Monkeypox, the resemblance of a defeated enemy
by Antonio Gregorio Dias Junior (twitter: @GregorioDias1)
edited by: Layal Liverpool (twitter: @layallivs)
Back in the old days, the use of animals for laboratory experimentation was not as tightly regulated as it is today. Consequently, several studies were routinely performed in wild animals caught in tropical rainforests from Asia and Africa. In one of these events, scientists in Denmark isolated the monkeypox virus (MPXV) for the first time in 1958 from a naturally-infected captive monkey. The virus was not believed to cause disease in humans until its first case detected in 1970 in the Democratic Republic of the Congo (DRC) in Africa. This finding was very alarming as it came during the World Health Organization (WHO)-led global vaccination campaign to eradicate smallpox (1966-1980). Within this context, one could ask what monkeypox has to do with smallpox and why its discovery in humans was so alarming?
Monkeypox as a threat during the smallpox eradication campaign
The smallpox-causing variola virus caused a high case-fatality disease in humans featuring hard and deep skin lesions initially on the face, which then spread to the rest of the body. The virus was known to be kept in nature through a high-rate of human-to-human transmission. Given this attribute, one strategy to eradicate smallpox involved vaccinating a great mass of the worldwide human population to prevent its transmission and thus eliminate the disease. It has worked! Nowadays, the virus only exists frozen in high-security laboratories in Russia and in the United States.
Monkeypox and variola (smallpox) viruses are relatives classified within the same taxonomical group: viral family, Poxviridae, and genus, Orthopoxvirus. Clinical symptoms are also somewhat similar and more information on this can be found here. Back in 1970 in the DRC, a patient presented with smallpox-like symptoms in a region where smallpox had already been believed to be eradicated. This event urged the public health system to find out whether smallpox had returned, or a new virus would be causing the ailment. MPXV was found as the causative agent and, even worse, it had an yet-to-be identified animal reservoir, i.e. unlike smallpox, monkeypox had two modes of transmissions: i) animal-to-human; and, ii) human-to-human.
Source: CDC Public Health Image Library (PHIL). Maculopapular monkeypox lesions in a 4-year old female that are similar to smallpox lesions.
This was very concerning as it was feared monkeypox would "replace" smallpox after its eradication. Besides, eliminating monkeypox would be very complicated due to the existence of an animal reservoir. Fortunately, some of these fears above never came into reality and here are some probable reasons why: i) monkeypox was found to contain a low potential for transmission among humans; ii) mortality rate is up to 10%, which is lower than for smallpox that is about 30%; iii) monkeypox is clinically less severe than smallpox. Therefore, this disease has been considered a rare condition leading to occasional outbreaks. But why have we been hearing more often about monkeypox cases in recent times?
Monkeypox has been put under the spotlight
Sporadic cases and outbreaks of monkeypox have been reported in about ten African countries since 1970. Nevertheless, the number of reported cases has increased recently, as exemplified by a recent outbreak in Nigeria (2017/2018). One of the reasons for this might be related to the improvements in the surveillance and detection systems for infectious diseases following the major Ebola outbreak in 2014-2016. Like monkeypox, Ebola is also a zoonotic disease: a disease transmitted to humans from animals, for example bats in the case of Ebola. Zoonotic diseases correspond to about 60% of human pathogens. This simply suggests that monkeypox has always been there but before 2014 it went unnoticed in many cases, especially in areas where it was not endemic. In conjunction with this, other facts might also help to explain monkeypox re-emergence.
It has been demonstrated that individuals that were vaccinated against smallpox are also cross-protected against monkeypox (up to 80% of protection). This is because orthopoxviruses have been known to generate cross-reactive protections - initial knowledge on this aspect dates back to 1798 when Edward Jenner published his results about the first vaccine against a human disease in the world, smallpox. Following smallpox eradication and safety concerns about its vaccine, smallpox vaccination has been halted since 1980. In turn, all vaccinated individuals nowadays are of adult age and, therefore, individuals born after this time are not protected against smallpox nor cross-protected against monkeypox. Hence, waning immunity to smallpox is probably another factor contributing to more recent cases of monkeypox.
In addition, several other factors might be analysed to help to explain the re-emergence of monkeypox, including areas with war zones driving human migration and intensification and exploitation of new venues of primitive agriculture-based subsistence. Nevertheless, more knowledge of the virus ecology and its maintenance in nature is yet to be gained. This information could help to inform public health policies to tackle and prevent new outbreaks of monkeypox, such as those occurring in- and out of Africa.
A small glance at monkeypox transmission in- and out of Africa
In Africa, transmission can occur from animals to humans through exposure to infected animals - including carcasses of dead animals, blood, and consumption of uncooked bushmeat. Monkeypox has been mostly linked with the proximity to rainforests and wild animals. Some species of squirrels (e.g. Funisciurus and Heliosciurus) might carry MPXV and some studies suggest they are potential candidates to maintain the virus in nature. Other animals, such as some species of monkeys and rats, might also be found naturally infected by MPXV, but their role as probable reservoir is less clear, i.e. it is not known whether they can be accidentally infected or whether they in fact sustain the virus circulation in nature. These aspects are very interesting to be identified because they can help to explain outbreak restriction to certain geographical areas as well as the emergence of new cases.
In 2003, an outbreak occurred in the United States (US) after the importation of Gambian rats from Ghana leading to infection of pet prairie-dogs that were co-housed with these rats. Ultimately, prairie-dogs' owners contracted the disease leading to more than 80 cases in the US. More recently, three cases have been identified in the UK, two of them in travellers coming from Nigeria, and one case of secondary transmission from a patient to a healthcare worker. As discussed above, its low rate of human-to-human transmission suggests that the cases in the UK are going to be self-limiting and should not lead to a major outbreak.
In sum, monkeypox, as a zoonotic disease, should be tackled as a relevant public health issue under the umbrella of the "One-health" animal-human-environment framework. Its features highlight the safety concerns related to human and animal health, animal trades, ecological systems, potential for disease (re)emergence, living conditions and nutritional habits of susceptible populations.
For further information, I would suggest to visit:
a) WHO's monkeypox website to access the "Fact Sheet" and other official publications;
b) Durski et al. 2018 (from page 125): Emergence of monkeypox in West Africa and Central Africa, 1970-2017.
c) Sklenovska & Ranst, 2018: Emergence of Monkeypox as the Most Important Orthopoxvirus Infection in Humans.
edited by: Layal Liverpool (twitter: @layallivs)
Back in the old days, the use of animals for laboratory experimentation was not as tightly regulated as it is today. Consequently, several studies were routinely performed in wild animals caught in tropical rainforests from Asia and Africa. In one of these events, scientists in Denmark isolated the monkeypox virus (MPXV) for the first time in 1958 from a naturally-infected captive monkey. The virus was not believed to cause disease in humans until its first case detected in 1970 in the Democratic Republic of the Congo (DRC) in Africa. This finding was very alarming as it came during the World Health Organization (WHO)-led global vaccination campaign to eradicate smallpox (1966-1980). Within this context, one could ask what monkeypox has to do with smallpox and why its discovery in humans was so alarming?
Monkeypox as a threat during the smallpox eradication campaign
The smallpox-causing variola virus caused a high case-fatality disease in humans featuring hard and deep skin lesions initially on the face, which then spread to the rest of the body. The virus was known to be kept in nature through a high-rate of human-to-human transmission. Given this attribute, one strategy to eradicate smallpox involved vaccinating a great mass of the worldwide human population to prevent its transmission and thus eliminate the disease. It has worked! Nowadays, the virus only exists frozen in high-security laboratories in Russia and in the United States.
Monkeypox and variola (smallpox) viruses are relatives classified within the same taxonomical group: viral family, Poxviridae, and genus, Orthopoxvirus. Clinical symptoms are also somewhat similar and more information on this can be found here. Back in 1970 in the DRC, a patient presented with smallpox-like symptoms in a region where smallpox had already been believed to be eradicated. This event urged the public health system to find out whether smallpox had returned, or a new virus would be causing the ailment. MPXV was found as the causative agent and, even worse, it had an yet-to-be identified animal reservoir, i.e. unlike smallpox, monkeypox had two modes of transmissions: i) animal-to-human; and, ii) human-to-human.
This was very concerning as it was feared monkeypox would "replace" smallpox after its eradication. Besides, eliminating monkeypox would be very complicated due to the existence of an animal reservoir. Fortunately, some of these fears above never came into reality and here are some probable reasons why: i) monkeypox was found to contain a low potential for transmission among humans; ii) mortality rate is up to 10%, which is lower than for smallpox that is about 30%; iii) monkeypox is clinically less severe than smallpox. Therefore, this disease has been considered a rare condition leading to occasional outbreaks. But why have we been hearing more often about monkeypox cases in recent times?
Monkeypox has been put under the spotlight
Sporadic cases and outbreaks of monkeypox have been reported in about ten African countries since 1970. Nevertheless, the number of reported cases has increased recently, as exemplified by a recent outbreak in Nigeria (2017/2018). One of the reasons for this might be related to the improvements in the surveillance and detection systems for infectious diseases following the major Ebola outbreak in 2014-2016. Like monkeypox, Ebola is also a zoonotic disease: a disease transmitted to humans from animals, for example bats in the case of Ebola. Zoonotic diseases correspond to about 60% of human pathogens. This simply suggests that monkeypox has always been there but before 2014 it went unnoticed in many cases, especially in areas where it was not endemic. In conjunction with this, other facts might also help to explain monkeypox re-emergence.
It has been demonstrated that individuals that were vaccinated against smallpox are also cross-protected against monkeypox (up to 80% of protection). This is because orthopoxviruses have been known to generate cross-reactive protections - initial knowledge on this aspect dates back to 1798 when Edward Jenner published his results about the first vaccine against a human disease in the world, smallpox. Following smallpox eradication and safety concerns about its vaccine, smallpox vaccination has been halted since 1980. In turn, all vaccinated individuals nowadays are of adult age and, therefore, individuals born after this time are not protected against smallpox nor cross-protected against monkeypox. Hence, waning immunity to smallpox is probably another factor contributing to more recent cases of monkeypox.
In addition, several other factors might be analysed to help to explain the re-emergence of monkeypox, including areas with war zones driving human migration and intensification and exploitation of new venues of primitive agriculture-based subsistence. Nevertheless, more knowledge of the virus ecology and its maintenance in nature is yet to be gained. This information could help to inform public health policies to tackle and prevent new outbreaks of monkeypox, such as those occurring in- and out of Africa.
A small glance at monkeypox transmission in- and out of Africa
In Africa, transmission can occur from animals to humans through exposure to infected animals - including carcasses of dead animals, blood, and consumption of uncooked bushmeat. Monkeypox has been mostly linked with the proximity to rainforests and wild animals. Some species of squirrels (e.g. Funisciurus and Heliosciurus) might carry MPXV and some studies suggest they are potential candidates to maintain the virus in nature. Other animals, such as some species of monkeys and rats, might also be found naturally infected by MPXV, but their role as probable reservoir is less clear, i.e. it is not known whether they can be accidentally infected or whether they in fact sustain the virus circulation in nature. These aspects are very interesting to be identified because they can help to explain outbreak restriction to certain geographical areas as well as the emergence of new cases.
In 2003, an outbreak occurred in the United States (US) after the importation of Gambian rats from Ghana leading to infection of pet prairie-dogs that were co-housed with these rats. Ultimately, prairie-dogs' owners contracted the disease leading to more than 80 cases in the US. More recently, three cases have been identified in the UK, two of them in travellers coming from Nigeria, and one case of secondary transmission from a patient to a healthcare worker. As discussed above, its low rate of human-to-human transmission suggests that the cases in the UK are going to be self-limiting and should not lead to a major outbreak.
In sum, monkeypox, as a zoonotic disease, should be tackled as a relevant public health issue under the umbrella of the "One-health" animal-human-environment framework. Its features highlight the safety concerns related to human and animal health, animal trades, ecological systems, potential for disease (re)emergence, living conditions and nutritional habits of susceptible populations.
For further information, I would suggest to visit:
a) WHO's monkeypox website to access the "Fact Sheet" and other official publications;
b) Durski et al. 2018 (from page 125): Emergence of monkeypox in West Africa and Central Africa, 1970-2017.
c) Sklenovska & Ranst, 2018: Emergence of Monkeypox as the Most Important Orthopoxvirus Infection in Humans.
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