Infectious Diseases

A new formulation of an existing antibacterial agent and a potential therapeutic approach to a challenging clinical problem were the focus of a session on potentially practice-changing clinical trials in antimicrobial therapy presented during IDWeek 2020, an annual scientific meeting on infectious diseases.

“I know it has been a big year for viral disease of course, with COVID, but there has been some really good work that has gone on in the bacterial space, and of course as those of you who are on service know, you may have your fair share of COVID patients, but these are infections that we still deal with on a daily basis,” said Michael Satlin, MD, an infectious disease specialist at Weill Cornell Medicine in New York.

He combed through studies published during the previous 12 months in leading medical journals, including the New England Journal of Medicine, JAMA network publications, Lancet Infectious Diseases, Lancet Respiratory Medicine, Clinical Infectious Diseases, and Clinical Microbiology and Infection, looking for randomized trials of interventions to treat bacterial infections, and selecting those most likely to change practice of U.S. infectious diseases practitioners.

He excluded meta-analyses, post hoc analyses, evaluations of diagnostic tests, stewardship, or any studies presented previously at IDWeek.

Two of the trials he highlighted are described here.
 

Fosfomycin for injection

In the United States, fosfomycin, the only antibiotic in its class, is currently available only in an oral sachet formulation (Monurol), “and typically we’ve only given this for patients with cystitis because we know that we don’t achieve significant levels [of drug] in the kidney or in the bloodstream for other types of infections,” Dr. Satlin said.

In Europe, however fosfomycin for injection (ZTI-01) has been available for several years.

“There’s been a lot of interest in fosfomycin because it has a different mechanism of action from other agents. It’s an epoxide antibiotic that inhibits early peptidoglycan synthesis by binding to MurA,” he explained.

The phase 2/3 randomized ZEUS trial compared ZTI-01 with piperacillin/tazobactam (pip/taz) for treatment of complicated urinary tract infection (UTI) including acute pyelonephritis.

A total of 465 hospitalized adults with suspected or microbiologically confirmed complicated UTI or acute pyelonephritis were randomized to 6 g of ZTI-01 every 8 hours or 4.5 g of intravenous pip/taz every 8 hours for a fixed 7-day course with no oral switch; patients with concomitant bacteremia (about 9% of the study population) could receive the assigned therapy for up to 14 days.

The primary endpoint of noninferiority of ZTI-01 was met and clinical cure rates were high and similar between the treatments, at approximately 91% each. Treatment-emergent adverse events, including hypokalemia and elevated serum aminotransferases, were mostly mild and transient.

The hypokalemia seen in the trial may be attributable to the high salt load of fosfomycin relative to pip/taz, Dr. Satlin said.

“How might this change your practice? Well, if IV fosfomycin is ever FDA [Food and Drug Administration] approved – and my understanding is that the delays have been more related to manufacturing than scientific quality of data – it could potentially be an alternative to beta-lactams and fluoroquinolones” and has activity against most extend spectrum beta-lactamase (ESBL)–producing Enterobacteriaceae, he said.

Fosfomycin susceptibility testing is challenging, however, with no Clinical & Laboratory Standards Institute (CLSI) or FDA breakpoints for Enterobacterales other than Escherichia coli, and there are questions about the step-down therapy.

“Do you just give a 3-gram sachet chaser when they walk out the door? Do you switch to another agent? I think that needs to be worked out,” he said.
 

Inhaled amikacin

“We know that some IV antibiotics, particularly for resistant organisms, may not achieve sufficient concentrations in the lung to treat pneumonia. We know that inhaled antibiotics can give a lot of concentration of that drug right at the at the site of infection, but we don’t really have [randomized controlled trial] data to see whether it really helps,” Dr. Satlin said.

The INHALE trial was a double-blind, placebo-controlled superiority trial to see whether adding inhaled amikacin to IV standard-of-care antibiotics could improve outcomes for mechanically ventilated patients with gram-negative pneumonia.

The investigators enrolled 725 adults who were receiving mechanical ventilation for pneumonia, 45% of who had ventilator-associated pneumonia (VAP). Of the total cohort, 508 patients analyzed for efficacy had gram-negative pathogens, including 32% with Pseudomonas aeurginosa, 29% with Acinetobacter baumannii, 30% with E. coli, and the remainder with Klebsiella pneumoniae.

Patients were randomized to standard-of-care intravenous antibiotics plus either inhaled amikacin 400 mg twice daily for 10 days or inhaled saline placebo.

“Of note, the median standard-of-care antibiotics in this study was 18 days, which is certainly longer than what our guidelines recommend.”

There was no significant difference between study arms in the primary endpoint of survival at days 28-32 for all patients who had received at least one dose of study drug, were infected with a gram-negative pathogen, and an Acute Physiology and Chronic Health Evaluation (APACHE) II score of at 10 or higher at diagnosis. The respective survival rates for the inhaled amikacin and placebo groups were 75% and 77%. The incidence of treatment-emergent adverse events or serious treatment-emergent adverse events were similar between the two treatment arms.

“No matter how you sliced and diced it – days of mechanical ventilation, duration of ICU stay – essentially they looked the same. Even for [extensively drug resistant] pathogens where you might expect that you’d see the benefit of inhaled amikacin, they didn’t really see a mortality benefit in this study,” Dr. Satlin said.

The study is practice changing, he said “because I think inhaled aminoglycosides should not be routinely added to the standard of care IV antibiotics for pneumonia in ventilated patients,” he said.

It’s still unclear whether inhaled aminoglycosides might play a role in the treatment of select patients infected with organisms resistant to all beta-lactams and fluoroquinolones, he added.
 

Tempting strategy

“Adding inhaled antibiotics is a tempting strategy for treatment of ventilated pneumonia, which often has poor outcomes,” commented Thomas Holland, MD, a hospitalist and infectious disease specialist at Duke University Hospital in Durham, N.C. “This is valuable and practical information as clinicians choose antibiotics regimens for this difficult-to-treat syndrome,” he said in an interview.

Dr. Holland comoderated the session in which Dr. Satlin presented the study findings and opinions.

No funding source for the presentation was reported. Dr. Satlin reported consulting for Shionogi and Achaogen and research grants from Allergan, Merck, and BioFire Diagnostics. Dr. Holland disclosed consulting fees and other material support from Basilea Pharmaceutica, Genetech, Karius and Theravance.

A new formulation of an existing antibacterial agent and a potential therapeutic approach to a challenging clinical problem were the focus of a session on potentially practice-changing clinical trials in antimicrobial therapy presented during IDWeek 2020, an annual scientific meeting on infectious diseases.

“I know it has been a big year for viral disease of course, with COVID, but there has been some really good work that has gone on in the bacterial space, and of course as those of you who are on service know, you may have your fair share of COVID patients, but these are infections that we still deal with on a daily basis,” said Michael Satlin, MD, an infectious disease specialist at Weill Cornell Medicine in New York.

He combed through studies published during the previous 12 months in leading medical journals, including the New England Journal of Medicine, JAMA network publications, Lancet Infectious Diseases, Lancet Respiratory Medicine, Clinical Infectious Diseases, and Clinical Microbiology and Infection, looking for randomized trials of interventions to treat bacterial infections, and selecting those most likely to change practice of U.S. infectious diseases practitioners.

He excluded meta-analyses, post hoc analyses, evaluations of diagnostic tests, stewardship, or any studies presented previously at IDWeek.

Two of the trials he highlighted are described here.
 

Fosfomycin for injection

In the United States, fosfomycin, the only antibiotic in its class, is currently available only in an oral sachet formulation (Monurol), “and typically we’ve only given this for patients with cystitis because we know that we don’t achieve significant levels [of drug] in the kidney or in the bloodstream for other types of infections,” Dr. Satlin said.

In Europe, however fosfomycin for injection (ZTI-01) has been available for several years.

“There’s been a lot of interest in fosfomycin because it has a different mechanism of action from other agents. It’s an epoxide antibiotic that inhibits early peptidoglycan synthesis by binding to MurA,” he explained.

The phase 2/3 randomized ZEUS trial compared ZTI-01 with piperacillin/tazobactam (pip/taz) for treatment of complicated urinary tract infection (UTI) including acute pyelonephritis.

A total of 465 hospitalized adults with suspected or microbiologically confirmed complicated UTI or acute pyelonephritis were randomized to 6 g of ZTI-01 every 8 hours or 4.5 g of intravenous pip/taz every 8 hours for a fixed 7-day course with no oral switch; patients with concomitant bacteremia (about 9% of the study population) could receive the assigned therapy for up to 14 days.

The primary endpoint of noninferiority of ZTI-01 was met and clinical cure rates were high and similar between the treatments, at approximately 91% each. Treatment-emergent adverse events, including hypokalemia and elevated serum aminotransferases, were mostly mild and transient.

The hypokalemia seen in the trial may be attributable to the high salt load of fosfomycin relative to pip/taz, Dr. Satlin said.

“How might this change your practice? Well, if IV fosfomycin is ever FDA [Food and Drug Administration] approved – and my understanding is that the delays have been more related to manufacturing than scientific quality of data – it could potentially be an alternative to beta-lactams and fluoroquinolones” and has activity against most extend spectrum beta-lactamase (ESBL)–producing Enterobacteriaceae, he said.

Fosfomycin susceptibility testing is challenging, however, with no Clinical & Laboratory Standards Institute (CLSI) or FDA breakpoints for Enterobacterales other than Escherichia coli, and there are questions about the step-down therapy.

“Do you just give a 3-gram sachet chaser when they walk out the door? Do you switch to another agent? I think that needs to be worked out,” he said.
 

Inhaled amikacin

“We know that some IV antibiotics, particularly for resistant organisms, may not achieve sufficient concentrations in the lung to treat pneumonia. We know that inhaled antibiotics can give a lot of concentration of that drug right at the at the site of infection, but we don’t really have [randomized controlled trial] data to see whether it really helps,” Dr. Satlin said.

The INHALE trial was a double-blind, placebo-controlled superiority trial to see whether adding inhaled amikacin to IV standard-of-care antibiotics could improve outcomes for mechanically ventilated patients with gram-negative pneumonia.

The investigators enrolled 725 adults who were receiving mechanical ventilation for pneumonia, 45% of who had ventilator-associated pneumonia (VAP). Of the total cohort, 508 patients analyzed for efficacy had gram-negative pathogens, including 32% with Pseudomonas aeurginosa, 29% with Acinetobacter baumannii, 30% with E. coli, and the remainder with Klebsiella pneumoniae.

Patients were randomized to standard-of-care intravenous antibiotics plus either inhaled amikacin 400 mg twice daily for 10 days or inhaled saline placebo.

“Of note, the median standard-of-care antibiotics in this study was 18 days, which is certainly longer than what our guidelines recommend.”

There was no significant difference between study arms in the primary endpoint of survival at days 28-32 for all patients who had received at least one dose of study drug, were infected with a gram-negative pathogen, and an Acute Physiology and Chronic Health Evaluation (APACHE) II score of at 10 or higher at diagnosis. The respective survival rates for the inhaled amikacin and placebo groups were 75% and 77%. The incidence of treatment-emergent adverse events or serious treatment-emergent adverse events were similar between the two treatment arms.

“No matter how you sliced and diced it – days of mechanical ventilation, duration of ICU stay – essentially they looked the same. Even for [extensively drug resistant] pathogens where you might expect that you’d see the benefit of inhaled amikacin, they didn’t really see a mortality benefit in this study,” Dr. Satlin said.

The study is practice changing, he said “because I think inhaled aminoglycosides should not be routinely added to the standard of care IV antibiotics for pneumonia in ventilated patients,” he said.

It’s still unclear whether inhaled aminoglycosides might play a role in the treatment of select patients infected with organisms resistant to all beta-lactams and fluoroquinolones, he added.
 

Tempting strategy

“Adding inhaled antibiotics is a tempting strategy for treatment of ventilated pneumonia, which often has poor outcomes,” commented Thomas Holland, MD, a hospitalist and infectious disease specialist at Duke University Hospital in Durham, N.C. “This is valuable and practical information as clinicians choose antibiotics regimens for this difficult-to-treat syndrome,” he said in an interview.

Dr. Holland comoderated the session in which Dr. Satlin presented the study findings and opinions.

No funding source for the presentation was reported. Dr. Satlin reported consulting for Shionogi and Achaogen and research grants from Allergan, Merck, and BioFire Diagnostics. Dr. Holland disclosed consulting fees and other material support from Basilea Pharmaceutica, Genetech, Karius and Theravance.

A new formulation of an existing antibacterial agent and a potential therapeutic approach to a challenging clinical problem were the focus of a session on potentially practice-changing clinical trials in antimicrobial therapy presented during IDWeek 2020, an annual scientific meeting on infectious diseases.

“I know it has been a big year for viral disease of course, with COVID, but there has been some really good work that has gone on in the bacterial space, and of course as those of you who are on service know, you may have your fair share of COVID patients, but these are infections that we still deal with on a daily basis,” said Michael Satlin, MD, an infectious disease specialist at Weill Cornell Medicine in New York.

He combed through studies published during the previous 12 months in leading medical journals, including the New England Journal of Medicine, JAMA network publications, Lancet Infectious Diseases, Lancet Respiratory Medicine, Clinical Infectious Diseases, and Clinical Microbiology and Infection, looking for randomized trials of interventions to treat bacterial infections, and selecting those most likely to change practice of U.S. infectious diseases practitioners.

He excluded meta-analyses, post hoc analyses, evaluations of diagnostic tests, stewardship, or any studies presented previously at IDWeek.

Two of the trials he highlighted are described here.
 

Fosfomycin for injection

In the United States, fosfomycin, the only antibiotic in its class, is currently available only in an oral sachet formulation (Monurol), “and typically we’ve only given this for patients with cystitis because we know that we don’t achieve significant levels [of drug] in the kidney or in the bloodstream for other types of infections,” Dr. Satlin said.

In Europe, however fosfomycin for injection (ZTI-01) has been available for several years.

“There’s been a lot of interest in fosfomycin because it has a different mechanism of action from other agents. It’s an epoxide antibiotic that inhibits early peptidoglycan synthesis by binding to MurA,” he explained.

The phase 2/3 randomized ZEUS trial compared ZTI-01 with piperacillin/tazobactam (pip/taz) for treatment of complicated urinary tract infection (UTI) including acute pyelonephritis.

A total of 465 hospitalized adults with suspected or microbiologically confirmed complicated UTI or acute pyelonephritis were randomized to 6 g of ZTI-01 every 8 hours or 4.5 g of intravenous pip/taz every 8 hours for a fixed 7-day course with no oral switch; patients with concomitant bacteremia (about 9% of the study population) could receive the assigned therapy for up to 14 days.

The primary endpoint of noninferiority of ZTI-01 was met and clinical cure rates were high and similar between the treatments, at approximately 91% each. Treatment-emergent adverse events, including hypokalemia and elevated serum aminotransferases, were mostly mild and transient.

The hypokalemia seen in the trial may be attributable to the high salt load of fosfomycin relative to pip/taz, Dr. Satlin said.

“How might this change your practice? Well, if IV fosfomycin is ever FDA [Food and Drug Administration] approved – and my understanding is that the delays have been more related to manufacturing than scientific quality of data – it could potentially be an alternative to beta-lactams and fluoroquinolones” and has activity against most extend spectrum beta-lactamase (ESBL)–producing Enterobacteriaceae, he said.

Fosfomycin susceptibility testing is challenging, however, with no Clinical & Laboratory Standards Institute (CLSI) or FDA breakpoints for Enterobacterales other than Escherichia coli, and there are questions about the step-down therapy.

“Do you just give a 3-gram sachet chaser when they walk out the door? Do you switch to another agent? I think that needs to be worked out,” he said.
 

Inhaled amikacin

“We know that some IV antibiotics, particularly for resistant organisms, may not achieve sufficient concentrations in the lung to treat pneumonia. We know that inhaled antibiotics can give a lot of concentration of that drug right at the at the site of infection, but we don’t really have [randomized controlled trial] data to see whether it really helps,” Dr. Satlin said.

The INHALE trial was a double-blind, placebo-controlled superiority trial to see whether adding inhaled amikacin to IV standard-of-care antibiotics could improve outcomes for mechanically ventilated patients with gram-negative pneumonia.

The investigators enrolled 725 adults who were receiving mechanical ventilation for pneumonia, 45% of who had ventilator-associated pneumonia (VAP). Of the total cohort, 508 patients analyzed for efficacy had gram-negative pathogens, including 32% with Pseudomonas aeurginosa, 29% with Acinetobacter baumannii, 30% with E. coli, and the remainder with Klebsiella pneumoniae.

Patients were randomized to standard-of-care intravenous antibiotics plus either inhaled amikacin 400 mg twice daily for 10 days or inhaled saline placebo.

“Of note, the median standard-of-care antibiotics in this study was 18 days, which is certainly longer than what our guidelines recommend.”

There was no significant difference between study arms in the primary endpoint of survival at days 28-32 for all patients who had received at least one dose of study drug, were infected with a gram-negative pathogen, and an Acute Physiology and Chronic Health Evaluation (APACHE) II score of at 10 or higher at diagnosis. The respective survival rates for the inhaled amikacin and placebo groups were 75% and 77%. The incidence of treatment-emergent adverse events or serious treatment-emergent adverse events were similar between the two treatment arms.

“No matter how you sliced and diced it – days of mechanical ventilation, duration of ICU stay – essentially they looked the same. Even for [extensively drug resistant] pathogens where you might expect that you’d see the benefit of inhaled amikacin, they didn’t really see a mortality benefit in this study,” Dr. Satlin said.

The study is practice changing, he said “because I think inhaled aminoglycosides should not be routinely added to the standard of care IV antibiotics for pneumonia in ventilated patients,” he said.

It’s still unclear whether inhaled aminoglycosides might play a role in the treatment of select patients infected with organisms resistant to all beta-lactams and fluoroquinolones, he added.
 

Tempting strategy

“Adding inhaled antibiotics is a tempting strategy for treatment of ventilated pneumonia, which often has poor outcomes,” commented Thomas Holland, MD, a hospitalist and infectious disease specialist at Duke University Hospital in Durham, N.C. “This is valuable and practical information as clinicians choose antibiotics regimens for this difficult-to-treat syndrome,” he said in an interview.

Dr. Holland comoderated the session in which Dr. Satlin presented the study findings and opinions.

No funding source for the presentation was reported. Dr. Satlin reported consulting for Shionogi and Achaogen and research grants from Allergan, Merck, and BioFire Diagnostics. Dr. Holland disclosed consulting fees and other material support from Basilea Pharmaceutica, Genetech, Karius and Theravance.

Vertebral fractures appear to be common in people with severe COVID-19, and also raise the mortality risk, findings from a retrospective cohort suggest.

Among 114 patients with COVID-19 who underwent lateral chest x-rays at the San Raffaele Hospital ED in Milan, more than a third were found to have thoracic vertebral fractures. And, those individuals were more than twice as likely to die as were those without vertebral fractures.

“Morphometric vertebral fractures are one of the most common comorbidities among adults hospitalized with COVID-19, and the presence of such fractures may predict the severity of disease outcomes,” lead investigator Andrea Giustina, MD, said in an interview.

This is the first study to examine vertebral fracture prevalence in any coronavirus disease, but such fractures have been linked to an increased risk of pneumonia and impaired respiratory function, including restrictive pulmonary dysfunction. One possible mechanism may be that they cause anatomical changes, such as kyphosis, which negatively impact respiratory function by decreasing vital capacity, forced expiratory volume in 1 second, and inspiratory time, explained Dr. Giustina, professor of endocrinology, San Raffaele Vita Salute University, Milan, and president of the European Society of Endocrinology. The results were published in the Journal of Clinical Endocrinology and Metabolism.

Clinically, the findings suggest that all patients with COVID-19 who are undergoing chest x-rays should have morphometric vertebral x-ray evaluation, said Dr. Giustina.

“One interesting aspect of the study is that without morphometry, approximatively two thirds of vertebral fractures [would have been] missed. Therefore, they are largely underestimated in clinical practice,” he noted.
 

Thoracic vertebral fractures assessed via lateral chest x-rays

The 114 study subjects included were those whose lateral chest x-rays allowed for a high-quality assessment and in which all the thoracic tract of T4-T12 were viewable and assessable. None had been using glucocorticoids and only 3% had a prior diagnosis of osteoporosis.

The majority (75%) were male, and median age was 57 years. Most (79%) were hospitalized after evaluation in the ED. Of those, 12% (13) were admitted to the ICU and 15% (16) died.

Thoracic vertebral fractures were detected on the lateral chest x-rays in 36% (41) of the patients. In contrast, in studies of women aged 50 years and older from the general European population, morphometric vertebral fracture prevalence ranged from 18% to 26%, the investigators noted.

Of the total 65 vertebral fractures detected, 60% were classified as mild (height ratio decrease <25%), 33.3% as moderate (25%-40% decrease) and 7.7% as severe (>40%). Patients with more than one vertebral fracture were classified by their most severe one.

Those with versus without vertebral fractures didn’t differ by sex, body mass index, or clinical or biological parameters evaluated in the ED. But, compared with those without vertebral fractures, those with them were significantly older (68 vs. 54 years) and were more likely to have arterial hypertension (56% vs. 30%) and coronary artery disease (22% vs. 7%).

In multivariate analysis, age was the only statistically significant predictor of vertebral fractures (odds ratio, 1.04; P < .001).

Mortality doubled, though not significantly

Those with vertebral fractures were more likely to be hospitalized, although not significantly (88% vs. 74%). There was no significant difference in ICU admission (11% vs. 12.5%).

However, those with vertebral fractures required noninvasive mechanical ventilation significantly more often (48.8% vs. 27.4%; P = .02), and were more than twice as likely to die (22% vs. 10%; P = .07). While the difference in overall mortality wasn’t quite statistically significant, those with severe vertebral fractures were significantly more likely to die, compared with those with mild or moderate fractures (60%, 7%, 24%, respectively, for severe, moderate, and mild; P = .04), despite no significant differences in clinical or laboratory parameters.

“Our data from the field reinforce the need of implementing previously published recommendations concerning the importance of bone fragility care during the COVID pandemic with at least those patients already treated with antiosteoporotic drugs maintaining their adherence to treatments including vitamin D, which have also been suggested very recently to have no relevant predisposing effect on COVID-19,” Dr. Giustina and colleagues wrote.

Moreover, they added, “continuity of care should also include bone density monitoring despite very restricted access to clinical facilities, during the COVID-19 pandemic. Finally, all patients with fractures should start antiresorptive treatment right away, even during hospital stay.”

The authors reported having no disclosures.

SOURCE: Giustina A et al. J Clin Endocrinol Metab. 2020 Oct 21. doi: 10.1210/clinem/dgaa738.

Vertebral fractures appear to be common in people with severe COVID-19, and also raise the mortality risk, findings from a retrospective cohort suggest.

Among 114 patients with COVID-19 who underwent lateral chest x-rays at the San Raffaele Hospital ED in Milan, more than a third were found to have thoracic vertebral fractures. And, those individuals were more than twice as likely to die as were those without vertebral fractures.

“Morphometric vertebral fractures are one of the most common comorbidities among adults hospitalized with COVID-19, and the presence of such fractures may predict the severity of disease outcomes,” lead investigator Andrea Giustina, MD, said in an interview.

This is the first study to examine vertebral fracture prevalence in any coronavirus disease, but such fractures have been linked to an increased risk of pneumonia and impaired respiratory function, including restrictive pulmonary dysfunction. One possible mechanism may be that they cause anatomical changes, such as kyphosis, which negatively impact respiratory function by decreasing vital capacity, forced expiratory volume in 1 second, and inspiratory time, explained Dr. Giustina, professor of endocrinology, San Raffaele Vita Salute University, Milan, and president of the European Society of Endocrinology. The results were published in the Journal of Clinical Endocrinology and Metabolism.

Clinically, the findings suggest that all patients with COVID-19 who are undergoing chest x-rays should have morphometric vertebral x-ray evaluation, said Dr. Giustina.

“One interesting aspect of the study is that without morphometry, approximatively two thirds of vertebral fractures [would have been] missed. Therefore, they are largely underestimated in clinical practice,” he noted.
 

Thoracic vertebral fractures assessed via lateral chest x-rays

The 114 study subjects included were those whose lateral chest x-rays allowed for a high-quality assessment and in which all the thoracic tract of T4-T12 were viewable and assessable. None had been using glucocorticoids and only 3% had a prior diagnosis of osteoporosis.

The majority (75%) were male, and median age was 57 years. Most (79%) were hospitalized after evaluation in the ED. Of those, 12% (13) were admitted to the ICU and 15% (16) died.

Thoracic vertebral fractures were detected on the lateral chest x-rays in 36% (41) of the patients. In contrast, in studies of women aged 50 years and older from the general European population, morphometric vertebral fracture prevalence ranged from 18% to 26%, the investigators noted.

Of the total 65 vertebral fractures detected, 60% were classified as mild (height ratio decrease <25%), 33.3% as moderate (25%-40% decrease) and 7.7% as severe (>40%). Patients with more than one vertebral fracture were classified by their most severe one.

Those with versus without vertebral fractures didn’t differ by sex, body mass index, or clinical or biological parameters evaluated in the ED. But, compared with those without vertebral fractures, those with them were significantly older (68 vs. 54 years) and were more likely to have arterial hypertension (56% vs. 30%) and coronary artery disease (22% vs. 7%).

In multivariate analysis, age was the only statistically significant predictor of vertebral fractures (odds ratio, 1.04; P < .001).

Mortality doubled, though not significantly

Those with vertebral fractures were more likely to be hospitalized, although not significantly (88% vs. 74%). There was no significant difference in ICU admission (11% vs. 12.5%).

However, those with vertebral fractures required noninvasive mechanical ventilation significantly more often (48.8% vs. 27.4%; P = .02), and were more than twice as likely to die (22% vs. 10%; P = .07). While the difference in overall mortality wasn’t quite statistically significant, those with severe vertebral fractures were significantly more likely to die, compared with those with mild or moderate fractures (60%, 7%, 24%, respectively, for severe, moderate, and mild; P = .04), despite no significant differences in clinical or laboratory parameters.

“Our data from the field reinforce the need of implementing previously published recommendations concerning the importance of bone fragility care during the COVID pandemic with at least those patients already treated with antiosteoporotic drugs maintaining their adherence to treatments including vitamin D, which have also been suggested very recently to have no relevant predisposing effect on COVID-19,” Dr. Giustina and colleagues wrote.

Moreover, they added, “continuity of care should also include bone density monitoring despite very restricted access to clinical facilities, during the COVID-19 pandemic. Finally, all patients with fractures should start antiresorptive treatment right away, even during hospital stay.”

The authors reported having no disclosures.

SOURCE: Giustina A et al. J Clin Endocrinol Metab. 2020 Oct 21. doi: 10.1210/clinem/dgaa738.

Vertebral fractures appear to be common in people with severe COVID-19, and also raise the mortality risk, findings from a retrospective cohort suggest.

Among 114 patients with COVID-19 who underwent lateral chest x-rays at the San Raffaele Hospital ED in Milan, more than a third were found to have thoracic vertebral fractures. And, those individuals were more than twice as likely to die as were those without vertebral fractures.

“Morphometric vertebral fractures are one of the most common comorbidities among adults hospitalized with COVID-19, and the presence of such fractures may predict the severity of disease outcomes,” lead investigator Andrea Giustina, MD, said in an interview.

This is the first study to examine vertebral fracture prevalence in any coronavirus disease, but such fractures have been linked to an increased risk of pneumonia and impaired respiratory function, including restrictive pulmonary dysfunction. One possible mechanism may be that they cause anatomical changes, such as kyphosis, which negatively impact respiratory function by decreasing vital capacity, forced expiratory volume in 1 second, and inspiratory time, explained Dr. Giustina, professor of endocrinology, San Raffaele Vita Salute University, Milan, and president of the European Society of Endocrinology. The results were published in the Journal of Clinical Endocrinology and Metabolism.

Clinically, the findings suggest that all patients with COVID-19 who are undergoing chest x-rays should have morphometric vertebral x-ray evaluation, said Dr. Giustina.

“One interesting aspect of the study is that without morphometry, approximatively two thirds of vertebral fractures [would have been] missed. Therefore, they are largely underestimated in clinical practice,” he noted.
 

Thoracic vertebral fractures assessed via lateral chest x-rays

The 114 study subjects included were those whose lateral chest x-rays allowed for a high-quality assessment and in which all the thoracic tract of T4-T12 were viewable and assessable. None had been using glucocorticoids and only 3% had a prior diagnosis of osteoporosis.

The majority (75%) were male, and median age was 57 years. Most (79%) were hospitalized after evaluation in the ED. Of those, 12% (13) were admitted to the ICU and 15% (16) died.

Thoracic vertebral fractures were detected on the lateral chest x-rays in 36% (41) of the patients. In contrast, in studies of women aged 50 years and older from the general European population, morphometric vertebral fracture prevalence ranged from 18% to 26%, the investigators noted.

Of the total 65 vertebral fractures detected, 60% were classified as mild (height ratio decrease <25%), 33.3% as moderate (25%-40% decrease) and 7.7% as severe (>40%). Patients with more than one vertebral fracture were classified by their most severe one.

Those with versus without vertebral fractures didn’t differ by sex, body mass index, or clinical or biological parameters evaluated in the ED. But, compared with those without vertebral fractures, those with them were significantly older (68 vs. 54 years) and were more likely to have arterial hypertension (56% vs. 30%) and coronary artery disease (22% vs. 7%).

In multivariate analysis, age was the only statistically significant predictor of vertebral fractures (odds ratio, 1.04; P < .001).

Mortality doubled, though not significantly

Those with vertebral fractures were more likely to be hospitalized, although not significantly (88% vs. 74%). There was no significant difference in ICU admission (11% vs. 12.5%).

However, those with vertebral fractures required noninvasive mechanical ventilation significantly more often (48.8% vs. 27.4%; P = .02), and were more than twice as likely to die (22% vs. 10%; P = .07). While the difference in overall mortality wasn’t quite statistically significant, those with severe vertebral fractures were significantly more likely to die, compared with those with mild or moderate fractures (60%, 7%, 24%, respectively, for severe, moderate, and mild; P = .04), despite no significant differences in clinical or laboratory parameters.

“Our data from the field reinforce the need of implementing previously published recommendations concerning the importance of bone fragility care during the COVID pandemic with at least those patients already treated with antiosteoporotic drugs maintaining their adherence to treatments including vitamin D, which have also been suggested very recently to have no relevant predisposing effect on COVID-19,” Dr. Giustina and colleagues wrote.

Moreover, they added, “continuity of care should also include bone density monitoring despite very restricted access to clinical facilities, during the COVID-19 pandemic. Finally, all patients with fractures should start antiresorptive treatment right away, even during hospital stay.”

The authors reported having no disclosures.

SOURCE: Giustina A et al. J Clin Endocrinol Metab. 2020 Oct 21. doi: 10.1210/clinem/dgaa738.

The United States just passed a dubious COVID-19 milestone: Just over 1% of all children have been infected by the coronavirus this year, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.

There have been 1,052 cases of COVID-19 per 100,000 children as of Oct. 22, and that works out to 1.05% of all children in the country. The cumulative number of pediatric cases is 792,188, and children now represent 11% of all COVID-19 cases, the AAP and the CHA reported Oct. 26.

There were just over 50,000 new child cases reported in the week ending Oct. 22, which was 13.6% of the national total of almost 370,000. That’s up slightly from the 13.3% the previous week but still down from the spike seen in mid-September, based on the data collected from the websites of 49 state health departments (New York does not report ages), along with the District of Columbia, New York City, Puerto Rico, and Guam.

The state-level data show that California has had more COVID-19 cases in children (92,864) than any other state, although Texas has reported ages for only 7% of its confirmed cases. Illinois is next with 46,006 cases, followed by Florida at 45,575, although Florida is using an age range of 0-14 years to define a child case, the AAP and CHA noted.

Other measures largely put small states at the extremes:

• North Dakota has the highest cumulative rate: 2,954 cases per 100,000 children.
• Vermont has the lowest cumulative rate: 190.5 per 100,000.
• Wyoming has the highest proportion of cases in children: 27.7%.
• New Jersey has the lowest proportion of child cases: 4.6%.

There were no COVID-19–related deaths in children reported the week ending Oct. 22, so the total number remains at 120, which is just 0.06% of the total for all ages, based on data from 42 states and New York City. Hospitalization figures put admissions at almost 5,600 in children, or 1.7% of all hospitalizations, although those data come from just 24 states and New York City, the AAP and CHA said.

rfranki@mdedge.com

The United States just passed a dubious COVID-19 milestone: Just over 1% of all children have been infected by the coronavirus this year, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.

There have been 1,052 cases of COVID-19 per 100,000 children as of Oct. 22, and that works out to 1.05% of all children in the country. The cumulative number of pediatric cases is 792,188, and children now represent 11% of all COVID-19 cases, the AAP and the CHA reported Oct. 26.

There were just over 50,000 new child cases reported in the week ending Oct. 22, which was 13.6% of the national total of almost 370,000. That’s up slightly from the 13.3% the previous week but still down from the spike seen in mid-September, based on the data collected from the websites of 49 state health departments (New York does not report ages), along with the District of Columbia, New York City, Puerto Rico, and Guam.

The state-level data show that California has had more COVID-19 cases in children (92,864) than any other state, although Texas has reported ages for only 7% of its confirmed cases. Illinois is next with 46,006 cases, followed by Florida at 45,575, although Florida is using an age range of 0-14 years to define a child case, the AAP and CHA noted.

Other measures largely put small states at the extremes:

• North Dakota has the highest cumulative rate: 2,954 cases per 100,000 children.
• Vermont has the lowest cumulative rate: 190.5 per 100,000.
• Wyoming has the highest proportion of cases in children: 27.7%.
• New Jersey has the lowest proportion of child cases: 4.6%.

There were no COVID-19–related deaths in children reported the week ending Oct. 22, so the total number remains at 120, which is just 0.06% of the total for all ages, based on data from 42 states and New York City. Hospitalization figures put admissions at almost 5,600 in children, or 1.7% of all hospitalizations, although those data come from just 24 states and New York City, the AAP and CHA said.

rfranki@mdedge.com

The United States just passed a dubious COVID-19 milestone: Just over 1% of all children have been infected by the coronavirus this year, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.

There have been 1,052 cases of COVID-19 per 100,000 children as of Oct. 22, and that works out to 1.05% of all children in the country. The cumulative number of pediatric cases is 792,188, and children now represent 11% of all COVID-19 cases, the AAP and the CHA reported Oct. 26.

There were just over 50,000 new child cases reported in the week ending Oct. 22, which was 13.6% of the national total of almost 370,000. That’s up slightly from the 13.3% the previous week but still down from the spike seen in mid-September, based on the data collected from the websites of 49 state health departments (New York does not report ages), along with the District of Columbia, New York City, Puerto Rico, and Guam.

The state-level data show that California has had more COVID-19 cases in children (92,864) than any other state, although Texas has reported ages for only 7% of its confirmed cases. Illinois is next with 46,006 cases, followed by Florida at 45,575, although Florida is using an age range of 0-14 years to define a child case, the AAP and CHA noted.

Other measures largely put small states at the extremes:

• North Dakota has the highest cumulative rate: 2,954 cases per 100,000 children.
• Vermont has the lowest cumulative rate: 190.5 per 100,000.
• Wyoming has the highest proportion of cases in children: 27.7%.
• New Jersey has the lowest proportion of child cases: 4.6%.

There were no COVID-19–related deaths in children reported the week ending Oct. 22, so the total number remains at 120, which is just 0.06% of the total for all ages, based on data from 42 states and New York City. Hospitalization figures put admissions at almost 5,600 in children, or 1.7% of all hospitalizations, although those data come from just 24 states and New York City, the AAP and CHA said.

rfranki@mdedge.com

Fewer than one-third of women hospitalized with influenza receive the recommended flu vaccine, according to a study using data over nine flu seasons.

Researchers analyzed data from 9,652 women ages 15-44 who were hospitalized with laboratory-confirmed influenza from October through April during the 2010-2019 influenza seasons. Data were pulled from the U.S. Influenza Hospitalization Surveillance Network (FluSurv-NET).

Of those women, 2,697 (28%) were pregnant. Median age was 28 and median gestational age was 32 weeks. Those studied included 36% who were non-Hispanic White; 29% non-Hispanic Black; and 20% Hispanic women.

Some 89% of the women, pregnant and nonpregnant, received antivirals while in the hospital but only 31% reported they had received the flu vaccine in the current season, despite guideline recommendations citing clear evidence that vaccination is safe for mother and baby.

Rachel Holstein, MPH, an epidemiology and information science fellow at the Centers for Disease Control and Prevention, who presented her team’s work as part of IDWeek 2020, explained that the mother’s vaccination can help protect the baby from flu infection for several months after birth, before the baby can be vaccinated.

She noted that pregnant women are at high risk for influenza-associated hospitalization.

“Changes in the immune system, heart, and lungs during pregnancy make pregnant women, and women up to 2 weeks post partum, more prone to severe illness from flu, including illness resulting in hospitalization,” she said in an interview

“Vaccination has been shown to reduce the risk of flu-associated acute respiratory infection in pregnant women by up to one-half,” she said. “A 2018 study showed that getting a flu shot reduced a pregnant woman’s risk of being hospitalized with flu by an average of 40%.»

FluSurv-NET data show hospitalizations were more common in the third trimester of pregnancy compared with the first and second, Holstein said. The most common underlying conditions among these women were asthma (23%) and obesity (10%), and 12% were current tobacco smokers. Overall, 5% of pregnant women with flu required ICU admission, 2% needed mechanical ventilation, and 6% developed pneumonia.
 

Vaccine uptake lowest in first two trimesters

Holstein said vaccine coverage was lowest among women in their first or second trimesters for all 9 seasons, and overall vaccination coverage increased significantly over time.

Uptake also differed by age. The data showed coverage was lower among women aged 15-34 years, compared with women 35 years and older (34% vs. 50%).

“It was as low as 15% among pregnant women aged 15-34 years in the 2011-12 season,” she added.

Jeanne Sheffield, MD, director of the division of maternal-fetal medicine at Johns Hopkins Medicine, Baltimore, said in an interview the low uptake of vaccine shown in this study is both familiar and frustrating.

She said education from health care providers has improved, but women are nonetheless frequently fearful. She pointed out the widespread phenomenon of vaccine hesitancy in the general population.

Coverage was 45.3% among adults in the 2018-2019 flu season, 8.2 percentage points higher than coverage during the 2017-18 season (37.1%) according to CDC estimates.

Added to that, she said, is further hesitancy when women believe vaccination could harm the unborn baby, despite “very good data that flu vaccine is safe in pregnancy, acceptable in pregnancy in all trimesters, and is optimal standard of care.”

Holstein added, “We know from past research that a range of factors – including negative attitudes and beliefs about vaccines, less knowledge about and access to vaccines, and a lack of trust in healthcare providers and vaccines – can contribute to lower vaccination rates.”

Healthcare providers play a key role in increasing flu vaccinations among pregnant women, she said.

“A provider recommendation, combined with an offer to administer a flu vaccine at the time of visit, remains one of the best ways to accomplish this,” Holstein said.

Holstein and Sheffield have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Fewer than one-third of women hospitalized with influenza receive the recommended flu vaccine, according to a study using data over nine flu seasons.

Researchers analyzed data from 9,652 women ages 15-44 who were hospitalized with laboratory-confirmed influenza from October through April during the 2010-2019 influenza seasons. Data were pulled from the U.S. Influenza Hospitalization Surveillance Network (FluSurv-NET).

Of those women, 2,697 (28%) were pregnant. Median age was 28 and median gestational age was 32 weeks. Those studied included 36% who were non-Hispanic White; 29% non-Hispanic Black; and 20% Hispanic women.

Some 89% of the women, pregnant and nonpregnant, received antivirals while in the hospital but only 31% reported they had received the flu vaccine in the current season, despite guideline recommendations citing clear evidence that vaccination is safe for mother and baby.

Rachel Holstein, MPH, an epidemiology and information science fellow at the Centers for Disease Control and Prevention, who presented her team’s work as part of IDWeek 2020, explained that the mother’s vaccination can help protect the baby from flu infection for several months after birth, before the baby can be vaccinated.

She noted that pregnant women are at high risk for influenza-associated hospitalization.

“Changes in the immune system, heart, and lungs during pregnancy make pregnant women, and women up to 2 weeks post partum, more prone to severe illness from flu, including illness resulting in hospitalization,” she said in an interview

“Vaccination has been shown to reduce the risk of flu-associated acute respiratory infection in pregnant women by up to one-half,” she said. “A 2018 study showed that getting a flu shot reduced a pregnant woman’s risk of being hospitalized with flu by an average of 40%.»

FluSurv-NET data show hospitalizations were more common in the third trimester of pregnancy compared with the first and second, Holstein said. The most common underlying conditions among these women were asthma (23%) and obesity (10%), and 12% were current tobacco smokers. Overall, 5% of pregnant women with flu required ICU admission, 2% needed mechanical ventilation, and 6% developed pneumonia.
 

Vaccine uptake lowest in first two trimesters

Holstein said vaccine coverage was lowest among women in their first or second trimesters for all 9 seasons, and overall vaccination coverage increased significantly over time.

Uptake also differed by age. The data showed coverage was lower among women aged 15-34 years, compared with women 35 years and older (34% vs. 50%).

“It was as low as 15% among pregnant women aged 15-34 years in the 2011-12 season,” she added.

Jeanne Sheffield, MD, director of the division of maternal-fetal medicine at Johns Hopkins Medicine, Baltimore, said in an interview the low uptake of vaccine shown in this study is both familiar and frustrating.

She said education from health care providers has improved, but women are nonetheless frequently fearful. She pointed out the widespread phenomenon of vaccine hesitancy in the general population.

Coverage was 45.3% among adults in the 2018-2019 flu season, 8.2 percentage points higher than coverage during the 2017-18 season (37.1%) according to CDC estimates.

Added to that, she said, is further hesitancy when women believe vaccination could harm the unborn baby, despite “very good data that flu vaccine is safe in pregnancy, acceptable in pregnancy in all trimesters, and is optimal standard of care.”

Holstein added, “We know from past research that a range of factors – including negative attitudes and beliefs about vaccines, less knowledge about and access to vaccines, and a lack of trust in healthcare providers and vaccines – can contribute to lower vaccination rates.”

Healthcare providers play a key role in increasing flu vaccinations among pregnant women, she said.

“A provider recommendation, combined with an offer to administer a flu vaccine at the time of visit, remains one of the best ways to accomplish this,” Holstein said.

Holstein and Sheffield have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Fewer than one-third of women hospitalized with influenza receive the recommended flu vaccine, according to a study using data over nine flu seasons.

Researchers analyzed data from 9,652 women ages 15-44 who were hospitalized with laboratory-confirmed influenza from October through April during the 2010-2019 influenza seasons. Data were pulled from the U.S. Influenza Hospitalization Surveillance Network (FluSurv-NET).

Of those women, 2,697 (28%) were pregnant. Median age was 28 and median gestational age was 32 weeks. Those studied included 36% who were non-Hispanic White; 29% non-Hispanic Black; and 20% Hispanic women.

Some 89% of the women, pregnant and nonpregnant, received antivirals while in the hospital but only 31% reported they had received the flu vaccine in the current season, despite guideline recommendations citing clear evidence that vaccination is safe for mother and baby.

Rachel Holstein, MPH, an epidemiology and information science fellow at the Centers for Disease Control and Prevention, who presented her team’s work as part of IDWeek 2020, explained that the mother’s vaccination can help protect the baby from flu infection for several months after birth, before the baby can be vaccinated.

She noted that pregnant women are at high risk for influenza-associated hospitalization.

“Changes in the immune system, heart, and lungs during pregnancy make pregnant women, and women up to 2 weeks post partum, more prone to severe illness from flu, including illness resulting in hospitalization,” she said in an interview

“Vaccination has been shown to reduce the risk of flu-associated acute respiratory infection in pregnant women by up to one-half,” she said. “A 2018 study showed that getting a flu shot reduced a pregnant woman’s risk of being hospitalized with flu by an average of 40%.»

FluSurv-NET data show hospitalizations were more common in the third trimester of pregnancy compared with the first and second, Holstein said. The most common underlying conditions among these women were asthma (23%) and obesity (10%), and 12% were current tobacco smokers. Overall, 5% of pregnant women with flu required ICU admission, 2% needed mechanical ventilation, and 6% developed pneumonia.
 

Vaccine uptake lowest in first two trimesters

Holstein said vaccine coverage was lowest among women in their first or second trimesters for all 9 seasons, and overall vaccination coverage increased significantly over time.

Uptake also differed by age. The data showed coverage was lower among women aged 15-34 years, compared with women 35 years and older (34% vs. 50%).

“It was as low as 15% among pregnant women aged 15-34 years in the 2011-12 season,” she added.

Jeanne Sheffield, MD, director of the division of maternal-fetal medicine at Johns Hopkins Medicine, Baltimore, said in an interview the low uptake of vaccine shown in this study is both familiar and frustrating.

She said education from health care providers has improved, but women are nonetheless frequently fearful. She pointed out the widespread phenomenon of vaccine hesitancy in the general population.

Coverage was 45.3% among adults in the 2018-2019 flu season, 8.2 percentage points higher than coverage during the 2017-18 season (37.1%) according to CDC estimates.

Added to that, she said, is further hesitancy when women believe vaccination could harm the unborn baby, despite “very good data that flu vaccine is safe in pregnancy, acceptable in pregnancy in all trimesters, and is optimal standard of care.”

Holstein added, “We know from past research that a range of factors – including negative attitudes and beliefs about vaccines, less knowledge about and access to vaccines, and a lack of trust in healthcare providers and vaccines – can contribute to lower vaccination rates.”

Healthcare providers play a key role in increasing flu vaccinations among pregnant women, she said.

“A provider recommendation, combined with an offer to administer a flu vaccine at the time of visit, remains one of the best ways to accomplish this,” Holstein said.

Holstein and Sheffield have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

The number of patients who presented with acute HIV infections at the University of Chicago’s ED more than doubled this year. At the same time, routine HIV visits dropped in the surrounding area.

David Pitrak, MD, an infectious diseases specialist at the University of Chicago Medicine, and colleagues found that the incidence ratio of acute HIV infection (AHI) jumped to 14.4 this year, compared with the 6.8 average for the previous 4 years (IR, 2.14; 95% confidence interval, 1.01-4.54; P < .05).

At a press conference at IDWeek 2020, he said that this year, acute patients made up one quarter of all new diagnoses (9 of 35), “the highest percentage we have ever seen.

“Patients with acute infection, especially those with symptoms, have extremely high viral loads and progress more rapidly. Because of those high viral loads, there’s risk of transmission to others, so rapid linkage to care and ART [antiretroviral treatment] is really important,” he said.

After the IDWeek abstract was submitted in September, Dr. Pitrak said, three additional AHI cases were diagnosed in the ED, bringing the IR of AHI during the pandemic to 2.57 (95% CI, 1.29-5.11).
 

Should all EDs link HIV screening to COVID-19 testing?

The ED at UCM incorporated blood draws for HIV screening as part of COVID-19 evaluations early on during the pandemic, and they recommend that practice for EDs across the nation.

After a positive test result, the ID team was able to quickly link the HIV patients to care and initiation of antiretroviral treatment without adding staff or resources, Dr. Pitrak said in an interview.

Dr. Pitrak and colleagues reviewed data from 13 health care centers on the south and west sides of Chicago. At most of the centers, fourth- and fifth-generation antibody tests were available. The investigators found that the number of HIV screens that were conducted dropped significantly during the COVID-19 pandemic.

At the height of the pandemic, HIV screening at the sites decreased an average of 58%, the researchers found. As of the end of June, the number was decreased by 32%.

“This is a global problem,” he said. “HIV services have been severely impacted worldwide, with the greatest impact on the LGBTQ community.”

UCM performed 19,111 HIV screens (11,133 in the ED) between Jan. 1 and Aug. 17 this year. It performed 14,754 COVID polymerase chain reaction tests in the ED between March 17 and Aug. 17. All of the acute cases were identified in the ED.

Dr. Pitrak mentioned some possible causes of an increase in the number of patients with acute cases who present in the ED. People who do not suspect they have AHI may be coming to the ED because they think they have COVID-19, inasmuch as many of the symptoms overlap. One of the AHI patients actually did have a coinfection, Dr. Pitrak noted.

“There is also the possibility that this could be bad news,” Dr. Pitrak said in an interview. “It could be that there are more acute cases presenting because there are more community transmissions.”

He noted that follow-up visits have been canceled or converted to telehealth visits during the pandemic, and the number of patients who are initiating pre-exposure prophylaxis has declined significantly.

“I hope we’re not seeing an increase in new transmissions after so much work has been done to decrease transmissions over the past few years,” he said.
 

Partnership with emergency physicians

Critical to screening these patients is building a solid partnership between ID and ED physicians.

Coauthor Kimberly Stanford, MD, MPH, an assistant professor in emergency medicine at UCM, said, “You need a champion within the emergency department who can help make sure that the work flow is not disrupted, that however you implement your screening program, you’re not putting extra work on the staff.

“We can feel extremely confident that if I send a test and it comes back positive, I know someone is going to call that patient and make sure they get into care.”

Although the testing is performed in the ED at UCM, the follow-up, linkage to care, and initiation of treatment are conducted by the ID specialists.

Beverly E. Sha, MD, professor in the division of infectious diseases, department of internal medicine, Rush Medical College, Chicago, said in an interview that although she agrees that HIV screening programs in EDs “make absolute sense,” there are different ways to conduct such programs. Dr. Sha was not involved in Dr. Pitrak’s study.

At Rush’s ED, she says, HIV testing is linked with a complete blood count.

“If someone presents with fever, we would often be doing that test as well,” she said. “I think just globally increasing screening [in the ED] is what makes the most sense.”

Dr. Sha said they have not seen a similar surge in acute cases in the ED at Rush during the pandemic.

She noted, however, that UCM tested more than 11,000 people for HIV in the ED this year, whereas “we probably only did about 3500.

“The reason testing is so important, whether for HIV or COVID, is the more you test, the more you’re going to find,” she said, “especially in cities like Chicago.”

Dr. Pitrak received grant support from Gilead Sciences. His coauthors and Dr. Sha reported no relevant financial relationships.

This article first appeared on Medscape.com.

The number of patients who presented with acute HIV infections at the University of Chicago’s ED more than doubled this year. At the same time, routine HIV visits dropped in the surrounding area.

David Pitrak, MD, an infectious diseases specialist at the University of Chicago Medicine, and colleagues found that the incidence ratio of acute HIV infection (AHI) jumped to 14.4 this year, compared with the 6.8 average for the previous 4 years (IR, 2.14; 95% confidence interval, 1.01-4.54; P < .05).

At a press conference at IDWeek 2020, he said that this year, acute patients made up one quarter of all new diagnoses (9 of 35), “the highest percentage we have ever seen.

“Patients with acute infection, especially those with symptoms, have extremely high viral loads and progress more rapidly. Because of those high viral loads, there’s risk of transmission to others, so rapid linkage to care and ART [antiretroviral treatment] is really important,” he said.

After the IDWeek abstract was submitted in September, Dr. Pitrak said, three additional AHI cases were diagnosed in the ED, bringing the IR of AHI during the pandemic to 2.57 (95% CI, 1.29-5.11).
 

Should all EDs link HIV screening to COVID-19 testing?

The ED at UCM incorporated blood draws for HIV screening as part of COVID-19 evaluations early on during the pandemic, and they recommend that practice for EDs across the nation.

After a positive test result, the ID team was able to quickly link the HIV patients to care and initiation of antiretroviral treatment without adding staff or resources, Dr. Pitrak said in an interview.

Dr. Pitrak and colleagues reviewed data from 13 health care centers on the south and west sides of Chicago. At most of the centers, fourth- and fifth-generation antibody tests were available. The investigators found that the number of HIV screens that were conducted dropped significantly during the COVID-19 pandemic.

At the height of the pandemic, HIV screening at the sites decreased an average of 58%, the researchers found. As of the end of June, the number was decreased by 32%.

“This is a global problem,” he said. “HIV services have been severely impacted worldwide, with the greatest impact on the LGBTQ community.”

UCM performed 19,111 HIV screens (11,133 in the ED) between Jan. 1 and Aug. 17 this year. It performed 14,754 COVID polymerase chain reaction tests in the ED between March 17 and Aug. 17. All of the acute cases were identified in the ED.

Dr. Pitrak mentioned some possible causes of an increase in the number of patients with acute cases who present in the ED. People who do not suspect they have AHI may be coming to the ED because they think they have COVID-19, inasmuch as many of the symptoms overlap. One of the AHI patients actually did have a coinfection, Dr. Pitrak noted.

“There is also the possibility that this could be bad news,” Dr. Pitrak said in an interview. “It could be that there are more acute cases presenting because there are more community transmissions.”

He noted that follow-up visits have been canceled or converted to telehealth visits during the pandemic, and the number of patients who are initiating pre-exposure prophylaxis has declined significantly.

“I hope we’re not seeing an increase in new transmissions after so much work has been done to decrease transmissions over the past few years,” he said.
 

Partnership with emergency physicians

Critical to screening these patients is building a solid partnership between ID and ED physicians.

Coauthor Kimberly Stanford, MD, MPH, an assistant professor in emergency medicine at UCM, said, “You need a champion within the emergency department who can help make sure that the work flow is not disrupted, that however you implement your screening program, you’re not putting extra work on the staff.

“We can feel extremely confident that if I send a test and it comes back positive, I know someone is going to call that patient and make sure they get into care.”

Although the testing is performed in the ED at UCM, the follow-up, linkage to care, and initiation of treatment are conducted by the ID specialists.

Beverly E. Sha, MD, professor in the division of infectious diseases, department of internal medicine, Rush Medical College, Chicago, said in an interview that although she agrees that HIV screening programs in EDs “make absolute sense,” there are different ways to conduct such programs. Dr. Sha was not involved in Dr. Pitrak’s study.

At Rush’s ED, she says, HIV testing is linked with a complete blood count.

“If someone presents with fever, we would often be doing that test as well,” she said. “I think just globally increasing screening [in the ED] is what makes the most sense.”

Dr. Sha said they have not seen a similar surge in acute cases in the ED at Rush during the pandemic.

She noted, however, that UCM tested more than 11,000 people for HIV in the ED this year, whereas “we probably only did about 3500.

“The reason testing is so important, whether for HIV or COVID, is the more you test, the more you’re going to find,” she said, “especially in cities like Chicago.”

Dr. Pitrak received grant support from Gilead Sciences. His coauthors and Dr. Sha reported no relevant financial relationships.

This article first appeared on Medscape.com.

The number of patients who presented with acute HIV infections at the University of Chicago’s ED more than doubled this year. At the same time, routine HIV visits dropped in the surrounding area.

David Pitrak, MD, an infectious diseases specialist at the University of Chicago Medicine, and colleagues found that the incidence ratio of acute HIV infection (AHI) jumped to 14.4 this year, compared with the 6.8 average for the previous 4 years (IR, 2.14; 95% confidence interval, 1.01-4.54; P < .05).

At a press conference at IDWeek 2020, he said that this year, acute patients made up one quarter of all new diagnoses (9 of 35), “the highest percentage we have ever seen.

“Patients with acute infection, especially those with symptoms, have extremely high viral loads and progress more rapidly. Because of those high viral loads, there’s risk of transmission to others, so rapid linkage to care and ART [antiretroviral treatment] is really important,” he said.

After the IDWeek abstract was submitted in September, Dr. Pitrak said, three additional AHI cases were diagnosed in the ED, bringing the IR of AHI during the pandemic to 2.57 (95% CI, 1.29-5.11).
 

Should all EDs link HIV screening to COVID-19 testing?

The ED at UCM incorporated blood draws for HIV screening as part of COVID-19 evaluations early on during the pandemic, and they recommend that practice for EDs across the nation.

After a positive test result, the ID team was able to quickly link the HIV patients to care and initiation of antiretroviral treatment without adding staff or resources, Dr. Pitrak said in an interview.

Dr. Pitrak and colleagues reviewed data from 13 health care centers on the south and west sides of Chicago. At most of the centers, fourth- and fifth-generation antibody tests were available. The investigators found that the number of HIV screens that were conducted dropped significantly during the COVID-19 pandemic.

At the height of the pandemic, HIV screening at the sites decreased an average of 58%, the researchers found. As of the end of June, the number was decreased by 32%.

“This is a global problem,” he said. “HIV services have been severely impacted worldwide, with the greatest impact on the LGBTQ community.”

UCM performed 19,111 HIV screens (11,133 in the ED) between Jan. 1 and Aug. 17 this year. It performed 14,754 COVID polymerase chain reaction tests in the ED between March 17 and Aug. 17. All of the acute cases were identified in the ED.

Dr. Pitrak mentioned some possible causes of an increase in the number of patients with acute cases who present in the ED. People who do not suspect they have AHI may be coming to the ED because they think they have COVID-19, inasmuch as many of the symptoms overlap. One of the AHI patients actually did have a coinfection, Dr. Pitrak noted.

“There is also the possibility that this could be bad news,” Dr. Pitrak said in an interview. “It could be that there are more acute cases presenting because there are more community transmissions.”

He noted that follow-up visits have been canceled or converted to telehealth visits during the pandemic, and the number of patients who are initiating pre-exposure prophylaxis has declined significantly.

“I hope we’re not seeing an increase in new transmissions after so much work has been done to decrease transmissions over the past few years,” he said.
 

Partnership with emergency physicians

Critical to screening these patients is building a solid partnership between ID and ED physicians.

Coauthor Kimberly Stanford, MD, MPH, an assistant professor in emergency medicine at UCM, said, “You need a champion within the emergency department who can help make sure that the work flow is not disrupted, that however you implement your screening program, you’re not putting extra work on the staff.

“We can feel extremely confident that if I send a test and it comes back positive, I know someone is going to call that patient and make sure they get into care.”

Although the testing is performed in the ED at UCM, the follow-up, linkage to care, and initiation of treatment are conducted by the ID specialists.

Beverly E. Sha, MD, professor in the division of infectious diseases, department of internal medicine, Rush Medical College, Chicago, said in an interview that although she agrees that HIV screening programs in EDs “make absolute sense,” there are different ways to conduct such programs. Dr. Sha was not involved in Dr. Pitrak’s study.

At Rush’s ED, she says, HIV testing is linked with a complete blood count.

“If someone presents with fever, we would often be doing that test as well,” she said. “I think just globally increasing screening [in the ED] is what makes the most sense.”

Dr. Sha said they have not seen a similar surge in acute cases in the ED at Rush during the pandemic.

She noted, however, that UCM tested more than 11,000 people for HIV in the ED this year, whereas “we probably only did about 3500.

“The reason testing is so important, whether for HIV or COVID, is the more you test, the more you’re going to find,” she said, “especially in cities like Chicago.”

Dr. Pitrak received grant support from Gilead Sciences. His coauthors and Dr. Sha reported no relevant financial relationships.

This article first appeared on Medscape.com.

Major thromboembolic complications and adverse cardiovascular events occurred with high frequency in patients with COVID-19, especially in the intensive care setting, despite a high use of thromboprophylaxis, in a new large observational U.S. study.

“Despite very high rate of antithrombotic prophylaxis there were a high rate of thromboembolic events suggesting that we are probably not providing enough thromboprophylaxis,” lead author Gregory Piazza, MD, Brigham and Women’s Hospital, Boston, said in an interview. 

“Standard prophylaxis as recommended in the guidelines is a low dose of low-molecular-weight heparin once daily, but these results suggest [patients] probably need higher doses,” he added.

However, Dr. Piazza cautioned that this is an observational study and randomized trials are needed to make changes in treatment strategies. Several such trials are currently underway.

The current study was published online ahead of print in the Nov. 3 issue of the Journal of the American College of Cardiology.
 

Rates similar to other very sick patients

The study showed that while thromboembolic complications were high, they were not as high as seen in some of the earlier studies from Asia and Europe, Dr. Piazza noted.

“The numbers we were seeing in early reports were so high we couldn’t figure out how that was possible,” he said. “Our study suggests that, in a U.S. population receiving thromboprophylaxis, the rate of thromboembolic complications [are] more in line with what we would expect to see in other very sick patients who end up in ICU.”

He suggested that the very high rates of thromboembolic complications in the early studies from Asia may have been because of the lack of thromboprophylaxis, which is not routine in hospitalized patients there. “Some of the earlier studies also used routine ultrasound and so picked up asymptomatic thrombotic events, which was not the case in our study. So our results are more representative of the U.S. population.”

Dr. Piazza attributed the high rate of thromboembolic complications being reported with COVID-19 to the sheer number of very sick patients being admitted to the hospital.

“We are accustomed to seeing a rare case of thrombosis despite prophylaxis in hospitalized patients, but we are seeing more in COVID patients. This is probably just because we have more critically ill patients,” he said.

“We are seeing an incredible influx of patients to the ICU that we have never experienced before, so the increase in thromboembolic complications is more obvious. In prior years we probably haven’t had enough critically ill patients at any one time to raise the flag about thromboprophylaxis,” he commented.

The study also found a high rate of cardiovascular complications. They are seeing an increase in the risk of MI, which is to be expected in such sick patients, but they also see quite a bit of new atrial fibrillation, myocarditis, and heart failure in patients who don’t always have underlying cardiovascular disease, he said.

“So this virus does appear to have a predilection to causing cardiovascular complications, but this is probably because it is making patients so sick,” Dr. Piazza said. “If flu was this virulent and resulted in such high rates of acute respiratory distress syndrome (ARDS), we would probably see similar cardiovascular complication rates.”

For the current report, the researchers analyzed a retrospective cohort of 1,114 patients with COVID-19 diagnosed through the Mass General Brigham integrated health network. Of these, 170 had been admitted to the ICU, 229 had been hospitalized but not treated in ICU, and 715 were outpatients. In terms of ethnicity, 22% were Hispanic/Latino and 44% were non-White. 

Cardiovascular risk factors were common, with 36% of patients having hypertension, 29% hyperlipidemia, and 18% diabetes. Prophylactic anticoagulation was prescribed in 89% of patients with COVID-19 in the intensive care cohort and 85% of those in the hospitalized non–intensive care setting.

Results showed that major arterial or venous thromboembolism (VTE) occurred in 35% of the intensive care cohort, 2.6% of those hospitalized but not treated in ICU, and 0% of outpatients.

Major adverse cardiovascular events occurred in 46% of the intensive care cohort, 6.1% of those hospitalized but non-ICU, and 0% of outpatients.

Symptomatic VTE occurred in 27% of those admitted to ICU, 2.2% of those hospitalized but non-ICU, and 0% of outpatients.

“We found that outpatients had a very low rate of thromboembolic complications, with the vast majority of the risk being in hospitalized patients, especially those in ICU,” Dr. Piazza said.

“These results suggest that we don’t need routine thromboprophylaxis for all outpatients with COVID-19, but there will probably be some patients who need it – those with risk factors for thromboembolism.”

Catheter- and device-associated deep vein thrombosis accounted for 76.9% of the DVTs observed in the study.

“Our finding of high frequency of catheter-associated DVT supports the judicious use of central venous catheters that have been widely implemented, especially in the ICU, to minimize recurrent health care team exposure and facilitate monitoring,” the researchers wrote.
 

ARDS biggest risk factor

Of all the markers of disease severity, the presence of ARDS had the strongest association with adverse outcomes, including major arterial or VTE, major adverse cardiovascular events, symptomatic VTE, and death.

“The severe inflammatory state associated with ARDS and other complications of COVID-19 and its resultant hypercoagulability may explain, at least in part, the high frequency of thromboembolic events. Improved risk stratification, utilizing biochemical markers of inflammation and activated coagulation as well as clinical indicators, such as ARDS, may play an important role in the early identification of patients with an increased likelihood of developing symptomatic VTE or arterial thrombosis,” the researchers wrote. “They may benefit from full- or intermediate-intensity antithrombotic therapy rather than prophylactic anticoagulation.”

They point out that this study provides a cross-sectional view of the cardiovascular complications of COVID-19 in a large health care network, consisting of two academic medical centers serving the greater Boston area, several community hospitals, and numerous outpatient care sites.

“The study incorporates a wide scope of clinically meaningful cardiovascular endpoints and utilizes a rigorous process of event adjudication. Although data on patients with COVID-19 in the ICU have been the subject of most reports, our study provides insights into the broad spectrum of all hospitalized and outpatient populations,” the authors noted.

“The high frequency of arterial or venous thromboembolism in hospitalized patients despite routine thromboprophylaxis suggests the need for improved risk stratification and enhanced preventive efforts,” they concluded.

The study is continuing, and the researchers expect to have data on 10,000 patients by the end of winter.
 

Wait for randomized trials

In an accompanying editorial, Robert McBane, MD, Mayo Clinic, Rochester, Minn., said that these data provide important real-world arterial and venous thrombotic event rates across a large, integrated health care network and an experienced roster of clinician-scientists devoted to thrombosis research.

Noting that whether to interpret these results as alarming or reassuring requires a comparison of expected thromboembolic event rates separate from the pandemic, he pointed out that, while the overall VTE rate among ICU patients was high, the vast majority of these events were attributable to central venous lines, and apart from these, the event rates do not appear inflated relative to prior published incidence rates from the pre–COVID-19 era.

“It is therefore important to resist the urge to overprevent or overtreat patients and expose them to the serious risks of major bleeding,” Dr. McBane wrote, adding that “the systematized approach to delivery of guideline-driven VTE prophylaxis across this large, integrated health network likely contributed to the relatively low rates of serious thrombotic outcomes reported.”

He further noted that, as the majority of VTE events were related to central venous lines in ICU patients, “this underscores the importance of a bundled care approach to central venous line management with daily assessment of the continued necessity of central access.

“A number of important clinical trials aimed at optimizing thromboprophylaxis during hospitalization, following hospital dismissal, and in ambulatory settings are underway. Until available, the lessons of thoughtful anticoagulant prophylaxis and treatment guidelines harvested from years of clinical research appear to apply,” he concluded.

This study was funded, in part, by a research grant from Janssen Pharmaceuticals. Dr. Piazza has received research grant support from EKOS Corporation, Bayer, Bristol-Myers Squibb/Pfizer, Portola Pharmaceuticals, and Janssen Pharmaceuticals; and has received consulting fees from Amgen, Pfizer, Boston Scientific, Agile, and Thrombolex. Dr. McBane reported no relevant disclosures.

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

Major thromboembolic complications and adverse cardiovascular events occurred with high frequency in patients with COVID-19, especially in the intensive care setting, despite a high use of thromboprophylaxis, in a new large observational U.S. study.

“Despite very high rate of antithrombotic prophylaxis there were a high rate of thromboembolic events suggesting that we are probably not providing enough thromboprophylaxis,” lead author Gregory Piazza, MD, Brigham and Women’s Hospital, Boston, said in an interview. 

“Standard prophylaxis as recommended in the guidelines is a low dose of low-molecular-weight heparin once daily, but these results suggest [patients] probably need higher doses,” he added.

However, Dr. Piazza cautioned that this is an observational study and randomized trials are needed to make changes in treatment strategies. Several such trials are currently underway.

The current study was published online ahead of print in the Nov. 3 issue of the Journal of the American College of Cardiology.
 

Rates similar to other very sick patients

The study showed that while thromboembolic complications were high, they were not as high as seen in some of the earlier studies from Asia and Europe, Dr. Piazza noted.

“The numbers we were seeing in early reports were so high we couldn’t figure out how that was possible,” he said. “Our study suggests that, in a U.S. population receiving thromboprophylaxis, the rate of thromboembolic complications [are] more in line with what we would expect to see in other very sick patients who end up in ICU.”

He suggested that the very high rates of thromboembolic complications in the early studies from Asia may have been because of the lack of thromboprophylaxis, which is not routine in hospitalized patients there. “Some of the earlier studies also used routine ultrasound and so picked up asymptomatic thrombotic events, which was not the case in our study. So our results are more representative of the U.S. population.”

Dr. Piazza attributed the high rate of thromboembolic complications being reported with COVID-19 to the sheer number of very sick patients being admitted to the hospital.

“We are accustomed to seeing a rare case of thrombosis despite prophylaxis in hospitalized patients, but we are seeing more in COVID patients. This is probably just because we have more critically ill patients,” he said.

“We are seeing an incredible influx of patients to the ICU that we have never experienced before, so the increase in thromboembolic complications is more obvious. In prior years we probably haven’t had enough critically ill patients at any one time to raise the flag about thromboprophylaxis,” he commented.

The study also found a high rate of cardiovascular complications. They are seeing an increase in the risk of MI, which is to be expected in such sick patients, but they also see quite a bit of new atrial fibrillation, myocarditis, and heart failure in patients who don’t always have underlying cardiovascular disease, he said.

“So this virus does appear to have a predilection to causing cardiovascular complications, but this is probably because it is making patients so sick,” Dr. Piazza said. “If flu was this virulent and resulted in such high rates of acute respiratory distress syndrome (ARDS), we would probably see similar cardiovascular complication rates.”

For the current report, the researchers analyzed a retrospective cohort of 1,114 patients with COVID-19 diagnosed through the Mass General Brigham integrated health network. Of these, 170 had been admitted to the ICU, 229 had been hospitalized but not treated in ICU, and 715 were outpatients. In terms of ethnicity, 22% were Hispanic/Latino and 44% were non-White. 

Cardiovascular risk factors were common, with 36% of patients having hypertension, 29% hyperlipidemia, and 18% diabetes. Prophylactic anticoagulation was prescribed in 89% of patients with COVID-19 in the intensive care cohort and 85% of those in the hospitalized non–intensive care setting.

Results showed that major arterial or venous thromboembolism (VTE) occurred in 35% of the intensive care cohort, 2.6% of those hospitalized but not treated in ICU, and 0% of outpatients.

Major adverse cardiovascular events occurred in 46% of the intensive care cohort, 6.1% of those hospitalized but non-ICU, and 0% of outpatients.

Symptomatic VTE occurred in 27% of those admitted to ICU, 2.2% of those hospitalized but non-ICU, and 0% of outpatients.

“We found that outpatients had a very low rate of thromboembolic complications, with the vast majority of the risk being in hospitalized patients, especially those in ICU,” Dr. Piazza said.

“These results suggest that we don’t need routine thromboprophylaxis for all outpatients with COVID-19, but there will probably be some patients who need it – those with risk factors for thromboembolism.”

Catheter- and device-associated deep vein thrombosis accounted for 76.9% of the DVTs observed in the study.

“Our finding of high frequency of catheter-associated DVT supports the judicious use of central venous catheters that have been widely implemented, especially in the ICU, to minimize recurrent health care team exposure and facilitate monitoring,” the researchers wrote.
 

ARDS biggest risk factor

Of all the markers of disease severity, the presence of ARDS had the strongest association with adverse outcomes, including major arterial or VTE, major adverse cardiovascular events, symptomatic VTE, and death.

“The severe inflammatory state associated with ARDS and other complications of COVID-19 and its resultant hypercoagulability may explain, at least in part, the high frequency of thromboembolic events. Improved risk stratification, utilizing biochemical markers of inflammation and activated coagulation as well as clinical indicators, such as ARDS, may play an important role in the early identification of patients with an increased likelihood of developing symptomatic VTE or arterial thrombosis,” the researchers wrote. “They may benefit from full- or intermediate-intensity antithrombotic therapy rather than prophylactic anticoagulation.”

They point out that this study provides a cross-sectional view of the cardiovascular complications of COVID-19 in a large health care network, consisting of two academic medical centers serving the greater Boston area, several community hospitals, and numerous outpatient care sites.

“The study incorporates a wide scope of clinically meaningful cardiovascular endpoints and utilizes a rigorous process of event adjudication. Although data on patients with COVID-19 in the ICU have been the subject of most reports, our study provides insights into the broad spectrum of all hospitalized and outpatient populations,” the authors noted.

“The high frequency of arterial or venous thromboembolism in hospitalized patients despite routine thromboprophylaxis suggests the need for improved risk stratification and enhanced preventive efforts,” they concluded.

The study is continuing, and the researchers expect to have data on 10,000 patients by the end of winter.
 

Wait for randomized trials

In an accompanying editorial, Robert McBane, MD, Mayo Clinic, Rochester, Minn., said that these data provide important real-world arterial and venous thrombotic event rates across a large, integrated health care network and an experienced roster of clinician-scientists devoted to thrombosis research.

Noting that whether to interpret these results as alarming or reassuring requires a comparison of expected thromboembolic event rates separate from the pandemic, he pointed out that, while the overall VTE rate among ICU patients was high, the vast majority of these events were attributable to central venous lines, and apart from these, the event rates do not appear inflated relative to prior published incidence rates from the pre–COVID-19 era.

“It is therefore important to resist the urge to overprevent or overtreat patients and expose them to the serious risks of major bleeding,” Dr. McBane wrote, adding that “the systematized approach to delivery of guideline-driven VTE prophylaxis across this large, integrated health network likely contributed to the relatively low rates of serious thrombotic outcomes reported.”

He further noted that, as the majority of VTE events were related to central venous lines in ICU patients, “this underscores the importance of a bundled care approach to central venous line management with daily assessment of the continued necessity of central access.

“A number of important clinical trials aimed at optimizing thromboprophylaxis during hospitalization, following hospital dismissal, and in ambulatory settings are underway. Until available, the lessons of thoughtful anticoagulant prophylaxis and treatment guidelines harvested from years of clinical research appear to apply,” he concluded.

This study was funded, in part, by a research grant from Janssen Pharmaceuticals. Dr. Piazza has received research grant support from EKOS Corporation, Bayer, Bristol-Myers Squibb/Pfizer, Portola Pharmaceuticals, and Janssen Pharmaceuticals; and has received consulting fees from Amgen, Pfizer, Boston Scientific, Agile, and Thrombolex. Dr. McBane reported no relevant disclosures.

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

Major thromboembolic complications and adverse cardiovascular events occurred with high frequency in patients with COVID-19, especially in the intensive care setting, despite a high use of thromboprophylaxis, in a new large observational U.S. study.

“Despite very high rate of antithrombotic prophylaxis there were a high rate of thromboembolic events suggesting that we are probably not providing enough thromboprophylaxis,” lead author Gregory Piazza, MD, Brigham and Women’s Hospital, Boston, said in an interview. 

“Standard prophylaxis as recommended in the guidelines is a low dose of low-molecular-weight heparin once daily, but these results suggest [patients] probably need higher doses,” he added.

However, Dr. Piazza cautioned that this is an observational study and randomized trials are needed to make changes in treatment strategies. Several such trials are currently underway.

The current study was published online ahead of print in the Nov. 3 issue of the Journal of the American College of Cardiology.
 

Rates similar to other very sick patients

The study showed that while thromboembolic complications were high, they were not as high as seen in some of the earlier studies from Asia and Europe, Dr. Piazza noted.

“The numbers we were seeing in early reports were so high we couldn’t figure out how that was possible,” he said. “Our study suggests that, in a U.S. population receiving thromboprophylaxis, the rate of thromboembolic complications [are] more in line with what we would expect to see in other very sick patients who end up in ICU.”

He suggested that the very high rates of thromboembolic complications in the early studies from Asia may have been because of the lack of thromboprophylaxis, which is not routine in hospitalized patients there. “Some of the earlier studies also used routine ultrasound and so picked up asymptomatic thrombotic events, which was not the case in our study. So our results are more representative of the U.S. population.”

Dr. Piazza attributed the high rate of thromboembolic complications being reported with COVID-19 to the sheer number of very sick patients being admitted to the hospital.

“We are accustomed to seeing a rare case of thrombosis despite prophylaxis in hospitalized patients, but we are seeing more in COVID patients. This is probably just because we have more critically ill patients,” he said.

“We are seeing an incredible influx of patients to the ICU that we have never experienced before, so the increase in thromboembolic complications is more obvious. In prior years we probably haven’t had enough critically ill patients at any one time to raise the flag about thromboprophylaxis,” he commented.

The study also found a high rate of cardiovascular complications. They are seeing an increase in the risk of MI, which is to be expected in such sick patients, but they also see quite a bit of new atrial fibrillation, myocarditis, and heart failure in patients who don’t always have underlying cardiovascular disease, he said.

“So this virus does appear to have a predilection to causing cardiovascular complications, but this is probably because it is making patients so sick,” Dr. Piazza said. “If flu was this virulent and resulted in such high rates of acute respiratory distress syndrome (ARDS), we would probably see similar cardiovascular complication rates.”

For the current report, the researchers analyzed a retrospective cohort of 1,114 patients with COVID-19 diagnosed through the Mass General Brigham integrated health network. Of these, 170 had been admitted to the ICU, 229 had been hospitalized but not treated in ICU, and 715 were outpatients. In terms of ethnicity, 22% were Hispanic/Latino and 44% were non-White. 

Cardiovascular risk factors were common, with 36% of patients having hypertension, 29% hyperlipidemia, and 18% diabetes. Prophylactic anticoagulation was prescribed in 89% of patients with COVID-19 in the intensive care cohort and 85% of those in the hospitalized non–intensive care setting.

Results showed that major arterial or venous thromboembolism (VTE) occurred in 35% of the intensive care cohort, 2.6% of those hospitalized but not treated in ICU, and 0% of outpatients.

Major adverse cardiovascular events occurred in 46% of the intensive care cohort, 6.1% of those hospitalized but non-ICU, and 0% of outpatients.

Symptomatic VTE occurred in 27% of those admitted to ICU, 2.2% of those hospitalized but non-ICU, and 0% of outpatients.

“We found that outpatients had a very low rate of thromboembolic complications, with the vast majority of the risk being in hospitalized patients, especially those in ICU,” Dr. Piazza said.

“These results suggest that we don’t need routine thromboprophylaxis for all outpatients with COVID-19, but there will probably be some patients who need it – those with risk factors for thromboembolism.”

Catheter- and device-associated deep vein thrombosis accounted for 76.9% of the DVTs observed in the study.

“Our finding of high frequency of catheter-associated DVT supports the judicious use of central venous catheters that have been widely implemented, especially in the ICU, to minimize recurrent health care team exposure and facilitate monitoring,” the researchers wrote.
 

ARDS biggest risk factor

Of all the markers of disease severity, the presence of ARDS had the strongest association with adverse outcomes, including major arterial or VTE, major adverse cardiovascular events, symptomatic VTE, and death.

“The severe inflammatory state associated with ARDS and other complications of COVID-19 and its resultant hypercoagulability may explain, at least in part, the high frequency of thromboembolic events. Improved risk stratification, utilizing biochemical markers of inflammation and activated coagulation as well as clinical indicators, such as ARDS, may play an important role in the early identification of patients with an increased likelihood of developing symptomatic VTE or arterial thrombosis,” the researchers wrote. “They may benefit from full- or intermediate-intensity antithrombotic therapy rather than prophylactic anticoagulation.”

They point out that this study provides a cross-sectional view of the cardiovascular complications of COVID-19 in a large health care network, consisting of two academic medical centers serving the greater Boston area, several community hospitals, and numerous outpatient care sites.

“The study incorporates a wide scope of clinically meaningful cardiovascular endpoints and utilizes a rigorous process of event adjudication. Although data on patients with COVID-19 in the ICU have been the subject of most reports, our study provides insights into the broad spectrum of all hospitalized and outpatient populations,” the authors noted.

“The high frequency of arterial or venous thromboembolism in hospitalized patients despite routine thromboprophylaxis suggests the need for improved risk stratification and enhanced preventive efforts,” they concluded.

The study is continuing, and the researchers expect to have data on 10,000 patients by the end of winter.
 

Wait for randomized trials

In an accompanying editorial, Robert McBane, MD, Mayo Clinic, Rochester, Minn., said that these data provide important real-world arterial and venous thrombotic event rates across a large, integrated health care network and an experienced roster of clinician-scientists devoted to thrombosis research.

Noting that whether to interpret these results as alarming or reassuring requires a comparison of expected thromboembolic event rates separate from the pandemic, he pointed out that, while the overall VTE rate among ICU patients was high, the vast majority of these events were attributable to central venous lines, and apart from these, the event rates do not appear inflated relative to prior published incidence rates from the pre–COVID-19 era.

“It is therefore important to resist the urge to overprevent or overtreat patients and expose them to the serious risks of major bleeding,” Dr. McBane wrote, adding that “the systematized approach to delivery of guideline-driven VTE prophylaxis across this large, integrated health network likely contributed to the relatively low rates of serious thrombotic outcomes reported.”

He further noted that, as the majority of VTE events were related to central venous lines in ICU patients, “this underscores the importance of a bundled care approach to central venous line management with daily assessment of the continued necessity of central access.

“A number of important clinical trials aimed at optimizing thromboprophylaxis during hospitalization, following hospital dismissal, and in ambulatory settings are underway. Until available, the lessons of thoughtful anticoagulant prophylaxis and treatment guidelines harvested from years of clinical research appear to apply,” he concluded.

This study was funded, in part, by a research grant from Janssen Pharmaceuticals. Dr. Piazza has received research grant support from EKOS Corporation, Bayer, Bristol-Myers Squibb/Pfizer, Portola Pharmaceuticals, and Janssen Pharmaceuticals; and has received consulting fees from Amgen, Pfizer, Boston Scientific, Agile, and Thrombolex. Dr. McBane reported no relevant disclosures.

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

COVID-19 cases are surging in rural places across the Mountain States and Midwest, and when it hits health care workers, ready reinforcements aren’t easy to find.

In Montana, pandemic-induced staffing shortages have shuttered a clinic in the state’s capital, led a northwestern regional hospital to ask employees exposed to COVID-19 to continue to work and emptied a health department 400 miles to the east.

“Just one more person out and we wouldn’t be able to keep the surgeries going,” said Dr. Shelly Harkins, MD, chief medical officer of St. Peter’s Health in Helena, a city of roughly 32,000 where cases continue to spread. “When the virus is just all around you, it’s almost impossible to not be deemed a contact at some point. One case can take out a whole team of people in a blink of an eye.”

In North Dakota, where cases per resident are growing faster than any other state, hospitals may once again curtail elective surgeries and possibly seek government aid to hire more nurses if the situation gets worse, North Dakota Hospital Association President Tim Blasl said.

“How long can we run at this rate with the workforce that we have?” Blasl said. “You can have all the licensed beds you want, but if you don’t have anybody to staff those beds, it doesn’t do you any good.”

The northern Rocky Mountains, Great Plains and Upper Midwest are seeing the highest surge of COVID-19 cases in the nation, as some residents have ignored recommendations for curtailing the virus, such as wearing masks and avoiding large gatherings. Montana, Idaho, Utah, Wyoming, North Dakota, South Dakota, Nebraska, Iowa, and Wisconsin have recently ranked among the top 10 U.S. states in confirmed cases per 100,000 residents over a 7-day period, according to an analysis  by the New York Times.

Such coronavirus infections – and the quarantines that occur because of them – are exacerbating the health care worker shortage that existed in these states well before the pandemic. Unlike in the nation’s metropolitan hubs, these outbreaks are scattered across hundreds of miles. And even in these states’ biggest cities, the ranks of medical professionals are in short supply. Specialists and registered nurses are sometimes harder to track down than ventilators, N95 masks or hospital beds. Without enough care providers, patients may not be able to get the medical attention they need.

Hospitals have asked staffers to cover extra shifts and learn new skills. They have brought in temporary workers from other parts of the country and transferred some patients to less-crowded hospitals. But, at St. Peter’s Health, if the hospital’s one kidney doctor gets sick or is told to quarantine, Dr. Harkins doesn’t expect to find a backup.

“We make a point to not have excessive staff because we have an obligation to keep the cost of health care down for a community – we just don’t have a lot of slack in our rope,” Dr. Harkins said. “What we don’t account for is a mass exodus of staff for 14 days.”

Some hospitals are already at patient capacity or are nearly there. That’s not just because of the growing number of COVID-19 patients. Elective surgeries have resumed, and medical emergencies don’t pause for a pandemic.

Some Montana hospitals formed agreements with local affiliates early in the pandemic to share staff if one came up short. But now that the disease is spreading fast – and widely – the hope is that their needs don’t peak all at once.

Montana state officials keep a list of primarily in-state volunteer workers ready to travel to towns with shortages of contact tracers, nurses and more. But during a press conference on Oct. 15, Democratic Gov. Steve Bullock said the state had exhausted that database, and its nationwide request for National Guard medical staffing hadn’t brought in new workers.

“If you are a registered nurse, licensed practical nurse, paramedic, EMT, CNA or contact tracer, and are able to join our workforce, please do consider joining our team,” Gov. Bullock said.

This month, Kalispell Regional Medical Center in northwestern Montana even stopped quarantining COVID-exposed staff who remain asymptomatic, a change allowed by Centers for Disease Control and Prevention guidelines for health facilities facing staffing shortages.

“That’s very telling for what staffing is going through right now,” said Andrea Lueck, a registered nurse at the center. “We’re so tight that employees are called off of quarantine.”

Financial pressure early in the pandemic led the hospital to furlough staff, but it had to bring most of them back to work because it needs those bodies more than ever. The regional hub is based in Flathead County, which has recorded the state’s second-highest number of active COVID-19 cases.

Mellody Sharpton, a hospital spokesperson, said hospital workers who are exposed to someone infected with the virus are tested within three to five days and monitored for symptoms. The hospital is also pulling in new workers, with 25 traveling health professionals on hand and another 25 temporary ones on the way.

But Ms. Sharpton said the best way to conserve the hospital’s workforce is to stop the disease surge in the community.

Earlier in the pandemic, Central Montana Medical Center in Lewistown, a town of fewer than 6,000, experienced an exodus of part-time workers or those close to retirement who decided their jobs weren’t worth the risk. The facility recently secured two traveling workers, but both backed out because they couldn’t find housing. And, so far, roughly 40 of the hospital’s 322 employees have missed work for reasons connected to COVID-19.

“We’re at a critical staffing shortage and have been since the beginning of COVID,” said Joanie Slaybaugh, Central Montana Medical Center’s director of human resources. “We’re small enough, everybody feels an obligation to protect themselves and to protect each other. But it doesn’t take much to take out our staff.”

Roosevelt County, where roughly 11,000 live on the northeastern edge of Montana, had one of the nation’s highest rates of new cases as of Oct. 15. But by the end of the month, the county health department will lose half of its registered nurses as one person is about to retire and another was hired through a grant that’s ending. That leaves only one registered nurse aside from its director, Patty Presser. The health department already had to close earlier during the pandemic because of COVID exposure and not enough staffers to cover the gap. Now, if Ms. Presser can’t find nurse replacements in time, she hopes volunteers will step in, though she added they typically stay for only a few weeks.

“I need someone to do immunizations for my community, and you don’t become an immunization nurse in 14 days,” she said. “We don’t have the workforce here to deal with this virus, not even right now, and then I’m going to have my best two people go.”

Back in Helena, Dr. Harkins said St. Peter’s Health had to close a specialty outpatient clinic that treats chronic diseases for two weeks at the end of September because the entire staff had to quarantine.

Now the hospital is considering having doctors take turns spending a week working from home, so that if another wave of quarantines hits in the hospital, at least one untainted person can be brought back to work. But that won’t help for some specialties, like the hospital’s sole kidney doctor.

Every time Dr. Harkins’ phone rings, she said, she takes a breath and hopes it’s not another case that will force a whole division to close.

“Because I think immediately of the hundreds of people that need that service and won’t have it for 14 days,” she said.

Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of KFF (Kaiser Family Foundation), which is not affiliated with Kaiser Permanente.

COVID-19 cases are surging in rural places across the Mountain States and Midwest, and when it hits health care workers, ready reinforcements aren’t easy to find.

In Montana, pandemic-induced staffing shortages have shuttered a clinic in the state’s capital, led a northwestern regional hospital to ask employees exposed to COVID-19 to continue to work and emptied a health department 400 miles to the east.

“Just one more person out and we wouldn’t be able to keep the surgeries going,” said Dr. Shelly Harkins, MD, chief medical officer of St. Peter’s Health in Helena, a city of roughly 32,000 where cases continue to spread. “When the virus is just all around you, it’s almost impossible to not be deemed a contact at some point. One case can take out a whole team of people in a blink of an eye.”

In North Dakota, where cases per resident are growing faster than any other state, hospitals may once again curtail elective surgeries and possibly seek government aid to hire more nurses if the situation gets worse, North Dakota Hospital Association President Tim Blasl said.

“How long can we run at this rate with the workforce that we have?” Blasl said. “You can have all the licensed beds you want, but if you don’t have anybody to staff those beds, it doesn’t do you any good.”

The northern Rocky Mountains, Great Plains and Upper Midwest are seeing the highest surge of COVID-19 cases in the nation, as some residents have ignored recommendations for curtailing the virus, such as wearing masks and avoiding large gatherings. Montana, Idaho, Utah, Wyoming, North Dakota, South Dakota, Nebraska, Iowa, and Wisconsin have recently ranked among the top 10 U.S. states in confirmed cases per 100,000 residents over a 7-day period, according to an analysis  by the New York Times.

Such coronavirus infections – and the quarantines that occur because of them – are exacerbating the health care worker shortage that existed in these states well before the pandemic. Unlike in the nation’s metropolitan hubs, these outbreaks are scattered across hundreds of miles. And even in these states’ biggest cities, the ranks of medical professionals are in short supply. Specialists and registered nurses are sometimes harder to track down than ventilators, N95 masks or hospital beds. Without enough care providers, patients may not be able to get the medical attention they need.

Hospitals have asked staffers to cover extra shifts and learn new skills. They have brought in temporary workers from other parts of the country and transferred some patients to less-crowded hospitals. But, at St. Peter’s Health, if the hospital’s one kidney doctor gets sick or is told to quarantine, Dr. Harkins doesn’t expect to find a backup.

“We make a point to not have excessive staff because we have an obligation to keep the cost of health care down for a community – we just don’t have a lot of slack in our rope,” Dr. Harkins said. “What we don’t account for is a mass exodus of staff for 14 days.”

Some hospitals are already at patient capacity or are nearly there. That’s not just because of the growing number of COVID-19 patients. Elective surgeries have resumed, and medical emergencies don’t pause for a pandemic.

Some Montana hospitals formed agreements with local affiliates early in the pandemic to share staff if one came up short. But now that the disease is spreading fast – and widely – the hope is that their needs don’t peak all at once.

Montana state officials keep a list of primarily in-state volunteer workers ready to travel to towns with shortages of contact tracers, nurses and more. But during a press conference on Oct. 15, Democratic Gov. Steve Bullock said the state had exhausted that database, and its nationwide request for National Guard medical staffing hadn’t brought in new workers.

“If you are a registered nurse, licensed practical nurse, paramedic, EMT, CNA or contact tracer, and are able to join our workforce, please do consider joining our team,” Gov. Bullock said.

This month, Kalispell Regional Medical Center in northwestern Montana even stopped quarantining COVID-exposed staff who remain asymptomatic, a change allowed by Centers for Disease Control and Prevention guidelines for health facilities facing staffing shortages.

“That’s very telling for what staffing is going through right now,” said Andrea Lueck, a registered nurse at the center. “We’re so tight that employees are called off of quarantine.”

Financial pressure early in the pandemic led the hospital to furlough staff, but it had to bring most of them back to work because it needs those bodies more than ever. The regional hub is based in Flathead County, which has recorded the state’s second-highest number of active COVID-19 cases.

Mellody Sharpton, a hospital spokesperson, said hospital workers who are exposed to someone infected with the virus are tested within three to five days and monitored for symptoms. The hospital is also pulling in new workers, with 25 traveling health professionals on hand and another 25 temporary ones on the way.

But Ms. Sharpton said the best way to conserve the hospital’s workforce is to stop the disease surge in the community.

Earlier in the pandemic, Central Montana Medical Center in Lewistown, a town of fewer than 6,000, experienced an exodus of part-time workers or those close to retirement who decided their jobs weren’t worth the risk. The facility recently secured two traveling workers, but both backed out because they couldn’t find housing. And, so far, roughly 40 of the hospital’s 322 employees have missed work for reasons connected to COVID-19.

“We’re at a critical staffing shortage and have been since the beginning of COVID,” said Joanie Slaybaugh, Central Montana Medical Center’s director of human resources. “We’re small enough, everybody feels an obligation to protect themselves and to protect each other. But it doesn’t take much to take out our staff.”

Roosevelt County, where roughly 11,000 live on the northeastern edge of Montana, had one of the nation’s highest rates of new cases as of Oct. 15. But by the end of the month, the county health department will lose half of its registered nurses as one person is about to retire and another was hired through a grant that’s ending. That leaves only one registered nurse aside from its director, Patty Presser. The health department already had to close earlier during the pandemic because of COVID exposure and not enough staffers to cover the gap. Now, if Ms. Presser can’t find nurse replacements in time, she hopes volunteers will step in, though she added they typically stay for only a few weeks.

“I need someone to do immunizations for my community, and you don’t become an immunization nurse in 14 days,” she said. “We don’t have the workforce here to deal with this virus, not even right now, and then I’m going to have my best two people go.”

Back in Helena, Dr. Harkins said St. Peter’s Health had to close a specialty outpatient clinic that treats chronic diseases for two weeks at the end of September because the entire staff had to quarantine.

Now the hospital is considering having doctors take turns spending a week working from home, so that if another wave of quarantines hits in the hospital, at least one untainted person can be brought back to work. But that won’t help for some specialties, like the hospital’s sole kidney doctor.

Every time Dr. Harkins’ phone rings, she said, she takes a breath and hopes it’s not another case that will force a whole division to close.

“Because I think immediately of the hundreds of people that need that service and won’t have it for 14 days,” she said.

Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of KFF (Kaiser Family Foundation), which is not affiliated with Kaiser Permanente.

COVID-19 cases are surging in rural places across the Mountain States and Midwest, and when it hits health care workers, ready reinforcements aren’t easy to find.

In Montana, pandemic-induced staffing shortages have shuttered a clinic in the state’s capital, led a northwestern regional hospital to ask employees exposed to COVID-19 to continue to work and emptied a health department 400 miles to the east.

“Just one more person out and we wouldn’t be able to keep the surgeries going,” said Dr. Shelly Harkins, MD, chief medical officer of St. Peter’s Health in Helena, a city of roughly 32,000 where cases continue to spread. “When the virus is just all around you, it’s almost impossible to not be deemed a contact at some point. One case can take out a whole team of people in a blink of an eye.”

In North Dakota, where cases per resident are growing faster than any other state, hospitals may once again curtail elective surgeries and possibly seek government aid to hire more nurses if the situation gets worse, North Dakota Hospital Association President Tim Blasl said.

“How long can we run at this rate with the workforce that we have?” Blasl said. “You can have all the licensed beds you want, but if you don’t have anybody to staff those beds, it doesn’t do you any good.”

The northern Rocky Mountains, Great Plains and Upper Midwest are seeing the highest surge of COVID-19 cases in the nation, as some residents have ignored recommendations for curtailing the virus, such as wearing masks and avoiding large gatherings. Montana, Idaho, Utah, Wyoming, North Dakota, South Dakota, Nebraska, Iowa, and Wisconsin have recently ranked among the top 10 U.S. states in confirmed cases per 100,000 residents over a 7-day period, according to an analysis  by the New York Times.

Such coronavirus infections – and the quarantines that occur because of them – are exacerbating the health care worker shortage that existed in these states well before the pandemic. Unlike in the nation’s metropolitan hubs, these outbreaks are scattered across hundreds of miles. And even in these states’ biggest cities, the ranks of medical professionals are in short supply. Specialists and registered nurses are sometimes harder to track down than ventilators, N95 masks or hospital beds. Without enough care providers, patients may not be able to get the medical attention they need.

Hospitals have asked staffers to cover extra shifts and learn new skills. They have brought in temporary workers from other parts of the country and transferred some patients to less-crowded hospitals. But, at St. Peter’s Health, if the hospital’s one kidney doctor gets sick or is told to quarantine, Dr. Harkins doesn’t expect to find a backup.

“We make a point to not have excessive staff because we have an obligation to keep the cost of health care down for a community – we just don’t have a lot of slack in our rope,” Dr. Harkins said. “What we don’t account for is a mass exodus of staff for 14 days.”

Some hospitals are already at patient capacity or are nearly there. That’s not just because of the growing number of COVID-19 patients. Elective surgeries have resumed, and medical emergencies don’t pause for a pandemic.

Some Montana hospitals formed agreements with local affiliates early in the pandemic to share staff if one came up short. But now that the disease is spreading fast – and widely – the hope is that their needs don’t peak all at once.

Montana state officials keep a list of primarily in-state volunteer workers ready to travel to towns with shortages of contact tracers, nurses and more. But during a press conference on Oct. 15, Democratic Gov. Steve Bullock said the state had exhausted that database, and its nationwide request for National Guard medical staffing hadn’t brought in new workers.

“If you are a registered nurse, licensed practical nurse, paramedic, EMT, CNA or contact tracer, and are able to join our workforce, please do consider joining our team,” Gov. Bullock said.

This month, Kalispell Regional Medical Center in northwestern Montana even stopped quarantining COVID-exposed staff who remain asymptomatic, a change allowed by Centers for Disease Control and Prevention guidelines for health facilities facing staffing shortages.

“That’s very telling for what staffing is going through right now,” said Andrea Lueck, a registered nurse at the center. “We’re so tight that employees are called off of quarantine.”

Financial pressure early in the pandemic led the hospital to furlough staff, but it had to bring most of them back to work because it needs those bodies more than ever. The regional hub is based in Flathead County, which has recorded the state’s second-highest number of active COVID-19 cases.

Mellody Sharpton, a hospital spokesperson, said hospital workers who are exposed to someone infected with the virus are tested within three to five days and monitored for symptoms. The hospital is also pulling in new workers, with 25 traveling health professionals on hand and another 25 temporary ones on the way.

But Ms. Sharpton said the best way to conserve the hospital’s workforce is to stop the disease surge in the community.

Earlier in the pandemic, Central Montana Medical Center in Lewistown, a town of fewer than 6,000, experienced an exodus of part-time workers or those close to retirement who decided their jobs weren’t worth the risk. The facility recently secured two traveling workers, but both backed out because they couldn’t find housing. And, so far, roughly 40 of the hospital’s 322 employees have missed work for reasons connected to COVID-19.

“We’re at a critical staffing shortage and have been since the beginning of COVID,” said Joanie Slaybaugh, Central Montana Medical Center’s director of human resources. “We’re small enough, everybody feels an obligation to protect themselves and to protect each other. But it doesn’t take much to take out our staff.”

Roosevelt County, where roughly 11,000 live on the northeastern edge of Montana, had one of the nation’s highest rates of new cases as of Oct. 15. But by the end of the month, the county health department will lose half of its registered nurses as one person is about to retire and another was hired through a grant that’s ending. That leaves only one registered nurse aside from its director, Patty Presser. The health department already had to close earlier during the pandemic because of COVID exposure and not enough staffers to cover the gap. Now, if Ms. Presser can’t find nurse replacements in time, she hopes volunteers will step in, though she added they typically stay for only a few weeks.

“I need someone to do immunizations for my community, and you don’t become an immunization nurse in 14 days,” she said. “We don’t have the workforce here to deal with this virus, not even right now, and then I’m going to have my best two people go.”

Back in Helena, Dr. Harkins said St. Peter’s Health had to close a specialty outpatient clinic that treats chronic diseases for two weeks at the end of September because the entire staff had to quarantine.

Now the hospital is considering having doctors take turns spending a week working from home, so that if another wave of quarantines hits in the hospital, at least one untainted person can be brought back to work. But that won’t help for some specialties, like the hospital’s sole kidney doctor.

Every time Dr. Harkins’ phone rings, she said, she takes a breath and hopes it’s not another case that will force a whole division to close.

“Because I think immediately of the hundreds of people that need that service and won’t have it for 14 days,” she said.

Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of KFF (Kaiser Family Foundation), which is not affiliated with Kaiser Permanente.

Although the efficacy of two pre-exposure prophylaxis (PrEP) regimens containing differing prodrug formulations of tenofovir are virtually identical, the balance between benefit and risk tips in favor of the combination using the older formulation, tenofovir disoproxil fumarate (TDF), a pharmacology researcher said.

An analysis of the pharmacologic profiles of TDF plus emtricitabine (FTC; Truvada and generic) with tenofovir alafenamide (TAF) plus FTC (Descovy) shows that the risk of decreased bone mineral density and renal toxicity with TDF are significantly lower than those of weight gain and related metabolic and cardiovascular problems associated with the newer tenofovir formulation TAF, according to pharmacology research fellow Andrew Hill, MD, PhD, from the University of Liverpool (England).

“I think when we’re comparing these two drugs overall, we have a clear benefit/risk, and we need to take both of these potential toxicities seriously, “ he said in an online presentation during IDWeek 2020, an annual scientific meeting on infectious diseases held virtually this year.

“But in my view, treating women – Black women – with TAF/FTC is a bad thing,” he continued. “I think it’s going lead to more harm, more myocardial infarctions, more cases of diabetes, and potentially more adverse birth outcomes, and I think that is a risk that is not worth taking, given that the apparent benefit in terms of bone mineral density and renal markers is a hypothesis at best, and is not translated into hard clinical endpoints.”
 

Adverse event profiles

Dr. Hill compared the side effect profiles of the two agents when used both in antiretroviral therapy (ART) in combination the integrase inhibitor dolutegravir (DTG; Tivicay), and in PrEP.

World Health Organization guidelines for first-line ART recommend the use of TDF/FTC/DTG, reserving TAF plus lamivudine (3TC) and DTG for use in special circumstances only, Dr. Hill noted.

He pointed to a pooled analysis of data from eight randomized, controlled trials of treatment-naive people living with HIV who started on ART from 2003 to 2015. The authors found that demographic factors associated with weight gain included lower CD4 cell counter, higher levels of HIV type 1 RNA, no injection drug use, female sex, and Black race.

They also found that, among nucleoside/nucleotide reverse transcriptase inhibitors, TAF was associated with more weight gain than TDF, abacavir, or zidovudine.

“This pattern is seen consistently across studies both of pre-exposure prophylaxis or treatment comparing tenofovir with either TAF or other nucleoside analogs,” he said.

The greater weight gain with TAF versus TDF was seen in both treatment trials and in the DISCOVER PrEP trial.

In addition, in a crossover trial conducted in Germany, patients who switched from TDF to TAF had an approximately 2 kg increase in body weight.

TAF has also been associated with higher grade 3 or 4 glucose and LDL cholesterol than TDF in clinical trials for the treatment of hepatitis B infections, and with higher LDL cholesterol and total cholesterol levels as well as diabetes in patients treated with the drugs in combination in the EMERALD HIV trial.

Clinical trials also tend to underestimate the real-world population of persons at highest risk for adverse events from TAF, Dr. Hill said, noting that the percentage of Black women in phase 3 trials for dolutegravir was 9%, compared with 42% among persons infected with HIV worldwide. The respective percentages for Black men are 16% versus 30%. These differences are similar across clinical trial programs for other ART agents.

“Generally, it’s women and Black people who seem to be at greatest risk for safety issues,” he said.

In the ADVANCE trial comparing TAF/FTC/DTG with TDF/FTC/DTG and a control arm of TDF, FTC and efavirenz, the mean change in weight among men after 3 years on the TAF-based regimen was a gain of 7.2 kg (15.9 lbs), compared with 5.5 kg (12 lbs) with TDF, and 2.6 kg (5.7 lbs) with the efavirenz-containing regimen.

In women enrolled in the same trial, the respective mean weight gains were 12.3 kg (27 lbs), 7.4 kg (16.3 lbs), and 5.5 kg (12 lbs).

“All of our analyses so far have shown that the weight continues to go up. We’re actually seeing people doubling in their body weight. We’ve seen some women come into clinic and their doctors don’t even recognize them because they’ve put on so much weight,” he said.

In women, most of the gain in weight occurs as limb or trunk fat, with a predominance of visceral fat.

People taking TAF in the trial were also at significantly greater risk for developing the metabolic syndrome, and at week 96, 27% of women on TAF/FTC/DTG had treatment-emergent obesity, compared with 17% for those on TDF/FTC/DTG and 11% for those on TDF/FTC/EFV. In men, the respective 96-week rates of treatment-emergent obesity were 7%, 3%, and 2%.

Clinical obesity itself is a risk factor for obstetric complications and birth outcomes, Alzheimer’s disease, type 2 diabetes, cardiovascular disease, hypertension and cancer, and an average 4-year reduction in life expectancy, Dr. Hill said. “I think it’s actually very unlikely that the [World Health Organization] guidelines will now change and allow the widespread use of TAF/FTC in combination with integrase inhibitors worldwide given these potential implications.”
 

Modern times

The bad rap that TDF gets for its alleged effects on bone mineral density and kidneys comes from studies where the drug was given in a boosted regimen that can amplify tenofovir toxicities, Dr. Hill said.

He noted that data from Gilead Sciences shows through 7 years of therapy in previously ART-naive patients, the combination of TDF/3TC/EFV showed sustained durable efficacy, no discontinuations to renal adverse effects, and no evidence of clinically relevant bone effects.

“I think we need to be very careful when we look at tenofovir and TAF. We need to look at the more modern way that these drugs are used, which is not with pharmacokinetic boosters anymore, and in that situation the toxicity profile of tenofovir/3TC – the original TDF – is very favorable,” he said.

Robert Goldstein, MD, PhD, an infectious disease specialist and medical director of the transgender health program at Massachusetts General Hospital in Boston, who comoderated the session where Dr. Hill presented his data, said that his clinical experience mirrors the pharmacokinetic findings.

“I certainly have strong feelings about the use of TDF in pre-exposure prophylaxis,” he said in an interview. “TDF is an effective and safe formulation of tenofovir to be used in pre-exposure prophylaxis, and one that we have more experience with. It’s the formulation of tenofovir that I use for all of my patients who are on pre-exposure prophylaxis, and I think it is the most cost-effective.’

No funding source was reported. Andrew Hill consults for Tibotec on clinical trial programs for darunavir, etravirine, and rilpivirine. Dr. Goldstein reported having no relevant disclosures.

Although the efficacy of two pre-exposure prophylaxis (PrEP) regimens containing differing prodrug formulations of tenofovir are virtually identical, the balance between benefit and risk tips in favor of the combination using the older formulation, tenofovir disoproxil fumarate (TDF), a pharmacology researcher said.

An analysis of the pharmacologic profiles of TDF plus emtricitabine (FTC; Truvada and generic) with tenofovir alafenamide (TAF) plus FTC (Descovy) shows that the risk of decreased bone mineral density and renal toxicity with TDF are significantly lower than those of weight gain and related metabolic and cardiovascular problems associated with the newer tenofovir formulation TAF, according to pharmacology research fellow Andrew Hill, MD, PhD, from the University of Liverpool (England).

“I think when we’re comparing these two drugs overall, we have a clear benefit/risk, and we need to take both of these potential toxicities seriously, “ he said in an online presentation during IDWeek 2020, an annual scientific meeting on infectious diseases held virtually this year.

“But in my view, treating women – Black women – with TAF/FTC is a bad thing,” he continued. “I think it’s going lead to more harm, more myocardial infarctions, more cases of diabetes, and potentially more adverse birth outcomes, and I think that is a risk that is not worth taking, given that the apparent benefit in terms of bone mineral density and renal markers is a hypothesis at best, and is not translated into hard clinical endpoints.”
 

Adverse event profiles

Dr. Hill compared the side effect profiles of the two agents when used both in antiretroviral therapy (ART) in combination the integrase inhibitor dolutegravir (DTG; Tivicay), and in PrEP.

World Health Organization guidelines for first-line ART recommend the use of TDF/FTC/DTG, reserving TAF plus lamivudine (3TC) and DTG for use in special circumstances only, Dr. Hill noted.

He pointed to a pooled analysis of data from eight randomized, controlled trials of treatment-naive people living with HIV who started on ART from 2003 to 2015. The authors found that demographic factors associated with weight gain included lower CD4 cell counter, higher levels of HIV type 1 RNA, no injection drug use, female sex, and Black race.

They also found that, among nucleoside/nucleotide reverse transcriptase inhibitors, TAF was associated with more weight gain than TDF, abacavir, or zidovudine.

“This pattern is seen consistently across studies both of pre-exposure prophylaxis or treatment comparing tenofovir with either TAF or other nucleoside analogs,” he said.

The greater weight gain with TAF versus TDF was seen in both treatment trials and in the DISCOVER PrEP trial.

In addition, in a crossover trial conducted in Germany, patients who switched from TDF to TAF had an approximately 2 kg increase in body weight.

TAF has also been associated with higher grade 3 or 4 glucose and LDL cholesterol than TDF in clinical trials for the treatment of hepatitis B infections, and with higher LDL cholesterol and total cholesterol levels as well as diabetes in patients treated with the drugs in combination in the EMERALD HIV trial.

Clinical trials also tend to underestimate the real-world population of persons at highest risk for adverse events from TAF, Dr. Hill said, noting that the percentage of Black women in phase 3 trials for dolutegravir was 9%, compared with 42% among persons infected with HIV worldwide. The respective percentages for Black men are 16% versus 30%. These differences are similar across clinical trial programs for other ART agents.

“Generally, it’s women and Black people who seem to be at greatest risk for safety issues,” he said.

In the ADVANCE trial comparing TAF/FTC/DTG with TDF/FTC/DTG and a control arm of TDF, FTC and efavirenz, the mean change in weight among men after 3 years on the TAF-based regimen was a gain of 7.2 kg (15.9 lbs), compared with 5.5 kg (12 lbs) with TDF, and 2.6 kg (5.7 lbs) with the efavirenz-containing regimen.

In women enrolled in the same trial, the respective mean weight gains were 12.3 kg (27 lbs), 7.4 kg (16.3 lbs), and 5.5 kg (12 lbs).

“All of our analyses so far have shown that the weight continues to go up. We’re actually seeing people doubling in their body weight. We’ve seen some women come into clinic and their doctors don’t even recognize them because they’ve put on so much weight,” he said.

In women, most of the gain in weight occurs as limb or trunk fat, with a predominance of visceral fat.

People taking TAF in the trial were also at significantly greater risk for developing the metabolic syndrome, and at week 96, 27% of women on TAF/FTC/DTG had treatment-emergent obesity, compared with 17% for those on TDF/FTC/DTG and 11% for those on TDF/FTC/EFV. In men, the respective 96-week rates of treatment-emergent obesity were 7%, 3%, and 2%.

Clinical obesity itself is a risk factor for obstetric complications and birth outcomes, Alzheimer’s disease, type 2 diabetes, cardiovascular disease, hypertension and cancer, and an average 4-year reduction in life expectancy, Dr. Hill said. “I think it’s actually very unlikely that the [World Health Organization] guidelines will now change and allow the widespread use of TAF/FTC in combination with integrase inhibitors worldwide given these potential implications.”
 

Modern times

The bad rap that TDF gets for its alleged effects on bone mineral density and kidneys comes from studies where the drug was given in a boosted regimen that can amplify tenofovir toxicities, Dr. Hill said.

He noted that data from Gilead Sciences shows through 7 years of therapy in previously ART-naive patients, the combination of TDF/3TC/EFV showed sustained durable efficacy, no discontinuations to renal adverse effects, and no evidence of clinically relevant bone effects.

“I think we need to be very careful when we look at tenofovir and TAF. We need to look at the more modern way that these drugs are used, which is not with pharmacokinetic boosters anymore, and in that situation the toxicity profile of tenofovir/3TC – the original TDF – is very favorable,” he said.

Robert Goldstein, MD, PhD, an infectious disease specialist and medical director of the transgender health program at Massachusetts General Hospital in Boston, who comoderated the session where Dr. Hill presented his data, said that his clinical experience mirrors the pharmacokinetic findings.

“I certainly have strong feelings about the use of TDF in pre-exposure prophylaxis,” he said in an interview. “TDF is an effective and safe formulation of tenofovir to be used in pre-exposure prophylaxis, and one that we have more experience with. It’s the formulation of tenofovir that I use for all of my patients who are on pre-exposure prophylaxis, and I think it is the most cost-effective.’

No funding source was reported. Andrew Hill consults for Tibotec on clinical trial programs for darunavir, etravirine, and rilpivirine. Dr. Goldstein reported having no relevant disclosures.

Although the efficacy of two pre-exposure prophylaxis (PrEP) regimens containing differing prodrug formulations of tenofovir are virtually identical, the balance between benefit and risk tips in favor of the combination using the older formulation, tenofovir disoproxil fumarate (TDF), a pharmacology researcher said.

An analysis of the pharmacologic profiles of TDF plus emtricitabine (FTC; Truvada and generic) with tenofovir alafenamide (TAF) plus FTC (Descovy) shows that the risk of decreased bone mineral density and renal toxicity with TDF are significantly lower than those of weight gain and related metabolic and cardiovascular problems associated with the newer tenofovir formulation TAF, according to pharmacology research fellow Andrew Hill, MD, PhD, from the University of Liverpool (England).

“I think when we’re comparing these two drugs overall, we have a clear benefit/risk, and we need to take both of these potential toxicities seriously, “ he said in an online presentation during IDWeek 2020, an annual scientific meeting on infectious diseases held virtually this year.

“But in my view, treating women – Black women – with TAF/FTC is a bad thing,” he continued. “I think it’s going lead to more harm, more myocardial infarctions, more cases of diabetes, and potentially more adverse birth outcomes, and I think that is a risk that is not worth taking, given that the apparent benefit in terms of bone mineral density and renal markers is a hypothesis at best, and is not translated into hard clinical endpoints.”
 

Adverse event profiles

Dr. Hill compared the side effect profiles of the two agents when used both in antiretroviral therapy (ART) in combination the integrase inhibitor dolutegravir (DTG; Tivicay), and in PrEP.

World Health Organization guidelines for first-line ART recommend the use of TDF/FTC/DTG, reserving TAF plus lamivudine (3TC) and DTG for use in special circumstances only, Dr. Hill noted.

He pointed to a pooled analysis of data from eight randomized, controlled trials of treatment-naive people living with HIV who started on ART from 2003 to 2015. The authors found that demographic factors associated with weight gain included lower CD4 cell counter, higher levels of HIV type 1 RNA, no injection drug use, female sex, and Black race.

They also found that, among nucleoside/nucleotide reverse transcriptase inhibitors, TAF was associated with more weight gain than TDF, abacavir, or zidovudine.

“This pattern is seen consistently across studies both of pre-exposure prophylaxis or treatment comparing tenofovir with either TAF or other nucleoside analogs,” he said.

The greater weight gain with TAF versus TDF was seen in both treatment trials and in the DISCOVER PrEP trial.

In addition, in a crossover trial conducted in Germany, patients who switched from TDF to TAF had an approximately 2 kg increase in body weight.

TAF has also been associated with higher grade 3 or 4 glucose and LDL cholesterol than TDF in clinical trials for the treatment of hepatitis B infections, and with higher LDL cholesterol and total cholesterol levels as well as diabetes in patients treated with the drugs in combination in the EMERALD HIV trial.

Clinical trials also tend to underestimate the real-world population of persons at highest risk for adverse events from TAF, Dr. Hill said, noting that the percentage of Black women in phase 3 trials for dolutegravir was 9%, compared with 42% among persons infected with HIV worldwide. The respective percentages for Black men are 16% versus 30%. These differences are similar across clinical trial programs for other ART agents.

“Generally, it’s women and Black people who seem to be at greatest risk for safety issues,” he said.

In the ADVANCE trial comparing TAF/FTC/DTG with TDF/FTC/DTG and a control arm of TDF, FTC and efavirenz, the mean change in weight among men after 3 years on the TAF-based regimen was a gain of 7.2 kg (15.9 lbs), compared with 5.5 kg (12 lbs) with TDF, and 2.6 kg (5.7 lbs) with the efavirenz-containing regimen.

In women enrolled in the same trial, the respective mean weight gains were 12.3 kg (27 lbs), 7.4 kg (16.3 lbs), and 5.5 kg (12 lbs).

“All of our analyses so far have shown that the weight continues to go up. We’re actually seeing people doubling in their body weight. We’ve seen some women come into clinic and their doctors don’t even recognize them because they’ve put on so much weight,” he said.

In women, most of the gain in weight occurs as limb or trunk fat, with a predominance of visceral fat.

People taking TAF in the trial were also at significantly greater risk for developing the metabolic syndrome, and at week 96, 27% of women on TAF/FTC/DTG had treatment-emergent obesity, compared with 17% for those on TDF/FTC/DTG and 11% for those on TDF/FTC/EFV. In men, the respective 96-week rates of treatment-emergent obesity were 7%, 3%, and 2%.

Clinical obesity itself is a risk factor for obstetric complications and birth outcomes, Alzheimer’s disease, type 2 diabetes, cardiovascular disease, hypertension and cancer, and an average 4-year reduction in life expectancy, Dr. Hill said. “I think it’s actually very unlikely that the [World Health Organization] guidelines will now change and allow the widespread use of TAF/FTC in combination with integrase inhibitors worldwide given these potential implications.”
 

Modern times

The bad rap that TDF gets for its alleged effects on bone mineral density and kidneys comes from studies where the drug was given in a boosted regimen that can amplify tenofovir toxicities, Dr. Hill said.

He noted that data from Gilead Sciences shows through 7 years of therapy in previously ART-naive patients, the combination of TDF/3TC/EFV showed sustained durable efficacy, no discontinuations to renal adverse effects, and no evidence of clinically relevant bone effects.

“I think we need to be very careful when we look at tenofovir and TAF. We need to look at the more modern way that these drugs are used, which is not with pharmacokinetic boosters anymore, and in that situation the toxicity profile of tenofovir/3TC – the original TDF – is very favorable,” he said.

Robert Goldstein, MD, PhD, an infectious disease specialist and medical director of the transgender health program at Massachusetts General Hospital in Boston, who comoderated the session where Dr. Hill presented his data, said that his clinical experience mirrors the pharmacokinetic findings.

“I certainly have strong feelings about the use of TDF in pre-exposure prophylaxis,” he said in an interview. “TDF is an effective and safe formulation of tenofovir to be used in pre-exposure prophylaxis, and one that we have more experience with. It’s the formulation of tenofovir that I use for all of my patients who are on pre-exposure prophylaxis, and I think it is the most cost-effective.’

No funding source was reported. Andrew Hill consults for Tibotec on clinical trial programs for darunavir, etravirine, and rilpivirine. Dr. Goldstein reported having no relevant disclosures.

To the Editor:

Cutaneous filariasis is a group of infectious diseases caused by more than 60 different nematode species and endemic to approximately 83 countries.^1,2 These infections are transmitted to humans by vectors such as mosquitoes, blackflies, biting midges, or Tabanid flies.¹ The blood meal taken by vectors allow microfilariae to enter the skin and develop into adult worms.^1-3 It is postulated that filarial infections were first described in 2000 bc by Egyptian statues demonstrating elephantiasis, or swollen limbs, caused by chronic infections.¹ Although there are numerous filarial nematode species that infect humans, each life cycle is similar. First, the arthropod vector transmits infective larvae through human skin during a blood meal. Then larvae migrate to host body parts where they mature into adults. Infective filariae require 1 to 2 weeks to form; arthropods may then have another blood meal and transmit the infection to another host.¹

Filarial parasites have been categorized into groups based on the site of adult worm stage habitat. The cutaneous group includes Loa loa, Onchocerca volvulus, Mansonella perstans, and Dipetalonema streptocerca. The lymphatic group includes Wuchereria bancrofti, Brugia malayi, and Brugia timori. Lastly, the body cavity group includes Mansonella ozzardi. Because humidity is required for survival of the infective larval stage, individuals from tropical countries in Africa, Central America, and South America most commonly are affected.¹ These diseases also are related to poor housing quality and inadequate sanitation.^1,3,4 Travel for business, medical missions, pleasure, or emigration has caused increased filarial infections globally. In fact, dermatologic disorders with infectious etiologies cause approximately 17% of travelers to seek medical attention.³

Dermatologic manifestations indicative of a potential cutaneous filarial infection include papules, nodules, excoriations with secondary xerosis, lichenification, skin pigment changes, and/or severe pruritus. However, individuals from filarial endemic regions may not demonstrate any clinical signs or symptoms, despite having microfilariae in their blood,¹ which enables the disease to propagate and poses a major public health concern. In fact, patients with chronic filarial infections are at increased risk for developing lymphedema, elephantiasis, or blindness, which are hypothesized to be the second largest cause of permanent disability worldwide.¹ Although rarely seen in US citizens, cutaneous filariasis should always be a diagnostic consideration in patients who present with a pruritic eruption and have a travel history to tropical countries. We report a case of cutaneous onchocerciasis in a US citizen who developed a pruritic eczematous eruption on the right upper arm following an arthropod assault while working in an Onchocerca endemic region approximately 1.5 years prior.

A 33-year-old woman presented to our outpatient dermatology clinic with the chief concern of a pruritic rash on the right arm (Figure 1). She revealed a history of travel to Peru, associated symptoms, prior diagnoses, and attempted treatment regimens. Over a 1.5-year period, the patient traveled for work-related reasons to Madre de Dios, Peru. During that time, the patient experienced 2 bouts of severe abdominal pain, nausea, and vomiting that she attributed to poor food and water quality. She did not immediately seek medical attention. She also developed skin manifestations that began as a pruritic and irritating pinpoint-sized red papule on the right eyelid, possibly a site of an arthropod assault. She then experienced episodic eyelash loss (Figure 2) and subsequent vision changes, including blurry vision, halos around lights, and dimming around the periphery. When the patient developed circular, pink, pruritic plaques on the right upper extremity, she sought medical attention in Lima, Peru. She was diagnosed with tinea corporis and prescribed an oral antibiotic and topical antifungal.

A few days after the treatment for the blastocystis, the gastrointestinal tract symptoms improved, but dermatologic, ocular, pulmonary, and cardiac symptoms persisted. She also began experiencing night sweats and hot flashes. In between visits to the primary care physician, she sought medical attention at an urgent care clinic for worsening pulmonary and cardiac symptoms. At that time, results of a chest radiograph were normal.

The primary care physician referred her to infectious disease and dermatology for further evaluation within a few weeks of returning to the United States. Upon presentation to dermatology, the patient described a waxing and waning nature to the rash on the arm with associated intermittent pain. Physical examination revealed several erythematous patches on the triceps and a 1-cm subcutaneous nodule on the right elbow with overlying skin discoloration. The patient stated that she first noticed the inflamed painful nodule when she returned to the United States. Since its discovery, the nodule increased in size and became firm. The patient also described occasional limited range of motion of the right arm due to the discomfort of the rash and inflamed nodule. Interestingly, the patient’s partner who accompanied her to Peru also developed a similar pruritic rash on the chest. He was evaluated by dermatology and infectious disease; however, biopsies of his rash performed at a different practice revealed nonspecific results. Due to her partner’s inconclusive results, our patient initially refused a biopsy; however, she returned to the office after 1 week with worsening symptoms, and a 4-mm punch biopsy of the right arm was obtained in addition to rapid plasma reagin and QuantiFERON-TB Gold test.

Based on the patient’s travel history, clinical course, and physical examination, the clinical differential diagnosis included nummular dermatitis, panniculitis/nodular vasculitis, tinea corporis, secondary syphilis, pinta, tuberculosis, or cutaneous filariasis. Rapid plasma reagin and QuantiFERON-TB Gold test results were negative, and a periodic acid–Schiff stain of the biopsy was negative for fungal elements. Dermatopathology revealed intradermal filarial nematodes of 120 to 150 µm in diameter and 1-to 2-mm cuticles eliciting a predominantly superficial and deep lymphohistiocytic reaction (Figure 3). The histopathologic differential diagnosis based on the diameter of the nematode included M perstans, W bancrofti, and O volvulus. Clinical correlation was highly recommended to obtain a final diagnosis and management plan. A portion of the biopsy was sent to the Centers for Disease Control and Prevention, which confirmed the presence of a filarial nematode consistent with a zoonotic Brugia but also with zoonotic Onchocerca as a possible differential. Therefore, considering the history, clinical course, and histopathologic analysis, the final diagnosis of cutaneous onchocerciasis was made.

Onchocerciasis is common in individuals who live or work in equatorial Africa, Central America, and South America. The disease process has dermatologic, ocular, and other systemic manifestations if the infection continues long-term without treatment.^2,5 Although rare, this infection has been observed in US citizens who have traveled to filarial endemic regions for a period of time ranging from 2 weeks to 39 years.^2,6,7

Blackflies (genus Simulium), the intermediate host of O volvulus, breed in areas close to freely flowing water. The blackfly bites a human host, and within 7 days the microfilariae undergo 2 molts to reach the infective stage. The larvae remain in the dermis and subcutaneous tissue for 2 additional molts until they develop into adult worms. Then, adult worms may become encapsulated, eliciting and forming subcutaneous nodules, also known as onchocercomas.^2,3

A fertilized female in the subcutaneous tissue releases microfilariae that may remain in the skin or travel to the eyes of the host.³ The host may demonstrate signs of infection within 3 to 15 months.² Most commonly, patients report localized or generalized pruritus, and one extremity develops swelling, papules, lymphadenopathy, and alterations of skin pigment (hypopigmentation or hyperpigmentation).^5-8 Our patient developed a pruritic eczematous eruption that only affected her right arm with an inflamed firm nodule overlying the elbow, a suspected onchocercoma. Onchocercomas are the direct result of adult worms coiled in the dermis, subcutaneous tissue, and deep fascia. These commonly are found in close proximity to bony prominences with the specific location pending the geographic area of infection.⁸ For example, onchocercomas more commonly are found over bony prominences in the head and upper body region in patients who acquired the disease from Central or South America, whereas individuals infected in Africa more commonly develop onchocercomas near the femoral, coccyx, or sacral regions.²

The immune response mounted by the infected host is responsible for the ocular signs and symptoms.² Specifically, the inflammatory reaction may impact the patient’s cornea, anterior uveal tract, chorioretinal zone, or optic nerve. In fact, onchocerciasis, or river blindness, is the leading cause of blindness in the world.² The host immune response also is responsible for the dermatologic manifestations of this disease. In addition to the dermatologic manifestations already mentioned, others include epidermal atrophy, ulcerations, femoral or inguinal lymphadenitis, lymphedema, and/or general wasting in more severe long-standing infections. Additionally, patients may experience systemic signs resulting from an underlying O volvulus infection.⁸ Our patient demonstrated a subjectively remarkable systemic response manifested by shortness of breath, dyspnea, cough, and palpitations, likely the result of her existing filarial infection.

Diagnosis of onchocerciasis is made by identification of microfilariae or adult worms in skin snips or punch biopsies. Histopathologic analysis of onchocerciasis has been described as several adult worms in the subcutaneous tissue surrounded by a granulomatous, fibrotic, calcified, or sometimes ossified inflammatory reaction.⁸ Microfilariae may migrate to the upper dermis and typically are surrounded by lymphocytes, histiocytes, plasma cells, and eosinophils with an absence of neutrophils,^5,8 which directly causes the overlying epidermis to undergo reactive changes. Measurement of filarial nematodes often helps differentiate species. For example, O volvulus typically measures 230 to 500 mm in length for females and 16 to 42 mm in length for males.⁸ The thickness of cuticles typically measures 4 to 8 µm for females and 3 to 5 µm for males. Microfilariae of O volvulus also have been identified in patient’s sputum, urine, blood, and spinal fluid.⁸ An alternative diagnostic method described by Stingl et al⁹ is a diethylcarbamazine (DEC) patch test that was 92% accurate in onchocerciasis cases diagnosed by skin snip analysis.⁹ Therefore, this test may be a practical alternative when skin specimens are inconclusive.

Management of onchocerciasis should include excision of subcutaneous nodules to remove adult worms. In the past, DEC with suramin was prescribed and kills both microfilariae and adult worms.⁸ However, DEC may induce pruritus, chorioretinal damage, and optic neuritis and suramin is nephrotoxic.² Therefore, oral ivermectin (0.15–0.20 mg/kg one-time dose, may be repeated in 3–12 months) is supported to be a less harmful option. Patients treated with ivermectin have a decreased risk for transmitting infection to the blackfly vector for up to 6 months after treatment, and it is a more effective microfilaricidal agent than DEC.^2,3 Oral doxycycline (100 mg/d for 6 weeks) commonly is added as adjuvant therapy because it kills Wolbachia species, a bacterium that is needed for O volvulus reproduction.³

Although rare in the United States, cutaneous filariasis has become a prevalent public health concern, especially in tropical countries. Individuals with chronic cutaneous filarial infections are at increased risk for debilitating complications that negatively affect their quality of life and productivity. Although the World Health Organization has attempted to eradicate cutaneous filarial infections by mass drug administration, transmission of these diseases remains a challenge. Further research on treatment and methods to prevent transmission by controlling arthropod vectors is required to avoid short-term and long-term health consequences caused by cutaneous filariasis.

Parasitic infections should always be a diagnostic consideration in individuals who present with a pruritic eruption and a history of travel to foreign countries located in Africa, Central America, and South America. Dermatologists in the United States should increase familiarity with these infections because of increased travel, economic globalization, and the impact of global climate change on the geographic distribution of vector arthropods. To control these infections, research efforts should focus on improved sanitation; drug treatment; transmission prevention; and improved education of their clinical manifestations, especially mucocutaneous signs.

To the Editor:

Cutaneous filariasis is a group of infectious diseases caused by more than 60 different nematode species and endemic to approximately 83 countries.^1,2 These infections are transmitted to humans by vectors such as mosquitoes, blackflies, biting midges, or Tabanid flies.¹ The blood meal taken by vectors allow microfilariae to enter the skin and develop into adult worms.^1-3 It is postulated that filarial infections were first described in 2000 bc by Egyptian statues demonstrating elephantiasis, or swollen limbs, caused by chronic infections.¹ Although there are numerous filarial nematode species that infect humans, each life cycle is similar. First, the arthropod vector transmits infective larvae through human skin during a blood meal. Then larvae migrate to host body parts where they mature into adults. Infective filariae require 1 to 2 weeks to form; arthropods may then have another blood meal and transmit the infection to another host.¹

Filarial parasites have been categorized into groups based on the site of adult worm stage habitat. The cutaneous group includes Loa loa, Onchocerca volvulus, Mansonella perstans, and Dipetalonema streptocerca. The lymphatic group includes Wuchereria bancrofti, Brugia malayi, and Brugia timori. Lastly, the body cavity group includes Mansonella ozzardi. Because humidity is required for survival of the infective larval stage, individuals from tropical countries in Africa, Central America, and South America most commonly are affected.¹ These diseases also are related to poor housing quality and inadequate sanitation.^1,3,4 Travel for business, medical missions, pleasure, or emigration has caused increased filarial infections globally. In fact, dermatologic disorders with infectious etiologies cause approximately 17% of travelers to seek medical attention.³

Dermatologic manifestations indicative of a potential cutaneous filarial infection include papules, nodules, excoriations with secondary xerosis, lichenification, skin pigment changes, and/or severe pruritus. However, individuals from filarial endemic regions may not demonstrate any clinical signs or symptoms, despite having microfilariae in their blood,¹ which enables the disease to propagate and poses a major public health concern. In fact, patients with chronic filarial infections are at increased risk for developing lymphedema, elephantiasis, or blindness, which are hypothesized to be the second largest cause of permanent disability worldwide.¹ Although rarely seen in US citizens, cutaneous filariasis should always be a diagnostic consideration in patients who present with a pruritic eruption and have a travel history to tropical countries. We report a case of cutaneous onchocerciasis in a US citizen who developed a pruritic eczematous eruption on the right upper arm following an arthropod assault while working in an Onchocerca endemic region approximately 1.5 years prior.

A 33-year-old woman presented to our outpatient dermatology clinic with the chief concern of a pruritic rash on the right arm (Figure 1). She revealed a history of travel to Peru, associated symptoms, prior diagnoses, and attempted treatment regimens. Over a 1.5-year period, the patient traveled for work-related reasons to Madre de Dios, Peru. During that time, the patient experienced 2 bouts of severe abdominal pain, nausea, and vomiting that she attributed to poor food and water quality. She did not immediately seek medical attention. She also developed skin manifestations that began as a pruritic and irritating pinpoint-sized red papule on the right eyelid, possibly a site of an arthropod assault. She then experienced episodic eyelash loss (Figure 2) and subsequent vision changes, including blurry vision, halos around lights, and dimming around the periphery. When the patient developed circular, pink, pruritic plaques on the right upper extremity, she sought medical attention in Lima, Peru. She was diagnosed with tinea corporis and prescribed an oral antibiotic and topical antifungal.

A few days after the treatment for the blastocystis, the gastrointestinal tract symptoms improved, but dermatologic, ocular, pulmonary, and cardiac symptoms persisted. She also began experiencing night sweats and hot flashes. In between visits to the primary care physician, she sought medical attention at an urgent care clinic for worsening pulmonary and cardiac symptoms. At that time, results of a chest radiograph were normal.

The primary care physician referred her to infectious disease and dermatology for further evaluation within a few weeks of returning to the United States. Upon presentation to dermatology, the patient described a waxing and waning nature to the rash on the arm with associated intermittent pain. Physical examination revealed several erythematous patches on the triceps and a 1-cm subcutaneous nodule on the right elbow with overlying skin discoloration. The patient stated that she first noticed the inflamed painful nodule when she returned to the United States. Since its discovery, the nodule increased in size and became firm. The patient also described occasional limited range of motion of the right arm due to the discomfort of the rash and inflamed nodule. Interestingly, the patient’s partner who accompanied her to Peru also developed a similar pruritic rash on the chest. He was evaluated by dermatology and infectious disease; however, biopsies of his rash performed at a different practice revealed nonspecific results. Due to her partner’s inconclusive results, our patient initially refused a biopsy; however, she returned to the office after 1 week with worsening symptoms, and a 4-mm punch biopsy of the right arm was obtained in addition to rapid plasma reagin and QuantiFERON-TB Gold test.

Based on the patient’s travel history, clinical course, and physical examination, the clinical differential diagnosis included nummular dermatitis, panniculitis/nodular vasculitis, tinea corporis, secondary syphilis, pinta, tuberculosis, or cutaneous filariasis. Rapid plasma reagin and QuantiFERON-TB Gold test results were negative, and a periodic acid–Schiff stain of the biopsy was negative for fungal elements. Dermatopathology revealed intradermal filarial nematodes of 120 to 150 µm in diameter and 1-to 2-mm cuticles eliciting a predominantly superficial and deep lymphohistiocytic reaction (Figure 3). The histopathologic differential diagnosis based on the diameter of the nematode included M perstans, W bancrofti, and O volvulus. Clinical correlation was highly recommended to obtain a final diagnosis and management plan. A portion of the biopsy was sent to the Centers for Disease Control and Prevention, which confirmed the presence of a filarial nematode consistent with a zoonotic Brugia but also with zoonotic Onchocerca as a possible differential. Therefore, considering the history, clinical course, and histopathologic analysis, the final diagnosis of cutaneous onchocerciasis was made.

Onchocerciasis is common in individuals who live or work in equatorial Africa, Central America, and South America. The disease process has dermatologic, ocular, and other systemic manifestations if the infection continues long-term without treatment.^2,5 Although rare, this infection has been observed in US citizens who have traveled to filarial endemic regions for a period of time ranging from 2 weeks to 39 years.^2,6,7

Blackflies (genus Simulium), the intermediate host of O volvulus, breed in areas close to freely flowing water. The blackfly bites a human host, and within 7 days the microfilariae undergo 2 molts to reach the infective stage. The larvae remain in the dermis and subcutaneous tissue for 2 additional molts until they develop into adult worms. Then, adult worms may become encapsulated, eliciting and forming subcutaneous nodules, also known as onchocercomas.^2,3

A fertilized female in the subcutaneous tissue releases microfilariae that may remain in the skin or travel to the eyes of the host.³ The host may demonstrate signs of infection within 3 to 15 months.² Most commonly, patients report localized or generalized pruritus, and one extremity develops swelling, papules, lymphadenopathy, and alterations of skin pigment (hypopigmentation or hyperpigmentation).^5-8 Our patient developed a pruritic eczematous eruption that only affected her right arm with an inflamed firm nodule overlying the elbow, a suspected onchocercoma. Onchocercomas are the direct result of adult worms coiled in the dermis, subcutaneous tissue, and deep fascia. These commonly are found in close proximity to bony prominences with the specific location pending the geographic area of infection.⁸ For example, onchocercomas more commonly are found over bony prominences in the head and upper body region in patients who acquired the disease from Central or South America, whereas individuals infected in Africa more commonly develop onchocercomas near the femoral, coccyx, or sacral regions.²

The immune response mounted by the infected host is responsible for the ocular signs and symptoms.² Specifically, the inflammatory reaction may impact the patient’s cornea, anterior uveal tract, chorioretinal zone, or optic nerve. In fact, onchocerciasis, or river blindness, is the leading cause of blindness in the world.² The host immune response also is responsible for the dermatologic manifestations of this disease. In addition to the dermatologic manifestations already mentioned, others include epidermal atrophy, ulcerations, femoral or inguinal lymphadenitis, lymphedema, and/or general wasting in more severe long-standing infections. Additionally, patients may experience systemic signs resulting from an underlying O volvulus infection.⁸ Our patient demonstrated a subjectively remarkable systemic response manifested by shortness of breath, dyspnea, cough, and palpitations, likely the result of her existing filarial infection.

Diagnosis of onchocerciasis is made by identification of microfilariae or adult worms in skin snips or punch biopsies. Histopathologic analysis of onchocerciasis has been described as several adult worms in the subcutaneous tissue surrounded by a granulomatous, fibrotic, calcified, or sometimes ossified inflammatory reaction.⁸ Microfilariae may migrate to the upper dermis and typically are surrounded by lymphocytes, histiocytes, plasma cells, and eosinophils with an absence of neutrophils,^5,8 which directly causes the overlying epidermis to undergo reactive changes. Measurement of filarial nematodes often helps differentiate species. For example, O volvulus typically measures 230 to 500 mm in length for females and 16 to 42 mm in length for males.⁸ The thickness of cuticles typically measures 4 to 8 µm for females and 3 to 5 µm for males. Microfilariae of O volvulus also have been identified in patient’s sputum, urine, blood, and spinal fluid.⁸ An alternative diagnostic method described by Stingl et al⁹ is a diethylcarbamazine (DEC) patch test that was 92% accurate in onchocerciasis cases diagnosed by skin snip analysis.⁹ Therefore, this test may be a practical alternative when skin specimens are inconclusive.

Management of onchocerciasis should include excision of subcutaneous nodules to remove adult worms. In the past, DEC with suramin was prescribed and kills both microfilariae and adult worms.⁸ However, DEC may induce pruritus, chorioretinal damage, and optic neuritis and suramin is nephrotoxic.² Therefore, oral ivermectin (0.15–0.20 mg/kg one-time dose, may be repeated in 3–12 months) is supported to be a less harmful option. Patients treated with ivermectin have a decreased risk for transmitting infection to the blackfly vector for up to 6 months after treatment, and it is a more effective microfilaricidal agent than DEC.^2,3 Oral doxycycline (100 mg/d for 6 weeks) commonly is added as adjuvant therapy because it kills Wolbachia species, a bacterium that is needed for O volvulus reproduction.³

Although rare in the United States, cutaneous filariasis has become a prevalent public health concern, especially in tropical countries. Individuals with chronic cutaneous filarial infections are at increased risk for debilitating complications that negatively affect their quality of life and productivity. Although the World Health Organization has attempted to eradicate cutaneous filarial infections by mass drug administration, transmission of these diseases remains a challenge. Further research on treatment and methods to prevent transmission by controlling arthropod vectors is required to avoid short-term and long-term health consequences caused by cutaneous filariasis.

Parasitic infections should always be a diagnostic consideration in individuals who present with a pruritic eruption and a history of travel to foreign countries located in Africa, Central America, and South America. Dermatologists in the United States should increase familiarity with these infections because of increased travel, economic globalization, and the impact of global climate change on the geographic distribution of vector arthropods. To control these infections, research efforts should focus on improved sanitation; drug treatment; transmission prevention; and improved education of their clinical manifestations, especially mucocutaneous signs.

To the Editor:

Cutaneous filariasis is a group of infectious diseases caused by more than 60 different nematode species and endemic to approximately 83 countries.^1,2 These infections are transmitted to humans by vectors such as mosquitoes, blackflies, biting midges, or Tabanid flies.¹ The blood meal taken by vectors allow microfilariae to enter the skin and develop into adult worms.^1-3 It is postulated that filarial infections were first described in 2000 bc by Egyptian statues demonstrating elephantiasis, or swollen limbs, caused by chronic infections.¹ Although there are numerous filarial nematode species that infect humans, each life cycle is similar. First, the arthropod vector transmits infective larvae through human skin during a blood meal. Then larvae migrate to host body parts where they mature into adults. Infective filariae require 1 to 2 weeks to form; arthropods may then have another blood meal and transmit the infection to another host.¹

Filarial parasites have been categorized into groups based on the site of adult worm stage habitat. The cutaneous group includes Loa loa, Onchocerca volvulus, Mansonella perstans, and Dipetalonema streptocerca. The lymphatic group includes Wuchereria bancrofti, Brugia malayi, and Brugia timori. Lastly, the body cavity group includes Mansonella ozzardi. Because humidity is required for survival of the infective larval stage, individuals from tropical countries in Africa, Central America, and South America most commonly are affected.¹ These diseases also are related to poor housing quality and inadequate sanitation.^1,3,4 Travel for business, medical missions, pleasure, or emigration has caused increased filarial infections globally. In fact, dermatologic disorders with infectious etiologies cause approximately 17% of travelers to seek medical attention.³

Dermatologic manifestations indicative of a potential cutaneous filarial infection include papules, nodules, excoriations with secondary xerosis, lichenification, skin pigment changes, and/or severe pruritus. However, individuals from filarial endemic regions may not demonstrate any clinical signs or symptoms, despite having microfilariae in their blood,¹ which enables the disease to propagate and poses a major public health concern. In fact, patients with chronic filarial infections are at increased risk for developing lymphedema, elephantiasis, or blindness, which are hypothesized to be the second largest cause of permanent disability worldwide.¹ Although rarely seen in US citizens, cutaneous filariasis should always be a diagnostic consideration in patients who present with a pruritic eruption and have a travel history to tropical countries. We report a case of cutaneous onchocerciasis in a US citizen who developed a pruritic eczematous eruption on the right upper arm following an arthropod assault while working in an Onchocerca endemic region approximately 1.5 years prior.

A 33-year-old woman presented to our outpatient dermatology clinic with the chief concern of a pruritic rash on the right arm (Figure 1). She revealed a history of travel to Peru, associated symptoms, prior diagnoses, and attempted treatment regimens. Over a 1.5-year period, the patient traveled for work-related reasons to Madre de Dios, Peru. During that time, the patient experienced 2 bouts of severe abdominal pain, nausea, and vomiting that she attributed to poor food and water quality. She did not immediately seek medical attention. She also developed skin manifestations that began as a pruritic and irritating pinpoint-sized red papule on the right eyelid, possibly a site of an arthropod assault. She then experienced episodic eyelash loss (Figure 2) and subsequent vision changes, including blurry vision, halos around lights, and dimming around the periphery. When the patient developed circular, pink, pruritic plaques on the right upper extremity, she sought medical attention in Lima, Peru. She was diagnosed with tinea corporis and prescribed an oral antibiotic and topical antifungal.

A few days after the treatment for the blastocystis, the gastrointestinal tract symptoms improved, but dermatologic, ocular, pulmonary, and cardiac symptoms persisted. She also began experiencing night sweats and hot flashes. In between visits to the primary care physician, she sought medical attention at an urgent care clinic for worsening pulmonary and cardiac symptoms. At that time, results of a chest radiograph were normal.

The primary care physician referred her to infectious disease and dermatology for further evaluation within a few weeks of returning to the United States. Upon presentation to dermatology, the patient described a waxing and waning nature to the rash on the arm with associated intermittent pain. Physical examination revealed several erythematous patches on the triceps and a 1-cm subcutaneous nodule on the right elbow with overlying skin discoloration. The patient stated that she first noticed the inflamed painful nodule when she returned to the United States. Since its discovery, the nodule increased in size and became firm. The patient also described occasional limited range of motion of the right arm due to the discomfort of the rash and inflamed nodule. Interestingly, the patient’s partner who accompanied her to Peru also developed a similar pruritic rash on the chest. He was evaluated by dermatology and infectious disease; however, biopsies of his rash performed at a different practice revealed nonspecific results. Due to her partner’s inconclusive results, our patient initially refused a biopsy; however, she returned to the office after 1 week with worsening symptoms, and a 4-mm punch biopsy of the right arm was obtained in addition to rapid plasma reagin and QuantiFERON-TB Gold test.

Based on the patient’s travel history, clinical course, and physical examination, the clinical differential diagnosis included nummular dermatitis, panniculitis/nodular vasculitis, tinea corporis, secondary syphilis, pinta, tuberculosis, or cutaneous filariasis. Rapid plasma reagin and QuantiFERON-TB Gold test results were negative, and a periodic acid–Schiff stain of the biopsy was negative for fungal elements. Dermatopathology revealed intradermal filarial nematodes of 120 to 150 µm in diameter and 1-to 2-mm cuticles eliciting a predominantly superficial and deep lymphohistiocytic reaction (Figure 3). The histopathologic differential diagnosis based on the diameter of the nematode included M perstans, W bancrofti, and O volvulus. Clinical correlation was highly recommended to obtain a final diagnosis and management plan. A portion of the biopsy was sent to the Centers for Disease Control and Prevention, which confirmed the presence of a filarial nematode consistent with a zoonotic Brugia but also with zoonotic Onchocerca as a possible differential. Therefore, considering the history, clinical course, and histopathologic analysis, the final diagnosis of cutaneous onchocerciasis was made.

Onchocerciasis is common in individuals who live or work in equatorial Africa, Central America, and South America. The disease process has dermatologic, ocular, and other systemic manifestations if the infection continues long-term without treatment.^2,5 Although rare, this infection has been observed in US citizens who have traveled to filarial endemic regions for a period of time ranging from 2 weeks to 39 years.^2,6,7

Blackflies (genus Simulium), the intermediate host of O volvulus, breed in areas close to freely flowing water. The blackfly bites a human host, and within 7 days the microfilariae undergo 2 molts to reach the infective stage. The larvae remain in the dermis and subcutaneous tissue for 2 additional molts until they develop into adult worms. Then, adult worms may become encapsulated, eliciting and forming subcutaneous nodules, also known as onchocercomas.^2,3

A fertilized female in the subcutaneous tissue releases microfilariae that may remain in the skin or travel to the eyes of the host.³ The host may demonstrate signs of infection within 3 to 15 months.² Most commonly, patients report localized or generalized pruritus, and one extremity develops swelling, papules, lymphadenopathy, and alterations of skin pigment (hypopigmentation or hyperpigmentation).^5-8 Our patient developed a pruritic eczematous eruption that only affected her right arm with an inflamed firm nodule overlying the elbow, a suspected onchocercoma. Onchocercomas are the direct result of adult worms coiled in the dermis, subcutaneous tissue, and deep fascia. These commonly are found in close proximity to bony prominences with the specific location pending the geographic area of infection.⁸ For example, onchocercomas more commonly are found over bony prominences in the head and upper body region in patients who acquired the disease from Central or South America, whereas individuals infected in Africa more commonly develop onchocercomas near the femoral, coccyx, or sacral regions.²

The immune response mounted by the infected host is responsible for the ocular signs and symptoms.² Specifically, the inflammatory reaction may impact the patient’s cornea, anterior uveal tract, chorioretinal zone, or optic nerve. In fact, onchocerciasis, or river blindness, is the leading cause of blindness in the world.² The host immune response also is responsible for the dermatologic manifestations of this disease. In addition to the dermatologic manifestations already mentioned, others include epidermal atrophy, ulcerations, femoral or inguinal lymphadenitis, lymphedema, and/or general wasting in more severe long-standing infections. Additionally, patients may experience systemic signs resulting from an underlying O volvulus infection.⁸ Our patient demonstrated a subjectively remarkable systemic response manifested by shortness of breath, dyspnea, cough, and palpitations, likely the result of her existing filarial infection.

Diagnosis of onchocerciasis is made by identification of microfilariae or adult worms in skin snips or punch biopsies. Histopathologic analysis of onchocerciasis has been described as several adult worms in the subcutaneous tissue surrounded by a granulomatous, fibrotic, calcified, or sometimes ossified inflammatory reaction.⁸ Microfilariae may migrate to the upper dermis and typically are surrounded by lymphocytes, histiocytes, plasma cells, and eosinophils with an absence of neutrophils,^5,8 which directly causes the overlying epidermis to undergo reactive changes. Measurement of filarial nematodes often helps differentiate species. For example, O volvulus typically measures 230 to 500 mm in length for females and 16 to 42 mm in length for males.⁸ The thickness of cuticles typically measures 4 to 8 µm for females and 3 to 5 µm for males. Microfilariae of O volvulus also have been identified in patient’s sputum, urine, blood, and spinal fluid.⁸ An alternative diagnostic method described by Stingl et al⁹ is a diethylcarbamazine (DEC) patch test that was 92% accurate in onchocerciasis cases diagnosed by skin snip analysis.⁹ Therefore, this test may be a practical alternative when skin specimens are inconclusive.

Management of onchocerciasis should include excision of subcutaneous nodules to remove adult worms. In the past, DEC with suramin was prescribed and kills both microfilariae and adult worms.⁸ However, DEC may induce pruritus, chorioretinal damage, and optic neuritis and suramin is nephrotoxic.² Therefore, oral ivermectin (0.15–0.20 mg/kg one-time dose, may be repeated in 3–12 months) is supported to be a less harmful option. Patients treated with ivermectin have a decreased risk for transmitting infection to the blackfly vector for up to 6 months after treatment, and it is a more effective microfilaricidal agent than DEC.^2,3 Oral doxycycline (100 mg/d for 6 weeks) commonly is added as adjuvant therapy because it kills Wolbachia species, a bacterium that is needed for O volvulus reproduction.³

Although rare in the United States, cutaneous filariasis has become a prevalent public health concern, especially in tropical countries. Individuals with chronic cutaneous filarial infections are at increased risk for debilitating complications that negatively affect their quality of life and productivity. Although the World Health Organization has attempted to eradicate cutaneous filarial infections by mass drug administration, transmission of these diseases remains a challenge. Further research on treatment and methods to prevent transmission by controlling arthropod vectors is required to avoid short-term and long-term health consequences caused by cutaneous filariasis.

Parasitic infections should always be a diagnostic consideration in individuals who present with a pruritic eruption and a history of travel to foreign countries located in Africa, Central America, and South America. Dermatologists in the United States should increase familiarity with these infections because of increased travel, economic globalization, and the impact of global climate change on the geographic distribution of vector arthropods. To control these infections, research efforts should focus on improved sanitation; drug treatment; transmission prevention; and improved education of their clinical manifestations, especially mucocutaneous signs.

Primitive human habits have withstood the test of time but can pose health risks. Exploring a nasal cavity with a finger might have first occurred shortly after whichever species first developed a nasal opening and a digit able to reach it. Humans have been keen on continuing the long-standing yet taboo habit of nose-picking (rhinotillexis).

Even though nose-picking is stigmatized, anonymous surveys show that almost all adolescents and adults do it.¹ People are typically unaware of the risks of regular rhinotillexis. Studies exploring the intranasal human microbiome have elicited asymptomatic yet potential disease-causing microbes, including the notorious bacterium Staphylococcus aureus. As many as 30% of humans are asymptomatically permanently colonized with S aureus in their anterior nares.² These natural reservoirs can be the source of opportunistic infection that increases morbidity, mortality, and overall health care costs.

With the rise of antimicrobial resistance, especially methicillin-resistant S aureus (MRSA), a more direct approach might be necessary to curb nasally sourced cutaneous infection. Since dermatology patients deal with a wide array of skin barrier defects that put them at risk for S aureus–related infection, a medical provider’s understanding about the role of nasal colonization and transmission is important. Addressing the awkward question of “Do you pick your nose?” and providing education on the topic might be uncomfortable, but it might be necessary for dermatology patients at risk for S aureus–related cutaneous disease.

Staphylococcus aureus colonizes the anterior nares of 20% to 80% of humans; nasal colonization can begin during the first days of life.² The anterior nares are noted as the main reservoir of chronic carriage of S aureus, but carriage can occur at various body sites, including the rectum, vagina, gastrointestinal tract, and axilla, as well as other cutaneous sites. Hands are noted as the main vector of S aureus transmission from source to nose; a positive correlation between nose-picking habits and nasal carriage of S aureus has been noted.²

The percentage of S aureus–colonized humans who harbor MRSA is unknown, but it is a topic of concern with the rise of MRSA-related infection. Multisite MRSA carriage increases the risk for nasal MRSA colonization, and nasal MRSA has been noted to be more difficult to decolonize than nonresistant strains. Health care workers carrying S aureus can trigger a potential hospital outbreak of MRSA. Studies have shown that bacterial transmission is increased 40-fold when the nasal host is co-infected by rhinovirus.² Health care workers can be a source of MRSA during outbreaks, but they have not been shown to be more likely to carry MRSA than the general population.² Understanding which patients might be at risk for S aureus–associated disease in dermatology can lead clinicians to consider decolonization strategies.

Nasal colonization has been noted more frequently in patients with predisposing risk factors, including human immunodeficiency virus infection, obesity, diabetes mellitus, granulomatosis with polyangiitis, HLA-DR3 phenotype, skin and soft-tissue infections, atopic dermatitis, impetigo, and recurrent furunculosis.²Staphylococcus aureus is the most frequently noted pathogen in diabetic foot infection. A study found that 36% of sampled diabetic foot-infection patients also had S aureus isolated from both nares and the foot wound, with 65% of isolated strains being identical.² Although there are clear data on decolonization of patients prior to heart and orthopedic surgery, more data are needed to determine the benefit of screening and treating nasal carriers in populations with diabetic foot ulcers.

Staphylococcus aureus nasal colonization also has been shown in approximately 60% of patients with recurrent furunculosis and impetigo.² Although it is clear that there is a correlation between S aureus–related skin infection and nasal colonization, it is unclear what role nose-picking might have in perpetuating these complications.

There are multiple approaches to S aureus decolonization, including intranasal mupirocin, chlorhexidine body wipes, bleach baths, and even oral antibiotics (eg, trimethoprim-sulfamethoxazole, clindamycin). The Infectious Diseases Society of America has published guidelines for treating recurrent MRSA infection, including 5 to 10 days of intranasal mupirocin plus either body decolonization with a daily chlorhexidine wash for 5 to 14 days or a 15-minute dilute bleach bath twice weekly for 3 months.^3,4

There are ample meta-analyses and systematic reviews regarding S aureus decolonization and management in patients undergoing dialysis or surgery but limited data when it comes to this topic in dermatology. Those limited studies do show a benefit to decolonization in several diseases, including atopic dermatitis, hand dermatitis, recurrent skin and soft-tissue infections, cutaneous T-cell lymphoma, and surgical infection following Mohs micrographic surgery.⁴ Typically, it also is necessary to treat those who might come in contact with the patient or caregiver; in theory, treating contacts helps reduce the chance that the patient will become recolonized shortly afterward, but the data are limited regarding long-term colonization status following treatment. Contact surfaces, especially cell phones, are noted to be a contributing factor to nares colonization; therefore, it also may be necessary to educate patients on surface-cleaning techniques.⁵ Because there are multiple sources of S aureus that patients can come in contact with after decolonization attempts, a nose-picking habit might play a vital role in recolonization.

Due to rising bacterial resistance to mupirocin and chlorhexidine decolonization strategies, there is a growing need for more effective, long-term decolonization strategies.⁴ These strategies must address patients’ environmental exposure and nasal-touching habits. Overcoming the habit of nose-picking might aid S aureus decolonization strategies and thus aid in preventing future antimicrobial resistance.

But are at-risk patients receiving sufficient screening and education on the dangers of a nose-picking habit? Effective strategies to assess these practices and recommend the discontinuation of the habit could have positive effects in maintaining long-term decolonization. Potential euphemistic ways to approach this somewhat taboo topic include questions that elicit information on whether the patient ever touches the inside of his/her nose, washes his/her hands before and after touching the inside of the nose, knows about transfer of bacteria from hand to nose, or understands what decolonization is doing for them. The patient might be inclined to deny such activity, but education on nasal hygiene should be provided regardless, especially in pediatric patients.

Staphylococcus aureus might be a normal human nasal inhabitant, but it can cause a range of problems for dermatologic disease. Although pharmacotherapeutic decolonization strategies can have a positive effect on dermatologic disease, growing antibiotic resistance calls for health care providers to assess patients’ nose picking-habits and educate them on effective ways to prevent finger-to-nose practices.

Primitive human habits have withstood the test of time but can pose health risks. Exploring a nasal cavity with a finger might have first occurred shortly after whichever species first developed a nasal opening and a digit able to reach it. Humans have been keen on continuing the long-standing yet taboo habit of nose-picking (rhinotillexis).

Even though nose-picking is stigmatized, anonymous surveys show that almost all adolescents and adults do it.¹ People are typically unaware of the risks of regular rhinotillexis. Studies exploring the intranasal human microbiome have elicited asymptomatic yet potential disease-causing microbes, including the notorious bacterium Staphylococcus aureus. As many as 30% of humans are asymptomatically permanently colonized with S aureus in their anterior nares.² These natural reservoirs can be the source of opportunistic infection that increases morbidity, mortality, and overall health care costs.

With the rise of antimicrobial resistance, especially methicillin-resistant S aureus (MRSA), a more direct approach might be necessary to curb nasally sourced cutaneous infection. Since dermatology patients deal with a wide array of skin barrier defects that put them at risk for S aureus–related infection, a medical provider’s understanding about the role of nasal colonization and transmission is important. Addressing the awkward question of “Do you pick your nose?” and providing education on the topic might be uncomfortable, but it might be necessary for dermatology patients at risk for S aureus–related cutaneous disease.

Staphylococcus aureus colonizes the anterior nares of 20% to 80% of humans; nasal colonization can begin during the first days of life.² The anterior nares are noted as the main reservoir of chronic carriage of S aureus, but carriage can occur at various body sites, including the rectum, vagina, gastrointestinal tract, and axilla, as well as other cutaneous sites. Hands are noted as the main vector of S aureus transmission from source to nose; a positive correlation between nose-picking habits and nasal carriage of S aureus has been noted.²

The percentage of S aureus–colonized humans who harbor MRSA is unknown, but it is a topic of concern with the rise of MRSA-related infection. Multisite MRSA carriage increases the risk for nasal MRSA colonization, and nasal MRSA has been noted to be more difficult to decolonize than nonresistant strains. Health care workers carrying S aureus can trigger a potential hospital outbreak of MRSA. Studies have shown that bacterial transmission is increased 40-fold when the nasal host is co-infected by rhinovirus.² Health care workers can be a source of MRSA during outbreaks, but they have not been shown to be more likely to carry MRSA than the general population.² Understanding which patients might be at risk for S aureus–associated disease in dermatology can lead clinicians to consider decolonization strategies.

Nasal colonization has been noted more frequently in patients with predisposing risk factors, including human immunodeficiency virus infection, obesity, diabetes mellitus, granulomatosis with polyangiitis, HLA-DR3 phenotype, skin and soft-tissue infections, atopic dermatitis, impetigo, and recurrent furunculosis.²Staphylococcus aureus is the most frequently noted pathogen in diabetic foot infection. A study found that 36% of sampled diabetic foot-infection patients also had S aureus isolated from both nares and the foot wound, with 65% of isolated strains being identical.² Although there are clear data on decolonization of patients prior to heart and orthopedic surgery, more data are needed to determine the benefit of screening and treating nasal carriers in populations with diabetic foot ulcers.

Staphylococcus aureus nasal colonization also has been shown in approximately 60% of patients with recurrent furunculosis and impetigo.² Although it is clear that there is a correlation between S aureus–related skin infection and nasal colonization, it is unclear what role nose-picking might have in perpetuating these complications.

There are multiple approaches to S aureus decolonization, including intranasal mupirocin, chlorhexidine body wipes, bleach baths, and even oral antibiotics (eg, trimethoprim-sulfamethoxazole, clindamycin). The Infectious Diseases Society of America has published guidelines for treating recurrent MRSA infection, including 5 to 10 days of intranasal mupirocin plus either body decolonization with a daily chlorhexidine wash for 5 to 14 days or a 15-minute dilute bleach bath twice weekly for 3 months.^3,4

There are ample meta-analyses and systematic reviews regarding S aureus decolonization and management in patients undergoing dialysis or surgery but limited data when it comes to this topic in dermatology. Those limited studies do show a benefit to decolonization in several diseases, including atopic dermatitis, hand dermatitis, recurrent skin and soft-tissue infections, cutaneous T-cell lymphoma, and surgical infection following Mohs micrographic surgery.⁴ Typically, it also is necessary to treat those who might come in contact with the patient or caregiver; in theory, treating contacts helps reduce the chance that the patient will become recolonized shortly afterward, but the data are limited regarding long-term colonization status following treatment. Contact surfaces, especially cell phones, are noted to be a contributing factor to nares colonization; therefore, it also may be necessary to educate patients on surface-cleaning techniques.⁵ Because there are multiple sources of S aureus that patients can come in contact with after decolonization attempts, a nose-picking habit might play a vital role in recolonization.

Due to rising bacterial resistance to mupirocin and chlorhexidine decolonization strategies, there is a growing need for more effective, long-term decolonization strategies.⁴ These strategies must address patients’ environmental exposure and nasal-touching habits. Overcoming the habit of nose-picking might aid S aureus decolonization strategies and thus aid in preventing future antimicrobial resistance.

But are at-risk patients receiving sufficient screening and education on the dangers of a nose-picking habit? Effective strategies to assess these practices and recommend the discontinuation of the habit could have positive effects in maintaining long-term decolonization. Potential euphemistic ways to approach this somewhat taboo topic include questions that elicit information on whether the patient ever touches the inside of his/her nose, washes his/her hands before and after touching the inside of the nose, knows about transfer of bacteria from hand to nose, or understands what decolonization is doing for them. The patient might be inclined to deny such activity, but education on nasal hygiene should be provided regardless, especially in pediatric patients.

Staphylococcus aureus might be a normal human nasal inhabitant, but it can cause a range of problems for dermatologic disease. Although pharmacotherapeutic decolonization strategies can have a positive effect on dermatologic disease, growing antibiotic resistance calls for health care providers to assess patients’ nose picking-habits and educate them on effective ways to prevent finger-to-nose practices.

Primitive human habits have withstood the test of time but can pose health risks. Exploring a nasal cavity with a finger might have first occurred shortly after whichever species first developed a nasal opening and a digit able to reach it. Humans have been keen on continuing the long-standing yet taboo habit of nose-picking (rhinotillexis).

Even though nose-picking is stigmatized, anonymous surveys show that almost all adolescents and adults do it.¹ People are typically unaware of the risks of regular rhinotillexis. Studies exploring the intranasal human microbiome have elicited asymptomatic yet potential disease-causing microbes, including the notorious bacterium Staphylococcus aureus. As many as 30% of humans are asymptomatically permanently colonized with S aureus in their anterior nares.² These natural reservoirs can be the source of opportunistic infection that increases morbidity, mortality, and overall health care costs.

With the rise of antimicrobial resistance, especially methicillin-resistant S aureus (MRSA), a more direct approach might be necessary to curb nasally sourced cutaneous infection. Since dermatology patients deal with a wide array of skin barrier defects that put them at risk for S aureus–related infection, a medical provider’s understanding about the role of nasal colonization and transmission is important. Addressing the awkward question of “Do you pick your nose?” and providing education on the topic might be uncomfortable, but it might be necessary for dermatology patients at risk for S aureus–related cutaneous disease.

Staphylococcus aureus colonizes the anterior nares of 20% to 80% of humans; nasal colonization can begin during the first days of life.² The anterior nares are noted as the main reservoir of chronic carriage of S aureus, but carriage can occur at various body sites, including the rectum, vagina, gastrointestinal tract, and axilla, as well as other cutaneous sites. Hands are noted as the main vector of S aureus transmission from source to nose; a positive correlation between nose-picking habits and nasal carriage of S aureus has been noted.²

The percentage of S aureus–colonized humans who harbor MRSA is unknown, but it is a topic of concern with the rise of MRSA-related infection. Multisite MRSA carriage increases the risk for nasal MRSA colonization, and nasal MRSA has been noted to be more difficult to decolonize than nonresistant strains. Health care workers carrying S aureus can trigger a potential hospital outbreak of MRSA. Studies have shown that bacterial transmission is increased 40-fold when the nasal host is co-infected by rhinovirus.² Health care workers can be a source of MRSA during outbreaks, but they have not been shown to be more likely to carry MRSA than the general population.² Understanding which patients might be at risk for S aureus–associated disease in dermatology can lead clinicians to consider decolonization strategies.

Nasal colonization has been noted more frequently in patients with predisposing risk factors, including human immunodeficiency virus infection, obesity, diabetes mellitus, granulomatosis with polyangiitis, HLA-DR3 phenotype, skin and soft-tissue infections, atopic dermatitis, impetigo, and recurrent furunculosis.²Staphylococcus aureus is the most frequently noted pathogen in diabetic foot infection. A study found that 36% of sampled diabetic foot-infection patients also had S aureus isolated from both nares and the foot wound, with 65% of isolated strains being identical.² Although there are clear data on decolonization of patients prior to heart and orthopedic surgery, more data are needed to determine the benefit of screening and treating nasal carriers in populations with diabetic foot ulcers.

Staphylococcus aureus nasal colonization also has been shown in approximately 60% of patients with recurrent furunculosis and impetigo.² Although it is clear that there is a correlation between S aureus–related skin infection and nasal colonization, it is unclear what role nose-picking might have in perpetuating these complications.

There are multiple approaches to S aureus decolonization, including intranasal mupirocin, chlorhexidine body wipes, bleach baths, and even oral antibiotics (eg, trimethoprim-sulfamethoxazole, clindamycin). The Infectious Diseases Society of America has published guidelines for treating recurrent MRSA infection, including 5 to 10 days of intranasal mupirocin plus either body decolonization with a daily chlorhexidine wash for 5 to 14 days or a 15-minute dilute bleach bath twice weekly for 3 months.^3,4

There are ample meta-analyses and systematic reviews regarding S aureus decolonization and management in patients undergoing dialysis or surgery but limited data when it comes to this topic in dermatology. Those limited studies do show a benefit to decolonization in several diseases, including atopic dermatitis, hand dermatitis, recurrent skin and soft-tissue infections, cutaneous T-cell lymphoma, and surgical infection following Mohs micrographic surgery.⁴ Typically, it also is necessary to treat those who might come in contact with the patient or caregiver; in theory, treating contacts helps reduce the chance that the patient will become recolonized shortly afterward, but the data are limited regarding long-term colonization status following treatment. Contact surfaces, especially cell phones, are noted to be a contributing factor to nares colonization; therefore, it also may be necessary to educate patients on surface-cleaning techniques.⁵ Because there are multiple sources of S aureus that patients can come in contact with after decolonization attempts, a nose-picking habit might play a vital role in recolonization.

Due to rising bacterial resistance to mupirocin and chlorhexidine decolonization strategies, there is a growing need for more effective, long-term decolonization strategies.⁴ These strategies must address patients’ environmental exposure and nasal-touching habits. Overcoming the habit of nose-picking might aid S aureus decolonization strategies and thus aid in preventing future antimicrobial resistance.

But are at-risk patients receiving sufficient screening and education on the dangers of a nose-picking habit? Effective strategies to assess these practices and recommend the discontinuation of the habit could have positive effects in maintaining long-term decolonization. Potential euphemistic ways to approach this somewhat taboo topic include questions that elicit information on whether the patient ever touches the inside of his/her nose, washes his/her hands before and after touching the inside of the nose, knows about transfer of bacteria from hand to nose, or understands what decolonization is doing for them. The patient might be inclined to deny such activity, but education on nasal hygiene should be provided regardless, especially in pediatric patients.

Staphylococcus aureus might be a normal human nasal inhabitant, but it can cause a range of problems for dermatologic disease. Although pharmacotherapeutic decolonization strategies can have a positive effect on dermatologic disease, growing antibiotic resistance calls for health care providers to assess patients’ nose picking-habits and educate them on effective ways to prevent finger-to-nose practices.