EXPERT REACTION: Australia's first cases of monkeypox

While the new clusters of monkeypox cases in the UK and Europe need to be monitored, there is no cause for panic. There are several reasons for this. First, the mode of transmission of viruses from this family does not present the explosive spreading power of respiratory viruses like SARS CoV-2 and influenza virus. Second, monkeypox is caused by a virus that is not new. It has been known to infect humans at least since the 1970s and is closely related to viruses we know how to combat. These so-called poxviruses include vaccinia virus, the namesake for vaccines, and variola virus, causing smallpox -  the only human disease to have been eradicated from nature.

Poxviruses are among the most complex viruses infecting humans and experts at subverting defence systems put up by their host. Yet, they are a bit like the elephants of the virus world. Their structure and replication make them easier to aim at than smaller, moving targets. Indeed, decades of basic research have revealed a few chinks in their armour. This has prepared us well to respond to such a threat as drugs and next generation vaccines have been developed against smallpox, providing options to respond to monkeypox should it develop further.

Why these cases have emerged now in Europe is not known yet. It is clear however that the virus has been circulating more actively in central and West Africa for decades as immunity to poxviruses conferred by the smallpox vaccine is waning in the general population.

What is monkeypox?

Monkeypox, a zoonotic disease caused by an orthopoxvirus, results in a smallpox-like disease in humans. Since monkeypox in humans was initially diagnosed in 1970 in the Democratic Republic of the Congo (DRC), it has spread to other regions of Africa (primarily West and Central), and cases outside Africa have emerged in recent years. Monkeypox typically presents clinically with fever, rash and swollen lymph nodes and may lead to a range of medical complications. It is usually a self-limited disease with the symptoms lasting from 2 to 4 weeks. Severe cases can occur. In recent times, the case fatality ratio has been around 3-6%. Monkeypox is transmitted to humans through close contact with an infected person or animal, or with material contaminated with the virus.

Re-emergence of monkeypox?

There has been concern worldwide about the reasons for the resurgence in monkeypox cases, the most prevailing being waning immunity, although deforestation may be a factor or can even act in potentiation. Monkeypox virus, variola virus (smallpox), and vaccinia virus (smallpox vaccination) are closely related orthopoxviruses. At the time when smallpox was rampant, no cases of monkeypox were reported. This could have been either because the focus was on smallpox and the presentation of the two diseases are similar or the lack of laboratory confirmation of the etiologic agent led to an assumption of smallpox. Historical data have shown that smallpox vaccination was approximately 85% protective against monkeypox.

A possible new pandemic?

The waning population immunity associated with discontinuation of smallpox vaccination has established the landscape for the resurgence of monkeypox. This is demonstrated by the increases in the recent number of cases recently outside of Africa. In light of the current environment for pandemic threats, the public health importance of monkeypox disease should not be underestimated. International support for increased surveillance and detection of monkeypox cases are essential tools for understanding the continuously changing epidemiology of this resurging disease.

What are the possibilities of a new virulent strain on monkey pox currently?

We still don’t have much data on this. The fact that so many cases are being reported in several countries certainly suggests that this strain is more transmissible than others. We still need to look at the current genomic data on the currently circulating strain to know more. One things for sure is that, the threat posed by this virus should not be taken lightly and increased surveillance and vigilance is definitely needed.   

Monkeypox is a viral infection that comes from the same family as smallpox. It is endemic to Africa with two clades (or strains) described: a milder West African clade and a more severe Congo Basin clade. The European Centre for Disease Prevention and Control confirms that the milder West African clade is the one found in Europe.

This outbreak is a bit unusual. Monkeypox cases found outside Africa are typically imported from travellers infected overseas or people exposed to infected animals brought into the country. But these human cases don't commonly infect other people; therefore, the amount of person-to-person transmission we're hearing about so far seems more than expected, but it's early days in the outbreak, so hopefully they might dwindle away. Or has the virus mutated to be more effective at person-to-person transmission?

We need more data. Following infection, after a 7-17 day incubation period, there is a flu-like illness with high fevers for a few days before the rash appears. It is quite an extensive rash that lasts for up to 4 weeks and can lead to permanent disfigurement. Pneumonia, diarrhoea and eye involvement can occur. The death rate is low. Previous smallpox vaccination can provide cross-protection but it is uncertain how much immunity there would be for people vaccinated decades ago. Some antiviral agents are available too.

If you’ve heard that Monkeypox is often spread by breathing in infected droplets, like influenza or COVID-19, this seems like another bad news story for people with existing lung diseases like asthma and COPD. However, it appears less easily transmitted than those viruses, and the simple measures you are familiar with like hand washing, mask wearing, and self-isolating if exposed are all protective. 

Respiratory problems are also very uncommon with Monkeypox, and tend to be due to infections with other organisms taking advantage of someone’s weakened immune system. With that in mind, ensure you and your lungs are in the best possible shape by avoiding cigarette smoke, taking regular preventer therapy, ensuring you exercise and eat healthily: that way you are likely to be one of the many people for whom viral infections are an inconvenience, not a serious illness.

Monkeypox is an orthopox virus like the smallpox virus, variola virus, vaccinia virus, and cowpox virus. Variola virus resulted in smallpox that killed more than 500 million people during the 1900s. These viruses are DNA viruses, and the chances of genomic mutations are minimal; therefore, there are no significant concerns with the emergence of new variants. Monkeypox is reported in parts of Africa (e.g., Nigeria and Congo). The virus is acquired by contact with animals that carry the virus (e.g., infected rodents) or from other infected people who are symptomatic.  
 
Monkeypox is less contagious/less transmissible and less likely to cause severe disease in humans. It is a self-limiting disease, and most people recover 2-3 weeks after developing symptoms. The virus is only infectious when the individual is symptomatic and in close contact with others, therefore there is a low risk of transmission in the general population. The virus can be transmitted from animal to human (zoonotic transmission), and human to human, through contact with symptomatic individuals (skin lesions that contain pus, respiratory tract droplets and contaminated bedding). Typically, with many viral infections, monkeypox infection results in fever, body ache and headache. Skin rash appears about one week after early fever symptoms. The rash initially appears as a small lesion and can become filled with pus, followed by the formation of dry scabs. The significant risk is to pregnant women as infection can affect foetal development. 
 
In the 2003 outbreak in the US - 73 cases were reported. There were also several past laboratory-confirmed cases related to the importation of infected rodents."

Cases of monkeypox have been found in Europe and North America. Given the already broad distribution in western countries and global travel, it was almost inevitable that we’d have a case in Australia eventually. The disease is caused by the monkeypox virus, which is endemic in various countries in Africa but has caused outbreaks elsewhere before. In Africa, people have become infected as a result of contact with infected animals, which includes a range of species including some rodents, not necessarily monkeys.

In the past these outbreaks into human populations have been limited because the spread of monkeypox between people is not very efficient. Monkeypox virus belongs to a wider family of viruses that includes the viruses that caused smallpox and the vaccine used to eradicate smallpox as a disease. The same vaccine can be used to protect against monkeypox and studies suggest that the vaccine can even be effective when given after an exposure to the virus.

This is now being done in a process referred to as “ring” vaccination, where contacts are identified and vaccinated. The current epidemiology of monkeypox cases is unusual, because most cases are unlinked and will mean that vigilance is required across the world, but unlike SARS-CoV-2 this virus is better understood and methods to prevent spread can be actioned swiftly.
 
The WHO has an excellent fact sheet: https://www.who.int/news-room/fact-sheets/detail/monkeypox

Monkeypox is caused by an orthopoxvirus that is closely related to the virus that caused smallpox, variola.  Smallpox only infects humans, but monkeypox is an animal virus that occasionally infects humans, and can sometimes spread from person to person. It is a respiratory virus, but does not usually spread easily between humans, and usually only in close contacts. Infection rates of contacts in previous studies are about 3%. There are two clades which cause 1% and 10% fatality respectively – the UK outbreak appears to be the less severe clade, but 1% is similar to COVID-19, so is a concern.

 
It was first identified in humans in 1970, in Africa. It is a re-emerging disease that's been causing very large outbreaks in Nigeria and DRC since 2017. Scientists have puzzled over why a previously rare infection is now becoming more common. The vaccine against smallpox also protects against monkeypox, but few people under 50 years have ever had it. Even fewer in Australia, where mass vaccination was never used.

Our research shows that the waning of immunity from smallpox vaccination may be contributing to the increasing outbreaks of monkeypox – it is more than 40-50 years since mass vaccination ceased.  In September 2018, a case of monkeypox occurred at a Naval base in Cornwall in the UK in a person who had travelled from Nigeria. Simultaneously, a second case occurred in Blackpool in an unrelated person returning from Nigeria. In 2017, there had been less than 200 cases of monkeypox in Nigeria, and in 2018, only 45 confirmed cases and 114 suspected cases.
 
The current epidemic in 2022 in the UK is the largest outside of Africa and has spread to many countries around the world. Clusters have occurred among men who have sex with men, not a pattern seen before.

Perhaps the initial importation was spread at a venue or within a community that resulted in more spread in the same group. Although genital rash is mentioned, I understand in the UK it is not solely a genital rash, but involves a rash on the rest of the body.

This is an unusual outbreak, with unrelated cases in different locations in the UK which has been speculated as being due to substantial numbers of asymptomatic infection also occurring. Asymptomatic infection may occur, but usually in people who have had the smallpox vaccine. In a well-studied outbreak in the US, only 3 in 20 cases were asymptomatic, and all other cases had the rash. Most people infected in the current epidemic are too young to have been vaccinated, so it would surprise me to see substantial asymptomatic transmission. 

We know that smallpox does not transmit in asymptomatic people, so it is unlikely monkeypox will be very different. Serological studies from the UK are being done and should shed more light on this hypothesis. Orthopoxviruses are stable DNA viruses, so rapid mutation is not expected – but we are awaiting information on the whole genome sequencing.  We are also waiting on information from the outbreak investigation to review risk factors for infection and the epidemiologic links between cases in the UK and elsewhere.
 
This is the first time there has been travel-related spread from outside of the African continent, where the virus is endemic in animals. There have been a number of travel related importations to the UK, Singapore and other countries from Nigeria and DRC since 2017, but now the source of spread appears to be the UK, which is unprecedented. Given it is a frequent travel destination/source for Australia, it is not surprising we have now got a case here.
 
There are effective vaccines against monkeypox – the second and third generation smallpox vaccines, both live virus vaccines using the vaccinia virus. Vaccinia is another orthopoxvirus that confers immunity against smallpox and monkeypox, but can have serious side effects in a few people, especially those with compromised immune systems.  The third generation vaccines do not replicate in the body and can be used in immunocompromised people. There are also effective antivirals against smallpox. It would be wise to ensure we have these and enough of both types of vaccines, together with regulatory processes to use them against monkeypox.  The best strategy is to identify contacts and vaccinate them, rather than mass vaccination. This is called 'ring vaccination' and was used to eradicate smallpox.

Monkeypox is not new and as the name suggests was first found in monkeys in Africa in the late 1950’s, with the first human case reported in 1970 in the Democratic Republic of Congo. It is a close relative of smallpox, the first human disease to be eradicated by vaccination in 1979. Fortunately, the smallpox vaccine also provides protection against Monkeypox, and perhaps the eradication of smallpox and the resulting cessation of the use of this vaccine has increased vulnerability to Monkeypox with infections in the Democratic Republic of Congo increasing 20-fold in the three decades after smallpox was eradicated.

Whilst mostly affecting African countries, there have been previous outbreaks in other countries including in the USA in 2003 relating to pet prairie dogs. Fortunately, this is an infection that’s relatively hard to transmit, with close contact with blood or bodily fluids including respiratory secretions or fluid from skin lesions required for transmission to occur.

Following an incubation period of around 6 to 13 days, systemic symptoms similar to many other viral infections are usually seen first including fever, headaches, muscle aches and swollen lymph nodes. Skin eruption often follows with a rash that can include flat lesions to larger fluid filled blisters. These lesions tend to be concentrated on the face and extremities rather than on the trunk.

Usually, the disease is self-limiting after around 2 to 4 weeks but can very rarely be fatal. There are varying figures quoted for mortality with differences depending on which strain, fortunately, it seems the strain with the lower mortality of around 1% is the one that is involved in this outbreak that now includes the UK, USA, Spain, Portugal and Canada. While it is important that awareness is raised, and we may well see cases in Australia, there are several important considerations with this virus that mean we do not need to overreact. It is relatively hard to spread, and we already have great vaccines and potentially some treatments available also.

Monkey pox virus belongs to the genus Orthopoxvirus. Other virus members capable of infecting humans are vaccinia, cowpox and variola virus, which causes smallpox. Although monkey pox virus is much less virulent than variola virus, strains can be fatal (1-10%).  These large viruses are “brick-like” in shape, contain around 200 genes and are clever at immune evasion.

 
Monkeypox is considered a rare zoonotic disease, often caught by consuming “exotic bush meat”. The virus can be found in rodents, squirrels, and non-human primates. Transmission also occurs through direct and indirect contact with an infected animal. However, only smallpox is transmitted by the respiratory route through droplets.
 
Smallpox was probably first identified 10,000 BC in a mummified Egyptian Pharaoh. It was known as the “speckled monster” because of the disfigurement left by scars from hundreds of virus lesions all over the body. In the 20th Century, smallpox caused about 500 million deaths.
 
In the past, the smallpox vaccine which contains a live attenuated vaccinia virus, also provided cross-reactive immunity to protect against monkeypox. However, since the eradication of smallpox in 1979, we are now seeing sporadic cases of monkeypox in largely non-immune populations as vaccination has stopped. So, it is very important to monitor virus outbreaks for biosecurity surveillance as smallpox and monkeypox look very similar in clinical appearance.

With the continued increase in international travel, it appears more than likely that cases of monkeypox will be found in Australia. Given the not yet determined nature of the chains of transmission in the clusters identified in Europe whether there will be localised transmission in Australia is not clear.

The early identification and notification of cases in Europe, Canada and America does allow Australia to be alert and warn incoming passengers to be mindful of symptoms which can then be reported early to health professionals. Monkeypox is generally spread through skin to skin contact, but respiratory secretions and items of clothing or bedding soiled with fluid/pus from lesions can cause transmission.

Monkeypox is not a new disease with health professionals and scientists from particularly Nigeria and Cameroon having a lot of experience in managing cases, learning from their expertise and experience is important. Transmission between people is often poor, with the disease being mostly self-limiting. This means that with careful public health education and early reporting it is unlikely large outbreaks would occur in Australia.