Infectious Diseases

Prompted by the “unprecedented” increase in the occurrence of infective endocarditis (IE) cases among people who inject drugs, the American Heart Association has issued a scientific statement devoted solely to this challenging patient population.

The statement provides a more in-depth focus on the management of IE among this unique population than what has been provided in prior AHA IE-related documents.

The statement stresses that managing IE in people who inject drugs is complex and requires a unique multidisciplinary approach that includes consultation with an addiction specialist.

The statement was published online in Circulation.
 

Poor long-term prognosis

In the United States from 2002 to 2016, the proportion of patients hospitalized with IE related to injection drug use doubled from 8% to about 16%.

The long-term prognosis for this population is “currently dismal for this relatively young group of individuals,” writing group Chair Daniel C. DeSimone, MD, with the Mayo Clinic in Rochester, Minn., notes in a news release.

To improve prognosis, the writing group advises a multidisciplinary team care approach that includes cardiologists, cardiac surgeons, and infectious diseases specialists as well as addiction medicine or addiction psychiatry specialists, pharmacists, social workers, and nurse specialists.

Nurse specialists can coordinate care from the initial IE hospitalization to outpatient and community care to support substance use disorder.

“Clinical teams must recognize that substance use disorder is a treatable chronic, relapsing medical illness and many people are able to enter sustained remission, particularly when they receive effective treatments,” the writing group emphasizes.

Although not all patients with injection drug–related IE have opioid addiction, for those who do, the “best practice” is to offer buprenorphine or methadone “as soon as possible” after the patient presents to the hospital, they advise.
 

Antimicrobial therapy

The writing group says it’s “reasonable” to offer people with injection drug–related IE standard treatment for IE, which is 6 weeks of intravenous antibiotics. They recognize, however, that this regimen is often not feasible in this patient population and say there is growing evidence that partial intravenous therapy followed by oral antibiotic treatment to complete a total of 6 weeks is a possible option.

They also highlight the “critical” importance of preventive measures in people who inject drugs who are successfully treated for an initial bout of IE because they remain at “extremely” high risk for subsequent bouts of IE, regardless of whether injection drug use is continued.

The writing group also stresses that people with IE who inject drugs should be considered for heart valve repair or replacement surgery regardless of current drug use if they have indications for valve surgery.

“There’s no evidence that indications for valve surgery are different for people who inject drugs compared to those who don’t, however, some treatment centers don’t offer surgery, especially if the patient currently injects drugs or has had a previous valve surgery,” Dr. DeSimone says in the release.

“Those who develop infective endocarditis require complex care delivered by professionals who look beyond stigma and bias to provide optimal and equitable care,” Dr. DeSimone adds.

The writing group acknowledges that while addiction medicine and addiction psychiatry expertise are critical to managing IE in injection drug users, these specific resources are currently not widely available.

They call on health care systems to attract individuals with addiction training and support addiction medicine consultative services, particularly in centers where drug use–related IE is common and expected to continue to increase.

This AHA scientific statement was prepared by the volunteer writing group on behalf of the AHA Rheumatic Fever, Endocarditis and Kawasaki Disease Committee of the Council on Lifelong Congenital Heart Disease and Heart Health in the Young; the Council on Cardiovascular Surgery and Anesthesia; the Council on Cardiovascular and Stroke Nursing; the Council on Clinical Cardiology; and the Council on Peripheral Vascular Disease.

This research had no commercial funding. Dr. DeSimone has no relevant disclosures.

A version of this article first appeared on Medscape.com.

Prompted by the “unprecedented” increase in the occurrence of infective endocarditis (IE) cases among people who inject drugs, the American Heart Association has issued a scientific statement devoted solely to this challenging patient population.

The statement provides a more in-depth focus on the management of IE among this unique population than what has been provided in prior AHA IE-related documents.

The statement stresses that managing IE in people who inject drugs is complex and requires a unique multidisciplinary approach that includes consultation with an addiction specialist.

The statement was published online in Circulation.
 

Poor long-term prognosis

In the United States from 2002 to 2016, the proportion of patients hospitalized with IE related to injection drug use doubled from 8% to about 16%.

The long-term prognosis for this population is “currently dismal for this relatively young group of individuals,” writing group Chair Daniel C. DeSimone, MD, with the Mayo Clinic in Rochester, Minn., notes in a news release.

To improve prognosis, the writing group advises a multidisciplinary team care approach that includes cardiologists, cardiac surgeons, and infectious diseases specialists as well as addiction medicine or addiction psychiatry specialists, pharmacists, social workers, and nurse specialists.

Nurse specialists can coordinate care from the initial IE hospitalization to outpatient and community care to support substance use disorder.

“Clinical teams must recognize that substance use disorder is a treatable chronic, relapsing medical illness and many people are able to enter sustained remission, particularly when they receive effective treatments,” the writing group emphasizes.

Although not all patients with injection drug–related IE have opioid addiction, for those who do, the “best practice” is to offer buprenorphine or methadone “as soon as possible” after the patient presents to the hospital, they advise.
 

Antimicrobial therapy

The writing group says it’s “reasonable” to offer people with injection drug–related IE standard treatment for IE, which is 6 weeks of intravenous antibiotics. They recognize, however, that this regimen is often not feasible in this patient population and say there is growing evidence that partial intravenous therapy followed by oral antibiotic treatment to complete a total of 6 weeks is a possible option.

They also highlight the “critical” importance of preventive measures in people who inject drugs who are successfully treated for an initial bout of IE because they remain at “extremely” high risk for subsequent bouts of IE, regardless of whether injection drug use is continued.

The writing group also stresses that people with IE who inject drugs should be considered for heart valve repair or replacement surgery regardless of current drug use if they have indications for valve surgery.

“There’s no evidence that indications for valve surgery are different for people who inject drugs compared to those who don’t, however, some treatment centers don’t offer surgery, especially if the patient currently injects drugs or has had a previous valve surgery,” Dr. DeSimone says in the release.

“Those who develop infective endocarditis require complex care delivered by professionals who look beyond stigma and bias to provide optimal and equitable care,” Dr. DeSimone adds.

The writing group acknowledges that while addiction medicine and addiction psychiatry expertise are critical to managing IE in injection drug users, these specific resources are currently not widely available.

They call on health care systems to attract individuals with addiction training and support addiction medicine consultative services, particularly in centers where drug use–related IE is common and expected to continue to increase.

This AHA scientific statement was prepared by the volunteer writing group on behalf of the AHA Rheumatic Fever, Endocarditis and Kawasaki Disease Committee of the Council on Lifelong Congenital Heart Disease and Heart Health in the Young; the Council on Cardiovascular Surgery and Anesthesia; the Council on Cardiovascular and Stroke Nursing; the Council on Clinical Cardiology; and the Council on Peripheral Vascular Disease.

This research had no commercial funding. Dr. DeSimone has no relevant disclosures.

A version of this article first appeared on Medscape.com.

Prompted by the “unprecedented” increase in the occurrence of infective endocarditis (IE) cases among people who inject drugs, the American Heart Association has issued a scientific statement devoted solely to this challenging patient population.

The statement provides a more in-depth focus on the management of IE among this unique population than what has been provided in prior AHA IE-related documents.

The statement stresses that managing IE in people who inject drugs is complex and requires a unique multidisciplinary approach that includes consultation with an addiction specialist.

The statement was published online in Circulation.
 

Poor long-term prognosis

In the United States from 2002 to 2016, the proportion of patients hospitalized with IE related to injection drug use doubled from 8% to about 16%.

The long-term prognosis for this population is “currently dismal for this relatively young group of individuals,” writing group Chair Daniel C. DeSimone, MD, with the Mayo Clinic in Rochester, Minn., notes in a news release.

To improve prognosis, the writing group advises a multidisciplinary team care approach that includes cardiologists, cardiac surgeons, and infectious diseases specialists as well as addiction medicine or addiction psychiatry specialists, pharmacists, social workers, and nurse specialists.

Nurse specialists can coordinate care from the initial IE hospitalization to outpatient and community care to support substance use disorder.

“Clinical teams must recognize that substance use disorder is a treatable chronic, relapsing medical illness and many people are able to enter sustained remission, particularly when they receive effective treatments,” the writing group emphasizes.

Although not all patients with injection drug–related IE have opioid addiction, for those who do, the “best practice” is to offer buprenorphine or methadone “as soon as possible” after the patient presents to the hospital, they advise.
 

Antimicrobial therapy

The writing group says it’s “reasonable” to offer people with injection drug–related IE standard treatment for IE, which is 6 weeks of intravenous antibiotics. They recognize, however, that this regimen is often not feasible in this patient population and say there is growing evidence that partial intravenous therapy followed by oral antibiotic treatment to complete a total of 6 weeks is a possible option.

They also highlight the “critical” importance of preventive measures in people who inject drugs who are successfully treated for an initial bout of IE because they remain at “extremely” high risk for subsequent bouts of IE, regardless of whether injection drug use is continued.

The writing group also stresses that people with IE who inject drugs should be considered for heart valve repair or replacement surgery regardless of current drug use if they have indications for valve surgery.

“There’s no evidence that indications for valve surgery are different for people who inject drugs compared to those who don’t, however, some treatment centers don’t offer surgery, especially if the patient currently injects drugs or has had a previous valve surgery,” Dr. DeSimone says in the release.

“Those who develop infective endocarditis require complex care delivered by professionals who look beyond stigma and bias to provide optimal and equitable care,” Dr. DeSimone adds.

The writing group acknowledges that while addiction medicine and addiction psychiatry expertise are critical to managing IE in injection drug users, these specific resources are currently not widely available.

They call on health care systems to attract individuals with addiction training and support addiction medicine consultative services, particularly in centers where drug use–related IE is common and expected to continue to increase.

This AHA scientific statement was prepared by the volunteer writing group on behalf of the AHA Rheumatic Fever, Endocarditis and Kawasaki Disease Committee of the Council on Lifelong Congenital Heart Disease and Heart Health in the Young; the Council on Cardiovascular Surgery and Anesthesia; the Council on Cardiovascular and Stroke Nursing; the Council on Clinical Cardiology; and the Council on Peripheral Vascular Disease.

This research had no commercial funding. Dr. DeSimone has no relevant disclosures.

A version of this article first appeared on Medscape.com.

Monkeypox, COVID, and polio: These three very different diseases have been dominating news cycles recently, but they share at least one common characteristic: some people can become infected – and in turn infect others – while showing no symptoms.

In 1883, the famous bacteriologist Friedrich Loeffler (1852-1915) recognized that an individual’s asymptomatic carriage of bacteria could lead to diphtheria in others. Now, as then, asymptomatically infected people present a conundrum: How do you fight the spread of a disease when you can’t identify some of the people who are spreading it?

“Typhoid Mary” is perhaps the quintessential example of asymptomatic transmission of infections leading to illness and death. At the turn of the 20th century, young Mary Mallon emigrated from Ireland to New York, where she soon became a cook for wealthy Manhattan families.

George Soper, a sanitary engineer, was hired by a stricken family to investigate. After epidemiologic study, he suspected that Mary was a carrier of Salmonella typhi, the bacterial cause of typhoid fever. He persuaded the New York Department of Health to test her – against her will – for infection. After her stool was found to test positive for Salmonella, Mary was forcibly moved to North Brother Island, where she remained largely isolated from others for the next 2 years. In 1910, she was released by a new commissioner after promising not to work as a cook.

However, working under an assumed name, Mary resumed cooking at the Sloane Hospital for Women in Manhattan. Over the next 3 months, at least 25 staff members became ill. Having been found out, Mary was again exiled to the island, where she spent the rest of her life. She died in 1938 after having infected at least 122 people, five of whom died.
 

COVID

Asymptomatic infections are primary drivers of COVID. Earlier in the pandemic, a meta-analysis suggested a 40% rate of asymptomatic infections, although some early reports arrived at lower estimates. A 2021 JAMA Network Open modeling study indicated a 60% rate.

Those rates are changing with the Omicron variants, of which even more cases are asymptomatic. Is this from a mutation in the virus? Some suggest that it is most likely attributable to prior vaccination resulting in boosted immunity and infections being milder. Of concern is that, although people may be asymptomatic, they still have the same viral load in their nose and can readily transmit infection.

Vincent Racaniello, PhD, a professor of virology at Columbia University in New York, told this news organization that “SARS-CoV-2 COVID is so effective at transmitting because it does this asymptomatic transmission. And so you’re out and about; you have no idea that you’re infected. You’re effectively doing what we call community transmission.”

This distinguishes SARS-CoV-2 from SARS-CoV-1. SARS-CoV-1 – which caused the SARS epidemic in 2002–2004 – had very little asymptomatic shedding. With COVID, on the other hand, “A lot of people are infected but never transmit,” Dr. Racaniello added. “I think 80% of transmissions are done by 20% of infected people because those are the ones who are shedding the most virus.”
 

Polio

The August case of paralytic polio in Rockland County, N.Y., is “the first case of polio reported in the United States in nearly 10 years, and only the second instance of community transmission identified in the U.S. since 1979,” a spokesperson for the Centers for Disease Control and Prevention said in an email. “Although no additional cases of polio have been reported at this time, recent wastewater findings elevate concerns that poliovirus is present in these communities, posing a risk to those who are unvaccinated.”

Poliovirus has now been found in the wastewater of New York City and three surrounding counties: Rockland, Orange, and Sullivan.

Unlike COVID, which is spread through air and respiratory secretions, polio has primarily fecal-oral transmission, meaning it is spread by people ingesting food or water contaminated with stool.

According to the World Health Organization, up to 90% of infections are unrecognized because the person has no to minimal symptoms. Symptoms are nonspecific in the remainder. Only a small proportion of those infected go on to develop paralysis.

Paul Offit, MD, a virologist and director of the Vaccine Education Center at the Children’s Hospital of Philadelphia, told this news organization that before widespread immunization, polio “caused 25,000 – 30,000 children every year to be paralyzed and 1,500 to die. Roughly 1 of every 200 children who was infected was paralyzed. We had the inactivated vaccine followed by the oral polio vaccine (OPV). The price that we paid for the OPV was that rarely it could revert to the so-called neurovirulent type, a paralytic type.”

Use of the OPV was discontinued in 2000 in the United States but is still widely used worldwide because it is inexpensive and easier to administer than injections. It appeared that we were close to completely eradicating polio, as we had smallpox, but then vaccine-derived polio virus (VDPV) started cropping up in Africa, the Middle East, and Asia. They are mainly from the type 2 virus, as is the New York case. There have been three other cases of VDPV in the United States since 2000.

Now, Dr. Offit estimates that only 1 in 2,000 of those infected become paralyzed. This is why the CDC and epidemiologists are so concerned about the Rockland patient – that one case of paralysis could represent a large pool of people who are infected with polio and are asymptomatic, continuing to shed infectious virus into the sewage.

The CDC confirmed that it began conducting wastewater testing for polio in August 2022. In their interviews for this article, Dr. Offit and Dr. Racaniello were both critical of this, stressing that it is essential to do wastewater testing nationally, since asymptomatic polio can be expected to crop up from international travelers who have received OPV.

Many countries conduct that kind of wastewater surveillance. Dr. Racaniello was particularly critical of the CDC. “We’ve been telling CDC for years, at least a decade, Why don’t you check the wastewater?,” Dr. Racaniello said, “It’s been known for many years that we should be looking to monitor the circulation of these viruses. So we are using paralysis as a sentinel to say that this virus is in the wastewater, which is just not acceptable!”

Apparently there was some concern that the public would not understand. Dr. Offit viewed it as one more piece of necessary education: “You shouldn’t be alarmed about this as long as you’re vaccinated. If you’re not vaccinated, realize that this is a risk you’re taking.”
 

Monkeypox

Monkeypox cases have been skyrocketing in the United States in recent weeks. More than 18,000 cases have been reported since the first case in Boston on May 19, 2022.

“Monkeypox was such a rare zoonotic disease, and the disease always historically was introduced through animal contact,” Stuart Isaacs, MD, a pox virologist at the University of Pennsylvania, said in an interview. “And then the infected person would have potential spread within the household as the most common human-to-human spread, The sexual transmission is driving a lot of this infection and potentially allowing this to efficiently spread from person to person.”

A recent study from Belgium, available only as a preprint, created concerns about potential asymptomatic transmission of monkeypox Three men had undergone testing for anogenital chlamydia and gonorrhea but showed no clinical signs of monkeypox. The same samples were later tested by polymerase chain reaction (PCR), and their viral load in anorectal swabs was similar to or slightly lower than that of symptomatic patients. While no cultures were done, the patients seroconverted by later antibody testing, confirming infection.

Via email, a CDC spokesperson noted, “At this time, CDC does not have enough data to support transmission from aerosolized virus for the ongoing monkeypox outbreak, or to assess the risks for transmission from asymptomatic people. The data supports the main source of transmission currently as close contact with someone who is infected with monkeypox.”

Dr. Isaacs agreed, saying studies of smallpox, a related orthopox virus, also suggested this.

In the United Kingdom, the Institute of Tropical Medicine is offering PCR testing for monkeypox to all patients who come for gonorrhea/chlamydia screening. Dr. Racaniello said, “I think that would be great to get a sense of who is infected. Then you could look at the results and say what fraction of people go on to develop lesions, and they give you a sense of the asymptomatic rate, which we don’t know at this point.”

Unfortunately, to be tested for monkeypox in the United States requires that the patient have a lesion. “This is part of the dropped ball of public health in the U.S.,” Dr. Racaniello said. “We’re not thinking about this. .... We need to be doing [infectivity] experiments. So then the question is, how much infectious virus do you need to transmit?”
 

Conclusion

We’ve seen that asymptomatic carriage of bacteria and viruses occurs readily with typhoid, COVID, diphtheria, and polio (among many other organisms, such as methicillin-resistant Staphylococcus aureus or group A strep) and is far less likely with monkeypox.

Two common denominators emerged from these interviews. The first and biggest hurdle is identifying asymptomatic carriers, which is hampered by the politicization of the CDC and funding cuts to public health. “It used to be the CDC was all about public health, and now it’s administrators, unfortunately,” said Dr. Racaniello, citing science writer Laurie Garrett, author of the influential 1994 book, “The Coming Plague”.

We don’t conduct proper surveillance, he pointed out. Wastewater surveillance has been neglected for more than a decade. It has been used for SARS-CoV-2 but is only now being initiated for polio and monkeypox. Norovirus testing would also be especially helpful in reducing foodborne outbreaks, Dr. Racaniello suggested.

The second common denominator is the need to increase the availability and uptake of vaccines. As Dr. Racaniello said about COVID, “The virus is here to stay. It’s never going to go away. It’s in humans. It’s in a lot of animals. So we’re stuck with it. We’re going to have outbreaks every year. So what do you do? Get vaccinated.” And he added, “Vaccination is the most important strategy to go on with our lives.”

Dr. Isaacs was a bit more tempered, not wanting to oversell the vaccine. He said, “The vaccine is just part of the toolkit,” which includes education, testing, isolation, and reducing risk, all of which decrease the transmission cycles.

Speaking of how antivaccine advocates had specifically targeted the Hasidic community in New York State’s Rockland County, Dr. Offit noted, “I don’t think it’s a knowledge deficit as much as a trust deficit.” He said officials should identify people in communities such as these who are trusted and have them become the influencers.

The final major hurdle to controlling these outbreaks remains global disparities in care. Monkeypox has been endemic in Nigeria for decades. It was only when it spread to Europe and America that it received attention. Polio has been actively circulating in Africa and the Middle East but is only getting attention because of the New York case.

Africa was unable to afford COVID vaccines until recently. While many in the United States are on their fourth booster, as of December 2021, more than 80% of people in Africa had not yet received a single dose, according to an article by Munyaradzi Makoni in The Lancet Respiratory Medicine.

Echoing Dr. Peter Hotez’s long-standing plea for “vaccine diplomacy,” Dr. Racaniello concluded, “My philosophy has always been we should give [vaccines] to them. I mean, we spend trillions on guns. Can’t we spend a few hundred million on vaccines? We should give away everything in terms of medicine to countries that need it, and people would like us a lot better than they do now. I think it would be such a great way of getting countries to like us. … So what if it costs a billion dollars a year? It’s a drop in the bucket for us.”

Given globalization, an infectious outbreak anywhere is a risk to all.

Dr. Racaniello and Dr. Offit report no relevant financial relationships. Dr. Isaacs receives royalties from UpToDate.

A version of this article first appeared on Medscape.com.

Monkeypox, COVID, and polio: These three very different diseases have been dominating news cycles recently, but they share at least one common characteristic: some people can become infected – and in turn infect others – while showing no symptoms.

In 1883, the famous bacteriologist Friedrich Loeffler (1852-1915) recognized that an individual’s asymptomatic carriage of bacteria could lead to diphtheria in others. Now, as then, asymptomatically infected people present a conundrum: How do you fight the spread of a disease when you can’t identify some of the people who are spreading it?

“Typhoid Mary” is perhaps the quintessential example of asymptomatic transmission of infections leading to illness and death. At the turn of the 20th century, young Mary Mallon emigrated from Ireland to New York, where she soon became a cook for wealthy Manhattan families.

George Soper, a sanitary engineer, was hired by a stricken family to investigate. After epidemiologic study, he suspected that Mary was a carrier of Salmonella typhi, the bacterial cause of typhoid fever. He persuaded the New York Department of Health to test her – against her will – for infection. After her stool was found to test positive for Salmonella, Mary was forcibly moved to North Brother Island, where she remained largely isolated from others for the next 2 years. In 1910, she was released by a new commissioner after promising not to work as a cook.

However, working under an assumed name, Mary resumed cooking at the Sloane Hospital for Women in Manhattan. Over the next 3 months, at least 25 staff members became ill. Having been found out, Mary was again exiled to the island, where she spent the rest of her life. She died in 1938 after having infected at least 122 people, five of whom died.
 

COVID

Asymptomatic infections are primary drivers of COVID. Earlier in the pandemic, a meta-analysis suggested a 40% rate of asymptomatic infections, although some early reports arrived at lower estimates. A 2021 JAMA Network Open modeling study indicated a 60% rate.

Those rates are changing with the Omicron variants, of which even more cases are asymptomatic. Is this from a mutation in the virus? Some suggest that it is most likely attributable to prior vaccination resulting in boosted immunity and infections being milder. Of concern is that, although people may be asymptomatic, they still have the same viral load in their nose and can readily transmit infection.

Vincent Racaniello, PhD, a professor of virology at Columbia University in New York, told this news organization that “SARS-CoV-2 COVID is so effective at transmitting because it does this asymptomatic transmission. And so you’re out and about; you have no idea that you’re infected. You’re effectively doing what we call community transmission.”

This distinguishes SARS-CoV-2 from SARS-CoV-1. SARS-CoV-1 – which caused the SARS epidemic in 2002–2004 – had very little asymptomatic shedding. With COVID, on the other hand, “A lot of people are infected but never transmit,” Dr. Racaniello added. “I think 80% of transmissions are done by 20% of infected people because those are the ones who are shedding the most virus.”
 

Polio

The August case of paralytic polio in Rockland County, N.Y., is “the first case of polio reported in the United States in nearly 10 years, and only the second instance of community transmission identified in the U.S. since 1979,” a spokesperson for the Centers for Disease Control and Prevention said in an email. “Although no additional cases of polio have been reported at this time, recent wastewater findings elevate concerns that poliovirus is present in these communities, posing a risk to those who are unvaccinated.”

Poliovirus has now been found in the wastewater of New York City and three surrounding counties: Rockland, Orange, and Sullivan.

Unlike COVID, which is spread through air and respiratory secretions, polio has primarily fecal-oral transmission, meaning it is spread by people ingesting food or water contaminated with stool.

According to the World Health Organization, up to 90% of infections are unrecognized because the person has no to minimal symptoms. Symptoms are nonspecific in the remainder. Only a small proportion of those infected go on to develop paralysis.

Paul Offit, MD, a virologist and director of the Vaccine Education Center at the Children’s Hospital of Philadelphia, told this news organization that before widespread immunization, polio “caused 25,000 – 30,000 children every year to be paralyzed and 1,500 to die. Roughly 1 of every 200 children who was infected was paralyzed. We had the inactivated vaccine followed by the oral polio vaccine (OPV). The price that we paid for the OPV was that rarely it could revert to the so-called neurovirulent type, a paralytic type.”

Use of the OPV was discontinued in 2000 in the United States but is still widely used worldwide because it is inexpensive and easier to administer than injections. It appeared that we were close to completely eradicating polio, as we had smallpox, but then vaccine-derived polio virus (VDPV) started cropping up in Africa, the Middle East, and Asia. They are mainly from the type 2 virus, as is the New York case. There have been three other cases of VDPV in the United States since 2000.

Now, Dr. Offit estimates that only 1 in 2,000 of those infected become paralyzed. This is why the CDC and epidemiologists are so concerned about the Rockland patient – that one case of paralysis could represent a large pool of people who are infected with polio and are asymptomatic, continuing to shed infectious virus into the sewage.

The CDC confirmed that it began conducting wastewater testing for polio in August 2022. In their interviews for this article, Dr. Offit and Dr. Racaniello were both critical of this, stressing that it is essential to do wastewater testing nationally, since asymptomatic polio can be expected to crop up from international travelers who have received OPV.

Many countries conduct that kind of wastewater surveillance. Dr. Racaniello was particularly critical of the CDC. “We’ve been telling CDC for years, at least a decade, Why don’t you check the wastewater?,” Dr. Racaniello said, “It’s been known for many years that we should be looking to monitor the circulation of these viruses. So we are using paralysis as a sentinel to say that this virus is in the wastewater, which is just not acceptable!”

Apparently there was some concern that the public would not understand. Dr. Offit viewed it as one more piece of necessary education: “You shouldn’t be alarmed about this as long as you’re vaccinated. If you’re not vaccinated, realize that this is a risk you’re taking.”
 

Monkeypox

Monkeypox cases have been skyrocketing in the United States in recent weeks. More than 18,000 cases have been reported since the first case in Boston on May 19, 2022.

“Monkeypox was such a rare zoonotic disease, and the disease always historically was introduced through animal contact,” Stuart Isaacs, MD, a pox virologist at the University of Pennsylvania, said in an interview. “And then the infected person would have potential spread within the household as the most common human-to-human spread, The sexual transmission is driving a lot of this infection and potentially allowing this to efficiently spread from person to person.”

A recent study from Belgium, available only as a preprint, created concerns about potential asymptomatic transmission of monkeypox Three men had undergone testing for anogenital chlamydia and gonorrhea but showed no clinical signs of monkeypox. The same samples were later tested by polymerase chain reaction (PCR), and their viral load in anorectal swabs was similar to or slightly lower than that of symptomatic patients. While no cultures were done, the patients seroconverted by later antibody testing, confirming infection.

Via email, a CDC spokesperson noted, “At this time, CDC does not have enough data to support transmission from aerosolized virus for the ongoing monkeypox outbreak, or to assess the risks for transmission from asymptomatic people. The data supports the main source of transmission currently as close contact with someone who is infected with monkeypox.”

Dr. Isaacs agreed, saying studies of smallpox, a related orthopox virus, also suggested this.

In the United Kingdom, the Institute of Tropical Medicine is offering PCR testing for monkeypox to all patients who come for gonorrhea/chlamydia screening. Dr. Racaniello said, “I think that would be great to get a sense of who is infected. Then you could look at the results and say what fraction of people go on to develop lesions, and they give you a sense of the asymptomatic rate, which we don’t know at this point.”

Unfortunately, to be tested for monkeypox in the United States requires that the patient have a lesion. “This is part of the dropped ball of public health in the U.S.,” Dr. Racaniello said. “We’re not thinking about this. .... We need to be doing [infectivity] experiments. So then the question is, how much infectious virus do you need to transmit?”
 

Conclusion

We’ve seen that asymptomatic carriage of bacteria and viruses occurs readily with typhoid, COVID, diphtheria, and polio (among many other organisms, such as methicillin-resistant Staphylococcus aureus or group A strep) and is far less likely with monkeypox.

Two common denominators emerged from these interviews. The first and biggest hurdle is identifying asymptomatic carriers, which is hampered by the politicization of the CDC and funding cuts to public health. “It used to be the CDC was all about public health, and now it’s administrators, unfortunately,” said Dr. Racaniello, citing science writer Laurie Garrett, author of the influential 1994 book, “The Coming Plague”.

We don’t conduct proper surveillance, he pointed out. Wastewater surveillance has been neglected for more than a decade. It has been used for SARS-CoV-2 but is only now being initiated for polio and monkeypox. Norovirus testing would also be especially helpful in reducing foodborne outbreaks, Dr. Racaniello suggested.

The second common denominator is the need to increase the availability and uptake of vaccines. As Dr. Racaniello said about COVID, “The virus is here to stay. It’s never going to go away. It’s in humans. It’s in a lot of animals. So we’re stuck with it. We’re going to have outbreaks every year. So what do you do? Get vaccinated.” And he added, “Vaccination is the most important strategy to go on with our lives.”

Dr. Isaacs was a bit more tempered, not wanting to oversell the vaccine. He said, “The vaccine is just part of the toolkit,” which includes education, testing, isolation, and reducing risk, all of which decrease the transmission cycles.

Speaking of how antivaccine advocates had specifically targeted the Hasidic community in New York State’s Rockland County, Dr. Offit noted, “I don’t think it’s a knowledge deficit as much as a trust deficit.” He said officials should identify people in communities such as these who are trusted and have them become the influencers.

The final major hurdle to controlling these outbreaks remains global disparities in care. Monkeypox has been endemic in Nigeria for decades. It was only when it spread to Europe and America that it received attention. Polio has been actively circulating in Africa and the Middle East but is only getting attention because of the New York case.

Africa was unable to afford COVID vaccines until recently. While many in the United States are on their fourth booster, as of December 2021, more than 80% of people in Africa had not yet received a single dose, according to an article by Munyaradzi Makoni in The Lancet Respiratory Medicine.

Echoing Dr. Peter Hotez’s long-standing plea for “vaccine diplomacy,” Dr. Racaniello concluded, “My philosophy has always been we should give [vaccines] to them. I mean, we spend trillions on guns. Can’t we spend a few hundred million on vaccines? We should give away everything in terms of medicine to countries that need it, and people would like us a lot better than they do now. I think it would be such a great way of getting countries to like us. … So what if it costs a billion dollars a year? It’s a drop in the bucket for us.”

Given globalization, an infectious outbreak anywhere is a risk to all.

Dr. Racaniello and Dr. Offit report no relevant financial relationships. Dr. Isaacs receives royalties from UpToDate.

A version of this article first appeared on Medscape.com.

Monkeypox, COVID, and polio: These three very different diseases have been dominating news cycles recently, but they share at least one common characteristic: some people can become infected – and in turn infect others – while showing no symptoms.

In 1883, the famous bacteriologist Friedrich Loeffler (1852-1915) recognized that an individual’s asymptomatic carriage of bacteria could lead to diphtheria in others. Now, as then, asymptomatically infected people present a conundrum: How do you fight the spread of a disease when you can’t identify some of the people who are spreading it?

“Typhoid Mary” is perhaps the quintessential example of asymptomatic transmission of infections leading to illness and death. At the turn of the 20th century, young Mary Mallon emigrated from Ireland to New York, where she soon became a cook for wealthy Manhattan families.

George Soper, a sanitary engineer, was hired by a stricken family to investigate. After epidemiologic study, he suspected that Mary was a carrier of Salmonella typhi, the bacterial cause of typhoid fever. He persuaded the New York Department of Health to test her – against her will – for infection. After her stool was found to test positive for Salmonella, Mary was forcibly moved to North Brother Island, where she remained largely isolated from others for the next 2 years. In 1910, she was released by a new commissioner after promising not to work as a cook.

However, working under an assumed name, Mary resumed cooking at the Sloane Hospital for Women in Manhattan. Over the next 3 months, at least 25 staff members became ill. Having been found out, Mary was again exiled to the island, where she spent the rest of her life. She died in 1938 after having infected at least 122 people, five of whom died.
 

COVID

Asymptomatic infections are primary drivers of COVID. Earlier in the pandemic, a meta-analysis suggested a 40% rate of asymptomatic infections, although some early reports arrived at lower estimates. A 2021 JAMA Network Open modeling study indicated a 60% rate.

Those rates are changing with the Omicron variants, of which even more cases are asymptomatic. Is this from a mutation in the virus? Some suggest that it is most likely attributable to prior vaccination resulting in boosted immunity and infections being milder. Of concern is that, although people may be asymptomatic, they still have the same viral load in their nose and can readily transmit infection.

Vincent Racaniello, PhD, a professor of virology at Columbia University in New York, told this news organization that “SARS-CoV-2 COVID is so effective at transmitting because it does this asymptomatic transmission. And so you’re out and about; you have no idea that you’re infected. You’re effectively doing what we call community transmission.”

This distinguishes SARS-CoV-2 from SARS-CoV-1. SARS-CoV-1 – which caused the SARS epidemic in 2002–2004 – had very little asymptomatic shedding. With COVID, on the other hand, “A lot of people are infected but never transmit,” Dr. Racaniello added. “I think 80% of transmissions are done by 20% of infected people because those are the ones who are shedding the most virus.”
 

Polio

The August case of paralytic polio in Rockland County, N.Y., is “the first case of polio reported in the United States in nearly 10 years, and only the second instance of community transmission identified in the U.S. since 1979,” a spokesperson for the Centers for Disease Control and Prevention said in an email. “Although no additional cases of polio have been reported at this time, recent wastewater findings elevate concerns that poliovirus is present in these communities, posing a risk to those who are unvaccinated.”

Poliovirus has now been found in the wastewater of New York City and three surrounding counties: Rockland, Orange, and Sullivan.

Unlike COVID, which is spread through air and respiratory secretions, polio has primarily fecal-oral transmission, meaning it is spread by people ingesting food or water contaminated with stool.

According to the World Health Organization, up to 90% of infections are unrecognized because the person has no to minimal symptoms. Symptoms are nonspecific in the remainder. Only a small proportion of those infected go on to develop paralysis.

Paul Offit, MD, a virologist and director of the Vaccine Education Center at the Children’s Hospital of Philadelphia, told this news organization that before widespread immunization, polio “caused 25,000 – 30,000 children every year to be paralyzed and 1,500 to die. Roughly 1 of every 200 children who was infected was paralyzed. We had the inactivated vaccine followed by the oral polio vaccine (OPV). The price that we paid for the OPV was that rarely it could revert to the so-called neurovirulent type, a paralytic type.”

Use of the OPV was discontinued in 2000 in the United States but is still widely used worldwide because it is inexpensive and easier to administer than injections. It appeared that we were close to completely eradicating polio, as we had smallpox, but then vaccine-derived polio virus (VDPV) started cropping up in Africa, the Middle East, and Asia. They are mainly from the type 2 virus, as is the New York case. There have been three other cases of VDPV in the United States since 2000.

Now, Dr. Offit estimates that only 1 in 2,000 of those infected become paralyzed. This is why the CDC and epidemiologists are so concerned about the Rockland patient – that one case of paralysis could represent a large pool of people who are infected with polio and are asymptomatic, continuing to shed infectious virus into the sewage.

The CDC confirmed that it began conducting wastewater testing for polio in August 2022. In their interviews for this article, Dr. Offit and Dr. Racaniello were both critical of this, stressing that it is essential to do wastewater testing nationally, since asymptomatic polio can be expected to crop up from international travelers who have received OPV.

Many countries conduct that kind of wastewater surveillance. Dr. Racaniello was particularly critical of the CDC. “We’ve been telling CDC for years, at least a decade, Why don’t you check the wastewater?,” Dr. Racaniello said, “It’s been known for many years that we should be looking to monitor the circulation of these viruses. So we are using paralysis as a sentinel to say that this virus is in the wastewater, which is just not acceptable!”

Apparently there was some concern that the public would not understand. Dr. Offit viewed it as one more piece of necessary education: “You shouldn’t be alarmed about this as long as you’re vaccinated. If you’re not vaccinated, realize that this is a risk you’re taking.”
 

Monkeypox

Monkeypox cases have been skyrocketing in the United States in recent weeks. More than 18,000 cases have been reported since the first case in Boston on May 19, 2022.

“Monkeypox was such a rare zoonotic disease, and the disease always historically was introduced through animal contact,” Stuart Isaacs, MD, a pox virologist at the University of Pennsylvania, said in an interview. “And then the infected person would have potential spread within the household as the most common human-to-human spread, The sexual transmission is driving a lot of this infection and potentially allowing this to efficiently spread from person to person.”

A recent study from Belgium, available only as a preprint, created concerns about potential asymptomatic transmission of monkeypox Three men had undergone testing for anogenital chlamydia and gonorrhea but showed no clinical signs of monkeypox. The same samples were later tested by polymerase chain reaction (PCR), and their viral load in anorectal swabs was similar to or slightly lower than that of symptomatic patients. While no cultures were done, the patients seroconverted by later antibody testing, confirming infection.

Via email, a CDC spokesperson noted, “At this time, CDC does not have enough data to support transmission from aerosolized virus for the ongoing monkeypox outbreak, or to assess the risks for transmission from asymptomatic people. The data supports the main source of transmission currently as close contact with someone who is infected with monkeypox.”

Dr. Isaacs agreed, saying studies of smallpox, a related orthopox virus, also suggested this.

In the United Kingdom, the Institute of Tropical Medicine is offering PCR testing for monkeypox to all patients who come for gonorrhea/chlamydia screening. Dr. Racaniello said, “I think that would be great to get a sense of who is infected. Then you could look at the results and say what fraction of people go on to develop lesions, and they give you a sense of the asymptomatic rate, which we don’t know at this point.”

Unfortunately, to be tested for monkeypox in the United States requires that the patient have a lesion. “This is part of the dropped ball of public health in the U.S.,” Dr. Racaniello said. “We’re not thinking about this. .... We need to be doing [infectivity] experiments. So then the question is, how much infectious virus do you need to transmit?”
 

Conclusion

We’ve seen that asymptomatic carriage of bacteria and viruses occurs readily with typhoid, COVID, diphtheria, and polio (among many other organisms, such as methicillin-resistant Staphylococcus aureus or group A strep) and is far less likely with monkeypox.

Two common denominators emerged from these interviews. The first and biggest hurdle is identifying asymptomatic carriers, which is hampered by the politicization of the CDC and funding cuts to public health. “It used to be the CDC was all about public health, and now it’s administrators, unfortunately,” said Dr. Racaniello, citing science writer Laurie Garrett, author of the influential 1994 book, “The Coming Plague”.

We don’t conduct proper surveillance, he pointed out. Wastewater surveillance has been neglected for more than a decade. It has been used for SARS-CoV-2 but is only now being initiated for polio and monkeypox. Norovirus testing would also be especially helpful in reducing foodborne outbreaks, Dr. Racaniello suggested.

The second common denominator is the need to increase the availability and uptake of vaccines. As Dr. Racaniello said about COVID, “The virus is here to stay. It’s never going to go away. It’s in humans. It’s in a lot of animals. So we’re stuck with it. We’re going to have outbreaks every year. So what do you do? Get vaccinated.” And he added, “Vaccination is the most important strategy to go on with our lives.”

Dr. Isaacs was a bit more tempered, not wanting to oversell the vaccine. He said, “The vaccine is just part of the toolkit,” which includes education, testing, isolation, and reducing risk, all of which decrease the transmission cycles.

Speaking of how antivaccine advocates had specifically targeted the Hasidic community in New York State’s Rockland County, Dr. Offit noted, “I don’t think it’s a knowledge deficit as much as a trust deficit.” He said officials should identify people in communities such as these who are trusted and have them become the influencers.

The final major hurdle to controlling these outbreaks remains global disparities in care. Monkeypox has been endemic in Nigeria for decades. It was only when it spread to Europe and America that it received attention. Polio has been actively circulating in Africa and the Middle East but is only getting attention because of the New York case.

Africa was unable to afford COVID vaccines until recently. While many in the United States are on their fourth booster, as of December 2021, more than 80% of people in Africa had not yet received a single dose, according to an article by Munyaradzi Makoni in The Lancet Respiratory Medicine.

Echoing Dr. Peter Hotez’s long-standing plea for “vaccine diplomacy,” Dr. Racaniello concluded, “My philosophy has always been we should give [vaccines] to them. I mean, we spend trillions on guns. Can’t we spend a few hundred million on vaccines? We should give away everything in terms of medicine to countries that need it, and people would like us a lot better than they do now. I think it would be such a great way of getting countries to like us. … So what if it costs a billion dollars a year? It’s a drop in the bucket for us.”

Given globalization, an infectious outbreak anywhere is a risk to all.

Dr. Racaniello and Dr. Offit report no relevant financial relationships. Dr. Isaacs receives royalties from UpToDate.

A version of this article first appeared on Medscape.com.

Life expectancy in the United States declined again in 2021, after a historic drop in 2020, to reach the lowest point in decades, according to new CDC data.

In 2021, the average American could expect to live until age 76, which fell from 77 in 2020 and 79 in 2019. That marks the lowest age since 1996 and the largest 2-year decline since 1923.

“Even small declines in life expectancy of a tenth or two-tenths of a year mean that on a population level, a lot more people are dying prematurely,” Robert Anderson, PhD, chief of mortality statistics at the National Center for Health Statistics, which produced the report, told The New York Times.

“This signals a huge impact on the population in terms of increased mortality,” he said.

COVID-19 played a major role, with excess death from the coronavirus contributing to half of the decline during the past 2 years. Drug overdose deaths also reached a record high in 2021, rising to about 109,000 people. Unintentional injuries, with about half due to drug overdose, were a leading cause of the decline in life expectancy, along with deaths from heart disease, chronic liver disease, cirrhosis, and suicide.

The decrease has been particularly devastating among Native Americans and Alaska Natives. Average life expectancy dropped by 4 years in 2020 alone and more than 6.5 years since the beginning of the pandemic. Now their life expectancy is 65, which was the average for all Americans in 1944.

“When I saw that in the report, I just – my jaw dropped,” Dr. Anderson told CNN.

“It was hard enough to fathom a 2.7-year decline over 2 years overall,” he said. “But then to see a 6.6-year decline for the American Indian population, it just shows the substantial impact that the pandemic has had on that population.”

Longstanding health issues and systemic problems, such as poverty, discrimination, and poor access to health care, led to the major declines among Native Americans and Alaska Natives, CNN reported.

“A lot of the talk is going to be around the pandemic, but we need to think about what has driven the conditions that have allowed certain communities to be more vulnerable,” Ruben Cantu, an associate program director with Prevention Institute, a nonprofit focused on health equity, told CNN.

The gap in life expectancy between women and men also became wider in 2021, growing to 5.9 years and marking the largest gap since 1996. The life expectancy for men in 2021 was 73.2, as compared with 79.1 for women.

The decline in overall U.S. life expectancy would have been even greater if there weren’t “offsetting effects,” the researchers wrote, such as declines in death due to the flu, pneumonia, chronic lower respiratory diseases, and Alzheimer’s disease.

The drop in U.S. life expectancy is “historic,” Steven Woolf, MD, retired director of the Center on Society and Health and Virginia Commonwealth University, told the Times.

Other high-income countries also saw a drop in life expectancy in 2020 due to the pandemic, but most began to recover last year due to major vaccine campaigns and behavior changes such as wearing masks, he said.

“None of them experienced a continuing fall in life expectancy like the U.S. did, and a good number of them saw life expectancy start inching back to normal,” he said. “The U.S. is clearly an outlier.”

A version of this article first appeared on WebMD.com.

Life expectancy in the United States declined again in 2021, after a historic drop in 2020, to reach the lowest point in decades, according to new CDC data.

In 2021, the average American could expect to live until age 76, which fell from 77 in 2020 and 79 in 2019. That marks the lowest age since 1996 and the largest 2-year decline since 1923.

“Even small declines in life expectancy of a tenth or two-tenths of a year mean that on a population level, a lot more people are dying prematurely,” Robert Anderson, PhD, chief of mortality statistics at the National Center for Health Statistics, which produced the report, told The New York Times.

“This signals a huge impact on the population in terms of increased mortality,” he said.

COVID-19 played a major role, with excess death from the coronavirus contributing to half of the decline during the past 2 years. Drug overdose deaths also reached a record high in 2021, rising to about 109,000 people. Unintentional injuries, with about half due to drug overdose, were a leading cause of the decline in life expectancy, along with deaths from heart disease, chronic liver disease, cirrhosis, and suicide.

The decrease has been particularly devastating among Native Americans and Alaska Natives. Average life expectancy dropped by 4 years in 2020 alone and more than 6.5 years since the beginning of the pandemic. Now their life expectancy is 65, which was the average for all Americans in 1944.

“When I saw that in the report, I just – my jaw dropped,” Dr. Anderson told CNN.

“It was hard enough to fathom a 2.7-year decline over 2 years overall,” he said. “But then to see a 6.6-year decline for the American Indian population, it just shows the substantial impact that the pandemic has had on that population.”

Longstanding health issues and systemic problems, such as poverty, discrimination, and poor access to health care, led to the major declines among Native Americans and Alaska Natives, CNN reported.

“A lot of the talk is going to be around the pandemic, but we need to think about what has driven the conditions that have allowed certain communities to be more vulnerable,” Ruben Cantu, an associate program director with Prevention Institute, a nonprofit focused on health equity, told CNN.

The gap in life expectancy between women and men also became wider in 2021, growing to 5.9 years and marking the largest gap since 1996. The life expectancy for men in 2021 was 73.2, as compared with 79.1 for women.

The decline in overall U.S. life expectancy would have been even greater if there weren’t “offsetting effects,” the researchers wrote, such as declines in death due to the flu, pneumonia, chronic lower respiratory diseases, and Alzheimer’s disease.

The drop in U.S. life expectancy is “historic,” Steven Woolf, MD, retired director of the Center on Society and Health and Virginia Commonwealth University, told the Times.

Other high-income countries also saw a drop in life expectancy in 2020 due to the pandemic, but most began to recover last year due to major vaccine campaigns and behavior changes such as wearing masks, he said.

“None of them experienced a continuing fall in life expectancy like the U.S. did, and a good number of them saw life expectancy start inching back to normal,” he said. “The U.S. is clearly an outlier.”

A version of this article first appeared on WebMD.com.

Life expectancy in the United States declined again in 2021, after a historic drop in 2020, to reach the lowest point in decades, according to new CDC data.

In 2021, the average American could expect to live until age 76, which fell from 77 in 2020 and 79 in 2019. That marks the lowest age since 1996 and the largest 2-year decline since 1923.

“Even small declines in life expectancy of a tenth or two-tenths of a year mean that on a population level, a lot more people are dying prematurely,” Robert Anderson, PhD, chief of mortality statistics at the National Center for Health Statistics, which produced the report, told The New York Times.

“This signals a huge impact on the population in terms of increased mortality,” he said.

COVID-19 played a major role, with excess death from the coronavirus contributing to half of the decline during the past 2 years. Drug overdose deaths also reached a record high in 2021, rising to about 109,000 people. Unintentional injuries, with about half due to drug overdose, were a leading cause of the decline in life expectancy, along with deaths from heart disease, chronic liver disease, cirrhosis, and suicide.

The decrease has been particularly devastating among Native Americans and Alaska Natives. Average life expectancy dropped by 4 years in 2020 alone and more than 6.5 years since the beginning of the pandemic. Now their life expectancy is 65, which was the average for all Americans in 1944.

“When I saw that in the report, I just – my jaw dropped,” Dr. Anderson told CNN.

“It was hard enough to fathom a 2.7-year decline over 2 years overall,” he said. “But then to see a 6.6-year decline for the American Indian population, it just shows the substantial impact that the pandemic has had on that population.”

Longstanding health issues and systemic problems, such as poverty, discrimination, and poor access to health care, led to the major declines among Native Americans and Alaska Natives, CNN reported.

“A lot of the talk is going to be around the pandemic, but we need to think about what has driven the conditions that have allowed certain communities to be more vulnerable,” Ruben Cantu, an associate program director with Prevention Institute, a nonprofit focused on health equity, told CNN.

The gap in life expectancy between women and men also became wider in 2021, growing to 5.9 years and marking the largest gap since 1996. The life expectancy for men in 2021 was 73.2, as compared with 79.1 for women.

The decline in overall U.S. life expectancy would have been even greater if there weren’t “offsetting effects,” the researchers wrote, such as declines in death due to the flu, pneumonia, chronic lower respiratory diseases, and Alzheimer’s disease.

The drop in U.S. life expectancy is “historic,” Steven Woolf, MD, retired director of the Center on Society and Health and Virginia Commonwealth University, told the Times.

Other high-income countries also saw a drop in life expectancy in 2020 due to the pandemic, but most began to recover last year due to major vaccine campaigns and behavior changes such as wearing masks, he said.

“None of them experienced a continuing fall in life expectancy like the U.S. did, and a good number of them saw life expectancy start inching back to normal,” he said. “The U.S. is clearly an outlier.”

A version of this article first appeared on WebMD.com.

BY WILL PASS

Don’t count on a runny nose. Young kids with COVID-19 often have no symptoms at all, even when they have a high viral load, according to a study supported by the Centers for Disease Control and Prevention.

Just 14% of adults who tested positive for SARS-CoV-2 were asymptomatic, versus 37% of children aged 0-4 years, in the paper. This raises concern that parents, childcare providers, and preschools may be underestimating infection in seemingly healthy young kids who have been exposed to COVID, wrote lead author Ruth A. Karron, MD, and colleagues in JAMA Network Open.

Methods

The new research involved 690 individuals from 175 households in Maryland who were monitored closely between November 2020 and October 2021. Every week for 8 months, participants completed online symptom checks and underwent PCR testing using nasal swabs, with symptomatic individuals submitting additional swabs for analysis.

“What was different about our study [compared with previous studies] was the intensity of our collection, and the fact that we collected specimens from asymptomatic people,” said Dr. Karron, a pediatrician and professor in the department of international health, Johns Hopkins University, Baltimore, in an interview. “You shed more virus earlier in the infection than later, and the fact that we were sampling every single week meant that we could pick up those early infections.”

The study also stands out for its focus on young children, Dr. Karron said. Enrollment required all households to have at least one child aged 0-4 years, so 256 out of 690 participants (37.1%) were in this youngest age group. The remainder of the population consisted of 100 older children aged 5-17 years (14.5%) and 334 adults aged 18-74 years (48.4%).

Children 4 and under more than twice as likely to be asymptomatic

By the end of the study, 51 participants had tested positive for SARS-CoV-2, among whom 14 had no symptoms. A closer look showed that children 0-4 years of age who contracted COVID were more than twice as likely to be asymptomatic as infected adults (36.8% vs. 14.3%).

The relationship between symptoms and viral load also differed between adults and young children.

While adults with high viral loads – suggesting greater contagiousness – typically had more severe COVID symptoms, no correlation was found in young kids, meaning children with mild or no symptoms could still be highly contagious.

Dr. Karron said these findings should help parents and other stakeholders make better-informed decisions based on known risks. She recommended testing young, asymptomatic children for COVID if they have been exposed to infected individuals, then acting accordingly based on the results.

“If a family is infected with the virus, and the 2-year-old is asymptomatic, and people are thinking about a visit to elderly grandparents who may be frail, one shouldn’t assume that the 2-year-old is uninfected,” Dr. Karron said. “That child should be tested along with other family members.”

Testing should also be considered for young children exposed to COVID at childcare facilities, she added.

But not every expert consulted for this piece shared these opinions of Dr. Karron.

“I question whether that effort is worth it,” said Dean Blumberg, MD, professor and chief of the division of pediatric infectious diseases at UC Davis Health, Sacramento, Calif.

He noted that recent Food and Drug Administration guidance for COVID testing calls for three negative at-home antigen tests to confirm lack of infection.

“That would take 4 days to get those tests done,” he said. “So, it’s a lot of testing. It’s a lot of record keeping, it’s inconvenient, it’s uncomfortable to be tested, and I just question whether it’s worth that effort.”

Applicability of findings to today questioned

Dr. Blumberg also questioned whether the study, which was completed almost a year ago, reflects the current pandemic landscape.

“At the time this study was done, it was predominantly Delta [variant instead of Omicron],” Dr. Blumberg said. “The other issue [with the study] is that … most of the children didn’t have preexisting immunity, so you have to take that into account.”

Preexisting immunity – whether from exposure or vaccination – could lower viral loads, so asymptomatic children today really could be less contagious than they were when the study was done, according to Dr. Blumberg. Kids without symptoms are also less likely to spread the virus, because they aren’t coughing or sneezing, he added.

Sara R. Kim, MD, and Janet A. Englund, MD, of the Seattle Children’s Research Institute, University of Washington, said it’s challenging to know how applicable the findings are, although they sided more with the investigators than Dr. Blumberg.

“Given the higher rate of transmissibility and infectivity of the Omicron variant, it is difficult to make direct associations between findings reported during this study period and those present in the current era during which the Omicron variant is circulating,” they wrote in an accompanying editorial. “However, the higher rates of asymptomatic infection observed among children in this study are likely to be consistent with those observed for current and future viral variants.”

Although the experts offered different interpretations of the findings, they shared similar perspectives on vaccination.

“The most important thing that parents can do is get their kids vaccinated, be vaccinated themselves, and have everybody in the household vaccinated and up to date for all doses that are indicated,” Dr. Blumberg said.

Dr. Karron noted that vaccination will be increasingly important in the coming months.

“Summer is ending; school is starting,” she said. “We’re going to be in large groups indoors again very soon. To keep young children safe, I think it’s really important for them to get vaccinated.”

The study was funded by the CDC. The investigators disclosed no other relationships. Dr. Englund disclosed relationships with AstraZeneca, GlaxoSmithKline, Merck, and others. Dr. Kim and Dr. Blumberg disclosed no relevant conflicts of interest.

BY WILL PASS

Don’t count on a runny nose. Young kids with COVID-19 often have no symptoms at all, even when they have a high viral load, according to a study supported by the Centers for Disease Control and Prevention.

Just 14% of adults who tested positive for SARS-CoV-2 were asymptomatic, versus 37% of children aged 0-4 years, in the paper. This raises concern that parents, childcare providers, and preschools may be underestimating infection in seemingly healthy young kids who have been exposed to COVID, wrote lead author Ruth A. Karron, MD, and colleagues in JAMA Network Open.

Methods

The new research involved 690 individuals from 175 households in Maryland who were monitored closely between November 2020 and October 2021. Every week for 8 months, participants completed online symptom checks and underwent PCR testing using nasal swabs, with symptomatic individuals submitting additional swabs for analysis.

“What was different about our study [compared with previous studies] was the intensity of our collection, and the fact that we collected specimens from asymptomatic people,” said Dr. Karron, a pediatrician and professor in the department of international health, Johns Hopkins University, Baltimore, in an interview. “You shed more virus earlier in the infection than later, and the fact that we were sampling every single week meant that we could pick up those early infections.”

The study also stands out for its focus on young children, Dr. Karron said. Enrollment required all households to have at least one child aged 0-4 years, so 256 out of 690 participants (37.1%) were in this youngest age group. The remainder of the population consisted of 100 older children aged 5-17 years (14.5%) and 334 adults aged 18-74 years (48.4%).

Children 4 and under more than twice as likely to be asymptomatic

By the end of the study, 51 participants had tested positive for SARS-CoV-2, among whom 14 had no symptoms. A closer look showed that children 0-4 years of age who contracted COVID were more than twice as likely to be asymptomatic as infected adults (36.8% vs. 14.3%).

The relationship between symptoms and viral load also differed between adults and young children.

While adults with high viral loads – suggesting greater contagiousness – typically had more severe COVID symptoms, no correlation was found in young kids, meaning children with mild or no symptoms could still be highly contagious.

Dr. Karron said these findings should help parents and other stakeholders make better-informed decisions based on known risks. She recommended testing young, asymptomatic children for COVID if they have been exposed to infected individuals, then acting accordingly based on the results.

“If a family is infected with the virus, and the 2-year-old is asymptomatic, and people are thinking about a visit to elderly grandparents who may be frail, one shouldn’t assume that the 2-year-old is uninfected,” Dr. Karron said. “That child should be tested along with other family members.”

Testing should also be considered for young children exposed to COVID at childcare facilities, she added.

But not every expert consulted for this piece shared these opinions of Dr. Karron.

“I question whether that effort is worth it,” said Dean Blumberg, MD, professor and chief of the division of pediatric infectious diseases at UC Davis Health, Sacramento, Calif.

He noted that recent Food and Drug Administration guidance for COVID testing calls for three negative at-home antigen tests to confirm lack of infection.

“That would take 4 days to get those tests done,” he said. “So, it’s a lot of testing. It’s a lot of record keeping, it’s inconvenient, it’s uncomfortable to be tested, and I just question whether it’s worth that effort.”

Applicability of findings to today questioned

Dr. Blumberg also questioned whether the study, which was completed almost a year ago, reflects the current pandemic landscape.

“At the time this study was done, it was predominantly Delta [variant instead of Omicron],” Dr. Blumberg said. “The other issue [with the study] is that … most of the children didn’t have preexisting immunity, so you have to take that into account.”

Preexisting immunity – whether from exposure or vaccination – could lower viral loads, so asymptomatic children today really could be less contagious than they were when the study was done, according to Dr. Blumberg. Kids without symptoms are also less likely to spread the virus, because they aren’t coughing or sneezing, he added.

Sara R. Kim, MD, and Janet A. Englund, MD, of the Seattle Children’s Research Institute, University of Washington, said it’s challenging to know how applicable the findings are, although they sided more with the investigators than Dr. Blumberg.

“Given the higher rate of transmissibility and infectivity of the Omicron variant, it is difficult to make direct associations between findings reported during this study period and those present in the current era during which the Omicron variant is circulating,” they wrote in an accompanying editorial. “However, the higher rates of asymptomatic infection observed among children in this study are likely to be consistent with those observed for current and future viral variants.”

Although the experts offered different interpretations of the findings, they shared similar perspectives on vaccination.

“The most important thing that parents can do is get their kids vaccinated, be vaccinated themselves, and have everybody in the household vaccinated and up to date for all doses that are indicated,” Dr. Blumberg said.

Dr. Karron noted that vaccination will be increasingly important in the coming months.

“Summer is ending; school is starting,” she said. “We’re going to be in large groups indoors again very soon. To keep young children safe, I think it’s really important for them to get vaccinated.”

The study was funded by the CDC. The investigators disclosed no other relationships. Dr. Englund disclosed relationships with AstraZeneca, GlaxoSmithKline, Merck, and others. Dr. Kim and Dr. Blumberg disclosed no relevant conflicts of interest.

BY WILL PASS

Don’t count on a runny nose. Young kids with COVID-19 often have no symptoms at all, even when they have a high viral load, according to a study supported by the Centers for Disease Control and Prevention.

Just 14% of adults who tested positive for SARS-CoV-2 were asymptomatic, versus 37% of children aged 0-4 years, in the paper. This raises concern that parents, childcare providers, and preschools may be underestimating infection in seemingly healthy young kids who have been exposed to COVID, wrote lead author Ruth A. Karron, MD, and colleagues in JAMA Network Open.

Methods

The new research involved 690 individuals from 175 households in Maryland who were monitored closely between November 2020 and October 2021. Every week for 8 months, participants completed online symptom checks and underwent PCR testing using nasal swabs, with symptomatic individuals submitting additional swabs for analysis.

“What was different about our study [compared with previous studies] was the intensity of our collection, and the fact that we collected specimens from asymptomatic people,” said Dr. Karron, a pediatrician and professor in the department of international health, Johns Hopkins University, Baltimore, in an interview. “You shed more virus earlier in the infection than later, and the fact that we were sampling every single week meant that we could pick up those early infections.”

The study also stands out for its focus on young children, Dr. Karron said. Enrollment required all households to have at least one child aged 0-4 years, so 256 out of 690 participants (37.1%) were in this youngest age group. The remainder of the population consisted of 100 older children aged 5-17 years (14.5%) and 334 adults aged 18-74 years (48.4%).

Children 4 and under more than twice as likely to be asymptomatic

By the end of the study, 51 participants had tested positive for SARS-CoV-2, among whom 14 had no symptoms. A closer look showed that children 0-4 years of age who contracted COVID were more than twice as likely to be asymptomatic as infected adults (36.8% vs. 14.3%).

The relationship between symptoms and viral load also differed between adults and young children.

While adults with high viral loads – suggesting greater contagiousness – typically had more severe COVID symptoms, no correlation was found in young kids, meaning children with mild or no symptoms could still be highly contagious.

Dr. Karron said these findings should help parents and other stakeholders make better-informed decisions based on known risks. She recommended testing young, asymptomatic children for COVID if they have been exposed to infected individuals, then acting accordingly based on the results.

“If a family is infected with the virus, and the 2-year-old is asymptomatic, and people are thinking about a visit to elderly grandparents who may be frail, one shouldn’t assume that the 2-year-old is uninfected,” Dr. Karron said. “That child should be tested along with other family members.”

Testing should also be considered for young children exposed to COVID at childcare facilities, she added.

But not every expert consulted for this piece shared these opinions of Dr. Karron.

“I question whether that effort is worth it,” said Dean Blumberg, MD, professor and chief of the division of pediatric infectious diseases at UC Davis Health, Sacramento, Calif.

He noted that recent Food and Drug Administration guidance for COVID testing calls for three negative at-home antigen tests to confirm lack of infection.

“That would take 4 days to get those tests done,” he said. “So, it’s a lot of testing. It’s a lot of record keeping, it’s inconvenient, it’s uncomfortable to be tested, and I just question whether it’s worth that effort.”

Applicability of findings to today questioned

Dr. Blumberg also questioned whether the study, which was completed almost a year ago, reflects the current pandemic landscape.

“At the time this study was done, it was predominantly Delta [variant instead of Omicron],” Dr. Blumberg said. “The other issue [with the study] is that … most of the children didn’t have preexisting immunity, so you have to take that into account.”

Preexisting immunity – whether from exposure or vaccination – could lower viral loads, so asymptomatic children today really could be less contagious than they were when the study was done, according to Dr. Blumberg. Kids without symptoms are also less likely to spread the virus, because they aren’t coughing or sneezing, he added.

Sara R. Kim, MD, and Janet A. Englund, MD, of the Seattle Children’s Research Institute, University of Washington, said it’s challenging to know how applicable the findings are, although they sided more with the investigators than Dr. Blumberg.

“Given the higher rate of transmissibility and infectivity of the Omicron variant, it is difficult to make direct associations between findings reported during this study period and those present in the current era during which the Omicron variant is circulating,” they wrote in an accompanying editorial. “However, the higher rates of asymptomatic infection observed among children in this study are likely to be consistent with those observed for current and future viral variants.”

Although the experts offered different interpretations of the findings, they shared similar perspectives on vaccination.

“The most important thing that parents can do is get their kids vaccinated, be vaccinated themselves, and have everybody in the household vaccinated and up to date for all doses that are indicated,” Dr. Blumberg said.

Dr. Karron noted that vaccination will be increasingly important in the coming months.

“Summer is ending; school is starting,” she said. “We’re going to be in large groups indoors again very soon. To keep young children safe, I think it’s really important for them to get vaccinated.”

The study was funded by the CDC. The investigators disclosed no other relationships. Dr. Englund disclosed relationships with AstraZeneca, GlaxoSmithKline, Merck, and others. Dr. Kim and Dr. Blumberg disclosed no relevant conflicts of interest.

The Food and Drug Administration today granted emergency use authorization to Omicron-specific COVID-19 vaccines made by Pfizer/BioNTech and Moderna.

The agency cited data to support the safety and efficacy of this next generation of mRNA vaccines targeted toward variants of concern.

The Pfizer EUA corresponds to the company’s combination booster shot that includes the original COVID-19 vaccine as well as a vaccine specifically designed to protect against the most recent Omicron variants, BA.4 and BA.5.

The Moderna combination vaccine will contain both the firm’s original COVID-19 vaccine and a vaccine to protect specifically against Omicron BA.4 and BA.5 subvariants.

As of Aug. 27, BA.4 and BA.4.6 account for about 11% of circulating variants and BA.5 accounts for almost all the remaining 89%, Centers for Disease Control and Prevention data show.

The next step will be review of the scientific data by the CDC’s Advisory Committee on Immunization Practices, which is set to meet Sept. 1 and 2. The final hurdle before distribution of the new vaccines will be sign-off on CDC recommendations for use by agency Director Rochelle Walensky, MD.

This is a developing story. A version of this article first appeared on WebMD.com.

The Food and Drug Administration today granted emergency use authorization to Omicron-specific COVID-19 vaccines made by Pfizer/BioNTech and Moderna.

The agency cited data to support the safety and efficacy of this next generation of mRNA vaccines targeted toward variants of concern.

The Pfizer EUA corresponds to the company’s combination booster shot that includes the original COVID-19 vaccine as well as a vaccine specifically designed to protect against the most recent Omicron variants, BA.4 and BA.5.

The Moderna combination vaccine will contain both the firm’s original COVID-19 vaccine and a vaccine to protect specifically against Omicron BA.4 and BA.5 subvariants.

As of Aug. 27, BA.4 and BA.4.6 account for about 11% of circulating variants and BA.5 accounts for almost all the remaining 89%, Centers for Disease Control and Prevention data show.

The next step will be review of the scientific data by the CDC’s Advisory Committee on Immunization Practices, which is set to meet Sept. 1 and 2. The final hurdle before distribution of the new vaccines will be sign-off on CDC recommendations for use by agency Director Rochelle Walensky, MD.

This is a developing story. A version of this article first appeared on WebMD.com.

The Food and Drug Administration today granted emergency use authorization to Omicron-specific COVID-19 vaccines made by Pfizer/BioNTech and Moderna.

The agency cited data to support the safety and efficacy of this next generation of mRNA vaccines targeted toward variants of concern.

The Pfizer EUA corresponds to the company’s combination booster shot that includes the original COVID-19 vaccine as well as a vaccine specifically designed to protect against the most recent Omicron variants, BA.4 and BA.5.

The Moderna combination vaccine will contain both the firm’s original COVID-19 vaccine and a vaccine to protect specifically against Omicron BA.4 and BA.5 subvariants.

As of Aug. 27, BA.4 and BA.4.6 account for about 11% of circulating variants and BA.5 accounts for almost all the remaining 89%, Centers for Disease Control and Prevention data show.

The next step will be review of the scientific data by the CDC’s Advisory Committee on Immunization Practices, which is set to meet Sept. 1 and 2. The final hurdle before distribution of the new vaccines will be sign-off on CDC recommendations for use by agency Director Rochelle Walensky, MD.

This is a developing story. A version of this article first appeared on WebMD.com.

Angiolymphoid hyperplasia with eosinophilia (ALHE) is a rare nodular unencapsulated mass that is characterized by benign anomalous vascular hyperplasia of epithelioidlike endothelial cells attached to dilated blood vessels. The mass is surrounded by lymphocytes and eosinophils that can present clinically as papules, plaques, or nodules.¹ The etiology of ALHE is unknown; it is hypothesized that it is a vascular neoplasm or a lymphoproliferative disorder.

Coccidioidomycosis (CM) is a prevalent deep fungal infection endemic to the southwestern United States caused by Coccidioides immitis and Coccidioides posadasii. Infection can occur from direct inoculation through abrasions or direct trauma but usually occurs through the inhalation of spores and can result in a reactive rash (eg, Sweet syndrome, erythema nodosum, interstitial granulomatous dermatitis).² Coccidioidomycosis also can result in respiratory pneumonia and dissemination from pulmonary infection of the skin. As such, it is important to distinguish CM and its immunologically mediated eruptions for accurate diagnosis and treatment.

We report a novel case of ALHE as a reactive dermatologic presentation in a patient with CM.

Case Report

A 72-year-old woman presented to the dermatology clinic with itchy papules and plaques on the arms and legs of 17 years’ duration. Her medical history included coronary artery disease and hypercholesterolemia as well as a remote history of cutaneous marginal zone B-cell lymphoma of the nose, which was confirmed by histology and treated more than 10 years prior and has remained in remission for 6 years. Her current medications included aspirin, atorvastatin, lisinopril, and metoprolol succinate.

Our patient first presented to our dermatology clinic for itchy nodules and papules on the legs and arms. The patient previously had been seen by another dermatologist 2 months prior for the same condition. At that time, biopsies of the lesions were reported as prurigo nodules. Physical examination at the current presentation revealed round, pink to flesh-colored, raised papules and plaques scattered on the arms and legs (Figure 1). The differential diagnosis included lymphomatoid papulosis, cutaneous B-cell lymphoma, pseudolymphoma, cutaneous CM, and papular mucinosis.

Four-mm punch biopsies of the right proximal pretibial region and left knee region were taken and sent for histologic analysis, direct immunofluorescence testing, and tissue culture. Testing for atypical mycobacteria and deep fungal infection was negative; bacterial cultures and sensitivity testing were negative. Direct immunofluorescence testing was negative. Microscopic examination of material from the right proximal pretibial region showed widely dilated, variously shaped, large blood vessels in a multinodular pattern; the vessels also were surrounded by an inflammatory cell infiltrate containing eosinophils. Histologic findings were consistent with ALHE.

Subsequent biopsies were completed 2 weeks and 1 month from the initial presentation. Both histology reports—from 2 different histopathology laboratories—were consistent with ALHE (Figure 2). Additional work-up during the patient’s initial visit to our clinic for the rash included CM serologic testing, which demonstrated IgM and IgG antibodies. Subsequently, chest radiography revealed a 2.2×2.3-cm mass in the right lower lobe of the lung. Follow-up computed tomography 1 month later confirmed the nodule in the same area to be 2.3×2.1×1.8 cm.

The patient was referred to pulmonology and was treated for pulmonary CM with oral fluconazole 200 mg twice daily for 4 months. Initial treatment also included clobetasol cream 0.05% applied twice daily, which did not produce marked improvement in pruritus. Narrowband UVB phototherapy was attempted, but the patient could not complete the course because of travel time to the office; however, the patient’s ALHE improved considerably with the fluconazole treatment for pulmonary CM.

Oral doxycycline 100 mg twice daily was added to the fluconazole 2 months after her initial visit to our office, which kept the ALHE at bay and helped with the pruritus (Figure 3). Pulmonology and primary care comanaged the pulmonary CM with oral fluconazole 200 mg twice daily. Repeat serologic testing for CM was negative for IgG and IgM after 14 months since the initial visit to the office.

Comment

Pulmonary CM infection has varying dermatologic manifestations. A PubMed search of articles indexed for MEDLINE using the terms ALHE and coccidioidomycosis yielded no case reports; in fact, there have been few reported cases of ALHE at all. Notable conditions associated with ALHE include membranous nephropathy and arteriovenous malformations treated with corticosteroids and surgery, respectively.^3,4 Our case is a rare presentation of CM infection manifesting with ALHE. Following treatment and remission for our patient’s CM infection, the ALHE lesion decreased in size.

Standard treatment of uncomplicated CM involves azole antifungals, typically oral fluconazole or itraconazole 400 to 600 mg/d. In more severe cases (eg, immunocompromised patients) amphotericin B can be used.⁵ Our patient was treated with oral fluconazole 200 mg twice daily for 4 months.

In the literature, treatment via surgical excision, steroid injection, pulsed-dye laser therapy, and radiotherapy also has been described.^6-8 Antibiotics including clindamycin, doxycycline, and amoxicillin-clavulanate also have been shown to be effective.⁹

In our patient, ALHE improved when oral doxycycline 100 mg twice daily was added to the oral fluconazole. In fact, after 4 months of treatment, the CM infection and ALHE lesions both improved to a point at which the lesions were not visible. When those lesions recurred 15 months later, they responded with another course of doxycycline and fluconazole.

Upon recurrence, the patient was asked to have her care transferred to her pulmonologist, who then managed the fluconazole regimen. During the pulmonologist’s workup, no peripheral eosinophilia was found. This is important because eosinophils can be a marker for CM infection; in this case, however, the ALHE lesion was a reactive process to the infection. Classically known to play a reactive role in fungal infection, these white blood cells demonstrate reactivity to the environmental fungus Alternaria alternata by contact-dependent killing, utilizing β2 integrins and CD11b to recognize and adhere to β-glucan. Eosinophils react through contact-dependent killing, releasing cytotoxic granule proteins and proinflammatory mediators, and have been documented to occur in CM and Paracoccidioides brasiliensis infection, in which they deposit major basic protein on the organism.¹⁰ Most pertinent to our case with ALHE and CM is the ability of eosinophils to communicate with other immune cells. Eosinophils play a role in the active inflammation of CM through cytokine signaling, which may propagate formation of ALHE.

The function of eosinophils in ALHE is poorly understood; it is unclear whether they act as a primary driver of pathogenesis or are simply indicators of secondary infiltration or infection. Our review of the current literature suggests that eosinophils are unnecessary for progression of ALHE but might be involved at its onset. As reported, even monoclonal antibody therapy (eg, mepolizumab and benralizumab) that effectively depletes eosinophil levels by negating IL-5 signaling do not slow progression of ALHE.¹¹ Symptomatic changes are modest at best (ie, simply softening the ALHE nodules).

Our patient had no peripheral eosinophilia, suggesting that the onset of ALHE might not be caused by eosinophilia but a different inflammatory process—in this patient, by CM. Because peripheral eosinophilia was not seen in our patient, the presence of eosinophils in the ALHE lesion likely is unnecessary for its onset or progression but is a secondary process that exacerbates the lesion. The pathogenesis is unknown but could be directed toward lymphocytes and plasma cells, with eosinophils as part of the dynamic process.¹¹

Conclusion

Because reports of an association between CM and ALHE are limited, our case is distinguished by a unique clinical presentation of ALHE. When a patient is given a diagnosis of ALHE, it therefore is important to consider exposure to CM as a cause, especially in patients who reside in or travel to a region where CM is endemic.

Angiolymphoid hyperplasia with eosinophilia (ALHE) is a rare nodular unencapsulated mass that is characterized by benign anomalous vascular hyperplasia of epithelioidlike endothelial cells attached to dilated blood vessels. The mass is surrounded by lymphocytes and eosinophils that can present clinically as papules, plaques, or nodules.¹ The etiology of ALHE is unknown; it is hypothesized that it is a vascular neoplasm or a lymphoproliferative disorder.

Coccidioidomycosis (CM) is a prevalent deep fungal infection endemic to the southwestern United States caused by Coccidioides immitis and Coccidioides posadasii. Infection can occur from direct inoculation through abrasions or direct trauma but usually occurs through the inhalation of spores and can result in a reactive rash (eg, Sweet syndrome, erythema nodosum, interstitial granulomatous dermatitis).² Coccidioidomycosis also can result in respiratory pneumonia and dissemination from pulmonary infection of the skin. As such, it is important to distinguish CM and its immunologically mediated eruptions for accurate diagnosis and treatment.

We report a novel case of ALHE as a reactive dermatologic presentation in a patient with CM.

Case Report

A 72-year-old woman presented to the dermatology clinic with itchy papules and plaques on the arms and legs of 17 years’ duration. Her medical history included coronary artery disease and hypercholesterolemia as well as a remote history of cutaneous marginal zone B-cell lymphoma of the nose, which was confirmed by histology and treated more than 10 years prior and has remained in remission for 6 years. Her current medications included aspirin, atorvastatin, lisinopril, and metoprolol succinate.

Our patient first presented to our dermatology clinic for itchy nodules and papules on the legs and arms. The patient previously had been seen by another dermatologist 2 months prior for the same condition. At that time, biopsies of the lesions were reported as prurigo nodules. Physical examination at the current presentation revealed round, pink to flesh-colored, raised papules and plaques scattered on the arms and legs (Figure 1). The differential diagnosis included lymphomatoid papulosis, cutaneous B-cell lymphoma, pseudolymphoma, cutaneous CM, and papular mucinosis.

Four-mm punch biopsies of the right proximal pretibial region and left knee region were taken and sent for histologic analysis, direct immunofluorescence testing, and tissue culture. Testing for atypical mycobacteria and deep fungal infection was negative; bacterial cultures and sensitivity testing were negative. Direct immunofluorescence testing was negative. Microscopic examination of material from the right proximal pretibial region showed widely dilated, variously shaped, large blood vessels in a multinodular pattern; the vessels also were surrounded by an inflammatory cell infiltrate containing eosinophils. Histologic findings were consistent with ALHE.

Subsequent biopsies were completed 2 weeks and 1 month from the initial presentation. Both histology reports—from 2 different histopathology laboratories—were consistent with ALHE (Figure 2). Additional work-up during the patient’s initial visit to our clinic for the rash included CM serologic testing, which demonstrated IgM and IgG antibodies. Subsequently, chest radiography revealed a 2.2×2.3-cm mass in the right lower lobe of the lung. Follow-up computed tomography 1 month later confirmed the nodule in the same area to be 2.3×2.1×1.8 cm.

The patient was referred to pulmonology and was treated for pulmonary CM with oral fluconazole 200 mg twice daily for 4 months. Initial treatment also included clobetasol cream 0.05% applied twice daily, which did not produce marked improvement in pruritus. Narrowband UVB phototherapy was attempted, but the patient could not complete the course because of travel time to the office; however, the patient’s ALHE improved considerably with the fluconazole treatment for pulmonary CM.

Oral doxycycline 100 mg twice daily was added to the fluconazole 2 months after her initial visit to our office, which kept the ALHE at bay and helped with the pruritus (Figure 3). Pulmonology and primary care comanaged the pulmonary CM with oral fluconazole 200 mg twice daily. Repeat serologic testing for CM was negative for IgG and IgM after 14 months since the initial visit to the office.

Comment

Pulmonary CM infection has varying dermatologic manifestations. A PubMed search of articles indexed for MEDLINE using the terms ALHE and coccidioidomycosis yielded no case reports; in fact, there have been few reported cases of ALHE at all. Notable conditions associated with ALHE include membranous nephropathy and arteriovenous malformations treated with corticosteroids and surgery, respectively.^3,4 Our case is a rare presentation of CM infection manifesting with ALHE. Following treatment and remission for our patient’s CM infection, the ALHE lesion decreased in size.

Standard treatment of uncomplicated CM involves azole antifungals, typically oral fluconazole or itraconazole 400 to 600 mg/d. In more severe cases (eg, immunocompromised patients) amphotericin B can be used.⁵ Our patient was treated with oral fluconazole 200 mg twice daily for 4 months.

In the literature, treatment via surgical excision, steroid injection, pulsed-dye laser therapy, and radiotherapy also has been described.^6-8 Antibiotics including clindamycin, doxycycline, and amoxicillin-clavulanate also have been shown to be effective.⁹

In our patient, ALHE improved when oral doxycycline 100 mg twice daily was added to the oral fluconazole. In fact, after 4 months of treatment, the CM infection and ALHE lesions both improved to a point at which the lesions were not visible. When those lesions recurred 15 months later, they responded with another course of doxycycline and fluconazole.

Upon recurrence, the patient was asked to have her care transferred to her pulmonologist, who then managed the fluconazole regimen. During the pulmonologist’s workup, no peripheral eosinophilia was found. This is important because eosinophils can be a marker for CM infection; in this case, however, the ALHE lesion was a reactive process to the infection. Classically known to play a reactive role in fungal infection, these white blood cells demonstrate reactivity to the environmental fungus Alternaria alternata by contact-dependent killing, utilizing β2 integrins and CD11b to recognize and adhere to β-glucan. Eosinophils react through contact-dependent killing, releasing cytotoxic granule proteins and proinflammatory mediators, and have been documented to occur in CM and Paracoccidioides brasiliensis infection, in which they deposit major basic protein on the organism.¹⁰ Most pertinent to our case with ALHE and CM is the ability of eosinophils to communicate with other immune cells. Eosinophils play a role in the active inflammation of CM through cytokine signaling, which may propagate formation of ALHE.

The function of eosinophils in ALHE is poorly understood; it is unclear whether they act as a primary driver of pathogenesis or are simply indicators of secondary infiltration or infection. Our review of the current literature suggests that eosinophils are unnecessary for progression of ALHE but might be involved at its onset. As reported, even monoclonal antibody therapy (eg, mepolizumab and benralizumab) that effectively depletes eosinophil levels by negating IL-5 signaling do not slow progression of ALHE.¹¹ Symptomatic changes are modest at best (ie, simply softening the ALHE nodules).

Our patient had no peripheral eosinophilia, suggesting that the onset of ALHE might not be caused by eosinophilia but a different inflammatory process—in this patient, by CM. Because peripheral eosinophilia was not seen in our patient, the presence of eosinophils in the ALHE lesion likely is unnecessary for its onset or progression but is a secondary process that exacerbates the lesion. The pathogenesis is unknown but could be directed toward lymphocytes and plasma cells, with eosinophils as part of the dynamic process.¹¹

Conclusion

Because reports of an association between CM and ALHE are limited, our case is distinguished by a unique clinical presentation of ALHE. When a patient is given a diagnosis of ALHE, it therefore is important to consider exposure to CM as a cause, especially in patients who reside in or travel to a region where CM is endemic.

Angiolymphoid hyperplasia with eosinophilia (ALHE) is a rare nodular unencapsulated mass that is characterized by benign anomalous vascular hyperplasia of epithelioidlike endothelial cells attached to dilated blood vessels. The mass is surrounded by lymphocytes and eosinophils that can present clinically as papules, plaques, or nodules.¹ The etiology of ALHE is unknown; it is hypothesized that it is a vascular neoplasm or a lymphoproliferative disorder.

Coccidioidomycosis (CM) is a prevalent deep fungal infection endemic to the southwestern United States caused by Coccidioides immitis and Coccidioides posadasii. Infection can occur from direct inoculation through abrasions or direct trauma but usually occurs through the inhalation of spores and can result in a reactive rash (eg, Sweet syndrome, erythema nodosum, interstitial granulomatous dermatitis).² Coccidioidomycosis also can result in respiratory pneumonia and dissemination from pulmonary infection of the skin. As such, it is important to distinguish CM and its immunologically mediated eruptions for accurate diagnosis and treatment.

We report a novel case of ALHE as a reactive dermatologic presentation in a patient with CM.

Case Report

A 72-year-old woman presented to the dermatology clinic with itchy papules and plaques on the arms and legs of 17 years’ duration. Her medical history included coronary artery disease and hypercholesterolemia as well as a remote history of cutaneous marginal zone B-cell lymphoma of the nose, which was confirmed by histology and treated more than 10 years prior and has remained in remission for 6 years. Her current medications included aspirin, atorvastatin, lisinopril, and metoprolol succinate.

Our patient first presented to our dermatology clinic for itchy nodules and papules on the legs and arms. The patient previously had been seen by another dermatologist 2 months prior for the same condition. At that time, biopsies of the lesions were reported as prurigo nodules. Physical examination at the current presentation revealed round, pink to flesh-colored, raised papules and plaques scattered on the arms and legs (Figure 1). The differential diagnosis included lymphomatoid papulosis, cutaneous B-cell lymphoma, pseudolymphoma, cutaneous CM, and papular mucinosis.

Four-mm punch biopsies of the right proximal pretibial region and left knee region were taken and sent for histologic analysis, direct immunofluorescence testing, and tissue culture. Testing for atypical mycobacteria and deep fungal infection was negative; bacterial cultures and sensitivity testing were negative. Direct immunofluorescence testing was negative. Microscopic examination of material from the right proximal pretibial region showed widely dilated, variously shaped, large blood vessels in a multinodular pattern; the vessels also were surrounded by an inflammatory cell infiltrate containing eosinophils. Histologic findings were consistent with ALHE.

Subsequent biopsies were completed 2 weeks and 1 month from the initial presentation. Both histology reports—from 2 different histopathology laboratories—were consistent with ALHE (Figure 2). Additional work-up during the patient’s initial visit to our clinic for the rash included CM serologic testing, which demonstrated IgM and IgG antibodies. Subsequently, chest radiography revealed a 2.2×2.3-cm mass in the right lower lobe of the lung. Follow-up computed tomography 1 month later confirmed the nodule in the same area to be 2.3×2.1×1.8 cm.

The patient was referred to pulmonology and was treated for pulmonary CM with oral fluconazole 200 mg twice daily for 4 months. Initial treatment also included clobetasol cream 0.05% applied twice daily, which did not produce marked improvement in pruritus. Narrowband UVB phototherapy was attempted, but the patient could not complete the course because of travel time to the office; however, the patient’s ALHE improved considerably with the fluconazole treatment for pulmonary CM.

Oral doxycycline 100 mg twice daily was added to the fluconazole 2 months after her initial visit to our office, which kept the ALHE at bay and helped with the pruritus (Figure 3). Pulmonology and primary care comanaged the pulmonary CM with oral fluconazole 200 mg twice daily. Repeat serologic testing for CM was negative for IgG and IgM after 14 months since the initial visit to the office.

Comment

Pulmonary CM infection has varying dermatologic manifestations. A PubMed search of articles indexed for MEDLINE using the terms ALHE and coccidioidomycosis yielded no case reports; in fact, there have been few reported cases of ALHE at all. Notable conditions associated with ALHE include membranous nephropathy and arteriovenous malformations treated with corticosteroids and surgery, respectively.^3,4 Our case is a rare presentation of CM infection manifesting with ALHE. Following treatment and remission for our patient’s CM infection, the ALHE lesion decreased in size.

Standard treatment of uncomplicated CM involves azole antifungals, typically oral fluconazole or itraconazole 400 to 600 mg/d. In more severe cases (eg, immunocompromised patients) amphotericin B can be used.⁵ Our patient was treated with oral fluconazole 200 mg twice daily for 4 months.

In the literature, treatment via surgical excision, steroid injection, pulsed-dye laser therapy, and radiotherapy also has been described.^6-8 Antibiotics including clindamycin, doxycycline, and amoxicillin-clavulanate also have been shown to be effective.⁹

In our patient, ALHE improved when oral doxycycline 100 mg twice daily was added to the oral fluconazole. In fact, after 4 months of treatment, the CM infection and ALHE lesions both improved to a point at which the lesions were not visible. When those lesions recurred 15 months later, they responded with another course of doxycycline and fluconazole.

Upon recurrence, the patient was asked to have her care transferred to her pulmonologist, who then managed the fluconazole regimen. During the pulmonologist’s workup, no peripheral eosinophilia was found. This is important because eosinophils can be a marker for CM infection; in this case, however, the ALHE lesion was a reactive process to the infection. Classically known to play a reactive role in fungal infection, these white blood cells demonstrate reactivity to the environmental fungus Alternaria alternata by contact-dependent killing, utilizing β2 integrins and CD11b to recognize and adhere to β-glucan. Eosinophils react through contact-dependent killing, releasing cytotoxic granule proteins and proinflammatory mediators, and have been documented to occur in CM and Paracoccidioides brasiliensis infection, in which they deposit major basic protein on the organism.¹⁰ Most pertinent to our case with ALHE and CM is the ability of eosinophils to communicate with other immune cells. Eosinophils play a role in the active inflammation of CM through cytokine signaling, which may propagate formation of ALHE.

The function of eosinophils in ALHE is poorly understood; it is unclear whether they act as a primary driver of pathogenesis or are simply indicators of secondary infiltration or infection. Our review of the current literature suggests that eosinophils are unnecessary for progression of ALHE but might be involved at its onset. As reported, even monoclonal antibody therapy (eg, mepolizumab and benralizumab) that effectively depletes eosinophil levels by negating IL-5 signaling do not slow progression of ALHE.¹¹ Symptomatic changes are modest at best (ie, simply softening the ALHE nodules).

Our patient had no peripheral eosinophilia, suggesting that the onset of ALHE might not be caused by eosinophilia but a different inflammatory process—in this patient, by CM. Because peripheral eosinophilia was not seen in our patient, the presence of eosinophils in the ALHE lesion likely is unnecessary for its onset or progression but is a secondary process that exacerbates the lesion. The pathogenesis is unknown but could be directed toward lymphocytes and plasma cells, with eosinophils as part of the dynamic process.¹¹

Conclusion

Because reports of an association between CM and ALHE are limited, our case is distinguished by a unique clinical presentation of ALHE. When a patient is given a diagnosis of ALHE, it therefore is important to consider exposure to CM as a cause, especially in patients who reside in or travel to a region where CM is endemic.

New cases of COVID-19 in children were up again after 2 weeks of declines, and preliminary data suggest that hospitalizations may be on the rise as well.

There were almost 87,000 new pediatric cases reported during the week of Aug. 18-25, which was an increase of close to 9% over the previous week and a reversal of the previous 2-week decline that saw cases drop by nearly 18%, based on data collected by the American Academy of Pediatrics and the Children’s Hospital Association from state and territorial health departments.

A similar increase seems to be reflected by hospital-level data. The latest 7-day (Aug. 21-27) average is 305 new admissions with diagnosed COVID per day among children aged 0-17 years, compared with 290 per day for the week of Aug. 14-20, the Centers for Disease Control and Prevention reported, while also noting the potential for reporting delays in the most recent 7-day period.

Daily hospital admissions for COVID had been headed downward through the first half of August, falling from 0.46 per 100,000 population at the end of July to 0.40 on Aug. 19, the CDC said on its COVID Data Tracker. Since then, however, admissions have gone the other way, with the preliminary nature of the latest data suggesting that the numbers will be even higher as more hospitals report over the next few days.
 

Vaccine initiations continue to fall

Initiations among school-age children have fallen for 3 consecutive weeks since Aug. 3, when numbers receiving their first vaccinations reached late-summer highs for those aged 5-11 and 12-17 years. Children under age 5, included in the CDC data for the first time on Aug. 11 as separate groups – under 2 years and 2-4 years – have had vaccine initiations drop by 8.0% and 19.8% over the 2 following weeks, the CDC said.

Through their first 8 weeks of vaccine eligibility (June 19 to Aug. 15), 4.8% of children under 5 years of age had received a first vaccination and 1.0% were fully vaccinated. For the two other age groups (5-11 and 12-15) who became eligible after the very first emergency authorization back in 2020, the respective proportions were 25.0% and 16.0% (5-11) and 33.8% and 26.1% (12-15) through the first 8 weeks, according to CDC data.

New cases of COVID-19 in children were up again after 2 weeks of declines, and preliminary data suggest that hospitalizations may be on the rise as well.

There were almost 87,000 new pediatric cases reported during the week of Aug. 18-25, which was an increase of close to 9% over the previous week and a reversal of the previous 2-week decline that saw cases drop by nearly 18%, based on data collected by the American Academy of Pediatrics and the Children’s Hospital Association from state and territorial health departments.

A similar increase seems to be reflected by hospital-level data. The latest 7-day (Aug. 21-27) average is 305 new admissions with diagnosed COVID per day among children aged 0-17 years, compared with 290 per day for the week of Aug. 14-20, the Centers for Disease Control and Prevention reported, while also noting the potential for reporting delays in the most recent 7-day period.

Daily hospital admissions for COVID had been headed downward through the first half of August, falling from 0.46 per 100,000 population at the end of July to 0.40 on Aug. 19, the CDC said on its COVID Data Tracker. Since then, however, admissions have gone the other way, with the preliminary nature of the latest data suggesting that the numbers will be even higher as more hospitals report over the next few days.
 

Vaccine initiations continue to fall

Initiations among school-age children have fallen for 3 consecutive weeks since Aug. 3, when numbers receiving their first vaccinations reached late-summer highs for those aged 5-11 and 12-17 years. Children under age 5, included in the CDC data for the first time on Aug. 11 as separate groups – under 2 years and 2-4 years – have had vaccine initiations drop by 8.0% and 19.8% over the 2 following weeks, the CDC said.

Through their first 8 weeks of vaccine eligibility (June 19 to Aug. 15), 4.8% of children under 5 years of age had received a first vaccination and 1.0% were fully vaccinated. For the two other age groups (5-11 and 12-15) who became eligible after the very first emergency authorization back in 2020, the respective proportions were 25.0% and 16.0% (5-11) and 33.8% and 26.1% (12-15) through the first 8 weeks, according to CDC data.

New cases of COVID-19 in children were up again after 2 weeks of declines, and preliminary data suggest that hospitalizations may be on the rise as well.

There were almost 87,000 new pediatric cases reported during the week of Aug. 18-25, which was an increase of close to 9% over the previous week and a reversal of the previous 2-week decline that saw cases drop by nearly 18%, based on data collected by the American Academy of Pediatrics and the Children’s Hospital Association from state and territorial health departments.

A similar increase seems to be reflected by hospital-level data. The latest 7-day (Aug. 21-27) average is 305 new admissions with diagnosed COVID per day among children aged 0-17 years, compared with 290 per day for the week of Aug. 14-20, the Centers for Disease Control and Prevention reported, while also noting the potential for reporting delays in the most recent 7-day period.

Daily hospital admissions for COVID had been headed downward through the first half of August, falling from 0.46 per 100,000 population at the end of July to 0.40 on Aug. 19, the CDC said on its COVID Data Tracker. Since then, however, admissions have gone the other way, with the preliminary nature of the latest data suggesting that the numbers will be even higher as more hospitals report over the next few days.
 

Vaccine initiations continue to fall

Initiations among school-age children have fallen for 3 consecutive weeks since Aug. 3, when numbers receiving their first vaccinations reached late-summer highs for those aged 5-11 and 12-17 years. Children under age 5, included in the CDC data for the first time on Aug. 11 as separate groups – under 2 years and 2-4 years – have had vaccine initiations drop by 8.0% and 19.8% over the 2 following weeks, the CDC said.

Through their first 8 weeks of vaccine eligibility (June 19 to Aug. 15), 4.8% of children under 5 years of age had received a first vaccination and 1.0% were fully vaccinated. For the two other age groups (5-11 and 12-15) who became eligible after the very first emergency authorization back in 2020, the respective proportions were 25.0% and 16.0% (5-11) and 33.8% and 26.1% (12-15) through the first 8 weeks, according to CDC data.

PORTLAND, ORE. – If a child presents with pseudoporphyria – a bullous photodermatosis with the clinical and histological features of porphyria cutanea tarda (PCT) but with normal porphyrins – chlorophyll water could be the culprit.

Commercially available, green pigment–infused chlorophyll water is marketed with claims that it supports cancer prevention and digestive health, facilitates weight loss, and improves skin complexion. “It also absorbs light, so lo and behold, if your patient is photosensitive, they might get pseudoporphyria,” Robert Sidbury, MD, MPH, chief of the division of dermatology at Seattle Children’s Hospital, said at the annual meeting of the Pacific Dermatologic Association.

This was one of the clinical pearls he shared during his presentation.

Dr. Sidbury added that the risk of photosensitivity increases in children who are taking other medications such as doxycycline, methotrexate, or even naproxen. At least two cases of pseudoporphyria following self-medication with chlorophyll have been described in the dermatology literature.
 

Is it SSSS or SJS?

Another clinical pearl that Dr. Sidbury shared at the meeting related to staphylococcal scalded skin syndrome (SSSS), which causes reddening and blistering of the skin that makes it appear scalded or burned. To rule out Stevens-Johnson Syndrome (SJS) in a child who presents with such skin manifestations, he routinely performs the unscientific lollipop test, which he learned from Bernard A. “Buddy” Cohen, MD, professor of dermatology and pediatrics at Johns Hopkins University, Baltimore.

kiliweb/Open Food Facts/CC BY-SA 3.0

“If they eat it, it’s Staph scalded skin,” said Dr. Sidbury, who is also professor of pediatrics at the University of Washington, Seattle. “If they don’t, it’s likely SJS. It’s not the most specific test, but it’s easy to do, because there’s no mucous membrane involvement in Staph scalded skin.”

In a poster presented during the 2022 annual meeting of the Society for Pediatric Dermatology, Sarah Cipriano, MD, MPH, and colleagues at the University of Utah, Salt Lake City, retrospectively study 85 patients aged younger than 18 years diagnosed with SSSS between Jan. 1, 2010, and Aug. 21, 2021. They found that ancillary blood cultures and CSF cultures did not improve diagnostic precision in SSSS patients.

“They don’t add anything unless there’s an indication beyond the Staph scalded skin,” said Dr. Sidbury, who was not involved in the study. “The researchers also found that clindamycin does not improve outcomes in these patients, so avoid using it.” Instead, a first-generation cephalosporin is indicated, and an alternate diagnosis should be considered if the patient does not improve within 48 hours.

Dr. Sidbury disclosed that he has conducted research for Regeneron, Galderma, and UCB. He is also an adviser for Leo Pharmaceuticals and a speaker for Biersdorf.

PORTLAND, ORE. – If a child presents with pseudoporphyria – a bullous photodermatosis with the clinical and histological features of porphyria cutanea tarda (PCT) but with normal porphyrins – chlorophyll water could be the culprit.

Commercially available, green pigment–infused chlorophyll water is marketed with claims that it supports cancer prevention and digestive health, facilitates weight loss, and improves skin complexion. “It also absorbs light, so lo and behold, if your patient is photosensitive, they might get pseudoporphyria,” Robert Sidbury, MD, MPH, chief of the division of dermatology at Seattle Children’s Hospital, said at the annual meeting of the Pacific Dermatologic Association.

This was one of the clinical pearls he shared during his presentation.

Dr. Sidbury added that the risk of photosensitivity increases in children who are taking other medications such as doxycycline, methotrexate, or even naproxen. At least two cases of pseudoporphyria following self-medication with chlorophyll have been described in the dermatology literature.
 

Is it SSSS or SJS?

Another clinical pearl that Dr. Sidbury shared at the meeting related to staphylococcal scalded skin syndrome (SSSS), which causes reddening and blistering of the skin that makes it appear scalded or burned. To rule out Stevens-Johnson Syndrome (SJS) in a child who presents with such skin manifestations, he routinely performs the unscientific lollipop test, which he learned from Bernard A. “Buddy” Cohen, MD, professor of dermatology and pediatrics at Johns Hopkins University, Baltimore.

kiliweb/Open Food Facts/CC BY-SA 3.0

“If they eat it, it’s Staph scalded skin,” said Dr. Sidbury, who is also professor of pediatrics at the University of Washington, Seattle. “If they don’t, it’s likely SJS. It’s not the most specific test, but it’s easy to do, because there’s no mucous membrane involvement in Staph scalded skin.”

In a poster presented during the 2022 annual meeting of the Society for Pediatric Dermatology, Sarah Cipriano, MD, MPH, and colleagues at the University of Utah, Salt Lake City, retrospectively study 85 patients aged younger than 18 years diagnosed with SSSS between Jan. 1, 2010, and Aug. 21, 2021. They found that ancillary blood cultures and CSF cultures did not improve diagnostic precision in SSSS patients.

“They don’t add anything unless there’s an indication beyond the Staph scalded skin,” said Dr. Sidbury, who was not involved in the study. “The researchers also found that clindamycin does not improve outcomes in these patients, so avoid using it.” Instead, a first-generation cephalosporin is indicated, and an alternate diagnosis should be considered if the patient does not improve within 48 hours.

Dr. Sidbury disclosed that he has conducted research for Regeneron, Galderma, and UCB. He is also an adviser for Leo Pharmaceuticals and a speaker for Biersdorf.

PORTLAND, ORE. – If a child presents with pseudoporphyria – a bullous photodermatosis with the clinical and histological features of porphyria cutanea tarda (PCT) but with normal porphyrins – chlorophyll water could be the culprit.

Commercially available, green pigment–infused chlorophyll water is marketed with claims that it supports cancer prevention and digestive health, facilitates weight loss, and improves skin complexion. “It also absorbs light, so lo and behold, if your patient is photosensitive, they might get pseudoporphyria,” Robert Sidbury, MD, MPH, chief of the division of dermatology at Seattle Children’s Hospital, said at the annual meeting of the Pacific Dermatologic Association.

This was one of the clinical pearls he shared during his presentation.

Dr. Sidbury added that the risk of photosensitivity increases in children who are taking other medications such as doxycycline, methotrexate, or even naproxen. At least two cases of pseudoporphyria following self-medication with chlorophyll have been described in the dermatology literature.
 

Is it SSSS or SJS?

Another clinical pearl that Dr. Sidbury shared at the meeting related to staphylococcal scalded skin syndrome (SSSS), which causes reddening and blistering of the skin that makes it appear scalded or burned. To rule out Stevens-Johnson Syndrome (SJS) in a child who presents with such skin manifestations, he routinely performs the unscientific lollipop test, which he learned from Bernard A. “Buddy” Cohen, MD, professor of dermatology and pediatrics at Johns Hopkins University, Baltimore.

kiliweb/Open Food Facts/CC BY-SA 3.0

“If they eat it, it’s Staph scalded skin,” said Dr. Sidbury, who is also professor of pediatrics at the University of Washington, Seattle. “If they don’t, it’s likely SJS. It’s not the most specific test, but it’s easy to do, because there’s no mucous membrane involvement in Staph scalded skin.”

In a poster presented during the 2022 annual meeting of the Society for Pediatric Dermatology, Sarah Cipriano, MD, MPH, and colleagues at the University of Utah, Salt Lake City, retrospectively study 85 patients aged younger than 18 years diagnosed with SSSS between Jan. 1, 2010, and Aug. 21, 2021. They found that ancillary blood cultures and CSF cultures did not improve diagnostic precision in SSSS patients.

“They don’t add anything unless there’s an indication beyond the Staph scalded skin,” said Dr. Sidbury, who was not involved in the study. “The researchers also found that clindamycin does not improve outcomes in these patients, so avoid using it.” Instead, a first-generation cephalosporin is indicated, and an alternate diagnosis should be considered if the patient does not improve within 48 hours.

Dr. Sidbury disclosed that he has conducted research for Regeneron, Galderma, and UCB. He is also an adviser for Leo Pharmaceuticals and a speaker for Biersdorf.

A new study in The Lancet Rheumatology examines the strength and duration of SARS-CoV-2 vaccine–induced immunoglobulin-G antibody responses over time for patients with a variety of autoimmune diseases, compared with healthy controls.

The presence of humoral antibodies to SARS-CoV-2 has been shown to correlate with protection against COVID infection. But for patients with immune-mediated inflammatory diseases (IMIDs), host response to COVID infection or to vaccination is affected by the immune dysfunction imposed by the IMID and by the use of immune-modulating drugs to treat it.

This new study finds a weaker – as shown previously – and less sustained immune response to SARS-CoV-2 vaccines in patients with a variety of IMIDs, including rheumatoid arthritis, spondyloarthritis, psoriasis, inflammatory bowel diseases, and other systemic autoimmune diseases such as lupus. It also points toward the possibility of adjusting treatment and vaccination schedules and strategies for these patients based on their antibody levels, among other factors, to preserve best protection against severe COVID.

Kmatta/Moment/Getty Images

“It is important to assess immune response in these patients to see if they still have protection against severe COVID infection,” said lead author David Simon, MD, senior clinical scientist in clinical immunology and rheumatology at University Hospital Erlangen (Germany). “We know that antibody response is an immune correlate. Therefore, it is important to see how large and durable the immune response is to the coronavirus vaccine in these IMID patients, and whether specific drugs or therapies have negative effects on their immune response.”
 

What was studied?

For this large prospective cohort study, researchers registered 5076 coronavirus-vaccinated individuals. They analyzed serum samples obtained between December 15, 2020, and December 1, 2021, from 2,535 patients diagnosed with IMIDs and participating in a prospective coronavirus study program at the Deutsches Zentrum Immuntherapie in Erlangen. The IMID patients had a mean age of 55.0 years, and 58.9% were women.

A healthy control group of 1,198 individuals without IMID who had a mean age of 40.7 years, including 53.8% men, was also recruited for the analysis. All approved coronavirus vaccines were included, following standard vaccination schedules. Antibody response was measured over time by an enzyme-linked immunosorbent assay from 8 weeks after first vaccination to week 40.

Among the findings, the healthy controls had higher postvaccine antibody levels than did those with IMIDs. But the majority of vaccinated patients with IMID were able to build up a humoral immune response to SARS-CoV-2. Patients who were taking B-cell inhibitors like rituximab (Rituxan, Genentech; and biosimilars) and T-cell inhibitors like abatacept (Orencia, Bristol Myers Squibb) for IMIDs had significantly poorer antibody response.

Greater age and the use of combination therapies for IMIDs, compared with monotherapy, further reduced immune response to the vaccine. In terms of vaccination modality, messenger RNA–based vaccines induced higher antibody levels than did vector-based vaccines. The researchers noted that patients with IMID who were given a third vaccine dose could actually catch up well with the antibody responses observed in healthy controls.

“We looked at whether different IMIDs had a different humoral response, and we also assessed if there are effects from different therapeutic strategies,” Dr. Simon explained. “It doesn’t matter so much what kind of IMID patients have; much more important is the specific drug treatment and its impact on their antibody response.” Some participants were advised to briefly stop taking some immunosuppressive treatments before or after vaccination.

One of Dr. Simon’s coauthors, statistician and rheumatologist Koray Tascilar, MD, added, “This research is important because we looked not only at who responded less, which has been previously established, but who are at greater risk of losing their immune response, and how quickly.”
 

Need to take care

“Most treatments we as rheumatologists give to our patients don’t affect their SARS-CoV-2 humoral response,” Dr. Simon said. “However, there are specific drugs that are associated with lower antibody response. With respect to those drugs, we have to be more careful.”

It is important to be able to tell patients which drugs are safe and won’t have a negative impact on their immune response to vaccinations, Dr. Tascilar said. “But it would be too strong to say we’re ready to choose therapies based on their potential impact on protection against COVID. Yes, there is a risk from catching COVID, but we need to balance that risk with the risk of not giving patients the medications that are necessary to treat their rheumatologic condition.”

These diseases are serious, sometimes life-threatening. “We might think of strategies for how to mitigate the risk of underprotection from COVID that is brought about by these treatments,” he said. For example, offering boosters sooner or more frequently, or prophylactically treating with monoclonal antibodies.

“This study, along other recent studies, has found that antibody levels in patients with immune-mediated diseases wane more rapidly than in healthy controls, and this is especially true of those on medications that interfere with the B and T cells and anticytokine therapies,” Rebecca Haberman, MD, assistant professor, division of rheumatology, New York University Langone Health, noted in an email to this news organization.

“While there is no known antibody level that specifically correlates with clinical protection, and each patient needs to be thought of individually, these findings support the use of supplemental booster dosing in patients with immune-mediated inflammatory diseases,” Dr. Haberman said, adding that her own research in this area has shown similar results.

“As a rheumatologist, I would be more likely to encourage my patients – especially those on immunomodulatory medications – to get boosted.”

Dr. Tascilar said his study does not directly answer the question of whether an earlier booster shot would be an effective strategy for patients with IMID. “In our department, we have an early boosting strategy, based on level of immune response.” But the decision of revaccination or not, and when, is based on a number of factors, not only on the level of antibodies. “It’s just part of the instruments we are using.”

The study was supported by the Deutsche Forschungsgemeinschaft. Dr. Simon and Dr. Tascilar declared no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A new study in The Lancet Rheumatology examines the strength and duration of SARS-CoV-2 vaccine–induced immunoglobulin-G antibody responses over time for patients with a variety of autoimmune diseases, compared with healthy controls.

The presence of humoral antibodies to SARS-CoV-2 has been shown to correlate with protection against COVID infection. But for patients with immune-mediated inflammatory diseases (IMIDs), host response to COVID infection or to vaccination is affected by the immune dysfunction imposed by the IMID and by the use of immune-modulating drugs to treat it.

This new study finds a weaker – as shown previously – and less sustained immune response to SARS-CoV-2 vaccines in patients with a variety of IMIDs, including rheumatoid arthritis, spondyloarthritis, psoriasis, inflammatory bowel diseases, and other systemic autoimmune diseases such as lupus. It also points toward the possibility of adjusting treatment and vaccination schedules and strategies for these patients based on their antibody levels, among other factors, to preserve best protection against severe COVID.

Kmatta/Moment/Getty Images

“It is important to assess immune response in these patients to see if they still have protection against severe COVID infection,” said lead author David Simon, MD, senior clinical scientist in clinical immunology and rheumatology at University Hospital Erlangen (Germany). “We know that antibody response is an immune correlate. Therefore, it is important to see how large and durable the immune response is to the coronavirus vaccine in these IMID patients, and whether specific drugs or therapies have negative effects on their immune response.”
 

What was studied?

For this large prospective cohort study, researchers registered 5076 coronavirus-vaccinated individuals. They analyzed serum samples obtained between December 15, 2020, and December 1, 2021, from 2,535 patients diagnosed with IMIDs and participating in a prospective coronavirus study program at the Deutsches Zentrum Immuntherapie in Erlangen. The IMID patients had a mean age of 55.0 years, and 58.9% were women.

A healthy control group of 1,198 individuals without IMID who had a mean age of 40.7 years, including 53.8% men, was also recruited for the analysis. All approved coronavirus vaccines were included, following standard vaccination schedules. Antibody response was measured over time by an enzyme-linked immunosorbent assay from 8 weeks after first vaccination to week 40.

Among the findings, the healthy controls had higher postvaccine antibody levels than did those with IMIDs. But the majority of vaccinated patients with IMID were able to build up a humoral immune response to SARS-CoV-2. Patients who were taking B-cell inhibitors like rituximab (Rituxan, Genentech; and biosimilars) and T-cell inhibitors like abatacept (Orencia, Bristol Myers Squibb) for IMIDs had significantly poorer antibody response.

Greater age and the use of combination therapies for IMIDs, compared with monotherapy, further reduced immune response to the vaccine. In terms of vaccination modality, messenger RNA–based vaccines induced higher antibody levels than did vector-based vaccines. The researchers noted that patients with IMID who were given a third vaccine dose could actually catch up well with the antibody responses observed in healthy controls.

“We looked at whether different IMIDs had a different humoral response, and we also assessed if there are effects from different therapeutic strategies,” Dr. Simon explained. “It doesn’t matter so much what kind of IMID patients have; much more important is the specific drug treatment and its impact on their antibody response.” Some participants were advised to briefly stop taking some immunosuppressive treatments before or after vaccination.

One of Dr. Simon’s coauthors, statistician and rheumatologist Koray Tascilar, MD, added, “This research is important because we looked not only at who responded less, which has been previously established, but who are at greater risk of losing their immune response, and how quickly.”
 

Need to take care

“Most treatments we as rheumatologists give to our patients don’t affect their SARS-CoV-2 humoral response,” Dr. Simon said. “However, there are specific drugs that are associated with lower antibody response. With respect to those drugs, we have to be more careful.”

It is important to be able to tell patients which drugs are safe and won’t have a negative impact on their immune response to vaccinations, Dr. Tascilar said. “But it would be too strong to say we’re ready to choose therapies based on their potential impact on protection against COVID. Yes, there is a risk from catching COVID, but we need to balance that risk with the risk of not giving patients the medications that are necessary to treat their rheumatologic condition.”

These diseases are serious, sometimes life-threatening. “We might think of strategies for how to mitigate the risk of underprotection from COVID that is brought about by these treatments,” he said. For example, offering boosters sooner or more frequently, or prophylactically treating with monoclonal antibodies.

“This study, along other recent studies, has found that antibody levels in patients with immune-mediated diseases wane more rapidly than in healthy controls, and this is especially true of those on medications that interfere with the B and T cells and anticytokine therapies,” Rebecca Haberman, MD, assistant professor, division of rheumatology, New York University Langone Health, noted in an email to this news organization.

“While there is no known antibody level that specifically correlates with clinical protection, and each patient needs to be thought of individually, these findings support the use of supplemental booster dosing in patients with immune-mediated inflammatory diseases,” Dr. Haberman said, adding that her own research in this area has shown similar results.

“As a rheumatologist, I would be more likely to encourage my patients – especially those on immunomodulatory medications – to get boosted.”

Dr. Tascilar said his study does not directly answer the question of whether an earlier booster shot would be an effective strategy for patients with IMID. “In our department, we have an early boosting strategy, based on level of immune response.” But the decision of revaccination or not, and when, is based on a number of factors, not only on the level of antibodies. “It’s just part of the instruments we are using.”

The study was supported by the Deutsche Forschungsgemeinschaft. Dr. Simon and Dr. Tascilar declared no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A new study in The Lancet Rheumatology examines the strength and duration of SARS-CoV-2 vaccine–induced immunoglobulin-G antibody responses over time for patients with a variety of autoimmune diseases, compared with healthy controls.

The presence of humoral antibodies to SARS-CoV-2 has been shown to correlate with protection against COVID infection. But for patients with immune-mediated inflammatory diseases (IMIDs), host response to COVID infection or to vaccination is affected by the immune dysfunction imposed by the IMID and by the use of immune-modulating drugs to treat it.

This new study finds a weaker – as shown previously – and less sustained immune response to SARS-CoV-2 vaccines in patients with a variety of IMIDs, including rheumatoid arthritis, spondyloarthritis, psoriasis, inflammatory bowel diseases, and other systemic autoimmune diseases such as lupus. It also points toward the possibility of adjusting treatment and vaccination schedules and strategies for these patients based on their antibody levels, among other factors, to preserve best protection against severe COVID.

Kmatta/Moment/Getty Images

“It is important to assess immune response in these patients to see if they still have protection against severe COVID infection,” said lead author David Simon, MD, senior clinical scientist in clinical immunology and rheumatology at University Hospital Erlangen (Germany). “We know that antibody response is an immune correlate. Therefore, it is important to see how large and durable the immune response is to the coronavirus vaccine in these IMID patients, and whether specific drugs or therapies have negative effects on their immune response.”
 

What was studied?

For this large prospective cohort study, researchers registered 5076 coronavirus-vaccinated individuals. They analyzed serum samples obtained between December 15, 2020, and December 1, 2021, from 2,535 patients diagnosed with IMIDs and participating in a prospective coronavirus study program at the Deutsches Zentrum Immuntherapie in Erlangen. The IMID patients had a mean age of 55.0 years, and 58.9% were women.

A healthy control group of 1,198 individuals without IMID who had a mean age of 40.7 years, including 53.8% men, was also recruited for the analysis. All approved coronavirus vaccines were included, following standard vaccination schedules. Antibody response was measured over time by an enzyme-linked immunosorbent assay from 8 weeks after first vaccination to week 40.

Among the findings, the healthy controls had higher postvaccine antibody levels than did those with IMIDs. But the majority of vaccinated patients with IMID were able to build up a humoral immune response to SARS-CoV-2. Patients who were taking B-cell inhibitors like rituximab (Rituxan, Genentech; and biosimilars) and T-cell inhibitors like abatacept (Orencia, Bristol Myers Squibb) for IMIDs had significantly poorer antibody response.

Greater age and the use of combination therapies for IMIDs, compared with monotherapy, further reduced immune response to the vaccine. In terms of vaccination modality, messenger RNA–based vaccines induced higher antibody levels than did vector-based vaccines. The researchers noted that patients with IMID who were given a third vaccine dose could actually catch up well with the antibody responses observed in healthy controls.

“We looked at whether different IMIDs had a different humoral response, and we also assessed if there are effects from different therapeutic strategies,” Dr. Simon explained. “It doesn’t matter so much what kind of IMID patients have; much more important is the specific drug treatment and its impact on their antibody response.” Some participants were advised to briefly stop taking some immunosuppressive treatments before or after vaccination.

One of Dr. Simon’s coauthors, statistician and rheumatologist Koray Tascilar, MD, added, “This research is important because we looked not only at who responded less, which has been previously established, but who are at greater risk of losing their immune response, and how quickly.”
 

Need to take care

“Most treatments we as rheumatologists give to our patients don’t affect their SARS-CoV-2 humoral response,” Dr. Simon said. “However, there are specific drugs that are associated with lower antibody response. With respect to those drugs, we have to be more careful.”

It is important to be able to tell patients which drugs are safe and won’t have a negative impact on their immune response to vaccinations, Dr. Tascilar said. “But it would be too strong to say we’re ready to choose therapies based on their potential impact on protection against COVID. Yes, there is a risk from catching COVID, but we need to balance that risk with the risk of not giving patients the medications that are necessary to treat their rheumatologic condition.”

These diseases are serious, sometimes life-threatening. “We might think of strategies for how to mitigate the risk of underprotection from COVID that is brought about by these treatments,” he said. For example, offering boosters sooner or more frequently, or prophylactically treating with monoclonal antibodies.

“This study, along other recent studies, has found that antibody levels in patients with immune-mediated diseases wane more rapidly than in healthy controls, and this is especially true of those on medications that interfere with the B and T cells and anticytokine therapies,” Rebecca Haberman, MD, assistant professor, division of rheumatology, New York University Langone Health, noted in an email to this news organization.

“While there is no known antibody level that specifically correlates with clinical protection, and each patient needs to be thought of individually, these findings support the use of supplemental booster dosing in patients with immune-mediated inflammatory diseases,” Dr. Haberman said, adding that her own research in this area has shown similar results.

“As a rheumatologist, I would be more likely to encourage my patients – especially those on immunomodulatory medications – to get boosted.”

Dr. Tascilar said his study does not directly answer the question of whether an earlier booster shot would be an effective strategy for patients with IMID. “In our department, we have an early boosting strategy, based on level of immune response.” But the decision of revaccination or not, and when, is based on a number of factors, not only on the level of antibodies. “It’s just part of the instruments we are using.”

The study was supported by the Deutsche Forschungsgemeinschaft. Dr. Simon and Dr. Tascilar declared no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Respiratory syncytial virus (RSV) is the leading cause of U.S. infant hospitalizations overall and across population subgroups, new data published in the Journal of Infectious Diseases confirm.

Acute bronchiolitis caused by RSV accounted for 9.6% (95% confidence interval, 9.4%-9.9%) and 9.3% (95% CI, 9.0%-9.6%) of total infant hospitalizations from January 2009 to September 2015 and October 2015 to December 2019, respectively.
 

Journal issue includes 14 RSV studies

The latest issue of the journal includes a special section with results from 14 studies related to the widespread, easy-to-catch virus, highlighting the urgency of finding a solution for all infants.

In one study, authors led by Mina Suh, MPH, with EpidStrategies, a division of ToxStrategies in Rockville, Md., reported that, in children under the age of 5 years in the United States, RSV caused 58,000 annual hospitalizations and from 100 to 500 annual deaths from 2009 to 2019 (the latest year data were available).

Globally, in 2015, among infants younger than 6 months, an estimated 1.4 million hospital admissions and 27,300 in-hospital deaths were attributed to RSV lower respiratory tract infection (LRTI).

The researchers used the largest publicly available, all-payer database in the United States – the National (Nationwide) Inpatient Sample – to describe the leading causes of infant hospitalizations.

The authors noted that, because clinicians don’t routinely perform lab tests for RSV, the true health care burden is likely higher and its public health impact greater than these numbers show.

Immunization candidates advance

There are no preventative options currently available to substantially cut RSV infections in all infants, though immunization candidates are advancing, showing safety and efficacy in clinical trials.

Palivizumab is currently the only available option in the United States to prevent RSV and is recommended only for a small group of infants with particular forms of heart or lung disease and those born prematurely at 29 weeks’ gestational age. Further, palivizumab has to be given monthly throughout the RSV season.

Another of the studies in the journal supplement concluded that a universal immunization strategy with one of the candidates, nirsevimab (Sanofi, AstraZeneca), an investigational long-acting monoclonal antibody, could substantially reduce the health burden and economic burden for U.S. infants in their first RSV season.

The researchers, led by Alexia Kieffer, MSc, MPH, with Sanofi, used static decision-analytic modeling for the estimates. Modeled RSV-related outcomes included primary care and ED visits, hospitalizations, including ICU admission and mechanical ventilations, and RSV-related deaths.

“The results of this model suggested that the use of nirsevimab in all infants could reduce health events by 55% and the overall costs to the payer by 49%,” the authors of the study wrote.

According to the study, universal immunization of all infants with nirsevimab is expected to reduce 290,174 RSV-related medically attended LRTI (MALRTI), 24,986 hospitalizations, and cut $612 million in costs to the health care system.

The authors wrote: “While this reduction would be driven by term infants, who account for most of the RSV-MALRTI burden; all infants, including palivizumab-eligible and preterm infants who suffer from significantly higher rates of disease, would benefit from this immunization strategy.”
 

Excitement for another option

Jörn-Hendrik Weitkamp, MD, professor of pediatrics and director for patient-oriented research at Monroe Carell Jr. Children’s Hospital at Vanderbilt University, Nashville, Tenn., said in an interview there is much excitement in the field for nirsevimab as it has significant advantages over palivizumab.

RSV “is a huge burden to the children, the families, the hospitals, and the medical system,” he said.

Ideally there would be a vaccine to offer the best protection, he noted.

“People have spent their lives, their careers trying to develop a vaccine for RSV,” he said, but that has been elusive for more than 60 years. Therefore, passive immunization is the best of the current options, he says, and nirsevimab “seems to be very effective.”

What’s not clear, Dr. Weitkamp said, is how much nirsevimab will cost as it is not yet approved by the Food and Drug Administration. However, it has the great advantage of being given only once before the season starts instead of monthly (as required for palivizumab) through the season, “which is painful, inconvenient, and traumatizing. We limit that one to the children at highest risk.”

Rolling out an infant nirsevimab program would likely vary by geographic region, Ms. Kieffer and colleagues said, to help ensure infants are protected during the peak of their region’s RSV season.

The journal’s RSV supplement was supported by Sanofi and AstraZeneca. The studies by Ms. Suh and colleagues and Ms. Kieffer and colleagues were supported by AstraZeneca and Sanofi. Ms. Suh and several coauthors are employees of EpidStrategies. One coauthor is an employee of Sanofi and may hold shares and/or stock options in the company. Ms. Kieffer and several coauthors are employees of Sanofi and may hold shares and/or stock options in the company. Dr. Weitkamp reported no relevant financial relationships.

Respiratory syncytial virus (RSV) is the leading cause of U.S. infant hospitalizations overall and across population subgroups, new data published in the Journal of Infectious Diseases confirm.

Acute bronchiolitis caused by RSV accounted for 9.6% (95% confidence interval, 9.4%-9.9%) and 9.3% (95% CI, 9.0%-9.6%) of total infant hospitalizations from January 2009 to September 2015 and October 2015 to December 2019, respectively.
 

Journal issue includes 14 RSV studies

The latest issue of the journal includes a special section with results from 14 studies related to the widespread, easy-to-catch virus, highlighting the urgency of finding a solution for all infants.

In one study, authors led by Mina Suh, MPH, with EpidStrategies, a division of ToxStrategies in Rockville, Md., reported that, in children under the age of 5 years in the United States, RSV caused 58,000 annual hospitalizations and from 100 to 500 annual deaths from 2009 to 2019 (the latest year data were available).

Globally, in 2015, among infants younger than 6 months, an estimated 1.4 million hospital admissions and 27,300 in-hospital deaths were attributed to RSV lower respiratory tract infection (LRTI).

The researchers used the largest publicly available, all-payer database in the United States – the National (Nationwide) Inpatient Sample – to describe the leading causes of infant hospitalizations.

The authors noted that, because clinicians don’t routinely perform lab tests for RSV, the true health care burden is likely higher and its public health impact greater than these numbers show.

Immunization candidates advance

There are no preventative options currently available to substantially cut RSV infections in all infants, though immunization candidates are advancing, showing safety and efficacy in clinical trials.

Palivizumab is currently the only available option in the United States to prevent RSV and is recommended only for a small group of infants with particular forms of heart or lung disease and those born prematurely at 29 weeks’ gestational age. Further, palivizumab has to be given monthly throughout the RSV season.

Another of the studies in the journal supplement concluded that a universal immunization strategy with one of the candidates, nirsevimab (Sanofi, AstraZeneca), an investigational long-acting monoclonal antibody, could substantially reduce the health burden and economic burden for U.S. infants in their first RSV season.

The researchers, led by Alexia Kieffer, MSc, MPH, with Sanofi, used static decision-analytic modeling for the estimates. Modeled RSV-related outcomes included primary care and ED visits, hospitalizations, including ICU admission and mechanical ventilations, and RSV-related deaths.

“The results of this model suggested that the use of nirsevimab in all infants could reduce health events by 55% and the overall costs to the payer by 49%,” the authors of the study wrote.

According to the study, universal immunization of all infants with nirsevimab is expected to reduce 290,174 RSV-related medically attended LRTI (MALRTI), 24,986 hospitalizations, and cut $612 million in costs to the health care system.

The authors wrote: “While this reduction would be driven by term infants, who account for most of the RSV-MALRTI burden; all infants, including palivizumab-eligible and preterm infants who suffer from significantly higher rates of disease, would benefit from this immunization strategy.”
 

Excitement for another option

Jörn-Hendrik Weitkamp, MD, professor of pediatrics and director for patient-oriented research at Monroe Carell Jr. Children’s Hospital at Vanderbilt University, Nashville, Tenn., said in an interview there is much excitement in the field for nirsevimab as it has significant advantages over palivizumab.

RSV “is a huge burden to the children, the families, the hospitals, and the medical system,” he said.

Ideally there would be a vaccine to offer the best protection, he noted.

“People have spent their lives, their careers trying to develop a vaccine for RSV,” he said, but that has been elusive for more than 60 years. Therefore, passive immunization is the best of the current options, he says, and nirsevimab “seems to be very effective.”

What’s not clear, Dr. Weitkamp said, is how much nirsevimab will cost as it is not yet approved by the Food and Drug Administration. However, it has the great advantage of being given only once before the season starts instead of monthly (as required for palivizumab) through the season, “which is painful, inconvenient, and traumatizing. We limit that one to the children at highest risk.”

Rolling out an infant nirsevimab program would likely vary by geographic region, Ms. Kieffer and colleagues said, to help ensure infants are protected during the peak of their region’s RSV season.

The journal’s RSV supplement was supported by Sanofi and AstraZeneca. The studies by Ms. Suh and colleagues and Ms. Kieffer and colleagues were supported by AstraZeneca and Sanofi. Ms. Suh and several coauthors are employees of EpidStrategies. One coauthor is an employee of Sanofi and may hold shares and/or stock options in the company. Ms. Kieffer and several coauthors are employees of Sanofi and may hold shares and/or stock options in the company. Dr. Weitkamp reported no relevant financial relationships.

Respiratory syncytial virus (RSV) is the leading cause of U.S. infant hospitalizations overall and across population subgroups, new data published in the Journal of Infectious Diseases confirm.

Acute bronchiolitis caused by RSV accounted for 9.6% (95% confidence interval, 9.4%-9.9%) and 9.3% (95% CI, 9.0%-9.6%) of total infant hospitalizations from January 2009 to September 2015 and October 2015 to December 2019, respectively.
 

Journal issue includes 14 RSV studies

The latest issue of the journal includes a special section with results from 14 studies related to the widespread, easy-to-catch virus, highlighting the urgency of finding a solution for all infants.

In one study, authors led by Mina Suh, MPH, with EpidStrategies, a division of ToxStrategies in Rockville, Md., reported that, in children under the age of 5 years in the United States, RSV caused 58,000 annual hospitalizations and from 100 to 500 annual deaths from 2009 to 2019 (the latest year data were available).

Globally, in 2015, among infants younger than 6 months, an estimated 1.4 million hospital admissions and 27,300 in-hospital deaths were attributed to RSV lower respiratory tract infection (LRTI).

The researchers used the largest publicly available, all-payer database in the United States – the National (Nationwide) Inpatient Sample – to describe the leading causes of infant hospitalizations.

The authors noted that, because clinicians don’t routinely perform lab tests for RSV, the true health care burden is likely higher and its public health impact greater than these numbers show.

Immunization candidates advance

There are no preventative options currently available to substantially cut RSV infections in all infants, though immunization candidates are advancing, showing safety and efficacy in clinical trials.

Palivizumab is currently the only available option in the United States to prevent RSV and is recommended only for a small group of infants with particular forms of heart or lung disease and those born prematurely at 29 weeks’ gestational age. Further, palivizumab has to be given monthly throughout the RSV season.

Another of the studies in the journal supplement concluded that a universal immunization strategy with one of the candidates, nirsevimab (Sanofi, AstraZeneca), an investigational long-acting monoclonal antibody, could substantially reduce the health burden and economic burden for U.S. infants in their first RSV season.

The researchers, led by Alexia Kieffer, MSc, MPH, with Sanofi, used static decision-analytic modeling for the estimates. Modeled RSV-related outcomes included primary care and ED visits, hospitalizations, including ICU admission and mechanical ventilations, and RSV-related deaths.

“The results of this model suggested that the use of nirsevimab in all infants could reduce health events by 55% and the overall costs to the payer by 49%,” the authors of the study wrote.

According to the study, universal immunization of all infants with nirsevimab is expected to reduce 290,174 RSV-related medically attended LRTI (MALRTI), 24,986 hospitalizations, and cut $612 million in costs to the health care system.

The authors wrote: “While this reduction would be driven by term infants, who account for most of the RSV-MALRTI burden; all infants, including palivizumab-eligible and preterm infants who suffer from significantly higher rates of disease, would benefit from this immunization strategy.”
 

Excitement for another option

Jörn-Hendrik Weitkamp, MD, professor of pediatrics and director for patient-oriented research at Monroe Carell Jr. Children’s Hospital at Vanderbilt University, Nashville, Tenn., said in an interview there is much excitement in the field for nirsevimab as it has significant advantages over palivizumab.

RSV “is a huge burden to the children, the families, the hospitals, and the medical system,” he said.

Ideally there would be a vaccine to offer the best protection, he noted.

“People have spent their lives, their careers trying to develop a vaccine for RSV,” he said, but that has been elusive for more than 60 years. Therefore, passive immunization is the best of the current options, he says, and nirsevimab “seems to be very effective.”

What’s not clear, Dr. Weitkamp said, is how much nirsevimab will cost as it is not yet approved by the Food and Drug Administration. However, it has the great advantage of being given only once before the season starts instead of monthly (as required for palivizumab) through the season, “which is painful, inconvenient, and traumatizing. We limit that one to the children at highest risk.”

Rolling out an infant nirsevimab program would likely vary by geographic region, Ms. Kieffer and colleagues said, to help ensure infants are protected during the peak of their region’s RSV season.

The journal’s RSV supplement was supported by Sanofi and AstraZeneca. The studies by Ms. Suh and colleagues and Ms. Kieffer and colleagues were supported by AstraZeneca and Sanofi. Ms. Suh and several coauthors are employees of EpidStrategies. One coauthor is an employee of Sanofi and may hold shares and/or stock options in the company. Ms. Kieffer and several coauthors are employees of Sanofi and may hold shares and/or stock options in the company. Dr. Weitkamp reported no relevant financial relationships.