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Occult HCV infection is correlated to unfavorable genotypes in hemophilia patients
The presence of occult hepatitis C virus infection is determined by finding HCV RNA in the liver and peripheral blood mononuclear cells, with no HCV RNA in the serum. Researchers have shown that the presence of occult HCV infection (OCI) was correlated with unfavorable polymorphisms near interferon lambda-3/4 (IFNL3/4), which has been associated with spontaneous HCV clearance.
This study was conducted to assess the frequency of OCI in 450 hemophilia patients in Iran with negative HCV markers, and to evaluate the association of three IFNL3 single nucleotide polymorphisms (rs8099917, rs12979860, and rs12980275) and the IFNL4 ss469415590 SNP with OCI positivity.
The estimated OCI rate was 10.2%. Among the 46 OCI patients, 56.5%, 23.9%, and 19.6% were infected with HCV-1b, HCV-1a, and HCV-3a, respectively. The researchers found that, compared with patients without OCI, unfavorable IFNL3 rs12979860, IFNL3 rs8099917, IFNL3 rs12980275, and IFNL4 ss469415590 genotypes were more frequently found in OCI patients. Multivariate analysis showed that ALT, cholesterol, triglyceride, as well as the aforementioned unfavorable interferon SNP geneotypes were associated with OCI positivity.
“10.2% of anti-HCV seronegative Iranian patients with hemophilia had OCI in our study; therefore, risk of this infection should be taken into consideration. We also showed that patients with unfavorable IFNL3 SNPs and IFNL4 ss469415590 genotypes were exposed to a higher risk of OCI, compared to hemophilia patients with other genotypes,” the researchers concluded.
The authors reported that they had no disclosures.
SOURCE: Nafari AH et al. Infect Genet Evol. 2019 Dec 13. doi: 10.1016/j.meegid.2019.104144.
The presence of occult hepatitis C virus infection is determined by finding HCV RNA in the liver and peripheral blood mononuclear cells, with no HCV RNA in the serum. Researchers have shown that the presence of occult HCV infection (OCI) was correlated with unfavorable polymorphisms near interferon lambda-3/4 (IFNL3/4), which has been associated with spontaneous HCV clearance.
This study was conducted to assess the frequency of OCI in 450 hemophilia patients in Iran with negative HCV markers, and to evaluate the association of three IFNL3 single nucleotide polymorphisms (rs8099917, rs12979860, and rs12980275) and the IFNL4 ss469415590 SNP with OCI positivity.
The estimated OCI rate was 10.2%. Among the 46 OCI patients, 56.5%, 23.9%, and 19.6% were infected with HCV-1b, HCV-1a, and HCV-3a, respectively. The researchers found that, compared with patients without OCI, unfavorable IFNL3 rs12979860, IFNL3 rs8099917, IFNL3 rs12980275, and IFNL4 ss469415590 genotypes were more frequently found in OCI patients. Multivariate analysis showed that ALT, cholesterol, triglyceride, as well as the aforementioned unfavorable interferon SNP geneotypes were associated with OCI positivity.
“10.2% of anti-HCV seronegative Iranian patients with hemophilia had OCI in our study; therefore, risk of this infection should be taken into consideration. We also showed that patients with unfavorable IFNL3 SNPs and IFNL4 ss469415590 genotypes were exposed to a higher risk of OCI, compared to hemophilia patients with other genotypes,” the researchers concluded.
The authors reported that they had no disclosures.
SOURCE: Nafari AH et al. Infect Genet Evol. 2019 Dec 13. doi: 10.1016/j.meegid.2019.104144.
The presence of occult hepatitis C virus infection is determined by finding HCV RNA in the liver and peripheral blood mononuclear cells, with no HCV RNA in the serum. Researchers have shown that the presence of occult HCV infection (OCI) was correlated with unfavorable polymorphisms near interferon lambda-3/4 (IFNL3/4), which has been associated with spontaneous HCV clearance.
This study was conducted to assess the frequency of OCI in 450 hemophilia patients in Iran with negative HCV markers, and to evaluate the association of three IFNL3 single nucleotide polymorphisms (rs8099917, rs12979860, and rs12980275) and the IFNL4 ss469415590 SNP with OCI positivity.
The estimated OCI rate was 10.2%. Among the 46 OCI patients, 56.5%, 23.9%, and 19.6% were infected with HCV-1b, HCV-1a, and HCV-3a, respectively. The researchers found that, compared with patients without OCI, unfavorable IFNL3 rs12979860, IFNL3 rs8099917, IFNL3 rs12980275, and IFNL4 ss469415590 genotypes were more frequently found in OCI patients. Multivariate analysis showed that ALT, cholesterol, triglyceride, as well as the aforementioned unfavorable interferon SNP geneotypes were associated with OCI positivity.
“10.2% of anti-HCV seronegative Iranian patients with hemophilia had OCI in our study; therefore, risk of this infection should be taken into consideration. We also showed that patients with unfavorable IFNL3 SNPs and IFNL4 ss469415590 genotypes were exposed to a higher risk of OCI, compared to hemophilia patients with other genotypes,” the researchers concluded.
The authors reported that they had no disclosures.
SOURCE: Nafari AH et al. Infect Genet Evol. 2019 Dec 13. doi: 10.1016/j.meegid.2019.104144.
FROM INFECTION, GENETICS AND EVOLUTION
ID Blog: Wuhan coronavirus – just a stop on the zoonotic highway
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.
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.
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%.
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.
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.
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.
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%.
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.
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.
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.
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%.
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.
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.
HCV a risk in HIV-negative MSM who use PrEP
Hepatitis C virus (HCV) is known to be a common sexually transmitted infection (STI) among HIV-positive men who have sex with men (MSM). To examine this relationship in HIV-negative MSM, researchers in the Amsterdam PrEP Project team in the HIV Transmission Elimination AMsterdam (H-TEAM) Initiative evaluated HCV-incidence and its risk-factors in this population, who were using pre-exposure prophylaxis (PrEP).
Participants in the Amsterdam PrEP project were tested for HCV antibodies or HCV-RNA every 6 months. During the period, participants used daily or event-driven PrEP and could switch regimens during follow-up, according to the report by published in the Journal of Hepatology.
HIV-negative MSM on PrEP are at risk for incident HCV-infection, while identified risk-factors are similar to those in HIV-positive MSM.
Among 350 participants, they detected 15 HCV infections in 14 participants, finding 8 primary infections and 7 reinfections. The researchers found that the factors associated with incident HCV-infection were higher number of receptive condomless anal sex acts with casual partners, anal STI, injecting drug use, and sharing straws when snorting drugs. These are similar risk-factors to those found among in HIV-positive MSM.
They concluded that, because HIV-negative MSM on PrEP are at risk for incident HCV-infection, regular HCV-testing was needed, especially for those with a previous HCV-infection.
Hepatitis C virus (HCV) is known to be a common sexually transmitted infection (STI) among HIV-positive men who have sex with men (MSM). To examine this relationship in HIV-negative MSM, researchers in the Amsterdam PrEP Project team in the HIV Transmission Elimination AMsterdam (H-TEAM) Initiative evaluated HCV-incidence and its risk-factors in this population, who were using pre-exposure prophylaxis (PrEP).
Participants in the Amsterdam PrEP project were tested for HCV antibodies or HCV-RNA every 6 months. During the period, participants used daily or event-driven PrEP and could switch regimens during follow-up, according to the report by published in the Journal of Hepatology.
HIV-negative MSM on PrEP are at risk for incident HCV-infection, while identified risk-factors are similar to those in HIV-positive MSM.
Among 350 participants, they detected 15 HCV infections in 14 participants, finding 8 primary infections and 7 reinfections. The researchers found that the factors associated with incident HCV-infection were higher number of receptive condomless anal sex acts with casual partners, anal STI, injecting drug use, and sharing straws when snorting drugs. These are similar risk-factors to those found among in HIV-positive MSM.
They concluded that, because HIV-negative MSM on PrEP are at risk for incident HCV-infection, regular HCV-testing was needed, especially for those with a previous HCV-infection.
Hepatitis C virus (HCV) is known to be a common sexually transmitted infection (STI) among HIV-positive men who have sex with men (MSM). To examine this relationship in HIV-negative MSM, researchers in the Amsterdam PrEP Project team in the HIV Transmission Elimination AMsterdam (H-TEAM) Initiative evaluated HCV-incidence and its risk-factors in this population, who were using pre-exposure prophylaxis (PrEP).
Participants in the Amsterdam PrEP project were tested for HCV antibodies or HCV-RNA every 6 months. During the period, participants used daily or event-driven PrEP and could switch regimens during follow-up, according to the report by published in the Journal of Hepatology.
HIV-negative MSM on PrEP are at risk for incident HCV-infection, while identified risk-factors are similar to those in HIV-positive MSM.
Among 350 participants, they detected 15 HCV infections in 14 participants, finding 8 primary infections and 7 reinfections. The researchers found that the factors associated with incident HCV-infection were higher number of receptive condomless anal sex acts with casual partners, anal STI, injecting drug use, and sharing straws when snorting drugs. These are similar risk-factors to those found among in HIV-positive MSM.
They concluded that, because HIV-negative MSM on PrEP are at risk for incident HCV-infection, regular HCV-testing was needed, especially for those with a previous HCV-infection.
FROM THE JOURNAL OF HEPATOLOGY
The rise of U.S. dermatology: A brief history from the 1800s to 1970
As Dermatology News (formerly Skin and Allergy News) reaches its 50th-year milestone, a reflection on the history of the discipline, especially in the United States, up to the time of the launch of this publication is in order. Such an overview must, of course, be cursory in this context. Yet, for those who want to learn more, a large body of historical references and research has been created to fill in the gaps, as modern dermatology has always been cognizant of the importance of its history, with many individuals and groups drawn to the subject.
Two excellent sources for the history of the field can be found in work by William Allen Pusey, MD (1865-1940), and Herbert Rattner, MD (1900-1962), “The History of Dermatology” published in 1933 and research by members of the History of Dermatology Society, founded in 1973 in New York.
Modern dermatology
The development of the field of modern dermatology can be traced back to the early to mid-19th century. During the first half of the 19th century, England and France dominated the study of dermatology, but by the middle of the century, the German revolution in microparasitology shifted that focus “with remarkable German discoveries,” according to Bernard S. Potter, MD, in his review of bibliographic landmarks of the history of dermatology (J Am Acad Dermatol 2003;48:919-32). For example, Johann Lucas Schoenlein (1793-1864) in 1839 discovered the fungal origin of favus, and in 1841 Jacob Henle (1809-1885) discovered Demodex folliculorum. Karl Ferdinand Eichstedt (1816-1892) in 1846 followed with the discovery of the causative agent of pityriasis versicolor, and Friedrich Wilhelm Felix von Barensprung (1822-1864) in 1862 coined the term erythrasma and named the organism responsible for this condition Microsporum minutissimum.
Dr. Potter described how American dermatology originated in New York City in 1836 when Henry Daggett Bulkley, MD, (1803-1872) opened the first dispensary for skin diseases, the Broome Street Infirmary for Diseases of the Skin, thus creating the first institution in the United States for the treatment of cutaneous disease. As the first American dermatologist, he was also the first in the United States to lecture on and to exclusively practice dermatology.
The rise of interest in the importance of dermatology led to the organization of the early American Dermatological Association in 1886.
However, the state of dermatology as a science in the 19th century was not always looked upon favorably, even by its practitioners, especially in the United States. In 1871, in a “Review on Modern Dermatology,” given as a series of lectures on skin disease at Harvard University, James C. White, MD (1833-1916) of Massachusetts General Hospital, stated that: “Were the literature of skin diseases previous to that of the last half-century absolutely annihilated, and with it, the influence it has exercised upon that of the present day, it would be an immense gain to dermatology, although much of real value would perish.” He lamented that America had contributed little so far to the study of dermatology, and that the discipline was only taught in some of its largest schools, and he urged that this be changed. He also lamented that The American Journal of Syphilography and Dermatology, established the year before, had so far proved itself heavy on syphilis, but light on dermatology, a situation he also hoped would change dramatically.
By the late-19th century, the conviction that diseases of the skin needed to be connected to the overall metabolism and physiology of the patient as a whole was becoming more mainstream.
“It has been, and still is, too much the custom to study diseases of the skin in the light of pathological pictures, to name the local manifestation and to so label it as disease. It is much easier to give the disease name and to label it than it is to comprehend the process at work. The former is comparatively unimportant for the patient, the latter point upon which recovery may depend. The nature and meaning of the process in connection with the cutaneous symptoms has not received enough attention, and I believe this to be one reason why the treatment of many of these diseases in the past has been so notoriously unsatisfactory,” Louis A. Duhring, MD (1845-1913) chided his colleagues in the Section of Dermatology and Syphilography, at the Forty-fourth Annual Meeting of the American Medical Association in 1894. (collections.nlm.nih.gov/ext/dw/101489447/PDF/101489447.pdf)
In the early-20th century, German dermatology influenced American dermatology more than any other, according to Karl Holubar, MD, of the Institute for the History of Medicine, University of Vienna, in his lecture on the history of European dermatopathology.
He stated that, with regard to dermatopathology, it was Oscar Gans, MD (1888-1983) who brought the latest knowledge into the United States by delivering a series of lectures at Mayo Clinic in the late 1920s upon the invitation of Paul A. O’Leary, MD, (1891-1955) who then headed the Mayo section of dermatology.
By the 1930s, a flurry of organizational activity overtook American dermatology. In 1932, the American Board of Dermatology was established, with its first exams given in 1933 (20 students passed, 7 failed). The Society for Investigative Dermatology was founded in 1937, and the American Academy of Dermatology and Syphilology (now the American Academy of Dermatology), founded in 1938.
The 1930s also saw a major influx of German and other European Jews fleeing Nazi oppression who would forever change the face of American dermatology. “Between 1933 and 1938, a series of repressive measures eliminated them from the practice of medicine in Germany and other countries. Although some died in concentration camps and others committed suicide, many were able to emigrate from Europe. Dermatology in the United States particularly benefited from the influx of several stellar Jewish dermatologists who were major contributors to the subsequent flowering of academic dermatology in the United States” (JAMA Derm. 2013;149[9]:1090-4).
“The overtures of the holocaust and the rising power of Hitler in Europe finally brought over to the United States the flower of dermatologists and investigators of the German School, e.g., Alexander and Walter Lever, Felix and Hermann Pinkus, the Epsteins, Erich Auerbach, Stephen Rothman, to name just a few. With this exodus and transfer of brain power, Europe lost its leading role to never again regain it,” according to Dr. Holubar. Walter F. Lever, MD (1909-1992) was especially well-known for his landmark textbook on dermatology, “Histopathology of the Skin,” published in the United States in 1949.
The therapeutic era
Throughout the 19th century, a variety of soaps and patent medicines were touted as cure-alls for a host of skin diseases. Other than their benefits to surface cleanliness and their antiseptic properties, however, they were of little effect.
It wasn’t until the 20th century that truly effective therapeutics entered the dermatologic pharmacopoeia. In their 1989 review, Diane Quintal, MD, and Robert Jackson, MD, discussed the origins of the most important of these drugs and pointed out that, “Until this century, the essence of dermatology resided in the realm of morphology. Early contributors largely confined their activities to the classification of skin diseases and to the elaboration of clinical dermatologic entities based on morphologic features. ... but “in the last 50 years, there have been significant scientific discoveries in the field of therapeutics that have revolutionized the practice of dermatology.“ (Clin Dermatol. 1989;7[3]38-47).
These key drugs comprised:
- Quinacrine was introduced in 1932 by Walter Kikuth, MD, as an antimalarial drug. But it was not until 1940, that A.J. Prokoptchouksi, MD, reported on its effectiveness 35 patients with lupus erythematosus.
- Para-aminobenzoic acid (PABA) came into prominence in 1942, when Stephen Rothman, MD, and Jack Rubin, MD, at the University of Chicago, published the results of their experiment, showing that when PABA was incorporated in an ointment base and applied to the skin, it could protect against sunburn.
- Dapsone. The effectiveness of sulfapyridine was demonstrated in 1947 by M.J. Costello, MD, who reported its usefulness in a patient with dermatitis herpetiformis, which he believed to be caused by a bacterial allergy. Sulfapyridine controlled the disease, but gastrointestinal intolerance and sulfonamide sensitivity were side effects. Ultimately, in 1951, Theodore Cornbleet, MD, introduced the use of sulfoxones in his article entitled “Sulfoxone (diasones) sodium for dermatitis herpetiformis,” considered more effective than sulfapyridine. Dapsone is the active principal ingredient.
- Hydrocortisone. In August 1952, Marion Sulzberger, MD, and Victor H. Witten, MD (both members of the first Skin & Allergy News editorial advisory board), described use of Compound F (17-hydroxycorticosterone-21-acetate, hydrocortisone) in seven cases of atopic dermatitis and one case of discoid or subacute lupus erythematosus, reporting improvement in all of these cases.
- Benzoyl peroxide. Canadian dermatologist William E. Pace, MD, reported on the beneficial effects of benzoyl peroxide on acne in 1953. The product had originally been used for chronic Staphylococcus aureus folliculitis of the beard.
- Griseofulvin, a metabolic byproduct of a number of species of Penicillium, was first isolated in 1939. But in 1958, Harvey Blank, MD, at the University of Miami (also on the first Skin & Allergy News editorial advisory board), and Stanley I. Cullen, MD, administered the drug to a patient with Trichophyton rubrum granuloma, in the first human trial. In 1959, they reported the drug’s benefits on 31 patients with various fungal infections.
- Methotrexate. In 1951, R. Gubner, MD, and colleagues noticed the rapid clearing of skin lesions in a patient with rheumatoid arthritis who had been treated with the folic acid antagonist, aminopterin. And in 1958, W.F. Edmundson, MD, and W.B. Guy, MD, reported on the oral use of the folic acid antagonist, methotrexate. This was followed by multiple reports on the successful use of methotrexate in psoriasis.
- 5-fluorouracil (5-FU). In 1957, 5-FU, an antimetabolite of uracil, was first synthesized. In 1962, G. Falkson, MD, and E.J. Schulz, MD, reported on skin changes observed in 85 patients being treated with systemic 5-FU for advanced carcinomatosis. They found that 31 of the 85 patients developed sensitivity to sunlight and subsequent disappearance of actinic keratoses in these same patients.
Technology in skin care also was developing in the era just before the launch of Skin & Allergy News. For example, Leon Goldman, MD, then chairman of the department of dermatology at the University of Cincinnati, was the first physician to use a laser for tattoo removal. His publication in 1965 helped to solidify its use, leading him to be “regarded by many in the dermatologic community as the ‘godfather of lasers in medicine and surgery’ ” (Clin Dermatol. 2007;25:434-42).
So, by 1970, dermatology as a field had established itself fully with a strong societal infrastructure, a vibrant base of journals and books, and an evolving set of scientific and technical tools. The launch of Skin & Allergy News (now Dermatology News) that year would chronicle dermatology’s commitment to the development of new therapeutics and technologies in service of patient needs – the stories of which would grace the newspaper’s pages for 5 decades and counting.
As Dermatology News (formerly Skin and Allergy News) reaches its 50th-year milestone, a reflection on the history of the discipline, especially in the United States, up to the time of the launch of this publication is in order. Such an overview must, of course, be cursory in this context. Yet, for those who want to learn more, a large body of historical references and research has been created to fill in the gaps, as modern dermatology has always been cognizant of the importance of its history, with many individuals and groups drawn to the subject.
Two excellent sources for the history of the field can be found in work by William Allen Pusey, MD (1865-1940), and Herbert Rattner, MD (1900-1962), “The History of Dermatology” published in 1933 and research by members of the History of Dermatology Society, founded in 1973 in New York.
Modern dermatology
The development of the field of modern dermatology can be traced back to the early to mid-19th century. During the first half of the 19th century, England and France dominated the study of dermatology, but by the middle of the century, the German revolution in microparasitology shifted that focus “with remarkable German discoveries,” according to Bernard S. Potter, MD, in his review of bibliographic landmarks of the history of dermatology (J Am Acad Dermatol 2003;48:919-32). For example, Johann Lucas Schoenlein (1793-1864) in 1839 discovered the fungal origin of favus, and in 1841 Jacob Henle (1809-1885) discovered Demodex folliculorum. Karl Ferdinand Eichstedt (1816-1892) in 1846 followed with the discovery of the causative agent of pityriasis versicolor, and Friedrich Wilhelm Felix von Barensprung (1822-1864) in 1862 coined the term erythrasma and named the organism responsible for this condition Microsporum minutissimum.
Dr. Potter described how American dermatology originated in New York City in 1836 when Henry Daggett Bulkley, MD, (1803-1872) opened the first dispensary for skin diseases, the Broome Street Infirmary for Diseases of the Skin, thus creating the first institution in the United States for the treatment of cutaneous disease. As the first American dermatologist, he was also the first in the United States to lecture on and to exclusively practice dermatology.
The rise of interest in the importance of dermatology led to the organization of the early American Dermatological Association in 1886.
However, the state of dermatology as a science in the 19th century was not always looked upon favorably, even by its practitioners, especially in the United States. In 1871, in a “Review on Modern Dermatology,” given as a series of lectures on skin disease at Harvard University, James C. White, MD (1833-1916) of Massachusetts General Hospital, stated that: “Were the literature of skin diseases previous to that of the last half-century absolutely annihilated, and with it, the influence it has exercised upon that of the present day, it would be an immense gain to dermatology, although much of real value would perish.” He lamented that America had contributed little so far to the study of dermatology, and that the discipline was only taught in some of its largest schools, and he urged that this be changed. He also lamented that The American Journal of Syphilography and Dermatology, established the year before, had so far proved itself heavy on syphilis, but light on dermatology, a situation he also hoped would change dramatically.
By the late-19th century, the conviction that diseases of the skin needed to be connected to the overall metabolism and physiology of the patient as a whole was becoming more mainstream.
“It has been, and still is, too much the custom to study diseases of the skin in the light of pathological pictures, to name the local manifestation and to so label it as disease. It is much easier to give the disease name and to label it than it is to comprehend the process at work. The former is comparatively unimportant for the patient, the latter point upon which recovery may depend. The nature and meaning of the process in connection with the cutaneous symptoms has not received enough attention, and I believe this to be one reason why the treatment of many of these diseases in the past has been so notoriously unsatisfactory,” Louis A. Duhring, MD (1845-1913) chided his colleagues in the Section of Dermatology and Syphilography, at the Forty-fourth Annual Meeting of the American Medical Association in 1894. (collections.nlm.nih.gov/ext/dw/101489447/PDF/101489447.pdf)
In the early-20th century, German dermatology influenced American dermatology more than any other, according to Karl Holubar, MD, of the Institute for the History of Medicine, University of Vienna, in his lecture on the history of European dermatopathology.
He stated that, with regard to dermatopathology, it was Oscar Gans, MD (1888-1983) who brought the latest knowledge into the United States by delivering a series of lectures at Mayo Clinic in the late 1920s upon the invitation of Paul A. O’Leary, MD, (1891-1955) who then headed the Mayo section of dermatology.
By the 1930s, a flurry of organizational activity overtook American dermatology. In 1932, the American Board of Dermatology was established, with its first exams given in 1933 (20 students passed, 7 failed). The Society for Investigative Dermatology was founded in 1937, and the American Academy of Dermatology and Syphilology (now the American Academy of Dermatology), founded in 1938.
The 1930s also saw a major influx of German and other European Jews fleeing Nazi oppression who would forever change the face of American dermatology. “Between 1933 and 1938, a series of repressive measures eliminated them from the practice of medicine in Germany and other countries. Although some died in concentration camps and others committed suicide, many were able to emigrate from Europe. Dermatology in the United States particularly benefited from the influx of several stellar Jewish dermatologists who were major contributors to the subsequent flowering of academic dermatology in the United States” (JAMA Derm. 2013;149[9]:1090-4).
“The overtures of the holocaust and the rising power of Hitler in Europe finally brought over to the United States the flower of dermatologists and investigators of the German School, e.g., Alexander and Walter Lever, Felix and Hermann Pinkus, the Epsteins, Erich Auerbach, Stephen Rothman, to name just a few. With this exodus and transfer of brain power, Europe lost its leading role to never again regain it,” according to Dr. Holubar. Walter F. Lever, MD (1909-1992) was especially well-known for his landmark textbook on dermatology, “Histopathology of the Skin,” published in the United States in 1949.
The therapeutic era
Throughout the 19th century, a variety of soaps and patent medicines were touted as cure-alls for a host of skin diseases. Other than their benefits to surface cleanliness and their antiseptic properties, however, they were of little effect.
It wasn’t until the 20th century that truly effective therapeutics entered the dermatologic pharmacopoeia. In their 1989 review, Diane Quintal, MD, and Robert Jackson, MD, discussed the origins of the most important of these drugs and pointed out that, “Until this century, the essence of dermatology resided in the realm of morphology. Early contributors largely confined their activities to the classification of skin diseases and to the elaboration of clinical dermatologic entities based on morphologic features. ... but “in the last 50 years, there have been significant scientific discoveries in the field of therapeutics that have revolutionized the practice of dermatology.“ (Clin Dermatol. 1989;7[3]38-47).
These key drugs comprised:
- Quinacrine was introduced in 1932 by Walter Kikuth, MD, as an antimalarial drug. But it was not until 1940, that A.J. Prokoptchouksi, MD, reported on its effectiveness 35 patients with lupus erythematosus.
- Para-aminobenzoic acid (PABA) came into prominence in 1942, when Stephen Rothman, MD, and Jack Rubin, MD, at the University of Chicago, published the results of their experiment, showing that when PABA was incorporated in an ointment base and applied to the skin, it could protect against sunburn.
- Dapsone. The effectiveness of sulfapyridine was demonstrated in 1947 by M.J. Costello, MD, who reported its usefulness in a patient with dermatitis herpetiformis, which he believed to be caused by a bacterial allergy. Sulfapyridine controlled the disease, but gastrointestinal intolerance and sulfonamide sensitivity were side effects. Ultimately, in 1951, Theodore Cornbleet, MD, introduced the use of sulfoxones in his article entitled “Sulfoxone (diasones) sodium for dermatitis herpetiformis,” considered more effective than sulfapyridine. Dapsone is the active principal ingredient.
- Hydrocortisone. In August 1952, Marion Sulzberger, MD, and Victor H. Witten, MD (both members of the first Skin & Allergy News editorial advisory board), described use of Compound F (17-hydroxycorticosterone-21-acetate, hydrocortisone) in seven cases of atopic dermatitis and one case of discoid or subacute lupus erythematosus, reporting improvement in all of these cases.
- Benzoyl peroxide. Canadian dermatologist William E. Pace, MD, reported on the beneficial effects of benzoyl peroxide on acne in 1953. The product had originally been used for chronic Staphylococcus aureus folliculitis of the beard.
- Griseofulvin, a metabolic byproduct of a number of species of Penicillium, was first isolated in 1939. But in 1958, Harvey Blank, MD, at the University of Miami (also on the first Skin & Allergy News editorial advisory board), and Stanley I. Cullen, MD, administered the drug to a patient with Trichophyton rubrum granuloma, in the first human trial. In 1959, they reported the drug’s benefits on 31 patients with various fungal infections.
- Methotrexate. In 1951, R. Gubner, MD, and colleagues noticed the rapid clearing of skin lesions in a patient with rheumatoid arthritis who had been treated with the folic acid antagonist, aminopterin. And in 1958, W.F. Edmundson, MD, and W.B. Guy, MD, reported on the oral use of the folic acid antagonist, methotrexate. This was followed by multiple reports on the successful use of methotrexate in psoriasis.
- 5-fluorouracil (5-FU). In 1957, 5-FU, an antimetabolite of uracil, was first synthesized. In 1962, G. Falkson, MD, and E.J. Schulz, MD, reported on skin changes observed in 85 patients being treated with systemic 5-FU for advanced carcinomatosis. They found that 31 of the 85 patients developed sensitivity to sunlight and subsequent disappearance of actinic keratoses in these same patients.
Technology in skin care also was developing in the era just before the launch of Skin & Allergy News. For example, Leon Goldman, MD, then chairman of the department of dermatology at the University of Cincinnati, was the first physician to use a laser for tattoo removal. His publication in 1965 helped to solidify its use, leading him to be “regarded by many in the dermatologic community as the ‘godfather of lasers in medicine and surgery’ ” (Clin Dermatol. 2007;25:434-42).
So, by 1970, dermatology as a field had established itself fully with a strong societal infrastructure, a vibrant base of journals and books, and an evolving set of scientific and technical tools. The launch of Skin & Allergy News (now Dermatology News) that year would chronicle dermatology’s commitment to the development of new therapeutics and technologies in service of patient needs – the stories of which would grace the newspaper’s pages for 5 decades and counting.
As Dermatology News (formerly Skin and Allergy News) reaches its 50th-year milestone, a reflection on the history of the discipline, especially in the United States, up to the time of the launch of this publication is in order. Such an overview must, of course, be cursory in this context. Yet, for those who want to learn more, a large body of historical references and research has been created to fill in the gaps, as modern dermatology has always been cognizant of the importance of its history, with many individuals and groups drawn to the subject.
Two excellent sources for the history of the field can be found in work by William Allen Pusey, MD (1865-1940), and Herbert Rattner, MD (1900-1962), “The History of Dermatology” published in 1933 and research by members of the History of Dermatology Society, founded in 1973 in New York.
Modern dermatology
The development of the field of modern dermatology can be traced back to the early to mid-19th century. During the first half of the 19th century, England and France dominated the study of dermatology, but by the middle of the century, the German revolution in microparasitology shifted that focus “with remarkable German discoveries,” according to Bernard S. Potter, MD, in his review of bibliographic landmarks of the history of dermatology (J Am Acad Dermatol 2003;48:919-32). For example, Johann Lucas Schoenlein (1793-1864) in 1839 discovered the fungal origin of favus, and in 1841 Jacob Henle (1809-1885) discovered Demodex folliculorum. Karl Ferdinand Eichstedt (1816-1892) in 1846 followed with the discovery of the causative agent of pityriasis versicolor, and Friedrich Wilhelm Felix von Barensprung (1822-1864) in 1862 coined the term erythrasma and named the organism responsible for this condition Microsporum minutissimum.
Dr. Potter described how American dermatology originated in New York City in 1836 when Henry Daggett Bulkley, MD, (1803-1872) opened the first dispensary for skin diseases, the Broome Street Infirmary for Diseases of the Skin, thus creating the first institution in the United States for the treatment of cutaneous disease. As the first American dermatologist, he was also the first in the United States to lecture on and to exclusively practice dermatology.
The rise of interest in the importance of dermatology led to the organization of the early American Dermatological Association in 1886.
However, the state of dermatology as a science in the 19th century was not always looked upon favorably, even by its practitioners, especially in the United States. In 1871, in a “Review on Modern Dermatology,” given as a series of lectures on skin disease at Harvard University, James C. White, MD (1833-1916) of Massachusetts General Hospital, stated that: “Were the literature of skin diseases previous to that of the last half-century absolutely annihilated, and with it, the influence it has exercised upon that of the present day, it would be an immense gain to dermatology, although much of real value would perish.” He lamented that America had contributed little so far to the study of dermatology, and that the discipline was only taught in some of its largest schools, and he urged that this be changed. He also lamented that The American Journal of Syphilography and Dermatology, established the year before, had so far proved itself heavy on syphilis, but light on dermatology, a situation he also hoped would change dramatically.
By the late-19th century, the conviction that diseases of the skin needed to be connected to the overall metabolism and physiology of the patient as a whole was becoming more mainstream.
“It has been, and still is, too much the custom to study diseases of the skin in the light of pathological pictures, to name the local manifestation and to so label it as disease. It is much easier to give the disease name and to label it than it is to comprehend the process at work. The former is comparatively unimportant for the patient, the latter point upon which recovery may depend. The nature and meaning of the process in connection with the cutaneous symptoms has not received enough attention, and I believe this to be one reason why the treatment of many of these diseases in the past has been so notoriously unsatisfactory,” Louis A. Duhring, MD (1845-1913) chided his colleagues in the Section of Dermatology and Syphilography, at the Forty-fourth Annual Meeting of the American Medical Association in 1894. (collections.nlm.nih.gov/ext/dw/101489447/PDF/101489447.pdf)
In the early-20th century, German dermatology influenced American dermatology more than any other, according to Karl Holubar, MD, of the Institute for the History of Medicine, University of Vienna, in his lecture on the history of European dermatopathology.
He stated that, with regard to dermatopathology, it was Oscar Gans, MD (1888-1983) who brought the latest knowledge into the United States by delivering a series of lectures at Mayo Clinic in the late 1920s upon the invitation of Paul A. O’Leary, MD, (1891-1955) who then headed the Mayo section of dermatology.
By the 1930s, a flurry of organizational activity overtook American dermatology. In 1932, the American Board of Dermatology was established, with its first exams given in 1933 (20 students passed, 7 failed). The Society for Investigative Dermatology was founded in 1937, and the American Academy of Dermatology and Syphilology (now the American Academy of Dermatology), founded in 1938.
The 1930s also saw a major influx of German and other European Jews fleeing Nazi oppression who would forever change the face of American dermatology. “Between 1933 and 1938, a series of repressive measures eliminated them from the practice of medicine in Germany and other countries. Although some died in concentration camps and others committed suicide, many were able to emigrate from Europe. Dermatology in the United States particularly benefited from the influx of several stellar Jewish dermatologists who were major contributors to the subsequent flowering of academic dermatology in the United States” (JAMA Derm. 2013;149[9]:1090-4).
“The overtures of the holocaust and the rising power of Hitler in Europe finally brought over to the United States the flower of dermatologists and investigators of the German School, e.g., Alexander and Walter Lever, Felix and Hermann Pinkus, the Epsteins, Erich Auerbach, Stephen Rothman, to name just a few. With this exodus and transfer of brain power, Europe lost its leading role to never again regain it,” according to Dr. Holubar. Walter F. Lever, MD (1909-1992) was especially well-known for his landmark textbook on dermatology, “Histopathology of the Skin,” published in the United States in 1949.
The therapeutic era
Throughout the 19th century, a variety of soaps and patent medicines were touted as cure-alls for a host of skin diseases. Other than their benefits to surface cleanliness and their antiseptic properties, however, they were of little effect.
It wasn’t until the 20th century that truly effective therapeutics entered the dermatologic pharmacopoeia. In their 1989 review, Diane Quintal, MD, and Robert Jackson, MD, discussed the origins of the most important of these drugs and pointed out that, “Until this century, the essence of dermatology resided in the realm of morphology. Early contributors largely confined their activities to the classification of skin diseases and to the elaboration of clinical dermatologic entities based on morphologic features. ... but “in the last 50 years, there have been significant scientific discoveries in the field of therapeutics that have revolutionized the practice of dermatology.“ (Clin Dermatol. 1989;7[3]38-47).
These key drugs comprised:
- Quinacrine was introduced in 1932 by Walter Kikuth, MD, as an antimalarial drug. But it was not until 1940, that A.J. Prokoptchouksi, MD, reported on its effectiveness 35 patients with lupus erythematosus.
- Para-aminobenzoic acid (PABA) came into prominence in 1942, when Stephen Rothman, MD, and Jack Rubin, MD, at the University of Chicago, published the results of their experiment, showing that when PABA was incorporated in an ointment base and applied to the skin, it could protect against sunburn.
- Dapsone. The effectiveness of sulfapyridine was demonstrated in 1947 by M.J. Costello, MD, who reported its usefulness in a patient with dermatitis herpetiformis, which he believed to be caused by a bacterial allergy. Sulfapyridine controlled the disease, but gastrointestinal intolerance and sulfonamide sensitivity were side effects. Ultimately, in 1951, Theodore Cornbleet, MD, introduced the use of sulfoxones in his article entitled “Sulfoxone (diasones) sodium for dermatitis herpetiformis,” considered more effective than sulfapyridine. Dapsone is the active principal ingredient.
- Hydrocortisone. In August 1952, Marion Sulzberger, MD, and Victor H. Witten, MD (both members of the first Skin & Allergy News editorial advisory board), described use of Compound F (17-hydroxycorticosterone-21-acetate, hydrocortisone) in seven cases of atopic dermatitis and one case of discoid or subacute lupus erythematosus, reporting improvement in all of these cases.
- Benzoyl peroxide. Canadian dermatologist William E. Pace, MD, reported on the beneficial effects of benzoyl peroxide on acne in 1953. The product had originally been used for chronic Staphylococcus aureus folliculitis of the beard.
- Griseofulvin, a metabolic byproduct of a number of species of Penicillium, was first isolated in 1939. But in 1958, Harvey Blank, MD, at the University of Miami (also on the first Skin & Allergy News editorial advisory board), and Stanley I. Cullen, MD, administered the drug to a patient with Trichophyton rubrum granuloma, in the first human trial. In 1959, they reported the drug’s benefits on 31 patients with various fungal infections.
- Methotrexate. In 1951, R. Gubner, MD, and colleagues noticed the rapid clearing of skin lesions in a patient with rheumatoid arthritis who had been treated with the folic acid antagonist, aminopterin. And in 1958, W.F. Edmundson, MD, and W.B. Guy, MD, reported on the oral use of the folic acid antagonist, methotrexate. This was followed by multiple reports on the successful use of methotrexate in psoriasis.
- 5-fluorouracil (5-FU). In 1957, 5-FU, an antimetabolite of uracil, was first synthesized. In 1962, G. Falkson, MD, and E.J. Schulz, MD, reported on skin changes observed in 85 patients being treated with systemic 5-FU for advanced carcinomatosis. They found that 31 of the 85 patients developed sensitivity to sunlight and subsequent disappearance of actinic keratoses in these same patients.
Technology in skin care also was developing in the era just before the launch of Skin & Allergy News. For example, Leon Goldman, MD, then chairman of the department of dermatology at the University of Cincinnati, was the first physician to use a laser for tattoo removal. His publication in 1965 helped to solidify its use, leading him to be “regarded by many in the dermatologic community as the ‘godfather of lasers in medicine and surgery’ ” (Clin Dermatol. 2007;25:434-42).
So, by 1970, dermatology as a field had established itself fully with a strong societal infrastructure, a vibrant base of journals and books, and an evolving set of scientific and technical tools. The launch of Skin & Allergy News (now Dermatology News) that year would chronicle dermatology’s commitment to the development of new therapeutics and technologies in service of patient needs – the stories of which would grace the newspaper’s pages for 5 decades and counting.
ID consult for Candida bloodstream infections can reduce mortality risk
findings from a large retrospective study suggest.
Mortality attributable to Candida bloodstream infection ranges between 15% and 47%, and delay in initiation of appropriate treatment has been associated with increased mortality. Previous small studies showed that ID consultation has conferred benefits to patients with Candida bloodstream infections. Carlos Mejia-Chew, MD, and colleagues from Washington University, St. Louis, sought to explore this further by performing a retrospective, single-center cohort study of 1,691 patients aged 18 years or older with Candida bloodstream infection from 2002 to 2015. They analyzed demographics, comorbidities, predisposing factors, all-cause mortality, antifungal use, central-line removal, and ophthalmological and echocardiographic evaluation in order to compare 90-day all-cause mortality between individuals with and without an ID consultation.
They found that those patients who received an ID consult for a Candida bloodstream infection had a significantly lower 90-day mortality rate than did those who did not (29% vs. 51%).
With a model using inverse weighting by the propensity score, they found that ID consultation was associated with a hazard ratio of 0.81 for mortality (95% confidence interval, 0.73-0.91; P less than .0001). In the ID consultation group, the median duration of antifungal therapy was significantly longer (18 vs. 14 days; P less than .0001); central-line removal was significantly more common (76% vs. 59%; P less than .0001); echocardiography use was more frequent (57% vs. 33%; P less than .0001); and ophthalmological examinations were performed more often (53% vs. 17%; P less than .0001). Importantly, fewer patients in the ID consultation group were untreated (2% vs. 14%; P less than .0001).
In an accompanying commentary, Katrien Lagrou, MD, and Eric Van Wijngaerden, MD, of the department of microbiology, immunology and transplantation, University Hospitals Leuven (Belgium) stated: “We think that the high proportion of patients (14%) with a Candida bloodstream infection who did not receive any antifungal treatment and did not have an infectious disease consultation is a particularly alarming finding. ... Ninety-day mortality in these untreated patients was high (67%).”
“We believe every hospital should have an expert management strategy addressing all individual cases of candidaemia. The need for such expert management should be incorporated in all future candidaemia management guidelines,” they concluded.
The study was funded by the Astellas Global Development Pharma, the Washington University Institute of Clinical and Translational Sciences, and the Agency for Healthcare Research and Quality. Several of the authors had financial connections to Astellas Global Development or other pharmaceutical companies. Dr. Lagrou and Dr. Van Wijngaerden both reported receiving personal fees and nonfinancial support from a number of pharmaceutical companies, but all outside the scope of the study.
SOURCE: Mejia-Chew C et al. Lancet Infect Dis. 2019;19:1336-44.
findings from a large retrospective study suggest.
Mortality attributable to Candida bloodstream infection ranges between 15% and 47%, and delay in initiation of appropriate treatment has been associated with increased mortality. Previous small studies showed that ID consultation has conferred benefits to patients with Candida bloodstream infections. Carlos Mejia-Chew, MD, and colleagues from Washington University, St. Louis, sought to explore this further by performing a retrospective, single-center cohort study of 1,691 patients aged 18 years or older with Candida bloodstream infection from 2002 to 2015. They analyzed demographics, comorbidities, predisposing factors, all-cause mortality, antifungal use, central-line removal, and ophthalmological and echocardiographic evaluation in order to compare 90-day all-cause mortality between individuals with and without an ID consultation.
They found that those patients who received an ID consult for a Candida bloodstream infection had a significantly lower 90-day mortality rate than did those who did not (29% vs. 51%).
With a model using inverse weighting by the propensity score, they found that ID consultation was associated with a hazard ratio of 0.81 for mortality (95% confidence interval, 0.73-0.91; P less than .0001). In the ID consultation group, the median duration of antifungal therapy was significantly longer (18 vs. 14 days; P less than .0001); central-line removal was significantly more common (76% vs. 59%; P less than .0001); echocardiography use was more frequent (57% vs. 33%; P less than .0001); and ophthalmological examinations were performed more often (53% vs. 17%; P less than .0001). Importantly, fewer patients in the ID consultation group were untreated (2% vs. 14%; P less than .0001).
In an accompanying commentary, Katrien Lagrou, MD, and Eric Van Wijngaerden, MD, of the department of microbiology, immunology and transplantation, University Hospitals Leuven (Belgium) stated: “We think that the high proportion of patients (14%) with a Candida bloodstream infection who did not receive any antifungal treatment and did not have an infectious disease consultation is a particularly alarming finding. ... Ninety-day mortality in these untreated patients was high (67%).”
“We believe every hospital should have an expert management strategy addressing all individual cases of candidaemia. The need for such expert management should be incorporated in all future candidaemia management guidelines,” they concluded.
The study was funded by the Astellas Global Development Pharma, the Washington University Institute of Clinical and Translational Sciences, and the Agency for Healthcare Research and Quality. Several of the authors had financial connections to Astellas Global Development or other pharmaceutical companies. Dr. Lagrou and Dr. Van Wijngaerden both reported receiving personal fees and nonfinancial support from a number of pharmaceutical companies, but all outside the scope of the study.
SOURCE: Mejia-Chew C et al. Lancet Infect Dis. 2019;19:1336-44.
findings from a large retrospective study suggest.
Mortality attributable to Candida bloodstream infection ranges between 15% and 47%, and delay in initiation of appropriate treatment has been associated with increased mortality. Previous small studies showed that ID consultation has conferred benefits to patients with Candida bloodstream infections. Carlos Mejia-Chew, MD, and colleagues from Washington University, St. Louis, sought to explore this further by performing a retrospective, single-center cohort study of 1,691 patients aged 18 years or older with Candida bloodstream infection from 2002 to 2015. They analyzed demographics, comorbidities, predisposing factors, all-cause mortality, antifungal use, central-line removal, and ophthalmological and echocardiographic evaluation in order to compare 90-day all-cause mortality between individuals with and without an ID consultation.
They found that those patients who received an ID consult for a Candida bloodstream infection had a significantly lower 90-day mortality rate than did those who did not (29% vs. 51%).
With a model using inverse weighting by the propensity score, they found that ID consultation was associated with a hazard ratio of 0.81 for mortality (95% confidence interval, 0.73-0.91; P less than .0001). In the ID consultation group, the median duration of antifungal therapy was significantly longer (18 vs. 14 days; P less than .0001); central-line removal was significantly more common (76% vs. 59%; P less than .0001); echocardiography use was more frequent (57% vs. 33%; P less than .0001); and ophthalmological examinations were performed more often (53% vs. 17%; P less than .0001). Importantly, fewer patients in the ID consultation group were untreated (2% vs. 14%; P less than .0001).
In an accompanying commentary, Katrien Lagrou, MD, and Eric Van Wijngaerden, MD, of the department of microbiology, immunology and transplantation, University Hospitals Leuven (Belgium) stated: “We think that the high proportion of patients (14%) with a Candida bloodstream infection who did not receive any antifungal treatment and did not have an infectious disease consultation is a particularly alarming finding. ... Ninety-day mortality in these untreated patients was high (67%).”
“We believe every hospital should have an expert management strategy addressing all individual cases of candidaemia. The need for such expert management should be incorporated in all future candidaemia management guidelines,” they concluded.
The study was funded by the Astellas Global Development Pharma, the Washington University Institute of Clinical and Translational Sciences, and the Agency for Healthcare Research and Quality. Several of the authors had financial connections to Astellas Global Development or other pharmaceutical companies. Dr. Lagrou and Dr. Van Wijngaerden both reported receiving personal fees and nonfinancial support from a number of pharmaceutical companies, but all outside the scope of the study.
SOURCE: Mejia-Chew C et al. Lancet Infect Dis. 2019;19:1336-44.
FROM LANCET: INFECTIOUS DISEASES
ID Blog: The waters of death
Diseases of the American Civil War, Part I
If cleanliness is next to godliness, then the average soldier in the American Civil War lived just down the street from hell. In a land at war, before the formal tenets of germ theory had spread beyond the confines of Louis Pasteur’s laboratory in France, the lack of basic hygiene, both cultural and situational, coupled to an almost complete lack of curative therapies created an appalling death toll. Waterborne diseases in particular spared neither general nor private, and neither doctor nor nurse.
“Of all the adversities that Union and Confederate soldiers confronted, none was more deadly or more prevalent than contaminated water,” according to Jeffrey S. Sartin, MD, in his survey of Civil War diseases.1
The Union Army records list 1,765,000 cases of diarrhea or dysentery with 45,000 deaths and 149,000 cases of typhoid fever with 35,000 deaths. Add to these the 1,316,000 cases of malaria (borne by mosquitoes breeding in the waters) with its 10,000 deaths, and it is easy to see how the battlefield itself took second place in service to the grim reaper. (Overall, there were roughly two deaths from disease for every one from wounds.)
The chief waterborne plague, infectious diarrhea – including bacterial, amoebic, and other parasites – as well as cholera and typhoid, was an all-year-long problem, and, with the typical wry humor of soldiers, these maladies were given popular names, including the “Tennessee trots” and the “Virginia quick-step.”
Unsanitary conditions in the camps were primarily to blame, and this problem of sanitation was obvious to many observers at the time.
Despite a lack of knowledge of germ theory, doctors were fully aware of the relationship of unsanitary conditions to disease, even if they ascribed the link to miasmas or particles of filth.
Hospitals, which were under more strict control than the regular army camps, were meticulous about the placement of latrines and about keeping high standards of cleanliness among the patients, including routine washing. However, this was insufficient for complete protection, because what passed for clean in the absence of the knowledge of bacterial contamination was often totally ineffective. As one Civil War surgeon stated: “We operated in old bloodstained and often pus-stained coats, we used undisinfected instruments from undisinfected plush-lined cases. If a sponge (if they had sponges) or instrument fell on the floor it was washed and squeezed in a basin of water and used as if it was clean.”2
Overall, efforts at what passed for sanitation remained a constant goal and constant struggle in the field.
After the First Battle of Bull Run, Women’s Central Association of Relief President Henry W. Bellows met with Secretary of War Simon Cameron to discuss the abysmal sanitary conditions witnessed by WCAR volunteers. This meeting led to the creation of what would become the U.S. Sanitary Commission, which was approved by President Abraham Lincoln on June 13, 1861.
The U.S. Sanitary Commission served as a means for funneling civilian assistance to the military, with volunteers providing assistance in the organization of military hospitals and camps and aiding in the transportation of the wounded. However, despite these efforts, the setup of army camps and the behavior of the soldiers were not often directed toward proper sanitation. “The principal causes of disease, however, in our camps were the same that we have always to deplore and find it so difficult to remedy, simply because citizens suddenly called to the field cannot comprehend that men in masses require the attention of their officers to enforce certain hygienic conditions without which health cannot be preserved.”3
Breaches of sanitation were common in the confines of the camps, despite regulations designed to protect the soldiers. According to one U.S. Army surgeon of the time: “Especially [needed] was policing of the latrines. The trench is generally too shallow, the daily covering ... with dirt is entirely neglected. Large numbers of the men will not use the sinks [latrines], ... but instead every clump of bushes, every fence border in the vicinity.” Another pointed out that, after the Battle of Seven Pines, “the only water was infiltrated with the decaying animal matter of the battlefield.” Commenting on the placement of latrines in one encampment, another surgeon described how “the sink [latrine] is the ground in the vicinity, which slopes down to the stream, from which all water from the camp is obtained.”4
Treatment for diarrhea and dysentery was varied. Opiates were one of the most common treatments for diarrhea, whether in an alcohol solution as laudanum or in pill form, with belladonna being used to treat intestinal cramps, according to Glenna R. Schroeder-Lein in her book “The Encyclopedia of Civil War Medicine.” However, useless or damaging treatments were also prescribed, including the use of calomel (a mercury compound), turpentine, castor oil, and quinine.5
Acute diarrhea and dysentery illnesses occurred in at least 641/1,000 troops per year in the Union army. And even though the death rate was comparatively low (20/1,000 cases), it frequently led to chronic diarrhea, which was responsible for 288 deaths per 1,000 cases, and was the third highest cause of medical discharge after gunshot wounds and tuberculosis, according to Ms. Schroeder-Lein.
Although the American Civil War was the last major conflict before the spread of the knowledge of germ theory, the struggle to prevent the spread of waterborne diseases under wartime conditions remains ongoing. Hygiene is difficult under conditions of abject poverty and especially under conditions of armed conflict, and until the era of curative antibiotics there was no recourse.
Antibiotics are not the final solution for antibiotic resistance in intestinal disease pathogens, as outlined in a recent CDC report, is an increasing problem.6 For example, nontyphoidal Salmonella causes an estimated 1.35 million infections, 26,500 hospitalizations, and 420 deaths each year in the United States, with 16% of strains being resistant to at least one essential antibiotic. On a global scale, according to the World Health Organization, poor sanitation causes up to 432,000 diarrheal deaths annually and is linked to the transmission of other diseases like cholera, dysentery, typhoid, hepatitis A, and polio.7
With regard to actual epidemics, the world is only a hygienic crisis away from a major outbreak of dysentery (the last occurring between 1969 and 1972, when 20,000 people in Central America died), according to researchers who have detected antibiotic resistance in all but 1% of circulating Shigella dysenteriae strains surveyed since the 1990s. “This bacterium is still in circulation, and could be responsible for future epidemics if conditions should prove favorable – such as a large gathering of people without access to drinking water or treatment of human waste,” wrote François-Xavier Weill of the Pasteur Institute’s Enteric Bacterial Pathogens Unit.8
References
1. Sartin JS. Clin Infec Dis. 1993;16:580-4. (Correction published in 2002).
2. Civil War Battlefield Surgery. eHistory. The Ohio State University.
3. “Myths About Antiseptics and Camp Life – George Wunderlich,” published online Oct. 11, 2011. http://civilwarscholars.com/2011/10/myths-about-antiseptics-and-camp-life-george-wunderlich/
4. Dorwart BB. “Death is in the Breeze: Disease during the American Civil War” (The National Museum of the American Civil War Press, 2009).
5. Glenna R, Schroeder-Lein GR. “The Encyclopedia of Civil War Medicine” (New York: M. E. Sharpe, 2008).
6. “Antibiotic resistance threats in the United States 2019” Centers for Disease Control and Prevention.
7. “New report exposes horror of working conditions for millions of sanitation workers in the developing world,” World Health Organization. 2019 Nov 14.
8. Grant B. Origins of Dysentery. The Scientist. Published online March 22, 2016.
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 & cellular biology at Georgetown University, Washington.
Diseases of the American Civil War, Part I
Diseases of the American Civil War, Part I
If cleanliness is next to godliness, then the average soldier in the American Civil War lived just down the street from hell. In a land at war, before the formal tenets of germ theory had spread beyond the confines of Louis Pasteur’s laboratory in France, the lack of basic hygiene, both cultural and situational, coupled to an almost complete lack of curative therapies created an appalling death toll. Waterborne diseases in particular spared neither general nor private, and neither doctor nor nurse.
“Of all the adversities that Union and Confederate soldiers confronted, none was more deadly or more prevalent than contaminated water,” according to Jeffrey S. Sartin, MD, in his survey of Civil War diseases.1
The Union Army records list 1,765,000 cases of diarrhea or dysentery with 45,000 deaths and 149,000 cases of typhoid fever with 35,000 deaths. Add to these the 1,316,000 cases of malaria (borne by mosquitoes breeding in the waters) with its 10,000 deaths, and it is easy to see how the battlefield itself took second place in service to the grim reaper. (Overall, there were roughly two deaths from disease for every one from wounds.)
The chief waterborne plague, infectious diarrhea – including bacterial, amoebic, and other parasites – as well as cholera and typhoid, was an all-year-long problem, and, with the typical wry humor of soldiers, these maladies were given popular names, including the “Tennessee trots” and the “Virginia quick-step.”
Unsanitary conditions in the camps were primarily to blame, and this problem of sanitation was obvious to many observers at the time.
Despite a lack of knowledge of germ theory, doctors were fully aware of the relationship of unsanitary conditions to disease, even if they ascribed the link to miasmas or particles of filth.
Hospitals, which were under more strict control than the regular army camps, were meticulous about the placement of latrines and about keeping high standards of cleanliness among the patients, including routine washing. However, this was insufficient for complete protection, because what passed for clean in the absence of the knowledge of bacterial contamination was often totally ineffective. As one Civil War surgeon stated: “We operated in old bloodstained and often pus-stained coats, we used undisinfected instruments from undisinfected plush-lined cases. If a sponge (if they had sponges) or instrument fell on the floor it was washed and squeezed in a basin of water and used as if it was clean.”2
Overall, efforts at what passed for sanitation remained a constant goal and constant struggle in the field.
After the First Battle of Bull Run, Women’s Central Association of Relief President Henry W. Bellows met with Secretary of War Simon Cameron to discuss the abysmal sanitary conditions witnessed by WCAR volunteers. This meeting led to the creation of what would become the U.S. Sanitary Commission, which was approved by President Abraham Lincoln on June 13, 1861.
The U.S. Sanitary Commission served as a means for funneling civilian assistance to the military, with volunteers providing assistance in the organization of military hospitals and camps and aiding in the transportation of the wounded. However, despite these efforts, the setup of army camps and the behavior of the soldiers were not often directed toward proper sanitation. “The principal causes of disease, however, in our camps were the same that we have always to deplore and find it so difficult to remedy, simply because citizens suddenly called to the field cannot comprehend that men in masses require the attention of their officers to enforce certain hygienic conditions without which health cannot be preserved.”3
Breaches of sanitation were common in the confines of the camps, despite regulations designed to protect the soldiers. According to one U.S. Army surgeon of the time: “Especially [needed] was policing of the latrines. The trench is generally too shallow, the daily covering ... with dirt is entirely neglected. Large numbers of the men will not use the sinks [latrines], ... but instead every clump of bushes, every fence border in the vicinity.” Another pointed out that, after the Battle of Seven Pines, “the only water was infiltrated with the decaying animal matter of the battlefield.” Commenting on the placement of latrines in one encampment, another surgeon described how “the sink [latrine] is the ground in the vicinity, which slopes down to the stream, from which all water from the camp is obtained.”4
Treatment for diarrhea and dysentery was varied. Opiates were one of the most common treatments for diarrhea, whether in an alcohol solution as laudanum or in pill form, with belladonna being used to treat intestinal cramps, according to Glenna R. Schroeder-Lein in her book “The Encyclopedia of Civil War Medicine.” However, useless or damaging treatments were also prescribed, including the use of calomel (a mercury compound), turpentine, castor oil, and quinine.5
Acute diarrhea and dysentery illnesses occurred in at least 641/1,000 troops per year in the Union army. And even though the death rate was comparatively low (20/1,000 cases), it frequently led to chronic diarrhea, which was responsible for 288 deaths per 1,000 cases, and was the third highest cause of medical discharge after gunshot wounds and tuberculosis, according to Ms. Schroeder-Lein.
Although the American Civil War was the last major conflict before the spread of the knowledge of germ theory, the struggle to prevent the spread of waterborne diseases under wartime conditions remains ongoing. Hygiene is difficult under conditions of abject poverty and especially under conditions of armed conflict, and until the era of curative antibiotics there was no recourse.
Antibiotics are not the final solution for antibiotic resistance in intestinal disease pathogens, as outlined in a recent CDC report, is an increasing problem.6 For example, nontyphoidal Salmonella causes an estimated 1.35 million infections, 26,500 hospitalizations, and 420 deaths each year in the United States, with 16% of strains being resistant to at least one essential antibiotic. On a global scale, according to the World Health Organization, poor sanitation causes up to 432,000 diarrheal deaths annually and is linked to the transmission of other diseases like cholera, dysentery, typhoid, hepatitis A, and polio.7
With regard to actual epidemics, the world is only a hygienic crisis away from a major outbreak of dysentery (the last occurring between 1969 and 1972, when 20,000 people in Central America died), according to researchers who have detected antibiotic resistance in all but 1% of circulating Shigella dysenteriae strains surveyed since the 1990s. “This bacterium is still in circulation, and could be responsible for future epidemics if conditions should prove favorable – such as a large gathering of people without access to drinking water or treatment of human waste,” wrote François-Xavier Weill of the Pasteur Institute’s Enteric Bacterial Pathogens Unit.8
References
1. Sartin JS. Clin Infec Dis. 1993;16:580-4. (Correction published in 2002).
2. Civil War Battlefield Surgery. eHistory. The Ohio State University.
3. “Myths About Antiseptics and Camp Life – George Wunderlich,” published online Oct. 11, 2011. http://civilwarscholars.com/2011/10/myths-about-antiseptics-and-camp-life-george-wunderlich/
4. Dorwart BB. “Death is in the Breeze: Disease during the American Civil War” (The National Museum of the American Civil War Press, 2009).
5. Glenna R, Schroeder-Lein GR. “The Encyclopedia of Civil War Medicine” (New York: M. E. Sharpe, 2008).
6. “Antibiotic resistance threats in the United States 2019” Centers for Disease Control and Prevention.
7. “New report exposes horror of working conditions for millions of sanitation workers in the developing world,” World Health Organization. 2019 Nov 14.
8. Grant B. Origins of Dysentery. The Scientist. Published online March 22, 2016.
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 & cellular biology at Georgetown University, Washington.
If cleanliness is next to godliness, then the average soldier in the American Civil War lived just down the street from hell. In a land at war, before the formal tenets of germ theory had spread beyond the confines of Louis Pasteur’s laboratory in France, the lack of basic hygiene, both cultural and situational, coupled to an almost complete lack of curative therapies created an appalling death toll. Waterborne diseases in particular spared neither general nor private, and neither doctor nor nurse.
“Of all the adversities that Union and Confederate soldiers confronted, none was more deadly or more prevalent than contaminated water,” according to Jeffrey S. Sartin, MD, in his survey of Civil War diseases.1
The Union Army records list 1,765,000 cases of diarrhea or dysentery with 45,000 deaths and 149,000 cases of typhoid fever with 35,000 deaths. Add to these the 1,316,000 cases of malaria (borne by mosquitoes breeding in the waters) with its 10,000 deaths, and it is easy to see how the battlefield itself took second place in service to the grim reaper. (Overall, there were roughly two deaths from disease for every one from wounds.)
The chief waterborne plague, infectious diarrhea – including bacterial, amoebic, and other parasites – as well as cholera and typhoid, was an all-year-long problem, and, with the typical wry humor of soldiers, these maladies were given popular names, including the “Tennessee trots” and the “Virginia quick-step.”
Unsanitary conditions in the camps were primarily to blame, and this problem of sanitation was obvious to many observers at the time.
Despite a lack of knowledge of germ theory, doctors were fully aware of the relationship of unsanitary conditions to disease, even if they ascribed the link to miasmas or particles of filth.
Hospitals, which were under more strict control than the regular army camps, were meticulous about the placement of latrines and about keeping high standards of cleanliness among the patients, including routine washing. However, this was insufficient for complete protection, because what passed for clean in the absence of the knowledge of bacterial contamination was often totally ineffective. As one Civil War surgeon stated: “We operated in old bloodstained and often pus-stained coats, we used undisinfected instruments from undisinfected plush-lined cases. If a sponge (if they had sponges) or instrument fell on the floor it was washed and squeezed in a basin of water and used as if it was clean.”2
Overall, efforts at what passed for sanitation remained a constant goal and constant struggle in the field.
After the First Battle of Bull Run, Women’s Central Association of Relief President Henry W. Bellows met with Secretary of War Simon Cameron to discuss the abysmal sanitary conditions witnessed by WCAR volunteers. This meeting led to the creation of what would become the U.S. Sanitary Commission, which was approved by President Abraham Lincoln on June 13, 1861.
The U.S. Sanitary Commission served as a means for funneling civilian assistance to the military, with volunteers providing assistance in the organization of military hospitals and camps and aiding in the transportation of the wounded. However, despite these efforts, the setup of army camps and the behavior of the soldiers were not often directed toward proper sanitation. “The principal causes of disease, however, in our camps were the same that we have always to deplore and find it so difficult to remedy, simply because citizens suddenly called to the field cannot comprehend that men in masses require the attention of their officers to enforce certain hygienic conditions without which health cannot be preserved.”3
Breaches of sanitation were common in the confines of the camps, despite regulations designed to protect the soldiers. According to one U.S. Army surgeon of the time: “Especially [needed] was policing of the latrines. The trench is generally too shallow, the daily covering ... with dirt is entirely neglected. Large numbers of the men will not use the sinks [latrines], ... but instead every clump of bushes, every fence border in the vicinity.” Another pointed out that, after the Battle of Seven Pines, “the only water was infiltrated with the decaying animal matter of the battlefield.” Commenting on the placement of latrines in one encampment, another surgeon described how “the sink [latrine] is the ground in the vicinity, which slopes down to the stream, from which all water from the camp is obtained.”4
Treatment for diarrhea and dysentery was varied. Opiates were one of the most common treatments for diarrhea, whether in an alcohol solution as laudanum or in pill form, with belladonna being used to treat intestinal cramps, according to Glenna R. Schroeder-Lein in her book “The Encyclopedia of Civil War Medicine.” However, useless or damaging treatments were also prescribed, including the use of calomel (a mercury compound), turpentine, castor oil, and quinine.5
Acute diarrhea and dysentery illnesses occurred in at least 641/1,000 troops per year in the Union army. And even though the death rate was comparatively low (20/1,000 cases), it frequently led to chronic diarrhea, which was responsible for 288 deaths per 1,000 cases, and was the third highest cause of medical discharge after gunshot wounds and tuberculosis, according to Ms. Schroeder-Lein.
Although the American Civil War was the last major conflict before the spread of the knowledge of germ theory, the struggle to prevent the spread of waterborne diseases under wartime conditions remains ongoing. Hygiene is difficult under conditions of abject poverty and especially under conditions of armed conflict, and until the era of curative antibiotics there was no recourse.
Antibiotics are not the final solution for antibiotic resistance in intestinal disease pathogens, as outlined in a recent CDC report, is an increasing problem.6 For example, nontyphoidal Salmonella causes an estimated 1.35 million infections, 26,500 hospitalizations, and 420 deaths each year in the United States, with 16% of strains being resistant to at least one essential antibiotic. On a global scale, according to the World Health Organization, poor sanitation causes up to 432,000 diarrheal deaths annually and is linked to the transmission of other diseases like cholera, dysentery, typhoid, hepatitis A, and polio.7
With regard to actual epidemics, the world is only a hygienic crisis away from a major outbreak of dysentery (the last occurring between 1969 and 1972, when 20,000 people in Central America died), according to researchers who have detected antibiotic resistance in all but 1% of circulating Shigella dysenteriae strains surveyed since the 1990s. “This bacterium is still in circulation, and could be responsible for future epidemics if conditions should prove favorable – such as a large gathering of people without access to drinking water or treatment of human waste,” wrote François-Xavier Weill of the Pasteur Institute’s Enteric Bacterial Pathogens Unit.8
References
1. Sartin JS. Clin Infec Dis. 1993;16:580-4. (Correction published in 2002).
2. Civil War Battlefield Surgery. eHistory. The Ohio State University.
3. “Myths About Antiseptics and Camp Life – George Wunderlich,” published online Oct. 11, 2011. http://civilwarscholars.com/2011/10/myths-about-antiseptics-and-camp-life-george-wunderlich/
4. Dorwart BB. “Death is in the Breeze: Disease during the American Civil War” (The National Museum of the American Civil War Press, 2009).
5. Glenna R, Schroeder-Lein GR. “The Encyclopedia of Civil War Medicine” (New York: M. E. Sharpe, 2008).
6. “Antibiotic resistance threats in the United States 2019” Centers for Disease Control and Prevention.
7. “New report exposes horror of working conditions for millions of sanitation workers in the developing world,” World Health Organization. 2019 Nov 14.
8. Grant B. Origins of Dysentery. The Scientist. Published online March 22, 2016.
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 & cellular biology at Georgetown University, Washington.
Dealing with off-label medical device use in vascular surgery
Off-label device use is common in vascular surgery, but few studies address off-label uses through both surgical and legal perspectives, according to Wei Li, MD, of the University of Maryland School of Medicine, Baltimore. Dr. Li will discuss the medical-legal landscape of off-label device use in her presentation on Friday morning.
She and her colleagues assessed the publicly accessible LexisNexis legal database and Manufacturer and User Facility Device Experience (MAUDE) from January 2012 to December 2017. Jury verdict and case law searches within the LexisNexis were performed in order to identify representative cases and related legal doctrines for entries related to three (off-label) stents deployed in the superficial femoral artery.
They categorized and compared the reported adverse events for all three stents.
Although off-label device use is both legal and unregulated, it can carry potential legal implications on billing practices and subsequent medical malpractice liability, according to the researchers.
They found that off-label device use was more widespread in the pediatric patient population because of an unmet demand that can require Humanitarian Device Exemption. Among 497 total entries of reportable adverse events in MAUDE, for the three stents, they found significant differences, and they also found that the highest malfunction was associated with stent delivery. No deaths were reported with off-label use.
Dr. Li will discuss how vascular specialists need to have more in-depth knowledge about the off-label devices they use to minimize the chance of complications. Their investigation found no evidence reportable adverse events bear a direct relationship with Food and Drug Administration–approved indications related to the three superficial femoral artery stents in question.
Off-label device use is common in vascular surgery, but few studies address off-label uses through both surgical and legal perspectives, according to Wei Li, MD, of the University of Maryland School of Medicine, Baltimore. Dr. Li will discuss the medical-legal landscape of off-label device use in her presentation on Friday morning.
She and her colleagues assessed the publicly accessible LexisNexis legal database and Manufacturer and User Facility Device Experience (MAUDE) from January 2012 to December 2017. Jury verdict and case law searches within the LexisNexis were performed in order to identify representative cases and related legal doctrines for entries related to three (off-label) stents deployed in the superficial femoral artery.
They categorized and compared the reported adverse events for all three stents.
Although off-label device use is both legal and unregulated, it can carry potential legal implications on billing practices and subsequent medical malpractice liability, according to the researchers.
They found that off-label device use was more widespread in the pediatric patient population because of an unmet demand that can require Humanitarian Device Exemption. Among 497 total entries of reportable adverse events in MAUDE, for the three stents, they found significant differences, and they also found that the highest malfunction was associated with stent delivery. No deaths were reported with off-label use.
Dr. Li will discuss how vascular specialists need to have more in-depth knowledge about the off-label devices they use to minimize the chance of complications. Their investigation found no evidence reportable adverse events bear a direct relationship with Food and Drug Administration–approved indications related to the three superficial femoral artery stents in question.
Off-label device use is common in vascular surgery, but few studies address off-label uses through both surgical and legal perspectives, according to Wei Li, MD, of the University of Maryland School of Medicine, Baltimore. Dr. Li will discuss the medical-legal landscape of off-label device use in her presentation on Friday morning.
She and her colleagues assessed the publicly accessible LexisNexis legal database and Manufacturer and User Facility Device Experience (MAUDE) from January 2012 to December 2017. Jury verdict and case law searches within the LexisNexis were performed in order to identify representative cases and related legal doctrines for entries related to three (off-label) stents deployed in the superficial femoral artery.
They categorized and compared the reported adverse events for all three stents.
Although off-label device use is both legal and unregulated, it can carry potential legal implications on billing practices and subsequent medical malpractice liability, according to the researchers.
They found that off-label device use was more widespread in the pediatric patient population because of an unmet demand that can require Humanitarian Device Exemption. Among 497 total entries of reportable adverse events in MAUDE, for the three stents, they found significant differences, and they also found that the highest malfunction was associated with stent delivery. No deaths were reported with off-label use.
Dr. Li will discuss how vascular specialists need to have more in-depth knowledge about the off-label devices they use to minimize the chance of complications. Their investigation found no evidence reportable adverse events bear a direct relationship with Food and Drug Administration–approved indications related to the three superficial femoral artery stents in question.
Proximal venous outflow obstruction associated with chronic lower back pain
An unexpected prevalence of chronic lower back pain (CLBP) was found among patients with proximal venous outflow obstruction (PVOO), according to Windsor Ting, MD, of the Icahn School of Medicine at Mount Sinai, New York and colleagues.
On Friday morning, Dr. Ting will present a study they performed to assess 168 consecutive patients (59% women; mean age 63 years) with PVOO who underwent iliac vein stent placement. PVOO was confirmed with venography and/or IVUS. The patients were queried regarding preoperative and postoperative CLBP, defined as consistent low back pain of a minimum 3-month duration.
They collected data on demographics, venous-related symptomatology, pain scores (0-10) as determined by a visual analog scale (VAS), characteristics of the CLBP. In addition, details of the vein stent procedure were collected.
The mean postoperative duration among the patients was 526 days. Preoperative CLBP was present in 104 (62%) patients; 29 (28%) used analgesics and 38 (37%) had a prior visit with a CLBP specialist. Standing (44%) and sitting (43%) were the two most common factors associated with CLBP pain exacerbation.
Dr. Ting will discuss how CLBP was unexpectedly prevalent among patients with PVOO prior to their iliac vein stent placement, and how their pain was significantly improved after iliac vein stent placement, with 32% of the patients reporting complete symptom resolution. This study is the first to report these unexpected findings, according to the researchers, but the pathophysiology of CLBP in PVOO is unclear.
An unexpected prevalence of chronic lower back pain (CLBP) was found among patients with proximal venous outflow obstruction (PVOO), according to Windsor Ting, MD, of the Icahn School of Medicine at Mount Sinai, New York and colleagues.
On Friday morning, Dr. Ting will present a study they performed to assess 168 consecutive patients (59% women; mean age 63 years) with PVOO who underwent iliac vein stent placement. PVOO was confirmed with venography and/or IVUS. The patients were queried regarding preoperative and postoperative CLBP, defined as consistent low back pain of a minimum 3-month duration.
They collected data on demographics, venous-related symptomatology, pain scores (0-10) as determined by a visual analog scale (VAS), characteristics of the CLBP. In addition, details of the vein stent procedure were collected.
The mean postoperative duration among the patients was 526 days. Preoperative CLBP was present in 104 (62%) patients; 29 (28%) used analgesics and 38 (37%) had a prior visit with a CLBP specialist. Standing (44%) and sitting (43%) were the two most common factors associated with CLBP pain exacerbation.
Dr. Ting will discuss how CLBP was unexpectedly prevalent among patients with PVOO prior to their iliac vein stent placement, and how their pain was significantly improved after iliac vein stent placement, with 32% of the patients reporting complete symptom resolution. This study is the first to report these unexpected findings, according to the researchers, but the pathophysiology of CLBP in PVOO is unclear.
An unexpected prevalence of chronic lower back pain (CLBP) was found among patients with proximal venous outflow obstruction (PVOO), according to Windsor Ting, MD, of the Icahn School of Medicine at Mount Sinai, New York and colleagues.
On Friday morning, Dr. Ting will present a study they performed to assess 168 consecutive patients (59% women; mean age 63 years) with PVOO who underwent iliac vein stent placement. PVOO was confirmed with venography and/or IVUS. The patients were queried regarding preoperative and postoperative CLBP, defined as consistent low back pain of a minimum 3-month duration.
They collected data on demographics, venous-related symptomatology, pain scores (0-10) as determined by a visual analog scale (VAS), characteristics of the CLBP. In addition, details of the vein stent procedure were collected.
The mean postoperative duration among the patients was 526 days. Preoperative CLBP was present in 104 (62%) patients; 29 (28%) used analgesics and 38 (37%) had a prior visit with a CLBP specialist. Standing (44%) and sitting (43%) were the two most common factors associated with CLBP pain exacerbation.
Dr. Ting will discuss how CLBP was unexpectedly prevalent among patients with PVOO prior to their iliac vein stent placement, and how their pain was significantly improved after iliac vein stent placement, with 32% of the patients reporting complete symptom resolution. This study is the first to report these unexpected findings, according to the researchers, but the pathophysiology of CLBP in PVOO is unclear.
What’s new and different with ESVS guidelines for aortoabdominal aortic and iliac aneurysms?
On Thursday afternoon, Karin Elisabeth Schmidt, MD, of the Center of Cardiovascular Surgery, Hospital Floridsdorf, Vienna, Austria, will discuss the guidelines of the European Society of Vascular Surgery (ESVS) for the management of abdominal and iliac aortic aneurysms, which were published in January 2019. “Since the last guideline, this field has experienced a rapid technological devices progress, significantly impacting our clinical practice as well as the care of the affected patients,” according to Dr. Schmidt and her colleagues.
They analyzed the different recommendations of the European, British and American guidelines for the treatment of abdominal aortic aneurysms was performed. The publications used for this literature study include the current and previous guidelines of the ESVS published in the European Journal of Vascular and Endovascular Surgery and the guideline published by the Society for Vascular Surgery (SVS) in January 2018, as well as the draft guideline of the National Institute for Health and Care Excellence (NICE) issued in May 2018.
There is consensus for the preference of endovascular treatment of a ruptured aortic aneurysm if this is anatomically possible, according to Dr. Schmidt. She will discuss how, for the majority of elective cases, endovascular care is favored in the SVS and ESVS guidelines in contrast to the NICE draft.
There are generally still more ambiguities than clear recommendations, especially regarding the preferred procedures for complex aortic pathologies, population screening, and follow-up after open and endovascular aortic intervention.
She recommended a critical analysis of the U.S. and European guidelines, as both partly cover different aspects.
The final version of the guideline for the United Kingdom is eagerly expected, according to Dr. Schmidt and her colleagues, as it currently prefers open surgical care in the elective setting. Many research possibilities exist in the search for biomarkers for better assessment of the progression of small aortic aneurysms coupled with functional imaging or pharmacologic influence on aneurysm growth progression. In addition, global platforms for data collection, in particular for newer devices (low profile) and their long-term performance with jointly defined endpoints, should be established.
Dr. Schmidt will discuss how techniques such as artificial intelligence and machine learning will be used in future for monitoring large amounts of data, finding patterns and thus gain new insights.
On Thursday afternoon, Karin Elisabeth Schmidt, MD, of the Center of Cardiovascular Surgery, Hospital Floridsdorf, Vienna, Austria, will discuss the guidelines of the European Society of Vascular Surgery (ESVS) for the management of abdominal and iliac aortic aneurysms, which were published in January 2019. “Since the last guideline, this field has experienced a rapid technological devices progress, significantly impacting our clinical practice as well as the care of the affected patients,” according to Dr. Schmidt and her colleagues.
They analyzed the different recommendations of the European, British and American guidelines for the treatment of abdominal aortic aneurysms was performed. The publications used for this literature study include the current and previous guidelines of the ESVS published in the European Journal of Vascular and Endovascular Surgery and the guideline published by the Society for Vascular Surgery (SVS) in January 2018, as well as the draft guideline of the National Institute for Health and Care Excellence (NICE) issued in May 2018.
There is consensus for the preference of endovascular treatment of a ruptured aortic aneurysm if this is anatomically possible, according to Dr. Schmidt. She will discuss how, for the majority of elective cases, endovascular care is favored in the SVS and ESVS guidelines in contrast to the NICE draft.
There are generally still more ambiguities than clear recommendations, especially regarding the preferred procedures for complex aortic pathologies, population screening, and follow-up after open and endovascular aortic intervention.
She recommended a critical analysis of the U.S. and European guidelines, as both partly cover different aspects.
The final version of the guideline for the United Kingdom is eagerly expected, according to Dr. Schmidt and her colleagues, as it currently prefers open surgical care in the elective setting. Many research possibilities exist in the search for biomarkers for better assessment of the progression of small aortic aneurysms coupled with functional imaging or pharmacologic influence on aneurysm growth progression. In addition, global platforms for data collection, in particular for newer devices (low profile) and their long-term performance with jointly defined endpoints, should be established.
Dr. Schmidt will discuss how techniques such as artificial intelligence and machine learning will be used in future for monitoring large amounts of data, finding patterns and thus gain new insights.
On Thursday afternoon, Karin Elisabeth Schmidt, MD, of the Center of Cardiovascular Surgery, Hospital Floridsdorf, Vienna, Austria, will discuss the guidelines of the European Society of Vascular Surgery (ESVS) for the management of abdominal and iliac aortic aneurysms, which were published in January 2019. “Since the last guideline, this field has experienced a rapid technological devices progress, significantly impacting our clinical practice as well as the care of the affected patients,” according to Dr. Schmidt and her colleagues.
They analyzed the different recommendations of the European, British and American guidelines for the treatment of abdominal aortic aneurysms was performed. The publications used for this literature study include the current and previous guidelines of the ESVS published in the European Journal of Vascular and Endovascular Surgery and the guideline published by the Society for Vascular Surgery (SVS) in January 2018, as well as the draft guideline of the National Institute for Health and Care Excellence (NICE) issued in May 2018.
There is consensus for the preference of endovascular treatment of a ruptured aortic aneurysm if this is anatomically possible, according to Dr. Schmidt. She will discuss how, for the majority of elective cases, endovascular care is favored in the SVS and ESVS guidelines in contrast to the NICE draft.
There are generally still more ambiguities than clear recommendations, especially regarding the preferred procedures for complex aortic pathologies, population screening, and follow-up after open and endovascular aortic intervention.
She recommended a critical analysis of the U.S. and European guidelines, as both partly cover different aspects.
The final version of the guideline for the United Kingdom is eagerly expected, according to Dr. Schmidt and her colleagues, as it currently prefers open surgical care in the elective setting. Many research possibilities exist in the search for biomarkers for better assessment of the progression of small aortic aneurysms coupled with functional imaging or pharmacologic influence on aneurysm growth progression. In addition, global platforms for data collection, in particular for newer devices (low profile) and their long-term performance with jointly defined endpoints, should be established.
Dr. Schmidt will discuss how techniques such as artificial intelligence and machine learning will be used in future for monitoring large amounts of data, finding patterns and thus gain new insights.
Dealing with complications associated with central venous access catheters
On Thursday morning, John T. Loree, a medical student at SUNY Upstate Medical School, Syracuse, will present a study that he and his colleagues performed to assess the risks and complications associated with the use of central venous access (CVA) catheters over the long term. They attempted to identify high-risk subgroups based upon patient characteristics and line type. The research is warranted so that modified follow-up regimens can be implemented to reduce risk and improve patient outcomes. In his presentation, Mr. Loree will discuss selected therapies for specific complications.
The researchers performed a PubMed data base search, which located 21 papers published between 2012 and 2018. In this sample, 6,781 catheters were placed in 6,183 patients, with a total dwell time of 2,538,323 days. Patients characteristics varied from children to adults. Various line types were used (peripherally inserted central catheter [PICC], central line, mediport, tunneled central venous catheter). Indications for catheterization included (chemotherapy, dialysis, total parenteral nutrition (TPN), and other medication infusion.
Mr. Loree will discuss the primary outcomes – overall complication rate and the infectious and mechanical complication rates per 1,000 catheter-days.
He and his colleagues found that port purpose was significantly predictive of infection rate, while port type was selectively predictive of overall and mechanical complication rate. Subgroup analysis demonstrated significantly increased overall complication rates in peripherally inserted catheters and patients receiving medications, and increased mechanical complication rates with central lines.
Mr. Loree will discuss how the complication rates associated with long-term use of CVA catheters were associated with factors easily identifiable at the initial patient visit.
Their data will show how, overall, PICC lines used for TPN/medication administration were associated with the highest complication rate, while mediports used for chemotherapy were associated with the lowest complication rate. Based on these patient characteristics, stricter follow-up to monitor for complications can be used in select patients to improve patient outcomes, according to Mr. Loree.
On Thursday morning, John T. Loree, a medical student at SUNY Upstate Medical School, Syracuse, will present a study that he and his colleagues performed to assess the risks and complications associated with the use of central venous access (CVA) catheters over the long term. They attempted to identify high-risk subgroups based upon patient characteristics and line type. The research is warranted so that modified follow-up regimens can be implemented to reduce risk and improve patient outcomes. In his presentation, Mr. Loree will discuss selected therapies for specific complications.
The researchers performed a PubMed data base search, which located 21 papers published between 2012 and 2018. In this sample, 6,781 catheters were placed in 6,183 patients, with a total dwell time of 2,538,323 days. Patients characteristics varied from children to adults. Various line types were used (peripherally inserted central catheter [PICC], central line, mediport, tunneled central venous catheter). Indications for catheterization included (chemotherapy, dialysis, total parenteral nutrition (TPN), and other medication infusion.
Mr. Loree will discuss the primary outcomes – overall complication rate and the infectious and mechanical complication rates per 1,000 catheter-days.
He and his colleagues found that port purpose was significantly predictive of infection rate, while port type was selectively predictive of overall and mechanical complication rate. Subgroup analysis demonstrated significantly increased overall complication rates in peripherally inserted catheters and patients receiving medications, and increased mechanical complication rates with central lines.
Mr. Loree will discuss how the complication rates associated with long-term use of CVA catheters were associated with factors easily identifiable at the initial patient visit.
Their data will show how, overall, PICC lines used for TPN/medication administration were associated with the highest complication rate, while mediports used for chemotherapy were associated with the lowest complication rate. Based on these patient characteristics, stricter follow-up to monitor for complications can be used in select patients to improve patient outcomes, according to Mr. Loree.
On Thursday morning, John T. Loree, a medical student at SUNY Upstate Medical School, Syracuse, will present a study that he and his colleagues performed to assess the risks and complications associated with the use of central venous access (CVA) catheters over the long term. They attempted to identify high-risk subgroups based upon patient characteristics and line type. The research is warranted so that modified follow-up regimens can be implemented to reduce risk and improve patient outcomes. In his presentation, Mr. Loree will discuss selected therapies for specific complications.
The researchers performed a PubMed data base search, which located 21 papers published between 2012 and 2018. In this sample, 6,781 catheters were placed in 6,183 patients, with a total dwell time of 2,538,323 days. Patients characteristics varied from children to adults. Various line types were used (peripherally inserted central catheter [PICC], central line, mediport, tunneled central venous catheter). Indications for catheterization included (chemotherapy, dialysis, total parenteral nutrition (TPN), and other medication infusion.
Mr. Loree will discuss the primary outcomes – overall complication rate and the infectious and mechanical complication rates per 1,000 catheter-days.
He and his colleagues found that port purpose was significantly predictive of infection rate, while port type was selectively predictive of overall and mechanical complication rate. Subgroup analysis demonstrated significantly increased overall complication rates in peripherally inserted catheters and patients receiving medications, and increased mechanical complication rates with central lines.
Mr. Loree will discuss how the complication rates associated with long-term use of CVA catheters were associated with factors easily identifiable at the initial patient visit.
Their data will show how, overall, PICC lines used for TPN/medication administration were associated with the highest complication rate, while mediports used for chemotherapy were associated with the lowest complication rate. Based on these patient characteristics, stricter follow-up to monitor for complications can be used in select patients to improve patient outcomes, according to Mr. Loree.