News & Events

PRI’s MPV (Monkeypox) Situation Update – September 8

Sep 8, 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)

US Updates/News

Global Updates/News

  • Hong Kong discovers first case of monkeypox (Reuters) Hong Kong has reported its first case of monkeypox, health authorities said on Tuesday, after symptoms were discovered in a 30-year old man who arrived from the Phillippines after travelling in the United States and Canada. 
  • EU secures more doses of Bavarian monkeypox vaccine (Reuters) The European Union said on Wednesday it had secured an additional 170,920 doses of monkeypox vaccine developed by biotech firm Bavarian Nordic amid concerns about the outbreak of the disease. 
  • Egypt records its first monkeypox case (Manila Bulletin) “The first case of monkeypox has been detected in Egypt. The 42-year-old man has a residence permit from a European country to which he regularly travels,” the health ministry of the Arab world’s most populous country said in a statement.

Official Guidance Sources

Articles by Category

Epi/Transmission/Mitigation

Public understanding, awareness, and response to monkeypox virus outbreak: A cross-sectional survey of the most affected communities in the United Kingdom during the 2022 public health emergency (Paparini et al., medRxiv)

In this cross-sectional study, researchers aimed to examine awareness, understanding, and response to the monkeypox (MPXV) outbreak among the most affected communities in the United Kingdom. A cross-sectional survey was administered between June 15 and July 27, 2022, targeting adults using LGBTQI community channels on social media platforms and the dating app, Grindr. 1932 respondents completed the survey, 1691 (90%) were cis or trans men who have sex with men. 1750/1932 identified as men, 88 as women and 64 as gender non-conforming. 1453 (77%) described their sexual identity as gay/ lesbian, 64 (3%) as queer, 221 as bisexual (12%), 81 (4%) as heterosexual, 37 (2%) as pansexual. 744 (39%) were under the age of 40. 71% (1366) self-identified as being from White, 3% (67) Black, 8% Asian (158), 2% LatinX(36) and 11% (203) ‘Mixed or Other’ heritage groups. 85% were employed and 79% had completed higher education. 137 (7%) identified themselves as living with HIV when asked if they lived with a long-term condition. Overall, 34% reported a limited understanding of public health information, 52% considered themselves at risk, 61% agreed people infected with MPXV should isolate for 21 days, 49% reported they would first attend a sexual health clinic if infected, 86% reported they would accept a vaccine and 59% believed MPXV originated from animals. Reported level of understanding of public health information, agreement to the need to isolate for 21 days, vaccine acceptance, and beliefs about the origins of MPXV varied by income level, education and heritage. Trust in healthcare providers, perception of risk of MPXV, and willingness to be vaccinated differed by gender and sexual identity. The most trusted sources of information were healthcare professionals (37%), official health agencies (29%), and mainstream media (12%). Younger participants were most likely to state they would not engage with clinical services if they had MPXV symptoms. In summary, in this group of respondents, largely made up of White, male, employed men who have sex with men with university education, vaccine acceptability was very high, yet public health information and advice were neither universally accepted nor correctly understood.

Clinical characteristics of monkeypox virus infections among men with and without HIV: A large outbreak cohort in Germany (Hoffmann et al., HIV Medicine)

This was a retrospective study of all confirmed monkeypox virus (MPXV) infections observed in HIV centers in Germany since 19 May 2022. Researchers conducted a chart review to evaluate clinical characteristics, comorbidities, and coinfections, including HIV, viral hepatitis, and sexually transmitted infections (STIs). By 30 June 2022, a total of 546 MPXV infections were reported from 42 German centers. All patients were men who have sex with men (MSM), of whom 256 (46.9%) were living with HIV, mostly with a preserved immune system and with viral suppression. In total, 232 (42.5%) MSM were also taking HIV pre-exposure prophylaxis (PrEP) and 58 (10.6%) MSM had no known HIV infection or PrEP use. The median age was 39 years (range 20–67), and comorbidities were rare. However, 52.4% and 29.4% of all patients had been diagnosed with at least one STI within the last 6 months or within the last 4 weeks, respectively. The most frequent localizations of MPXV infection were genital (49.9%) and anal (47.9%), whereas fever (53.2%) and lymphadenopathy (42.6%) were the most frequent general symptoms. The hospitalization rate was low (4.0%), and no fatal course was observed. The clinical picture showed no apparent differences between MSM with or without HIV. In summary, his preliminary cohort analysis from a current large outbreak among MSM in Germany found that the clinical picture of MPXV infection did not differ between MSM with and without HIV infection. Severe courses were rare and hospitalization rates were low. However, most patients were relatively healthy, and only a few people living with HIV were viremic or severely immunosuppressed.

Monkeypox among Men who Have Sex with Men in Africa: The Need for Testing and Vaccination beyond Stigma (Manirambona et al., Journal of Medical Virology)

The Monkeypox virus (MPX) outbreak has been classified at the highest-level alert because of an upsurge in cases worldwide. It has been prominent in European countries and the United Kingdom, where it has significantly impacted men who have sex with men (MSM). There have been sporadic reports of MPX cases and mortality in Africa, which has had numerous negative effects. However, even among newly confirmed cases, no reports of MSM have been made in Africa. This lack of MPX cases among African MSM is probably due to insufficient testing resources. Most importantly, the stigma that MSM face in African society prevents them from seeking timely medical attention and leaves them feeling neglected or uncared for. Although an effective preventive strategy to reduce MPX cases among MSM is to reduce the number of sexual partners and avoid contact with suspected people, it is crucial to defend the marginalised MSM community in Africa via MSM testing and vaccination. It would be crucial to conduct MPX testing among the African MSM community to confirm the incidence rate and inform policymakers to implement the necessary precautions. In order to protect the community and promote health equity, vaccination of MSM should be a top priority.

Model-Based Theoretical Evaluation of the Feasibility of Using Wastewater-Based Epidemiology to Monitor Monkeypox (Chen et al., Environmental Science & Technology Letters)

Monkeypox is an orthopoxvirus that is spreading rapidly globally. Gaps in current clinical testing availability and the lag from infection to symptoms suggest the potential utility of wastewater-based epidemiology (WBE) to monitor community level spread and prevalence. Here, we estimate the distributions of Monkeypox DNA wastewater concentrations based upon prior shedding reports and use Monte Carlo modeling to estimate the probability of detection in wastewater. Stool shedding drives total Monkeypox DNA wastewater concentrations, with a median daily shedding of 7.78 log10 genome copies (GC) per infected individual. Using a process limit of detection of 1.0 log10 GC/L, the average United States wastewater treatment plant (WWTP) could feasibly detect 7 infections out of 100 000 people. The UK, Spain, Nigeria, and the Democratic Republic of Congo (DRC) have respective minimum infection rates of 54.7%, 44.5%, 3.1%, and 8.0% that of the US due to decreased median per capita wastewater flow rates. We also develop a strategy to select the number of replicate PCR assays based upon expected case rates to optimize sewage Monkeypox detection. This model demonstrates a framework to evaluate WBE applications without the associated laboratory expense and highlights the key need for improved shedding data to develop robust WBE programs and interpretation of results. 

Monkeypox virus infections in children in Spain during the first months of the 2022 outbreak (Aguilera-Alonso et al., The Lancet)

Currently, Spain has the second highest number of monkeypox cases worldwide.1 As of Aug 3, 2022, 4663 laboratory-confirmed cases of monkeypox have been reported in Spain, with two patients having died of complications associated with encephalitis. Only 16 (0·3%) patients were younger than 18 years (males n=10, females n=6; table and appendix p 1), all of whom had their infection confirmed by monkeypox virus or orthopoxvirus generic real-time PCR. These 16 patients were in two age groups, with different transmission routes: four were children younger than 4 years (aged 7, 10, and 13 months, and 3 years) and 12 were adolescents aged 13–17 years (appendix p 2). In three patients in the younger age group, the transmission route was through household contact with their parents, and in one patient the transmission route was unknown. In the older age group, nine patients were infected via an outbreak in a tattoo and piercing studio, probably by contaminated material, and in three patients, transmission was via sexual close contact. All cases were considered autochthonous, and home isolation was recommended for the duration of illness. Only one (6%) of 16 patients developed an acute complication (bacterial superinfection that required drainage of an abscess), but no patient required hospital admission and all were followed up on an outpatient basis (by telephone or in person). All 16 patients survived without sequelae. This study involved the use of patient medical data from the National Epidemiological Surveillance Network (RENAVE). Individual informed consent is not required for data to be included in RENAVE, and all data are pseudonymised, meeting all considerations regarding personal data protection. As this work is in line with alert, response, and surveillance activities, no explicit ethics assessment was required (appendix p 4).

Testing

Orthopoxvirus Testing Challenges for Persons in Populations at Low Risk or Without Known Epidemiologic Link to Monkeypox — United States, 2022 (Minhaj et al., MMWR)

Monkeypox virus (MPXV) spreads from person to person through close, prolonged contact; a small number of cases have occurred in populations who are not MSM (e.g., women and children), and testing is recommended for persons who meet the suspected case definition. CDC previously developed five real-time polymerase chain reaction (PCR) assays for detection of orthopoxviruses from lesion specimens. CDC was granted 510(k) clearance for the nonvariola-orthopoxvirus (NVO)–specific PCR assay by the Food and Drug Administration. This assay was implemented within the Laboratory Response Network (LRN) in the early 2000s and became critical for early detection of MPXV and implementation of public health action in previous travel-associated cases as well as during the current outbreak. PCR assays (NVO and other Orthopoxvirus laboratory developed tests [LDT]) represent the primary tool for monkeypox diagnosis. These tests are highly sensitive, and cross-contamination from other MPXV specimens being processed, tested, or both alongside negative specimens can occasionally lead to false-positive results. This report describes three patients who had atypical rashes and no epidemiologic link to a monkeypox case or known risk factors; these persons received diagnoses of monkeypox based on late cycle threshold (Ct) values ≥34, which were false-positive test results. The initial diagnoses were followed by administration of antiviral treatment (i.e., tecovirimat) and JYNNEOS vaccine postexposure prophylaxis (PEP) to patients’ close contacts. After receiving subsequent testing, none of the three patients was confirmed to have monkeypox. Knowledge gained from these and other cases resulted in changes to CDC guidance. When testing for monkeypox in specimens from patients without an epidemiologic link or risk factors or who do not meet clinical criteria (or where these are unknown), the US CDC recommends laboratory scientists should reextract and retest specimens with late Ct values (based on this report, Ct ≥34 is recommended).

Vaccine

Breakthrough infections after post-exposure vaccination against Monkeypox (Thy et al., MedRxiv Pre-Print)

A third-generation smallpox vaccine was recommended in France for individuals who had a high-risk contact with a PCR-confirmed Monkeypox patient. Researchers aimed to describe the outcomes of high-risk contacts receiving third-generation smallpox vaccine as an early post-exposure ring vaccination (EPRV) especially tolerance and potential breakthrough infections after the first dose. Tjeu performed an observational analysis of all consecutive individuals vaccinated with the IMVANEX® smallpox vaccine after a high-risk contact defined as close skin-to-skin or mucosal contact and/or indirect contact on textile or surface and/or droplets exposure defined by a contact at less than 2 meters during at least 3 hours with a PCR-confirmed Monkeypox patient. Between May 27th and July 13th, 2022, 276 individuals received one dose of IMVANEX® with a median delay of 11 days [IQR 8-14] after exposure with a confirmed Monkeypox patient. Mode of exposure was droplets for 240 patients (91%), indirect contact for 189 (71%) and unprotected sexual intercourse for 146 (54%). Most of the patients were men (91%, n=250) and men who have sex with men (88%, n=233). The vaccine was well tolerated with no severe adverse event. Among the 276 vaccinated individuals, 12 (4%) had a confirmed Monkeypox breakthrough infection with no severe infection. Ten out of 12 patients developed a Monkeypox infection in the five days following vaccination and two had a breakthrough infection at 22 and 25 days. In summary. EPRV with a third-generation smallpox vaccine was well tolerated and effective against Monkeypox but did not completely prevent breakthrough infections.

Intradermal Vaccination for Monkeypox — Benefits for Individual and Public Health (Brooks et al., The New England Journal of Medicine) 

Intradermal vaccination delivers antigen into the space between the epidermis and the dermis. This space is an anatomically favorable site for immune stimulation, enriched in a heterogenous population of dendritic cells, macrophages, and monocytes that endow this tissue with a potent capacity to detect and respond robustly to immunologic stimuli, including those present in vaccines. For these reasons, the role of the dermis in adaptive immunity has been exploited for allergen testing and tuberculosis skin testing. And smallpox vaccination was developed by Jenner using something similar to intradermal administration: variolation, or the practice of scratching immunizing material into the skin. Intradermal vaccination has been extensively studied for prevention of a wide range of viral diseases, including influenza (for which there is a licensed intradermal vaccine), Japanese encephalitis, hepatitis A, hepatitis B, human papillomavirus disease, polio, rabies, varicella zoster, and yellow fever. In the 1970s, Germany’s smallpox eradication campaign deployed it for vaccinating more than 100,000 persons with modified vaccinia Ankara (MVA), which forms the basis for the JYNNEOS vaccine currently being used to combat monkeypox.  

Treatment

Monkeypox treatment with tecovirimat in the Central African Republic under an Expanded Access Programme (Mbrenga et al., medRxiv)

In this article, authors present the results of the first phase of an Expanded Access Programme (EAP) of tecovirimat for monkeypox conducted in the Central African Republic (CAR) from December 2021 to February 2022. Patients with confirmed monkeypox received tecovirimat according to the recommended dosing. Data on clinical signs and symptoms were recorded daily during treatment and at follow-up visits. Blood or lesion samples were taken during treatment and at day 28 to assess viral presence of monkeypox by PCR. Adverse events and clinical outcomes were monitored by evaluating the total number and location of lesions, temperature, degree of incapacity, presence of adverse events, patient survival, and viral presence throughout treatment and follow-up. Outcomes in 14 patients who were enrolled between December 2021 and February 2022 were reported. Muscle pain, headache, lymphadenopathy, lesions, fever, back pain, and upper respiratory symptoms were commonly reported at admission and during follow-up. The rate of appearance of active lesions gradually decreased throughout treatment, with the median time to no new lesions being 5 days following the start of treatment. No death attributable to monkeypox occurred in this cohort. Authors conclude that data collected through this EAP can help improve knowledge about the use of tecovirimat for monkeypox. Furthermore, the efforts have been able to document systematically the presentation and clinical and virological evolution of monkeypox under treatment.

Virology

Monkeypox DNA levels correlate with virus infectivity in clinical samples, Israel, 2022 (Paran et al., EuroSurveillance)

Presently, the rapid detection and identification of MPXV relies on a PCR from a patient (or an environmental) sample being positive for MPXV genetic material (DNA). However, the presence of viral DNA in a clinical specimen does not imply its infectivity, restricting risk assessment. In this study, the researchers test for a correlation between MPXV DNA copies in patient specimens, as measured by PCR, and infectious virus, as measured by plaque assay. They also estimate a threshold value in PCR that may inform decision-making on MPXV infection control. Based on their data, a Cq value of ≥ 35 predicts no or very low infectivity. This concurs with recent results who reported the successful recovery of MPXV from semen, in a sample with a Cq value of 29. They further calculated a ratio of 172 DNA copies for 1 pfu. Previous reports suggest values of 10–100 DNA copies for 1 pfu for orthopox viruses originating from cultured cells. This difference could be due to the presence of viral DNA not associated with infectious particles in their samples, or because viruses originating from clinical specimens might have a reduced infectivity towards cell lines, compared to viruses originating from culture. However, based on prior unpublished work in their laboratory, poxvirus infectivity seems to be maintained following 24 hours of incubation at 4 °C and marginally affected upon incubation for 48 hours at the same temperature (up to 1.5-fold reduction). Recent preliminary results with clinical specimens from the current MPXV outbreak additionally suggest that the virus infectivity is not affected after up to 48 hours of incubation at 4 °C. This is in line with previous studies showing that poxviruses maintain their infection capacity for a relatively long time and across different conditions. In conclusion, this work highlights the strong correlation of MPXV Cq values to virus infectivity and defines a threshold (Cq ≥ 35; viral DNA ≤ 4,300 copies/mL) that predicts poorly- or non-infectious specimens Overall, they suggest that a Cq value of ≥ 35 (≤ 4,300 DNA copies/mL) corresponds with non or marginal infectivity. Altogether, infectiousness should also be evaluated in context of the overall clinical manifestation including the course of disease, lesion location and stage, etc.

Rapid adaptation of established high-throughput molecular testing infrastructure for detection of monkeypoxvirus (preprint) (Noerz et al., medRxiv)

Since May 2022, a rising number of monkeypox-cases has been reported in non-endemic countries of the northern hemisphere. In contrast to previous clusters, infections seem predominantly driven by human-to-human transmission, rather than animal sources. In this study, we adapted two published qPCR assays (non-variola orthopoxvirus and monkeypox virus specific) for use as a lab-developed dual-target monkeypoxvirus-test on widely used automated high-throughput PCR-systems (cobas5800/6800/8800). Selected assays were checked for in-silico inclusivity and exclusivity in current orthopoxvirus sequences, as well as for multiplex compatibility. Analytic performance was determined by serial dilution of monkeypoxvirus reference material, quantified by digital PCR. Cross reactivity was ruled out through a clinical exclusivity set containing various bloodborne and respiratory pathogens. Clinical performance was compared to a commercial manual RUO-kit using clinical remnant samples. Analytic lower limit of detection (LoD) was determined as 4.795 dcp/ml (CI95% 3.598 – 8.633 dcp/ml) for both assays combined, with a dynamic range of at least 5 log-steps. The assay showed 100% positive and negative agreement with the manual RUO orthopoxvirus PCR test kit in clinical swab samples. While the full extend of the ongoing monkeypox outbreak remains to be established, the WHO and local health authorities are calling for increased awareness and efforts to limit further spread. For this, timely and scalable PCR tests are an important prerequisite. The assay presented here allows streamlined high-throughput molecular testing for monkeypoxvirus on existing hardware, broadly established previously for SARS-CoV-2 diagnostics.

More News