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More selective antibiotic shows promise for C. diff. infection
An investigational, novel oral antibiotic with greater selectivity than vancomycin, metronidazole, and even fidaxomicin may offer improved protection of healthy gut bacteria during the treatment of Clostridium difficile infection (CDI), according to ongoing research.
“CDI treatment has historically been dominated by metronidazole and vancomycin,” said Katherine Johnson, DO, from the Western Infectious Disease Consultants, P.C., Denver. However, these broad-spectrum drugs negatively affect healthy bacteria in the gut and increase the risk of CDI recurrence.
This is also a problem for drugs in the CDI antibiotic pipeline: Many candidate drugs have failed because of their broad-spectrum activity, she added during a session at the Peggy Lillis Foundation 2022 National C. diff. Advocacy Summit.
“An ideal CDI therapy would be a very narrow-spectrum antibiotic that has a minimal effect on normal gut bacteria,” she said.
Dr. Johnson is currently working on a phase 2 clinical trial that is evaluating the novel antibiotic, dubbed CRS3123, for the treatment of primary CDI and first-recurrence CDI. The investigational agent targets and inhibits a form of the methionyl tRNA synthetase enzyme, which is strictly required for protein biosynthesis in C. diff. and is therefore an ideal target for treatment of primary and recurrent CDI.
In her session, Dr. Johnson reported that CRS3123 inhibits the damaging toxins produced by C. diff., potentially resulting in more rapid symptom resolution. Additionally, owing to its novel mode of action, no strains are currently resistant to CRS3123.
She presented findings from an animal study that showed that CRS3123 was superior to vancomycin in terms of prolonging survival. She also presented findings from phase 1 clinical trials that showed that most adverse events (AEs) associated with CRS3123 were mild. No serious AEs were reported.
A ‘huge infectious burden’
If successful in further research, CRS3123 could offer significant value to patients with C. diff., especially those with recurrent infection, given the sometimes extreme clinical, quality-of-life, and economic burdens associated with CDI.
“CDI is a huge infectious burden to the U.S. health care system and globally has been listed by the Centers for Disease Control and Prevention as an urgent threat,” Byron Vaughn, MD, from the University of Minnesota, told this news organization.
“Despite a number of antibiotic stewardship and infection control and prevention efforts, we haven’t seen much of a change in the incidence of CDI,” he said. He said that the risk of recurrence can be as high as 30%.
While oral vancomycin is effective for treating C. diff., Dr. Vaughn noted that the antibiotic lacks selectivity and destroys healthy gut bacteria, resulting in substantial dysbiosis. “Dysbiosis is really the key to getting recurrent C. diff.,” he explained, “because if you have healthy gut bacteria, you will inherently resist CDI.”
Dr. Vaughn stated that his center is in the startup phase for being a site for a clinical trial of CRS3123. The hope is that CRS3123, because its spectrum is narrower than that of fidaxomicin and vancomycin, doesn’t induce intestinal dysbiosis. “It really just treats the C. diff. and leaves every other bug alone so that your gut bacteria can recover while the C. diff. is being treated,” he said. “And then when you stop CRS3123, you have healthy gut bacteria already present to prevent recurrence.”
If this is confirmed in large-scale trials, there could be a “dramatic decrease” in the rates of recurrent C. diff., said Dr. Vaughn.
Aside from the potential clinical impact, the economic implications of a novel selective antibiotic that preserves healthy gut bacteria could be significant, he added. “Depending on exactly what population you’re looking at, probably about a third of the cost of C. diff. is actually attributable to recurrence. That’s a huge economic burden that could be improved.”
Dr. Johnson is an employee of Crestone, which is developing CRS3123. Dr. Vaughn reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
An investigational, novel oral antibiotic with greater selectivity than vancomycin, metronidazole, and even fidaxomicin may offer improved protection of healthy gut bacteria during the treatment of Clostridium difficile infection (CDI), according to ongoing research.
“CDI treatment has historically been dominated by metronidazole and vancomycin,” said Katherine Johnson, DO, from the Western Infectious Disease Consultants, P.C., Denver. However, these broad-spectrum drugs negatively affect healthy bacteria in the gut and increase the risk of CDI recurrence.
This is also a problem for drugs in the CDI antibiotic pipeline: Many candidate drugs have failed because of their broad-spectrum activity, she added during a session at the Peggy Lillis Foundation 2022 National C. diff. Advocacy Summit.
“An ideal CDI therapy would be a very narrow-spectrum antibiotic that has a minimal effect on normal gut bacteria,” she said.
Dr. Johnson is currently working on a phase 2 clinical trial that is evaluating the novel antibiotic, dubbed CRS3123, for the treatment of primary CDI and first-recurrence CDI. The investigational agent targets and inhibits a form of the methionyl tRNA synthetase enzyme, which is strictly required for protein biosynthesis in C. diff. and is therefore an ideal target for treatment of primary and recurrent CDI.
In her session, Dr. Johnson reported that CRS3123 inhibits the damaging toxins produced by C. diff., potentially resulting in more rapid symptom resolution. Additionally, owing to its novel mode of action, no strains are currently resistant to CRS3123.
She presented findings from an animal study that showed that CRS3123 was superior to vancomycin in terms of prolonging survival. She also presented findings from phase 1 clinical trials that showed that most adverse events (AEs) associated with CRS3123 were mild. No serious AEs were reported.
A ‘huge infectious burden’
If successful in further research, CRS3123 could offer significant value to patients with C. diff., especially those with recurrent infection, given the sometimes extreme clinical, quality-of-life, and economic burdens associated with CDI.
“CDI is a huge infectious burden to the U.S. health care system and globally has been listed by the Centers for Disease Control and Prevention as an urgent threat,” Byron Vaughn, MD, from the University of Minnesota, told this news organization.
“Despite a number of antibiotic stewardship and infection control and prevention efforts, we haven’t seen much of a change in the incidence of CDI,” he said. He said that the risk of recurrence can be as high as 30%.
While oral vancomycin is effective for treating C. diff., Dr. Vaughn noted that the antibiotic lacks selectivity and destroys healthy gut bacteria, resulting in substantial dysbiosis. “Dysbiosis is really the key to getting recurrent C. diff.,” he explained, “because if you have healthy gut bacteria, you will inherently resist CDI.”
Dr. Vaughn stated that his center is in the startup phase for being a site for a clinical trial of CRS3123. The hope is that CRS3123, because its spectrum is narrower than that of fidaxomicin and vancomycin, doesn’t induce intestinal dysbiosis. “It really just treats the C. diff. and leaves every other bug alone so that your gut bacteria can recover while the C. diff. is being treated,” he said. “And then when you stop CRS3123, you have healthy gut bacteria already present to prevent recurrence.”
If this is confirmed in large-scale trials, there could be a “dramatic decrease” in the rates of recurrent C. diff., said Dr. Vaughn.
Aside from the potential clinical impact, the economic implications of a novel selective antibiotic that preserves healthy gut bacteria could be significant, he added. “Depending on exactly what population you’re looking at, probably about a third of the cost of C. diff. is actually attributable to recurrence. That’s a huge economic burden that could be improved.”
Dr. Johnson is an employee of Crestone, which is developing CRS3123. Dr. Vaughn reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
An investigational, novel oral antibiotic with greater selectivity than vancomycin, metronidazole, and even fidaxomicin may offer improved protection of healthy gut bacteria during the treatment of Clostridium difficile infection (CDI), according to ongoing research.
“CDI treatment has historically been dominated by metronidazole and vancomycin,” said Katherine Johnson, DO, from the Western Infectious Disease Consultants, P.C., Denver. However, these broad-spectrum drugs negatively affect healthy bacteria in the gut and increase the risk of CDI recurrence.
This is also a problem for drugs in the CDI antibiotic pipeline: Many candidate drugs have failed because of their broad-spectrum activity, she added during a session at the Peggy Lillis Foundation 2022 National C. diff. Advocacy Summit.
“An ideal CDI therapy would be a very narrow-spectrum antibiotic that has a minimal effect on normal gut bacteria,” she said.
Dr. Johnson is currently working on a phase 2 clinical trial that is evaluating the novel antibiotic, dubbed CRS3123, for the treatment of primary CDI and first-recurrence CDI. The investigational agent targets and inhibits a form of the methionyl tRNA synthetase enzyme, which is strictly required for protein biosynthesis in C. diff. and is therefore an ideal target for treatment of primary and recurrent CDI.
In her session, Dr. Johnson reported that CRS3123 inhibits the damaging toxins produced by C. diff., potentially resulting in more rapid symptom resolution. Additionally, owing to its novel mode of action, no strains are currently resistant to CRS3123.
She presented findings from an animal study that showed that CRS3123 was superior to vancomycin in terms of prolonging survival. She also presented findings from phase 1 clinical trials that showed that most adverse events (AEs) associated with CRS3123 were mild. No serious AEs were reported.
A ‘huge infectious burden’
If successful in further research, CRS3123 could offer significant value to patients with C. diff., especially those with recurrent infection, given the sometimes extreme clinical, quality-of-life, and economic burdens associated with CDI.
“CDI is a huge infectious burden to the U.S. health care system and globally has been listed by the Centers for Disease Control and Prevention as an urgent threat,” Byron Vaughn, MD, from the University of Minnesota, told this news organization.
“Despite a number of antibiotic stewardship and infection control and prevention efforts, we haven’t seen much of a change in the incidence of CDI,” he said. He said that the risk of recurrence can be as high as 30%.
While oral vancomycin is effective for treating C. diff., Dr. Vaughn noted that the antibiotic lacks selectivity and destroys healthy gut bacteria, resulting in substantial dysbiosis. “Dysbiosis is really the key to getting recurrent C. diff.,” he explained, “because if you have healthy gut bacteria, you will inherently resist CDI.”
Dr. Vaughn stated that his center is in the startup phase for being a site for a clinical trial of CRS3123. The hope is that CRS3123, because its spectrum is narrower than that of fidaxomicin and vancomycin, doesn’t induce intestinal dysbiosis. “It really just treats the C. diff. and leaves every other bug alone so that your gut bacteria can recover while the C. diff. is being treated,” he said. “And then when you stop CRS3123, you have healthy gut bacteria already present to prevent recurrence.”
If this is confirmed in large-scale trials, there could be a “dramatic decrease” in the rates of recurrent C. diff., said Dr. Vaughn.
Aside from the potential clinical impact, the economic implications of a novel selective antibiotic that preserves healthy gut bacteria could be significant, he added. “Depending on exactly what population you’re looking at, probably about a third of the cost of C. diff. is actually attributable to recurrence. That’s a huge economic burden that could be improved.”
Dr. Johnson is an employee of Crestone, which is developing CRS3123. Dr. Vaughn reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The importance of toxin testing in C. difficile infection: Understanding the results
Clostridioides difficile infection is often confirmed through toxin testing, yet toxin tests alone may not be sufficient for diagnosing and guiding treatment decisions for patients with CDI.
“The presence of a toxigenic strain does not always equal disease,” said David Lyerly, PhD, during a session on C. difficile toxin testing at the Peggy Lillis Foundation 2022 National C. diff Advocacy Summit.
Dr. Lyerly, the chief science officer at Techlab, explained that exotoxins A and B are produced by specific strains of C. difficile and are involved in infections, but some patients who test positive for these toxins by polymerase chain reaction or other tests do not have CDI or they are not appropriate candidates for CDI treatment.
Several studies conducted during the past decade, however, support the importance of toxin detection. Some research has suggested that toxin-positive patients tend to have more clinically severe disease than those who test negative, he noted.
Although its use is limited when it is used alone, toxin testing is needed to confirm a CDI diagnosis and to ensure antibiotic stewardship, Dr. Lyerly said.
He suggested that, in addition to toxin testing, there is a need for molecular measures and other improved diagnostics to identify candidates most likely to benefit from CDI treatment.
“Because we generally detect toxin genes instead of toxin proteins, you can identify persons colonized with toxigenic C. difficile who do not actually have CDI,” Kevin W. Garey, PharmD, from the University of Houston, said in an interview.
Dr. Garey added that a person could likewise have low levels of toxins that aren’t detected by toxin tests but could still have CDI.
“Given this, better diagnostics that incorporate active toxin production and your body’s response to those toxins are needed,” he said, especially since C. difficile toxins are responsible for disease sequelae, including gastroenteritis, colonic perforation, sepsis, and death.
Toxin testing a ‘controversial area’
“C. difficile toxin testing has been a controversial area for almost a decade or more,” Shruti K. Gohil, MD, from University of California, Irvine, Health Epidemiology and Infection Prevention, said in an interview.
Dr. Gohil noted that toxin testing is a better test for clinical C. difficile colitis but by itself can miss C. difficile. “So, we are in this conundrum nationally,” she said.
“Many facilities will use a double- or triple-test strategy to make sure that you have a true C. difficile case mandating the use of antibiotics,” she explained. “The reason we test specifically with the enzyme immunoassay or toxin test is to know whether or not you have real C. difficile that’s actively producing the toxin for colitis.”
A patient with C. difficile who has been treated and is in recovery may still test positive on a C. difficile toxin test, added Dr. Gohil. “It would be great if we had a test that could really judge an active, clinical C. difficile infection. This [test] would help in identifying the right patients who need treatment and would also be able to tell if a patient has been cleared of C. difficile.”
Dr. Lyerly is an employee of Techlab. Dr. Garey and Dr. Gohil reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Clostridioides difficile infection is often confirmed through toxin testing, yet toxin tests alone may not be sufficient for diagnosing and guiding treatment decisions for patients with CDI.
“The presence of a toxigenic strain does not always equal disease,” said David Lyerly, PhD, during a session on C. difficile toxin testing at the Peggy Lillis Foundation 2022 National C. diff Advocacy Summit.
Dr. Lyerly, the chief science officer at Techlab, explained that exotoxins A and B are produced by specific strains of C. difficile and are involved in infections, but some patients who test positive for these toxins by polymerase chain reaction or other tests do not have CDI or they are not appropriate candidates for CDI treatment.
Several studies conducted during the past decade, however, support the importance of toxin detection. Some research has suggested that toxin-positive patients tend to have more clinically severe disease than those who test negative, he noted.
Although its use is limited when it is used alone, toxin testing is needed to confirm a CDI diagnosis and to ensure antibiotic stewardship, Dr. Lyerly said.
He suggested that, in addition to toxin testing, there is a need for molecular measures and other improved diagnostics to identify candidates most likely to benefit from CDI treatment.
“Because we generally detect toxin genes instead of toxin proteins, you can identify persons colonized with toxigenic C. difficile who do not actually have CDI,” Kevin W. Garey, PharmD, from the University of Houston, said in an interview.
Dr. Garey added that a person could likewise have low levels of toxins that aren’t detected by toxin tests but could still have CDI.
“Given this, better diagnostics that incorporate active toxin production and your body’s response to those toxins are needed,” he said, especially since C. difficile toxins are responsible for disease sequelae, including gastroenteritis, colonic perforation, sepsis, and death.
Toxin testing a ‘controversial area’
“C. difficile toxin testing has been a controversial area for almost a decade or more,” Shruti K. Gohil, MD, from University of California, Irvine, Health Epidemiology and Infection Prevention, said in an interview.
Dr. Gohil noted that toxin testing is a better test for clinical C. difficile colitis but by itself can miss C. difficile. “So, we are in this conundrum nationally,” she said.
“Many facilities will use a double- or triple-test strategy to make sure that you have a true C. difficile case mandating the use of antibiotics,” she explained. “The reason we test specifically with the enzyme immunoassay or toxin test is to know whether or not you have real C. difficile that’s actively producing the toxin for colitis.”
A patient with C. difficile who has been treated and is in recovery may still test positive on a C. difficile toxin test, added Dr. Gohil. “It would be great if we had a test that could really judge an active, clinical C. difficile infection. This [test] would help in identifying the right patients who need treatment and would also be able to tell if a patient has been cleared of C. difficile.”
Dr. Lyerly is an employee of Techlab. Dr. Garey and Dr. Gohil reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Clostridioides difficile infection is often confirmed through toxin testing, yet toxin tests alone may not be sufficient for diagnosing and guiding treatment decisions for patients with CDI.
“The presence of a toxigenic strain does not always equal disease,” said David Lyerly, PhD, during a session on C. difficile toxin testing at the Peggy Lillis Foundation 2022 National C. diff Advocacy Summit.
Dr. Lyerly, the chief science officer at Techlab, explained that exotoxins A and B are produced by specific strains of C. difficile and are involved in infections, but some patients who test positive for these toxins by polymerase chain reaction or other tests do not have CDI or they are not appropriate candidates for CDI treatment.
Several studies conducted during the past decade, however, support the importance of toxin detection. Some research has suggested that toxin-positive patients tend to have more clinically severe disease than those who test negative, he noted.
Although its use is limited when it is used alone, toxin testing is needed to confirm a CDI diagnosis and to ensure antibiotic stewardship, Dr. Lyerly said.
He suggested that, in addition to toxin testing, there is a need for molecular measures and other improved diagnostics to identify candidates most likely to benefit from CDI treatment.
“Because we generally detect toxin genes instead of toxin proteins, you can identify persons colonized with toxigenic C. difficile who do not actually have CDI,” Kevin W. Garey, PharmD, from the University of Houston, said in an interview.
Dr. Garey added that a person could likewise have low levels of toxins that aren’t detected by toxin tests but could still have CDI.
“Given this, better diagnostics that incorporate active toxin production and your body’s response to those toxins are needed,” he said, especially since C. difficile toxins are responsible for disease sequelae, including gastroenteritis, colonic perforation, sepsis, and death.
Toxin testing a ‘controversial area’
“C. difficile toxin testing has been a controversial area for almost a decade or more,” Shruti K. Gohil, MD, from University of California, Irvine, Health Epidemiology and Infection Prevention, said in an interview.
Dr. Gohil noted that toxin testing is a better test for clinical C. difficile colitis but by itself can miss C. difficile. “So, we are in this conundrum nationally,” she said.
“Many facilities will use a double- or triple-test strategy to make sure that you have a true C. difficile case mandating the use of antibiotics,” she explained. “The reason we test specifically with the enzyme immunoassay or toxin test is to know whether or not you have real C. difficile that’s actively producing the toxin for colitis.”
A patient with C. difficile who has been treated and is in recovery may still test positive on a C. difficile toxin test, added Dr. Gohil. “It would be great if we had a test that could really judge an active, clinical C. difficile infection. This [test] would help in identifying the right patients who need treatment and would also be able to tell if a patient has been cleared of C. difficile.”
Dr. Lyerly is an employee of Techlab. Dr. Garey and Dr. Gohil reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Alarming global rise in pediatric hepatitis: Expert Q&A
This spring, global health advisories have been issued regarding an alarming – and as-yet unexplained – uptick of hepatitis in children. Currently, over 200 cases have been reported worldwide, a relatively small amount that nonetheless belies a considerable toll, including several deaths and the need for liver transplantation in a number of patients. The long-term implications are not yet known. Global health officials are working hard to determine a cause, with many focusing on the underlying cases of adenovirus that several patients have presented with.
To understand more, this news organization reached out to frequent contributor William F. Balistreri, MD, a specialist in pediatric gastroenterology and hepatology at Cincinnati Children’s Hospital Medical Center, where to date they have treated at least six cases of hepatitis in otherwise healthy young children, with one requiring a liver transplant. Dr. Balistreri discussed how the outbreak has developed to date, his advice to hepatologists and pediatricians, and where we stand now in this fast-evolving crisis.
Tracing the outbreak in the United States
How has this outbreak played out thus far in the United States, and what have we learned from that?
Sporadic reports of cases in multiple states are appearing. On April 21, 2022, a health alert was issued by the Centers for Disease Control and Prevention, recommending testing for adenovirus in children with acute hepatitis of an unknown etiology.
Baker and colleagues recently described five children with severe hepatitis and adenovirus viremia who were admitted to a children’s hospital in Birmingham, Ala., between October and November 2021. In collaboration with local and state officials, the CDC reviewed clinical records in order to identify patients with hepatitis and concomitant adenovirus infection, confirmed by polymerase chain reaction (PCR).
By February 2022, a total of nine children were identified. There was no epidemiologic linkage among these nine patients; all were well and immunocompetent. The prodromal features were somewhat similar: upper respiratory infection, vomiting, diarrhea, and jaundice. All children had markedly elevated aminotransferase levels and variably elevated total bilirubin levels. Extensive workup for other causes of acute liver injury (for example, other viruses, toxins/drugs, metabolic and autoimmune diseases) was unrevealing.
Specifically, none had documented SARS-CoV-2 infection. However, in all nine children, adenovirus was detected in whole blood samples. In the six children who underwent liver biopsy, there was nonspecific hepatitis, without inclusions or immunohistochemical detection of viral agents, including adenovirus. In three patients, the liver injury progressed, and despite the administration of antiviral agents, two underwent liver transplantation.
Baker and colleagues also suggested that measurement of adenovirus titers in whole blood (rather than plasma) may be more sensitive.
The CDC has recommended monitoring and surveillance in order to more fully understand the nature of the illness.
European and global cases
What has been the experience with this in Europe and elsewhere globally?
In mid-to-late 2021, several cases of acute hepatitis of unknown nature in children were identified in Europe. Public health officials in the United Kingdom investigated the high number of cases seen in children from England, Scotland, and Wales. They noted approximately 60 cases in England, mostly in children aged 2-5 years.
Marsh and colleagues reported a cluster of cases of severe hepatitis of unknown origin in Scotland affecting children aged 3-5 years. In Scotland, admitted cases were routinely tested for SARS-CoV-2. Of the 13 cases, five had a recent positive test. They discussed the possibility of increased severity of disease following infection with Omicron BA.2 (the dominant SARS-CoV-2 virus circulating in Scotland at that time) or infection by an uncharacterized SARS-CoV-2 variant. None of the children had been vaccinated for SARS-CoV-2.
On April 15, 2022, the World Health Organization Disease Outbreak News published a report of acute hepatitis of unknown etiology occurring in Great Britain and Northern Ireland. By April 21, 2022, 169 cases of acute hepatitis of unknown origin in children younger than 16 years had been reported from 11 countries in the WHO European region and 1 country in the WHO region of the Americas. Approximately 10% required a liver transplantation and at least one death was reported.
What has been established about the possible connection to the SARS-CoV-2 virus, particularly as it relates to coinfection with adenovirus?
In that WHO report of 169 cases, adenovirus was detected in 74 and SARS-CoV-2 in 20. Of note, 19 cases had a SARS-CoV-2 and adenovirus coinfection.
The report’s authors emphasized that, “while adenovirus is a possible hypothesis, investigations are ongoing for the causative agent.” The authors questioned whether this represents a continuing increase in cases of hepatitis or reflects an increased awareness.
The stated priority of the WHO is to determine the cause and to further refine control and prevention actions.
Given the worldwide nature of this outbreak, have connections between any of the cases been made yet?
Not to my knowledge.
What clinicians need to know
What makes this outbreak of hepatitis cases particularly concerning to the health care community, in comparison to other childhood diseases that occur globally? Is it because the cause is unknown or is it for other reasons?
It may be a collective heightened concern following the emergence of COVID.
Whether it represents a new form of acute hepatitis, a continuing increase in cases of hepatitis, or an increased awareness because of the well-publicized alerts remains to be determined. We certainly saw “viral-induced hepatitis” in the past.
Young patients may first be brought to pediatricians. What, if anything, should pediatricians be on the lookout for? Do they need a heightened index of suspicion or are the cases too rare at this point?
An awareness of the “outbreak” may allow the clinician to extend the typical workup of a child presenting with an undefined, presumably viral illness.
In the cases reported, the prodromal and/or presenting symptoms were respiratory and gastrointestinal in nature. They include nausea, vomiting, diarrhea, and abdominal pain.
Specifically, if jaundice and/or scleral icterus is noted, then hepatitis should be suspected.
Should pediatricians consider early referral to a pediatric gastroenterologist or hepatologist?
Yes, because there is the potential for finding a treatable cause (for example, autoimmune hepatitis or a specific metabolic disease) in a patient presenting in this fashion.
In addition, the potential for progression to acute liver failure (with coagulopathy and encephalopathy), albeit rare, exists.
What do hepatologists need to be doing when presented with suspected cases?
The typical clinical picture holds and the workup is standard. The one new key, given the recent data, is to test for adenovirus, using whole blood versus plasma, as the former may be more sensitive.
In addition, it is prudent to check for SARS-CoV-2 by PCR.
What are the major questions that remain and that you’d like to see elucidated going forward?
There are many. Is this a new disease? A new variant of adenovirus? A synergy or susceptibility related to SARS-CoV-2? Is it related to a variant of SARS-CoV-2? Is it triggering an adverse immune response? Are there other epigenetic factors involved? And finally, is this an increase, or is it related to a collective heightened concern following the pandemic?
Dr. Balistreri is the Dorothy M.M. Kersten Professor of Pediatrics, director emeritus of the Pediatric Liver Care Center, medical director emeritus of liver transplantation, and professor at the University of Cincinnati; he is also with the department of pediatrics at Cincinnati Children’s Hospital Medical Center.
A version of this article first appeared on Medscape.com.
This spring, global health advisories have been issued regarding an alarming – and as-yet unexplained – uptick of hepatitis in children. Currently, over 200 cases have been reported worldwide, a relatively small amount that nonetheless belies a considerable toll, including several deaths and the need for liver transplantation in a number of patients. The long-term implications are not yet known. Global health officials are working hard to determine a cause, with many focusing on the underlying cases of adenovirus that several patients have presented with.
To understand more, this news organization reached out to frequent contributor William F. Balistreri, MD, a specialist in pediatric gastroenterology and hepatology at Cincinnati Children’s Hospital Medical Center, where to date they have treated at least six cases of hepatitis in otherwise healthy young children, with one requiring a liver transplant. Dr. Balistreri discussed how the outbreak has developed to date, his advice to hepatologists and pediatricians, and where we stand now in this fast-evolving crisis.
Tracing the outbreak in the United States
How has this outbreak played out thus far in the United States, and what have we learned from that?
Sporadic reports of cases in multiple states are appearing. On April 21, 2022, a health alert was issued by the Centers for Disease Control and Prevention, recommending testing for adenovirus in children with acute hepatitis of an unknown etiology.
Baker and colleagues recently described five children with severe hepatitis and adenovirus viremia who were admitted to a children’s hospital in Birmingham, Ala., between October and November 2021. In collaboration with local and state officials, the CDC reviewed clinical records in order to identify patients with hepatitis and concomitant adenovirus infection, confirmed by polymerase chain reaction (PCR).
By February 2022, a total of nine children were identified. There was no epidemiologic linkage among these nine patients; all were well and immunocompetent. The prodromal features were somewhat similar: upper respiratory infection, vomiting, diarrhea, and jaundice. All children had markedly elevated aminotransferase levels and variably elevated total bilirubin levels. Extensive workup for other causes of acute liver injury (for example, other viruses, toxins/drugs, metabolic and autoimmune diseases) was unrevealing.
Specifically, none had documented SARS-CoV-2 infection. However, in all nine children, adenovirus was detected in whole blood samples. In the six children who underwent liver biopsy, there was nonspecific hepatitis, without inclusions or immunohistochemical detection of viral agents, including adenovirus. In three patients, the liver injury progressed, and despite the administration of antiviral agents, two underwent liver transplantation.
Baker and colleagues also suggested that measurement of adenovirus titers in whole blood (rather than plasma) may be more sensitive.
The CDC has recommended monitoring and surveillance in order to more fully understand the nature of the illness.
European and global cases
What has been the experience with this in Europe and elsewhere globally?
In mid-to-late 2021, several cases of acute hepatitis of unknown nature in children were identified in Europe. Public health officials in the United Kingdom investigated the high number of cases seen in children from England, Scotland, and Wales. They noted approximately 60 cases in England, mostly in children aged 2-5 years.
Marsh and colleagues reported a cluster of cases of severe hepatitis of unknown origin in Scotland affecting children aged 3-5 years. In Scotland, admitted cases were routinely tested for SARS-CoV-2. Of the 13 cases, five had a recent positive test. They discussed the possibility of increased severity of disease following infection with Omicron BA.2 (the dominant SARS-CoV-2 virus circulating in Scotland at that time) or infection by an uncharacterized SARS-CoV-2 variant. None of the children had been vaccinated for SARS-CoV-2.
On April 15, 2022, the World Health Organization Disease Outbreak News published a report of acute hepatitis of unknown etiology occurring in Great Britain and Northern Ireland. By April 21, 2022, 169 cases of acute hepatitis of unknown origin in children younger than 16 years had been reported from 11 countries in the WHO European region and 1 country in the WHO region of the Americas. Approximately 10% required a liver transplantation and at least one death was reported.
What has been established about the possible connection to the SARS-CoV-2 virus, particularly as it relates to coinfection with adenovirus?
In that WHO report of 169 cases, adenovirus was detected in 74 and SARS-CoV-2 in 20. Of note, 19 cases had a SARS-CoV-2 and adenovirus coinfection.
The report’s authors emphasized that, “while adenovirus is a possible hypothesis, investigations are ongoing for the causative agent.” The authors questioned whether this represents a continuing increase in cases of hepatitis or reflects an increased awareness.
The stated priority of the WHO is to determine the cause and to further refine control and prevention actions.
Given the worldwide nature of this outbreak, have connections between any of the cases been made yet?
Not to my knowledge.
What clinicians need to know
What makes this outbreak of hepatitis cases particularly concerning to the health care community, in comparison to other childhood diseases that occur globally? Is it because the cause is unknown or is it for other reasons?
It may be a collective heightened concern following the emergence of COVID.
Whether it represents a new form of acute hepatitis, a continuing increase in cases of hepatitis, or an increased awareness because of the well-publicized alerts remains to be determined. We certainly saw “viral-induced hepatitis” in the past.
Young patients may first be brought to pediatricians. What, if anything, should pediatricians be on the lookout for? Do they need a heightened index of suspicion or are the cases too rare at this point?
An awareness of the “outbreak” may allow the clinician to extend the typical workup of a child presenting with an undefined, presumably viral illness.
In the cases reported, the prodromal and/or presenting symptoms were respiratory and gastrointestinal in nature. They include nausea, vomiting, diarrhea, and abdominal pain.
Specifically, if jaundice and/or scleral icterus is noted, then hepatitis should be suspected.
Should pediatricians consider early referral to a pediatric gastroenterologist or hepatologist?
Yes, because there is the potential for finding a treatable cause (for example, autoimmune hepatitis or a specific metabolic disease) in a patient presenting in this fashion.
In addition, the potential for progression to acute liver failure (with coagulopathy and encephalopathy), albeit rare, exists.
What do hepatologists need to be doing when presented with suspected cases?
The typical clinical picture holds and the workup is standard. The one new key, given the recent data, is to test for adenovirus, using whole blood versus plasma, as the former may be more sensitive.
In addition, it is prudent to check for SARS-CoV-2 by PCR.
What are the major questions that remain and that you’d like to see elucidated going forward?
There are many. Is this a new disease? A new variant of adenovirus? A synergy or susceptibility related to SARS-CoV-2? Is it related to a variant of SARS-CoV-2? Is it triggering an adverse immune response? Are there other epigenetic factors involved? And finally, is this an increase, or is it related to a collective heightened concern following the pandemic?
Dr. Balistreri is the Dorothy M.M. Kersten Professor of Pediatrics, director emeritus of the Pediatric Liver Care Center, medical director emeritus of liver transplantation, and professor at the University of Cincinnati; he is also with the department of pediatrics at Cincinnati Children’s Hospital Medical Center.
A version of this article first appeared on Medscape.com.
This spring, global health advisories have been issued regarding an alarming – and as-yet unexplained – uptick of hepatitis in children. Currently, over 200 cases have been reported worldwide, a relatively small amount that nonetheless belies a considerable toll, including several deaths and the need for liver transplantation in a number of patients. The long-term implications are not yet known. Global health officials are working hard to determine a cause, with many focusing on the underlying cases of adenovirus that several patients have presented with.
To understand more, this news organization reached out to frequent contributor William F. Balistreri, MD, a specialist in pediatric gastroenterology and hepatology at Cincinnati Children’s Hospital Medical Center, where to date they have treated at least six cases of hepatitis in otherwise healthy young children, with one requiring a liver transplant. Dr. Balistreri discussed how the outbreak has developed to date, his advice to hepatologists and pediatricians, and where we stand now in this fast-evolving crisis.
Tracing the outbreak in the United States
How has this outbreak played out thus far in the United States, and what have we learned from that?
Sporadic reports of cases in multiple states are appearing. On April 21, 2022, a health alert was issued by the Centers for Disease Control and Prevention, recommending testing for adenovirus in children with acute hepatitis of an unknown etiology.
Baker and colleagues recently described five children with severe hepatitis and adenovirus viremia who were admitted to a children’s hospital in Birmingham, Ala., between October and November 2021. In collaboration with local and state officials, the CDC reviewed clinical records in order to identify patients with hepatitis and concomitant adenovirus infection, confirmed by polymerase chain reaction (PCR).
By February 2022, a total of nine children were identified. There was no epidemiologic linkage among these nine patients; all were well and immunocompetent. The prodromal features were somewhat similar: upper respiratory infection, vomiting, diarrhea, and jaundice. All children had markedly elevated aminotransferase levels and variably elevated total bilirubin levels. Extensive workup for other causes of acute liver injury (for example, other viruses, toxins/drugs, metabolic and autoimmune diseases) was unrevealing.
Specifically, none had documented SARS-CoV-2 infection. However, in all nine children, adenovirus was detected in whole blood samples. In the six children who underwent liver biopsy, there was nonspecific hepatitis, without inclusions or immunohistochemical detection of viral agents, including adenovirus. In three patients, the liver injury progressed, and despite the administration of antiviral agents, two underwent liver transplantation.
Baker and colleagues also suggested that measurement of adenovirus titers in whole blood (rather than plasma) may be more sensitive.
The CDC has recommended monitoring and surveillance in order to more fully understand the nature of the illness.
European and global cases
What has been the experience with this in Europe and elsewhere globally?
In mid-to-late 2021, several cases of acute hepatitis of unknown nature in children were identified in Europe. Public health officials in the United Kingdom investigated the high number of cases seen in children from England, Scotland, and Wales. They noted approximately 60 cases in England, mostly in children aged 2-5 years.
Marsh and colleagues reported a cluster of cases of severe hepatitis of unknown origin in Scotland affecting children aged 3-5 years. In Scotland, admitted cases were routinely tested for SARS-CoV-2. Of the 13 cases, five had a recent positive test. They discussed the possibility of increased severity of disease following infection with Omicron BA.2 (the dominant SARS-CoV-2 virus circulating in Scotland at that time) or infection by an uncharacterized SARS-CoV-2 variant. None of the children had been vaccinated for SARS-CoV-2.
On April 15, 2022, the World Health Organization Disease Outbreak News published a report of acute hepatitis of unknown etiology occurring in Great Britain and Northern Ireland. By April 21, 2022, 169 cases of acute hepatitis of unknown origin in children younger than 16 years had been reported from 11 countries in the WHO European region and 1 country in the WHO region of the Americas. Approximately 10% required a liver transplantation and at least one death was reported.
What has been established about the possible connection to the SARS-CoV-2 virus, particularly as it relates to coinfection with adenovirus?
In that WHO report of 169 cases, adenovirus was detected in 74 and SARS-CoV-2 in 20. Of note, 19 cases had a SARS-CoV-2 and adenovirus coinfection.
The report’s authors emphasized that, “while adenovirus is a possible hypothesis, investigations are ongoing for the causative agent.” The authors questioned whether this represents a continuing increase in cases of hepatitis or reflects an increased awareness.
The stated priority of the WHO is to determine the cause and to further refine control and prevention actions.
Given the worldwide nature of this outbreak, have connections between any of the cases been made yet?
Not to my knowledge.
What clinicians need to know
What makes this outbreak of hepatitis cases particularly concerning to the health care community, in comparison to other childhood diseases that occur globally? Is it because the cause is unknown or is it for other reasons?
It may be a collective heightened concern following the emergence of COVID.
Whether it represents a new form of acute hepatitis, a continuing increase in cases of hepatitis, or an increased awareness because of the well-publicized alerts remains to be determined. We certainly saw “viral-induced hepatitis” in the past.
Young patients may first be brought to pediatricians. What, if anything, should pediatricians be on the lookout for? Do they need a heightened index of suspicion or are the cases too rare at this point?
An awareness of the “outbreak” may allow the clinician to extend the typical workup of a child presenting with an undefined, presumably viral illness.
In the cases reported, the prodromal and/or presenting symptoms were respiratory and gastrointestinal in nature. They include nausea, vomiting, diarrhea, and abdominal pain.
Specifically, if jaundice and/or scleral icterus is noted, then hepatitis should be suspected.
Should pediatricians consider early referral to a pediatric gastroenterologist or hepatologist?
Yes, because there is the potential for finding a treatable cause (for example, autoimmune hepatitis or a specific metabolic disease) in a patient presenting in this fashion.
In addition, the potential for progression to acute liver failure (with coagulopathy and encephalopathy), albeit rare, exists.
What do hepatologists need to be doing when presented with suspected cases?
The typical clinical picture holds and the workup is standard. The one new key, given the recent data, is to test for adenovirus, using whole blood versus plasma, as the former may be more sensitive.
In addition, it is prudent to check for SARS-CoV-2 by PCR.
What are the major questions that remain and that you’d like to see elucidated going forward?
There are many. Is this a new disease? A new variant of adenovirus? A synergy or susceptibility related to SARS-CoV-2? Is it related to a variant of SARS-CoV-2? Is it triggering an adverse immune response? Are there other epigenetic factors involved? And finally, is this an increase, or is it related to a collective heightened concern following the pandemic?
Dr. Balistreri is the Dorothy M.M. Kersten Professor of Pediatrics, director emeritus of the Pediatric Liver Care Center, medical director emeritus of liver transplantation, and professor at the University of Cincinnati; he is also with the department of pediatrics at Cincinnati Children’s Hospital Medical Center.
A version of this article first appeared on Medscape.com.
Flu vaccine linked to lower risk for stroke: INTERSTROKE
in a large new case-control study.
“While influenza vaccination is a cost-effective method to prevent influenza, it is also an effective way to reduce the burden of stroke,” said study author Christopher Schwarzbach, MD, of Ludwigshafen (Germany) Hospital.
“Our results therefore encourage the wider use of influenza vaccination,” he concluded.
Dr. Schwarzbach presented these data from the INTERSTROKE study at the 2022 European Stroke Organisation Conference.
He explained that acute inflammatory disease is thought to increase the risk for cerebrovascular events, and the seasonality of influenza-like illness appears to be associated with the seasonality of cardiovascular and cerebrovascular events. Previous observational studies have also shown a link between influenza vaccination and a reduced risk for stroke.
The current INTERSTROKE study was a large international case-control study conducted between 2007 and 2015 that involved 13,447 cases (patients within 5 days of their first stroke) and a similar number of age- and gender-matched people from 32 countries across the world.
All cases and control subjects were systematically asked whether they had acute febrile illness in the previous 4 weeks and whether they had received an influenza vaccination within the previous year.
Conditional logistical regression was used to quantify the results, with adjustment for 13 different possible confounding factors, including hypertension, activity, smoking, cardiovascular risk factors, and socioeconomic factors.
Results showed that having had an acute febrile illness in the previous 4 weeks was more commonly reported in the patients with an acute ischemic stroke (8.7%) than in control patients (5.6%). After adjustment for confounding factors, this gives an adjusted risk ratio of 1.18, which was of borderline statistical significance (95% confidence limits, 1.01-1.39), Dr. Schwarzbach reported.
The association between recent febrile illness and acute ischemic stroke was stronger when compared with community control subjects (adjusted odds ratio, 2.0), but it was absent when compared with hospital control subjects.
The association was also only apparent in Australia, China, North America, and Western Europe; it was not seen in other parts of the world.
There was no association between acute febrile illness and acute cerebral hemorrhage.
Flu vaccine linked to halving of stroke risk
Having received a flu vaccine in the previous year was strongly associated with a lower risk for any type of stroke (aOR, 0.53), ischemic stroke (aOR, 0.57), and hemorrhagic stroke (aOR, 0.34).
Dr. Schwarzbach noted that these results were also consistent in an extended statistical model that included variables that might reflect a willingness to be vaccinated and when compared with both community and hospital-based control subjects.
The strength of the association between influenza vaccination and reduced risk for stroke was similar when compared with either community or hospital control subjects, and was only moderately stronger during than outside the influenza season.
The association was also seen in all regions of the world apart from Africa and South Asia, Dr. Schwarzbach reported, but he noted that vaccination rates in these two regions were extremely low.
The researchers also found that the magnitude of the associations between flu vaccination and lower risk for stroke were stronger in individuals who had multiple annual vaccinations, with an odds ratio of 0.54 in those who had received a vaccine every year for the previous 5 years, and of 0.79 in those who had received one to four vaccinations in the previous 5 years.
Mechanism: Immune stimulation?
Discussing possible mechanisms behind these results, Dr. Schwarzbach noted that the finding that the association with influenza vaccination and reduced stroke risk was independent of seasonality was surprising. “We had expected the protective effect of vaccination to be bigger during the influenza season, but this wasn’t the case.”
He suggested that one explanation might be the inclusion of regions of the world where this seasonality doesn’t exist.
But he pointed out that the finding of a stronger association between flu vaccination and lower stroke risk in those who had received more vaccinations has given rise to another theory: that it is the stimulation of the immune system rather than the protection of infection against influenza that is the key factor.
In an interview with Dr. Schwarzbach, Guillaume Turk, MD, professor of neurology at GHU Paris, pointed out that causal inferences are always difficult in case-control studies and in clinical epidemiology in general.
“What makes you think that this association between influenza vaccination and decreased risk is causal rather than due to unmeasured confounders? For example, patients who received vaccination may have received more medical attention and may have been more aware of the risk factors for stroke,” he asked.
Dr. Schwarzbach replied: “Yes, this is the issue of healthy user bias, which is always a problem in this type of research and is hard to address.”
“What we tried to do here is to adjust for variables that might influence the willingness of people to get vaccinated,” he added. “These were mainly socioeconomic factors. But, of course, this is something that we can’t rule out.”
Dr. Schwarzbach noted that, for more reliable information on this association, prospective studies are needed.
‘A plausible effect’
Discussing the study after the presentation, William Whiteley, BM, PhD, a clinical epidemiologist at the University of Edinburgh and a consultant neurologist in NHS Lothian, said vaccination was a potentially important way to reduce stroke.
“In this study, there was a plausible effect on reducing stroke incidence from vaccination against influenza, and also a plausible increase in the risk of stroke from having a recent febrile illness, which we have seen in other studies,” he commented.
Dr. Whiteley noted that this observation was particularly relevant now because of the COVID-19 pandemic.
“We’ve all been worried about the risk of heart attack and stroke after COVID, where we’ve seen quite early high risks, and we are also optimistic about the effect of vaccination on reducing those incidences. We’ve seen data from the U.K. that there may be around a 20% reduction in risk of stroke from vaccination. So, it’s all quite plausible, but at the moment it’s all based on observational evidence and we really need some randomized evidence,” he said.
“Vaccination and infections have all sorts of odd confounders,” he added. “People who get vaccines tend to be more healthy than those who don’t get vaccines, so you can start to see quite implausible effects of vaccination on overall mortality, which probably aren’t real, and you probably can’t get rid of that totally with statistical methods.”
Alastair Webb, MD, University of Oxford (England), asked how reliable the current findings were, given that the occurrence of febrile illnesses and receipt of vaccines were all self-reported, and although there was an association for ischemic stroke and febrile illness, this seemed to go in the opposite direction for hemorrhagic stroke. He also noted that the 50% reduction in stroke risk with vaccination in this study seemed “quite a large magnitude of effect.”
Dr. Whiteley replied: “Yes, it is large, but it is promising.” He cited a previous meta-analysis of randomized studies that showed a roughly 25%-35% reduction in vascular events after flu vaccination, but noted that there was a lot of heterogeneity between studies.
“I’m not sure we’re going to see much more randomized evidence, but I think we can probably all agree that having a vaccine against flu or COVID is a good thing for all of us,” Dr. Whiteley concluded.
The INTERSTROKE study was funded by the Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Canadian Stroke Network, Health Research Board Ireland, Swedish Research Council, Swedish Heart and Lung Foundation, The Health & Medical Care Committee of the Regional Executive Board, Region Vastra Gotaland (Sweden), AstraZeneca, Boehringer Ingelheim, Pfizer, MSD, Chest, Heart and Stroke Scotland, and The Stroke Association, with support from The UK Stroke Research Network. The authors reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
in a large new case-control study.
“While influenza vaccination is a cost-effective method to prevent influenza, it is also an effective way to reduce the burden of stroke,” said study author Christopher Schwarzbach, MD, of Ludwigshafen (Germany) Hospital.
“Our results therefore encourage the wider use of influenza vaccination,” he concluded.
Dr. Schwarzbach presented these data from the INTERSTROKE study at the 2022 European Stroke Organisation Conference.
He explained that acute inflammatory disease is thought to increase the risk for cerebrovascular events, and the seasonality of influenza-like illness appears to be associated with the seasonality of cardiovascular and cerebrovascular events. Previous observational studies have also shown a link between influenza vaccination and a reduced risk for stroke.
The current INTERSTROKE study was a large international case-control study conducted between 2007 and 2015 that involved 13,447 cases (patients within 5 days of their first stroke) and a similar number of age- and gender-matched people from 32 countries across the world.
All cases and control subjects were systematically asked whether they had acute febrile illness in the previous 4 weeks and whether they had received an influenza vaccination within the previous year.
Conditional logistical regression was used to quantify the results, with adjustment for 13 different possible confounding factors, including hypertension, activity, smoking, cardiovascular risk factors, and socioeconomic factors.
Results showed that having had an acute febrile illness in the previous 4 weeks was more commonly reported in the patients with an acute ischemic stroke (8.7%) than in control patients (5.6%). After adjustment for confounding factors, this gives an adjusted risk ratio of 1.18, which was of borderline statistical significance (95% confidence limits, 1.01-1.39), Dr. Schwarzbach reported.
The association between recent febrile illness and acute ischemic stroke was stronger when compared with community control subjects (adjusted odds ratio, 2.0), but it was absent when compared with hospital control subjects.
The association was also only apparent in Australia, China, North America, and Western Europe; it was not seen in other parts of the world.
There was no association between acute febrile illness and acute cerebral hemorrhage.
Flu vaccine linked to halving of stroke risk
Having received a flu vaccine in the previous year was strongly associated with a lower risk for any type of stroke (aOR, 0.53), ischemic stroke (aOR, 0.57), and hemorrhagic stroke (aOR, 0.34).
Dr. Schwarzbach noted that these results were also consistent in an extended statistical model that included variables that might reflect a willingness to be vaccinated and when compared with both community and hospital-based control subjects.
The strength of the association between influenza vaccination and reduced risk for stroke was similar when compared with either community or hospital control subjects, and was only moderately stronger during than outside the influenza season.
The association was also seen in all regions of the world apart from Africa and South Asia, Dr. Schwarzbach reported, but he noted that vaccination rates in these two regions were extremely low.
The researchers also found that the magnitude of the associations between flu vaccination and lower risk for stroke were stronger in individuals who had multiple annual vaccinations, with an odds ratio of 0.54 in those who had received a vaccine every year for the previous 5 years, and of 0.79 in those who had received one to four vaccinations in the previous 5 years.
Mechanism: Immune stimulation?
Discussing possible mechanisms behind these results, Dr. Schwarzbach noted that the finding that the association with influenza vaccination and reduced stroke risk was independent of seasonality was surprising. “We had expected the protective effect of vaccination to be bigger during the influenza season, but this wasn’t the case.”
He suggested that one explanation might be the inclusion of regions of the world where this seasonality doesn’t exist.
But he pointed out that the finding of a stronger association between flu vaccination and lower stroke risk in those who had received more vaccinations has given rise to another theory: that it is the stimulation of the immune system rather than the protection of infection against influenza that is the key factor.
In an interview with Dr. Schwarzbach, Guillaume Turk, MD, professor of neurology at GHU Paris, pointed out that causal inferences are always difficult in case-control studies and in clinical epidemiology in general.
“What makes you think that this association between influenza vaccination and decreased risk is causal rather than due to unmeasured confounders? For example, patients who received vaccination may have received more medical attention and may have been more aware of the risk factors for stroke,” he asked.
Dr. Schwarzbach replied: “Yes, this is the issue of healthy user bias, which is always a problem in this type of research and is hard to address.”
“What we tried to do here is to adjust for variables that might influence the willingness of people to get vaccinated,” he added. “These were mainly socioeconomic factors. But, of course, this is something that we can’t rule out.”
Dr. Schwarzbach noted that, for more reliable information on this association, prospective studies are needed.
‘A plausible effect’
Discussing the study after the presentation, William Whiteley, BM, PhD, a clinical epidemiologist at the University of Edinburgh and a consultant neurologist in NHS Lothian, said vaccination was a potentially important way to reduce stroke.
“In this study, there was a plausible effect on reducing stroke incidence from vaccination against influenza, and also a plausible increase in the risk of stroke from having a recent febrile illness, which we have seen in other studies,” he commented.
Dr. Whiteley noted that this observation was particularly relevant now because of the COVID-19 pandemic.
“We’ve all been worried about the risk of heart attack and stroke after COVID, where we’ve seen quite early high risks, and we are also optimistic about the effect of vaccination on reducing those incidences. We’ve seen data from the U.K. that there may be around a 20% reduction in risk of stroke from vaccination. So, it’s all quite plausible, but at the moment it’s all based on observational evidence and we really need some randomized evidence,” he said.
“Vaccination and infections have all sorts of odd confounders,” he added. “People who get vaccines tend to be more healthy than those who don’t get vaccines, so you can start to see quite implausible effects of vaccination on overall mortality, which probably aren’t real, and you probably can’t get rid of that totally with statistical methods.”
Alastair Webb, MD, University of Oxford (England), asked how reliable the current findings were, given that the occurrence of febrile illnesses and receipt of vaccines were all self-reported, and although there was an association for ischemic stroke and febrile illness, this seemed to go in the opposite direction for hemorrhagic stroke. He also noted that the 50% reduction in stroke risk with vaccination in this study seemed “quite a large magnitude of effect.”
Dr. Whiteley replied: “Yes, it is large, but it is promising.” He cited a previous meta-analysis of randomized studies that showed a roughly 25%-35% reduction in vascular events after flu vaccination, but noted that there was a lot of heterogeneity between studies.
“I’m not sure we’re going to see much more randomized evidence, but I think we can probably all agree that having a vaccine against flu or COVID is a good thing for all of us,” Dr. Whiteley concluded.
The INTERSTROKE study was funded by the Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Canadian Stroke Network, Health Research Board Ireland, Swedish Research Council, Swedish Heart and Lung Foundation, The Health & Medical Care Committee of the Regional Executive Board, Region Vastra Gotaland (Sweden), AstraZeneca, Boehringer Ingelheim, Pfizer, MSD, Chest, Heart and Stroke Scotland, and The Stroke Association, with support from The UK Stroke Research Network. The authors reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
in a large new case-control study.
“While influenza vaccination is a cost-effective method to prevent influenza, it is also an effective way to reduce the burden of stroke,” said study author Christopher Schwarzbach, MD, of Ludwigshafen (Germany) Hospital.
“Our results therefore encourage the wider use of influenza vaccination,” he concluded.
Dr. Schwarzbach presented these data from the INTERSTROKE study at the 2022 European Stroke Organisation Conference.
He explained that acute inflammatory disease is thought to increase the risk for cerebrovascular events, and the seasonality of influenza-like illness appears to be associated with the seasonality of cardiovascular and cerebrovascular events. Previous observational studies have also shown a link between influenza vaccination and a reduced risk for stroke.
The current INTERSTROKE study was a large international case-control study conducted between 2007 and 2015 that involved 13,447 cases (patients within 5 days of their first stroke) and a similar number of age- and gender-matched people from 32 countries across the world.
All cases and control subjects were systematically asked whether they had acute febrile illness in the previous 4 weeks and whether they had received an influenza vaccination within the previous year.
Conditional logistical regression was used to quantify the results, with adjustment for 13 different possible confounding factors, including hypertension, activity, smoking, cardiovascular risk factors, and socioeconomic factors.
Results showed that having had an acute febrile illness in the previous 4 weeks was more commonly reported in the patients with an acute ischemic stroke (8.7%) than in control patients (5.6%). After adjustment for confounding factors, this gives an adjusted risk ratio of 1.18, which was of borderline statistical significance (95% confidence limits, 1.01-1.39), Dr. Schwarzbach reported.
The association between recent febrile illness and acute ischemic stroke was stronger when compared with community control subjects (adjusted odds ratio, 2.0), but it was absent when compared with hospital control subjects.
The association was also only apparent in Australia, China, North America, and Western Europe; it was not seen in other parts of the world.
There was no association between acute febrile illness and acute cerebral hemorrhage.
Flu vaccine linked to halving of stroke risk
Having received a flu vaccine in the previous year was strongly associated with a lower risk for any type of stroke (aOR, 0.53), ischemic stroke (aOR, 0.57), and hemorrhagic stroke (aOR, 0.34).
Dr. Schwarzbach noted that these results were also consistent in an extended statistical model that included variables that might reflect a willingness to be vaccinated and when compared with both community and hospital-based control subjects.
The strength of the association between influenza vaccination and reduced risk for stroke was similar when compared with either community or hospital control subjects, and was only moderately stronger during than outside the influenza season.
The association was also seen in all regions of the world apart from Africa and South Asia, Dr. Schwarzbach reported, but he noted that vaccination rates in these two regions were extremely low.
The researchers also found that the magnitude of the associations between flu vaccination and lower risk for stroke were stronger in individuals who had multiple annual vaccinations, with an odds ratio of 0.54 in those who had received a vaccine every year for the previous 5 years, and of 0.79 in those who had received one to four vaccinations in the previous 5 years.
Mechanism: Immune stimulation?
Discussing possible mechanisms behind these results, Dr. Schwarzbach noted that the finding that the association with influenza vaccination and reduced stroke risk was independent of seasonality was surprising. “We had expected the protective effect of vaccination to be bigger during the influenza season, but this wasn’t the case.”
He suggested that one explanation might be the inclusion of regions of the world where this seasonality doesn’t exist.
But he pointed out that the finding of a stronger association between flu vaccination and lower stroke risk in those who had received more vaccinations has given rise to another theory: that it is the stimulation of the immune system rather than the protection of infection against influenza that is the key factor.
In an interview with Dr. Schwarzbach, Guillaume Turk, MD, professor of neurology at GHU Paris, pointed out that causal inferences are always difficult in case-control studies and in clinical epidemiology in general.
“What makes you think that this association between influenza vaccination and decreased risk is causal rather than due to unmeasured confounders? For example, patients who received vaccination may have received more medical attention and may have been more aware of the risk factors for stroke,” he asked.
Dr. Schwarzbach replied: “Yes, this is the issue of healthy user bias, which is always a problem in this type of research and is hard to address.”
“What we tried to do here is to adjust for variables that might influence the willingness of people to get vaccinated,” he added. “These were mainly socioeconomic factors. But, of course, this is something that we can’t rule out.”
Dr. Schwarzbach noted that, for more reliable information on this association, prospective studies are needed.
‘A plausible effect’
Discussing the study after the presentation, William Whiteley, BM, PhD, a clinical epidemiologist at the University of Edinburgh and a consultant neurologist in NHS Lothian, said vaccination was a potentially important way to reduce stroke.
“In this study, there was a plausible effect on reducing stroke incidence from vaccination against influenza, and also a plausible increase in the risk of stroke from having a recent febrile illness, which we have seen in other studies,” he commented.
Dr. Whiteley noted that this observation was particularly relevant now because of the COVID-19 pandemic.
“We’ve all been worried about the risk of heart attack and stroke after COVID, where we’ve seen quite early high risks, and we are also optimistic about the effect of vaccination on reducing those incidences. We’ve seen data from the U.K. that there may be around a 20% reduction in risk of stroke from vaccination. So, it’s all quite plausible, but at the moment it’s all based on observational evidence and we really need some randomized evidence,” he said.
“Vaccination and infections have all sorts of odd confounders,” he added. “People who get vaccines tend to be more healthy than those who don’t get vaccines, so you can start to see quite implausible effects of vaccination on overall mortality, which probably aren’t real, and you probably can’t get rid of that totally with statistical methods.”
Alastair Webb, MD, University of Oxford (England), asked how reliable the current findings were, given that the occurrence of febrile illnesses and receipt of vaccines were all self-reported, and although there was an association for ischemic stroke and febrile illness, this seemed to go in the opposite direction for hemorrhagic stroke. He also noted that the 50% reduction in stroke risk with vaccination in this study seemed “quite a large magnitude of effect.”
Dr. Whiteley replied: “Yes, it is large, but it is promising.” He cited a previous meta-analysis of randomized studies that showed a roughly 25%-35% reduction in vascular events after flu vaccination, but noted that there was a lot of heterogeneity between studies.
“I’m not sure we’re going to see much more randomized evidence, but I think we can probably all agree that having a vaccine against flu or COVID is a good thing for all of us,” Dr. Whiteley concluded.
The INTERSTROKE study was funded by the Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Canadian Stroke Network, Health Research Board Ireland, Swedish Research Council, Swedish Heart and Lung Foundation, The Health & Medical Care Committee of the Regional Executive Board, Region Vastra Gotaland (Sweden), AstraZeneca, Boehringer Ingelheim, Pfizer, MSD, Chest, Heart and Stroke Scotland, and The Stroke Association, with support from The UK Stroke Research Network. The authors reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
FDA approves two vonoprazan therapies for H. pylori eradication
: Voquezna Triple Pak (vonoprazan, amoxicillin, clarithromycin) and Voquezna Dual Pak (vonoprazan, amoxicillin), both from Phathom Pharmaceuticals.
Vonoprazan is an oral potassium-competitive acid blocker and “the first innovative acid suppressant from a new drug class approved in the United States in over 30 years,” the company said in a news release announcing the approval.
“The approval of Voquezna treatment regimens offers physicians and patients two therapeutic options that showed superior eradication rates compared to proton pump inhibitor-based (PPI) lansoprazole triple therapy in the overall patient population in a pivotal trial,” Terrie Curran, president and CEO of Phathom Pharmaceuticals, said in the release.
“H. pylori eradication rates continue to decline in part due to antibiotic resistance, inadequate acid suppression, and complex treatment regimens, resulting in treatment failures and complications for patients,” Ms. Curran noted.
“New therapies that have the potential to address the limitations of current treatments are needed, and we look forward to bringing these innovative vonoprazan-based treatment options to the millions of H pylori sufferers in the United States,” Ms. Curran said.
FDA approval of vonoprazan triple and dual therapy was based on safety and efficacy data from the phase 3 PHALCON-HP trial involving 1,046 patients.
As earlier reported, both treatment regimens were noninferior to PPI-based triple therapy (lansoprazole with amoxicillin and clarithromycin) in patients with H. pylori strains that were not resistant to clarithromycin or amoxicillin at baseline.
In this analysis, the eradication rate was 78.8% with PPI-based triple therapy, compared with 84.7% with vonoprazan triple therapy and 78.5% with vonoprazan dual therapy.
Vonoprazan triple and dual therapy were both superior to PPI-based triple therapy among all patients, including patients with clarithromycin-resistant H. pylori.
Among patients with clarithromycin-resistant H. pylori, 31.9% achieved eradication with PPI triple therapy, compared with 65.8% with vonoprazan triple therapy and 69.6% with vonoprazan dual therapy.
Among all patients, 68.5% achieved eradication with PPI triple therapy, 80.8% with vonoprazan triple therapy and 77.2% with vonoprazan dual therapy.
Adverse event rates for the vonoprazan-based regimens were comparable to lansoprazole triple therapy. Full prescribing information is available online.
“As a practicing physician, I am excited about the potential of two novel, first-line H. pylori treatment options,” William D. Chey, MD, chief of gastroenterology & hepatology at the University of Michigan, Ann Arbor, said in the news release.
“I believe the added flexibility of having two additional effective therapies, including a dual therapy option that does not contain clarithromycin, offers the potential to improve clinical outcomes in patients with H. pylori infection,” Dr. Chey added.
The company expects to launch both products in the third quarter of 2022. Both treatment regimens will be supplied in convenient blister packs to help promote compliance.
A version of this article first appeared on Medscape.com.
: Voquezna Triple Pak (vonoprazan, amoxicillin, clarithromycin) and Voquezna Dual Pak (vonoprazan, amoxicillin), both from Phathom Pharmaceuticals.
Vonoprazan is an oral potassium-competitive acid blocker and “the first innovative acid suppressant from a new drug class approved in the United States in over 30 years,” the company said in a news release announcing the approval.
“The approval of Voquezna treatment regimens offers physicians and patients two therapeutic options that showed superior eradication rates compared to proton pump inhibitor-based (PPI) lansoprazole triple therapy in the overall patient population in a pivotal trial,” Terrie Curran, president and CEO of Phathom Pharmaceuticals, said in the release.
“H. pylori eradication rates continue to decline in part due to antibiotic resistance, inadequate acid suppression, and complex treatment regimens, resulting in treatment failures and complications for patients,” Ms. Curran noted.
“New therapies that have the potential to address the limitations of current treatments are needed, and we look forward to bringing these innovative vonoprazan-based treatment options to the millions of H pylori sufferers in the United States,” Ms. Curran said.
FDA approval of vonoprazan triple and dual therapy was based on safety and efficacy data from the phase 3 PHALCON-HP trial involving 1,046 patients.
As earlier reported, both treatment regimens were noninferior to PPI-based triple therapy (lansoprazole with amoxicillin and clarithromycin) in patients with H. pylori strains that were not resistant to clarithromycin or amoxicillin at baseline.
In this analysis, the eradication rate was 78.8% with PPI-based triple therapy, compared with 84.7% with vonoprazan triple therapy and 78.5% with vonoprazan dual therapy.
Vonoprazan triple and dual therapy were both superior to PPI-based triple therapy among all patients, including patients with clarithromycin-resistant H. pylori.
Among patients with clarithromycin-resistant H. pylori, 31.9% achieved eradication with PPI triple therapy, compared with 65.8% with vonoprazan triple therapy and 69.6% with vonoprazan dual therapy.
Among all patients, 68.5% achieved eradication with PPI triple therapy, 80.8% with vonoprazan triple therapy and 77.2% with vonoprazan dual therapy.
Adverse event rates for the vonoprazan-based regimens were comparable to lansoprazole triple therapy. Full prescribing information is available online.
“As a practicing physician, I am excited about the potential of two novel, first-line H. pylori treatment options,” William D. Chey, MD, chief of gastroenterology & hepatology at the University of Michigan, Ann Arbor, said in the news release.
“I believe the added flexibility of having two additional effective therapies, including a dual therapy option that does not contain clarithromycin, offers the potential to improve clinical outcomes in patients with H. pylori infection,” Dr. Chey added.
The company expects to launch both products in the third quarter of 2022. Both treatment regimens will be supplied in convenient blister packs to help promote compliance.
A version of this article first appeared on Medscape.com.
: Voquezna Triple Pak (vonoprazan, amoxicillin, clarithromycin) and Voquezna Dual Pak (vonoprazan, amoxicillin), both from Phathom Pharmaceuticals.
Vonoprazan is an oral potassium-competitive acid blocker and “the first innovative acid suppressant from a new drug class approved in the United States in over 30 years,” the company said in a news release announcing the approval.
“The approval of Voquezna treatment regimens offers physicians and patients two therapeutic options that showed superior eradication rates compared to proton pump inhibitor-based (PPI) lansoprazole triple therapy in the overall patient population in a pivotal trial,” Terrie Curran, president and CEO of Phathom Pharmaceuticals, said in the release.
“H. pylori eradication rates continue to decline in part due to antibiotic resistance, inadequate acid suppression, and complex treatment regimens, resulting in treatment failures and complications for patients,” Ms. Curran noted.
“New therapies that have the potential to address the limitations of current treatments are needed, and we look forward to bringing these innovative vonoprazan-based treatment options to the millions of H pylori sufferers in the United States,” Ms. Curran said.
FDA approval of vonoprazan triple and dual therapy was based on safety and efficacy data from the phase 3 PHALCON-HP trial involving 1,046 patients.
As earlier reported, both treatment regimens were noninferior to PPI-based triple therapy (lansoprazole with amoxicillin and clarithromycin) in patients with H. pylori strains that were not resistant to clarithromycin or amoxicillin at baseline.
In this analysis, the eradication rate was 78.8% with PPI-based triple therapy, compared with 84.7% with vonoprazan triple therapy and 78.5% with vonoprazan dual therapy.
Vonoprazan triple and dual therapy were both superior to PPI-based triple therapy among all patients, including patients with clarithromycin-resistant H. pylori.
Among patients with clarithromycin-resistant H. pylori, 31.9% achieved eradication with PPI triple therapy, compared with 65.8% with vonoprazan triple therapy and 69.6% with vonoprazan dual therapy.
Among all patients, 68.5% achieved eradication with PPI triple therapy, 80.8% with vonoprazan triple therapy and 77.2% with vonoprazan dual therapy.
Adverse event rates for the vonoprazan-based regimens were comparable to lansoprazole triple therapy. Full prescribing information is available online.
“As a practicing physician, I am excited about the potential of two novel, first-line H. pylori treatment options,” William D. Chey, MD, chief of gastroenterology & hepatology at the University of Michigan, Ann Arbor, said in the news release.
“I believe the added flexibility of having two additional effective therapies, including a dual therapy option that does not contain clarithromycin, offers the potential to improve clinical outcomes in patients with H. pylori infection,” Dr. Chey added.
The company expects to launch both products in the third quarter of 2022. Both treatment regimens will be supplied in convenient blister packs to help promote compliance.
A version of this article first appeared on Medscape.com.
Worst TB outbreak in 20 years reported in Washington state
Tuberculosis cases are increasing in Washington, which has put public health officials on “heightened alert,” according to a recent announcement from the Washington State Department of Health.
Widespread disruptions in health care and missed tuberculosis diagnoses during the COVID-19 pandemic have likely added to the increase – both locally and globally.
“It’s been 20 years since we saw a cluster of TB cases like this,” Tao Sheng Kwan-Gett, MD, the state’s chief science officer, said in the announcement.
“The pandemic has likely contributed to the rise in cases and the outbreak in at least one correctional facility,” he said. “Increased access to TB testing and treatment in the community is going to be key to getting TB under control.”
Case numbers appeared to fall in Washington during the first year of the pandemic, possibly because of less reporting and missed diagnoses. But in 2021, cases rose quickly. The state reported 199 cases, marking a 22% increase from 2020.
So far this year, 70 cases have been reported, including 17 new cases that all have connections with each other and several state prisons.
The state’s Department of Corrections, Department of Health, and the Centers for Disease Control and Prevention are working together on testing and decreasing spread, MaryAnn Curl, MD, the chief medical officer for the Department of Corrections, said in the statement.
Tuberculosis cases are increasing worldwide. For the first time in more than a decade, TB deaths increased to about 1.5 million, according to the World Health Organization’s 2021 Global Tuberculosis Report.
Across the U.S., the number of reported TB cases significantly declined at the beginning of the pandemic in 2020 but increased again in 2021, according to a recent CDC study.
The Kansas Department of Health also reported an outbreak of TB cases in March, according to USA Today.
At the beginning of the pandemic, some people with TB may have been diagnosed with COVID-19 because both are infectious diseases that attack the lungs and have similar symptoms, the Washington Health Department said.
Like COVID-19, tuberculosis can spread through the air when an infected person coughs or sneezes. But unlike COVID-19, TB typically requires that you have prolonged exposure to become infected.
Symptoms of tuberculosis can include chest pain and coughing, with or without blood, as well as fever, night sweats, weight loss, and fatigue.
Tuberculosis is preventable, treatable, and curable, the Washington Health Department said. Those who travel to countries where TB is more common face higher risks for exposure, as well as those who live or work in settings where TB may spread, such as homeless shelters, prisons, jails, and nursing homes.
People can develop inactive TB, also called latent TB, which doesn’t have any symptoms and isn’t contagious. If people with inactive TB don’t get quick diagnosis or treatment, the infection can become active TB and cause symptoms. State health officials estimated that about 200,000 people in Washington have inactive TB.
Tuberculosis treatment can take a minimum of 6 months, and if it’s not followed carefully, symptoms can become more severe, the Health Department said. Incomplete treatment can also contribute to the spread of antibiotic-resistant strains of tuberculosis.
A version of this article first appeared on WebMD.com.
Tuberculosis cases are increasing in Washington, which has put public health officials on “heightened alert,” according to a recent announcement from the Washington State Department of Health.
Widespread disruptions in health care and missed tuberculosis diagnoses during the COVID-19 pandemic have likely added to the increase – both locally and globally.
“It’s been 20 years since we saw a cluster of TB cases like this,” Tao Sheng Kwan-Gett, MD, the state’s chief science officer, said in the announcement.
“The pandemic has likely contributed to the rise in cases and the outbreak in at least one correctional facility,” he said. “Increased access to TB testing and treatment in the community is going to be key to getting TB under control.”
Case numbers appeared to fall in Washington during the first year of the pandemic, possibly because of less reporting and missed diagnoses. But in 2021, cases rose quickly. The state reported 199 cases, marking a 22% increase from 2020.
So far this year, 70 cases have been reported, including 17 new cases that all have connections with each other and several state prisons.
The state’s Department of Corrections, Department of Health, and the Centers for Disease Control and Prevention are working together on testing and decreasing spread, MaryAnn Curl, MD, the chief medical officer for the Department of Corrections, said in the statement.
Tuberculosis cases are increasing worldwide. For the first time in more than a decade, TB deaths increased to about 1.5 million, according to the World Health Organization’s 2021 Global Tuberculosis Report.
Across the U.S., the number of reported TB cases significantly declined at the beginning of the pandemic in 2020 but increased again in 2021, according to a recent CDC study.
The Kansas Department of Health also reported an outbreak of TB cases in March, according to USA Today.
At the beginning of the pandemic, some people with TB may have been diagnosed with COVID-19 because both are infectious diseases that attack the lungs and have similar symptoms, the Washington Health Department said.
Like COVID-19, tuberculosis can spread through the air when an infected person coughs or sneezes. But unlike COVID-19, TB typically requires that you have prolonged exposure to become infected.
Symptoms of tuberculosis can include chest pain and coughing, with or without blood, as well as fever, night sweats, weight loss, and fatigue.
Tuberculosis is preventable, treatable, and curable, the Washington Health Department said. Those who travel to countries where TB is more common face higher risks for exposure, as well as those who live or work in settings where TB may spread, such as homeless shelters, prisons, jails, and nursing homes.
People can develop inactive TB, also called latent TB, which doesn’t have any symptoms and isn’t contagious. If people with inactive TB don’t get quick diagnosis or treatment, the infection can become active TB and cause symptoms. State health officials estimated that about 200,000 people in Washington have inactive TB.
Tuberculosis treatment can take a minimum of 6 months, and if it’s not followed carefully, symptoms can become more severe, the Health Department said. Incomplete treatment can also contribute to the spread of antibiotic-resistant strains of tuberculosis.
A version of this article first appeared on WebMD.com.
Tuberculosis cases are increasing in Washington, which has put public health officials on “heightened alert,” according to a recent announcement from the Washington State Department of Health.
Widespread disruptions in health care and missed tuberculosis diagnoses during the COVID-19 pandemic have likely added to the increase – both locally and globally.
“It’s been 20 years since we saw a cluster of TB cases like this,” Tao Sheng Kwan-Gett, MD, the state’s chief science officer, said in the announcement.
“The pandemic has likely contributed to the rise in cases and the outbreak in at least one correctional facility,” he said. “Increased access to TB testing and treatment in the community is going to be key to getting TB under control.”
Case numbers appeared to fall in Washington during the first year of the pandemic, possibly because of less reporting and missed diagnoses. But in 2021, cases rose quickly. The state reported 199 cases, marking a 22% increase from 2020.
So far this year, 70 cases have been reported, including 17 new cases that all have connections with each other and several state prisons.
The state’s Department of Corrections, Department of Health, and the Centers for Disease Control and Prevention are working together on testing and decreasing spread, MaryAnn Curl, MD, the chief medical officer for the Department of Corrections, said in the statement.
Tuberculosis cases are increasing worldwide. For the first time in more than a decade, TB deaths increased to about 1.5 million, according to the World Health Organization’s 2021 Global Tuberculosis Report.
Across the U.S., the number of reported TB cases significantly declined at the beginning of the pandemic in 2020 but increased again in 2021, according to a recent CDC study.
The Kansas Department of Health also reported an outbreak of TB cases in March, according to USA Today.
At the beginning of the pandemic, some people with TB may have been diagnosed with COVID-19 because both are infectious diseases that attack the lungs and have similar symptoms, the Washington Health Department said.
Like COVID-19, tuberculosis can spread through the air when an infected person coughs or sneezes. But unlike COVID-19, TB typically requires that you have prolonged exposure to become infected.
Symptoms of tuberculosis can include chest pain and coughing, with or without blood, as well as fever, night sweats, weight loss, and fatigue.
Tuberculosis is preventable, treatable, and curable, the Washington Health Department said. Those who travel to countries where TB is more common face higher risks for exposure, as well as those who live or work in settings where TB may spread, such as homeless shelters, prisons, jails, and nursing homes.
People can develop inactive TB, also called latent TB, which doesn’t have any symptoms and isn’t contagious. If people with inactive TB don’t get quick diagnosis or treatment, the infection can become active TB and cause symptoms. State health officials estimated that about 200,000 people in Washington have inactive TB.
Tuberculosis treatment can take a minimum of 6 months, and if it’s not followed carefully, symptoms can become more severe, the Health Department said. Incomplete treatment can also contribute to the spread of antibiotic-resistant strains of tuberculosis.
A version of this article first appeared on WebMD.com.
New HIV care guidelines from the European AIDS Clinical Society
Version 11.0 of the 2021 revised European AIDS Clinical Society (EACS) Guidelines updates all aspects of HIV care and adds recommendations on COVID-19 and antiretroviral treatment (ART) in children and adolescents, the guidelines authors reported in HIV Medicine.
“Conducting a systematic and timely annual revision of all guidelines recommendations is an EACS cornerstone,” EACS Guidelines coordinator Lene Ryom, MD, PhD, DMSc, a researcher at the University of Copenhagen, said in an interview. “These revisions ensure that the EACS Guidelines remain clinically relevant, are updated with the latest scientific evidence, and that they cover all key aspects related to HIV management.”
Key revisions in this update include:
Antiretroviral therapy (ART)
- Six recommended treatment options for first-line regimens for ART-naive adults include triple-drug regimens consisting of tenofovir (either tenofovir disoproxil fumarate or tenofovir alafenamide) with either lamivudine or emtricitabine plus dolutegravir, raltegravir, bictegravir, or doravirine; abacavir/lamivudine plus dolutegravir; or dual therapy with emtricitabine plus dolutegravir. These drug combinations are recommended in single-tablet form if available.
- Alternatives consisting of triple-drug tenofovir-based regimens along with efavirenz, rilpivirine, or boosted darunavir, are advised when no recommended regimens are feasible.
- Bimonthly injections with long-acting cabotegravir plus rilpivirine are now advised as a switch option for people who are virologically suppressed.
- Pre-exposure prophylaxis on demand is advised for cisgender men, and PrEP may be continued during pregnancy and breastfeeding for people at risk of acquiring HIV.
Drug-drug interactions (DDIs) and other prescribing issues
- Four new DDI tables cover antituberculosis drugs, anxiolytics, hormone therapy, and COVID-19 therapies.
Comorbidities
- This update acknowledged the impact of the COVID-19 pandemic on routine health care, provides recommendations, and highlights the role of shared care and consultation for anxiety and other mental health disorders.
- Treatments involving diabetes, hypertension, cardiovascular disease, heart failure, chronic kidney disease, hypercholesterolemia, obesity, cancer, and sexual health have been updated, with new information about elderly and frail patients, women’s sexual health, and special considerations for transgender people.
Viral hepatitis coinfection
Immediate treatment of recently acquired hepatitis C is recommended for people living with HIV and ongoing risk behavior. Bulevirtide is added as a treatment option for hepatitis Delta virus.
Opportunistic infections and COVID-19
- The revision adds new guidance on management of HIV and COVID-19, covering epidemiology, risk factors for severe COVID-19, COVID-19 management, HIV care during a pandemic, HIV management during COVID-19 treatment, and management of long-term COVID-19 symptoms and prophylaxis.
- It includes guidance on management of tuberculosis meningitis, cryptococcosis, Pneumocystis jirovecii pneumonia, and drug-resistant tuberculosis.
Pediatric HIV infection treatments
- This new section, developed with the European pediatric research organization Penta, updates guidance for the use of preferred and alternative first-line drugs from birth to adolescence. Combinations include new child-friendly formulations of dolutegravir as early as 4 weeks of age and 3 kg (6.6 lb) of weight as well as an increased emphasis on dolutegravir as first-line preferred agent for all children except newborns. Abacavir is recommended for children younger than 3 months.
- ART regimens for children with infectious hepatitis or tuberculosis are also provided.
Laura Jane Waters, MD, a genitourinary consultant and HIV and hepatitis lead at Central and North West London National Health Service Mortimer Market Centre, and chair of the British HIV Association (BHIVA), shared her perspective on the revision. She was not involved with the EACS Guidelines revision.
“The addition of a section on COVID-19 in people with HIV, including management, drug interactions, and vaccination, is welcomed, as is the inclusion of key references and, for selected references, the key findings,” Dr. Waters said in an interview.
“Finally, for the first time, EACS covers pediatric HIV treatment by integrating with the Penta guidelines,” she added. “This is an important evolution, considering there are still cases of vertical HIV transmission in Europe, not to mention children living with HIV who have immigrated. Ensuring high and equitable standards of HIV treatment for young people is crucial.”
“This update to the always-pragmatic EACS guidelines further diverges from the United States Department of Health & Human Services guidelines,” Dr. Waters explained. “For 6 months, both guidelines preferred the same ... regimens for first-line therapy, but since DHSS removed raltegravir-based ART in June 2021 and EACS added doravirine-based regimens in October 2021, we’re back in the more familiar territory of EACS offering a broader range of preferred choices.”
Dr. Ryom noted that modern HIV care needs to consider managing coinfections, opportunistic diseases, comorbidities, aging, addictions, and mental health.
“Ensuring an integrated and personalized approach to HIV management is becoming increasingly important in an aging population living with HIV with the potential for complex needs,” she said.
The guidelines are available in several formats: as a free smartphone app, an interactive web version, and an online PDF.
Funding information was not provided. Dr. Ryom and several coauthors disclosed no relevant financial relationships. Most of the guideline coauthors declared financial relationships with pharmaceutical companies “outside the submitted work.” Dr. Waters provided no information on conflicts of interest.
A version of this article first appeared on Medscape.com.
Version 11.0 of the 2021 revised European AIDS Clinical Society (EACS) Guidelines updates all aspects of HIV care and adds recommendations on COVID-19 and antiretroviral treatment (ART) in children and adolescents, the guidelines authors reported in HIV Medicine.
“Conducting a systematic and timely annual revision of all guidelines recommendations is an EACS cornerstone,” EACS Guidelines coordinator Lene Ryom, MD, PhD, DMSc, a researcher at the University of Copenhagen, said in an interview. “These revisions ensure that the EACS Guidelines remain clinically relevant, are updated with the latest scientific evidence, and that they cover all key aspects related to HIV management.”
Key revisions in this update include:
Antiretroviral therapy (ART)
- Six recommended treatment options for first-line regimens for ART-naive adults include triple-drug regimens consisting of tenofovir (either tenofovir disoproxil fumarate or tenofovir alafenamide) with either lamivudine or emtricitabine plus dolutegravir, raltegravir, bictegravir, or doravirine; abacavir/lamivudine plus dolutegravir; or dual therapy with emtricitabine plus dolutegravir. These drug combinations are recommended in single-tablet form if available.
- Alternatives consisting of triple-drug tenofovir-based regimens along with efavirenz, rilpivirine, or boosted darunavir, are advised when no recommended regimens are feasible.
- Bimonthly injections with long-acting cabotegravir plus rilpivirine are now advised as a switch option for people who are virologically suppressed.
- Pre-exposure prophylaxis on demand is advised for cisgender men, and PrEP may be continued during pregnancy and breastfeeding for people at risk of acquiring HIV.
Drug-drug interactions (DDIs) and other prescribing issues
- Four new DDI tables cover antituberculosis drugs, anxiolytics, hormone therapy, and COVID-19 therapies.
Comorbidities
- This update acknowledged the impact of the COVID-19 pandemic on routine health care, provides recommendations, and highlights the role of shared care and consultation for anxiety and other mental health disorders.
- Treatments involving diabetes, hypertension, cardiovascular disease, heart failure, chronic kidney disease, hypercholesterolemia, obesity, cancer, and sexual health have been updated, with new information about elderly and frail patients, women’s sexual health, and special considerations for transgender people.
Viral hepatitis coinfection
Immediate treatment of recently acquired hepatitis C is recommended for people living with HIV and ongoing risk behavior. Bulevirtide is added as a treatment option for hepatitis Delta virus.
Opportunistic infections and COVID-19
- The revision adds new guidance on management of HIV and COVID-19, covering epidemiology, risk factors for severe COVID-19, COVID-19 management, HIV care during a pandemic, HIV management during COVID-19 treatment, and management of long-term COVID-19 symptoms and prophylaxis.
- It includes guidance on management of tuberculosis meningitis, cryptococcosis, Pneumocystis jirovecii pneumonia, and drug-resistant tuberculosis.
Pediatric HIV infection treatments
- This new section, developed with the European pediatric research organization Penta, updates guidance for the use of preferred and alternative first-line drugs from birth to adolescence. Combinations include new child-friendly formulations of dolutegravir as early as 4 weeks of age and 3 kg (6.6 lb) of weight as well as an increased emphasis on dolutegravir as first-line preferred agent for all children except newborns. Abacavir is recommended for children younger than 3 months.
- ART regimens for children with infectious hepatitis or tuberculosis are also provided.
Laura Jane Waters, MD, a genitourinary consultant and HIV and hepatitis lead at Central and North West London National Health Service Mortimer Market Centre, and chair of the British HIV Association (BHIVA), shared her perspective on the revision. She was not involved with the EACS Guidelines revision.
“The addition of a section on COVID-19 in people with HIV, including management, drug interactions, and vaccination, is welcomed, as is the inclusion of key references and, for selected references, the key findings,” Dr. Waters said in an interview.
“Finally, for the first time, EACS covers pediatric HIV treatment by integrating with the Penta guidelines,” she added. “This is an important evolution, considering there are still cases of vertical HIV transmission in Europe, not to mention children living with HIV who have immigrated. Ensuring high and equitable standards of HIV treatment for young people is crucial.”
“This update to the always-pragmatic EACS guidelines further diverges from the United States Department of Health & Human Services guidelines,” Dr. Waters explained. “For 6 months, both guidelines preferred the same ... regimens for first-line therapy, but since DHSS removed raltegravir-based ART in June 2021 and EACS added doravirine-based regimens in October 2021, we’re back in the more familiar territory of EACS offering a broader range of preferred choices.”
Dr. Ryom noted that modern HIV care needs to consider managing coinfections, opportunistic diseases, comorbidities, aging, addictions, and mental health.
“Ensuring an integrated and personalized approach to HIV management is becoming increasingly important in an aging population living with HIV with the potential for complex needs,” she said.
The guidelines are available in several formats: as a free smartphone app, an interactive web version, and an online PDF.
Funding information was not provided. Dr. Ryom and several coauthors disclosed no relevant financial relationships. Most of the guideline coauthors declared financial relationships with pharmaceutical companies “outside the submitted work.” Dr. Waters provided no information on conflicts of interest.
A version of this article first appeared on Medscape.com.
Version 11.0 of the 2021 revised European AIDS Clinical Society (EACS) Guidelines updates all aspects of HIV care and adds recommendations on COVID-19 and antiretroviral treatment (ART) in children and adolescents, the guidelines authors reported in HIV Medicine.
“Conducting a systematic and timely annual revision of all guidelines recommendations is an EACS cornerstone,” EACS Guidelines coordinator Lene Ryom, MD, PhD, DMSc, a researcher at the University of Copenhagen, said in an interview. “These revisions ensure that the EACS Guidelines remain clinically relevant, are updated with the latest scientific evidence, and that they cover all key aspects related to HIV management.”
Key revisions in this update include:
Antiretroviral therapy (ART)
- Six recommended treatment options for first-line regimens for ART-naive adults include triple-drug regimens consisting of tenofovir (either tenofovir disoproxil fumarate or tenofovir alafenamide) with either lamivudine or emtricitabine plus dolutegravir, raltegravir, bictegravir, or doravirine; abacavir/lamivudine plus dolutegravir; or dual therapy with emtricitabine plus dolutegravir. These drug combinations are recommended in single-tablet form if available.
- Alternatives consisting of triple-drug tenofovir-based regimens along with efavirenz, rilpivirine, or boosted darunavir, are advised when no recommended regimens are feasible.
- Bimonthly injections with long-acting cabotegravir plus rilpivirine are now advised as a switch option for people who are virologically suppressed.
- Pre-exposure prophylaxis on demand is advised for cisgender men, and PrEP may be continued during pregnancy and breastfeeding for people at risk of acquiring HIV.
Drug-drug interactions (DDIs) and other prescribing issues
- Four new DDI tables cover antituberculosis drugs, anxiolytics, hormone therapy, and COVID-19 therapies.
Comorbidities
- This update acknowledged the impact of the COVID-19 pandemic on routine health care, provides recommendations, and highlights the role of shared care and consultation for anxiety and other mental health disorders.
- Treatments involving diabetes, hypertension, cardiovascular disease, heart failure, chronic kidney disease, hypercholesterolemia, obesity, cancer, and sexual health have been updated, with new information about elderly and frail patients, women’s sexual health, and special considerations for transgender people.
Viral hepatitis coinfection
Immediate treatment of recently acquired hepatitis C is recommended for people living with HIV and ongoing risk behavior. Bulevirtide is added as a treatment option for hepatitis Delta virus.
Opportunistic infections and COVID-19
- The revision adds new guidance on management of HIV and COVID-19, covering epidemiology, risk factors for severe COVID-19, COVID-19 management, HIV care during a pandemic, HIV management during COVID-19 treatment, and management of long-term COVID-19 symptoms and prophylaxis.
- It includes guidance on management of tuberculosis meningitis, cryptococcosis, Pneumocystis jirovecii pneumonia, and drug-resistant tuberculosis.
Pediatric HIV infection treatments
- This new section, developed with the European pediatric research organization Penta, updates guidance for the use of preferred and alternative first-line drugs from birth to adolescence. Combinations include new child-friendly formulations of dolutegravir as early as 4 weeks of age and 3 kg (6.6 lb) of weight as well as an increased emphasis on dolutegravir as first-line preferred agent for all children except newborns. Abacavir is recommended for children younger than 3 months.
- ART regimens for children with infectious hepatitis or tuberculosis are also provided.
Laura Jane Waters, MD, a genitourinary consultant and HIV and hepatitis lead at Central and North West London National Health Service Mortimer Market Centre, and chair of the British HIV Association (BHIVA), shared her perspective on the revision. She was not involved with the EACS Guidelines revision.
“The addition of a section on COVID-19 in people with HIV, including management, drug interactions, and vaccination, is welcomed, as is the inclusion of key references and, for selected references, the key findings,” Dr. Waters said in an interview.
“Finally, for the first time, EACS covers pediatric HIV treatment by integrating with the Penta guidelines,” she added. “This is an important evolution, considering there are still cases of vertical HIV transmission in Europe, not to mention children living with HIV who have immigrated. Ensuring high and equitable standards of HIV treatment for young people is crucial.”
“This update to the always-pragmatic EACS guidelines further diverges from the United States Department of Health & Human Services guidelines,” Dr. Waters explained. “For 6 months, both guidelines preferred the same ... regimens for first-line therapy, but since DHSS removed raltegravir-based ART in June 2021 and EACS added doravirine-based regimens in October 2021, we’re back in the more familiar territory of EACS offering a broader range of preferred choices.”
Dr. Ryom noted that modern HIV care needs to consider managing coinfections, opportunistic diseases, comorbidities, aging, addictions, and mental health.
“Ensuring an integrated and personalized approach to HIV management is becoming increasingly important in an aging population living with HIV with the potential for complex needs,” she said.
The guidelines are available in several formats: as a free smartphone app, an interactive web version, and an online PDF.
Funding information was not provided. Dr. Ryom and several coauthors disclosed no relevant financial relationships. Most of the guideline coauthors declared financial relationships with pharmaceutical companies “outside the submitted work.” Dr. Waters provided no information on conflicts of interest.
A version of this article first appeared on Medscape.com.
FROM HIV MEDICINE
Most at-home STI testing kits fail to meet young people’s needs
The wide majority of at-home sexually transmitted infection testing kits in the United States appear to be limited to use by adults, a new study finds, and many have limitations that make them less than ideal for young people to use.
While at-home kits do allow more access to STI testing, “we need to create programs that are specific for youth because they have extra needs,” said lead author Saumya Sao, a research assistant at the department of gynecology & obstetrics at Johns Hopkins University, Baltimore, in an interview. “The only platform that did meet our needs was the program that we developed specifically.”
The findings were released ahead of the study’s scheduled presentation at the 2022 annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists (Session A117).
According to Ms. Sao, companies began to offer more at-home testing kits during the pandemic as in-person STI clinics shut down. Still, “the fact that we only found 13 self-collect mail-in STI programs shows you that this is pretty new,” she said. “There are not too many companies that do it. We found a lot more platforms that allow users to place orders for testing online, but you’re still required to go into a lab and actually do the testing.”
The researchers gathered information about 13 programs, including the one that they developed at Johns Hopkins known as Violet. Of those, seven limited testing to adults aged 18 and up, and one didn’t list an age requirement. The rest had some age requirements (such as 14 and up) or no age requirements.
The lack of full access for teens is problematic, Ms. Sao said. According to the study, “access to testing among young people is especially important because youth (ages 13-24) bear a disproportionate burden of sexually transmitted infection, accounting for 50% of cases but only 25% of the sexually active population.”
Research has suggested that young people are often wary of visiting STI clinics because they fear stigma from medical professionals or worry about being seen there, Ms. Sao said.
Tests are free in only three of the programs analyzed in the new study. Among the other programs, tests for Chlamydia trachomatis and Neisseria gonorrhoeae cost $45-$179; only two accepted insurance. “These out-of-pocket costs are really high in regard to what a young person might be able to afford for testing, especially if they would need to do repeat testing between partners, or 3 months after testing positive,” Ms. Sao said.
Most of the programs will link users to medical professionals if they test positive. This is a key feature, Ms. Sao said, in order to make sure young people have support.
As for location, most of the programs – including all those that offer free testing – are limited to certain states. Planned Parenthood, for example, only offers at-home STI testing in Maine, New Hampshire, and Vermont. The program charges patients on a sliding scale, accepts insurance, and is available for ages 14 and up. It connects users who test positive to physicians.
Another free program, TakeMeHome, is restricted to 16 states. It includes an HIV panel for ages 17+ (although it doesn’t have vaginal swab testing). It recommends that patients who are positive consult a doctor.
The researchers also found that some, but not all, of the programs send testing material in discreet packaging. This is important to young people because they may not want their parents to know that they’re getting tested.
Some of the testing programs analyzed don’t make it clear on their web sites whether their packaging is discreet, Ms. Sao said.
At Johns Hopkins, Ms. Sao has helped develop the Violet Project, which is designed to meet the needs of young people and offers free STI testing to residents of Maryland of any age for Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis. Mailing packages are discreet, and physicians reach out to those who test positive. Fees are covered.
“We don’t have money yet to expand beyond Maryland, but we’re hopeful,” she said.
In an interview, Loma Linda (Calif.) University Health maternal-fetal medicine specialist Sarah Smithson, DO, MS, praised the study and said she supports optimizing at-home testing for young people. It may be useful for youths who first get tested in a clinic but then need follow-up testing or testing of their partners, she said.
Dr. Smithson added that transportation is often a challenge for young people. At her pregnancy clinic in California’s Inland Empire, she said, some patients live in remote areas and make virtual doctor visits because of the distance. STI testing is crucial for pregnant women, she said, “and this could be a game changer for them.”
The wide majority of at-home sexually transmitted infection testing kits in the United States appear to be limited to use by adults, a new study finds, and many have limitations that make them less than ideal for young people to use.
While at-home kits do allow more access to STI testing, “we need to create programs that are specific for youth because they have extra needs,” said lead author Saumya Sao, a research assistant at the department of gynecology & obstetrics at Johns Hopkins University, Baltimore, in an interview. “The only platform that did meet our needs was the program that we developed specifically.”
The findings were released ahead of the study’s scheduled presentation at the 2022 annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists (Session A117).
According to Ms. Sao, companies began to offer more at-home testing kits during the pandemic as in-person STI clinics shut down. Still, “the fact that we only found 13 self-collect mail-in STI programs shows you that this is pretty new,” she said. “There are not too many companies that do it. We found a lot more platforms that allow users to place orders for testing online, but you’re still required to go into a lab and actually do the testing.”
The researchers gathered information about 13 programs, including the one that they developed at Johns Hopkins known as Violet. Of those, seven limited testing to adults aged 18 and up, and one didn’t list an age requirement. The rest had some age requirements (such as 14 and up) or no age requirements.
The lack of full access for teens is problematic, Ms. Sao said. According to the study, “access to testing among young people is especially important because youth (ages 13-24) bear a disproportionate burden of sexually transmitted infection, accounting for 50% of cases but only 25% of the sexually active population.”
Research has suggested that young people are often wary of visiting STI clinics because they fear stigma from medical professionals or worry about being seen there, Ms. Sao said.
Tests are free in only three of the programs analyzed in the new study. Among the other programs, tests for Chlamydia trachomatis and Neisseria gonorrhoeae cost $45-$179; only two accepted insurance. “These out-of-pocket costs are really high in regard to what a young person might be able to afford for testing, especially if they would need to do repeat testing between partners, or 3 months after testing positive,” Ms. Sao said.
Most of the programs will link users to medical professionals if they test positive. This is a key feature, Ms. Sao said, in order to make sure young people have support.
As for location, most of the programs – including all those that offer free testing – are limited to certain states. Planned Parenthood, for example, only offers at-home STI testing in Maine, New Hampshire, and Vermont. The program charges patients on a sliding scale, accepts insurance, and is available for ages 14 and up. It connects users who test positive to physicians.
Another free program, TakeMeHome, is restricted to 16 states. It includes an HIV panel for ages 17+ (although it doesn’t have vaginal swab testing). It recommends that patients who are positive consult a doctor.
The researchers also found that some, but not all, of the programs send testing material in discreet packaging. This is important to young people because they may not want their parents to know that they’re getting tested.
Some of the testing programs analyzed don’t make it clear on their web sites whether their packaging is discreet, Ms. Sao said.
At Johns Hopkins, Ms. Sao has helped develop the Violet Project, which is designed to meet the needs of young people and offers free STI testing to residents of Maryland of any age for Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis. Mailing packages are discreet, and physicians reach out to those who test positive. Fees are covered.
“We don’t have money yet to expand beyond Maryland, but we’re hopeful,” she said.
In an interview, Loma Linda (Calif.) University Health maternal-fetal medicine specialist Sarah Smithson, DO, MS, praised the study and said she supports optimizing at-home testing for young people. It may be useful for youths who first get tested in a clinic but then need follow-up testing or testing of their partners, she said.
Dr. Smithson added that transportation is often a challenge for young people. At her pregnancy clinic in California’s Inland Empire, she said, some patients live in remote areas and make virtual doctor visits because of the distance. STI testing is crucial for pregnant women, she said, “and this could be a game changer for them.”
The wide majority of at-home sexually transmitted infection testing kits in the United States appear to be limited to use by adults, a new study finds, and many have limitations that make them less than ideal for young people to use.
While at-home kits do allow more access to STI testing, “we need to create programs that are specific for youth because they have extra needs,” said lead author Saumya Sao, a research assistant at the department of gynecology & obstetrics at Johns Hopkins University, Baltimore, in an interview. “The only platform that did meet our needs was the program that we developed specifically.”
The findings were released ahead of the study’s scheduled presentation at the 2022 annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists (Session A117).
According to Ms. Sao, companies began to offer more at-home testing kits during the pandemic as in-person STI clinics shut down. Still, “the fact that we only found 13 self-collect mail-in STI programs shows you that this is pretty new,” she said. “There are not too many companies that do it. We found a lot more platforms that allow users to place orders for testing online, but you’re still required to go into a lab and actually do the testing.”
The researchers gathered information about 13 programs, including the one that they developed at Johns Hopkins known as Violet. Of those, seven limited testing to adults aged 18 and up, and one didn’t list an age requirement. The rest had some age requirements (such as 14 and up) or no age requirements.
The lack of full access for teens is problematic, Ms. Sao said. According to the study, “access to testing among young people is especially important because youth (ages 13-24) bear a disproportionate burden of sexually transmitted infection, accounting for 50% of cases but only 25% of the sexually active population.”
Research has suggested that young people are often wary of visiting STI clinics because they fear stigma from medical professionals or worry about being seen there, Ms. Sao said.
Tests are free in only three of the programs analyzed in the new study. Among the other programs, tests for Chlamydia trachomatis and Neisseria gonorrhoeae cost $45-$179; only two accepted insurance. “These out-of-pocket costs are really high in regard to what a young person might be able to afford for testing, especially if they would need to do repeat testing between partners, or 3 months after testing positive,” Ms. Sao said.
Most of the programs will link users to medical professionals if they test positive. This is a key feature, Ms. Sao said, in order to make sure young people have support.
As for location, most of the programs – including all those that offer free testing – are limited to certain states. Planned Parenthood, for example, only offers at-home STI testing in Maine, New Hampshire, and Vermont. The program charges patients on a sliding scale, accepts insurance, and is available for ages 14 and up. It connects users who test positive to physicians.
Another free program, TakeMeHome, is restricted to 16 states. It includes an HIV panel for ages 17+ (although it doesn’t have vaginal swab testing). It recommends that patients who are positive consult a doctor.
The researchers also found that some, but not all, of the programs send testing material in discreet packaging. This is important to young people because they may not want their parents to know that they’re getting tested.
Some of the testing programs analyzed don’t make it clear on their web sites whether their packaging is discreet, Ms. Sao said.
At Johns Hopkins, Ms. Sao has helped develop the Violet Project, which is designed to meet the needs of young people and offers free STI testing to residents of Maryland of any age for Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis. Mailing packages are discreet, and physicians reach out to those who test positive. Fees are covered.
“We don’t have money yet to expand beyond Maryland, but we’re hopeful,” she said.
In an interview, Loma Linda (Calif.) University Health maternal-fetal medicine specialist Sarah Smithson, DO, MS, praised the study and said she supports optimizing at-home testing for young people. It may be useful for youths who first get tested in a clinic but then need follow-up testing or testing of their partners, she said.
Dr. Smithson added that transportation is often a challenge for young people. At her pregnancy clinic in California’s Inland Empire, she said, some patients live in remote areas and make virtual doctor visits because of the distance. STI testing is crucial for pregnant women, she said, “and this could be a game changer for them.”
FROM ACOG 2022
Porcine virus a suspect in man’s death after pig heart transplant
A porcine cytomegalovirus (PCMV) in the heart had gone undetected before the operation and may or may not have been instrumental in David Bennett’s death 2 months later, according to a report published in MIT Technology Review. 
“The issue is now a subject of wide discussion among specialists, who think the infection was a potential contributor to Mr. Bennett’s death and a possible reason why the heart did not last longer,” states the article, written by staff journalist Antonio Regalado.
As described in the story, the xenotransplant saga’s new twist comes from the surgeon who performed the operation, Bartley P. Griffith, MD, University of Maryland, Baltimore, who related the PCMV finding in an April 20 online presentation hosted by the American Society of Transplantation.
Mr. Bennett’s initially promising but later turbulent clinical course, described by his surgeons and widely reported upon his death, included repeated skirmishes with infection and retaliatory adjustments to his immunosuppressant regimen. Those episodes were thought to have contributed to his death, the actual cause of which is undetermined or at least not yet reported.
“We are beginning to learn why he passed on,” Dr. Griffith said in Mr. Regalado’s article, acknowledging further that the porcine virus “maybe was the actor, or could be the actor,” that set off the events leading to Bennett’s death.
Xenotransplant specialists know that PCMV is a potential problem with pig organs and know to test for it before attempting the procedure in animal models, notes the article. It refers to a published series of pig-heart transplants to baboons in Germany. The hearts “lasted only a couple of weeks if the virus was present, while organs free from the infection could survive more than half a year.”
The heart Mr. Bennett received had been extensively screened for bacteria, viruses, and other issues that could have threatened the organ and Mr. Bennett, but the effort apparently fell short. In the MIT Technology Review story, the first author of the German baboon series speculates on how the University of Maryland team might have missed PCMV.
“The U.S. team appears to have tested the pig’s snout for the virus, but often it is lurking deeper in the tissues,” Joachim Denner, PhD, Institute of Virology, Free University of Berlin, said in the article. The virus, he contended, “can be detected and easily removed from pig populations, but unfortunately they didn’t use a good assay and didn’t detect the virus.”
That PCMV escaped detection before the operation “could now factor into some people’s questions over whether the experiment should have taken place at all,” the MIT Technology Review article proposes. “It’s a big red flag,” bioethicist Arthur Caplan, PhD, New York University, said in a quote, adding: “If doctors can’t prevent or control infection, ‘then such experiments are tough to justify.’ ”
A version of this article first appeared on Medscape.com.
A porcine cytomegalovirus (PCMV) in the heart had gone undetected before the operation and may or may not have been instrumental in David Bennett’s death 2 months later, according to a report published in MIT Technology Review.
“The issue is now a subject of wide discussion among specialists, who think the infection was a potential contributor to Mr. Bennett’s death and a possible reason why the heart did not last longer,” states the article, written by staff journalist Antonio Regalado.
As described in the story, the xenotransplant saga’s new twist comes from the surgeon who performed the operation, Bartley P. Griffith, MD, University of Maryland, Baltimore, who related the PCMV finding in an April 20 online presentation hosted by the American Society of Transplantation.
Mr. Bennett’s initially promising but later turbulent clinical course, described by his surgeons and widely reported upon his death, included repeated skirmishes with infection and retaliatory adjustments to his immunosuppressant regimen. Those episodes were thought to have contributed to his death, the actual cause of which is undetermined or at least not yet reported.
“We are beginning to learn why he passed on,” Dr. Griffith said in Mr. Regalado’s article, acknowledging further that the porcine virus “maybe was the actor, or could be the actor,” that set off the events leading to Bennett’s death.
Xenotransplant specialists know that PCMV is a potential problem with pig organs and know to test for it before attempting the procedure in animal models, notes the article. It refers to a published series of pig-heart transplants to baboons in Germany. The hearts “lasted only a couple of weeks if the virus was present, while organs free from the infection could survive more than half a year.”
The heart Mr. Bennett received had been extensively screened for bacteria, viruses, and other issues that could have threatened the organ and Mr. Bennett, but the effort apparently fell short. In the MIT Technology Review story, the first author of the German baboon series speculates on how the University of Maryland team might have missed PCMV.
“The U.S. team appears to have tested the pig’s snout for the virus, but often it is lurking deeper in the tissues,” Joachim Denner, PhD, Institute of Virology, Free University of Berlin, said in the article. The virus, he contended, “can be detected and easily removed from pig populations, but unfortunately they didn’t use a good assay and didn’t detect the virus.”
That PCMV escaped detection before the operation “could now factor into some people’s questions over whether the experiment should have taken place at all,” the MIT Technology Review article proposes. “It’s a big red flag,” bioethicist Arthur Caplan, PhD, New York University, said in a quote, adding: “If doctors can’t prevent or control infection, ‘then such experiments are tough to justify.’ ”
A version of this article first appeared on Medscape.com.
A porcine cytomegalovirus (PCMV) in the heart had gone undetected before the operation and may or may not have been instrumental in David Bennett’s death 2 months later, according to a report published in MIT Technology Review.
“The issue is now a subject of wide discussion among specialists, who think the infection was a potential contributor to Mr. Bennett’s death and a possible reason why the heart did not last longer,” states the article, written by staff journalist Antonio Regalado.
As described in the story, the xenotransplant saga’s new twist comes from the surgeon who performed the operation, Bartley P. Griffith, MD, University of Maryland, Baltimore, who related the PCMV finding in an April 20 online presentation hosted by the American Society of Transplantation.
Mr. Bennett’s initially promising but later turbulent clinical course, described by his surgeons and widely reported upon his death, included repeated skirmishes with infection and retaliatory adjustments to his immunosuppressant regimen. Those episodes were thought to have contributed to his death, the actual cause of which is undetermined or at least not yet reported.
“We are beginning to learn why he passed on,” Dr. Griffith said in Mr. Regalado’s article, acknowledging further that the porcine virus “maybe was the actor, or could be the actor,” that set off the events leading to Bennett’s death.
Xenotransplant specialists know that PCMV is a potential problem with pig organs and know to test for it before attempting the procedure in animal models, notes the article. It refers to a published series of pig-heart transplants to baboons in Germany. The hearts “lasted only a couple of weeks if the virus was present, while organs free from the infection could survive more than half a year.”
The heart Mr. Bennett received had been extensively screened for bacteria, viruses, and other issues that could have threatened the organ and Mr. Bennett, but the effort apparently fell short. In the MIT Technology Review story, the first author of the German baboon series speculates on how the University of Maryland team might have missed PCMV.
“The U.S. team appears to have tested the pig’s snout for the virus, but often it is lurking deeper in the tissues,” Joachim Denner, PhD, Institute of Virology, Free University of Berlin, said in the article. The virus, he contended, “can be detected and easily removed from pig populations, but unfortunately they didn’t use a good assay and didn’t detect the virus.”
That PCMV escaped detection before the operation “could now factor into some people’s questions over whether the experiment should have taken place at all,” the MIT Technology Review article proposes. “It’s a big red flag,” bioethicist Arthur Caplan, PhD, New York University, said in a quote, adding: “If doctors can’t prevent or control infection, ‘then such experiments are tough to justify.’ ”
A version of this article first appeared on Medscape.com.
FROM MIT TECHNOLOGY REVIEW
Don’t let FOMI lead to antibiotic overuse
Is fear of missing an infection – call it “FOMI” – leading you to overprescribe antibiotics to your patients?
Inappropriate use of antibiotics can result in adverse events and toxicity, superinfections such as Clostridioides difficile and Methicillin-resistant Staphylococcus aureus, excess mortality and costs, and resistance to the drugs.
All that has been well-known for years, and antibiotic resistance has become a leading public health concern. So why are physicians continuing to overprescribe the drugs?
Speaking at the 2022 annual Internal Medicine Meeting of the American College of Physicians, James “Brad” Cutrell, MD, medical director of antimicrobial stewardship, University of Texas Southwestern Medical Center, Dallas, said clinicians in the United States and elsewhere appear to be falling into a three-part fallacy when it comes to using the drugs: fear of “missing an infection,” coupled with patient expectations that they will leave the office with a prescription and combined with an overemphasis on the potential benefit to the individual at the expense of the risk to society of antibiotic resistance.
Antibiotics are the only drugs that lose their efficacy for all patients over time the more they are used. “For example, if I give a beta blocker to a patient, it’s not going to affect other patients down the road,” Dr. Cutrell said. “It’s not going to lose its efficacy.”
“What we need in medicine is a new culture around antibiotic use,” Dr. Cutrell added. “We need more respect for the dangers of antibiotic misuse and to have confidence in [their] benefits and when they can be used wisely.”
Rampant misuse
Outpatient prescriptions account for at least 60% of antibiotic use in the United States. The rate is even higher in other countries, Dr. Cutrell said during a presentation at the 2022 annual Internal Medicine Meeting of the American College of Physicians.
“About 10% of adult visits and 20% of pediatric visits will result in an antibiotic prescription,” said Dr. Cutrell, noting that prescribing patterns vary widely across the country, with as much as a three-fold difference in some locations. But at least 30% of outpatient antibiotic prescriptions are inappropriately ordered, he said.
“When we look at acute respiratory infections, upwards of 50% are not indicated at all,” he said. Imagine, he added, if the same error rate applied to other medical practices: “What if surgeons were only right 50% of the time, or if the oncologist was only giving the right treatment 50% of the time?”
The most recent Antibiotic Threats Report from the U.S. Centers for Disease Control and Prevention estimated that antibiotic-resistant bacteria and fungi cause more than 2.8 million infections and about 36,000 deaths annually in the United States alone.
How to be a better steward
The core elements for antimicrobial stewardship in the outpatient setting, according to Dr. Cutrell, include making a commitment to optimize prescribing, implementing at least one policy or practice to improve prescribing, monitoring prescribing practices and offering feedback to clinicians, and educating both patients and clinicians.
All that is similar to in-patient stewardship, he said, but outpatient clinicians face a few unique challenges. “Patients are lower acuity, and there is less diagnostic data, and program resources and time are more limited,” he said. Patient satisfaction is also a major driver, and it is also more difficult to measure and track ambulatory antibiotic use.
Interventions have been identified, however, that can help improve stewardship. One is auditing and feedback with peers. “Another [is] commitment posters, which can be placed around the clinic, and that helps set the culture,” he said. “Clinical education and practice guidelines are also important.”
Clinicians should also:
- Observe antibiotic best practices
- Optimize antibiotic selection and dosing
- Practice effective diagnostic stewardship
- Use the shortest duration of therapy necessary
- Avoid antibiotics for inappropriate indications
- Educate patients on when antibiotics are needed
- Follow and become good antibiotic stewardship mentors
“Multiple antibiotic stewardship interventions are effective, particularly those focused on behavioral interventions,” Dr. Cutrell said. “Every provider should follow antibiotic ‘best practices’ and other simple steps to prescribe antibiotics more wisely and to improve patient care.”
Dr. Cutrell reported financial relationships with Gilead Sciences and Regeneron Pharmaceuticals.
A version of this article first appeared on Medscape.com.
Is fear of missing an infection – call it “FOMI” – leading you to overprescribe antibiotics to your patients?
Inappropriate use of antibiotics can result in adverse events and toxicity, superinfections such as Clostridioides difficile and Methicillin-resistant Staphylococcus aureus, excess mortality and costs, and resistance to the drugs.
All that has been well-known for years, and antibiotic resistance has become a leading public health concern. So why are physicians continuing to overprescribe the drugs?
Speaking at the 2022 annual Internal Medicine Meeting of the American College of Physicians, James “Brad” Cutrell, MD, medical director of antimicrobial stewardship, University of Texas Southwestern Medical Center, Dallas, said clinicians in the United States and elsewhere appear to be falling into a three-part fallacy when it comes to using the drugs: fear of “missing an infection,” coupled with patient expectations that they will leave the office with a prescription and combined with an overemphasis on the potential benefit to the individual at the expense of the risk to society of antibiotic resistance.
Antibiotics are the only drugs that lose their efficacy for all patients over time the more they are used. “For example, if I give a beta blocker to a patient, it’s not going to affect other patients down the road,” Dr. Cutrell said. “It’s not going to lose its efficacy.”
“What we need in medicine is a new culture around antibiotic use,” Dr. Cutrell added. “We need more respect for the dangers of antibiotic misuse and to have confidence in [their] benefits and when they can be used wisely.”
Rampant misuse
Outpatient prescriptions account for at least 60% of antibiotic use in the United States. The rate is even higher in other countries, Dr. Cutrell said during a presentation at the 2022 annual Internal Medicine Meeting of the American College of Physicians.
“About 10% of adult visits and 20% of pediatric visits will result in an antibiotic prescription,” said Dr. Cutrell, noting that prescribing patterns vary widely across the country, with as much as a three-fold difference in some locations. But at least 30% of outpatient antibiotic prescriptions are inappropriately ordered, he said.
“When we look at acute respiratory infections, upwards of 50% are not indicated at all,” he said. Imagine, he added, if the same error rate applied to other medical practices: “What if surgeons were only right 50% of the time, or if the oncologist was only giving the right treatment 50% of the time?”
The most recent Antibiotic Threats Report from the U.S. Centers for Disease Control and Prevention estimated that antibiotic-resistant bacteria and fungi cause more than 2.8 million infections and about 36,000 deaths annually in the United States alone.
How to be a better steward
The core elements for antimicrobial stewardship in the outpatient setting, according to Dr. Cutrell, include making a commitment to optimize prescribing, implementing at least one policy or practice to improve prescribing, monitoring prescribing practices and offering feedback to clinicians, and educating both patients and clinicians.
All that is similar to in-patient stewardship, he said, but outpatient clinicians face a few unique challenges. “Patients are lower acuity, and there is less diagnostic data, and program resources and time are more limited,” he said. Patient satisfaction is also a major driver, and it is also more difficult to measure and track ambulatory antibiotic use.
Interventions have been identified, however, that can help improve stewardship. One is auditing and feedback with peers. “Another [is] commitment posters, which can be placed around the clinic, and that helps set the culture,” he said. “Clinical education and practice guidelines are also important.”
Clinicians should also:
- Observe antibiotic best practices
- Optimize antibiotic selection and dosing
- Practice effective diagnostic stewardship
- Use the shortest duration of therapy necessary
- Avoid antibiotics for inappropriate indications
- Educate patients on when antibiotics are needed
- Follow and become good antibiotic stewardship mentors
“Multiple antibiotic stewardship interventions are effective, particularly those focused on behavioral interventions,” Dr. Cutrell said. “Every provider should follow antibiotic ‘best practices’ and other simple steps to prescribe antibiotics more wisely and to improve patient care.”
Dr. Cutrell reported financial relationships with Gilead Sciences and Regeneron Pharmaceuticals.
A version of this article first appeared on Medscape.com.
Is fear of missing an infection – call it “FOMI” – leading you to overprescribe antibiotics to your patients?
Inappropriate use of antibiotics can result in adverse events and toxicity, superinfections such as Clostridioides difficile and Methicillin-resistant Staphylococcus aureus, excess mortality and costs, and resistance to the drugs.
All that has been well-known for years, and antibiotic resistance has become a leading public health concern. So why are physicians continuing to overprescribe the drugs?
Speaking at the 2022 annual Internal Medicine Meeting of the American College of Physicians, James “Brad” Cutrell, MD, medical director of antimicrobial stewardship, University of Texas Southwestern Medical Center, Dallas, said clinicians in the United States and elsewhere appear to be falling into a three-part fallacy when it comes to using the drugs: fear of “missing an infection,” coupled with patient expectations that they will leave the office with a prescription and combined with an overemphasis on the potential benefit to the individual at the expense of the risk to society of antibiotic resistance.
Antibiotics are the only drugs that lose their efficacy for all patients over time the more they are used. “For example, if I give a beta blocker to a patient, it’s not going to affect other patients down the road,” Dr. Cutrell said. “It’s not going to lose its efficacy.”
“What we need in medicine is a new culture around antibiotic use,” Dr. Cutrell added. “We need more respect for the dangers of antibiotic misuse and to have confidence in [their] benefits and when they can be used wisely.”
Rampant misuse
Outpatient prescriptions account for at least 60% of antibiotic use in the United States. The rate is even higher in other countries, Dr. Cutrell said during a presentation at the 2022 annual Internal Medicine Meeting of the American College of Physicians.
“About 10% of adult visits and 20% of pediatric visits will result in an antibiotic prescription,” said Dr. Cutrell, noting that prescribing patterns vary widely across the country, with as much as a three-fold difference in some locations. But at least 30% of outpatient antibiotic prescriptions are inappropriately ordered, he said.
“When we look at acute respiratory infections, upwards of 50% are not indicated at all,” he said. Imagine, he added, if the same error rate applied to other medical practices: “What if surgeons were only right 50% of the time, or if the oncologist was only giving the right treatment 50% of the time?”
The most recent Antibiotic Threats Report from the U.S. Centers for Disease Control and Prevention estimated that antibiotic-resistant bacteria and fungi cause more than 2.8 million infections and about 36,000 deaths annually in the United States alone.
How to be a better steward
The core elements for antimicrobial stewardship in the outpatient setting, according to Dr. Cutrell, include making a commitment to optimize prescribing, implementing at least one policy or practice to improve prescribing, monitoring prescribing practices and offering feedback to clinicians, and educating both patients and clinicians.
All that is similar to in-patient stewardship, he said, but outpatient clinicians face a few unique challenges. “Patients are lower acuity, and there is less diagnostic data, and program resources and time are more limited,” he said. Patient satisfaction is also a major driver, and it is also more difficult to measure and track ambulatory antibiotic use.
Interventions have been identified, however, that can help improve stewardship. One is auditing and feedback with peers. “Another [is] commitment posters, which can be placed around the clinic, and that helps set the culture,” he said. “Clinical education and practice guidelines are also important.”
Clinicians should also:
- Observe antibiotic best practices
- Optimize antibiotic selection and dosing
- Practice effective diagnostic stewardship
- Use the shortest duration of therapy necessary
- Avoid antibiotics for inappropriate indications
- Educate patients on when antibiotics are needed
- Follow and become good antibiotic stewardship mentors
“Multiple antibiotic stewardship interventions are effective, particularly those focused on behavioral interventions,” Dr. Cutrell said. “Every provider should follow antibiotic ‘best practices’ and other simple steps to prescribe antibiotics more wisely and to improve patient care.”
Dr. Cutrell reported financial relationships with Gilead Sciences and Regeneron Pharmaceuticals.
A version of this article first appeared on Medscape.com.
FROM INTERNAL MEDICINE 2022