Wednesday, September 19, 2018

Report: UK PHE Imports Smallpox Vaccine For HCWs Caring For Monkeypox Cases

Smallpox vaccination - Credit CDC


Aside from the two initial announcements (see here and here) from the UK's PHE (Public Health England), we're heard surprisingly little about the two imported Monkeypox cases in the UK. 
Both cases arrived separately from Nigeria earlier this month, and the Nigerian CDC has promised an epidemiological investigation, but thus far we've heard nothing. (Note: The Nigerian CDC website appears to be temporarily offline this morning).
Nigeria, which saw its first Monkeypox outbreak in nearly 40 years last fall, issued their last SitRep on the outbreak in February (see An Update of Monkeypox Outbreak in Nigeria for Week 9), one which indicated the outbreak was winding down.

What we do have is a press release from Bavarian Nordic - a European Bio-Tech company and vaccine manufacturer - stating that at the request of the PHE, they've shipped a supply of smallpox vaccine to the UK, and that health care workers and others treating these two patients have now been vaccinated.
Smallpox vaccine -  while not an exact match to the Monkeypox virus - confers about an 85% protection to the recipient. Since smallpox was eradicated in the 1970s, relatively few people under the age of 50 have received the vaccine. 
This decline in smallpox immunity appears to have led to an increase in Monkeypox cases over the past 20 years in central Africa (see 2010 PNAS study Major increase in human monkeypox incidence 30 years after smallpox vaccination campaigns cease in the Democratic Republic of Congo).

First the press release, then I'll return with more.
Bavarian Nordic Delivers Smallpox Vaccine to England in Response to Current Monkeypox Cases
September 19, 2018 01:31 ET | Source: Bavarian Nordic A/S
English health authorities have ordered IMVANEX smallpox vaccine in response to monkeypox cases
Immediate response ensured rapid delivery and deployment of vaccines

COPENHAGEN, Denmark, September 19, 2018 - After the confirmation on Friday 7th September 2018 of the first case of human monkeypox in England, Public Health England (PHE), as part of their response, engaged Bavarian Nordic to assist in the supply of its IMVANEX® smallpox vaccine, which is approved in the European Union. The vaccine has now been used to vaccinate healthcare workers treating the patients and those involved in their care.
IMVANEX is not approved for monkeypox, however, in the past when smallpox vaccines were routinely administered, they were shown also to be highly efficacious in preventing monkeypox.

Only a few days after the first case, a second, unrelated case was reported in the UK. According to PHE, both patients are believed to have acquired the infection in Nigeria, which recently experienced a large outbreak of monkeypox. Bavarian Nordic continues to work closely with PHE to ensure a sufficient and rapid supply of additional vaccines, should the need arise.

Monkeypox is similar to human smallpox, although it is less transmissible human-to-human and less deadly with an estimated fatality rate of 1-10%. There are no approved vaccines for the prevention of monkeypox.

Currently, a field study is ongoing to evaluate IMVANEX (also known as IMVAMUNE) for the prevention of monkeypox in the Democratic Republic of the Congo, where the virus is naturally occurring, and is known to infect humans. The study, which is conducted in collaboration between Bavarian Nordic, local health authorities and the U.S. Centers for Disease Control and Prevention (CDC) who is also sponsor of the study, has enrolled over 1,000 healthcare and frontline workers who in their daily work are at high risk of being infected with the virus.
(Continue . . . )

As an emerging infectious disease Monkeypox is taken very seriously by public health officials. 

Although normally restricted to small outbreaks in Africa, in 2003 we saw a rare outbreak in the United States when a Texas animal distributor imported hundreds of small animals from Ghana, which in turn infected prairie dogs that were subsequently sold to the public (see MMWR Update On Monkeypox 2003). 
By the time that outbreak was quashed, the U.S. saw 37 confirmed, 12 probable, and 22 suspected human cases. Among the confirmed cases 5 were categorized as being severely ill, while 9 were hospitalized for > 48 hrs; although no patients died (cite).
The smallpox vaccine was used to curb that outbreak as well. From the MMWR report:

Use of Smallpox Vaccine

To prevent transmission of monkeypox, 30 persons (28 adults and two children) in six states have received smallpox vaccine since June 13. Vaccine was administered pre-exposure to seven persons (three veterinarians, two laboratory workers, and two health-care workers) and post-exposure to 23 persons (10 health-care workers, seven household contacts, three laboratory workers, one public health veterinarian, one public health epidemiologist, and one work contact).
No serious adverse events were reported following smallpox vaccination, and no requests for vaccinia immune globulin have been received. Among the 30 persons who received smallpox vaccine, three (10%) reported rash within 2 weeks of vaccination. One of the three was confirmed as having monkeypox; another person had two skin lesion specimens that tested negative for orthopoxvirus and varicella zoster virus at the state health laboratory; no specimens were obtained for the third person who reported a single, dime-sized, pruritic and erythematous skin lesion (not pustular) remote from the vaccination site that appeared 4 days after vaccination and faded within a week.
In addition to growing societal susceptibility to the virus due to waning vaccine protection, there are also concerns the virus could evolve into a more dangerous pathogen. In a 2014 EID Journal article Genomic Variability of Monkeypox Virus among Humans, Democratic Republic of the Congo, the authors cautioned:

Small genetic changes could favor adaptation to a human host, and this potential is greatest for pathogens with moderate transmission rates (such as MPXV) (40). The ability to spread rapidly and efficiently from human to human could enhance spread by travelers to new regions.
While the smallpox vaccine is not approved for use against Monkeypox, the CDC has issued some advice in the past on its use in an emergency setting.
Smallpox Vaccine Guidance

When properly administered before exposure to monkeyox, smallpox vaccine is effective at protecting people against monkeypox .
Smallpox vaccine is made from live vaccinia virus, a virus closely related to variola virus (smallpox).

The current licensed vaccine available in the United States is ACAM2000®. ACAM2000 is administered as a live virus preparation that is inoculated into the skin by pricking the skin surface.

Following a successful inoculation, a lesion will develop at the site of the vaccination. The virus growing at the site of this inoculation lesion can be spread to other parts of the body or even to other people. Individuals who receive vaccination with ACAM2000 must take precautions to prevent the spread of the vaccine virus.

CDC, in conjunction with the Advisory Committee on Immunization Practices (ACIP), provides recommendations on who should receive smallpox vaccination in a non-emergency setting. At this time, vaccination is recommended for laboratorians working with certain orthopoxviruses and military personnel.
Vaccine Effectiveness
Smallpox vaccine is effective at protecting people against monkeypox when given before exposure to monkeypox. Experts also believe that vaccination after a monkeypox exposure may help prevent the disease or make it less severe.

Because monkeypox virus is closely related to the virus that causes smallpox, the smallpox vaccine can protect people from getting monkeypox. Past data from Africa suggests that the smallpox vaccine is at least 85% effective in preventing monkeypox.
Smallpox vaccine is effective at protecting people against monkeypox when given before exposure to monkeypox. Experts also believe that vaccination after a monkeypox exposure may help prevent the disease or make it less severe.
Receiving Vaccine After Exposure to Monkeypox Virus

Smallpox vaccination after exposure to monkeypox virus is still possible. However, the sooner an exposed person gets the vaccine, the better.

CDC recommends that the vaccine be given within 4 days from the date of exposure in order to prevent onset of the disease. If given between 4–14 days after the date of exposure, vaccination may reduce the symptoms of disease, but may not prevent the disease.
Revaccination After Exposure

Persons exposed to monkeypox virus and who have not received the smallpox vaccine within the last 3 years, should get the smallpox vaccine.

The sooner the person receives the vaccine, the more effective it will be in protecting against monkeypox virus.
Smallpox Vaccine Risks vs. Monkeypox Disease

For most persons who have been exposed to monkeypox, the risks from monkeypox disease are greater than the risks from the smallpox vaccine.

Monkeypox is a serious disease. It causes fever, headache, muscle aches, backache, swollen lymph nodes, a general feeling of discomfort, exhaustion, and severe rash. Studies of monkeypox in Central Africa—where people live in remote areas and are medically underserved—showed that the disease killed 1–10% of people infected.
In contrast, most people who get the smallpox vaccine have only minor reactions, like mild fever, tiredness, swollen glands, and redness and itching at the place where the vaccine is given. However, the smallpox vaccine does have more serious risks, too.
Based on past experience, it is estimated that between 1 and 2 people out of every 1 million people vaccinated will die as a result of life-threatening complications from the vaccine.

For a more detailed look at Monkeypox, and particularly the recent emergence of the virus in West Africa, you may wish to revisit:

MMWR: Emergence of Monkeypox — West and Central Africa, 1970–2017

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