virology

Validation Study of a Direct Real-Time PCR Protocol for Detection of Monkeypox Virus (Chelsky et al., The Journal of Molecular Diagnostics) 

Monkeypox has recently been described as a public health emergency of international concern by the World Health Organization and a public health emergency by the United States. If the outbreak continues to grow, rapid scalability of laboratory testing will be imperative. During the early days of the coronavirus disease 2019 (COVID-19) pandemic, laboratories improved the scalability of testing by using a direct-to-PCR approach. To improve the scalability of monkeypox testing, a direct real-time PCR protocol for the detection of monkeypox virus was validated. The assay retains the sensitivity and accuracy of the indirect assay while eliminating the need for nucleic acid extraction kits, reducing laboratory technologist time per sample and decreasing exposure to an infectious agent. The direct method will make it easier for laboratories across the world to rapidly develop, validate, and scale testing for monkeypox virus. Monkeypox virus, an encapsulated double-stranded DNA virus and member of the Poxviridae family, is responsible for the recent monkeypox outbreak that has been declared a public health emergency of international concern by the World Health Organization and a public health emergency by the United States. Prompt identification of infected individuals followed by contact tracing is important for stemming the spread of disease. The characteristic rash of monkeypox progresses through multiple stages, beginning with a macular phase, progressing through papular, vesicular, and pustular phases, and ending with a scab phase. Its appearance can be similar to rashes associated with other infections, including varicella zoster, herpes, and syphilis; thus, testing of the lesion is important for accurate diagnosis.1 The CDC monkeypox diagnostic assay is in use in many laboratories across the United States. It is a real-time PCR-based assay utilizing a nucleic acid extraction step before amplification.2 Other reported monkeypox diagnostic assays also utilize a nucleic acid extraction step.

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