CHEST Physician

A number of years ago, a patient I was treating mentioned that she was not eating tomatoes. There had been stories in the news about people contracting bacterial infections from tomatoes, but I paused for a moment, then asked her: “Have there been any contaminated tomatoes here in Maryland?” There had not been and I was still happily eating salsa, but my patient thought about this differently: If disease-causing tomatoes were to come to our state, someone would be the first person to become ill. She did not want to take any risks. My patient, however, was a heavy smoker and already grappling with health issues that were caused by smoking, so I found her choice of what she should worry about and how it influenced her behavior to be perplexing. I realize it’s not the same; nicotine is an addiction, while tomatoes remain a choice for most of us, and it’s common for people to worry about very unlikely events even when we are surrounded by very real and statistically more probable threats to our well-being.

Today’s news reports are filled with stories about 2019 Novel Coronavirus (2019-nCoV), an illness that started in Wuhan, China; as of Jan. 31, 2020, there were 9,776 confirmed cases and 213 deaths. There have been an additional 118 cases reported outside of mainland China, including 6 in the United States, and no one outside of China has died.

The response to the virus has been remarkable: Wuhan, a city of more than 11 million inhabitants, is on lockdown, as are 15 other cities in China; 46 million people have been affected, the largest quarantine in human history. Travel is restricted in parts of China, airports all over the world are screening those who fly in from Wuhan, foreign governments are bringing their citizens home from Wuhan, and even Starbucks has temporarily closed half its stores in China. The economics of containing this virus are astounding.

In the meantime, the Centers for Disease Control and Prevention reports that, as of the week of Jan. 25, there have been 19 million cases of the flu in the United States. Of those stricken, 180,000 people have been hospitalized and 10,000 have died, including 68 pediatric patients. No cities are on lockdown, public transportation runs as usual, airports don’t screen passengers for flu symptoms, and Starbucks continues to serve vanilla lattes to any willing customer. Anxiety about illness is not new; we’ve seen it with SARS, Ebola, measles, and even around Chipotle’s food poisoning cases – to name just a few recent scares. We have also seen a lot of media on vaping-related deaths, and as of early January 2020, vaping-related illnesses affected 2,602 people with 59 deaths. It has been a topic of discussion among legislators, with an emphasis on either outlawing the flavoring that might appeal to younger people or simply outlawing e-cigarettes. No one, however, is talking about outlawing regular cigarettes, despite the fact that many people have switched from cigarettes to vaping products as a way to quit smoking. So, while vaping has caused 59 deaths since 2018, cigarettes are responsible for 480,000 fatalities a year in the United States and smokers live, on average, 10 years less than nonsmokers.

So what fuels anxiety about the latest health scare, and why aren’t we more anxious about the more common causes of premature mortality? Certainly, the newness and the unknown are factors in the coronavirus scare. It’s not certain how this illness was introduced into the human population, although one theory is that it started with the consumption of bats who carry the virus. It’s spreading fast, and in some people, it has been lethal. The incubation period is not known, or whether it is contagious before symptoms appear. Coronavirus is getting a lot of public health attention and the World Health Organization just announced that the virus is a public health emergency of international concern. On the televised news on Jan. 29, 2020, coronavirus was the top story in the United States, even though an impeachment trial is in progress for our country’s president.

The public health response of locking down cities may help contain the outbreak and prevent a global epidemic, although millions of people had already left Wuhan, so the heavy-handed attempt to prevent spread of the virus may well be too late. In the case of the Ebola virus – a much more lethal disease that was also thought to be introduced by bats – public health measures certainly curtailed global spread, and the epidemic of 2014-2016 was limited to 28,600 cases and 11,325 deaths, nearly all of them in West Africa.

Most of the things that cause people to die are not new and are not topics the media chooses to sensationalize. Dissemination of news has changed over the decades, with so much more of it, instant reports on social media, and competition for viewers that leads journalists to pull at our emotions. We might worry about getting food poisoning from romaine lettuce – if that is what the news is focusing on – but we don’t worry when we enter our cars, keep firearms in our homes, or light up cigarettes. And while we may, or may not, get flu shots and avoid those who have the flu, how and where we position both our anxiety and our resources does not always make sense. Certainly some people are predisposed to worry about both common and uncommon dangers, while others seem never to worry and engage in acts that many of us would consider dangerous. If we are looking for logic, it may be hard to find – there are those who would happily go bungee jumping but wouldn’t dream of leaving the house out without hand sanitizer.

The repercussions from this massive response to the Wuhan coronavirus are significant. For the millions of people on lockdown in China, each day gets emotionally harder; some may begin to have issues procuring food, and the financial losses for the economy will be significant. It’s not really possible to know yet if this response is warranted; we do know that infectious diseases can kill millions. The AIDS pandemic has taken the lives of 36 million people since 1981, and the influenza pandemic of 1918 resulted in an estimated 20 million to 50 million deaths after infecting 500 million people. Still, one might wonder if other, more mundane causes of morbidity and mortality – the ones that no longer garner our dread or make it to the front pages – might also be worthy of more hype and resources.

Dr. Miller is coauthor with Annette Hanson, MD, of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins, both in Baltimore.

A number of years ago, a patient I was treating mentioned that she was not eating tomatoes. There had been stories in the news about people contracting bacterial infections from tomatoes, but I paused for a moment, then asked her: “Have there been any contaminated tomatoes here in Maryland?” There had not been and I was still happily eating salsa, but my patient thought about this differently: If disease-causing tomatoes were to come to our state, someone would be the first person to become ill. She did not want to take any risks. My patient, however, was a heavy smoker and already grappling with health issues that were caused by smoking, so I found her choice of what she should worry about and how it influenced her behavior to be perplexing. I realize it’s not the same; nicotine is an addiction, while tomatoes remain a choice for most of us, and it’s common for people to worry about very unlikely events even when we are surrounded by very real and statistically more probable threats to our well-being.

Today’s news reports are filled with stories about 2019 Novel Coronavirus (2019-nCoV), an illness that started in Wuhan, China; as of Jan. 31, 2020, there were 9,776 confirmed cases and 213 deaths. There have been an additional 118 cases reported outside of mainland China, including 6 in the United States, and no one outside of China has died.

The response to the virus has been remarkable: Wuhan, a city of more than 11 million inhabitants, is on lockdown, as are 15 other cities in China; 46 million people have been affected, the largest quarantine in human history. Travel is restricted in parts of China, airports all over the world are screening those who fly in from Wuhan, foreign governments are bringing their citizens home from Wuhan, and even Starbucks has temporarily closed half its stores in China. The economics of containing this virus are astounding.

In the meantime, the Centers for Disease Control and Prevention reports that, as of the week of Jan. 25, there have been 19 million cases of the flu in the United States. Of those stricken, 180,000 people have been hospitalized and 10,000 have died, including 68 pediatric patients. No cities are on lockdown, public transportation runs as usual, airports don’t screen passengers for flu symptoms, and Starbucks continues to serve vanilla lattes to any willing customer. Anxiety about illness is not new; we’ve seen it with SARS, Ebola, measles, and even around Chipotle’s food poisoning cases – to name just a few recent scares. We have also seen a lot of media on vaping-related deaths, and as of early January 2020, vaping-related illnesses affected 2,602 people with 59 deaths. It has been a topic of discussion among legislators, with an emphasis on either outlawing the flavoring that might appeal to younger people or simply outlawing e-cigarettes. No one, however, is talking about outlawing regular cigarettes, despite the fact that many people have switched from cigarettes to vaping products as a way to quit smoking. So, while vaping has caused 59 deaths since 2018, cigarettes are responsible for 480,000 fatalities a year in the United States and smokers live, on average, 10 years less than nonsmokers.

So what fuels anxiety about the latest health scare, and why aren’t we more anxious about the more common causes of premature mortality? Certainly, the newness and the unknown are factors in the coronavirus scare. It’s not certain how this illness was introduced into the human population, although one theory is that it started with the consumption of bats who carry the virus. It’s spreading fast, and in some people, it has been lethal. The incubation period is not known, or whether it is contagious before symptoms appear. Coronavirus is getting a lot of public health attention and the World Health Organization just announced that the virus is a public health emergency of international concern. On the televised news on Jan. 29, 2020, coronavirus was the top story in the United States, even though an impeachment trial is in progress for our country’s president.

The public health response of locking down cities may help contain the outbreak and prevent a global epidemic, although millions of people had already left Wuhan, so the heavy-handed attempt to prevent spread of the virus may well be too late. In the case of the Ebola virus – a much more lethal disease that was also thought to be introduced by bats – public health measures certainly curtailed global spread, and the epidemic of 2014-2016 was limited to 28,600 cases and 11,325 deaths, nearly all of them in West Africa.

Most of the things that cause people to die are not new and are not topics the media chooses to sensationalize. Dissemination of news has changed over the decades, with so much more of it, instant reports on social media, and competition for viewers that leads journalists to pull at our emotions. We might worry about getting food poisoning from romaine lettuce – if that is what the news is focusing on – but we don’t worry when we enter our cars, keep firearms in our homes, or light up cigarettes. And while we may, or may not, get flu shots and avoid those who have the flu, how and where we position both our anxiety and our resources does not always make sense. Certainly some people are predisposed to worry about both common and uncommon dangers, while others seem never to worry and engage in acts that many of us would consider dangerous. If we are looking for logic, it may be hard to find – there are those who would happily go bungee jumping but wouldn’t dream of leaving the house out without hand sanitizer.

The repercussions from this massive response to the Wuhan coronavirus are significant. For the millions of people on lockdown in China, each day gets emotionally harder; some may begin to have issues procuring food, and the financial losses for the economy will be significant. It’s not really possible to know yet if this response is warranted; we do know that infectious diseases can kill millions. The AIDS pandemic has taken the lives of 36 million people since 1981, and the influenza pandemic of 1918 resulted in an estimated 20 million to 50 million deaths after infecting 500 million people. Still, one might wonder if other, more mundane causes of morbidity and mortality – the ones that no longer garner our dread or make it to the front pages – might also be worthy of more hype and resources.

Dr. Miller is coauthor with Annette Hanson, MD, of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins, both in Baltimore.

A number of years ago, a patient I was treating mentioned that she was not eating tomatoes. There had been stories in the news about people contracting bacterial infections from tomatoes, but I paused for a moment, then asked her: “Have there been any contaminated tomatoes here in Maryland?” There had not been and I was still happily eating salsa, but my patient thought about this differently: If disease-causing tomatoes were to come to our state, someone would be the first person to become ill. She did not want to take any risks. My patient, however, was a heavy smoker and already grappling with health issues that were caused by smoking, so I found her choice of what she should worry about and how it influenced her behavior to be perplexing. I realize it’s not the same; nicotine is an addiction, while tomatoes remain a choice for most of us, and it’s common for people to worry about very unlikely events even when we are surrounded by very real and statistically more probable threats to our well-being.

Today’s news reports are filled with stories about 2019 Novel Coronavirus (2019-nCoV), an illness that started in Wuhan, China; as of Jan. 31, 2020, there were 9,776 confirmed cases and 213 deaths. There have been an additional 118 cases reported outside of mainland China, including 6 in the United States, and no one outside of China has died.

The response to the virus has been remarkable: Wuhan, a city of more than 11 million inhabitants, is on lockdown, as are 15 other cities in China; 46 million people have been affected, the largest quarantine in human history. Travel is restricted in parts of China, airports all over the world are screening those who fly in from Wuhan, foreign governments are bringing their citizens home from Wuhan, and even Starbucks has temporarily closed half its stores in China. The economics of containing this virus are astounding.

In the meantime, the Centers for Disease Control and Prevention reports that, as of the week of Jan. 25, there have been 19 million cases of the flu in the United States. Of those stricken, 180,000 people have been hospitalized and 10,000 have died, including 68 pediatric patients. No cities are on lockdown, public transportation runs as usual, airports don’t screen passengers for flu symptoms, and Starbucks continues to serve vanilla lattes to any willing customer. Anxiety about illness is not new; we’ve seen it with SARS, Ebola, measles, and even around Chipotle’s food poisoning cases – to name just a few recent scares. We have also seen a lot of media on vaping-related deaths, and as of early January 2020, vaping-related illnesses affected 2,602 people with 59 deaths. It has been a topic of discussion among legislators, with an emphasis on either outlawing the flavoring that might appeal to younger people or simply outlawing e-cigarettes. No one, however, is talking about outlawing regular cigarettes, despite the fact that many people have switched from cigarettes to vaping products as a way to quit smoking. So, while vaping has caused 59 deaths since 2018, cigarettes are responsible for 480,000 fatalities a year in the United States and smokers live, on average, 10 years less than nonsmokers.

So what fuels anxiety about the latest health scare, and why aren’t we more anxious about the more common causes of premature mortality? Certainly, the newness and the unknown are factors in the coronavirus scare. It’s not certain how this illness was introduced into the human population, although one theory is that it started with the consumption of bats who carry the virus. It’s spreading fast, and in some people, it has been lethal. The incubation period is not known, or whether it is contagious before symptoms appear. Coronavirus is getting a lot of public health attention and the World Health Organization just announced that the virus is a public health emergency of international concern. On the televised news on Jan. 29, 2020, coronavirus was the top story in the United States, even though an impeachment trial is in progress for our country’s president.

The public health response of locking down cities may help contain the outbreak and prevent a global epidemic, although millions of people had already left Wuhan, so the heavy-handed attempt to prevent spread of the virus may well be too late. In the case of the Ebola virus – a much more lethal disease that was also thought to be introduced by bats – public health measures certainly curtailed global spread, and the epidemic of 2014-2016 was limited to 28,600 cases and 11,325 deaths, nearly all of them in West Africa.

Most of the things that cause people to die are not new and are not topics the media chooses to sensationalize. Dissemination of news has changed over the decades, with so much more of it, instant reports on social media, and competition for viewers that leads journalists to pull at our emotions. We might worry about getting food poisoning from romaine lettuce – if that is what the news is focusing on – but we don’t worry when we enter our cars, keep firearms in our homes, or light up cigarettes. And while we may, or may not, get flu shots and avoid those who have the flu, how and where we position both our anxiety and our resources does not always make sense. Certainly some people are predisposed to worry about both common and uncommon dangers, while others seem never to worry and engage in acts that many of us would consider dangerous. If we are looking for logic, it may be hard to find – there are those who would happily go bungee jumping but wouldn’t dream of leaving the house out without hand sanitizer.

The repercussions from this massive response to the Wuhan coronavirus are significant. For the millions of people on lockdown in China, each day gets emotionally harder; some may begin to have issues procuring food, and the financial losses for the economy will be significant. It’s not really possible to know yet if this response is warranted; we do know that infectious diseases can kill millions. The AIDS pandemic has taken the lives of 36 million people since 1981, and the influenza pandemic of 1918 resulted in an estimated 20 million to 50 million deaths after infecting 500 million people. Still, one might wonder if other, more mundane causes of morbidity and mortality – the ones that no longer garner our dread or make it to the front pages – might also be worthy of more hype and resources.

Dr. Miller is coauthor with Annette Hanson, MD, of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins, both in Baltimore.

Amid the rising spread of the 2019 Novel Coronavirus (2019-nCoV), the World Health Organization (WHO) has declared the virus outbreak a public health emergency of international concern (PHEIC).

WHO.int

The declaration was made during a press briefing on Jan. 30 after a week of growing concern and pressure on WHO to designate the virus at a higher emergency level. WHO’s Emergency Committee made the nearly unanimous decision after considering the increasing number of coronavirus cases in China, the rising infections outside of China, and the questionable measures some countries are taking regarding travel, said committee chair Didier Houssin, MD, said during the press conference.

As of Jan. 30, there were 8,236 confirmed cases of the coronavirus in China and 171 deaths, with another 112 cases identified outside of China in 21 other countries.

“Declaring a Public Health Emergency of International Concern is likely to facilitate [WHO’s] leadership role for public health measures, holding countries to account concerning additional measures they may take regarding travel, trade, quarantine or screening, research efforts, global coordination and anticipation of economic impact [and] support to vulnerable states,” Dr. Houssin said during the press conference. “Declaring a PHEIC should certainly not be seen as manifestation of distrust in the Chinese authorities and people which are doing tremendous efforts on the frontlines of this outbreak, with transparency, and let us hope, with success.”
 

What happens next?

Once a PHEIC is declared, WHO launches a series of steps, including the release of temporary recommendations for the affected country on health measures to implement and guidance for other countries on preventing and reducing the international spread of the disease, WHO spokesman Tarik Jasarevic said in an interview.

“The purpose of declaring a PHEIC is to advise the world on what measures need to be taken to enhance global health security by preventing international transmission of an infectious hazard,” he said.

Following the Jan. 30 press conference, WHO released temporary guidance for China and for other countries regarding identifying, managing, containing, and preventing the virus. China is advised to continue updating the population about the outbreak, continue enhancing its public health measures for containment and surveillance of cases, and to continue collaboration with WHO and other partners to investigate the epidemiology and evolution of the outbreak and share data on all human cases.

Other countries should be prepared for containment, including the active surveillance, early detection, isolation, case management, and prevention of virus transmission and to share full data with WHO, according to the recommendations.

Under the International Health Regulations (IHR), countries are required to share information and data with WHO. Additionally, WHO leaders advised the global community to support low- and middle-income countries with their response to the coronavirus and to facilitate diagnostics, potential vaccines, and therapeutics in these areas.

The IHR requires that countries implementing health measures that go beyond what WHO recommends must send to WHO the public health rationale and justification within 48 hours of their implementation for WHO review, Mr. Jasarevic noted.

“WHO is obliged to share the information about measures and the justification received with other countries involved,” he said.
 

PHEIC travel and resource impact

Declaration of a PHEIC means WHO will now oversee any travel restrictions made by other countries in response to 2019-nCoV. The agency recommends that countries conduct a risk and cost-benefit analysis before enacting travel restrictions and other countries are required to inform WHO about any travel measures taken.

“Countries will be asked to provide public health justification for any travel or trade measures that are not scientifically based, such as refusal of entry of suspect cases or unaffected persons to affected areas,” Mr. Jasarevic said in an interview.

As far as resources, the PHEIC mechanism is not a fundraising mechanism, but some donors might consider a PHEIC declaration as a trigger for releasing additional funding to respond to the health threat, he said.

Allison T. Chamberlain, PhD, acting director for the Emory Center for Public Health Preparedness and Research at the Emory Rollins School of Public Health in Atlanta, said national governments and nongovernmental aid organizations are among the most affected by a PHEIC because they are looked at to provide assistance to the most heavily affected areas and to bolster public health preparedness within their own borders.

“In terms of resources that are deployed, a Public Health Emergency of International Concern raises levels of international support and commitment to stopping the emergency,” Dr. Chamberlain said in an interview. “By doing so, it gives countries the needed flexibility to release financial resources of their own accord to support things like response teams that might go into heavily affected areas to assist, for instance.”

WHO Director-General Dr. Tedros Adhanom Ghebreyesus stressed that cooperation among countries is key during the PHEIC.

“We can only stop it together,” he said during the press conference. “This is the time for facts, not fear. This is the time for science, not rumors. This is the time for solidarity, not stigma.”

This is the sixth PHEIC declared by WHO in the last 10 years. Such declarations were made for the 2009 H1NI influenza pandemic, the 2014 polio resurgence, the 2014 Ebola outbreak in West Africa, the 2016 Zika virus, and the 2019 Kivu Ebola outbreak in the Democratic Republic of Congo.

[email protected]

Amid the rising spread of the 2019 Novel Coronavirus (2019-nCoV), the World Health Organization (WHO) has declared the virus outbreak a public health emergency of international concern (PHEIC).

WHO.int

The declaration was made during a press briefing on Jan. 30 after a week of growing concern and pressure on WHO to designate the virus at a higher emergency level. WHO’s Emergency Committee made the nearly unanimous decision after considering the increasing number of coronavirus cases in China, the rising infections outside of China, and the questionable measures some countries are taking regarding travel, said committee chair Didier Houssin, MD, said during the press conference.

As of Jan. 30, there were 8,236 confirmed cases of the coronavirus in China and 171 deaths, with another 112 cases identified outside of China in 21 other countries.

“Declaring a Public Health Emergency of International Concern is likely to facilitate [WHO’s] leadership role for public health measures, holding countries to account concerning additional measures they may take regarding travel, trade, quarantine or screening, research efforts, global coordination and anticipation of economic impact [and] support to vulnerable states,” Dr. Houssin said during the press conference. “Declaring a PHEIC should certainly not be seen as manifestation of distrust in the Chinese authorities and people which are doing tremendous efforts on the frontlines of this outbreak, with transparency, and let us hope, with success.”
 

What happens next?

Once a PHEIC is declared, WHO launches a series of steps, including the release of temporary recommendations for the affected country on health measures to implement and guidance for other countries on preventing and reducing the international spread of the disease, WHO spokesman Tarik Jasarevic said in an interview.

“The purpose of declaring a PHEIC is to advise the world on what measures need to be taken to enhance global health security by preventing international transmission of an infectious hazard,” he said.

Following the Jan. 30 press conference, WHO released temporary guidance for China and for other countries regarding identifying, managing, containing, and preventing the virus. China is advised to continue updating the population about the outbreak, continue enhancing its public health measures for containment and surveillance of cases, and to continue collaboration with WHO and other partners to investigate the epidemiology and evolution of the outbreak and share data on all human cases.

Other countries should be prepared for containment, including the active surveillance, early detection, isolation, case management, and prevention of virus transmission and to share full data with WHO, according to the recommendations.

Under the International Health Regulations (IHR), countries are required to share information and data with WHO. Additionally, WHO leaders advised the global community to support low- and middle-income countries with their response to the coronavirus and to facilitate diagnostics, potential vaccines, and therapeutics in these areas.

The IHR requires that countries implementing health measures that go beyond what WHO recommends must send to WHO the public health rationale and justification within 48 hours of their implementation for WHO review, Mr. Jasarevic noted.

“WHO is obliged to share the information about measures and the justification received with other countries involved,” he said.
 

PHEIC travel and resource impact

Declaration of a PHEIC means WHO will now oversee any travel restrictions made by other countries in response to 2019-nCoV. The agency recommends that countries conduct a risk and cost-benefit analysis before enacting travel restrictions and other countries are required to inform WHO about any travel measures taken.

“Countries will be asked to provide public health justification for any travel or trade measures that are not scientifically based, such as refusal of entry of suspect cases or unaffected persons to affected areas,” Mr. Jasarevic said in an interview.

As far as resources, the PHEIC mechanism is not a fundraising mechanism, but some donors might consider a PHEIC declaration as a trigger for releasing additional funding to respond to the health threat, he said.

Allison T. Chamberlain, PhD, acting director for the Emory Center for Public Health Preparedness and Research at the Emory Rollins School of Public Health in Atlanta, said national governments and nongovernmental aid organizations are among the most affected by a PHEIC because they are looked at to provide assistance to the most heavily affected areas and to bolster public health preparedness within their own borders.

“In terms of resources that are deployed, a Public Health Emergency of International Concern raises levels of international support and commitment to stopping the emergency,” Dr. Chamberlain said in an interview. “By doing so, it gives countries the needed flexibility to release financial resources of their own accord to support things like response teams that might go into heavily affected areas to assist, for instance.”

WHO Director-General Dr. Tedros Adhanom Ghebreyesus stressed that cooperation among countries is key during the PHEIC.

“We can only stop it together,” he said during the press conference. “This is the time for facts, not fear. This is the time for science, not rumors. This is the time for solidarity, not stigma.”

This is the sixth PHEIC declared by WHO in the last 10 years. Such declarations were made for the 2009 H1NI influenza pandemic, the 2014 polio resurgence, the 2014 Ebola outbreak in West Africa, the 2016 Zika virus, and the 2019 Kivu Ebola outbreak in the Democratic Republic of Congo.

[email protected]

Amid the rising spread of the 2019 Novel Coronavirus (2019-nCoV), the World Health Organization (WHO) has declared the virus outbreak a public health emergency of international concern (PHEIC).

WHO.int

The declaration was made during a press briefing on Jan. 30 after a week of growing concern and pressure on WHO to designate the virus at a higher emergency level. WHO’s Emergency Committee made the nearly unanimous decision after considering the increasing number of coronavirus cases in China, the rising infections outside of China, and the questionable measures some countries are taking regarding travel, said committee chair Didier Houssin, MD, said during the press conference.

As of Jan. 30, there were 8,236 confirmed cases of the coronavirus in China and 171 deaths, with another 112 cases identified outside of China in 21 other countries.

“Declaring a Public Health Emergency of International Concern is likely to facilitate [WHO’s] leadership role for public health measures, holding countries to account concerning additional measures they may take regarding travel, trade, quarantine or screening, research efforts, global coordination and anticipation of economic impact [and] support to vulnerable states,” Dr. Houssin said during the press conference. “Declaring a PHEIC should certainly not be seen as manifestation of distrust in the Chinese authorities and people which are doing tremendous efforts on the frontlines of this outbreak, with transparency, and let us hope, with success.”
 

What happens next?

Once a PHEIC is declared, WHO launches a series of steps, including the release of temporary recommendations for the affected country on health measures to implement and guidance for other countries on preventing and reducing the international spread of the disease, WHO spokesman Tarik Jasarevic said in an interview.

“The purpose of declaring a PHEIC is to advise the world on what measures need to be taken to enhance global health security by preventing international transmission of an infectious hazard,” he said.

Following the Jan. 30 press conference, WHO released temporary guidance for China and for other countries regarding identifying, managing, containing, and preventing the virus. China is advised to continue updating the population about the outbreak, continue enhancing its public health measures for containment and surveillance of cases, and to continue collaboration with WHO and other partners to investigate the epidemiology and evolution of the outbreak and share data on all human cases.

Other countries should be prepared for containment, including the active surveillance, early detection, isolation, case management, and prevention of virus transmission and to share full data with WHO, according to the recommendations.

Under the International Health Regulations (IHR), countries are required to share information and data with WHO. Additionally, WHO leaders advised the global community to support low- and middle-income countries with their response to the coronavirus and to facilitate diagnostics, potential vaccines, and therapeutics in these areas.

The IHR requires that countries implementing health measures that go beyond what WHO recommends must send to WHO the public health rationale and justification within 48 hours of their implementation for WHO review, Mr. Jasarevic noted.

“WHO is obliged to share the information about measures and the justification received with other countries involved,” he said.
 

PHEIC travel and resource impact

Declaration of a PHEIC means WHO will now oversee any travel restrictions made by other countries in response to 2019-nCoV. The agency recommends that countries conduct a risk and cost-benefit analysis before enacting travel restrictions and other countries are required to inform WHO about any travel measures taken.

“Countries will be asked to provide public health justification for any travel or trade measures that are not scientifically based, such as refusal of entry of suspect cases or unaffected persons to affected areas,” Mr. Jasarevic said in an interview.

As far as resources, the PHEIC mechanism is not a fundraising mechanism, but some donors might consider a PHEIC declaration as a trigger for releasing additional funding to respond to the health threat, he said.

Allison T. Chamberlain, PhD, acting director for the Emory Center for Public Health Preparedness and Research at the Emory Rollins School of Public Health in Atlanta, said national governments and nongovernmental aid organizations are among the most affected by a PHEIC because they are looked at to provide assistance to the most heavily affected areas and to bolster public health preparedness within their own borders.

“In terms of resources that are deployed, a Public Health Emergency of International Concern raises levels of international support and commitment to stopping the emergency,” Dr. Chamberlain said in an interview. “By doing so, it gives countries the needed flexibility to release financial resources of their own accord to support things like response teams that might go into heavily affected areas to assist, for instance.”

WHO Director-General Dr. Tedros Adhanom Ghebreyesus stressed that cooperation among countries is key during the PHEIC.

“We can only stop it together,” he said during the press conference. “This is the time for facts, not fear. This is the time for science, not rumors. This is the time for solidarity, not stigma.”

This is the sixth PHEIC declared by WHO in the last 10 years. Such declarations were made for the 2009 H1NI influenza pandemic, the 2014 polio resurgence, the 2014 Ebola outbreak in West Africa, the 2016 Zika virus, and the 2019 Kivu Ebola outbreak in the Democratic Republic of Congo.

[email protected]

The 2019 Novel Coronavirus (2019-nCoV) outbreak has unfolded so rapidly that many clinicians are scrambling to stay on top of it. Here are the answers to some frequently asked questions about how to prepare your clinic to respond to this outbreak.

Keep in mind that the outbreak is moving rapidly. Though scientific and epidemiologic knowledge has increased at unprecedented speed, there is much we don’t know, and some of what we think we know will change. Follow the links for the most up-to-date information.

What should our clinic do first?

Plan ahead with the following:

• Develop a plan for office staff to take travel histories from anyone with a respiratory illness and provide training for those who need it. Travel history at present should include asking about travel to China in the past 14 days, specifically Wuhan city or Hubei province.
• Review up-to-date infection control practices with all office staff and provide training for those who need it.
• Take an inventory of supplies of personal protective equipment (PPE), such as gowns, gloves, masks, eye protection, and N95 respirators or powered air-purifying respirators (PAPRs), and order items that are missing or low in stock.
• Fit-test users of N95 masks for maximal effectiveness.
• Plan where a potential patient would be isolated while obtaining expert advice.
• Know whom to contact at the state or local health department if you have a patient with the appropriate travel history.

The Centers for Disease Control and Prevention has prepared a toolkit to help frontline health care professionals prepare for this virus. Providers need to stay up to date on the latest recommendations, as the situation is changing rapidly.

When should I suspect 2019-nCoV illness, and what should I do?

Take the following steps to assess the concern and respond:

• If a patient with respiratory illness has traveled to China in the past 14 days, immediately put a mask on the patient and move the individual to a private room. Use a negative-pressure room if available.
• Put on appropriate PPE (including gloves, gown, eye protection, and mask) for contact, droplet, and airborne precautions. CDC recommends an N95 respirator mask if available, although we don’t know yet if there is true airborne spread.
• Obtain an accurate travel history, including dates and cities. (Tip: Get the correct spelling, as the English spelling of cities in China can cause confusion.)
• If the patient meets the current CDC definition of “person under investigation” or PUI, or if you need guidance on how to proceed, notify infection control (if you are in a facility that has it) and call your state or local health department immediately.
• Contact public health authorities who can help decide whether the patient should be admitted to airborne isolation or monitored at home with appropriate precautions.

What is the definition of a PUI?

The current definition of a PUI is a person who has fever and symptoms of a respiratory infection (cough, shortness of breath) AND who has EITHER been in Wuhan city or Hubei province in the past 14 days OR had close contact with a person either under investigation for 2019-nCoV infection or with confirmed infection. The definition of a PUI will change over time, so check this link.

How can I test for 2019-nCoV?

As of Jan. 30, 2020, testing is by polymerase chain reaction (PCR) and is available in the United States only through the CDC in Atlanta. Testing should soon be available in state health department laboratories. If public health authorities decide that your patient should be tested, they will instruct you on which samples to obtain.

The full sequence of 2019-nCoV has been shared, so some reference laboratories may develop and validate tests, ideally with assistance from CDC. If testing becomes available, make certain that it is a reputable lab that has carefully validated the test.

Should I test for other viruses?

Because the symptoms of 2019-nCoV infection overlap with those of influenza and other respiratory viruses, PCR testing for other viruses should be considered if it will change management (i.e., change the decision to provide influenza antivirals). Use appropriate PPE while collecting specimens, including eye protection. If 2019-nCoV is a consideration, you may want to send the specimen to a hospital lab for testing, where the sample will be processed under a biosafety hood, rather than doing point-of-care testing in the office.

How dangerous is 2019-nCoV?

The current estimated mortality rate is 2%-3%. That is probably an overestimate, as those with severe disease and those who die are more likely to be tested and reported early in an epidemic.

Our current knowledge is based on preliminary reports from hospitalized patients and will probably change. From the speed of spread and a single family cluster, it seems likely that there are milder cases and perhaps asymptomatic infection.

What else do I need to know about coronaviruses?

Coronaviruses are a large and diverse group of viruses, many of which are animal viruses. Before the discovery of the 2019-nCoV, six coronaviruses were known to infect humans. Four of these (HKU1, NL63, OC43, and 229E) predominantly caused mild to moderate upper respiratory illness, and they are thought to be responsible for 10%-30% of colds. They occasionally cause viral pneumonia and can be detected by some commercial multiplex panels.

Two other coronaviruses have caused outbreaks of severe respiratory illness in people: SARS, which emerged in Southern China in 2002, and MERS in the Middle East, in 2012. Unlike SARS, sporadic cases of MERS continue to occur.

The current outbreak is caused by 2019-nCoV, a previously unknown beta coronavirus. It is most closely related (~96%) to a bat virus and shares about 80% sequence homology with SARS CoV.

Andrew T. Pavia, MD, is the George and Esther Gross Presidential Professor and chief of the division of pediatric infectious disease in the department of pediatrics at the University of Utah, Salt Lake City. He is also director of hospital epidemiology and associate director of antimicrobial stewardship at Primary Children’s Hospital, Salt Lake City. Dr. Pavia has disclosed that he has served as a consultant for Genentech, Merck, and Seqirus and that he has served as associate editor for The Sanford Guide.

This article first appeared on Medscape.com.

The 2019 Novel Coronavirus (2019-nCoV) outbreak has unfolded so rapidly that many clinicians are scrambling to stay on top of it. Here are the answers to some frequently asked questions about how to prepare your clinic to respond to this outbreak.

Keep in mind that the outbreak is moving rapidly. Though scientific and epidemiologic knowledge has increased at unprecedented speed, there is much we don’t know, and some of what we think we know will change. Follow the links for the most up-to-date information.

What should our clinic do first?

Plan ahead with the following:

• Develop a plan for office staff to take travel histories from anyone with a respiratory illness and provide training for those who need it. Travel history at present should include asking about travel to China in the past 14 days, specifically Wuhan city or Hubei province.
• Review up-to-date infection control practices with all office staff and provide training for those who need it.
• Take an inventory of supplies of personal protective equipment (PPE), such as gowns, gloves, masks, eye protection, and N95 respirators or powered air-purifying respirators (PAPRs), and order items that are missing or low in stock.
• Fit-test users of N95 masks for maximal effectiveness.
• Plan where a potential patient would be isolated while obtaining expert advice.
• Know whom to contact at the state or local health department if you have a patient with the appropriate travel history.

The Centers for Disease Control and Prevention has prepared a toolkit to help frontline health care professionals prepare for this virus. Providers need to stay up to date on the latest recommendations, as the situation is changing rapidly.

When should I suspect 2019-nCoV illness, and what should I do?

Take the following steps to assess the concern and respond:

• If a patient with respiratory illness has traveled to China in the past 14 days, immediately put a mask on the patient and move the individual to a private room. Use a negative-pressure room if available.
• Put on appropriate PPE (including gloves, gown, eye protection, and mask) for contact, droplet, and airborne precautions. CDC recommends an N95 respirator mask if available, although we don’t know yet if there is true airborne spread.
• Obtain an accurate travel history, including dates and cities. (Tip: Get the correct spelling, as the English spelling of cities in China can cause confusion.)
• If the patient meets the current CDC definition of “person under investigation” or PUI, or if you need guidance on how to proceed, notify infection control (if you are in a facility that has it) and call your state or local health department immediately.
• Contact public health authorities who can help decide whether the patient should be admitted to airborne isolation or monitored at home with appropriate precautions.

What is the definition of a PUI?

The current definition of a PUI is a person who has fever and symptoms of a respiratory infection (cough, shortness of breath) AND who has EITHER been in Wuhan city or Hubei province in the past 14 days OR had close contact with a person either under investigation for 2019-nCoV infection or with confirmed infection. The definition of a PUI will change over time, so check this link.

How can I test for 2019-nCoV?

As of Jan. 30, 2020, testing is by polymerase chain reaction (PCR) and is available in the United States only through the CDC in Atlanta. Testing should soon be available in state health department laboratories. If public health authorities decide that your patient should be tested, they will instruct you on which samples to obtain.

The full sequence of 2019-nCoV has been shared, so some reference laboratories may develop and validate tests, ideally with assistance from CDC. If testing becomes available, make certain that it is a reputable lab that has carefully validated the test.

Should I test for other viruses?

Because the symptoms of 2019-nCoV infection overlap with those of influenza and other respiratory viruses, PCR testing for other viruses should be considered if it will change management (i.e., change the decision to provide influenza antivirals). Use appropriate PPE while collecting specimens, including eye protection. If 2019-nCoV is a consideration, you may want to send the specimen to a hospital lab for testing, where the sample will be processed under a biosafety hood, rather than doing point-of-care testing in the office.

How dangerous is 2019-nCoV?

The current estimated mortality rate is 2%-3%. That is probably an overestimate, as those with severe disease and those who die are more likely to be tested and reported early in an epidemic.

Our current knowledge is based on preliminary reports from hospitalized patients and will probably change. From the speed of spread and a single family cluster, it seems likely that there are milder cases and perhaps asymptomatic infection.

What else do I need to know about coronaviruses?

Coronaviruses are a large and diverse group of viruses, many of which are animal viruses. Before the discovery of the 2019-nCoV, six coronaviruses were known to infect humans. Four of these (HKU1, NL63, OC43, and 229E) predominantly caused mild to moderate upper respiratory illness, and they are thought to be responsible for 10%-30% of colds. They occasionally cause viral pneumonia and can be detected by some commercial multiplex panels.

Two other coronaviruses have caused outbreaks of severe respiratory illness in people: SARS, which emerged in Southern China in 2002, and MERS in the Middle East, in 2012. Unlike SARS, sporadic cases of MERS continue to occur.

The current outbreak is caused by 2019-nCoV, a previously unknown beta coronavirus. It is most closely related (~96%) to a bat virus and shares about 80% sequence homology with SARS CoV.

Andrew T. Pavia, MD, is the George and Esther Gross Presidential Professor and chief of the division of pediatric infectious disease in the department of pediatrics at the University of Utah, Salt Lake City. He is also director of hospital epidemiology and associate director of antimicrobial stewardship at Primary Children’s Hospital, Salt Lake City. Dr. Pavia has disclosed that he has served as a consultant for Genentech, Merck, and Seqirus and that he has served as associate editor for The Sanford Guide.

This article first appeared on Medscape.com.

The 2019 Novel Coronavirus (2019-nCoV) outbreak has unfolded so rapidly that many clinicians are scrambling to stay on top of it. Here are the answers to some frequently asked questions about how to prepare your clinic to respond to this outbreak.

Keep in mind that the outbreak is moving rapidly. Though scientific and epidemiologic knowledge has increased at unprecedented speed, there is much we don’t know, and some of what we think we know will change. Follow the links for the most up-to-date information.

What should our clinic do first?

Plan ahead with the following:

• Develop a plan for office staff to take travel histories from anyone with a respiratory illness and provide training for those who need it. Travel history at present should include asking about travel to China in the past 14 days, specifically Wuhan city or Hubei province.
• Review up-to-date infection control practices with all office staff and provide training for those who need it.
• Take an inventory of supplies of personal protective equipment (PPE), such as gowns, gloves, masks, eye protection, and N95 respirators or powered air-purifying respirators (PAPRs), and order items that are missing or low in stock.
• Fit-test users of N95 masks for maximal effectiveness.
• Plan where a potential patient would be isolated while obtaining expert advice.
• Know whom to contact at the state or local health department if you have a patient with the appropriate travel history.

The Centers for Disease Control and Prevention has prepared a toolkit to help frontline health care professionals prepare for this virus. Providers need to stay up to date on the latest recommendations, as the situation is changing rapidly.

When should I suspect 2019-nCoV illness, and what should I do?

Take the following steps to assess the concern and respond:

• If a patient with respiratory illness has traveled to China in the past 14 days, immediately put a mask on the patient and move the individual to a private room. Use a negative-pressure room if available.
• Put on appropriate PPE (including gloves, gown, eye protection, and mask) for contact, droplet, and airborne precautions. CDC recommends an N95 respirator mask if available, although we don’t know yet if there is true airborne spread.
• Obtain an accurate travel history, including dates and cities. (Tip: Get the correct spelling, as the English spelling of cities in China can cause confusion.)
• If the patient meets the current CDC definition of “person under investigation” or PUI, or if you need guidance on how to proceed, notify infection control (if you are in a facility that has it) and call your state or local health department immediately.
• Contact public health authorities who can help decide whether the patient should be admitted to airborne isolation or monitored at home with appropriate precautions.

What is the definition of a PUI?

The current definition of a PUI is a person who has fever and symptoms of a respiratory infection (cough, shortness of breath) AND who has EITHER been in Wuhan city or Hubei province in the past 14 days OR had close contact with a person either under investigation for 2019-nCoV infection or with confirmed infection. The definition of a PUI will change over time, so check this link.

How can I test for 2019-nCoV?

As of Jan. 30, 2020, testing is by polymerase chain reaction (PCR) and is available in the United States only through the CDC in Atlanta. Testing should soon be available in state health department laboratories. If public health authorities decide that your patient should be tested, they will instruct you on which samples to obtain.

The full sequence of 2019-nCoV has been shared, so some reference laboratories may develop and validate tests, ideally with assistance from CDC. If testing becomes available, make certain that it is a reputable lab that has carefully validated the test.

Should I test for other viruses?

Because the symptoms of 2019-nCoV infection overlap with those of influenza and other respiratory viruses, PCR testing for other viruses should be considered if it will change management (i.e., change the decision to provide influenza antivirals). Use appropriate PPE while collecting specimens, including eye protection. If 2019-nCoV is a consideration, you may want to send the specimen to a hospital lab for testing, where the sample will be processed under a biosafety hood, rather than doing point-of-care testing in the office.

How dangerous is 2019-nCoV?

The current estimated mortality rate is 2%-3%. That is probably an overestimate, as those with severe disease and those who die are more likely to be tested and reported early in an epidemic.

Our current knowledge is based on preliminary reports from hospitalized patients and will probably change. From the speed of spread and a single family cluster, it seems likely that there are milder cases and perhaps asymptomatic infection.

What else do I need to know about coronaviruses?

Coronaviruses are a large and diverse group of viruses, many of which are animal viruses. Before the discovery of the 2019-nCoV, six coronaviruses were known to infect humans. Four of these (HKU1, NL63, OC43, and 229E) predominantly caused mild to moderate upper respiratory illness, and they are thought to be responsible for 10%-30% of colds. They occasionally cause viral pneumonia and can be detected by some commercial multiplex panels.

Two other coronaviruses have caused outbreaks of severe respiratory illness in people: SARS, which emerged in Southern China in 2002, and MERS in the Middle East, in 2012. Unlike SARS, sporadic cases of MERS continue to occur.

The current outbreak is caused by 2019-nCoV, a previously unknown beta coronavirus. It is most closely related (~96%) to a bat virus and shares about 80% sequence homology with SARS CoV.

Andrew T. Pavia, MD, is the George and Esther Gross Presidential Professor and chief of the division of pediatric infectious disease in the department of pediatrics at the University of Utah, Salt Lake City. He is also director of hospital epidemiology and associate director of antimicrobial stewardship at Primary Children’s Hospital, Salt Lake City. Dr. Pavia has disclosed that he has served as a consultant for Genentech, Merck, and Seqirus and that he has served as associate editor for The Sanford Guide.

This article first appeared on Medscape.com.

A Chicago woman in her 60s who tested positive for the 2019 Novel Coronavirus (2019-nCoV) after returning from Wuhan, China, earlier this month has infected her husband, becoming the first known instance of person-to-person transmission of the 2019-nCoV in the United States.

James Gathany/Centers for Disease Control and Prevention

“Limited person-to-person spread of this new virus outside of China has already been seen in nine close contacts, where travelers were infected and transmitted the virus to someone else,” Robert R. Redfield, MD, director of the Centers for Disease Control and Prevention, said during a press briefing on Jan. 30, 2020. “However, the full picture of how easy and how sustainable this virus can spread is unclear. Today’s news underscores the important risk-dependent exposure. The vast majority of Americans have not had recent travel to China, where sustained human-to-human transmission is occurring. Individuals who are close personal contacts of cases, though, could have a risk.”

The affected man, also in his 60s, is the spouse of the first confirmed travel-associated case of 2019-nCoV to be reported in the state of Illinois, according to Ngozi O. Ezike, MD, director of the Illinois Department of Public Health. The man had no history of recent travel to China. “This person-to-person spread was between two very close contacts: a wife and husband,” said Dr. Ezike, who added that 21 individuals in the state are under investigation for 2019-nCoV. “The virus is not spreading widely across the community. At this time, we are not recommending that people in the general public take additional precautions such as canceling activities or avoiding going out. While there is concern with this second case, public health officials are actively monitoring close contacts, including health care workers, and we believe that people in Illinois are at low risk.”

Jennifer Layden, MD, state epidemiologist at the Illinois Department of Public Health, said that the infected Chicago woman returned from Wuhan, China on Jan. 13, 2020. She is hospitalized in stable condition “and continues to do well,” Dr. Layden said. “Public health officials have been actively and closely monitoring individuals who had contacts with her, including her husband, who had close contact for symptoms. He recently began reporting symptoms and was immediately admitted to the hospital and placed in an isolation room, where he is in stable condition. We are actively monitoring individuals such as health care workers, household contacts, and others who were in contact with either of the confirmed cases in the goal to contain and reduce the risk of additional transmission.”

Nancy Messonnier, MD, director, National Center for Immunization and Respiratory Diseases, expects that more cases of 2019-nCoV will transpire in the United States.

“More cases means the potential for more person-to-person spread,” Dr. Messonnier said. “We’re trying to strike a balance in our response right now. We want to be aggressive, but we want our actions to be evidence-based and appropriate for the current circumstance. For example, CDC does not currently recommend use of face masks for the general public. The virus is not spreading in the general community.”

[email protected]

A Chicago woman in her 60s who tested positive for the 2019 Novel Coronavirus (2019-nCoV) after returning from Wuhan, China, earlier this month has infected her husband, becoming the first known instance of person-to-person transmission of the 2019-nCoV in the United States.

James Gathany/Centers for Disease Control and Prevention

“Limited person-to-person spread of this new virus outside of China has already been seen in nine close contacts, where travelers were infected and transmitted the virus to someone else,” Robert R. Redfield, MD, director of the Centers for Disease Control and Prevention, said during a press briefing on Jan. 30, 2020. “However, the full picture of how easy and how sustainable this virus can spread is unclear. Today’s news underscores the important risk-dependent exposure. The vast majority of Americans have not had recent travel to China, where sustained human-to-human transmission is occurring. Individuals who are close personal contacts of cases, though, could have a risk.”

The affected man, also in his 60s, is the spouse of the first confirmed travel-associated case of 2019-nCoV to be reported in the state of Illinois, according to Ngozi O. Ezike, MD, director of the Illinois Department of Public Health. The man had no history of recent travel to China. “This person-to-person spread was between two very close contacts: a wife and husband,” said Dr. Ezike, who added that 21 individuals in the state are under investigation for 2019-nCoV. “The virus is not spreading widely across the community. At this time, we are not recommending that people in the general public take additional precautions such as canceling activities or avoiding going out. While there is concern with this second case, public health officials are actively monitoring close contacts, including health care workers, and we believe that people in Illinois are at low risk.”

Jennifer Layden, MD, state epidemiologist at the Illinois Department of Public Health, said that the infected Chicago woman returned from Wuhan, China on Jan. 13, 2020. She is hospitalized in stable condition “and continues to do well,” Dr. Layden said. “Public health officials have been actively and closely monitoring individuals who had contacts with her, including her husband, who had close contact for symptoms. He recently began reporting symptoms and was immediately admitted to the hospital and placed in an isolation room, where he is in stable condition. We are actively monitoring individuals such as health care workers, household contacts, and others who were in contact with either of the confirmed cases in the goal to contain and reduce the risk of additional transmission.”

Nancy Messonnier, MD, director, National Center for Immunization and Respiratory Diseases, expects that more cases of 2019-nCoV will transpire in the United States.

“More cases means the potential for more person-to-person spread,” Dr. Messonnier said. “We’re trying to strike a balance in our response right now. We want to be aggressive, but we want our actions to be evidence-based and appropriate for the current circumstance. For example, CDC does not currently recommend use of face masks for the general public. The virus is not spreading in the general community.”

[email protected]

A Chicago woman in her 60s who tested positive for the 2019 Novel Coronavirus (2019-nCoV) after returning from Wuhan, China, earlier this month has infected her husband, becoming the first known instance of person-to-person transmission of the 2019-nCoV in the United States.

James Gathany/Centers for Disease Control and Prevention

“Limited person-to-person spread of this new virus outside of China has already been seen in nine close contacts, where travelers were infected and transmitted the virus to someone else,” Robert R. Redfield, MD, director of the Centers for Disease Control and Prevention, said during a press briefing on Jan. 30, 2020. “However, the full picture of how easy and how sustainable this virus can spread is unclear. Today’s news underscores the important risk-dependent exposure. The vast majority of Americans have not had recent travel to China, where sustained human-to-human transmission is occurring. Individuals who are close personal contacts of cases, though, could have a risk.”

The affected man, also in his 60s, is the spouse of the first confirmed travel-associated case of 2019-nCoV to be reported in the state of Illinois, according to Ngozi O. Ezike, MD, director of the Illinois Department of Public Health. The man had no history of recent travel to China. “This person-to-person spread was between two very close contacts: a wife and husband,” said Dr. Ezike, who added that 21 individuals in the state are under investigation for 2019-nCoV. “The virus is not spreading widely across the community. At this time, we are not recommending that people in the general public take additional precautions such as canceling activities or avoiding going out. While there is concern with this second case, public health officials are actively monitoring close contacts, including health care workers, and we believe that people in Illinois are at low risk.”

Jennifer Layden, MD, state epidemiologist at the Illinois Department of Public Health, said that the infected Chicago woman returned from Wuhan, China on Jan. 13, 2020. She is hospitalized in stable condition “and continues to do well,” Dr. Layden said. “Public health officials have been actively and closely monitoring individuals who had contacts with her, including her husband, who had close contact for symptoms. He recently began reporting symptoms and was immediately admitted to the hospital and placed in an isolation room, where he is in stable condition. We are actively monitoring individuals such as health care workers, household contacts, and others who were in contact with either of the confirmed cases in the goal to contain and reduce the risk of additional transmission.”

Nancy Messonnier, MD, director, National Center for Immunization and Respiratory Diseases, expects that more cases of 2019-nCoV will transpire in the United States.

“More cases means the potential for more person-to-person spread,” Dr. Messonnier said. “We’re trying to strike a balance in our response right now. We want to be aggressive, but we want our actions to be evidence-based and appropriate for the current circumstance. For example, CDC does not currently recommend use of face masks for the general public. The virus is not spreading in the general community.”

[email protected]

England’s ban on smoking in cars carrying children led to a 72% relative reduction in the percentage of children self-reporting exposure to tobacco smoke in cars.

“Given children’s known vulnerability to secondhand smoke, reductions in exposure will probably result in improved health,” wrote Anthony A. Laverty, PhD, of Imperial College London and coauthors. Their findings were published in Thorax.

To determine the impact of a 2015 ban on smoking in cars carrying children in England and a 2016 ban in Scotland, the researchers analyzed survey data from 2012, 2014, and 2016 for each of the two countries. In England, children aged 13-15 years were asked, “In the past year, how often were you in a car with somebody smoking?” In Scotland, they were asked, “Are you regularly exposed to other people’s tobacco smoke in any of these places?” with cars/vehicles being one of the options.

Overall, 15,318 responses were received in England and 822 were received in Scotland. In England, self-reported regular exposure to smoke in cars was 6% in 2012, 6% in 2014 and 2% in 2016. In Scotland, it was 3% in 2012, 2% in 2014 and 1% in 2016. From 2014-2016 in England, implementation of the smoke-free policy was associated with a 4% absolute reduction – or a 72% relative reduction – in the percentage of children self-reporting exposure.

The authors acknowledged their study’s limitations, including exposure being based on self-reporting alone and the analyses using only three data points. “Future analyses with more data are recommended,” they wrote, “and may provide discrepant results.”

The study was funded by the National Institute for Health Research School for Public Health Research. One author was funded by the Medical Research Council on a clinician scientist fellowship. The others reported no potential conflicts of interest.

SOURCE: Laverty AA et al. Thorax. 2020 Jan 27. doi: 10.1136/thoraxjnl-2019-213998.

England’s ban on smoking in cars carrying children led to a 72% relative reduction in the percentage of children self-reporting exposure to tobacco smoke in cars.

“Given children’s known vulnerability to secondhand smoke, reductions in exposure will probably result in improved health,” wrote Anthony A. Laverty, PhD, of Imperial College London and coauthors. Their findings were published in Thorax.

To determine the impact of a 2015 ban on smoking in cars carrying children in England and a 2016 ban in Scotland, the researchers analyzed survey data from 2012, 2014, and 2016 for each of the two countries. In England, children aged 13-15 years were asked, “In the past year, how often were you in a car with somebody smoking?” In Scotland, they were asked, “Are you regularly exposed to other people’s tobacco smoke in any of these places?” with cars/vehicles being one of the options.

Overall, 15,318 responses were received in England and 822 were received in Scotland. In England, self-reported regular exposure to smoke in cars was 6% in 2012, 6% in 2014 and 2% in 2016. In Scotland, it was 3% in 2012, 2% in 2014 and 1% in 2016. From 2014-2016 in England, implementation of the smoke-free policy was associated with a 4% absolute reduction – or a 72% relative reduction – in the percentage of children self-reporting exposure.

The authors acknowledged their study’s limitations, including exposure being based on self-reporting alone and the analyses using only three data points. “Future analyses with more data are recommended,” they wrote, “and may provide discrepant results.”

The study was funded by the National Institute for Health Research School for Public Health Research. One author was funded by the Medical Research Council on a clinician scientist fellowship. The others reported no potential conflicts of interest.

SOURCE: Laverty AA et al. Thorax. 2020 Jan 27. doi: 10.1136/thoraxjnl-2019-213998.

England’s ban on smoking in cars carrying children led to a 72% relative reduction in the percentage of children self-reporting exposure to tobacco smoke in cars.

“Given children’s known vulnerability to secondhand smoke, reductions in exposure will probably result in improved health,” wrote Anthony A. Laverty, PhD, of Imperial College London and coauthors. Their findings were published in Thorax.

To determine the impact of a 2015 ban on smoking in cars carrying children in England and a 2016 ban in Scotland, the researchers analyzed survey data from 2012, 2014, and 2016 for each of the two countries. In England, children aged 13-15 years were asked, “In the past year, how often were you in a car with somebody smoking?” In Scotland, they were asked, “Are you regularly exposed to other people’s tobacco smoke in any of these places?” with cars/vehicles being one of the options.

Overall, 15,318 responses were received in England and 822 were received in Scotland. In England, self-reported regular exposure to smoke in cars was 6% in 2012, 6% in 2014 and 2% in 2016. In Scotland, it was 3% in 2012, 2% in 2014 and 1% in 2016. From 2014-2016 in England, implementation of the smoke-free policy was associated with a 4% absolute reduction – or a 72% relative reduction – in the percentage of children self-reporting exposure.

The authors acknowledged their study’s limitations, including exposure being based on self-reporting alone and the analyses using only three data points. “Future analyses with more data are recommended,” they wrote, “and may provide discrepant results.”

The study was funded by the National Institute for Health Research School for Public Health Research. One author was funded by the Medical Research Council on a clinician scientist fellowship. The others reported no potential conflicts of interest.

SOURCE: Laverty AA et al. Thorax. 2020 Jan 27. doi: 10.1136/thoraxjnl-2019-213998.

SNOWMASS, COLO. – The concept that silent myocardial ischemia is clinically detrimental has fallen by the wayside, and routine screening for this phenomenon can no longer be recommended, Patrick T. O’Gara, MD, said at the annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.

Bruce Jancin/MDedge News

What a difference a decade or 2 can make.

“Think about where we were 25 years ago, when we worried about people who had transient ST-segment depression without angina on Holter monitoring. We would wig out, chase them down the street, try to tackle them and load them up with medications and think about balloon [percutaneous transluminal coronary angioplasty]. And now we’re at the point where it doesn’t seem to help with respect to quality of life, let alone death or myocardial infarction,” observed Dr. O’Gara, director of clinical cardiology at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, both in Boston.

The end of the line for the now-discredited notion that silent ischemia carries clinical significance approaching that of ischemia plus angina pectoris was the landmark ISCHEMIA trial, reported in November 2019 at the annual scientific sessions of the American Heart Association. This randomized trial asked the question: Is there any high-risk subgroup of patients with stable ischemic heart disease not involving the left main coronary artery for whom a strategy of routine revascularization improves hard outcomes in the current era of highly effective, guideline-directed medical therapy?

The answer turned out to be no. At 5 years of follow-up of 5,179 randomized patients with baseline stable coronary artery disease (CAD) and rigorously determined baseline moderate or severe ischemia affecting more than 10% of the myocardium, there was no difference between patients randomized to routine revascularization plus optimal medical therapy versus those on optimal medical therapy alone in the primary combined outcome of cardiovascular death, MI, heart failure, cardiac arrest, or hospitalization for unstable angina.

Of note, 35% of participants in the ISCHEMIA trial had moderate or severe silent ischemia. Like those who had angina, they achieved no additional benefit from a strategy of routine revascularization in terms of the primary outcome. ISCHEMIA participants with angina did show significant and durable improvements in quality of life and angina control with routine revascularization; however, those with silent ischemia showed little or no such improvement with an invasive strategy.

That being said, Dr. O’Gara added that he supports the ISCHEMIA investigators’ efforts to obtain funding from the National Institutes of Health for another 5 years or so of follow-up in order to determine whether revascularization actually does lead to improvement in the hard outcomes.

“Remember, in the STICH trial it took 10 years to show superiority of CABG [coronary artery bypass surgery] versus medical therapy to treat ischemic cardiomyopathy [N Engl J Med 2016; 374:1511-20]. My own view is that it’s too premature to throw the baby out with the bathwater. I think shared decision making is still very important, and I think, for many of our patients, relief of angina and improved quality of life are legitimate reasons in a low-risk situation with a good interventionalist to proceed,” he said.

Dr. O’Gara traced the history of medical thinking about silent ischemia. The notion that silent ischemia carried a clinical significance comparable with ischemia with angina gained wide credence more than 30 years ago, when investigators from the National Institutes of Health–sponsored Coronary Artery Surgery Study registry reported: “Patients with either silent or symptomatic ischemia during exercise testing have a similar risk of developing an acute myocardial infarction or sudden death – except in the three-vessel CAD subgroup, where the risk is greater in silent ischemia” (Am J Cardiol. 1988 Dec 1;62[17]:1155-8).

“This was a very important observation and led to many, many recommendations about screening and making sure that you took the expression of ST-segment depression on exercise treadmill testing pretty seriously, even if your patient did not have angina,” Dr. O’Gara recalled.

The prevailing wisdom that silent ischemia was detrimental took a hit in the Detection of Ischemia in Asymptomatic Diabetics (DIAC) trial. DIAC was conducted at a time when it had become clear that type 2 diabetes was a condition associated with increased cardiovascular risk, and that various methods of imaging were more accurate than treadmill exercise testing for the detection of underlying CAD. But when 1,123 DIAC participants with type 2 diabetes were randomized to screening with adenosine-stress radionuclide myocardial perfusion imaging or not and prospectively followed for roughly 5 years, it turned out there was no between-group difference in cardiac death or MI (JAMA. 2009 Apr 15;301[15]:1547-55).

“This pretty much put the lid on going out of one’s way to do routine screening of this nature in persons with diabetes who were considered to be at higher than average risk for the development of coronary disease,” the cardiologist commented.

Another fissure in the idea that silent ischemia was worth searching for and treating came from CLARIFY, an observational international registry of more than 20,000 individuals with stable CAD, roughly 12% of whom had silent ischemia, a figure in line with the prevalence reported in other studies. The 2-year rate of cardiovascular death or MI in the group with silent ischemia didn’t differ from the rate in patients with neither angina nor provocable ischemia. In contrast, rates of cardiovascular death or MI were significantly higher in the groups with angina but no ischemia or angina with ischemia (JAMA Intern Med. 2014 Oct;174[10]:1651-9).

“There’s something about the expression of angina that’s a very key clinical marker,” Dr. O’Gara observed.

He noted that just a few months before the ISCHEMIA trial results were released, a report from the far-smaller, randomized second Medicine, Angioplasty, or Surgery Study “threw cold water” on the notion that stress-induced ischemia in patients with multivessel CAD is a bad thing. Over 10 years of follow-up, the risk of major adverse cardiovascular events or deterioration in left ventricular function was identical in patients with or without baseline ischemia on stress testing performed after percutaneous coronary intervention, CABG surgery, or initiation of medical therapy (JAMA Intern Med. 2019 Jul 22. doi: 10.1001/jamainternmed.2019.2227).
 

What the guidelines say

The 6-year-old U.S. guidelines on the diagnosis and management of patients with stable ischemic heart disease are clearly out of date on the topic of silent ischemia (Circulation. 2014 Nov 4;130[19]:1749-67). The recommendations are based on expert opinion formed prior to the massive amount of new evidence that has since become available. For example, the current guidelines state as a class IIa, level of evidence C recommendation that exercise or pharmacologic stress can be useful for follow-up assessment at 2-year or greater intervals in patients with stable ischemic heart disease with prior evidence of silent ischemia.

“This is a very weak recommendation. The class of recommendation says it would be reasonable, but in the absence of an evidence base and in light of newer information, I’m not sure that it approaches even a class IIa level of recommendation,” according to Dr. O’Gara.

The 2019 European Society of Cardiology guidelines on chronic coronary syndromes are similarly weak on silent ischemia. The European guidelines state that patients with diabetes or chronic kidney disease may have a higher burden of silent ischemia, might be at higher risk for atherosclerotic cardiovascular disease events, and that periodic ECGs and functional testing every 3-5 years might be considered.

“Obviously there’s a lot of leeway there in how you wish to interpret that,” Dr. O’Gara said. “And this did not rise to the level where they’d put it in the table of recommendations, but it’s simply included as part of the explanatory text.”
 

What’s coming next in stable ischemic heart disease

“Nowadays all the rage has to do with coronary microvascular dysfunction,” according to Dr. O’Gara. “I think all of the research interest currently is focused on the coronary microcirculation as perhaps the next frontier in our understanding of why it is that ischemia can occur in the absence of epicardial coronary disease.”

He highly recommended a review article entitled: “Reappraisal of Ischemic Heart Disease,” in which an international trio of prominent cardiologists asserted that coronary microvascular dysfunction not only plays a pivotal pathogenic role in angina pectoris, but also in a phenomenon known as microvascular angina – that is, angina in the absence of obstructive CAD. Microvascular angina may explain the roughly one-third of patients who experience acute coronary syndrome without epicardial coronary artery stenosis or thrombosis. The authors delved into the structural and functional mechanisms underlying coronary microvascular dysfunction, while noting that effective treatment of this common phenomenon remains a major unmet need (Circulation. 2018 Oct 2;138[14]:1463-80).

Dr. O’Gara reported receiving funding from the National Heart, Lung, and Blood Institute; from Medtronic in conjunction with the ongoing pivotal APOLLO transcatheter mitral valve replacement trial; from Edwards Lifesciences for the ongoing EARLY TAVR trial; and from Medtrace Pharma, a Danish company developing an innovative form of PET diagnostic imaging.

[email protected]

SNOWMASS, COLO. – The concept that silent myocardial ischemia is clinically detrimental has fallen by the wayside, and routine screening for this phenomenon can no longer be recommended, Patrick T. O’Gara, MD, said at the annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.

Bruce Jancin/MDedge News

What a difference a decade or 2 can make.

“Think about where we were 25 years ago, when we worried about people who had transient ST-segment depression without angina on Holter monitoring. We would wig out, chase them down the street, try to tackle them and load them up with medications and think about balloon [percutaneous transluminal coronary angioplasty]. And now we’re at the point where it doesn’t seem to help with respect to quality of life, let alone death or myocardial infarction,” observed Dr. O’Gara, director of clinical cardiology at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, both in Boston.

The end of the line for the now-discredited notion that silent ischemia carries clinical significance approaching that of ischemia plus angina pectoris was the landmark ISCHEMIA trial, reported in November 2019 at the annual scientific sessions of the American Heart Association. This randomized trial asked the question: Is there any high-risk subgroup of patients with stable ischemic heart disease not involving the left main coronary artery for whom a strategy of routine revascularization improves hard outcomes in the current era of highly effective, guideline-directed medical therapy?

The answer turned out to be no. At 5 years of follow-up of 5,179 randomized patients with baseline stable coronary artery disease (CAD) and rigorously determined baseline moderate or severe ischemia affecting more than 10% of the myocardium, there was no difference between patients randomized to routine revascularization plus optimal medical therapy versus those on optimal medical therapy alone in the primary combined outcome of cardiovascular death, MI, heart failure, cardiac arrest, or hospitalization for unstable angina.

Of note, 35% of participants in the ISCHEMIA trial had moderate or severe silent ischemia. Like those who had angina, they achieved no additional benefit from a strategy of routine revascularization in terms of the primary outcome. ISCHEMIA participants with angina did show significant and durable improvements in quality of life and angina control with routine revascularization; however, those with silent ischemia showed little or no such improvement with an invasive strategy.

That being said, Dr. O’Gara added that he supports the ISCHEMIA investigators’ efforts to obtain funding from the National Institutes of Health for another 5 years or so of follow-up in order to determine whether revascularization actually does lead to improvement in the hard outcomes.

“Remember, in the STICH trial it took 10 years to show superiority of CABG [coronary artery bypass surgery] versus medical therapy to treat ischemic cardiomyopathy [N Engl J Med 2016; 374:1511-20]. My own view is that it’s too premature to throw the baby out with the bathwater. I think shared decision making is still very important, and I think, for many of our patients, relief of angina and improved quality of life are legitimate reasons in a low-risk situation with a good interventionalist to proceed,” he said.

Dr. O’Gara traced the history of medical thinking about silent ischemia. The notion that silent ischemia carried a clinical significance comparable with ischemia with angina gained wide credence more than 30 years ago, when investigators from the National Institutes of Health–sponsored Coronary Artery Surgery Study registry reported: “Patients with either silent or symptomatic ischemia during exercise testing have a similar risk of developing an acute myocardial infarction or sudden death – except in the three-vessel CAD subgroup, where the risk is greater in silent ischemia” (Am J Cardiol. 1988 Dec 1;62[17]:1155-8).

“This was a very important observation and led to many, many recommendations about screening and making sure that you took the expression of ST-segment depression on exercise treadmill testing pretty seriously, even if your patient did not have angina,” Dr. O’Gara recalled.

The prevailing wisdom that silent ischemia was detrimental took a hit in the Detection of Ischemia in Asymptomatic Diabetics (DIAC) trial. DIAC was conducted at a time when it had become clear that type 2 diabetes was a condition associated with increased cardiovascular risk, and that various methods of imaging were more accurate than treadmill exercise testing for the detection of underlying CAD. But when 1,123 DIAC participants with type 2 diabetes were randomized to screening with adenosine-stress radionuclide myocardial perfusion imaging or not and prospectively followed for roughly 5 years, it turned out there was no between-group difference in cardiac death or MI (JAMA. 2009 Apr 15;301[15]:1547-55).

“This pretty much put the lid on going out of one’s way to do routine screening of this nature in persons with diabetes who were considered to be at higher than average risk for the development of coronary disease,” the cardiologist commented.

Another fissure in the idea that silent ischemia was worth searching for and treating came from CLARIFY, an observational international registry of more than 20,000 individuals with stable CAD, roughly 12% of whom had silent ischemia, a figure in line with the prevalence reported in other studies. The 2-year rate of cardiovascular death or MI in the group with silent ischemia didn’t differ from the rate in patients with neither angina nor provocable ischemia. In contrast, rates of cardiovascular death or MI were significantly higher in the groups with angina but no ischemia or angina with ischemia (JAMA Intern Med. 2014 Oct;174[10]:1651-9).

“There’s something about the expression of angina that’s a very key clinical marker,” Dr. O’Gara observed.

He noted that just a few months before the ISCHEMIA trial results were released, a report from the far-smaller, randomized second Medicine, Angioplasty, or Surgery Study “threw cold water” on the notion that stress-induced ischemia in patients with multivessel CAD is a bad thing. Over 10 years of follow-up, the risk of major adverse cardiovascular events or deterioration in left ventricular function was identical in patients with or without baseline ischemia on stress testing performed after percutaneous coronary intervention, CABG surgery, or initiation of medical therapy (JAMA Intern Med. 2019 Jul 22. doi: 10.1001/jamainternmed.2019.2227).
 

What the guidelines say

The 6-year-old U.S. guidelines on the diagnosis and management of patients with stable ischemic heart disease are clearly out of date on the topic of silent ischemia (Circulation. 2014 Nov 4;130[19]:1749-67). The recommendations are based on expert opinion formed prior to the massive amount of new evidence that has since become available. For example, the current guidelines state as a class IIa, level of evidence C recommendation that exercise or pharmacologic stress can be useful for follow-up assessment at 2-year or greater intervals in patients with stable ischemic heart disease with prior evidence of silent ischemia.

“This is a very weak recommendation. The class of recommendation says it would be reasonable, but in the absence of an evidence base and in light of newer information, I’m not sure that it approaches even a class IIa level of recommendation,” according to Dr. O’Gara.

The 2019 European Society of Cardiology guidelines on chronic coronary syndromes are similarly weak on silent ischemia. The European guidelines state that patients with diabetes or chronic kidney disease may have a higher burden of silent ischemia, might be at higher risk for atherosclerotic cardiovascular disease events, and that periodic ECGs and functional testing every 3-5 years might be considered.

“Obviously there’s a lot of leeway there in how you wish to interpret that,” Dr. O’Gara said. “And this did not rise to the level where they’d put it in the table of recommendations, but it’s simply included as part of the explanatory text.”
 

What’s coming next in stable ischemic heart disease

“Nowadays all the rage has to do with coronary microvascular dysfunction,” according to Dr. O’Gara. “I think all of the research interest currently is focused on the coronary microcirculation as perhaps the next frontier in our understanding of why it is that ischemia can occur in the absence of epicardial coronary disease.”

He highly recommended a review article entitled: “Reappraisal of Ischemic Heart Disease,” in which an international trio of prominent cardiologists asserted that coronary microvascular dysfunction not only plays a pivotal pathogenic role in angina pectoris, but also in a phenomenon known as microvascular angina – that is, angina in the absence of obstructive CAD. Microvascular angina may explain the roughly one-third of patients who experience acute coronary syndrome without epicardial coronary artery stenosis or thrombosis. The authors delved into the structural and functional mechanisms underlying coronary microvascular dysfunction, while noting that effective treatment of this common phenomenon remains a major unmet need (Circulation. 2018 Oct 2;138[14]:1463-80).

Dr. O’Gara reported receiving funding from the National Heart, Lung, and Blood Institute; from Medtronic in conjunction with the ongoing pivotal APOLLO transcatheter mitral valve replacement trial; from Edwards Lifesciences for the ongoing EARLY TAVR trial; and from Medtrace Pharma, a Danish company developing an innovative form of PET diagnostic imaging.

[email protected]

SNOWMASS, COLO. – The concept that silent myocardial ischemia is clinically detrimental has fallen by the wayside, and routine screening for this phenomenon can no longer be recommended, Patrick T. O’Gara, MD, said at the annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.

Bruce Jancin/MDedge News

What a difference a decade or 2 can make.

“Think about where we were 25 years ago, when we worried about people who had transient ST-segment depression without angina on Holter monitoring. We would wig out, chase them down the street, try to tackle them and load them up with medications and think about balloon [percutaneous transluminal coronary angioplasty]. And now we’re at the point where it doesn’t seem to help with respect to quality of life, let alone death or myocardial infarction,” observed Dr. O’Gara, director of clinical cardiology at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, both in Boston.

The end of the line for the now-discredited notion that silent ischemia carries clinical significance approaching that of ischemia plus angina pectoris was the landmark ISCHEMIA trial, reported in November 2019 at the annual scientific sessions of the American Heart Association. This randomized trial asked the question: Is there any high-risk subgroup of patients with stable ischemic heart disease not involving the left main coronary artery for whom a strategy of routine revascularization improves hard outcomes in the current era of highly effective, guideline-directed medical therapy?

The answer turned out to be no. At 5 years of follow-up of 5,179 randomized patients with baseline stable coronary artery disease (CAD) and rigorously determined baseline moderate or severe ischemia affecting more than 10% of the myocardium, there was no difference between patients randomized to routine revascularization plus optimal medical therapy versus those on optimal medical therapy alone in the primary combined outcome of cardiovascular death, MI, heart failure, cardiac arrest, or hospitalization for unstable angina.

Of note, 35% of participants in the ISCHEMIA trial had moderate or severe silent ischemia. Like those who had angina, they achieved no additional benefit from a strategy of routine revascularization in terms of the primary outcome. ISCHEMIA participants with angina did show significant and durable improvements in quality of life and angina control with routine revascularization; however, those with silent ischemia showed little or no such improvement with an invasive strategy.

That being said, Dr. O’Gara added that he supports the ISCHEMIA investigators’ efforts to obtain funding from the National Institutes of Health for another 5 years or so of follow-up in order to determine whether revascularization actually does lead to improvement in the hard outcomes.

“Remember, in the STICH trial it took 10 years to show superiority of CABG [coronary artery bypass surgery] versus medical therapy to treat ischemic cardiomyopathy [N Engl J Med 2016; 374:1511-20]. My own view is that it’s too premature to throw the baby out with the bathwater. I think shared decision making is still very important, and I think, for many of our patients, relief of angina and improved quality of life are legitimate reasons in a low-risk situation with a good interventionalist to proceed,” he said.

Dr. O’Gara traced the history of medical thinking about silent ischemia. The notion that silent ischemia carried a clinical significance comparable with ischemia with angina gained wide credence more than 30 years ago, when investigators from the National Institutes of Health–sponsored Coronary Artery Surgery Study registry reported: “Patients with either silent or symptomatic ischemia during exercise testing have a similar risk of developing an acute myocardial infarction or sudden death – except in the three-vessel CAD subgroup, where the risk is greater in silent ischemia” (Am J Cardiol. 1988 Dec 1;62[17]:1155-8).

“This was a very important observation and led to many, many recommendations about screening and making sure that you took the expression of ST-segment depression on exercise treadmill testing pretty seriously, even if your patient did not have angina,” Dr. O’Gara recalled.

The prevailing wisdom that silent ischemia was detrimental took a hit in the Detection of Ischemia in Asymptomatic Diabetics (DIAC) trial. DIAC was conducted at a time when it had become clear that type 2 diabetes was a condition associated with increased cardiovascular risk, and that various methods of imaging were more accurate than treadmill exercise testing for the detection of underlying CAD. But when 1,123 DIAC participants with type 2 diabetes were randomized to screening with adenosine-stress radionuclide myocardial perfusion imaging or not and prospectively followed for roughly 5 years, it turned out there was no between-group difference in cardiac death or MI (JAMA. 2009 Apr 15;301[15]:1547-55).

“This pretty much put the lid on going out of one’s way to do routine screening of this nature in persons with diabetes who were considered to be at higher than average risk for the development of coronary disease,” the cardiologist commented.

Another fissure in the idea that silent ischemia was worth searching for and treating came from CLARIFY, an observational international registry of more than 20,000 individuals with stable CAD, roughly 12% of whom had silent ischemia, a figure in line with the prevalence reported in other studies. The 2-year rate of cardiovascular death or MI in the group with silent ischemia didn’t differ from the rate in patients with neither angina nor provocable ischemia. In contrast, rates of cardiovascular death or MI were significantly higher in the groups with angina but no ischemia or angina with ischemia (JAMA Intern Med. 2014 Oct;174[10]:1651-9).

“There’s something about the expression of angina that’s a very key clinical marker,” Dr. O’Gara observed.

He noted that just a few months before the ISCHEMIA trial results were released, a report from the far-smaller, randomized second Medicine, Angioplasty, or Surgery Study “threw cold water” on the notion that stress-induced ischemia in patients with multivessel CAD is a bad thing. Over 10 years of follow-up, the risk of major adverse cardiovascular events or deterioration in left ventricular function was identical in patients with or without baseline ischemia on stress testing performed after percutaneous coronary intervention, CABG surgery, or initiation of medical therapy (JAMA Intern Med. 2019 Jul 22. doi: 10.1001/jamainternmed.2019.2227).
 

What the guidelines say

The 6-year-old U.S. guidelines on the diagnosis and management of patients with stable ischemic heart disease are clearly out of date on the topic of silent ischemia (Circulation. 2014 Nov 4;130[19]:1749-67). The recommendations are based on expert opinion formed prior to the massive amount of new evidence that has since become available. For example, the current guidelines state as a class IIa, level of evidence C recommendation that exercise or pharmacologic stress can be useful for follow-up assessment at 2-year or greater intervals in patients with stable ischemic heart disease with prior evidence of silent ischemia.

“This is a very weak recommendation. The class of recommendation says it would be reasonable, but in the absence of an evidence base and in light of newer information, I’m not sure that it approaches even a class IIa level of recommendation,” according to Dr. O’Gara.

The 2019 European Society of Cardiology guidelines on chronic coronary syndromes are similarly weak on silent ischemia. The European guidelines state that patients with diabetes or chronic kidney disease may have a higher burden of silent ischemia, might be at higher risk for atherosclerotic cardiovascular disease events, and that periodic ECGs and functional testing every 3-5 years might be considered.

“Obviously there’s a lot of leeway there in how you wish to interpret that,” Dr. O’Gara said. “And this did not rise to the level where they’d put it in the table of recommendations, but it’s simply included as part of the explanatory text.”
 

What’s coming next in stable ischemic heart disease

“Nowadays all the rage has to do with coronary microvascular dysfunction,” according to Dr. O’Gara. “I think all of the research interest currently is focused on the coronary microcirculation as perhaps the next frontier in our understanding of why it is that ischemia can occur in the absence of epicardial coronary disease.”

He highly recommended a review article entitled: “Reappraisal of Ischemic Heart Disease,” in which an international trio of prominent cardiologists asserted that coronary microvascular dysfunction not only plays a pivotal pathogenic role in angina pectoris, but also in a phenomenon known as microvascular angina – that is, angina in the absence of obstructive CAD. Microvascular angina may explain the roughly one-third of patients who experience acute coronary syndrome without epicardial coronary artery stenosis or thrombosis. The authors delved into the structural and functional mechanisms underlying coronary microvascular dysfunction, while noting that effective treatment of this common phenomenon remains a major unmet need (Circulation. 2018 Oct 2;138[14]:1463-80).

Dr. O’Gara reported receiving funding from the National Heart, Lung, and Blood Institute; from Medtronic in conjunction with the ongoing pivotal APOLLO transcatheter mitral valve replacement trial; from Edwards Lifesciences for the ongoing EARLY TAVR trial; and from Medtrace Pharma, a Danish company developing an innovative form of PET diagnostic imaging.

[email protected]

A total of 165 persons in the United States are under investigation for infection with the 2019 Novel Coronavirus (2019-nCoV), with 68 testing negative and only 5 confirming positive, according to data presented Jan. 29 during a Centers for Disease Control and Prevention (CDC) briefing. 

The remaining samples are in transit or are being processed at the CDC for testing, Nancy Messonnier, MD, director of the National Center for Immunization and Respiratory Diseases, said during the briefing.

“The genetic sequence for all five viruses detected in the United States to date has been uploaded to the CDC website,” she said. “We are working quickly through the process to get the CDC-developed test into the hands of public health partners in the U.S. and internationally.”

Dr. Messonnier reported that the CDC is expanding screening efforts to U.S. ports of entry that house CDC quarantine stations. Also, in collaboration with U.S. Customs and Border Protection, the agency is expanding distribution of travel health education materials to all travelers from China.

“The good news here is that, despite an aggressive public health investigation to find new cases [of 2019-nCoV], we have not,” she said. “The situation in China is concerning, however, we are looking hard here in the U.S. We will continue to be proactive. I still expect that we will find additional cases.”

In another development, the federal government facilitated the return of a plane full of U.S. citizens living in Wuhan, China, to March Air Reserve Force Base in Riverside County, Calif. “We have taken every precaution to ensure their safety while also continuing to protect the health of our nation and the people around them,” Dr. Messonnier said.

All 195 passengers have been screened, monitored, and evaluated by medical personnel “every step of the way,” including before takeoff, during the flight, during a refueling stop in Alaska, and again upon landing at March Air Reserve Force Base on Jan. 28. “All 195 patients are without the symptoms of the novel coronavirus, and all have been assigned living quarters at the Air Force base,” Dr. Messonnier said.

The CDC has launched a second stage of further screening and information gathering from the passengers, who will be offered testing as part of a thorough risk assessment.

“I understand that many people in the U.S. are worried about this virus and whether it will affect them,” Dr. Messonnier said. “Outbreaks like this are always concerning, particularly when a new virus is emerging. But we are well prepared and working closely with federal, state, and local partners to protect our communities and others nationwide from this public health threat. At this time, we continue to believe that the immediate health risk from this new virus to the general American public is low.”

[email protected]

A total of 165 persons in the United States are under investigation for infection with the 2019 Novel Coronavirus (2019-nCoV), with 68 testing negative and only 5 confirming positive, according to data presented Jan. 29 during a Centers for Disease Control and Prevention (CDC) briefing. 

The remaining samples are in transit or are being processed at the CDC for testing, Nancy Messonnier, MD, director of the National Center for Immunization and Respiratory Diseases, said during the briefing.

“The genetic sequence for all five viruses detected in the United States to date has been uploaded to the CDC website,” she said. “We are working quickly through the process to get the CDC-developed test into the hands of public health partners in the U.S. and internationally.”

Dr. Messonnier reported that the CDC is expanding screening efforts to U.S. ports of entry that house CDC quarantine stations. Also, in collaboration with U.S. Customs and Border Protection, the agency is expanding distribution of travel health education materials to all travelers from China.

“The good news here is that, despite an aggressive public health investigation to find new cases [of 2019-nCoV], we have not,” she said. “The situation in China is concerning, however, we are looking hard here in the U.S. We will continue to be proactive. I still expect that we will find additional cases.”

In another development, the federal government facilitated the return of a plane full of U.S. citizens living in Wuhan, China, to March Air Reserve Force Base in Riverside County, Calif. “We have taken every precaution to ensure their safety while also continuing to protect the health of our nation and the people around them,” Dr. Messonnier said.

All 195 passengers have been screened, monitored, and evaluated by medical personnel “every step of the way,” including before takeoff, during the flight, during a refueling stop in Alaska, and again upon landing at March Air Reserve Force Base on Jan. 28. “All 195 patients are without the symptoms of the novel coronavirus, and all have been assigned living quarters at the Air Force base,” Dr. Messonnier said.

The CDC has launched a second stage of further screening and information gathering from the passengers, who will be offered testing as part of a thorough risk assessment.

“I understand that many people in the U.S. are worried about this virus and whether it will affect them,” Dr. Messonnier said. “Outbreaks like this are always concerning, particularly when a new virus is emerging. But we are well prepared and working closely with federal, state, and local partners to protect our communities and others nationwide from this public health threat. At this time, we continue to believe that the immediate health risk from this new virus to the general American public is low.”

[email protected]

A total of 165 persons in the United States are under investigation for infection with the 2019 Novel Coronavirus (2019-nCoV), with 68 testing negative and only 5 confirming positive, according to data presented Jan. 29 during a Centers for Disease Control and Prevention (CDC) briefing. 

The remaining samples are in transit or are being processed at the CDC for testing, Nancy Messonnier, MD, director of the National Center for Immunization and Respiratory Diseases, said during the briefing.

“The genetic sequence for all five viruses detected in the United States to date has been uploaded to the CDC website,” she said. “We are working quickly through the process to get the CDC-developed test into the hands of public health partners in the U.S. and internationally.”

Dr. Messonnier reported that the CDC is expanding screening efforts to U.S. ports of entry that house CDC quarantine stations. Also, in collaboration with U.S. Customs and Border Protection, the agency is expanding distribution of travel health education materials to all travelers from China.

“The good news here is that, despite an aggressive public health investigation to find new cases [of 2019-nCoV], we have not,” she said. “The situation in China is concerning, however, we are looking hard here in the U.S. We will continue to be proactive. I still expect that we will find additional cases.”

In another development, the federal government facilitated the return of a plane full of U.S. citizens living in Wuhan, China, to March Air Reserve Force Base in Riverside County, Calif. “We have taken every precaution to ensure their safety while also continuing to protect the health of our nation and the people around them,” Dr. Messonnier said.

All 195 passengers have been screened, monitored, and evaluated by medical personnel “every step of the way,” including before takeoff, during the flight, during a refueling stop in Alaska, and again upon landing at March Air Reserve Force Base on Jan. 28. “All 195 patients are without the symptoms of the novel coronavirus, and all have been assigned living quarters at the Air Force base,” Dr. Messonnier said.

The CDC has launched a second stage of further screening and information gathering from the passengers, who will be offered testing as part of a thorough risk assessment.

“I understand that many people in the U.S. are worried about this virus and whether it will affect them,” Dr. Messonnier said. “Outbreaks like this are always concerning, particularly when a new virus is emerging. But we are well prepared and working closely with federal, state, and local partners to protect our communities and others nationwide from this public health threat. At this time, we continue to believe that the immediate health risk from this new virus to the general American public is low.”

[email protected]

The cost of health care is keeping more Americans from seeing a doctor, even as the number of individuals with insurance coverage increases, according to a new study.

“Despite short-term gains owing to the [Affordable Care Act], over the past 20 years the portion of adults aged 18-64 years unable to see a physician owing to the cost increased, mostly because of an increase among persons with insurance,” Laura Hawks, MD, of Cambridge (Mass.) Health Alliance and Harvard Medical School in Boston and colleagues wrote in a new research report published in JAMA Internal Medicine.

“In 2017, nearly one-fifth of individuals with any chronic condition (diabetes, obesity, or cardiovascular disease) said they were unable to see a physician owing to cost,” they continued.

Researchers examined 20 years of data (January 1998 through December 2017) from the Centers for Disease Control and Prevention’s Behavioral Risk Factor Surveillance System to identify trends in unmet need for physician and preventive services.

Among adults aged 18-64 years who responded to the survey in 1998 and 2017, uninsurance decreased by 2.1 percentage points, falling from 16.9% to 14.8%. But at the same time, the portion of adults who were unable to see a physician because of cost rose by 2.7 percentage points, from 11.4% to 15.7%. Looking specifically at adults who had insurance coverage, the researchers found that cost was a barrier for 11.5% of them in 2017, up from 7.1% in 1998.

These results come against a backdrop of growing medical costs, increasing deductibles and copayments, an increasing use of cost containment measures like prior authorization, and narrow provider networks in the wake of the transition to value-based payment structures, the authors noted.

“Our finding that financial access to physician care worsened is concerning,” Dr. Hawks and her colleagues wrote. “Persons with conditions such as diabetes, hypertension, cardiovascular disease, and poor health status risk substantial harms if they forgo physician care. Financial barriers to care have been associated with increased hospitalizations and worse health outcomes in patients with cardiovascular disease and hypertension and increased morbidity among patients with diabetes.”

One of the trends highlighted by the study authors is the growing number of employers offering plans with a high deductible.

“Enrollment in a high-deductible health plan, which has become increasingly common in the last decade, a trend uninterrupted by the ACA, is associated with forgoing needed care, especially among those of lower socioeconomic status,” the authors wrote. “Other changes in insurance benefit design, such as imposing tiered copayments and coinsurance obligations, eliminating coverage for some services (e.g., eyeglasses) and narrowing provider networks (which can force some patients to go out-of-network for care) may also have undermined the affordability of care.”

There was some positive news among the findings, however.

“The main encouraging finding from our analysis is the increase in the proportion of persons – both insured and uninsured – receiving cholesterol checks and flu shots,” Dr. Hawk and her colleagues wrote, adding that this increase “may be attributable to the increasing implementation of quality metrics, financial incentives, and improved systems for the delivery of these services.”

However, not all preventive services that had cost barriers eliminated under the ACA saw improvement, such as cancer screening. They note that the proportion of women who did not receive mammography increased during the study period and then plateaued, but did not improve following the implementation of the ACA. The authors described the reasons for this as “unclear.”

Dr. Hawks received funding support from an Institutional National Research Service award and from Cambridge Health Alliance, her employer. Other authors reported membership in Physicians for a National Health Program.

[email protected]

SOURCE: Hawks L et al. JAMA Intern Med. 2020 Jan 27. doi: 10.1001/jamainternmed.2019.6538.

The cost of health care is keeping more Americans from seeing a doctor, even as the number of individuals with insurance coverage increases, according to a new study.

“Despite short-term gains owing to the [Affordable Care Act], over the past 20 years the portion of adults aged 18-64 years unable to see a physician owing to the cost increased, mostly because of an increase among persons with insurance,” Laura Hawks, MD, of Cambridge (Mass.) Health Alliance and Harvard Medical School in Boston and colleagues wrote in a new research report published in JAMA Internal Medicine.

“In 2017, nearly one-fifth of individuals with any chronic condition (diabetes, obesity, or cardiovascular disease) said they were unable to see a physician owing to cost,” they continued.

Researchers examined 20 years of data (January 1998 through December 2017) from the Centers for Disease Control and Prevention’s Behavioral Risk Factor Surveillance System to identify trends in unmet need for physician and preventive services.

Among adults aged 18-64 years who responded to the survey in 1998 and 2017, uninsurance decreased by 2.1 percentage points, falling from 16.9% to 14.8%. But at the same time, the portion of adults who were unable to see a physician because of cost rose by 2.7 percentage points, from 11.4% to 15.7%. Looking specifically at adults who had insurance coverage, the researchers found that cost was a barrier for 11.5% of them in 2017, up from 7.1% in 1998.

These results come against a backdrop of growing medical costs, increasing deductibles and copayments, an increasing use of cost containment measures like prior authorization, and narrow provider networks in the wake of the transition to value-based payment structures, the authors noted.

“Our finding that financial access to physician care worsened is concerning,” Dr. Hawks and her colleagues wrote. “Persons with conditions such as diabetes, hypertension, cardiovascular disease, and poor health status risk substantial harms if they forgo physician care. Financial barriers to care have been associated with increased hospitalizations and worse health outcomes in patients with cardiovascular disease and hypertension and increased morbidity among patients with diabetes.”

One of the trends highlighted by the study authors is the growing number of employers offering plans with a high deductible.

“Enrollment in a high-deductible health plan, which has become increasingly common in the last decade, a trend uninterrupted by the ACA, is associated with forgoing needed care, especially among those of lower socioeconomic status,” the authors wrote. “Other changes in insurance benefit design, such as imposing tiered copayments and coinsurance obligations, eliminating coverage for some services (e.g., eyeglasses) and narrowing provider networks (which can force some patients to go out-of-network for care) may also have undermined the affordability of care.”

There was some positive news among the findings, however.

“The main encouraging finding from our analysis is the increase in the proportion of persons – both insured and uninsured – receiving cholesterol checks and flu shots,” Dr. Hawk and her colleagues wrote, adding that this increase “may be attributable to the increasing implementation of quality metrics, financial incentives, and improved systems for the delivery of these services.”

However, not all preventive services that had cost barriers eliminated under the ACA saw improvement, such as cancer screening. They note that the proportion of women who did not receive mammography increased during the study period and then plateaued, but did not improve following the implementation of the ACA. The authors described the reasons for this as “unclear.”

Dr. Hawks received funding support from an Institutional National Research Service award and from Cambridge Health Alliance, her employer. Other authors reported membership in Physicians for a National Health Program.

[email protected]

SOURCE: Hawks L et al. JAMA Intern Med. 2020 Jan 27. doi: 10.1001/jamainternmed.2019.6538.

The cost of health care is keeping more Americans from seeing a doctor, even as the number of individuals with insurance coverage increases, according to a new study.

“Despite short-term gains owing to the [Affordable Care Act], over the past 20 years the portion of adults aged 18-64 years unable to see a physician owing to the cost increased, mostly because of an increase among persons with insurance,” Laura Hawks, MD, of Cambridge (Mass.) Health Alliance and Harvard Medical School in Boston and colleagues wrote in a new research report published in JAMA Internal Medicine.

“In 2017, nearly one-fifth of individuals with any chronic condition (diabetes, obesity, or cardiovascular disease) said they were unable to see a physician owing to cost,” they continued.

Researchers examined 20 years of data (January 1998 through December 2017) from the Centers for Disease Control and Prevention’s Behavioral Risk Factor Surveillance System to identify trends in unmet need for physician and preventive services.

Among adults aged 18-64 years who responded to the survey in 1998 and 2017, uninsurance decreased by 2.1 percentage points, falling from 16.9% to 14.8%. But at the same time, the portion of adults who were unable to see a physician because of cost rose by 2.7 percentage points, from 11.4% to 15.7%. Looking specifically at adults who had insurance coverage, the researchers found that cost was a barrier for 11.5% of them in 2017, up from 7.1% in 1998.

These results come against a backdrop of growing medical costs, increasing deductibles and copayments, an increasing use of cost containment measures like prior authorization, and narrow provider networks in the wake of the transition to value-based payment structures, the authors noted.

“Our finding that financial access to physician care worsened is concerning,” Dr. Hawks and her colleagues wrote. “Persons with conditions such as diabetes, hypertension, cardiovascular disease, and poor health status risk substantial harms if they forgo physician care. Financial barriers to care have been associated with increased hospitalizations and worse health outcomes in patients with cardiovascular disease and hypertension and increased morbidity among patients with diabetes.”

One of the trends highlighted by the study authors is the growing number of employers offering plans with a high deductible.

“Enrollment in a high-deductible health plan, which has become increasingly common in the last decade, a trend uninterrupted by the ACA, is associated with forgoing needed care, especially among those of lower socioeconomic status,” the authors wrote. “Other changes in insurance benefit design, such as imposing tiered copayments and coinsurance obligations, eliminating coverage for some services (e.g., eyeglasses) and narrowing provider networks (which can force some patients to go out-of-network for care) may also have undermined the affordability of care.”

There was some positive news among the findings, however.

“The main encouraging finding from our analysis is the increase in the proportion of persons – both insured and uninsured – receiving cholesterol checks and flu shots,” Dr. Hawk and her colleagues wrote, adding that this increase “may be attributable to the increasing implementation of quality metrics, financial incentives, and improved systems for the delivery of these services.”

However, not all preventive services that had cost barriers eliminated under the ACA saw improvement, such as cancer screening. They note that the proportion of women who did not receive mammography increased during the study period and then plateaued, but did not improve following the implementation of the ACA. The authors described the reasons for this as “unclear.”

Dr. Hawks received funding support from an Institutional National Research Service award and from Cambridge Health Alliance, her employer. Other authors reported membership in Physicians for a National Health Program.

[email protected]

SOURCE: Hawks L et al. JAMA Intern Med. 2020 Jan 27. doi: 10.1001/jamainternmed.2019.6538.

CT scan screening of older people with heavy smoking histories – using lesion volume, not diameter, as a trigger for further work-up – reduced lung cancer deaths by about 30% in a randomized trial from the Netherlands and Belgium with almost 16,000 current and former smokers, investigators reported in the New England Journal of Medicine.

The Dutch-Belgian lung-cancer screening trial (Nederlands-Leuvens Longkanker Screenings Onderzoek [NELSON]) is “arguably the only adequately powered trial other than the” National Lung Screening Trial (NLST) in the United States to assess the role of CT scan screening among smokers, wrote University of London cancer epidemiologist Stephen Duffy, MSc, and University of Liverpool molecular oncology professor John Field, PhD, in an accompanying editorial.

NLST, which used lesion diameter, found an approximately 20% lower lung cancer mortality than screening with chest x-rays among 53,454 heavy smokers after a median follow-up of 6.5 years. The trial ultimately led the U.S. Preventive Services Task Force to recommend annual screening for people aged 55-80 years with a history of at least 30 pack-years.

European countries have considered similar programs but have hesitated “partly due to doubts fostered by the early publication of inconclusive results of a number of smaller trials in Europe. These doubts should be laid to rest,” Mr. Duffy and Dr. Field wrote.

“With the NELSON results, the efficacy of low-dose CT screening for lung cancer is confirmed. Our job is no longer to assess whether low-dose CT screening for lung cancer works; it does. Our job is to identify the target population in which it will be acceptable and cost effective,” they added.

The 15,789 NELSON participants (84% men, with a median age of 58 years and 38 pack-year history) were randomized about 1:1 to either low-dose CT scan screening at baseline and 1, 3, and 5.5 years, or to no screening.

At 10 years follow-up, there were 5.58 lung cancer cases and 2.5 deaths per 1,000 person-years in the screened group versus 4.91 cases and 3.3 deaths per 1,000 person-years among controls. Lung-cancer mortality was 24% lower among screened subjects overall, and 33% lower among screened women. The team estimated that screening prevented about 60 lung cancer deaths.

Using volume instead of diameter “resulted in low[er] referral rates” – 2.1% with a positive predictive value of 43.5% versus 24% with a positive predictive value of 3.8% in NLST – for additional work-up, explained investigators led by H.J. de Koning, MD, PhD, of the department of public health at Erasmus University Medical Center in Rotterdam, the Netherlands.

The upper limit of overdiagnosis risk – a major concern with any screening program – was 18.5% with NLST versus 8.9% with NELSON, they wrote.

In short: “Volume CT screening enabled a significant reduction of harms (e.g., false positive tests and unnecessary work-up procedures) without jeopardizing favorable outcomes,” the investigators wrote. Indeed, an ad hoc analysis suggested “more-favorable effects on lung-cancer mortality than in the NLST, despite lower referral rates for suspicious lesions” and the fact that NLST used annual screening.

“Recently,” Mr. Duffy and Dr. Field explained in their editorial, “the NELSON investigators evaluated both diameter and volume measurement to estimate lung-nodule size as an imaging biomarker for nodule management; this provided evidence that using mean or maximum axial diameter to assess nodule volume led to a substantial overestimation of nodule volume.” Direct measurement of volume “resulted in a substantial number of early-stage cancers identified at the time of diagnosis and avoided false positives from the overestimation incurred by management based on diameter.”

“The lung-nodule management system used in the NELSON trial has been advocated in the European position statement on lung-cancer screening. This will improve the acceptability of the intervention, because the rate of further investigation has been a major concern in lung cancer screening,” they wrote.

Baseline characteristics did not differ significantly between the screened and unscreened in NELSON, except for a slightly longer duration of smoking in the screened group.

The work was funded by the Netherlands Organization of Health Research and Development, among others. Mr. Duffy and Dr. de Koning didn’t report any disclosures. Dr. Field is an advisor for AstraZeneca, Epigenomics, and Nucleix, and has a research grant to his university from Janssen.
 

SOURCE: de Honing HJ et al. N Engl J Med. 2020 Jan 29. doi: 10.1056/NEJMoa1911793.

CT scan screening of older people with heavy smoking histories – using lesion volume, not diameter, as a trigger for further work-up – reduced lung cancer deaths by about 30% in a randomized trial from the Netherlands and Belgium with almost 16,000 current and former smokers, investigators reported in the New England Journal of Medicine.

The Dutch-Belgian lung-cancer screening trial (Nederlands-Leuvens Longkanker Screenings Onderzoek [NELSON]) is “arguably the only adequately powered trial other than the” National Lung Screening Trial (NLST) in the United States to assess the role of CT scan screening among smokers, wrote University of London cancer epidemiologist Stephen Duffy, MSc, and University of Liverpool molecular oncology professor John Field, PhD, in an accompanying editorial.

NLST, which used lesion diameter, found an approximately 20% lower lung cancer mortality than screening with chest x-rays among 53,454 heavy smokers after a median follow-up of 6.5 years. The trial ultimately led the U.S. Preventive Services Task Force to recommend annual screening for people aged 55-80 years with a history of at least 30 pack-years.

European countries have considered similar programs but have hesitated “partly due to doubts fostered by the early publication of inconclusive results of a number of smaller trials in Europe. These doubts should be laid to rest,” Mr. Duffy and Dr. Field wrote.

“With the NELSON results, the efficacy of low-dose CT screening for lung cancer is confirmed. Our job is no longer to assess whether low-dose CT screening for lung cancer works; it does. Our job is to identify the target population in which it will be acceptable and cost effective,” they added.

The 15,789 NELSON participants (84% men, with a median age of 58 years and 38 pack-year history) were randomized about 1:1 to either low-dose CT scan screening at baseline and 1, 3, and 5.5 years, or to no screening.

At 10 years follow-up, there were 5.58 lung cancer cases and 2.5 deaths per 1,000 person-years in the screened group versus 4.91 cases and 3.3 deaths per 1,000 person-years among controls. Lung-cancer mortality was 24% lower among screened subjects overall, and 33% lower among screened women. The team estimated that screening prevented about 60 lung cancer deaths.

Using volume instead of diameter “resulted in low[er] referral rates” – 2.1% with a positive predictive value of 43.5% versus 24% with a positive predictive value of 3.8% in NLST – for additional work-up, explained investigators led by H.J. de Koning, MD, PhD, of the department of public health at Erasmus University Medical Center in Rotterdam, the Netherlands.

The upper limit of overdiagnosis risk – a major concern with any screening program – was 18.5% with NLST versus 8.9% with NELSON, they wrote.

In short: “Volume CT screening enabled a significant reduction of harms (e.g., false positive tests and unnecessary work-up procedures) without jeopardizing favorable outcomes,” the investigators wrote. Indeed, an ad hoc analysis suggested “more-favorable effects on lung-cancer mortality than in the NLST, despite lower referral rates for suspicious lesions” and the fact that NLST used annual screening.

“Recently,” Mr. Duffy and Dr. Field explained in their editorial, “the NELSON investigators evaluated both diameter and volume measurement to estimate lung-nodule size as an imaging biomarker for nodule management; this provided evidence that using mean or maximum axial diameter to assess nodule volume led to a substantial overestimation of nodule volume.” Direct measurement of volume “resulted in a substantial number of early-stage cancers identified at the time of diagnosis and avoided false positives from the overestimation incurred by management based on diameter.”

“The lung-nodule management system used in the NELSON trial has been advocated in the European position statement on lung-cancer screening. This will improve the acceptability of the intervention, because the rate of further investigation has been a major concern in lung cancer screening,” they wrote.

Baseline characteristics did not differ significantly between the screened and unscreened in NELSON, except for a slightly longer duration of smoking in the screened group.

The work was funded by the Netherlands Organization of Health Research and Development, among others. Mr. Duffy and Dr. de Koning didn’t report any disclosures. Dr. Field is an advisor for AstraZeneca, Epigenomics, and Nucleix, and has a research grant to his university from Janssen.
 

SOURCE: de Honing HJ et al. N Engl J Med. 2020 Jan 29. doi: 10.1056/NEJMoa1911793.

CT scan screening of older people with heavy smoking histories – using lesion volume, not diameter, as a trigger for further work-up – reduced lung cancer deaths by about 30% in a randomized trial from the Netherlands and Belgium with almost 16,000 current and former smokers, investigators reported in the New England Journal of Medicine.

The Dutch-Belgian lung-cancer screening trial (Nederlands-Leuvens Longkanker Screenings Onderzoek [NELSON]) is “arguably the only adequately powered trial other than the” National Lung Screening Trial (NLST) in the United States to assess the role of CT scan screening among smokers, wrote University of London cancer epidemiologist Stephen Duffy, MSc, and University of Liverpool molecular oncology professor John Field, PhD, in an accompanying editorial.

NLST, which used lesion diameter, found an approximately 20% lower lung cancer mortality than screening with chest x-rays among 53,454 heavy smokers after a median follow-up of 6.5 years. The trial ultimately led the U.S. Preventive Services Task Force to recommend annual screening for people aged 55-80 years with a history of at least 30 pack-years.

European countries have considered similar programs but have hesitated “partly due to doubts fostered by the early publication of inconclusive results of a number of smaller trials in Europe. These doubts should be laid to rest,” Mr. Duffy and Dr. Field wrote.

“With the NELSON results, the efficacy of low-dose CT screening for lung cancer is confirmed. Our job is no longer to assess whether low-dose CT screening for lung cancer works; it does. Our job is to identify the target population in which it will be acceptable and cost effective,” they added.

The 15,789 NELSON participants (84% men, with a median age of 58 years and 38 pack-year history) were randomized about 1:1 to either low-dose CT scan screening at baseline and 1, 3, and 5.5 years, or to no screening.

At 10 years follow-up, there were 5.58 lung cancer cases and 2.5 deaths per 1,000 person-years in the screened group versus 4.91 cases and 3.3 deaths per 1,000 person-years among controls. Lung-cancer mortality was 24% lower among screened subjects overall, and 33% lower among screened women. The team estimated that screening prevented about 60 lung cancer deaths.

Using volume instead of diameter “resulted in low[er] referral rates” – 2.1% with a positive predictive value of 43.5% versus 24% with a positive predictive value of 3.8% in NLST – for additional work-up, explained investigators led by H.J. de Koning, MD, PhD, of the department of public health at Erasmus University Medical Center in Rotterdam, the Netherlands.

The upper limit of overdiagnosis risk – a major concern with any screening program – was 18.5% with NLST versus 8.9% with NELSON, they wrote.

In short: “Volume CT screening enabled a significant reduction of harms (e.g., false positive tests and unnecessary work-up procedures) without jeopardizing favorable outcomes,” the investigators wrote. Indeed, an ad hoc analysis suggested “more-favorable effects on lung-cancer mortality than in the NLST, despite lower referral rates for suspicious lesions” and the fact that NLST used annual screening.

“Recently,” Mr. Duffy and Dr. Field explained in their editorial, “the NELSON investigators evaluated both diameter and volume measurement to estimate lung-nodule size as an imaging biomarker for nodule management; this provided evidence that using mean or maximum axial diameter to assess nodule volume led to a substantial overestimation of nodule volume.” Direct measurement of volume “resulted in a substantial number of early-stage cancers identified at the time of diagnosis and avoided false positives from the overestimation incurred by management based on diameter.”

“The lung-nodule management system used in the NELSON trial has been advocated in the European position statement on lung-cancer screening. This will improve the acceptability of the intervention, because the rate of further investigation has been a major concern in lung cancer screening,” they wrote.

Baseline characteristics did not differ significantly between the screened and unscreened in NELSON, except for a slightly longer duration of smoking in the screened group.

The work was funded by the Netherlands Organization of Health Research and Development, among others. Mr. Duffy and Dr. de Koning didn’t report any disclosures. Dr. Field is an advisor for AstraZeneca, Epigenomics, and Nucleix, and has a research grant to his university from Janssen.
 

SOURCE: de Honing HJ et al. N Engl J Med. 2020 Jan 29. doi: 10.1056/NEJMoa1911793.

Emerging viruses that spread to humans from an animal host are commonplace and represent some of the deadliest diseases known. Given the details of the Wuhan coronavirus (2019-nCoV) outbreak, including the genetic profile of the disease agent, the hypothesis of a snake origin was the first raised in the peer-reviewed literature.

SISTEMA 12/Wikimedia Commons/CC BY-SA 4.0

It is a highly controversial origin story, however, given that mammals have been the sources of all other such zoonotic coronaviruses, as well as a host of other zoonotic diseases.

An animal source for emerging infections such as the 2019-nCoV is the default hypothesis, because “around 60% of all infectious diseases in humans are zoonotic, as are 75% of all emerging infectious diseases,” according to a United Nations report. The report goes on to say that, “on average, one new infectious disease emerges in humans every 4 months.”

To appreciate the emergence and nature of 2019-nCoV, it is important to examine the history of zoonotic outbreaks of other such diseases, especially with regard to the “mixing-vessel” phenomenon, which has been noted in closely related coronaviruses, including SARS and MERS, as well as the widely disparate HIV, Ebola, and influenza viruses.
 

Mutants in the mixing vessel

The mixing-vessel phenomenon is conceptually easy but molecularly complex. A single animal is coinfected with two related viruses; the virus genomes recombine together (virus “sex”) in that animal to form a new variant of virus. Such new mutant viruses can be more or less infective, more or less deadly, and more or less able to jump the species or even genus barrier. An emerging viral zoonosis can occur when a human being is exposed to one of these new viruses (either from the origin species or another species intermediate) that is capable of also infecting a human cell. Such exposure can occur from close proximity to animal waste or body fluids, as in the farm environment, or from wildlife pets or the capturing and slaughtering of wildlife for food, as is proposed in the case of the Wuhan seafood market scenario. In fact, the scientists who postulated a snake intermediary as the potential mixing vessel also stated that 2019‐nCoV appears to be a recombinant virus between a bat coronavirus and an origin‐unknown coronavirus.

Coronaviruses in particular have a history of moving from animal to human hosts (and even back again), and their detailed genetic pattern and taxonomy can reveal the animal origin of these diseases.
 

Going batty

Bats, in particular, have been shown to be a reservoir species for both alphacoronaviruses and betacoronaviruses. Given their ecology and behavior, they have been found to play a key role in transmitting coronaviruses between species. A highly pertinent example of this is the SARS coronavirus, which was shown to have likely originated in Chinese horseshoe bats. The SARS virus, which is genetically closely related to the new Wuhan coronavirus, first infected humans in the Guangdong province of southern China in 2002.

Scientists speculate that the virus was then either transmitted directly to humans from bats, or passed through an intermediate host species, with SARS-like viruses isolated from Himalayan palm civets found in a live-animal market in Guangdong. The virus infection was also detected in other animals (including a raccoon dog, Nyctereutes procyonoides) and in humans working at the market.

The MERS coronavirus is a betacoronavirus that was first reported in Saudi Arabia in 2012. It turned out to be far more deadly than either SARS or the Wuhan virus (at least as far as current estimates of the new coronavirus’s behavior). The MERS genotype was found to be closely related to MERS-like viruses in bats in Saudi Arabia, Africa, Europe, and Asia. Studies done on the cell receptor for MERS showed an apparently conserved viral receptor in both bats and humans. And an identical strain of MERS was found in bats in a nearby cave and near the workplace of the first known human patient.

Wikimedia Commons/Mickey Samuni-Blank

However, in many of the other locations of the outbreak in the Middle East, there appeared to be limited contact between bats and humans, so scientists looked for another vector species, perhaps one that was acting as an intermediate. A high seroprevalence of MERS-CoV or a closely related virus was found in camels across the Arabian Peninsula and parts of eastern and northern Africa, while tests for MERS antibodies were negative in the most-likely other species of livestock or pet animals, including chickens, cows, goats, horses, and sheep.

In addition, the MERS-related CoV carried by camels was genetically highly similar to that detected in humans, as demonstrated in one particular outbreak on a farm in Qatar where the genetic sequences of MERS-CoV in the nasal swabs from 3 of 14 seropositive camels were similar to those of 2 human cases on the same farm. Similar genomic results were found in MERS-CoV from nasal swabs from camels in Saudi Arabia.
 

Other mixing-vessel zoonoses

HIV, the viral cause of AIDS, provides an almost-textbook origin story of the rise of a zoonotic supervillain. The virus was genetically traced to have a chimpanzee-to-human origin, but it was found to be more complicated than that. The virus first emerged in the 1920s in Africa in what is now the Democratic Republic of the Congo, well before its rise to a global pandemic in the 1980s.

Researchers believe the chimpanzee virus is a hybrid of the simian immunodeficiency viruses (SIVs) naturally infecting two different monkey species: the red-capped mangabey (Cercocebus torquatus) and the greater spot-nosed monkey (Cercopithecus nictitans). Chimpanzees kill and eat monkeys, which is likely how they acquired the monkey viruses. The viruses hybridized in a chimpanzee; the hybrid virus then spread through the chimpanzee population and was later transmitted to humans who captured and slaughtered chimps for meat (becoming exposed to their blood). This was the most likely origin of HIV-1.

HIV-1 also shows one of the major risks of zoonotic infections. They can continue to mutate in its human host, increasing the risk of greater virulence, but also interfering with the production of a universally effective vaccine. Since its transmission to humans, for example, many subtypes of the HIV-1 strain have developed, with genetic differences even in the same subtypes found to be up to 20%.

CDC/Frederick A. Murphy

Ebolavirus, first detected in 1976, is another case of bats being the potential culprit. Genetic analysis has shown that African fruit bats are likely involved in the spread of the virus and may be its reservoir host. Further evidence of this was found in the most recent human-infecting Bombali variant of the virus, which was identified in samples from bats collected from Sierra Leone.

It was also found that pigs can also become infected with Zaire ebolavirus, leading to the fear that pigs could serve as a mixing vessel for it and other filoviruses. Pigs have their own forms of Ebola-like disease viruses, which are not currently transmissible to humans, but could provide a potential mixing-vessel reservoir.
 

Emergent influenzas

The Western world has been most affected by these highly mutable, multispecies zoonotic viruses. The 1957 and 1968 flu pandemics contained a mixture of gene segments from human and avian influenza viruses. “What is clear from genetic analysis of the viruses that caused these past pandemics is that reassortment (gene swapping) occurred to produce novel influenza viruses that caused the pandemics. In both of these cases, the new viruses that emerged showed major differences from the parent viruses,” according to the Centers for Disease Control and Prevention.

Influenza is, however, a good example that all zoonoses are not the result of a mixing-vessel phenomenon, with evidence showing that the origin of the catastrophic 1918 virus pandemic likely resulted from a bird influenza virus directly infecting humans and pigs at about the same time without reassortment, according to the CDC.
 

Building a protective infrastructure

The first 2 decades of the 21st century saw a huge increase in efforts to develop an infrastructure to monitor and potentially prevent the spread of new zoonoses. As part of a global effort led by the United Nations, the U.S. Agency for International AID developed the PREDICT program in 2009 “to strengthen global capacity for detection and discovery of zoonotic viruses with pandemic potential. Those include coronaviruses, the family to which SARS and MERS belong; paramyxoviruses, like Nipah virus; influenza viruses; and filoviruses, like the ebolavirus.”

PREDICT funding to the EcoHealth Alliance led to discovery of the likely bat origins of the Zaire ebolavirus during the 2013-2016 outbreak. And throughout the existence of PREDICT, more than 145,000 animals and people were surveyed in areas of likely zoonotic outbreaks, leading to the detection of more than “1,100 unique viruses, including zoonotic diseases of public health concern such as Bombali ebolavirus, Zaire ebolavirus, Marburg virus, and MERS- and SARS-like coronaviruses,” according to PREDICT partner, the University of California, Davis.

PREDICT-2 was launched in 2014 with the continuing goals of “identifying and better characterizing pathogens of known epidemic and unknown pandemic potential; recognizing animal reservoirs and amplification hosts of human-infectious viruses; and efficiently targeting intervention action at human behaviors which amplify disease transmission at critical animal-animal and animal-human interfaces in hotspots of viral evolution, spillover, amplification, and spread.”

However, in October 2019, the Trump administration cut all funding to the PREDICT program, leading to its shutdown. In a New York Times interview, Peter Daszak, president of the EcoHealth Alliance, stated: “PREDICT was an approach to heading off pandemics, instead of sitting there waiting for them to emerge and then mobilizing.”

Ultimately, in addition to its human cost, the current Wuhan coronavirus outbreak can be looked at an object lesson – a test of the pandemic surveillance and control systems currently in place, and a practice run for the next and potentially deadlier zoonotic outbreaks to come. Perhaps it is also a reminder that cutting resources to detect zoonoses at their source in their animal hosts – before they enter the human chain– is perhaps not the most prudent of ideas.

[email protected]

Mark Lesney is the managing editor of MDedge.com/IDPractioner. He has a PhD in plant virology and a PhD in the history of science, with a focus on the history of biotechnology and medicine. He has served as an adjunct assistant professor of the department of biochemistry and molecular & celluar biology at Georgetown University, Washington.

Emerging viruses that spread to humans from an animal host are commonplace and represent some of the deadliest diseases known. Given the details of the Wuhan coronavirus (2019-nCoV) outbreak, including the genetic profile of the disease agent, the hypothesis of a snake origin was the first raised in the peer-reviewed literature.

SISTEMA 12/Wikimedia Commons/CC BY-SA 4.0

It is a highly controversial origin story, however, given that mammals have been the sources of all other such zoonotic coronaviruses, as well as a host of other zoonotic diseases.

An animal source for emerging infections such as the 2019-nCoV is the default hypothesis, because “around 60% of all infectious diseases in humans are zoonotic, as are 75% of all emerging infectious diseases,” according to a United Nations report. The report goes on to say that, “on average, one new infectious disease emerges in humans every 4 months.”

To appreciate the emergence and nature of 2019-nCoV, it is important to examine the history of zoonotic outbreaks of other such diseases, especially with regard to the “mixing-vessel” phenomenon, which has been noted in closely related coronaviruses, including SARS and MERS, as well as the widely disparate HIV, Ebola, and influenza viruses.
 

Mutants in the mixing vessel

The mixing-vessel phenomenon is conceptually easy but molecularly complex. A single animal is coinfected with two related viruses; the virus genomes recombine together (virus “sex”) in that animal to form a new variant of virus. Such new mutant viruses can be more or less infective, more or less deadly, and more or less able to jump the species or even genus barrier. An emerging viral zoonosis can occur when a human being is exposed to one of these new viruses (either from the origin species or another species intermediate) that is capable of also infecting a human cell. Such exposure can occur from close proximity to animal waste or body fluids, as in the farm environment, or from wildlife pets or the capturing and slaughtering of wildlife for food, as is proposed in the case of the Wuhan seafood market scenario. In fact, the scientists who postulated a snake intermediary as the potential mixing vessel also stated that 2019‐nCoV appears to be a recombinant virus between a bat coronavirus and an origin‐unknown coronavirus.

Coronaviruses in particular have a history of moving from animal to human hosts (and even back again), and their detailed genetic pattern and taxonomy can reveal the animal origin of these diseases.
 

Going batty

Bats, in particular, have been shown to be a reservoir species for both alphacoronaviruses and betacoronaviruses. Given their ecology and behavior, they have been found to play a key role in transmitting coronaviruses between species. A highly pertinent example of this is the SARS coronavirus, which was shown to have likely originated in Chinese horseshoe bats. The SARS virus, which is genetically closely related to the new Wuhan coronavirus, first infected humans in the Guangdong province of southern China in 2002.

Scientists speculate that the virus was then either transmitted directly to humans from bats, or passed through an intermediate host species, with SARS-like viruses isolated from Himalayan palm civets found in a live-animal market in Guangdong. The virus infection was also detected in other animals (including a raccoon dog, Nyctereutes procyonoides) and in humans working at the market.

The MERS coronavirus is a betacoronavirus that was first reported in Saudi Arabia in 2012. It turned out to be far more deadly than either SARS or the Wuhan virus (at least as far as current estimates of the new coronavirus’s behavior). The MERS genotype was found to be closely related to MERS-like viruses in bats in Saudi Arabia, Africa, Europe, and Asia. Studies done on the cell receptor for MERS showed an apparently conserved viral receptor in both bats and humans. And an identical strain of MERS was found in bats in a nearby cave and near the workplace of the first known human patient.

Wikimedia Commons/Mickey Samuni-Blank

However, in many of the other locations of the outbreak in the Middle East, there appeared to be limited contact between bats and humans, so scientists looked for another vector species, perhaps one that was acting as an intermediate. A high seroprevalence of MERS-CoV or a closely related virus was found in camels across the Arabian Peninsula and parts of eastern and northern Africa, while tests for MERS antibodies were negative in the most-likely other species of livestock or pet animals, including chickens, cows, goats, horses, and sheep.

In addition, the MERS-related CoV carried by camels was genetically highly similar to that detected in humans, as demonstrated in one particular outbreak on a farm in Qatar where the genetic sequences of MERS-CoV in the nasal swabs from 3 of 14 seropositive camels were similar to those of 2 human cases on the same farm. Similar genomic results were found in MERS-CoV from nasal swabs from camels in Saudi Arabia.
 

Other mixing-vessel zoonoses

HIV, the viral cause of AIDS, provides an almost-textbook origin story of the rise of a zoonotic supervillain. The virus was genetically traced to have a chimpanzee-to-human origin, but it was found to be more complicated than that. The virus first emerged in the 1920s in Africa in what is now the Democratic Republic of the Congo, well before its rise to a global pandemic in the 1980s.

Researchers believe the chimpanzee virus is a hybrid of the simian immunodeficiency viruses (SIVs) naturally infecting two different monkey species: the red-capped mangabey (Cercocebus torquatus) and the greater spot-nosed monkey (Cercopithecus nictitans). Chimpanzees kill and eat monkeys, which is likely how they acquired the monkey viruses. The viruses hybridized in a chimpanzee; the hybrid virus then spread through the chimpanzee population and was later transmitted to humans who captured and slaughtered chimps for meat (becoming exposed to their blood). This was the most likely origin of HIV-1.

HIV-1 also shows one of the major risks of zoonotic infections. They can continue to mutate in its human host, increasing the risk of greater virulence, but also interfering with the production of a universally effective vaccine. Since its transmission to humans, for example, many subtypes of the HIV-1 strain have developed, with genetic differences even in the same subtypes found to be up to 20%.

CDC/Frederick A. Murphy

Ebolavirus, first detected in 1976, is another case of bats being the potential culprit. Genetic analysis has shown that African fruit bats are likely involved in the spread of the virus and may be its reservoir host. Further evidence of this was found in the most recent human-infecting Bombali variant of the virus, which was identified in samples from bats collected from Sierra Leone.

It was also found that pigs can also become infected with Zaire ebolavirus, leading to the fear that pigs could serve as a mixing vessel for it and other filoviruses. Pigs have their own forms of Ebola-like disease viruses, which are not currently transmissible to humans, but could provide a potential mixing-vessel reservoir.
 

Emergent influenzas

The Western world has been most affected by these highly mutable, multispecies zoonotic viruses. The 1957 and 1968 flu pandemics contained a mixture of gene segments from human and avian influenza viruses. “What is clear from genetic analysis of the viruses that caused these past pandemics is that reassortment (gene swapping) occurred to produce novel influenza viruses that caused the pandemics. In both of these cases, the new viruses that emerged showed major differences from the parent viruses,” according to the Centers for Disease Control and Prevention.

Influenza is, however, a good example that all zoonoses are not the result of a mixing-vessel phenomenon, with evidence showing that the origin of the catastrophic 1918 virus pandemic likely resulted from a bird influenza virus directly infecting humans and pigs at about the same time without reassortment, according to the CDC.
 

Building a protective infrastructure

The first 2 decades of the 21st century saw a huge increase in efforts to develop an infrastructure to monitor and potentially prevent the spread of new zoonoses. As part of a global effort led by the United Nations, the U.S. Agency for International AID developed the PREDICT program in 2009 “to strengthen global capacity for detection and discovery of zoonotic viruses with pandemic potential. Those include coronaviruses, the family to which SARS and MERS belong; paramyxoviruses, like Nipah virus; influenza viruses; and filoviruses, like the ebolavirus.”

PREDICT funding to the EcoHealth Alliance led to discovery of the likely bat origins of the Zaire ebolavirus during the 2013-2016 outbreak. And throughout the existence of PREDICT, more than 145,000 animals and people were surveyed in areas of likely zoonotic outbreaks, leading to the detection of more than “1,100 unique viruses, including zoonotic diseases of public health concern such as Bombali ebolavirus, Zaire ebolavirus, Marburg virus, and MERS- and SARS-like coronaviruses,” according to PREDICT partner, the University of California, Davis.

PREDICT-2 was launched in 2014 with the continuing goals of “identifying and better characterizing pathogens of known epidemic and unknown pandemic potential; recognizing animal reservoirs and amplification hosts of human-infectious viruses; and efficiently targeting intervention action at human behaviors which amplify disease transmission at critical animal-animal and animal-human interfaces in hotspots of viral evolution, spillover, amplification, and spread.”

However, in October 2019, the Trump administration cut all funding to the PREDICT program, leading to its shutdown. In a New York Times interview, Peter Daszak, president of the EcoHealth Alliance, stated: “PREDICT was an approach to heading off pandemics, instead of sitting there waiting for them to emerge and then mobilizing.”

Ultimately, in addition to its human cost, the current Wuhan coronavirus outbreak can be looked at an object lesson – a test of the pandemic surveillance and control systems currently in place, and a practice run for the next and potentially deadlier zoonotic outbreaks to come. Perhaps it is also a reminder that cutting resources to detect zoonoses at their source in their animal hosts – before they enter the human chain– is perhaps not the most prudent of ideas.

[email protected]

Mark Lesney is the managing editor of MDedge.com/IDPractioner. He has a PhD in plant virology and a PhD in the history of science, with a focus on the history of biotechnology and medicine. He has served as an adjunct assistant professor of the department of biochemistry and molecular & celluar biology at Georgetown University, Washington.

Emerging viruses that spread to humans from an animal host are commonplace and represent some of the deadliest diseases known. Given the details of the Wuhan coronavirus (2019-nCoV) outbreak, including the genetic profile of the disease agent, the hypothesis of a snake origin was the first raised in the peer-reviewed literature.

SISTEMA 12/Wikimedia Commons/CC BY-SA 4.0

It is a highly controversial origin story, however, given that mammals have been the sources of all other such zoonotic coronaviruses, as well as a host of other zoonotic diseases.

An animal source for emerging infections such as the 2019-nCoV is the default hypothesis, because “around 60% of all infectious diseases in humans are zoonotic, as are 75% of all emerging infectious diseases,” according to a United Nations report. The report goes on to say that, “on average, one new infectious disease emerges in humans every 4 months.”

To appreciate the emergence and nature of 2019-nCoV, it is important to examine the history of zoonotic outbreaks of other such diseases, especially with regard to the “mixing-vessel” phenomenon, which has been noted in closely related coronaviruses, including SARS and MERS, as well as the widely disparate HIV, Ebola, and influenza viruses.
 

Mutants in the mixing vessel

The mixing-vessel phenomenon is conceptually easy but molecularly complex. A single animal is coinfected with two related viruses; the virus genomes recombine together (virus “sex”) in that animal to form a new variant of virus. Such new mutant viruses can be more or less infective, more or less deadly, and more or less able to jump the species or even genus barrier. An emerging viral zoonosis can occur when a human being is exposed to one of these new viruses (either from the origin species or another species intermediate) that is capable of also infecting a human cell. Such exposure can occur from close proximity to animal waste or body fluids, as in the farm environment, or from wildlife pets or the capturing and slaughtering of wildlife for food, as is proposed in the case of the Wuhan seafood market scenario. In fact, the scientists who postulated a snake intermediary as the potential mixing vessel also stated that 2019‐nCoV appears to be a recombinant virus between a bat coronavirus and an origin‐unknown coronavirus.

Coronaviruses in particular have a history of moving from animal to human hosts (and even back again), and their detailed genetic pattern and taxonomy can reveal the animal origin of these diseases.
 

Going batty

Bats, in particular, have been shown to be a reservoir species for both alphacoronaviruses and betacoronaviruses. Given their ecology and behavior, they have been found to play a key role in transmitting coronaviruses between species. A highly pertinent example of this is the SARS coronavirus, which was shown to have likely originated in Chinese horseshoe bats. The SARS virus, which is genetically closely related to the new Wuhan coronavirus, first infected humans in the Guangdong province of southern China in 2002.

Scientists speculate that the virus was then either transmitted directly to humans from bats, or passed through an intermediate host species, with SARS-like viruses isolated from Himalayan palm civets found in a live-animal market in Guangdong. The virus infection was also detected in other animals (including a raccoon dog, Nyctereutes procyonoides) and in humans working at the market.

The MERS coronavirus is a betacoronavirus that was first reported in Saudi Arabia in 2012. It turned out to be far more deadly than either SARS or the Wuhan virus (at least as far as current estimates of the new coronavirus’s behavior). The MERS genotype was found to be closely related to MERS-like viruses in bats in Saudi Arabia, Africa, Europe, and Asia. Studies done on the cell receptor for MERS showed an apparently conserved viral receptor in both bats and humans. And an identical strain of MERS was found in bats in a nearby cave and near the workplace of the first known human patient.

Wikimedia Commons/Mickey Samuni-Blank

However, in many of the other locations of the outbreak in the Middle East, there appeared to be limited contact between bats and humans, so scientists looked for another vector species, perhaps one that was acting as an intermediate. A high seroprevalence of MERS-CoV or a closely related virus was found in camels across the Arabian Peninsula and parts of eastern and northern Africa, while tests for MERS antibodies were negative in the most-likely other species of livestock or pet animals, including chickens, cows, goats, horses, and sheep.

In addition, the MERS-related CoV carried by camels was genetically highly similar to that detected in humans, as demonstrated in one particular outbreak on a farm in Qatar where the genetic sequences of MERS-CoV in the nasal swabs from 3 of 14 seropositive camels were similar to those of 2 human cases on the same farm. Similar genomic results were found in MERS-CoV from nasal swabs from camels in Saudi Arabia.
 

Other mixing-vessel zoonoses

HIV, the viral cause of AIDS, provides an almost-textbook origin story of the rise of a zoonotic supervillain. The virus was genetically traced to have a chimpanzee-to-human origin, but it was found to be more complicated than that. The virus first emerged in the 1920s in Africa in what is now the Democratic Republic of the Congo, well before its rise to a global pandemic in the 1980s.

Researchers believe the chimpanzee virus is a hybrid of the simian immunodeficiency viruses (SIVs) naturally infecting two different monkey species: the red-capped mangabey (Cercocebus torquatus) and the greater spot-nosed monkey (Cercopithecus nictitans). Chimpanzees kill and eat monkeys, which is likely how they acquired the monkey viruses. The viruses hybridized in a chimpanzee; the hybrid virus then spread through the chimpanzee population and was later transmitted to humans who captured and slaughtered chimps for meat (becoming exposed to their blood). This was the most likely origin of HIV-1.

HIV-1 also shows one of the major risks of zoonotic infections. They can continue to mutate in its human host, increasing the risk of greater virulence, but also interfering with the production of a universally effective vaccine. Since its transmission to humans, for example, many subtypes of the HIV-1 strain have developed, with genetic differences even in the same subtypes found to be up to 20%.

CDC/Frederick A. Murphy

Ebolavirus, first detected in 1976, is another case of bats being the potential culprit. Genetic analysis has shown that African fruit bats are likely involved in the spread of the virus and may be its reservoir host. Further evidence of this was found in the most recent human-infecting Bombali variant of the virus, which was identified in samples from bats collected from Sierra Leone.

It was also found that pigs can also become infected with Zaire ebolavirus, leading to the fear that pigs could serve as a mixing vessel for it and other filoviruses. Pigs have their own forms of Ebola-like disease viruses, which are not currently transmissible to humans, but could provide a potential mixing-vessel reservoir.
 

Emergent influenzas

The Western world has been most affected by these highly mutable, multispecies zoonotic viruses. The 1957 and 1968 flu pandemics contained a mixture of gene segments from human and avian influenza viruses. “What is clear from genetic analysis of the viruses that caused these past pandemics is that reassortment (gene swapping) occurred to produce novel influenza viruses that caused the pandemics. In both of these cases, the new viruses that emerged showed major differences from the parent viruses,” according to the Centers for Disease Control and Prevention.

Influenza is, however, a good example that all zoonoses are not the result of a mixing-vessel phenomenon, with evidence showing that the origin of the catastrophic 1918 virus pandemic likely resulted from a bird influenza virus directly infecting humans and pigs at about the same time without reassortment, according to the CDC.
 

Building a protective infrastructure

The first 2 decades of the 21st century saw a huge increase in efforts to develop an infrastructure to monitor and potentially prevent the spread of new zoonoses. As part of a global effort led by the United Nations, the U.S. Agency for International AID developed the PREDICT program in 2009 “to strengthen global capacity for detection and discovery of zoonotic viruses with pandemic potential. Those include coronaviruses, the family to which SARS and MERS belong; paramyxoviruses, like Nipah virus; influenza viruses; and filoviruses, like the ebolavirus.”

PREDICT funding to the EcoHealth Alliance led to discovery of the likely bat origins of the Zaire ebolavirus during the 2013-2016 outbreak. And throughout the existence of PREDICT, more than 145,000 animals and people were surveyed in areas of likely zoonotic outbreaks, leading to the detection of more than “1,100 unique viruses, including zoonotic diseases of public health concern such as Bombali ebolavirus, Zaire ebolavirus, Marburg virus, and MERS- and SARS-like coronaviruses,” according to PREDICT partner, the University of California, Davis.

PREDICT-2 was launched in 2014 with the continuing goals of “identifying and better characterizing pathogens of known epidemic and unknown pandemic potential; recognizing animal reservoirs and amplification hosts of human-infectious viruses; and efficiently targeting intervention action at human behaviors which amplify disease transmission at critical animal-animal and animal-human interfaces in hotspots of viral evolution, spillover, amplification, and spread.”

However, in October 2019, the Trump administration cut all funding to the PREDICT program, leading to its shutdown. In a New York Times interview, Peter Daszak, president of the EcoHealth Alliance, stated: “PREDICT was an approach to heading off pandemics, instead of sitting there waiting for them to emerge and then mobilizing.”

Ultimately, in addition to its human cost, the current Wuhan coronavirus outbreak can be looked at an object lesson – a test of the pandemic surveillance and control systems currently in place, and a practice run for the next and potentially deadlier zoonotic outbreaks to come. Perhaps it is also a reminder that cutting resources to detect zoonoses at their source in their animal hosts – before they enter the human chain– is perhaps not the most prudent of ideas.

[email protected]

Mark Lesney is the managing editor of MDedge.com/IDPractioner. He has a PhD in plant virology and a PhD in the history of science, with a focus on the history of biotechnology and medicine. He has served as an adjunct assistant professor of the department of biochemistry and molecular & celluar biology at Georgetown University, Washington.