Infectious Disease Practitioner

An air monitor made by researchers at Washington University in St. Louis can detect COVID-19 in a room with an infected person within 5 minutes.

The project was a collaboration among researchers from the university’s engineering and medical schools; the results were published in Nature Communications.

One of the challenges the team had to overcome is that detecting the virus in a roomful of air “is like finding a needle in a haystack,” researcher and associate engineering professor Rajan Chakrabarty, PhD, said in a statement.

The team overcame that challenge using a technology called wet cyclone that samples the equivalent of 176 cubic feet of air in 5 minutes. A light on the device turns from green to red when the virus is detected, which the researchers said indicates that increased air circulation is needed. 

The device stands just 10 inches tall and 1 foot wide and is considered a proof of concept. The next step would be to implement the technology into a prototype to see how a commercial or household design could be achieved. The researchers foresee potential for the device to be used in hospitals and schools, as well as to be able to detect other respiratory viruses such as influenza and respiratory syncytial virus.

Current methods used for detecting viruses in the air take between 1 and 24 hours to collect and analyze samples. The existing methods usually require skilled labor, resulting in a process that doesn’t allow for real-time information that could translate into reducing risk or the spread of the virus, the researchers wrote.

The team tested their device both in laboratory experiments where they released aerosolized SARS-CoV-2 into a room-sized chamber, as well as in the apartments of two people who were COVID positive.

“There is nothing at the moment that tells us how safe a room is,” Washington University neurology professor John Cirrito, PhD, said in a statement. “If you are in a room with 100 people, you don’t want to find out 5 days later whether you could be sick or not. The idea with this device is that you can know essentially in real time, or every 5 minutes, if there is a live virus in the air.”

Their goal is to develop a commercially available air quality monitor, the researchers said. 

The study authors reported that they had no conflicts of interest.

A version of this article appeared on WebMD.com.

An air monitor made by researchers at Washington University in St. Louis can detect COVID-19 in a room with an infected person within 5 minutes.

The project was a collaboration among researchers from the university’s engineering and medical schools; the results were published in Nature Communications.

One of the challenges the team had to overcome is that detecting the virus in a roomful of air “is like finding a needle in a haystack,” researcher and associate engineering professor Rajan Chakrabarty, PhD, said in a statement.

The team overcame that challenge using a technology called wet cyclone that samples the equivalent of 176 cubic feet of air in 5 minutes. A light on the device turns from green to red when the virus is detected, which the researchers said indicates that increased air circulation is needed. 

The device stands just 10 inches tall and 1 foot wide and is considered a proof of concept. The next step would be to implement the technology into a prototype to see how a commercial or household design could be achieved. The researchers foresee potential for the device to be used in hospitals and schools, as well as to be able to detect other respiratory viruses such as influenza and respiratory syncytial virus.

Current methods used for detecting viruses in the air take between 1 and 24 hours to collect and analyze samples. The existing methods usually require skilled labor, resulting in a process that doesn’t allow for real-time information that could translate into reducing risk or the spread of the virus, the researchers wrote.

The team tested their device both in laboratory experiments where they released aerosolized SARS-CoV-2 into a room-sized chamber, as well as in the apartments of two people who were COVID positive.

“There is nothing at the moment that tells us how safe a room is,” Washington University neurology professor John Cirrito, PhD, said in a statement. “If you are in a room with 100 people, you don’t want to find out 5 days later whether you could be sick or not. The idea with this device is that you can know essentially in real time, or every 5 minutes, if there is a live virus in the air.”

Their goal is to develop a commercially available air quality monitor, the researchers said. 

The study authors reported that they had no conflicts of interest.

A version of this article appeared on WebMD.com.

An air monitor made by researchers at Washington University in St. Louis can detect COVID-19 in a room with an infected person within 5 minutes.

The project was a collaboration among researchers from the university’s engineering and medical schools; the results were published in Nature Communications.

One of the challenges the team had to overcome is that detecting the virus in a roomful of air “is like finding a needle in a haystack,” researcher and associate engineering professor Rajan Chakrabarty, PhD, said in a statement.

The team overcame that challenge using a technology called wet cyclone that samples the equivalent of 176 cubic feet of air in 5 minutes. A light on the device turns from green to red when the virus is detected, which the researchers said indicates that increased air circulation is needed. 

The device stands just 10 inches tall and 1 foot wide and is considered a proof of concept. The next step would be to implement the technology into a prototype to see how a commercial or household design could be achieved. The researchers foresee potential for the device to be used in hospitals and schools, as well as to be able to detect other respiratory viruses such as influenza and respiratory syncytial virus.

Current methods used for detecting viruses in the air take between 1 and 24 hours to collect and analyze samples. The existing methods usually require skilled labor, resulting in a process that doesn’t allow for real-time information that could translate into reducing risk or the spread of the virus, the researchers wrote.

The team tested their device both in laboratory experiments where they released aerosolized SARS-CoV-2 into a room-sized chamber, as well as in the apartments of two people who were COVID positive.

“There is nothing at the moment that tells us how safe a room is,” Washington University neurology professor John Cirrito, PhD, said in a statement. “If you are in a room with 100 people, you don’t want to find out 5 days later whether you could be sick or not. The idea with this device is that you can know essentially in real time, or every 5 minutes, if there is a live virus in the air.”

Their goal is to develop a commercially available air quality monitor, the researchers said. 

The study authors reported that they had no conflicts of interest.

A version of this article appeared on WebMD.com.

Testing children with acute sinusitis symptoms for specific bacteria may dramatically decrease unnecessary antibiotic use, new research suggests.

The study, published in JAMA, found that children with positive nasopharyngeal tests for one or more of Haemophilus influenzae, Streptococcus pneumoniae, or Moraxella catarrhalis had better resolution of symptoms with antibiotics than those without these bacteria.

If antibiotic use was limited to children with H. influenzae or S. pneumoniae in their nasopharynx at the time of diagnosis, antibiotic use would decrease by 53%, according to the study authors.

Sinusitis is common in children, and symptoms are similar with uncomplicated viral upper respiratory infections.

“We have not had a good way to predict which children will benefit from antibiotics,” said Nader Shaikh, MD, MPH, professor of pediatrics and clinical and translational science at the University of Pittsburgh, and the lead study author. “When a child comes in with a sore throat, we test for strep. If the test is positive, we prescribe antibiotics.”

Dr. Shaikh and his colleagues found that the same approach – swabbing the nose and testing for various bacteria – worked for children with sinusitis.

“Children who tested negative for bacteria did not benefit from antibiotics,” Dr. Shaikh said.

In the double-blind clinical trial, Dr. Shaikh and his colleagues randomized 510 children between ages 2 and 11 with acute sinusitis at six academic primary care offices over a 6-year period. Almost two-thirds of participants were between ages 2 and 5, around half were male, and around half were White. All participants had an initial score of nine or higher on the validated Pediatric Rhinosinusitis Symptom Scale (PRSS).

For 10 days, 254 children received oral amoxicillin (90 mg/kg/day) and clavulanate (6.4mg/kg/day) and 256 received placebo.

In children receiving antibiotics, symptoms resolved over a median of 7 days, compared with 9 days for those given placebo (P = .003).

Children without detected nasopharyngeal pathogens did not benefit from antibiotics as much as those with the pathogens, the researchers found. Among those with pathogens, the mean symptom burden score was 1.95 points lower in the group that received antibiotics, compared with the group that received placebo. For those without pathogens, there was a 0.88-point difference between the antibiotic and placebo groups (P = .02).

The researchers also took nasal swabs at the first and final study visits and tested for S. pneumoniae, H. influenzae, and M. catarrhalis. During that time, parents or caregivers used the PRSS to assess their child’s symptoms, and they recorded the nasal discharge color. Nasal discharge color, Dr. Shaikh and colleagues found, was not linked with antibiotic effect.
 

Welcome findings

Pediatricians and primary care providers face a significant clinical dilemma when they consider using antibiotics with upper respiratory tract infections (URTIs), according to John H. Greinwald Jr., MD, professor in the department of pediatrics at Cincinnati Children’s Hospital Medical Center.

“These findings certainly make sense because most respiratory infections in children are viral,” Dr. Greinwald said. “The investigators follow the appropriate clinical guidelines for considering antibiotic use in patients with URTIs, which include URTI symptoms lasting longer than 10 days or symptoms initially getting better, then worsening again day 6 through 10.”

Not only is antibiotic resistance a major public health concern, but the drugs can have side effects such as diarrhea, and their long-term effects on the microbiome are unknown.

“Differentiating who has acute sinusitis from who has a viral infection is difficult for primary care providers,” said Eelam A. Adil, MD, MBA, assistant professor of otolaryngology at Harvard Medical School in Boston.

The findings may help clinicians be more selective with antibiotic prescriptions, according to Jacob G. Eide, MD, a head and neck surgeon at Henry Ford Health in Detroit.

“However, we do not want to deny antibiotics when they are beneficial,” Dr. Eide said. “And the difficulty and costs involved in developing the tests need to be considered.”

Dr. Shaikh and his team are studying ways to bring nasal testing into clinical practice, potentially utilizing commercially available molecular testing and rapid antigen tests that work like COVID-19 at-home tests. They are also exploring if other biomarkers in nasal discharge may indicate the presence of bacteria.

All study authors as well as outside experts reported no relevant financial relationships. The study was supported by the National Institute of Allergy and Infectious Diseases.

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

Testing children with acute sinusitis symptoms for specific bacteria may dramatically decrease unnecessary antibiotic use, new research suggests.

The study, published in JAMA, found that children with positive nasopharyngeal tests for one or more of Haemophilus influenzae, Streptococcus pneumoniae, or Moraxella catarrhalis had better resolution of symptoms with antibiotics than those without these bacteria.

If antibiotic use was limited to children with H. influenzae or S. pneumoniae in their nasopharynx at the time of diagnosis, antibiotic use would decrease by 53%, according to the study authors.

Sinusitis is common in children, and symptoms are similar with uncomplicated viral upper respiratory infections.

“We have not had a good way to predict which children will benefit from antibiotics,” said Nader Shaikh, MD, MPH, professor of pediatrics and clinical and translational science at the University of Pittsburgh, and the lead study author. “When a child comes in with a sore throat, we test for strep. If the test is positive, we prescribe antibiotics.”

Dr. Shaikh and his colleagues found that the same approach – swabbing the nose and testing for various bacteria – worked for children with sinusitis.

“Children who tested negative for bacteria did not benefit from antibiotics,” Dr. Shaikh said.

In the double-blind clinical trial, Dr. Shaikh and his colleagues randomized 510 children between ages 2 and 11 with acute sinusitis at six academic primary care offices over a 6-year period. Almost two-thirds of participants were between ages 2 and 5, around half were male, and around half were White. All participants had an initial score of nine or higher on the validated Pediatric Rhinosinusitis Symptom Scale (PRSS).

For 10 days, 254 children received oral amoxicillin (90 mg/kg/day) and clavulanate (6.4mg/kg/day) and 256 received placebo.

In children receiving antibiotics, symptoms resolved over a median of 7 days, compared with 9 days for those given placebo (P = .003).

Children without detected nasopharyngeal pathogens did not benefit from antibiotics as much as those with the pathogens, the researchers found. Among those with pathogens, the mean symptom burden score was 1.95 points lower in the group that received antibiotics, compared with the group that received placebo. For those without pathogens, there was a 0.88-point difference between the antibiotic and placebo groups (P = .02).

The researchers also took nasal swabs at the first and final study visits and tested for S. pneumoniae, H. influenzae, and M. catarrhalis. During that time, parents or caregivers used the PRSS to assess their child’s symptoms, and they recorded the nasal discharge color. Nasal discharge color, Dr. Shaikh and colleagues found, was not linked with antibiotic effect.
 

Welcome findings

Pediatricians and primary care providers face a significant clinical dilemma when they consider using antibiotics with upper respiratory tract infections (URTIs), according to John H. Greinwald Jr., MD, professor in the department of pediatrics at Cincinnati Children’s Hospital Medical Center.

“These findings certainly make sense because most respiratory infections in children are viral,” Dr. Greinwald said. “The investigators follow the appropriate clinical guidelines for considering antibiotic use in patients with URTIs, which include URTI symptoms lasting longer than 10 days or symptoms initially getting better, then worsening again day 6 through 10.”

Not only is antibiotic resistance a major public health concern, but the drugs can have side effects such as diarrhea, and their long-term effects on the microbiome are unknown.

“Differentiating who has acute sinusitis from who has a viral infection is difficult for primary care providers,” said Eelam A. Adil, MD, MBA, assistant professor of otolaryngology at Harvard Medical School in Boston.

The findings may help clinicians be more selective with antibiotic prescriptions, according to Jacob G. Eide, MD, a head and neck surgeon at Henry Ford Health in Detroit.

“However, we do not want to deny antibiotics when they are beneficial,” Dr. Eide said. “And the difficulty and costs involved in developing the tests need to be considered.”

Dr. Shaikh and his team are studying ways to bring nasal testing into clinical practice, potentially utilizing commercially available molecular testing and rapid antigen tests that work like COVID-19 at-home tests. They are also exploring if other biomarkers in nasal discharge may indicate the presence of bacteria.

All study authors as well as outside experts reported no relevant financial relationships. The study was supported by the National Institute of Allergy and Infectious Diseases.

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

Testing children with acute sinusitis symptoms for specific bacteria may dramatically decrease unnecessary antibiotic use, new research suggests.

The study, published in JAMA, found that children with positive nasopharyngeal tests for one or more of Haemophilus influenzae, Streptococcus pneumoniae, or Moraxella catarrhalis had better resolution of symptoms with antibiotics than those without these bacteria.

If antibiotic use was limited to children with H. influenzae or S. pneumoniae in their nasopharynx at the time of diagnosis, antibiotic use would decrease by 53%, according to the study authors.

Sinusitis is common in children, and symptoms are similar with uncomplicated viral upper respiratory infections.

“We have not had a good way to predict which children will benefit from antibiotics,” said Nader Shaikh, MD, MPH, professor of pediatrics and clinical and translational science at the University of Pittsburgh, and the lead study author. “When a child comes in with a sore throat, we test for strep. If the test is positive, we prescribe antibiotics.”

Dr. Shaikh and his colleagues found that the same approach – swabbing the nose and testing for various bacteria – worked for children with sinusitis.

“Children who tested negative for bacteria did not benefit from antibiotics,” Dr. Shaikh said.

In the double-blind clinical trial, Dr. Shaikh and his colleagues randomized 510 children between ages 2 and 11 with acute sinusitis at six academic primary care offices over a 6-year period. Almost two-thirds of participants were between ages 2 and 5, around half were male, and around half were White. All participants had an initial score of nine or higher on the validated Pediatric Rhinosinusitis Symptom Scale (PRSS).

For 10 days, 254 children received oral amoxicillin (90 mg/kg/day) and clavulanate (6.4mg/kg/day) and 256 received placebo.

In children receiving antibiotics, symptoms resolved over a median of 7 days, compared with 9 days for those given placebo (P = .003).

Children without detected nasopharyngeal pathogens did not benefit from antibiotics as much as those with the pathogens, the researchers found. Among those with pathogens, the mean symptom burden score was 1.95 points lower in the group that received antibiotics, compared with the group that received placebo. For those without pathogens, there was a 0.88-point difference between the antibiotic and placebo groups (P = .02).

The researchers also took nasal swabs at the first and final study visits and tested for S. pneumoniae, H. influenzae, and M. catarrhalis. During that time, parents or caregivers used the PRSS to assess their child’s symptoms, and they recorded the nasal discharge color. Nasal discharge color, Dr. Shaikh and colleagues found, was not linked with antibiotic effect.
 

Welcome findings

Pediatricians and primary care providers face a significant clinical dilemma when they consider using antibiotics with upper respiratory tract infections (URTIs), according to John H. Greinwald Jr., MD, professor in the department of pediatrics at Cincinnati Children’s Hospital Medical Center.

“These findings certainly make sense because most respiratory infections in children are viral,” Dr. Greinwald said. “The investigators follow the appropriate clinical guidelines for considering antibiotic use in patients with URTIs, which include URTI symptoms lasting longer than 10 days or symptoms initially getting better, then worsening again day 6 through 10.”

Not only is antibiotic resistance a major public health concern, but the drugs can have side effects such as diarrhea, and their long-term effects on the microbiome are unknown.

“Differentiating who has acute sinusitis from who has a viral infection is difficult for primary care providers,” said Eelam A. Adil, MD, MBA, assistant professor of otolaryngology at Harvard Medical School in Boston.

The findings may help clinicians be more selective with antibiotic prescriptions, according to Jacob G. Eide, MD, a head and neck surgeon at Henry Ford Health in Detroit.

“However, we do not want to deny antibiotics when they are beneficial,” Dr. Eide said. “And the difficulty and costs involved in developing the tests need to be considered.”

Dr. Shaikh and his team are studying ways to bring nasal testing into clinical practice, potentially utilizing commercially available molecular testing and rapid antigen tests that work like COVID-19 at-home tests. They are also exploring if other biomarkers in nasal discharge may indicate the presence of bacteria.

All study authors as well as outside experts reported no relevant financial relationships. The study was supported by the National Institute of Allergy and Infectious Diseases.

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

TOPLINE

A new American Academy of Pediatrics study reveals that 17.2% of toddlers started but did not finish at least one recommended early childhood vaccine series.

METHODOLOGY

• Examined data collected in 2019 from the National Immunization Survey – Child.
• 16,365 children ages 19-35 months were included.
• Vaccines for diphtheria, tetanus, acellular pertussis, pneumococcal infections, Haemophilus influenzae type b, hepatitis B, polio, measles, mumps, rubella, and varicella were included.

TAKEAWAY

• 72.9% of toddlers completed the seven-vaccine series.
• 17.2% initiated but did not complete one or more of a multidose vaccine series.
• The strongest association with not completing the vaccine series was moving across state lines and not having insurance.
• Children with more siblings at home were less likely to complete a vaccine series.

IN PRACTICE

The study suggests that the “children experienced structural barriers to vaccination,” and the authors urge an “increased focus on strategies to encourage multidose series completion ... to optimize protection from preventable diseases and achieve vaccination coverage goals.”

SOURCE

The study was funded by the National Institutes of Health and published online July 25 in Pediatrics. Sarah Y. Michels, an epidemiology specialist from the University of Montana in Missoula, was the lead author.

LIMITATIONS

Though the researchers studied the risk factors for series noncompletion, they did not have information on the specific reasons why children were missing vaccine doses. Children whose parents chose to participate in the National Immunization Survey – Child may have had higher vaccination coverage than children whose parents declined participation.

DISCLOSURES

The authors have reported no relevant financial relationships.

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

TOPLINE

A new American Academy of Pediatrics study reveals that 17.2% of toddlers started but did not finish at least one recommended early childhood vaccine series.

METHODOLOGY

• Examined data collected in 2019 from the National Immunization Survey – Child.
• 16,365 children ages 19-35 months were included.
• Vaccines for diphtheria, tetanus, acellular pertussis, pneumococcal infections, Haemophilus influenzae type b, hepatitis B, polio, measles, mumps, rubella, and varicella were included.

TAKEAWAY

• 72.9% of toddlers completed the seven-vaccine series.
• 17.2% initiated but did not complete one or more of a multidose vaccine series.
• The strongest association with not completing the vaccine series was moving across state lines and not having insurance.
• Children with more siblings at home were less likely to complete a vaccine series.

IN PRACTICE

The study suggests that the “children experienced structural barriers to vaccination,” and the authors urge an “increased focus on strategies to encourage multidose series completion ... to optimize protection from preventable diseases and achieve vaccination coverage goals.”

SOURCE

The study was funded by the National Institutes of Health and published online July 25 in Pediatrics. Sarah Y. Michels, an epidemiology specialist from the University of Montana in Missoula, was the lead author.

LIMITATIONS

Though the researchers studied the risk factors for series noncompletion, they did not have information on the specific reasons why children were missing vaccine doses. Children whose parents chose to participate in the National Immunization Survey – Child may have had higher vaccination coverage than children whose parents declined participation.

DISCLOSURES

The authors have reported no relevant financial relationships.

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

TOPLINE

A new American Academy of Pediatrics study reveals that 17.2% of toddlers started but did not finish at least one recommended early childhood vaccine series.

METHODOLOGY

• Examined data collected in 2019 from the National Immunization Survey – Child.
• 16,365 children ages 19-35 months were included.
• Vaccines for diphtheria, tetanus, acellular pertussis, pneumococcal infections, Haemophilus influenzae type b, hepatitis B, polio, measles, mumps, rubella, and varicella were included.

TAKEAWAY

• 72.9% of toddlers completed the seven-vaccine series.
• 17.2% initiated but did not complete one or more of a multidose vaccine series.
• The strongest association with not completing the vaccine series was moving across state lines and not having insurance.
• Children with more siblings at home were less likely to complete a vaccine series.

IN PRACTICE

The study suggests that the “children experienced structural barriers to vaccination,” and the authors urge an “increased focus on strategies to encourage multidose series completion ... to optimize protection from preventable diseases and achieve vaccination coverage goals.”

SOURCE

The study was funded by the National Institutes of Health and published online July 25 in Pediatrics. Sarah Y. Michels, an epidemiology specialist from the University of Montana in Missoula, was the lead author.

LIMITATIONS

Though the researchers studied the risk factors for series noncompletion, they did not have information on the specific reasons why children were missing vaccine doses. Children whose parents chose to participate in the National Immunization Survey – Child may have had higher vaccination coverage than children whose parents declined participation.

DISCLOSURES

The authors have reported no relevant financial relationships.

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

BRISBANE, AUSTRALIA – People with undetectable or very low HIV levels have zero or “almost zero” risk of transmitting the virus sexually if they are taking suppression medication, according to new guidelines from the World Health Organization.

The announcement was made concurrently with the publication of definitive new research in The Lancet. The findings were presented virtually at the International AIDS Society conference on HIV Science.

The WHO estimates that 76% of the 39 million people worldwide living with HIV take antiretroviral therapy (ART).

“Antiretroviral therapy continues to transform the lives of people living with HIV,” a WHO news release stated. “People living with HIV who are diagnosed and treated early, and take their medication as prescribed, can expect to have the same health and life expectancy as their HIV-negative counterparts.”

The Lancet study showed that people who have a viral load of less than 1,000 copies per milliliter of blood have a tiny chance of transmitting the virus to sexual partners. Of 320 cases of transmission reviewed during the study, only 2 transmissions involved a partner with a load below that threshold. Those cases may have been affected by viral loads rising between the time of testing and transmission. The previous guideline for zero risk of transmission was 200 copies per milliliter.

People living with HIV who do not take ART can have viral loads ranging from 30,000 to more than 500,000 copies per milliliter, according a summary of the study distributed by The Lancet to the media.

The new findings do not apply to the transmission of HIV from mother to child, including during pregnancy, childbirth, and breastfeeding.

“The ultimate goal of antiretroviral therapy for people living with HIV is to maintain undetectable viral loads, which will improve their own health and prevent transmission to their sexual partners and children,” said researcher Lara Vojnov, PhD, diagnostics advisor to the WHO Department of Global HIV, Hepatitis and STI Programmes, in a statement. “But these new findings are also significant as they indicate that the risk of sexual transmission of HIV at low viral loads is almost zero. This provides a powerful opportunity to help destigmatize HIV, promote the benefits of adhering to antiretroviral therapy, and support people living with HIV.”

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

BRISBANE, AUSTRALIA – People with undetectable or very low HIV levels have zero or “almost zero” risk of transmitting the virus sexually if they are taking suppression medication, according to new guidelines from the World Health Organization.

The announcement was made concurrently with the publication of definitive new research in The Lancet. The findings were presented virtually at the International AIDS Society conference on HIV Science.

The WHO estimates that 76% of the 39 million people worldwide living with HIV take antiretroviral therapy (ART).

“Antiretroviral therapy continues to transform the lives of people living with HIV,” a WHO news release stated. “People living with HIV who are diagnosed and treated early, and take their medication as prescribed, can expect to have the same health and life expectancy as their HIV-negative counterparts.”

The Lancet study showed that people who have a viral load of less than 1,000 copies per milliliter of blood have a tiny chance of transmitting the virus to sexual partners. Of 320 cases of transmission reviewed during the study, only 2 transmissions involved a partner with a load below that threshold. Those cases may have been affected by viral loads rising between the time of testing and transmission. The previous guideline for zero risk of transmission was 200 copies per milliliter.

People living with HIV who do not take ART can have viral loads ranging from 30,000 to more than 500,000 copies per milliliter, according a summary of the study distributed by The Lancet to the media.

The new findings do not apply to the transmission of HIV from mother to child, including during pregnancy, childbirth, and breastfeeding.

“The ultimate goal of antiretroviral therapy for people living with HIV is to maintain undetectable viral loads, which will improve their own health and prevent transmission to their sexual partners and children,” said researcher Lara Vojnov, PhD, diagnostics advisor to the WHO Department of Global HIV, Hepatitis and STI Programmes, in a statement. “But these new findings are also significant as they indicate that the risk of sexual transmission of HIV at low viral loads is almost zero. This provides a powerful opportunity to help destigmatize HIV, promote the benefits of adhering to antiretroviral therapy, and support people living with HIV.”

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

BRISBANE, AUSTRALIA – People with undetectable or very low HIV levels have zero or “almost zero” risk of transmitting the virus sexually if they are taking suppression medication, according to new guidelines from the World Health Organization.

The announcement was made concurrently with the publication of definitive new research in The Lancet. The findings were presented virtually at the International AIDS Society conference on HIV Science.

The WHO estimates that 76% of the 39 million people worldwide living with HIV take antiretroviral therapy (ART).

“Antiretroviral therapy continues to transform the lives of people living with HIV,” a WHO news release stated. “People living with HIV who are diagnosed and treated early, and take their medication as prescribed, can expect to have the same health and life expectancy as their HIV-negative counterparts.”

The Lancet study showed that people who have a viral load of less than 1,000 copies per milliliter of blood have a tiny chance of transmitting the virus to sexual partners. Of 320 cases of transmission reviewed during the study, only 2 transmissions involved a partner with a load below that threshold. Those cases may have been affected by viral loads rising between the time of testing and transmission. The previous guideline for zero risk of transmission was 200 copies per milliliter.

People living with HIV who do not take ART can have viral loads ranging from 30,000 to more than 500,000 copies per milliliter, according a summary of the study distributed by The Lancet to the media.

The new findings do not apply to the transmission of HIV from mother to child, including during pregnancy, childbirth, and breastfeeding.

“The ultimate goal of antiretroviral therapy for people living with HIV is to maintain undetectable viral loads, which will improve their own health and prevent transmission to their sexual partners and children,” said researcher Lara Vojnov, PhD, diagnostics advisor to the WHO Department of Global HIV, Hepatitis and STI Programmes, in a statement. “But these new findings are also significant as they indicate that the risk of sexual transmission of HIV at low viral loads is almost zero. This provides a powerful opportunity to help destigmatize HIV, promote the benefits of adhering to antiretroviral therapy, and support people living with HIV.”

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

Two newly approved respiratory syncytial virus (RSV) vaccines for adults aged 60 years and older may be able to prevent illness in those at risk for severe RSV disease.

Most adult RSV illness occurs among the older age group and results in an estimated 60,000-160,000 hospitalizations and 6,000-10,000 deaths per year among people aged at least 65 years.

Older adults deciding whether to get the vaccines should weigh risks and their own preferences and make the decision in consultation with their clinicians, said authors of a Centers for Disease Control and Prevention report.

Michael Melgar, MD, with the Coronavirus and Other Respiratory Viruses Division at the CDC, was lead author on the report, published in the Morbidity and Mortality Weekly Report.
 

Two new vaccines

In May, the Food and Drug Administration approved the first of two vaccines for preventing RSV lower respiratory tract disease for adults aged at least 60 years.

On June 21, the Advisory Committee on Immunization Practices (ACIP) recommended that people in that age group receive a single dose of RSV vaccine using shared decision-making.

The recommendation for shared decision-making makes the ACIP decision different from routine and risk-based vaccine recommendations. Rather than targeting all in a particular age group or risk group, the decision calls for consideration of a patients’ risk for disease and their characteristics, preferences, and values; the health care professional’s clinical discretion; and performance of the vaccine.

Dr. Melgar and colleagues reported that vaccination with one dose of the GSK or Pfizer RSV vaccines has proved moderately to highly effective in preventing symptomatic RSV-associated lower respiratory tract disease over two consecutive RSV seasons among people aged 60 and older.

The trials that led to approval weren’t powered to gauge efficacy against RSV-associated hospitalization and death. However, the authors wrote, the prevention of lower respiratory tract disease, including medically attended illness, suggests that the shots might prevent considerable morbidity from RSV disease among those aged 60 and older.

Both vaccines were generally well tolerated with a good safety profile. However, six cases of inflammatory neurologic events (including Guillain-Barré Syndrome, acute disseminated encephalomyelitis, and others) were reported in clinical trials after RSV vaccination.

“Whether these events occurred due to chance, or whether RSV vaccination increases the risk for inflammatory neurologic events, is currently unknown,” the authors wrote.

Postmarketing surveillance may help clarify the existence of any potential risk, but until those results are clearer, the CDC researchers said, RSV vaccinations should be targeted to older adults at highest risk for severe RSV and those most likely to benefit from the shots.
 

At higher risk

Some adults with certain medical conditions have a higher risk for RSV-associated hospitalization, according to the report.

Those conditions include chronic obstructive pulmonary disease, asthma, heart failure, coronary artery disease, cerebrovascular disease, diabetes mellitus, and chronic kidney disease.

People who are frail and of advanced age also are at higher risk for RSV hospitalization. That risk increases with age and the highest risk is for people aged at least 75 years.

The researchers added that RSV can cause severe disease in those with compromised immunity, including people who have received hematopoietic stem cell transplants and patients taking immunosuppressive drugs such as those used with solid organ transplants, cancer treatment, or other conditions.

As for when physicians should offer the vaccinations, shots are optimally given before the start of the RSV season.

However, the COVID-19 pandemic interrupted the seasonality and the timing has not yet returned to prepandemic patterns.

For the 2023-24 season, this report states, clinicians should offer RSV vaccination to adults aged at least 60 years using shared clinical decision-making as early as vaccine supply is available and should continue to offer vaccination to eligible adults who remain unvaccinated.

RSV vaccines can be administered with other adult vaccines during the same visit, the authors confirmed.
 

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

Two newly approved respiratory syncytial virus (RSV) vaccines for adults aged 60 years and older may be able to prevent illness in those at risk for severe RSV disease.

Most adult RSV illness occurs among the older age group and results in an estimated 60,000-160,000 hospitalizations and 6,000-10,000 deaths per year among people aged at least 65 years.

Older adults deciding whether to get the vaccines should weigh risks and their own preferences and make the decision in consultation with their clinicians, said authors of a Centers for Disease Control and Prevention report.

Michael Melgar, MD, with the Coronavirus and Other Respiratory Viruses Division at the CDC, was lead author on the report, published in the Morbidity and Mortality Weekly Report.
 

Two new vaccines

In May, the Food and Drug Administration approved the first of two vaccines for preventing RSV lower respiratory tract disease for adults aged at least 60 years.

On June 21, the Advisory Committee on Immunization Practices (ACIP) recommended that people in that age group receive a single dose of RSV vaccine using shared decision-making.

The recommendation for shared decision-making makes the ACIP decision different from routine and risk-based vaccine recommendations. Rather than targeting all in a particular age group or risk group, the decision calls for consideration of a patients’ risk for disease and their characteristics, preferences, and values; the health care professional’s clinical discretion; and performance of the vaccine.

Dr. Melgar and colleagues reported that vaccination with one dose of the GSK or Pfizer RSV vaccines has proved moderately to highly effective in preventing symptomatic RSV-associated lower respiratory tract disease over two consecutive RSV seasons among people aged 60 and older.

The trials that led to approval weren’t powered to gauge efficacy against RSV-associated hospitalization and death. However, the authors wrote, the prevention of lower respiratory tract disease, including medically attended illness, suggests that the shots might prevent considerable morbidity from RSV disease among those aged 60 and older.

Both vaccines were generally well tolerated with a good safety profile. However, six cases of inflammatory neurologic events (including Guillain-Barré Syndrome, acute disseminated encephalomyelitis, and others) were reported in clinical trials after RSV vaccination.

“Whether these events occurred due to chance, or whether RSV vaccination increases the risk for inflammatory neurologic events, is currently unknown,” the authors wrote.

Postmarketing surveillance may help clarify the existence of any potential risk, but until those results are clearer, the CDC researchers said, RSV vaccinations should be targeted to older adults at highest risk for severe RSV and those most likely to benefit from the shots.
 

At higher risk

Some adults with certain medical conditions have a higher risk for RSV-associated hospitalization, according to the report.

Those conditions include chronic obstructive pulmonary disease, asthma, heart failure, coronary artery disease, cerebrovascular disease, diabetes mellitus, and chronic kidney disease.

People who are frail and of advanced age also are at higher risk for RSV hospitalization. That risk increases with age and the highest risk is for people aged at least 75 years.

The researchers added that RSV can cause severe disease in those with compromised immunity, including people who have received hematopoietic stem cell transplants and patients taking immunosuppressive drugs such as those used with solid organ transplants, cancer treatment, or other conditions.

As for when physicians should offer the vaccinations, shots are optimally given before the start of the RSV season.

However, the COVID-19 pandemic interrupted the seasonality and the timing has not yet returned to prepandemic patterns.

For the 2023-24 season, this report states, clinicians should offer RSV vaccination to adults aged at least 60 years using shared clinical decision-making as early as vaccine supply is available and should continue to offer vaccination to eligible adults who remain unvaccinated.

RSV vaccines can be administered with other adult vaccines during the same visit, the authors confirmed.
 

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

Two newly approved respiratory syncytial virus (RSV) vaccines for adults aged 60 years and older may be able to prevent illness in those at risk for severe RSV disease.

Most adult RSV illness occurs among the older age group and results in an estimated 60,000-160,000 hospitalizations and 6,000-10,000 deaths per year among people aged at least 65 years.

Older adults deciding whether to get the vaccines should weigh risks and their own preferences and make the decision in consultation with their clinicians, said authors of a Centers for Disease Control and Prevention report.

Michael Melgar, MD, with the Coronavirus and Other Respiratory Viruses Division at the CDC, was lead author on the report, published in the Morbidity and Mortality Weekly Report.
 

Two new vaccines

In May, the Food and Drug Administration approved the first of two vaccines for preventing RSV lower respiratory tract disease for adults aged at least 60 years.

On June 21, the Advisory Committee on Immunization Practices (ACIP) recommended that people in that age group receive a single dose of RSV vaccine using shared decision-making.

The recommendation for shared decision-making makes the ACIP decision different from routine and risk-based vaccine recommendations. Rather than targeting all in a particular age group or risk group, the decision calls for consideration of a patients’ risk for disease and their characteristics, preferences, and values; the health care professional’s clinical discretion; and performance of the vaccine.

Dr. Melgar and colleagues reported that vaccination with one dose of the GSK or Pfizer RSV vaccines has proved moderately to highly effective in preventing symptomatic RSV-associated lower respiratory tract disease over two consecutive RSV seasons among people aged 60 and older.

The trials that led to approval weren’t powered to gauge efficacy against RSV-associated hospitalization and death. However, the authors wrote, the prevention of lower respiratory tract disease, including medically attended illness, suggests that the shots might prevent considerable morbidity from RSV disease among those aged 60 and older.

Both vaccines were generally well tolerated with a good safety profile. However, six cases of inflammatory neurologic events (including Guillain-Barré Syndrome, acute disseminated encephalomyelitis, and others) were reported in clinical trials after RSV vaccination.

“Whether these events occurred due to chance, or whether RSV vaccination increases the risk for inflammatory neurologic events, is currently unknown,” the authors wrote.

Postmarketing surveillance may help clarify the existence of any potential risk, but until those results are clearer, the CDC researchers said, RSV vaccinations should be targeted to older adults at highest risk for severe RSV and those most likely to benefit from the shots.
 

At higher risk

Some adults with certain medical conditions have a higher risk for RSV-associated hospitalization, according to the report.

Those conditions include chronic obstructive pulmonary disease, asthma, heart failure, coronary artery disease, cerebrovascular disease, diabetes mellitus, and chronic kidney disease.

People who are frail and of advanced age also are at higher risk for RSV hospitalization. That risk increases with age and the highest risk is for people aged at least 75 years.

The researchers added that RSV can cause severe disease in those with compromised immunity, including people who have received hematopoietic stem cell transplants and patients taking immunosuppressive drugs such as those used with solid organ transplants, cancer treatment, or other conditions.

As for when physicians should offer the vaccinations, shots are optimally given before the start of the RSV season.

However, the COVID-19 pandemic interrupted the seasonality and the timing has not yet returned to prepandemic patterns.

For the 2023-24 season, this report states, clinicians should offer RSV vaccination to adults aged at least 60 years using shared clinical decision-making as early as vaccine supply is available and should continue to offer vaccination to eligible adults who remain unvaccinated.

RSV vaccines can be administered with other adult vaccines during the same visit, the authors confirmed.
 

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

The presence of a positive fungal culture in patients with bronchiectasis does not appear to correlate with disease severity or any increased risk of an adverse outcome, according to data pulled from the Bronchiectasis and NTM Registry and presented at the 6th World Bronchiectasis & NTM Conference.

“The question we were asking is whether there is some signal that suggests we need to take care of these patients differently, and the answer is no,” reported Pamela J. McShane, MD, a pulmonologist on the faculty at the University of Texas Health Science Center at Tyler.

When compared for outcome over time, those with a positive fungal culture at initial evaluation did not have more exacerbations, more hospitalizations, or other signs of a more severe disease or more complex course than did those without a positive fungal culture.

When fungal infections are detected in an initial microbiologic evaluation of patients with bronchiectasis or other lung diseases, first-line clinicians generally assume that coverage is needed. Dr. McShane noted that many of the patients referred to her with bronchiectasis and a positive fungal culture were already on an antifungal.

These data are not supportive of treatment in the absence of fungal-related complications. Dr. McShane suggested they even raise questions about the value of culturing beyond bacterial pathogens in the absence of suspicion that fungal organisms are playing a role in symptoms. She cautioned, however, that more studies specifically studying this possibility are needed.
 

Study details

The data were drawn in December 2022 from the U.S.-based Bronchiectasis and NTM Registry, which at that time had 22 participating sites. Of the more than 5,000 patients enrolled, the study looked at 2,230 after several exclusions, such as a diagnosis of allergic bronchopulmonary aspergillosis (ABPA).

Of these 2,230 patients, 949 had a fungal infection at the time of diagnosis and 1,281 did not. Those with a fungal infection were further subdivided into those with an aspergillosis (331 patients) and those with a nonaspergillosis fungal infection (751 patients). The total of these two numbers is greater than the total number of fungal infections because these were not mutually exclusive.

At enrollment into the registry, there were no statistical differences between groups for age. Some statistical differences were observed among groups stratified by race, but Dr. McShane doubted that these were clinically significant with the exception of a potential disparity among Asians that might deserve further analysis.
 

Infection results

Of clinical features evaluated for their association with fungal infection, there was no correlation with either body mass index or history of asthma. Eosinophilia was associated significantly with positive fungal cultures.

Baseline FEV₁ was slightly lower among those with a positive fungal culture even if the difference was highly significant (P = .0006). Again, Dr. McShane questioned the clinical significance of values that varied by only a few percentage points, even though she was willing to acknowledge that higher is always preferable to a lower FEV₁.

In the context of other pathogens, “generally speaking, those with a positive bacterial culture were more likely to have a fungal infection,” Dr. McShane reported, although there was some variation when looking at pathogenicity of the bacteria and other variables.

“Whether this [higher rate of fungal infection] just involves the environment or our antibiotics are driving the opportunity to permit the fungi to exist, we do not have the answer,” she added.

Nontuberculosis mycobacteria (NTM) infection was similarly represented in those with or without a fungal infection, according to Dr. McShane. Noting the high use of antibiotics in an NTM population, Dr. McShane conceded that this challenges the theory that antibiotic use is driving the risk of fungal infection, but these are what the data say.  

Steroid use was associated with a statistically significant risk of fungal infection, but Dr. McShane said it is unclear whether steroid use drives the risk or is an epiphenomenon.

“We looked at this a lot of different ways: oral vs. inhaled and oral vs. inhaled and oral, and it did not make much difference. Generally speaking, the fungal cultures were more likely to be positive in patients on any kind of steroid,” she said.

Finally, with the exception of the slightly lower FEV₁ in patients with fungal infections, Dr. McShane said that there was no discernible relationship between the presence of a fungal infection and severity of bronchiectasis.

Because of this evidence, Dr. McShane concluded that the presence of fungus in the culture of patients with bronchiectasis does not appear to correlate with outcome or severity. Since completing the study, she said she is now using these data to reassure patients who have a positive fungal culture.

While these data do not affect the need to diagnosis fungal infections in patients who are not responding typically to therapy or otherwise have an abnormal course of bronchiectasis, raising suspicion that fungal infection is participating in the disease course, the data provide a basis for questioning whether routine cultures are needed, according to the discussion that followed Dr. McShane’s presentation.
 

Expert opinion

Several of the experts at the presentation provided an opinion. Some reported that they would continue to order fungal cultures on a routine basis, while others said that they now, on the basis of these data, plan to order cultures only at the first visit or when fungal infection is suspected of exacerbating the disease.

Of this latter group, which seemed to be dominant, Juzar Ali, MD, professor of medicine, Louisiana State University, New Orleans, said that he has not been ordering fungal cultures on every visit. Rather, he has been doing so selectively. Examples include those who are on steroids or those with an unusual pattern of exacerbations.

“The value of these data is that they have now provided some data to support this approach,” Dr. Ali said in an interview. Noting that this is the first large study to address this question in a systematic way, he considers this to be a valuable contribution for approaching a common clinical issue.

Dr. McShane reports no relevant financial relationships. Dr. Ali reports a financial relationship with Insmed.
 

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

The presence of a positive fungal culture in patients with bronchiectasis does not appear to correlate with disease severity or any increased risk of an adverse outcome, according to data pulled from the Bronchiectasis and NTM Registry and presented at the 6th World Bronchiectasis & NTM Conference.

“The question we were asking is whether there is some signal that suggests we need to take care of these patients differently, and the answer is no,” reported Pamela J. McShane, MD, a pulmonologist on the faculty at the University of Texas Health Science Center at Tyler.

When compared for outcome over time, those with a positive fungal culture at initial evaluation did not have more exacerbations, more hospitalizations, or other signs of a more severe disease or more complex course than did those without a positive fungal culture.

When fungal infections are detected in an initial microbiologic evaluation of patients with bronchiectasis or other lung diseases, first-line clinicians generally assume that coverage is needed. Dr. McShane noted that many of the patients referred to her with bronchiectasis and a positive fungal culture were already on an antifungal.

These data are not supportive of treatment in the absence of fungal-related complications. Dr. McShane suggested they even raise questions about the value of culturing beyond bacterial pathogens in the absence of suspicion that fungal organisms are playing a role in symptoms. She cautioned, however, that more studies specifically studying this possibility are needed.
 

Study details

The data were drawn in December 2022 from the U.S.-based Bronchiectasis and NTM Registry, which at that time had 22 participating sites. Of the more than 5,000 patients enrolled, the study looked at 2,230 after several exclusions, such as a diagnosis of allergic bronchopulmonary aspergillosis (ABPA).

Of these 2,230 patients, 949 had a fungal infection at the time of diagnosis and 1,281 did not. Those with a fungal infection were further subdivided into those with an aspergillosis (331 patients) and those with a nonaspergillosis fungal infection (751 patients). The total of these two numbers is greater than the total number of fungal infections because these were not mutually exclusive.

At enrollment into the registry, there were no statistical differences between groups for age. Some statistical differences were observed among groups stratified by race, but Dr. McShane doubted that these were clinically significant with the exception of a potential disparity among Asians that might deserve further analysis.
 

Infection results

Of clinical features evaluated for their association with fungal infection, there was no correlation with either body mass index or history of asthma. Eosinophilia was associated significantly with positive fungal cultures.

Baseline FEV₁ was slightly lower among those with a positive fungal culture even if the difference was highly significant (P = .0006). Again, Dr. McShane questioned the clinical significance of values that varied by only a few percentage points, even though she was willing to acknowledge that higher is always preferable to a lower FEV₁.

In the context of other pathogens, “generally speaking, those with a positive bacterial culture were more likely to have a fungal infection,” Dr. McShane reported, although there was some variation when looking at pathogenicity of the bacteria and other variables.

“Whether this [higher rate of fungal infection] just involves the environment or our antibiotics are driving the opportunity to permit the fungi to exist, we do not have the answer,” she added.

Nontuberculosis mycobacteria (NTM) infection was similarly represented in those with or without a fungal infection, according to Dr. McShane. Noting the high use of antibiotics in an NTM population, Dr. McShane conceded that this challenges the theory that antibiotic use is driving the risk of fungal infection, but these are what the data say.  

Steroid use was associated with a statistically significant risk of fungal infection, but Dr. McShane said it is unclear whether steroid use drives the risk or is an epiphenomenon.

“We looked at this a lot of different ways: oral vs. inhaled and oral vs. inhaled and oral, and it did not make much difference. Generally speaking, the fungal cultures were more likely to be positive in patients on any kind of steroid,” she said.

Finally, with the exception of the slightly lower FEV₁ in patients with fungal infections, Dr. McShane said that there was no discernible relationship between the presence of a fungal infection and severity of bronchiectasis.

Because of this evidence, Dr. McShane concluded that the presence of fungus in the culture of patients with bronchiectasis does not appear to correlate with outcome or severity. Since completing the study, she said she is now using these data to reassure patients who have a positive fungal culture.

While these data do not affect the need to diagnosis fungal infections in patients who are not responding typically to therapy or otherwise have an abnormal course of bronchiectasis, raising suspicion that fungal infection is participating in the disease course, the data provide a basis for questioning whether routine cultures are needed, according to the discussion that followed Dr. McShane’s presentation.
 

Expert opinion

Several of the experts at the presentation provided an opinion. Some reported that they would continue to order fungal cultures on a routine basis, while others said that they now, on the basis of these data, plan to order cultures only at the first visit or when fungal infection is suspected of exacerbating the disease.

Of this latter group, which seemed to be dominant, Juzar Ali, MD, professor of medicine, Louisiana State University, New Orleans, said that he has not been ordering fungal cultures on every visit. Rather, he has been doing so selectively. Examples include those who are on steroids or those with an unusual pattern of exacerbations.

“The value of these data is that they have now provided some data to support this approach,” Dr. Ali said in an interview. Noting that this is the first large study to address this question in a systematic way, he considers this to be a valuable contribution for approaching a common clinical issue.

Dr. McShane reports no relevant financial relationships. Dr. Ali reports a financial relationship with Insmed.
 

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

The presence of a positive fungal culture in patients with bronchiectasis does not appear to correlate with disease severity or any increased risk of an adverse outcome, according to data pulled from the Bronchiectasis and NTM Registry and presented at the 6th World Bronchiectasis & NTM Conference.

“The question we were asking is whether there is some signal that suggests we need to take care of these patients differently, and the answer is no,” reported Pamela J. McShane, MD, a pulmonologist on the faculty at the University of Texas Health Science Center at Tyler.

When compared for outcome over time, those with a positive fungal culture at initial evaluation did not have more exacerbations, more hospitalizations, or other signs of a more severe disease or more complex course than did those without a positive fungal culture.

When fungal infections are detected in an initial microbiologic evaluation of patients with bronchiectasis or other lung diseases, first-line clinicians generally assume that coverage is needed. Dr. McShane noted that many of the patients referred to her with bronchiectasis and a positive fungal culture were already on an antifungal.

These data are not supportive of treatment in the absence of fungal-related complications. Dr. McShane suggested they even raise questions about the value of culturing beyond bacterial pathogens in the absence of suspicion that fungal organisms are playing a role in symptoms. She cautioned, however, that more studies specifically studying this possibility are needed.
 

Study details

The data were drawn in December 2022 from the U.S.-based Bronchiectasis and NTM Registry, which at that time had 22 participating sites. Of the more than 5,000 patients enrolled, the study looked at 2,230 after several exclusions, such as a diagnosis of allergic bronchopulmonary aspergillosis (ABPA).

Of these 2,230 patients, 949 had a fungal infection at the time of diagnosis and 1,281 did not. Those with a fungal infection were further subdivided into those with an aspergillosis (331 patients) and those with a nonaspergillosis fungal infection (751 patients). The total of these two numbers is greater than the total number of fungal infections because these were not mutually exclusive.

At enrollment into the registry, there were no statistical differences between groups for age. Some statistical differences were observed among groups stratified by race, but Dr. McShane doubted that these were clinically significant with the exception of a potential disparity among Asians that might deserve further analysis.
 

Infection results

Of clinical features evaluated for their association with fungal infection, there was no correlation with either body mass index or history of asthma. Eosinophilia was associated significantly with positive fungal cultures.

Baseline FEV₁ was slightly lower among those with a positive fungal culture even if the difference was highly significant (P = .0006). Again, Dr. McShane questioned the clinical significance of values that varied by only a few percentage points, even though she was willing to acknowledge that higher is always preferable to a lower FEV₁.

In the context of other pathogens, “generally speaking, those with a positive bacterial culture were more likely to have a fungal infection,” Dr. McShane reported, although there was some variation when looking at pathogenicity of the bacteria and other variables.

“Whether this [higher rate of fungal infection] just involves the environment or our antibiotics are driving the opportunity to permit the fungi to exist, we do not have the answer,” she added.

Nontuberculosis mycobacteria (NTM) infection was similarly represented in those with or without a fungal infection, according to Dr. McShane. Noting the high use of antibiotics in an NTM population, Dr. McShane conceded that this challenges the theory that antibiotic use is driving the risk of fungal infection, but these are what the data say.  

Steroid use was associated with a statistically significant risk of fungal infection, but Dr. McShane said it is unclear whether steroid use drives the risk or is an epiphenomenon.

“We looked at this a lot of different ways: oral vs. inhaled and oral vs. inhaled and oral, and it did not make much difference. Generally speaking, the fungal cultures were more likely to be positive in patients on any kind of steroid,” she said.

Finally, with the exception of the slightly lower FEV₁ in patients with fungal infections, Dr. McShane said that there was no discernible relationship between the presence of a fungal infection and severity of bronchiectasis.

Because of this evidence, Dr. McShane concluded that the presence of fungus in the culture of patients with bronchiectasis does not appear to correlate with outcome or severity. Since completing the study, she said she is now using these data to reassure patients who have a positive fungal culture.

While these data do not affect the need to diagnosis fungal infections in patients who are not responding typically to therapy or otherwise have an abnormal course of bronchiectasis, raising suspicion that fungal infection is participating in the disease course, the data provide a basis for questioning whether routine cultures are needed, according to the discussion that followed Dr. McShane’s presentation.
 

Expert opinion

Several of the experts at the presentation provided an opinion. Some reported that they would continue to order fungal cultures on a routine basis, while others said that they now, on the basis of these data, plan to order cultures only at the first visit or when fungal infection is suspected of exacerbating the disease.

Of this latter group, which seemed to be dominant, Juzar Ali, MD, professor of medicine, Louisiana State University, New Orleans, said that he has not been ordering fungal cultures on every visit. Rather, he has been doing so selectively. Examples include those who are on steroids or those with an unusual pattern of exacerbations.

“The value of these data is that they have now provided some data to support this approach,” Dr. Ali said in an interview. Noting that this is the first large study to address this question in a systematic way, he considers this to be a valuable contribution for approaching a common clinical issue.

Dr. McShane reports no relevant financial relationships. Dr. Ali reports a financial relationship with Insmed.
 

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

TOPLINE:

Immunological and quantitative mRNA assays support a pathogenesis role for histamine-releasing factor (HRF), its interaction with HRF-reactive immunoglobulin E and rhinovirus (RV) in asthma severity and exacerbation.

METHODOLOGY:

• Clinical data for healthy controls (HCs) were compared with data from patients with asthma for three distinct cohorts recruited from programs located in Pittsburg, Boston, and Virginia.
• Cohorts differed primarily by total number of participants, median age, description of asthma severity, RV status, and longitudinal follow-up.
• Enzyme-linked immunoassay tests quantified for comparisons total IgE, IgGs, and IgG1 levels occurring in human sera samples and for HRF-reactive IgE, IgG1, and IgG2b in sera from mice inoculated with mouse .
• Anti-IgE stimulation experiments characterized bronchoalveolar lavage (BAL) cell supernatants for tryptase and PGD2 by ELISA and the mRNAs for tryptase and FCER1A
• Effect of inoculated RV infections and/or house dust mite allergen on stimulating HRF secretion from respiratory epithelial cells and in vitro–grown lung BEAS-2B cells was evaluated by Western blots.

TAKEAWAY:

• HRF-reactive IgE and total IgE levels in serum were significantly higher from patients with severe asthma than from HCs and showed a rising trend as severity increased.
• HRF-reactive IgGs and IgG1 levels in serum were lower in people with asthma than in HCs.
• People with asthma with high HRF-reactive IgE, compared with those with low levels, tended to release more tryptase prostaglandin D2 with anti-IgE stimulation of BAL cells.
• RV infection induced HFR secretions from both in vivo– and in vitro–grown respiratory epithelial cells and was associated with higher levels of HRF-IgE at the time of asthma exacerbations, compared with after resolution.

IN PRACTICE:

Inhibiting HRF and HRF-reactive IgE interactions “can be a preventative/therapeutic target” for severe and RV-induced exacerbated asthma conditions.

SOURCE:

The study led by Yu Kawakami, MD, of La Jolla Institute for Allergy & Immunology, California, and colleagues was published in the Journal of Allergy and Clinical Immunology

LIMITATIONS:

Small sample sizes, large median age differences between cohorts, and lack of data for other demographic traits and variant asthma phenotypes or endotypes in some cohorts are noted limitations that may affect result extrapolations and conclusions.

DISCLOSURES:

The authors report there are no conflicts of interest directly related to this study.

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

TOPLINE:

Immunological and quantitative mRNA assays support a pathogenesis role for histamine-releasing factor (HRF), its interaction with HRF-reactive immunoglobulin E and rhinovirus (RV) in asthma severity and exacerbation.

METHODOLOGY:

• Clinical data for healthy controls (HCs) were compared with data from patients with asthma for three distinct cohorts recruited from programs located in Pittsburg, Boston, and Virginia.
• Cohorts differed primarily by total number of participants, median age, description of asthma severity, RV status, and longitudinal follow-up.
• Enzyme-linked immunoassay tests quantified for comparisons total IgE, IgGs, and IgG1 levels occurring in human sera samples and for HRF-reactive IgE, IgG1, and IgG2b in sera from mice inoculated with mouse .
• Anti-IgE stimulation experiments characterized bronchoalveolar lavage (BAL) cell supernatants for tryptase and PGD2 by ELISA and the mRNAs for tryptase and FCER1A
• Effect of inoculated RV infections and/or house dust mite allergen on stimulating HRF secretion from respiratory epithelial cells and in vitro–grown lung BEAS-2B cells was evaluated by Western blots.

TAKEAWAY:

• HRF-reactive IgE and total IgE levels in serum were significantly higher from patients with severe asthma than from HCs and showed a rising trend as severity increased.
• HRF-reactive IgGs and IgG1 levels in serum were lower in people with asthma than in HCs.
• People with asthma with high HRF-reactive IgE, compared with those with low levels, tended to release more tryptase prostaglandin D2 with anti-IgE stimulation of BAL cells.
• RV infection induced HFR secretions from both in vivo– and in vitro–grown respiratory epithelial cells and was associated with higher levels of HRF-IgE at the time of asthma exacerbations, compared with after resolution.

IN PRACTICE:

Inhibiting HRF and HRF-reactive IgE interactions “can be a preventative/therapeutic target” for severe and RV-induced exacerbated asthma conditions.

SOURCE:

The study led by Yu Kawakami, MD, of La Jolla Institute for Allergy & Immunology, California, and colleagues was published in the Journal of Allergy and Clinical Immunology

LIMITATIONS:

Small sample sizes, large median age differences between cohorts, and lack of data for other demographic traits and variant asthma phenotypes or endotypes in some cohorts are noted limitations that may affect result extrapolations and conclusions.

DISCLOSURES:

The authors report there are no conflicts of interest directly related to this study.

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

TOPLINE:

Immunological and quantitative mRNA assays support a pathogenesis role for histamine-releasing factor (HRF), its interaction with HRF-reactive immunoglobulin E and rhinovirus (RV) in asthma severity and exacerbation.

METHODOLOGY:

• Clinical data for healthy controls (HCs) were compared with data from patients with asthma for three distinct cohorts recruited from programs located in Pittsburg, Boston, and Virginia.
• Cohorts differed primarily by total number of participants, median age, description of asthma severity, RV status, and longitudinal follow-up.
• Enzyme-linked immunoassay tests quantified for comparisons total IgE, IgGs, and IgG1 levels occurring in human sera samples and for HRF-reactive IgE, IgG1, and IgG2b in sera from mice inoculated with mouse .
• Anti-IgE stimulation experiments characterized bronchoalveolar lavage (BAL) cell supernatants for tryptase and PGD2 by ELISA and the mRNAs for tryptase and FCER1A
• Effect of inoculated RV infections and/or house dust mite allergen on stimulating HRF secretion from respiratory epithelial cells and in vitro–grown lung BEAS-2B cells was evaluated by Western blots.

TAKEAWAY:

• HRF-reactive IgE and total IgE levels in serum were significantly higher from patients with severe asthma than from HCs and showed a rising trend as severity increased.
• HRF-reactive IgGs and IgG1 levels in serum were lower in people with asthma than in HCs.
• People with asthma with high HRF-reactive IgE, compared with those with low levels, tended to release more tryptase prostaglandin D2 with anti-IgE stimulation of BAL cells.
• RV infection induced HFR secretions from both in vivo– and in vitro–grown respiratory epithelial cells and was associated with higher levels of HRF-IgE at the time of asthma exacerbations, compared with after resolution.

IN PRACTICE:

Inhibiting HRF and HRF-reactive IgE interactions “can be a preventative/therapeutic target” for severe and RV-induced exacerbated asthma conditions.

SOURCE:

The study led by Yu Kawakami, MD, of La Jolla Institute for Allergy & Immunology, California, and colleagues was published in the Journal of Allergy and Clinical Immunology

LIMITATIONS:

Small sample sizes, large median age differences between cohorts, and lack of data for other demographic traits and variant asthma phenotypes or endotypes in some cohorts are noted limitations that may affect result extrapolations and conclusions.

DISCLOSURES:

The authors report there are no conflicts of interest directly related to this study.

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

Private equity ownership of medical practices was linked to consumer price increases for 8 of 10 specialties examined in a new report, with the most notable gains reported for oncology and gastroenterology.

The report was a collaboration of University of California, Berkeley, staff and researchers from two nonprofits, the American Antitrust Institute and the Washington Center for Equitable Growth. It provides “convincing evidence that incentives to put profits before patients have grown stronger with an increase in private equity ownership of physician practices,” lead author Richard Scheffler, PhD, of UC Berkeley said in a statement.

The report also noted that private equity acquisitions of physician groups have risen sixfold in just a decade, increasing from 75 deals in 2012 to 484 deals in 2021.

Separately, the American Medical Association earlier released a separate report on trends in physician practice arrangements, finding that the percentage of physicians working in private equity–owned groups was 4.5% in 2022, the same as in its previous 2020 report. The share of physicians working in private practices fell by 13 percentage points from 60.1% to 46.7% between 2012 and 2022, the AMA reported.

The Berkeley report and the AMA update come amid rising concerns about the effects of the decline of independent physician practices. The U.S. Senate Finance Committee, which oversees most federal health spending, held a June hearing examining the causes and consequences of increased corporate ownership in health care, including a look at physician practices.

“It’s increasingly clear that consolidation in health care is not lowering costs or increasing the quality of Americans’ health care,” Senate Finance Chairman Ron Wyden (D-Ore.) said in an email. “For private equity in health care in particular, there needs to be more transparency around ownership so the effect on these business relationships can be better understood.”

Federal and state agencies do not generally track acquisitions of physician practices.

The UC Berkeley report impressively documents the rising influence of private equity in health care, for which it’s tough to find good data, said Karen Joynt Maddox, MD, MPH, of Washington University in St. Louis. Dr. Maddox, a cardiologist and policy researcher who also has studied the effects of consolidation in health care, examined the new report at the request of this news organization.

“They did a great job with the data,” Dr. Maddox said. “One of the big issues around private equity, and in general, ‘corporatization’ and consolidation of health care, is that there’s not a great way to track ownership changes. It’s really difficult to study.”

Dr. Scheffler and colleagues used data from the commercial firm PitchBook to identify acquisitions of physician practices by private equity firms. They consulted IQVIA’s physician databases – OneKey and SK&A Office-Based Physicians Database – to learn about the location, size, and specialties of acquired practices. They also used data from the nonprofit Health Care Cost Institute, which tracks commercial health plan claims, to assess how private equity acquisitions affected prices.

The researchers then matched the findings for practices acquired by private equity firms from 2015 to 2021 against those for comparable physician practices that remained independent from 2012 to 2021.

The authors then tied private-equity ownership to the following price increases:

• Gastroenterology (14%; 95% confidence interval, 7.9%-20.4%
• Oncology (16.4%; 95% CI, 5.5%-28.4%)
• Dermatology (4.0%; 95% CI, 1%-7.1%)
• Ob.gyn. (8.8%; 95% CI, 3.8%-14%)
• Ophthalmology (8.7%; 95% CI, 5.1%-12.3%)
• Radiology (8.2%; 95% CI, 0.8%-16.1%)
• Orthopedics (7.1%; 95% CI, 2.2%-12.3%)
• Primary care (4.1%; 95% CI, 1.3%-7%)

The analysis also found higher prices for cardiology (8.7%; 95% CI, –6.4% to 26.1%) and urology (4.2%; 95% CI, –2.3% to 11.1%), but neither of these findings was statistically significant, one of the authors, Daniel R. Arnold, PhD, of UC Berkeley, said in an email. This was most likely caused by smaller sample sizes for these fields.
 

Factors driving consolidation

The two reports and the Senate Finance consolidation hearing raised similar issues, including calls to look at the factors driving more physicians out of independent practice, including Medicare reimbursement that may not keep up with rising inflation.

The Berkeley report authors called for Congress to add a broad inflation component to the Medicare physician fee schedule. It also called on Congress to add cases where Medicare, the biggest U.S. purchaser of health care, pays less for services when performed in independent practices than in hospital-affiliated ones.

Shawn Martin, executive vice president and CEO of the American Academy of Family Physicians, said his group appreciates how the report from UC Berkeley and nonprofit groups echoed recommendations many clinicians have made, including the call for a broad inflation adjustment for the fee schedule.

“To move the needle forward, Congress must advance site-neutral payment policies while also addressing the administrative requirements that take physicians away from the important work of caring for patients,” Mr. Martin said in an email.

Arnold Ventures provided funding for the report, which was a joint project of the American Antitrust Institute, the Nicholas C. Petris Center on Health Care Markets and Consumer Welfare, UC Berkeley, and the Washington Center for Equitable Growth.

A version of this article appeared on Medscape.com.

Private equity ownership of medical practices was linked to consumer price increases for 8 of 10 specialties examined in a new report, with the most notable gains reported for oncology and gastroenterology.

The report was a collaboration of University of California, Berkeley, staff and researchers from two nonprofits, the American Antitrust Institute and the Washington Center for Equitable Growth. It provides “convincing evidence that incentives to put profits before patients have grown stronger with an increase in private equity ownership of physician practices,” lead author Richard Scheffler, PhD, of UC Berkeley said in a statement.

The report also noted that private equity acquisitions of physician groups have risen sixfold in just a decade, increasing from 75 deals in 2012 to 484 deals in 2021.

Separately, the American Medical Association earlier released a separate report on trends in physician practice arrangements, finding that the percentage of physicians working in private equity–owned groups was 4.5% in 2022, the same as in its previous 2020 report. The share of physicians working in private practices fell by 13 percentage points from 60.1% to 46.7% between 2012 and 2022, the AMA reported.

The Berkeley report and the AMA update come amid rising concerns about the effects of the decline of independent physician practices. The U.S. Senate Finance Committee, which oversees most federal health spending, held a June hearing examining the causes and consequences of increased corporate ownership in health care, including a look at physician practices.

“It’s increasingly clear that consolidation in health care is not lowering costs or increasing the quality of Americans’ health care,” Senate Finance Chairman Ron Wyden (D-Ore.) said in an email. “For private equity in health care in particular, there needs to be more transparency around ownership so the effect on these business relationships can be better understood.”

Federal and state agencies do not generally track acquisitions of physician practices.

The UC Berkeley report impressively documents the rising influence of private equity in health care, for which it’s tough to find good data, said Karen Joynt Maddox, MD, MPH, of Washington University in St. Louis. Dr. Maddox, a cardiologist and policy researcher who also has studied the effects of consolidation in health care, examined the new report at the request of this news organization.

“They did a great job with the data,” Dr. Maddox said. “One of the big issues around private equity, and in general, ‘corporatization’ and consolidation of health care, is that there’s not a great way to track ownership changes. It’s really difficult to study.”

Dr. Scheffler and colleagues used data from the commercial firm PitchBook to identify acquisitions of physician practices by private equity firms. They consulted IQVIA’s physician databases – OneKey and SK&A Office-Based Physicians Database – to learn about the location, size, and specialties of acquired practices. They also used data from the nonprofit Health Care Cost Institute, which tracks commercial health plan claims, to assess how private equity acquisitions affected prices.

The researchers then matched the findings for practices acquired by private equity firms from 2015 to 2021 against those for comparable physician practices that remained independent from 2012 to 2021.

The authors then tied private-equity ownership to the following price increases:

• Gastroenterology (14%; 95% confidence interval, 7.9%-20.4%
• Oncology (16.4%; 95% CI, 5.5%-28.4%)
• Dermatology (4.0%; 95% CI, 1%-7.1%)
• Ob.gyn. (8.8%; 95% CI, 3.8%-14%)
• Ophthalmology (8.7%; 95% CI, 5.1%-12.3%)
• Radiology (8.2%; 95% CI, 0.8%-16.1%)
• Orthopedics (7.1%; 95% CI, 2.2%-12.3%)
• Primary care (4.1%; 95% CI, 1.3%-7%)

The analysis also found higher prices for cardiology (8.7%; 95% CI, –6.4% to 26.1%) and urology (4.2%; 95% CI, –2.3% to 11.1%), but neither of these findings was statistically significant, one of the authors, Daniel R. Arnold, PhD, of UC Berkeley, said in an email. This was most likely caused by smaller sample sizes for these fields.
 

Factors driving consolidation

The two reports and the Senate Finance consolidation hearing raised similar issues, including calls to look at the factors driving more physicians out of independent practice, including Medicare reimbursement that may not keep up with rising inflation.

The Berkeley report authors called for Congress to add a broad inflation component to the Medicare physician fee schedule. It also called on Congress to add cases where Medicare, the biggest U.S. purchaser of health care, pays less for services when performed in independent practices than in hospital-affiliated ones.

Shawn Martin, executive vice president and CEO of the American Academy of Family Physicians, said his group appreciates how the report from UC Berkeley and nonprofit groups echoed recommendations many clinicians have made, including the call for a broad inflation adjustment for the fee schedule.

“To move the needle forward, Congress must advance site-neutral payment policies while also addressing the administrative requirements that take physicians away from the important work of caring for patients,” Mr. Martin said in an email.

Arnold Ventures provided funding for the report, which was a joint project of the American Antitrust Institute, the Nicholas C. Petris Center on Health Care Markets and Consumer Welfare, UC Berkeley, and the Washington Center for Equitable Growth.

A version of this article appeared on Medscape.com.

Private equity ownership of medical practices was linked to consumer price increases for 8 of 10 specialties examined in a new report, with the most notable gains reported for oncology and gastroenterology.

The report was a collaboration of University of California, Berkeley, staff and researchers from two nonprofits, the American Antitrust Institute and the Washington Center for Equitable Growth. It provides “convincing evidence that incentives to put profits before patients have grown stronger with an increase in private equity ownership of physician practices,” lead author Richard Scheffler, PhD, of UC Berkeley said in a statement.

The report also noted that private equity acquisitions of physician groups have risen sixfold in just a decade, increasing from 75 deals in 2012 to 484 deals in 2021.

Separately, the American Medical Association earlier released a separate report on trends in physician practice arrangements, finding that the percentage of physicians working in private equity–owned groups was 4.5% in 2022, the same as in its previous 2020 report. The share of physicians working in private practices fell by 13 percentage points from 60.1% to 46.7% between 2012 and 2022, the AMA reported.

The Berkeley report and the AMA update come amid rising concerns about the effects of the decline of independent physician practices. The U.S. Senate Finance Committee, which oversees most federal health spending, held a June hearing examining the causes and consequences of increased corporate ownership in health care, including a look at physician practices.

“It’s increasingly clear that consolidation in health care is not lowering costs or increasing the quality of Americans’ health care,” Senate Finance Chairman Ron Wyden (D-Ore.) said in an email. “For private equity in health care in particular, there needs to be more transparency around ownership so the effect on these business relationships can be better understood.”

Federal and state agencies do not generally track acquisitions of physician practices.

The UC Berkeley report impressively documents the rising influence of private equity in health care, for which it’s tough to find good data, said Karen Joynt Maddox, MD, MPH, of Washington University in St. Louis. Dr. Maddox, a cardiologist and policy researcher who also has studied the effects of consolidation in health care, examined the new report at the request of this news organization.

“They did a great job with the data,” Dr. Maddox said. “One of the big issues around private equity, and in general, ‘corporatization’ and consolidation of health care, is that there’s not a great way to track ownership changes. It’s really difficult to study.”

Dr. Scheffler and colleagues used data from the commercial firm PitchBook to identify acquisitions of physician practices by private equity firms. They consulted IQVIA’s physician databases – OneKey and SK&A Office-Based Physicians Database – to learn about the location, size, and specialties of acquired practices. They also used data from the nonprofit Health Care Cost Institute, which tracks commercial health plan claims, to assess how private equity acquisitions affected prices.

The researchers then matched the findings for practices acquired by private equity firms from 2015 to 2021 against those for comparable physician practices that remained independent from 2012 to 2021.

The authors then tied private-equity ownership to the following price increases:

• Gastroenterology (14%; 95% confidence interval, 7.9%-20.4%
• Oncology (16.4%; 95% CI, 5.5%-28.4%)
• Dermatology (4.0%; 95% CI, 1%-7.1%)
• Ob.gyn. (8.8%; 95% CI, 3.8%-14%)
• Ophthalmology (8.7%; 95% CI, 5.1%-12.3%)
• Radiology (8.2%; 95% CI, 0.8%-16.1%)
• Orthopedics (7.1%; 95% CI, 2.2%-12.3%)
• Primary care (4.1%; 95% CI, 1.3%-7%)

The analysis also found higher prices for cardiology (8.7%; 95% CI, –6.4% to 26.1%) and urology (4.2%; 95% CI, –2.3% to 11.1%), but neither of these findings was statistically significant, one of the authors, Daniel R. Arnold, PhD, of UC Berkeley, said in an email. This was most likely caused by smaller sample sizes for these fields.
 

Factors driving consolidation

The two reports and the Senate Finance consolidation hearing raised similar issues, including calls to look at the factors driving more physicians out of independent practice, including Medicare reimbursement that may not keep up with rising inflation.

The Berkeley report authors called for Congress to add a broad inflation component to the Medicare physician fee schedule. It also called on Congress to add cases where Medicare, the biggest U.S. purchaser of health care, pays less for services when performed in independent practices than in hospital-affiliated ones.

Shawn Martin, executive vice president and CEO of the American Academy of Family Physicians, said his group appreciates how the report from UC Berkeley and nonprofit groups echoed recommendations many clinicians have made, including the call for a broad inflation adjustment for the fee schedule.

“To move the needle forward, Congress must advance site-neutral payment policies while also addressing the administrative requirements that take physicians away from the important work of caring for patients,” Mr. Martin said in an email.

Arnold Ventures provided funding for the report, which was a joint project of the American Antitrust Institute, the Nicholas C. Petris Center on Health Care Markets and Consumer Welfare, UC Berkeley, and the Washington Center for Equitable Growth.

A version of this article appeared on Medscape.com.

Experience with long COVID has shone a spotlight on persistent Lyme disease and other often debilitating chronic illnesses that follow known or suspected infections – and on the urgent need for a common and well-funded research agenda, education of physicians, growth of multidisciplinary clinics, and financially supported clinical care.

“We critically need to understand the epidemiology and pathogenesis of chronic symptoms, and identify more effective ways to manage, treat, and potentially cure these illnesses,” Lyle Petersen, MD, MPH, director of the division of vector-borne diseases at the Centers for Disease Control and Prevention, said at the start of a 2-day National Academies of Science, Engineering, and Medicine (NASEM) workshop, “Toward a Common Research Agenda in Infection-Associated Chronic Illnesses.”

Thinking about infection-associated chronic illnesses as an entity – one predicated on commonalities in chronic symptoms and in leading hypotheses for causes – represents a paradigm shift that researchers and patient advocates said can avoid research redundancies and is essential to address what the NASEM calls an overlooked, growing public health problem.

An estimated 2 million people in the United States are living with what’s called posttreatment Lyme disease (PTLD) – a subset of patients with persistent or chronic Lyme disease – and an estimated 1.7-3.3 million people in the United States have diagnoses of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). More than 700,000 people are living with multiple sclerosis. And as of January 2023, 11% of people in the United States reported having long COVID symptoms; the incidence of long COVID is currently estimated at 10%-30% of nonhospitalized cases of COVID-19.

These illnesses “have come under one umbrella,” said Avindra Nath, MD, clinical director of the National Institute of Neurologic Disorders and Stroke (NINDS), Bethesda, Md.

Dr. Nath

Persistent infection, viral reactivation

RNA viral infections can lead to persistent inflammation and dysregulated immunity, with or without viral persistence over time, Timothy J. Henrich, MD, MMSc, associate professor of medicine at the University of California, San Francisco, said in a keynote address.

Research on Ebola survivors has documented long-lasting inflammation and severe immune dysfunction 2 years after infection, for instance. And it’s well known that HIV-1 leads to aberrant immune responses, inflammation, and organ damage despite antiretroviral therapy, said Dr. Henrich, who leads a laboratory/research group that studies approaches to HIV-1 cure and PET-based imaging approaches to characterize viral reservoirs and immune sequelae.

Viral persistence, which can be difficult to measure, has also been documented in Ebola survivors. And in patients living with HIV-1, HIV-1 RNA and protein expression have been shown to persist, again despite antiretroviral therapy. The UCSF Long-Term Immunological Impact of Novel Coronavirus (LIINC) study, for which Dr. Henrich is the principal investigator, found spike RNA in colorectal tissue more than 22 months post COVID, and other research documented viral protein in gut tissue for up to 6 months, he said.

“I think we’re appreciating now, in at least the scientific and treatment community, that there’s a potential for ‘acute’ infections to exhibit some degree of persistence leading to clinical morbidity,” said Dr. Henrich, one of several speakers to describe reports of pathogen persistence. Regarding long COVID, its “etiology is likely heterogeneous,” he said, but persistence of SARS-CoV-2 “may lay behind” other described mechanisms, from clotting/microvascular dysfunction to inflammation and tissue damage to immune dysregulation.

Reactivation of existing latent viral infections in the setting of new acute microbial illness may also play an etiologic role in chronic illnesses, Dr. Henrich said. Epstein-Barr virus (EBV) reactivation has been shown in some studies, including their UCSF COVID-19 cohort, to be associated with long COVID.

“Physicians have been trained to be skeptical about the role [of latent viral infections],” Michael Peluso, MD, an infectious disease physician and assistant professor at UCSF, said during a talk on viral reactivation. This skepticism needs to be “reexamined and overcome,” he said.

Herpesviruses have frequently been associated with ME/CFS, he noted. And evidence of a strong association between EBV and multiple sclerosis came recently from a prospective study of 10 million military recruits that found a 32-fold increased risk of MS after EBV infection but no increase after infection with other viruses, Dr. Peluso and Dr. Henrich both noted.
 

Research needs, treatment trials

Research needs are vast: The need to learn more about the mechanisms of pathogen persistence and immune evasion, for instance, and the need for more biomarker studies, more imaging studies and tissue analyses, more study of microbiome composition and activity, and continued development and application of metagenomic next-generation sequencing.

Workshop participants also spoke of the need to better understand the molecular mimicry that can occur between pathogen-produced proteins and self-antigens, for instance, and the effects of inflammation and infection-related immune changes on neuronal and microglial function in the brain.

“We should perform similar forms of analysis [across] patients with different infection-associated chronic conditions,” said Amy Proal, PhD, president of the PolyBio Research Foundation, which funds research on infection-associated chronic infections. And within individual conditions and well-characterized study groups “we should perform many different forms of analysis … so we can define endotypes and get more solid biomarkers so that industry [will have more confidence] to run clinical trials.”

In the meantime, patients need fast-moving treatment trials for long COVID, long Lyme, and other infection-associated chronic illnesses, speakers emphasized. “We all agree that treatment trials are overdue,” said the NINDS’ Dr. Nath. “We can’t afford to wait for another decade until we understand all the mechanisms, but rather we can do clinical trials based on what we understand now and study the pathophysiology in the context of the clinical trials.”

Just as was done with HIV, said Steven G. Deeks, MD, professor of medicine at UCSF, researchers must “practice experimental medicine” and select pathways and mechanisms of interest, interrupt those pathways in a controlled manner, and assess impact. “Much of this can be done by repurposing existing drugs,” he said, like antivirals for persistent viral infection, EBV-directed therapies for EBV reactivation, anti-inflammatory drugs for inflammation, B–cell-directed therapies for autoantibodies, and antiplatelet drugs for microvascular disease.

When done correctly, he said, such “probe” studies can deepen mechanistic understandings, lead to biomarkers, and provide proof-of-concept that “will encourage massive investment in developing new therapies” for long COVID and other infection-associated chronic illnesses.

Trials of treatments for long COVID “are starting, so I’m optimistic,” said Dr. Deeks, an expert on HIV pathogenesis and treatment and a principal investigator of the Researching COVID to Enhance Recovery (RECOVER) study. Among the trials: A study of intravenous immunoglobulin (IVIG) for neurologic long COVID; a study of an anti-SARS-CoV-2 monoclonal antibody that can deplete tissue/cellular reservoirs of viral particles (replicating or not); and a study evaluating baricitinib (Olumiant), a Janus kinase inhibitor, for neurocognitive impairment and cardiopulmonary symptoms of long COVID.

Alessio Fasano, MD, professor of pediatrics at Harvard Medical School and professor of nutrition at the Harvard T.H. Chan School of Public Health, Boston, described at the workshop how he began investigating the use of larazotide acetate – an inhibitor of the protein zonulin, which increases intestinal permeability – in children with COVID-19 Multisystem Inflammatory Syndrome (MIS-C) after learning that SARS-CoV-2 viral particles persist in the gastrointestinal tract, causing dysbiosis and zonulin upregulation.

In an ongoing phase 2, double-blind, placebo-controlled trial, the agent thus far has expedited the resolution of gastrointestinal symptoms and clearance of spike protein from the circulation, he said. A phase 2 trial of the agent for pediatric patients with long COVID and SARS-CoV-2 antigenemia is underway. “What if we were to stop [chains of events] by stopping the passage of elements from the virus into circulation?’ he said.

In the realm of Lyme disease, a recently launched Clinical Trials Network for Lyme and Other Tick-Borne Diseases has awarded pilot study grants to evaluate treatments aimed at a variety of possible disease mechanisms that, notably, are similar to those of other chronic illnesses: persistence of infection or remnants of infection, immune dysregulation and autoimmune reactions, neural dysfunction, and gut microbiome changes. (Microclots and mitochondrial dysfunction have not been as well studied in Lyme.)

Current and upcoming studies include evaluations of transcutaneous auricular vagus nerve stimulation for those with persistent Lyme fatigue, transcranial direct current stimulation with cognitive retraining for Lyme brain fog, and tetracycline for PTLD, said Brian Fallon, MD, MPH, professor of clinical psychiatry at Columbia University, New York, who directs the Lyme & Tick-Borne Diseases Research Center and the coordinating center of the new network.

Columbia University Irving Medical Center

Calls for a new NIH center and patient involvement

Patients and patient advocacy organizations have played a vital role in research thus far: They’ve documented post-COVID symptoms that academic researchers said they would not otherwise have known of. Leaders of the Patient-Led Research Collaborative have coauthored published reviews with leading long COVID experts. And patients with tick-borne illnesses have enrolled in the MyLymeData patient registry run by LymeDisease.org, which has documented patient-experienced efficacy of alternative treatments and described antibiotic responders and nonresponders.

At the workshop, they shared findings alongside academic experts, and researchers called for their continued involvement. “Patient engagement at every step of the research process is critical,” Dr. Nath said.

“We need to ensure that research is reflective of lived experiences … and [that we’re] accelerating clinical trials of therapeutics that are of priority to the patient community,” said Lisa McCorkell, cofounder of the long COVID-focused Patient-Led Research Collaborative.

Ms. McCorkell also called for the creation of an office for infection-associated chronic illnesses in the NIH director’s office. Others voiced their support. “I think it’s a great idea to have an NIH center for infection-associated chronic illnesses,” said Dr. Fallon. “I think it would have a profound impact.”

The other great need, of course, is funding. “We have ideas, we have drugs that can be repurposed, we have a highly informed and engaged community that will enroll in and be retained in studies, and we have outcomes we can measure,” Dr. Deeks said. “What we’re missing is industry engagement and funding. We need massive engagement from the NIH.”
 

Real-world treatment needs

In the meantime, patients are seeking treatment, and “clinicians need to have uncertainty tolerance” and try multiple treatments simultaneously, said David Putrino, PT, PhD, director of rehabilitation innovation for the Mount Sinai Health System and professor of rehabilitation and human performance at the Icahn School of Medicine at Mount Sinai, New York. He oversees a multidisciplinary hybrid clinical care research center that has seen over 1,500 patients with long COVID and is beginning to see patients with other infection-associated chronic illnesses.

Claudia Paul

It’s a model that should be replicated to help fill the “enormous unmet clinical need” of patients with infection-associated chronic illness, said Peter Rowe, MD, professor of pediatrics at the Johns Hopkins School of Medicine and an expert on ME/CFS. And “as we request [more research funding], we will also need [financial] support for clinical care,” he emphasized, to provide equitable access for patients and to attract treating physicians.

Moreover, said Linda Geng, MD, PhD, the culture of stigma needs to change. Right now, patients with long COVID often feel dismissed not only by friends, families, and coworkers, but by clinicians who find it find it hard “to grasp that this is real and a biological condition.”

And it’s not just conditions such as long COVID that are stigmatized, but treatments as well, she said. For instance, some clinicians view low-dose naltrexone, a treatment increasingly being used for inflammation, with suspicion because it is used for opioid use disorder and alcohol use disorder – or because the “low-dose” label summons mistrust of homeopathy. “Even with therapies, there are preconceived notions and biases,” said Dr. Geng, cofounder and codirector of the Stanford (Calif.) Long COVID program.

“What almost killed me,” said Meghan O’Rourke, who has ongoing effects from long-undiagnosed tick-borne illness, “was the invisibility of the illness.” Ms. O’Rourke teaches at Yale University and is the author of “The Invisible Kingdom: Reimagining Chronic Illness.”

Teaching young physicians about these illnesses would help, she and others said. During a question and answer session, Dr. Putrino shared that the Icahn School of Medicine has recently committed to “create a complex chronic illness medical curriculum” that will impact medical education from the first year of medical school through residencies. Dr. Putrino said his team is also working on materials to help other clinics develop care models similar to those at his Mount Sinai clinic.

The NASEM workshop did not collect or require disclosures of its participants.

Experience with long COVID has shone a spotlight on persistent Lyme disease and other often debilitating chronic illnesses that follow known or suspected infections – and on the urgent need for a common and well-funded research agenda, education of physicians, growth of multidisciplinary clinics, and financially supported clinical care.

“We critically need to understand the epidemiology and pathogenesis of chronic symptoms, and identify more effective ways to manage, treat, and potentially cure these illnesses,” Lyle Petersen, MD, MPH, director of the division of vector-borne diseases at the Centers for Disease Control and Prevention, said at the start of a 2-day National Academies of Science, Engineering, and Medicine (NASEM) workshop, “Toward a Common Research Agenda in Infection-Associated Chronic Illnesses.”

Thinking about infection-associated chronic illnesses as an entity – one predicated on commonalities in chronic symptoms and in leading hypotheses for causes – represents a paradigm shift that researchers and patient advocates said can avoid research redundancies and is essential to address what the NASEM calls an overlooked, growing public health problem.

An estimated 2 million people in the United States are living with what’s called posttreatment Lyme disease (PTLD) – a subset of patients with persistent or chronic Lyme disease – and an estimated 1.7-3.3 million people in the United States have diagnoses of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). More than 700,000 people are living with multiple sclerosis. And as of January 2023, 11% of people in the United States reported having long COVID symptoms; the incidence of long COVID is currently estimated at 10%-30% of nonhospitalized cases of COVID-19.

These illnesses “have come under one umbrella,” said Avindra Nath, MD, clinical director of the National Institute of Neurologic Disorders and Stroke (NINDS), Bethesda, Md.

Dr. Nath

Persistent infection, viral reactivation

RNA viral infections can lead to persistent inflammation and dysregulated immunity, with or without viral persistence over time, Timothy J. Henrich, MD, MMSc, associate professor of medicine at the University of California, San Francisco, said in a keynote address.

Research on Ebola survivors has documented long-lasting inflammation and severe immune dysfunction 2 years after infection, for instance. And it’s well known that HIV-1 leads to aberrant immune responses, inflammation, and organ damage despite antiretroviral therapy, said Dr. Henrich, who leads a laboratory/research group that studies approaches to HIV-1 cure and PET-based imaging approaches to characterize viral reservoirs and immune sequelae.

Viral persistence, which can be difficult to measure, has also been documented in Ebola survivors. And in patients living with HIV-1, HIV-1 RNA and protein expression have been shown to persist, again despite antiretroviral therapy. The UCSF Long-Term Immunological Impact of Novel Coronavirus (LIINC) study, for which Dr. Henrich is the principal investigator, found spike RNA in colorectal tissue more than 22 months post COVID, and other research documented viral protein in gut tissue for up to 6 months, he said.

“I think we’re appreciating now, in at least the scientific and treatment community, that there’s a potential for ‘acute’ infections to exhibit some degree of persistence leading to clinical morbidity,” said Dr. Henrich, one of several speakers to describe reports of pathogen persistence. Regarding long COVID, its “etiology is likely heterogeneous,” he said, but persistence of SARS-CoV-2 “may lay behind” other described mechanisms, from clotting/microvascular dysfunction to inflammation and tissue damage to immune dysregulation.

Reactivation of existing latent viral infections in the setting of new acute microbial illness may also play an etiologic role in chronic illnesses, Dr. Henrich said. Epstein-Barr virus (EBV) reactivation has been shown in some studies, including their UCSF COVID-19 cohort, to be associated with long COVID.

“Physicians have been trained to be skeptical about the role [of latent viral infections],” Michael Peluso, MD, an infectious disease physician and assistant professor at UCSF, said during a talk on viral reactivation. This skepticism needs to be “reexamined and overcome,” he said.

Herpesviruses have frequently been associated with ME/CFS, he noted. And evidence of a strong association between EBV and multiple sclerosis came recently from a prospective study of 10 million military recruits that found a 32-fold increased risk of MS after EBV infection but no increase after infection with other viruses, Dr. Peluso and Dr. Henrich both noted.
 

Research needs, treatment trials

Research needs are vast: The need to learn more about the mechanisms of pathogen persistence and immune evasion, for instance, and the need for more biomarker studies, more imaging studies and tissue analyses, more study of microbiome composition and activity, and continued development and application of metagenomic next-generation sequencing.

Workshop participants also spoke of the need to better understand the molecular mimicry that can occur between pathogen-produced proteins and self-antigens, for instance, and the effects of inflammation and infection-related immune changes on neuronal and microglial function in the brain.

“We should perform similar forms of analysis [across] patients with different infection-associated chronic conditions,” said Amy Proal, PhD, president of the PolyBio Research Foundation, which funds research on infection-associated chronic infections. And within individual conditions and well-characterized study groups “we should perform many different forms of analysis … so we can define endotypes and get more solid biomarkers so that industry [will have more confidence] to run clinical trials.”

In the meantime, patients need fast-moving treatment trials for long COVID, long Lyme, and other infection-associated chronic illnesses, speakers emphasized. “We all agree that treatment trials are overdue,” said the NINDS’ Dr. Nath. “We can’t afford to wait for another decade until we understand all the mechanisms, but rather we can do clinical trials based on what we understand now and study the pathophysiology in the context of the clinical trials.”

Just as was done with HIV, said Steven G. Deeks, MD, professor of medicine at UCSF, researchers must “practice experimental medicine” and select pathways and mechanisms of interest, interrupt those pathways in a controlled manner, and assess impact. “Much of this can be done by repurposing existing drugs,” he said, like antivirals for persistent viral infection, EBV-directed therapies for EBV reactivation, anti-inflammatory drugs for inflammation, B–cell-directed therapies for autoantibodies, and antiplatelet drugs for microvascular disease.

When done correctly, he said, such “probe” studies can deepen mechanistic understandings, lead to biomarkers, and provide proof-of-concept that “will encourage massive investment in developing new therapies” for long COVID and other infection-associated chronic illnesses.

Trials of treatments for long COVID “are starting, so I’m optimistic,” said Dr. Deeks, an expert on HIV pathogenesis and treatment and a principal investigator of the Researching COVID to Enhance Recovery (RECOVER) study. Among the trials: A study of intravenous immunoglobulin (IVIG) for neurologic long COVID; a study of an anti-SARS-CoV-2 monoclonal antibody that can deplete tissue/cellular reservoirs of viral particles (replicating or not); and a study evaluating baricitinib (Olumiant), a Janus kinase inhibitor, for neurocognitive impairment and cardiopulmonary symptoms of long COVID.

Alessio Fasano, MD, professor of pediatrics at Harvard Medical School and professor of nutrition at the Harvard T.H. Chan School of Public Health, Boston, described at the workshop how he began investigating the use of larazotide acetate – an inhibitor of the protein zonulin, which increases intestinal permeability – in children with COVID-19 Multisystem Inflammatory Syndrome (MIS-C) after learning that SARS-CoV-2 viral particles persist in the gastrointestinal tract, causing dysbiosis and zonulin upregulation.

In an ongoing phase 2, double-blind, placebo-controlled trial, the agent thus far has expedited the resolution of gastrointestinal symptoms and clearance of spike protein from the circulation, he said. A phase 2 trial of the agent for pediatric patients with long COVID and SARS-CoV-2 antigenemia is underway. “What if we were to stop [chains of events] by stopping the passage of elements from the virus into circulation?’ he said.

In the realm of Lyme disease, a recently launched Clinical Trials Network for Lyme and Other Tick-Borne Diseases has awarded pilot study grants to evaluate treatments aimed at a variety of possible disease mechanisms that, notably, are similar to those of other chronic illnesses: persistence of infection or remnants of infection, immune dysregulation and autoimmune reactions, neural dysfunction, and gut microbiome changes. (Microclots and mitochondrial dysfunction have not been as well studied in Lyme.)

Current and upcoming studies include evaluations of transcutaneous auricular vagus nerve stimulation for those with persistent Lyme fatigue, transcranial direct current stimulation with cognitive retraining for Lyme brain fog, and tetracycline for PTLD, said Brian Fallon, MD, MPH, professor of clinical psychiatry at Columbia University, New York, who directs the Lyme & Tick-Borne Diseases Research Center and the coordinating center of the new network.

Columbia University Irving Medical Center

Calls for a new NIH center and patient involvement

Patients and patient advocacy organizations have played a vital role in research thus far: They’ve documented post-COVID symptoms that academic researchers said they would not otherwise have known of. Leaders of the Patient-Led Research Collaborative have coauthored published reviews with leading long COVID experts. And patients with tick-borne illnesses have enrolled in the MyLymeData patient registry run by LymeDisease.org, which has documented patient-experienced efficacy of alternative treatments and described antibiotic responders and nonresponders.

At the workshop, they shared findings alongside academic experts, and researchers called for their continued involvement. “Patient engagement at every step of the research process is critical,” Dr. Nath said.

“We need to ensure that research is reflective of lived experiences … and [that we’re] accelerating clinical trials of therapeutics that are of priority to the patient community,” said Lisa McCorkell, cofounder of the long COVID-focused Patient-Led Research Collaborative.

Ms. McCorkell also called for the creation of an office for infection-associated chronic illnesses in the NIH director’s office. Others voiced their support. “I think it’s a great idea to have an NIH center for infection-associated chronic illnesses,” said Dr. Fallon. “I think it would have a profound impact.”

The other great need, of course, is funding. “We have ideas, we have drugs that can be repurposed, we have a highly informed and engaged community that will enroll in and be retained in studies, and we have outcomes we can measure,” Dr. Deeks said. “What we’re missing is industry engagement and funding. We need massive engagement from the NIH.”
 

Real-world treatment needs

In the meantime, patients are seeking treatment, and “clinicians need to have uncertainty tolerance” and try multiple treatments simultaneously, said David Putrino, PT, PhD, director of rehabilitation innovation for the Mount Sinai Health System and professor of rehabilitation and human performance at the Icahn School of Medicine at Mount Sinai, New York. He oversees a multidisciplinary hybrid clinical care research center that has seen over 1,500 patients with long COVID and is beginning to see patients with other infection-associated chronic illnesses.

Claudia Paul

It’s a model that should be replicated to help fill the “enormous unmet clinical need” of patients with infection-associated chronic illness, said Peter Rowe, MD, professor of pediatrics at the Johns Hopkins School of Medicine and an expert on ME/CFS. And “as we request [more research funding], we will also need [financial] support for clinical care,” he emphasized, to provide equitable access for patients and to attract treating physicians.

Moreover, said Linda Geng, MD, PhD, the culture of stigma needs to change. Right now, patients with long COVID often feel dismissed not only by friends, families, and coworkers, but by clinicians who find it find it hard “to grasp that this is real and a biological condition.”

And it’s not just conditions such as long COVID that are stigmatized, but treatments as well, she said. For instance, some clinicians view low-dose naltrexone, a treatment increasingly being used for inflammation, with suspicion because it is used for opioid use disorder and alcohol use disorder – or because the “low-dose” label summons mistrust of homeopathy. “Even with therapies, there are preconceived notions and biases,” said Dr. Geng, cofounder and codirector of the Stanford (Calif.) Long COVID program.

“What almost killed me,” said Meghan O’Rourke, who has ongoing effects from long-undiagnosed tick-borne illness, “was the invisibility of the illness.” Ms. O’Rourke teaches at Yale University and is the author of “The Invisible Kingdom: Reimagining Chronic Illness.”

Teaching young physicians about these illnesses would help, she and others said. During a question and answer session, Dr. Putrino shared that the Icahn School of Medicine has recently committed to “create a complex chronic illness medical curriculum” that will impact medical education from the first year of medical school through residencies. Dr. Putrino said his team is also working on materials to help other clinics develop care models similar to those at his Mount Sinai clinic.

The NASEM workshop did not collect or require disclosures of its participants.

Experience with long COVID has shone a spotlight on persistent Lyme disease and other often debilitating chronic illnesses that follow known or suspected infections – and on the urgent need for a common and well-funded research agenda, education of physicians, growth of multidisciplinary clinics, and financially supported clinical care.

“We critically need to understand the epidemiology and pathogenesis of chronic symptoms, and identify more effective ways to manage, treat, and potentially cure these illnesses,” Lyle Petersen, MD, MPH, director of the division of vector-borne diseases at the Centers for Disease Control and Prevention, said at the start of a 2-day National Academies of Science, Engineering, and Medicine (NASEM) workshop, “Toward a Common Research Agenda in Infection-Associated Chronic Illnesses.”

Thinking about infection-associated chronic illnesses as an entity – one predicated on commonalities in chronic symptoms and in leading hypotheses for causes – represents a paradigm shift that researchers and patient advocates said can avoid research redundancies and is essential to address what the NASEM calls an overlooked, growing public health problem.

An estimated 2 million people in the United States are living with what’s called posttreatment Lyme disease (PTLD) – a subset of patients with persistent or chronic Lyme disease – and an estimated 1.7-3.3 million people in the United States have diagnoses of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). More than 700,000 people are living with multiple sclerosis. And as of January 2023, 11% of people in the United States reported having long COVID symptoms; the incidence of long COVID is currently estimated at 10%-30% of nonhospitalized cases of COVID-19.

These illnesses “have come under one umbrella,” said Avindra Nath, MD, clinical director of the National Institute of Neurologic Disorders and Stroke (NINDS), Bethesda, Md.

Dr. Nath

Persistent infection, viral reactivation

RNA viral infections can lead to persistent inflammation and dysregulated immunity, with or without viral persistence over time, Timothy J. Henrich, MD, MMSc, associate professor of medicine at the University of California, San Francisco, said in a keynote address.

Research on Ebola survivors has documented long-lasting inflammation and severe immune dysfunction 2 years after infection, for instance. And it’s well known that HIV-1 leads to aberrant immune responses, inflammation, and organ damage despite antiretroviral therapy, said Dr. Henrich, who leads a laboratory/research group that studies approaches to HIV-1 cure and PET-based imaging approaches to characterize viral reservoirs and immune sequelae.

Viral persistence, which can be difficult to measure, has also been documented in Ebola survivors. And in patients living with HIV-1, HIV-1 RNA and protein expression have been shown to persist, again despite antiretroviral therapy. The UCSF Long-Term Immunological Impact of Novel Coronavirus (LIINC) study, for which Dr. Henrich is the principal investigator, found spike RNA in colorectal tissue more than 22 months post COVID, and other research documented viral protein in gut tissue for up to 6 months, he said.

“I think we’re appreciating now, in at least the scientific and treatment community, that there’s a potential for ‘acute’ infections to exhibit some degree of persistence leading to clinical morbidity,” said Dr. Henrich, one of several speakers to describe reports of pathogen persistence. Regarding long COVID, its “etiology is likely heterogeneous,” he said, but persistence of SARS-CoV-2 “may lay behind” other described mechanisms, from clotting/microvascular dysfunction to inflammation and tissue damage to immune dysregulation.

Reactivation of existing latent viral infections in the setting of new acute microbial illness may also play an etiologic role in chronic illnesses, Dr. Henrich said. Epstein-Barr virus (EBV) reactivation has been shown in some studies, including their UCSF COVID-19 cohort, to be associated with long COVID.

“Physicians have been trained to be skeptical about the role [of latent viral infections],” Michael Peluso, MD, an infectious disease physician and assistant professor at UCSF, said during a talk on viral reactivation. This skepticism needs to be “reexamined and overcome,” he said.

Herpesviruses have frequently been associated with ME/CFS, he noted. And evidence of a strong association between EBV and multiple sclerosis came recently from a prospective study of 10 million military recruits that found a 32-fold increased risk of MS after EBV infection but no increase after infection with other viruses, Dr. Peluso and Dr. Henrich both noted.
 

Research needs, treatment trials

Research needs are vast: The need to learn more about the mechanisms of pathogen persistence and immune evasion, for instance, and the need for more biomarker studies, more imaging studies and tissue analyses, more study of microbiome composition and activity, and continued development and application of metagenomic next-generation sequencing.

Workshop participants also spoke of the need to better understand the molecular mimicry that can occur between pathogen-produced proteins and self-antigens, for instance, and the effects of inflammation and infection-related immune changes on neuronal and microglial function in the brain.

“We should perform similar forms of analysis [across] patients with different infection-associated chronic conditions,” said Amy Proal, PhD, president of the PolyBio Research Foundation, which funds research on infection-associated chronic infections. And within individual conditions and well-characterized study groups “we should perform many different forms of analysis … so we can define endotypes and get more solid biomarkers so that industry [will have more confidence] to run clinical trials.”

In the meantime, patients need fast-moving treatment trials for long COVID, long Lyme, and other infection-associated chronic illnesses, speakers emphasized. “We all agree that treatment trials are overdue,” said the NINDS’ Dr. Nath. “We can’t afford to wait for another decade until we understand all the mechanisms, but rather we can do clinical trials based on what we understand now and study the pathophysiology in the context of the clinical trials.”

Just as was done with HIV, said Steven G. Deeks, MD, professor of medicine at UCSF, researchers must “practice experimental medicine” and select pathways and mechanisms of interest, interrupt those pathways in a controlled manner, and assess impact. “Much of this can be done by repurposing existing drugs,” he said, like antivirals for persistent viral infection, EBV-directed therapies for EBV reactivation, anti-inflammatory drugs for inflammation, B–cell-directed therapies for autoantibodies, and antiplatelet drugs for microvascular disease.

When done correctly, he said, such “probe” studies can deepen mechanistic understandings, lead to biomarkers, and provide proof-of-concept that “will encourage massive investment in developing new therapies” for long COVID and other infection-associated chronic illnesses.

Trials of treatments for long COVID “are starting, so I’m optimistic,” said Dr. Deeks, an expert on HIV pathogenesis and treatment and a principal investigator of the Researching COVID to Enhance Recovery (RECOVER) study. Among the trials: A study of intravenous immunoglobulin (IVIG) for neurologic long COVID; a study of an anti-SARS-CoV-2 monoclonal antibody that can deplete tissue/cellular reservoirs of viral particles (replicating or not); and a study evaluating baricitinib (Olumiant), a Janus kinase inhibitor, for neurocognitive impairment and cardiopulmonary symptoms of long COVID.

Alessio Fasano, MD, professor of pediatrics at Harvard Medical School and professor of nutrition at the Harvard T.H. Chan School of Public Health, Boston, described at the workshop how he began investigating the use of larazotide acetate – an inhibitor of the protein zonulin, which increases intestinal permeability – in children with COVID-19 Multisystem Inflammatory Syndrome (MIS-C) after learning that SARS-CoV-2 viral particles persist in the gastrointestinal tract, causing dysbiosis and zonulin upregulation.

In an ongoing phase 2, double-blind, placebo-controlled trial, the agent thus far has expedited the resolution of gastrointestinal symptoms and clearance of spike protein from the circulation, he said. A phase 2 trial of the agent for pediatric patients with long COVID and SARS-CoV-2 antigenemia is underway. “What if we were to stop [chains of events] by stopping the passage of elements from the virus into circulation?’ he said.

In the realm of Lyme disease, a recently launched Clinical Trials Network for Lyme and Other Tick-Borne Diseases has awarded pilot study grants to evaluate treatments aimed at a variety of possible disease mechanisms that, notably, are similar to those of other chronic illnesses: persistence of infection or remnants of infection, immune dysregulation and autoimmune reactions, neural dysfunction, and gut microbiome changes. (Microclots and mitochondrial dysfunction have not been as well studied in Lyme.)

Current and upcoming studies include evaluations of transcutaneous auricular vagus nerve stimulation for those with persistent Lyme fatigue, transcranial direct current stimulation with cognitive retraining for Lyme brain fog, and tetracycline for PTLD, said Brian Fallon, MD, MPH, professor of clinical psychiatry at Columbia University, New York, who directs the Lyme & Tick-Borne Diseases Research Center and the coordinating center of the new network.

Columbia University Irving Medical Center

Calls for a new NIH center and patient involvement

Patients and patient advocacy organizations have played a vital role in research thus far: They’ve documented post-COVID symptoms that academic researchers said they would not otherwise have known of. Leaders of the Patient-Led Research Collaborative have coauthored published reviews with leading long COVID experts. And patients with tick-borne illnesses have enrolled in the MyLymeData patient registry run by LymeDisease.org, which has documented patient-experienced efficacy of alternative treatments and described antibiotic responders and nonresponders.

At the workshop, they shared findings alongside academic experts, and researchers called for their continued involvement. “Patient engagement at every step of the research process is critical,” Dr. Nath said.

“We need to ensure that research is reflective of lived experiences … and [that we’re] accelerating clinical trials of therapeutics that are of priority to the patient community,” said Lisa McCorkell, cofounder of the long COVID-focused Patient-Led Research Collaborative.

Ms. McCorkell also called for the creation of an office for infection-associated chronic illnesses in the NIH director’s office. Others voiced their support. “I think it’s a great idea to have an NIH center for infection-associated chronic illnesses,” said Dr. Fallon. “I think it would have a profound impact.”

The other great need, of course, is funding. “We have ideas, we have drugs that can be repurposed, we have a highly informed and engaged community that will enroll in and be retained in studies, and we have outcomes we can measure,” Dr. Deeks said. “What we’re missing is industry engagement and funding. We need massive engagement from the NIH.”
 

Real-world treatment needs

In the meantime, patients are seeking treatment, and “clinicians need to have uncertainty tolerance” and try multiple treatments simultaneously, said David Putrino, PT, PhD, director of rehabilitation innovation for the Mount Sinai Health System and professor of rehabilitation and human performance at the Icahn School of Medicine at Mount Sinai, New York. He oversees a multidisciplinary hybrid clinical care research center that has seen over 1,500 patients with long COVID and is beginning to see patients with other infection-associated chronic illnesses.

Claudia Paul

It’s a model that should be replicated to help fill the “enormous unmet clinical need” of patients with infection-associated chronic illness, said Peter Rowe, MD, professor of pediatrics at the Johns Hopkins School of Medicine and an expert on ME/CFS. And “as we request [more research funding], we will also need [financial] support for clinical care,” he emphasized, to provide equitable access for patients and to attract treating physicians.

Moreover, said Linda Geng, MD, PhD, the culture of stigma needs to change. Right now, patients with long COVID often feel dismissed not only by friends, families, and coworkers, but by clinicians who find it find it hard “to grasp that this is real and a biological condition.”

And it’s not just conditions such as long COVID that are stigmatized, but treatments as well, she said. For instance, some clinicians view low-dose naltrexone, a treatment increasingly being used for inflammation, with suspicion because it is used for opioid use disorder and alcohol use disorder – or because the “low-dose” label summons mistrust of homeopathy. “Even with therapies, there are preconceived notions and biases,” said Dr. Geng, cofounder and codirector of the Stanford (Calif.) Long COVID program.

“What almost killed me,” said Meghan O’Rourke, who has ongoing effects from long-undiagnosed tick-borne illness, “was the invisibility of the illness.” Ms. O’Rourke teaches at Yale University and is the author of “The Invisible Kingdom: Reimagining Chronic Illness.”

Teaching young physicians about these illnesses would help, she and others said. During a question and answer session, Dr. Putrino shared that the Icahn School of Medicine has recently committed to “create a complex chronic illness medical curriculum” that will impact medical education from the first year of medical school through residencies. Dr. Putrino said his team is also working on materials to help other clinics develop care models similar to those at his Mount Sinai clinic.

The NASEM workshop did not collect or require disclosures of its participants.

Several recent developments in Lyme disease treatment and diagnosis may pave the way forward for combating disease that persists following missed or delayed diagnoses or remains following standard treatment. These include combination therapy to address “persister” bacteria and diagnostic tests that test directly for the pathogen and/or indirectly test for host response, according to experts who presented at a 2-day National Academies of Science, Engineering and Medicine workshop on infection-associated chronic illnesses.

Research has shown that 60% of people who are infected and not treated during the early or early disseminated stages of Lyme disease go on to develop late Lyme arthritis, said John Aucott, MD, director of the Johns Hopkins Lyme Disease Clinical Research Center in Baltimore. And in the real world, there’s an additional category of patients: Those who are misdiagnosed and develop infection-related persistent symptoms – such as fatigue, brain fog/cognitive dysfunction, and musculoskeletal problems – that don’t match the “textbook schematic” involving late Lyme arthritis and late neurologic disease.

Moreover, of patients who are treated with protocols recommended by the Infectious Diseases Society of America (IDSA), about 15% go on to develop persistent symptoms at 6 months – again, symptoms that don’t match textbook manifestations and do match symptoms of other infection-associated chronic illnesses. As a “research construct,” this has been coined posttreatment Lyme disease (PTLD), he said at the workshop, “Toward a Common Research Agenda in Infection-Associated Chronic Illnesses.”

(On a practical level, it is hard to know clinically who has early disseminated disease unless they have multiple erythema migrans rashes or neurologic or cardiac involvement, he said after the meeting.)

All this points to the need for tests that are sensitive and specific for diagnosis at all stages of infection and disease, he said in a talk on diagnostics. Currently available tests – those that fit into the widely used two-tiered enzyme-linked immunosorbent assay, Western Blot serology testing – have significant limitations in sensitivity and specificity, including for acute infection when the body has not generated enough antibodies, yet treatment is most likely to succeed.
 

Move toward combination therapy research

Lyme disease is most commonly treated with doxycycline, and that’s problematic because the antibiotic is a microstatic whose efficacy relies on immune clearance of static bacteria, said Monica E. Embers, PhD, director of vector-borne disease at the Tulane National Primate Research Center and associate professor of immunology at Tulane University, New Orleans.

courtesy Tulane University-Paula Burch-Celentano

“But we know that Borrelia burgdorferi has the capability to evade the host immune response in almost every way possible. Persistence is the norm in an immunocompetent host ... [and] dormant bacteria/persisters are more tolerant of microstatic antibiotics,” she said.

Other considerations for antibiotic efficacy include the fact that B. burgdorferi survives for many months inside ticks without nutrient replenishment or replication, “so dormancy is part of their life cycle,” she said. Moreover, the bacteria can be found deep in connective tissues and joints.

The efficacy of accepted regimens of antibiotic treatment has been “a very contentious issue,” she said, noting that guidelines from the International Lyme and Associated Diseases Society “leave open the possibility for antibiotic retreatment when a chronic infection is judged to be a possible cause [of ongoing symptoms].”

The development of persister B. burgdorferi in the presence of antibiotics has been well studied in vitro, which has limitations, Dr. Embers said. But her group specializes in animal models and has shown persistence of antimicrobial-tolerant B. burgdorferi in tick-inoculated rhesus macaques 8-9 months after treatment with oral doxycycline.

“We [also] saw persistence of mild-moderate inflammation in the brain, peripheral nerves, spinal cord, joints and skeletal muscle, and in the heart,” Dr. Embers said, who coauthored a 2022 review of B. burgdorferi antimicrobial-tolerant persistence in Lyme disease and PTLD.

Her work has also shown that ceftriaxone, which is recommended by IDSA for patients with clinically evident neurological and/or cardiac involvement, does not clear infection in mice. “In general, single drugs have not been capable of clearing the infection, yet combinations show promise,” she said.

Dr. Embers has combed large drug libraries looking for combinations of antibiotics that employ different mechanisms of action in hopes of eliminating persister spirochetes. Certain combinations have shown promise in mice and have been tested in her rhesus macaque model; data analyses are underway.

Other research teams, such as that of Ying Zhang, MD, PhD, at Johns Hopkins, have similarly been screening combinations of antibiotics and other compounds, identifying candidates for further testing.

During a question and answer period, Dr. Embers said her team is also investigating the pathophysiology and long-term effects of tick-borne coinfections, including Bartonella, and is pursuing a hypothesis that infection with Borrelia allows Bartonella to cause more extensive disease and persist longer. “I think Lyme is at the core because of its ability to evade and suppress the immune response so effectively.”
 

Diagnostic possibilities, biomarkers for PTLD

Direct diagnostic tests for microbial nucleic acid and proteins “are promising alternatives for indirect serologic tests,” Dr. Aucott said. For instance, in addition to polymerase chain reaction tests, which “are making advances,” it may be possible to target the B. burgdorferi peptidoglycan for antigen detection.

Researchers have shown that peptidoglycan, a component of the B. burgdorferi cell envelope, is a persistent antigen in the synovial fluid of patients with Lyme arthritis who have been treated with oral and intravenous antibiotics, and that it likely contributes to inflammation.

“Maybe the infection is gone but parts of the bacteria are still there that are driving inflammation,” said Dr. Aucott, also associate professor of medicine at John Hopkins.

Researchers have also been looking at the host response to B. burgdorferi – including cytokines, chemokines, and autoantibiodies – to identify biomarkers for PTLD and to identify patients during posttreatment follow-up who are at increased risk of developing PTLD, with the hope of someday intervening. Persistently high levels of interleukin-23, CCL19, and interferon-alpha have each been associated in different studies with persistent symptoms after treatment, Dr. Aucott said.

In addition, metabolomics research is showing that patients with PTLD have metabolic fingerprints that are different from those who return to good health after treatment, and it may be possible to identify an epigenetic signature for Lyme disease. A project sponsored by the Defense Advanced Research Projects Agency called ECHO (Epigenetic Characterization and Observation) aims to identify epigenetic signatures of exposures to various threats, including B. burgdorferi.

“At the very proximal end of [indirectly testing for host response], there are modifications of the DNA that can occur in response to infectious insults ... and that changed DNA changes RNA expression and protein synthesis,” Dr. Aucott explained. DARPA’s project is “exciting because their goal [at DARPA] is to have a diagnostic test quickly as a result of this epigenetics work.”

Imaging research is also fast offering diagnostic opportunities, Dr. Aucott said. Levels of microglial activation on brain PET imaging have been found to correlate with PTLD, and a study at Johns Hopkins of multimodal neuroimaging with functional MRI and diffusion tensor imaging has shown distinct changes to white matter activation within the frontal lobe of patients with PTLD, compared with controls.

The NASEM workshop did not collect or require disclosures of its participants.

Several recent developments in Lyme disease treatment and diagnosis may pave the way forward for combating disease that persists following missed or delayed diagnoses or remains following standard treatment. These include combination therapy to address “persister” bacteria and diagnostic tests that test directly for the pathogen and/or indirectly test for host response, according to experts who presented at a 2-day National Academies of Science, Engineering and Medicine workshop on infection-associated chronic illnesses.

Research has shown that 60% of people who are infected and not treated during the early or early disseminated stages of Lyme disease go on to develop late Lyme arthritis, said John Aucott, MD, director of the Johns Hopkins Lyme Disease Clinical Research Center in Baltimore. And in the real world, there’s an additional category of patients: Those who are misdiagnosed and develop infection-related persistent symptoms – such as fatigue, brain fog/cognitive dysfunction, and musculoskeletal problems – that don’t match the “textbook schematic” involving late Lyme arthritis and late neurologic disease.

Moreover, of patients who are treated with protocols recommended by the Infectious Diseases Society of America (IDSA), about 15% go on to develop persistent symptoms at 6 months – again, symptoms that don’t match textbook manifestations and do match symptoms of other infection-associated chronic illnesses. As a “research construct,” this has been coined posttreatment Lyme disease (PTLD), he said at the workshop, “Toward a Common Research Agenda in Infection-Associated Chronic Illnesses.”

(On a practical level, it is hard to know clinically who has early disseminated disease unless they have multiple erythema migrans rashes or neurologic or cardiac involvement, he said after the meeting.)

All this points to the need for tests that are sensitive and specific for diagnosis at all stages of infection and disease, he said in a talk on diagnostics. Currently available tests – those that fit into the widely used two-tiered enzyme-linked immunosorbent assay, Western Blot serology testing – have significant limitations in sensitivity and specificity, including for acute infection when the body has not generated enough antibodies, yet treatment is most likely to succeed.
 

Move toward combination therapy research

Lyme disease is most commonly treated with doxycycline, and that’s problematic because the antibiotic is a microstatic whose efficacy relies on immune clearance of static bacteria, said Monica E. Embers, PhD, director of vector-borne disease at the Tulane National Primate Research Center and associate professor of immunology at Tulane University, New Orleans.

courtesy Tulane University-Paula Burch-Celentano

“But we know that Borrelia burgdorferi has the capability to evade the host immune response in almost every way possible. Persistence is the norm in an immunocompetent host ... [and] dormant bacteria/persisters are more tolerant of microstatic antibiotics,” she said.

Other considerations for antibiotic efficacy include the fact that B. burgdorferi survives for many months inside ticks without nutrient replenishment or replication, “so dormancy is part of their life cycle,” she said. Moreover, the bacteria can be found deep in connective tissues and joints.

The efficacy of accepted regimens of antibiotic treatment has been “a very contentious issue,” she said, noting that guidelines from the International Lyme and Associated Diseases Society “leave open the possibility for antibiotic retreatment when a chronic infection is judged to be a possible cause [of ongoing symptoms].”

The development of persister B. burgdorferi in the presence of antibiotics has been well studied in vitro, which has limitations, Dr. Embers said. But her group specializes in animal models and has shown persistence of antimicrobial-tolerant B. burgdorferi in tick-inoculated rhesus macaques 8-9 months after treatment with oral doxycycline.

“We [also] saw persistence of mild-moderate inflammation in the brain, peripheral nerves, spinal cord, joints and skeletal muscle, and in the heart,” Dr. Embers said, who coauthored a 2022 review of B. burgdorferi antimicrobial-tolerant persistence in Lyme disease and PTLD.

Her work has also shown that ceftriaxone, which is recommended by IDSA for patients with clinically evident neurological and/or cardiac involvement, does not clear infection in mice. “In general, single drugs have not been capable of clearing the infection, yet combinations show promise,” she said.

Dr. Embers has combed large drug libraries looking for combinations of antibiotics that employ different mechanisms of action in hopes of eliminating persister spirochetes. Certain combinations have shown promise in mice and have been tested in her rhesus macaque model; data analyses are underway.

Other research teams, such as that of Ying Zhang, MD, PhD, at Johns Hopkins, have similarly been screening combinations of antibiotics and other compounds, identifying candidates for further testing.

During a question and answer period, Dr. Embers said her team is also investigating the pathophysiology and long-term effects of tick-borne coinfections, including Bartonella, and is pursuing a hypothesis that infection with Borrelia allows Bartonella to cause more extensive disease and persist longer. “I think Lyme is at the core because of its ability to evade and suppress the immune response so effectively.”
 

Diagnostic possibilities, biomarkers for PTLD

Direct diagnostic tests for microbial nucleic acid and proteins “are promising alternatives for indirect serologic tests,” Dr. Aucott said. For instance, in addition to polymerase chain reaction tests, which “are making advances,” it may be possible to target the B. burgdorferi peptidoglycan for antigen detection.

Researchers have shown that peptidoglycan, a component of the B. burgdorferi cell envelope, is a persistent antigen in the synovial fluid of patients with Lyme arthritis who have been treated with oral and intravenous antibiotics, and that it likely contributes to inflammation.

“Maybe the infection is gone but parts of the bacteria are still there that are driving inflammation,” said Dr. Aucott, also associate professor of medicine at John Hopkins.

Researchers have also been looking at the host response to B. burgdorferi – including cytokines, chemokines, and autoantibiodies – to identify biomarkers for PTLD and to identify patients during posttreatment follow-up who are at increased risk of developing PTLD, with the hope of someday intervening. Persistently high levels of interleukin-23, CCL19, and interferon-alpha have each been associated in different studies with persistent symptoms after treatment, Dr. Aucott said.

In addition, metabolomics research is showing that patients with PTLD have metabolic fingerprints that are different from those who return to good health after treatment, and it may be possible to identify an epigenetic signature for Lyme disease. A project sponsored by the Defense Advanced Research Projects Agency called ECHO (Epigenetic Characterization and Observation) aims to identify epigenetic signatures of exposures to various threats, including B. burgdorferi.

“At the very proximal end of [indirectly testing for host response], there are modifications of the DNA that can occur in response to infectious insults ... and that changed DNA changes RNA expression and protein synthesis,” Dr. Aucott explained. DARPA’s project is “exciting because their goal [at DARPA] is to have a diagnostic test quickly as a result of this epigenetics work.”

Imaging research is also fast offering diagnostic opportunities, Dr. Aucott said. Levels of microglial activation on brain PET imaging have been found to correlate with PTLD, and a study at Johns Hopkins of multimodal neuroimaging with functional MRI and diffusion tensor imaging has shown distinct changes to white matter activation within the frontal lobe of patients with PTLD, compared with controls.

The NASEM workshop did not collect or require disclosures of its participants.

Several recent developments in Lyme disease treatment and diagnosis may pave the way forward for combating disease that persists following missed or delayed diagnoses or remains following standard treatment. These include combination therapy to address “persister” bacteria and diagnostic tests that test directly for the pathogen and/or indirectly test for host response, according to experts who presented at a 2-day National Academies of Science, Engineering and Medicine workshop on infection-associated chronic illnesses.

Research has shown that 60% of people who are infected and not treated during the early or early disseminated stages of Lyme disease go on to develop late Lyme arthritis, said John Aucott, MD, director of the Johns Hopkins Lyme Disease Clinical Research Center in Baltimore. And in the real world, there’s an additional category of patients: Those who are misdiagnosed and develop infection-related persistent symptoms – such as fatigue, brain fog/cognitive dysfunction, and musculoskeletal problems – that don’t match the “textbook schematic” involving late Lyme arthritis and late neurologic disease.

Moreover, of patients who are treated with protocols recommended by the Infectious Diseases Society of America (IDSA), about 15% go on to develop persistent symptoms at 6 months – again, symptoms that don’t match textbook manifestations and do match symptoms of other infection-associated chronic illnesses. As a “research construct,” this has been coined posttreatment Lyme disease (PTLD), he said at the workshop, “Toward a Common Research Agenda in Infection-Associated Chronic Illnesses.”

(On a practical level, it is hard to know clinically who has early disseminated disease unless they have multiple erythema migrans rashes or neurologic or cardiac involvement, he said after the meeting.)

All this points to the need for tests that are sensitive and specific for diagnosis at all stages of infection and disease, he said in a talk on diagnostics. Currently available tests – those that fit into the widely used two-tiered enzyme-linked immunosorbent assay, Western Blot serology testing – have significant limitations in sensitivity and specificity, including for acute infection when the body has not generated enough antibodies, yet treatment is most likely to succeed.
 

Move toward combination therapy research

Lyme disease is most commonly treated with doxycycline, and that’s problematic because the antibiotic is a microstatic whose efficacy relies on immune clearance of static bacteria, said Monica E. Embers, PhD, director of vector-borne disease at the Tulane National Primate Research Center and associate professor of immunology at Tulane University, New Orleans.

courtesy Tulane University-Paula Burch-Celentano

“But we know that Borrelia burgdorferi has the capability to evade the host immune response in almost every way possible. Persistence is the norm in an immunocompetent host ... [and] dormant bacteria/persisters are more tolerant of microstatic antibiotics,” she said.

Other considerations for antibiotic efficacy include the fact that B. burgdorferi survives for many months inside ticks without nutrient replenishment or replication, “so dormancy is part of their life cycle,” she said. Moreover, the bacteria can be found deep in connective tissues and joints.

The efficacy of accepted regimens of antibiotic treatment has been “a very contentious issue,” she said, noting that guidelines from the International Lyme and Associated Diseases Society “leave open the possibility for antibiotic retreatment when a chronic infection is judged to be a possible cause [of ongoing symptoms].”

The development of persister B. burgdorferi in the presence of antibiotics has been well studied in vitro, which has limitations, Dr. Embers said. But her group specializes in animal models and has shown persistence of antimicrobial-tolerant B. burgdorferi in tick-inoculated rhesus macaques 8-9 months after treatment with oral doxycycline.

“We [also] saw persistence of mild-moderate inflammation in the brain, peripheral nerves, spinal cord, joints and skeletal muscle, and in the heart,” Dr. Embers said, who coauthored a 2022 review of B. burgdorferi antimicrobial-tolerant persistence in Lyme disease and PTLD.

Her work has also shown that ceftriaxone, which is recommended by IDSA for patients with clinically evident neurological and/or cardiac involvement, does not clear infection in mice. “In general, single drugs have not been capable of clearing the infection, yet combinations show promise,” she said.

Dr. Embers has combed large drug libraries looking for combinations of antibiotics that employ different mechanisms of action in hopes of eliminating persister spirochetes. Certain combinations have shown promise in mice and have been tested in her rhesus macaque model; data analyses are underway.

Other research teams, such as that of Ying Zhang, MD, PhD, at Johns Hopkins, have similarly been screening combinations of antibiotics and other compounds, identifying candidates for further testing.

During a question and answer period, Dr. Embers said her team is also investigating the pathophysiology and long-term effects of tick-borne coinfections, including Bartonella, and is pursuing a hypothesis that infection with Borrelia allows Bartonella to cause more extensive disease and persist longer. “I think Lyme is at the core because of its ability to evade and suppress the immune response so effectively.”
 

Diagnostic possibilities, biomarkers for PTLD

Direct diagnostic tests for microbial nucleic acid and proteins “are promising alternatives for indirect serologic tests,” Dr. Aucott said. For instance, in addition to polymerase chain reaction tests, which “are making advances,” it may be possible to target the B. burgdorferi peptidoglycan for antigen detection.

Researchers have shown that peptidoglycan, a component of the B. burgdorferi cell envelope, is a persistent antigen in the synovial fluid of patients with Lyme arthritis who have been treated with oral and intravenous antibiotics, and that it likely contributes to inflammation.

“Maybe the infection is gone but parts of the bacteria are still there that are driving inflammation,” said Dr. Aucott, also associate professor of medicine at John Hopkins.

Researchers have also been looking at the host response to B. burgdorferi – including cytokines, chemokines, and autoantibiodies – to identify biomarkers for PTLD and to identify patients during posttreatment follow-up who are at increased risk of developing PTLD, with the hope of someday intervening. Persistently high levels of interleukin-23, CCL19, and interferon-alpha have each been associated in different studies with persistent symptoms after treatment, Dr. Aucott said.

In addition, metabolomics research is showing that patients with PTLD have metabolic fingerprints that are different from those who return to good health after treatment, and it may be possible to identify an epigenetic signature for Lyme disease. A project sponsored by the Defense Advanced Research Projects Agency called ECHO (Epigenetic Characterization and Observation) aims to identify epigenetic signatures of exposures to various threats, including B. burgdorferi.

“At the very proximal end of [indirectly testing for host response], there are modifications of the DNA that can occur in response to infectious insults ... and that changed DNA changes RNA expression and protein synthesis,” Dr. Aucott explained. DARPA’s project is “exciting because their goal [at DARPA] is to have a diagnostic test quickly as a result of this epigenetics work.”

Imaging research is also fast offering diagnostic opportunities, Dr. Aucott said. Levels of microglial activation on brain PET imaging have been found to correlate with PTLD, and a study at Johns Hopkins of multimodal neuroimaging with functional MRI and diffusion tensor imaging has shown distinct changes to white matter activation within the frontal lobe of patients with PTLD, compared with controls.

The NASEM workshop did not collect or require disclosures of its participants.