PRI’s MPV (Monkeypox) Situation Update – August 25

Aug 25, 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: {NEW} 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:15,909 (8.24.2022). (full version). 
  • NY State: As of August 22 2022, a total of 3,038 confirmed MPV cases – a designation established by the Centers for Disease Control and Prevention (CDC). (NY Sit Rep and County List)
  • Pivoting to new monkeypox vaccine strategy could take weeks, NYC health commissioner says (Gothamist) Part of the holdup stems from the additional training health care workers will need for the new strategy, which is known as intradermal dosing. It works via a shallow injection of a vaccine in between the body’s skin layers, rather than the normal tactic of plunging all the way into a person’s muscles. Intradermal dosing requires more delicacy and smaller needles, which can be harder to work with — but it also uses smaller volumes of the vaccine.
  • CDC releases new monkeypox guidance for schools and day cares. Here are 5 key takeaways (Fort-Worth Star-Telegram) You should consult your doctor and particularly keep an eye on those symptoms if you know you or your child was exposed to someone with monkeypox. According to the CDC, several illnesses can cause a rash and fever in children, such as hand-foot-mouth disease and chickenpox. A healthcare provider can determine what treatment or testing the child needs, the CDC said. Some symptoms in young children may also be difficult to recognize promptly, the CDC warns. 

US Updates/News

  • Elementary student tests positive for monkeypox; 2nd student being tested, district says (WSB-TV) After receiving information from the Gwinnett-Newton-Rockdale Health Department, the Newton County School District confirmed it has one student at Mansfield Elementary with monkeypox and another suspected case at Flint Hill Elementary School in Oxford. Department of Health officials are still awaiting test results from that second student. Because of privacy laws, the district could not release any other information about the students.
  • Monkeypox (MPX) Cases and Vaccinations by Race/Ethnicity (KFF) Data from 43 states, DC, and Puerto Rico show that Black people made up 26% of MPX cases compared to 12% of the population, and Hispanic people accounted for 28% of cases versus 19% of the population. Data were not separately reported for American Indian and Alaska Native (AIAN) or Native Hawaiian or Other Pacific Islander (NHOPI) people.
  • White House strategy for monkeypox vaccines causing ‘chaos out in the field’ (Politico) The Biden administration’s strategy for stretching scarce monkeypox shots is instead leading to fewer vaccinations and could worsen racial health disparities. The federal government last week slashed the number of vials states received in anticipation of each being able to vaccinate up to five people per vial instead of one. 

Global Updates/News

Official Guidance Sources

Articles by Category

Epi/Transmission/Mitigation

First case of monkeypox virus, SARS-CoV-2 and HIV co-infection (Nolasco et al., Journal of Infection)

Here, the authors present the clinical features and diagnostic procedure of the first documented case of co-infection with monkeypox virus, SARS-CoV-2 and HIV-1. The patient, an Italian 36-year-old male spent 5 days in Spain from 16 to 20 June 2022. Nine days after, he developed fever, accompanied by sore throat, fatigue, headache and right inguinal lymphadenomegaly. On 2 July he resulted positive for SARS-CoV-2, of which he was vaccinated for. On the afternoon of the same day a rash started to develop on his left arm. The following day small, painful vesicles surrounded by an erythematous halo appeared on the torso, lower limbs, face and glutes. On 5 July, due to a progressive and uninterrupted spread of vesicles that began to evolve into umbilicated pustules, he went to the emergency department. He reported having condomless intercourse with men during his stay in Spain. On physical examination his body was dotted, including the palm of the right hand and the perianal region, with skin lesions in various stages of progression and umbilicated plaques. On the second day of admission (July 6, 2022), given the high suspicion of monkeypox supported by suggestive skin lesions and a recent trip to Spain, swabs of pustule exudate and nasopharynx secretions were taken and tested. The specimens were confirmed positive to monkeypox virus and SARS-CoV-2. The first belonged to the West African clade, the variant responsible for the Spanish outbreak. The third day almost all skin lesions began to turn to crusts. Sotrovimab 500 mg was infused intravenously. On day 5 (July 9, 2022), almost all constitutional symptoms were resolved and previously altered laboratory test values normalized. On day 6 (July 11, 2022), nasopharyngeal swabs for SARS-CoV-2 and monkeypox virus were still positive, despite the absence of new skin lesions. Since symptoms had resolved, the patient was discharged to home isolation. On 19 July 2022 he returned to their institute and underwent a new oropharyngeal swab for monkeypox virus, which was still positive. This case highlights how monkeypox and COVID-19 symptoms may overlap, and corroborates how in case of co-infection, anamnestic collection and sexual habits are crucial to perform the correct diagnosis. The case emphasizes that sexual intercourse could be the predominant way of transmission. Therefore, complete STI screening is recommended after a diagnosis of monkeypox.

Clinical characteristics of ambulatory and hospitalised patients with monkeypox virus infection: an observational cohort study (Mailhe et al., Clinical Microbiology and Infection) 

The objectives of this study were to describe the clinical characteristics and complications of patients with a monkeypox infection. All consecutive patients with a PCR-confirmed monkeypox infection seen in a French referral center were included. Between May 21st and July 5th 2022, 264 patients had a PCR-confirmed monkeypox infection. Among them, 262 (262/264, 99%) were men, 245 (245/259, 95%) were men who have sex with men (MSM) and 90 (90/216, 42%) practiced chemsex in the last 3 months. Seventy-three (73/256, 29%) were living with HIV and 120 (120/169, 71%) were taking pre-exposure prophylaxis against HIV infection. Overall, 112 patients (112/236, 47%) had a contact with a confirmed monkeypox case, of a sexual nature for 95% of the contacts (86/91). Monkeypox PCR was positive on the skin in 252 patients, on oro-pharyngeal sample in 150 patients and in blood in 8 patients. The majority of patients presented with fever (171/253, 68%) and adenopathy (174/251, 69%). Skin lesions mostly affected the genital (135/252, 54%) and perianal (100/251, 40%) areas. Overall, 17 (17/264, 6%) patients were hospitalised, none of them immunocompromised. Complications requiring hospitalization included cellulitis (n=4), paronychia (n=3), severe anal and digestive involvement (n=4), non-cardia angina with dysphagia (n=4), blepharitis (n=1) and keratitis (n=1). Surgical management was required in four patients. In summary, the current outbreak of monkeypox infections has specific characteristics: it occurs in the MSM community, known contact is mostly sexual, perineal and anal areas are frequently affected and severe complications include superinfected skin lesions, paronychia, cellulitis, anal and digestive involvement, angina with dysphagia and ocular involvement.

Monkeypox: A focused narrative review for emergency medicine clinicians (Long et al., The American Journal of Emergency Medicine)

Monkeypox is an orthopoxvirus endemic to central and western Africa. An outbreak in May and June 2022 across Asia, Europe, North America, and South America was declared a global health emergency in July 2022. The disease can be transmitted via contact with an infected animal or human, as well as contact with a contaminated material. The disease presents with a prodromal flu-like illness and lymphadenopathy. A rash spreading in a centrifugal manner involving the oral mucosa, face, palms, and soles is typical. Lesions progress along various stages. Complications such as bacterial skin infection, pneumonitis, ocular conditions, and encephalitis are uncommon. Confirmation typically includes polymerase chain reaction testing. The majority of patients improve with symptomatic therapy, and as of July 2022, there are no United States Food and Drug Administration-approved treatments specifically for monkeypox. However, antiviral treatment should be considered for several patient populations at risk for severe outcomes.

While emergency medicine clinicians can be involved in all four vaccine strategies, during periods of heightened Monkeypox contagion, the emergency medicine clinician is most likely to deliver PEP to patients only in the post-exposure prophylaxis strategy (i.e., considering the use of the vaccine in patients who have been exposed to a suspected or confirmed case). The PEP strategy is most effective in preventing infection if the vaccine is administered within four days of exposure. If given between 4 and 14 days post-exposure, the likelihood of preventing infection is much lower but can still reduce the severity of the illness should it develop. It is also recommended to consider administering the vaccine from a PEP strategic perspective beyond 14 days exposure to those individuals at higher risk of adverse outcome, such as those patients with significant immunosuppression. 

Risk of monkeypox virus infection in children (Lampejo, Journal of Medical Virology)

keypox virus (MPXV) has gained global attention in view of the current multi-country outbreak affecting non-endemic regions including several European countries, Canada, the US and Australia, and without known epidemiological links to endemic settings in most cases. The first ever diagnosed human case of MPXV infection was in 1970 in a male infant in the Democratic Republic of Congo (DRC, formerly known as Zaire), and further cases have since occurred predominantly in West and Central Africa. The limited data available from previous outbreaks suggest that children may be at greater risk of severe forms of disease with potential complications including sepsis, encephalitis and death. Jezek et al. reported on the clinical features and outcomes of 282 patients with monkeypox between 1980 and 1985 in the DRC; 90% of patients were <15 years old (the youngest being one month old). Amongst unvaccinated patients mortality in their study was 11% but was higher in the youngest children at 15%. In a retrospective study of a 2003 US monkeypox outbreak (due to the West African clade) associated with imported pet prairie dogs, the first outbreak occurring outside of an endemic region, seventy one percent (24/34) of cases were in adults. However, paediatric patients were admitted to the intensive care unit at a significantly higher rate than adults (50% vs 9%, p = 0.02) and the most critically ill patients in the outbreak were two young children whose complications included retropharyngeal abscess and encephalopathy. It however important to note that the age-specific epidemiology of monkeypox has changed over time; the median age at presentation has evolved from young children (4 years old in the 1970s) to young adults (21 years old) in 2010-2019

Treatment

Compassionate Use of Tecovirimat for the Treatment of Monkeypox Infection (Desai et al., JAMA)

In this preliminary study, researchers assessed adverse events and clinical resolution of systemic symptoms and lesions in an uncontrolled cohort study of patients with monkeypox who were treated with tecovirimat on a compassionate use basis. Patients were eligible for tecovirimat treatment following laboratory confirmation of orthopoxvirus infection from skin lesions by PCR. Outpatients referred to UC Davis primarily through the Sacramento County Department of Public Health and who had disseminated disease or lesions in sensitive areas including the face or genital region were offered treatment. As of August 13, 2022, 25 patients with confirmed monkeypox infection had completed a course of tecovirimat therapy. All patients were self-reported male; median age was 40.7 years (range, 26-76). 9 patients had HIV, 1 patient had received the smallpox vaccine more than 25 years prior, and 4 received 1 dose of JYNNEOS vaccination after symptom onset. At the time of treatment, systemic symptoms, lesions, or both were present for a mean of 12 days (range, 6-24). Systemic symptoms included fever in 19 patients (76%), headache in 8 (32%), fatigue in 7 (28%), sore throat in 5 (20%), chills in 5 (20%), backache in 3 (12%), myalgia in 2 (8%), nausea in 1 (4%), and diarrhea in 1 (4%). Almost all patients (23 [92%]) had genital and/or perianal lesions, and 13 (52%) had fewer than 10 lesions over their entire body. All patients had pain associated with lesions. All besides one patient were treated for 14 days. Complete resolution of lesions was reported in 10 patients (40%) on day 7 of therapy, while 23 (92%) had resolution of lesions and pain by day 21. Treatment with tecovirimat was generally well tolerated with no patient discontinuing therapy. The most frequently reported adverse events on day 7 of therapy included the following: fatigue in 7 patients (28%), headache in 5 (20%), nausea in 4 (16%), itching in 2 (8%), and diarrhea in 2 (8%). In summary, this study found that oral tecovirimat was well tolerated by all patients with monkeypox infection, with minimal adverse effects. However, adverse effects could not always be differentiated from symptoms related to the infection.

Monkeypox is a global public health emergency: The role of repurposing cholesterol lowering drugs not to be forgotten (Vuorio et al., Journal of Clinical Lipidology)

The interest to repurposing cholesterol lowering drugs, particularly statins, is best known among COVID-19 patients. Moreover, there are several examples of this repurposing strategy regarding other severe infections. Statins have been repurposed in the treatment of influenza and Ebola. With Ebola infection, statins may result in the production of fusion-inefficient Ebola virus particles. PCSK9 inhibitors have been used to treat Dengue virus infection because PCSK9 inhibitors enhance secretion of type I interferons.14 Fenofibrate has been shown to decrease mortality and morbidity among Japanese encephalitis patients. Compared to Japanese encephalitis vaccination Sehkal and coauthors mention the potential usefulness of fenofibrate especially when treating endemic infections. While currently there is clearly a lack of studies repurposing cholesterol lowering drugs for the treatment of Monkeypox more attention needs to be given how such viral infections effect the re-distribution of cellular cholesterol. For example, the efficient endosomal re-distribution of cholesterol is essential for viral life cycles. If this cholesterol re-distribution can be disrupted the viral life cycles may be inhibited or even collapse. Fenofibrate also seems to have this ability, at least in vitro. Taken together, monkeypox appears to become yet another global public health problem, and, as such, it is a reminiscent of the current COVID-19 pandemic and its predecessors. Therefore, the potential beneficial role of repurposing cholesterol lowering drugs should not be forgotten in this newly emerging viral outbreak. Patients with severe hypercholesterolemia should not stop taking cholesterol-lowering medication after contracting Monkeypox. If tecovirimat medication is started for Monkeypox, simvastatin should be changed to another statin, analogously when treating SARS-CoV-2 infection with Paxlovid.

Vaccine

Early estimates on monkeypox incubation period, generation time and reproduction number in Italy, May-June 2022 (Guzzetta et al., arXiv pre-print server)

In this study, researchers analyzed the first 255 PCR-confirmed cases of monkeypox that occurred in Italy in 2022. All except two were males, and 190 men out of 200 (95%) for which the information was disclosed reported having sex with men; the median age was 37 years (range: 20 – 71 years). For 139 out of 184 cases for whom the information was available, the rash was localized at the genital/perianal area. Fever was reported in 151 out of 222 cases for whom this information was available. Information about travelling was available for 228 cases; 86 (37.7%) had travelled abroad, and 25 of these 86 (29.1%) had spent a vacation period on the Canary Islands, suggesting the occurrence of a major amplifying event. Only one case had travelled to West Africa and was symptomatic at arrival in Italy. The mean incubation period was estimated to be 9.1 days (95% CI of the mean: 6.5-10.9; 5th and 95th percentiles of the distribution: 1-24). The mean generation time (i.e. the time elapsed between the date of exposure of a confirmed case and those of his secondary cases) was estimated to be 12.5 days (95%CI of the mean: 7.5-17.3; 5th and 95th percentiles of the distribution: 4-26). By assuming a mean generation time of 12.5 days and importation from Canary Islands, the mean net reproduction number (mean number of cases generated by a single index case) during the first week of June was estimated at 2.43 (95%CI 1.82-3.26). After June 12, 2022 a progressive decrease of the reproduction number was estimated. This analysis of virus genome strongly suggests that the epidemic is caused by the clade II (West African) of the MPX virus; however, with the exception of two men who reported travels to Western African countries, at least 60% of cases were locally acquired. 

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