With recent outbreaks of the Monkeypox virus in Europe and the United States, interest in Monkeypox prevention and treatment has increased. Similar to Variola, the causative agent of smallpox, the Monkeypox virus belongs to the genus Orthopoxvirus. It is a large, complex, double-stranded DNA virus that can infect homo sapiens as well as non-human primates. In fact, it can infect a wide variety of mammalian species. Current evidence points to rodents as key reservoir hosts. Transmission occurs via saliva/respiratory excretions or contact with lesion exudate or crust material, either via contact with infected animals or person-to-person transmission. The secondary attack rate among unvaccinated contacts within households is about 9%, so it is much less transmissible than smallpox. Wearing a face mask and avoiding close contact can reduce the risk of transmission.

The incubation period is about 2 weeks (~7-17 days) and an initial febrile prodrome is followed by generalized headache and fatigue. A key distinguishing feature of monkeypox, when compared to smallpox and varicella-zoster, is the presence of lymphadenopathy in most patients (but not all). Fever usually declines up to 3 days after rash onset with subsequent development of lesions as first macular, then papular, then vesicular, and pustular. About 40% of patients develop complications such as bacterial skin infections, respiratory disorders, gastrointestinal disorders, and keratitis. The overall mortality rate is about 10%, up to 15% in unvaccinated children.

There are 2 distinct phylogenetic clades of Monkeypox viruses: the West Africa clade and the Congo Basin clade. The West Africa clade, endemic in West Africa, generally exhibits a less severe illness with a mortality rate of about 3-4%. The Congo Basin clade, which occurs in Central Africa, exhibits a more severe illness with a mortality rate of about 10-11%. Nextstrain.org is now tracking reported Monkeypox genome data. The recent outbreaks in Europe and the United States seem to be based on the West African clade.

The 2022 ACIP Guidelines for Preexposure Vaccination of Persons at Risk for Occupational Exposure to Orthopoxviruses was recently published. There are currently 2 orthopoxvirus vaccines available: ACAM2000, which is a live replication-competent vaccinia virus, and Jynneos, which is a replication-deficient modified vaccinia Ankara.

CDC recommends preexposure vaccination for persons at risk for occupational exposure to orthopoxviruses, persons who administer ACAM2000 or care for patients with infection with replication-competent viruses.

ACAM2000 is approved for anyone over the age of 1 year, in the absence of contraindications, and Jynneos is approved for persons over the age of 18 years. While Jynneos is recommended as an alternative to ACAM2000, it’s important to keep in mind contraindications to receipt of ACAM2000.

Full guideline text can be found here: https://www.cdc.gov/mmwr/volumes/71/wr/mm7122e1.htm

Treatment options for orthopoxviruses are limited. Acyclovir, ganciclovir, foscarnet, and HIV NRTIs and NNRTIs are inactive in vitro. Entecavir has in vitro activity, but there’s limited evidence for its use for poxviruses. Cidofovir has in vitro activity and established animal data but it’s limited to its severe toxicity profile with many black box warnings. Tecovirimat and brincidofovir are oral options that have recently been approved via FDA’s Animal Rule for the treatment of smallpox and may be used for the treatment of monkeypox.

The choice between brincidofovir (dosed twice daily for 14 days) and tecovirimat (dosed once weekly for 2 doses) is based on many factors including tolerability, adherence, potential risks of carcinogenecity, teratogenecity, and infertility. Overall, tecovirimat seems to have an advantage over brincidofovir due to its apparently better safety profile (based on very limited evidence, primarily driven by animal studies).

More information can be found here:

What is Omicron? The new B.1.1.529 variant (Omicron) clade 21K, which harbors many mutations, particularly in the spike protein, was first detected in South Africa. Unlike the other variants of concern, B.1.1.529 has emerged independently from mid-2020 strains of SARS-CoV-2.

Why South Africa? It is possible, but unlikely, that this variant emerged in South Africa. South Africa has excellent scientists, a great surveillance program, transparency, and sharing of data!

Anytime there’s a new variant of SARS-CoV-2, there are at least 4 concerning things to consider: 1) Is it more transmissible than currently circulating strains? 2) Does it evade neutralization by antibodies (i.e., antibodies from natural infection, immunization, or monoclonal antibodies)? 3) Does it evade immunity due to vaccination (i.e., antibodies, T cell response)? 4) Does it cause a more severe (or milder) disease?

1) Is it really more transmissible than Delta? It’s too soon to tell. Superspreader events, which are outliers, get noticed early and can result in a very high estimation of basic reproduction number (R0). However, it does seem like B.1.1.529 (Omicron) is outcompeting B.1.617.2 (Delta) in South Africa.

2) Does it evade neutralization by antibodies? Omicron seems to have many more S1 mutations than previously circulating variants, which might be very problematic. While we don’t know for sure yet, its mutation profile predicts significant immune evasion.

3) Does it evade immunity due to vaccination (i.e., antibodies, T cell response)? We don’t know yet.

4) Does it cause a more severe (or milder) disease? We don’t know yet.

We need more studies to understand this variant and its impact more. In the meantime, please get vaccinated and wear a mask!

[All images from IDTwitter]

Last night (8/12/21), the FDA extended the emergency use authorizations (EUA) for Pfizer-BioNTech’s BNT162b2 (currently for age 12 years and older) and Moderna’s mRNA-1273 (currently for age 18 years and older) to allow for the use of an additional dose in certain immunocompromised individuals, such as solid organ transplant recipients or those who are diagnosed with conditions that are considered to have an equivalent level of immunocompromise (https://bit.ly/37DWxk3).

Today (8/13/21), the CDC’s ACIP voted 11-0 to approve a 3rd dose following a primary 2-dose series in immunocompromised people. Of note, whenever possible, vaccination should be given at least 2 weeks prior to initiation of immunosuppressive therapies. Who’s considered immunocompromised? Here’s a slide from ACIP meeting:

What about individuals who received a single dose of Johnson & Johnson’s Ad26.COV2.S vaccine? No recommendations yet due to lack of data, but probably best to get at least one mRNA vaccine booster.

The good news is that influenza was very scarce last year (2020-21) in the Northern Hemisphere and remained scarce this summer in the Southern Hemisphere. As well described by Uyeki et al (doi:10.1001/jama.2021.6125), this could generally be attributed to three factors: 1) community mitigation measures (e.g., masking, social distancing, workplace closures, school closures, virtual school instruction, indoor dining restrictions), 2) behavioral changes (e.g., staying at home, working from home, reduced domestic and international travel, or international travel with subsequent quarantine upon arrival, and 3) influenza vaccination. Last flu season set a record for vaccine distribution (194 million doses), with more than 55% of adults getting immunized in the U.S. What to expect this year? Anything from a repeat of last season’s numbers to an explosion of cases is possible.

Let’s look at the first factor, community mitigation measures. Schools are open, which means that children are in a position to accelerate the transmission of influenza in the community. Many people who are vaccinated against COVID-19 have eased masking and social distancing, increasing their exposure to influenza. Indoor dining is almost back to normal, where social distancing and masking are difficult to follow. Let’s look at the second factor, behavioral changes. People are more comfortably resuming normal activities because they are vaccinated against COVID-19, including international and domestic air travel. All of these make factor three, influenza vaccination, more important than ever. The CDC released the new Prevention and Control of Seasonal Influenza with Vaccines recommendations for the 2021-22 influenza season last week. Here are a few takeaways:

https://www.cdc.gov/mmwr/volumes/70/rr/rr7005a1.htm

• Routine annual seasonal influenza immunization is recommended for all persons aged ≥6 months who do not have contraindications
• No preferential recommendation is made for one influenza vaccine product over another
• Vaccination should be offered by the end of October and continued through flu season
• For nonpregnant adults, early vaccination (i.e., in July and August) should be avoided unless there is concern that later vaccination might not be possible
• Revaccination later in the season of persons already vaccinated is not recommended
• COVID-19 vaccines can be co-administered with influenza vaccines

Influenza vaccine formulations available:

New recommendations regarding severe allergy to influenza vaccines:

• Can consider 3 different groups: egg-based vaccines, cell-cultured, and recombinant
• Precaution use should occur in an inpatient or outpatient medical setting under the supervision of a provider who can recognize and manage a severe allergic reaction

Influenza season typically peaks between Christmas and Valentine’s day, most often closer to Valentine’s day. Get your flu vaccine by November and be ready for Christmas and Valentine’s day!