Infectious Diseases

Up-to-date vaccination rates rose significantly in a neonatal ICU after implementation of five interventions targeting root causes of low immunization, according to a study in Pediatrics.

MarianVejcik/Getty Images

Investigators led by Raymond C. Stetson, MD, of the Mayo Clinic in Rochester, Minn., identified three root causes of underimmunization in a NICU at Mayo Clinic: providers’ lack of knowledge about recommended immunization schedules; immunizations not being ordered when they were due; and parental hesitancy toward vaccination. They addressed these causes with the following five phases of intervention: an intranet resource educating providers about vaccine schedules and dosing intervals; a spreadsheet-based checklist to track and flag immunization status; an intranet resource aimed at discussion with vaccine-hesitant parents; education about safety in providing immunization and review of material from the first three interventions; and education about documentation, including parental consent.

Over the project period, 1,242 infants were discharged or transferred from the NICU. The study included a 6-month “improve phase,” during which interventions were implemented, and a “control phase,” during which the ongoing effects after implementation were observed. At baseline, the rate of fully immunized infants in the NICU was only 56% by time of discharge or transfer, but during the combined improve and control phases, it was 93% with a P value of less than .001.

One of the limitations of the study is that the first three interventions were introduced simultaneously, which makes it hard to determine how much effect each might have had.

“Infants treated in NICUs represent a vulnerable population with the potential for high morbidity and mortality from vaccine-preventable infections,” the investigators wrote. “Our [quality improvement] effort, and others, demonstrate that this population is at risk for underimmunization and that immunization rates can be improved with a small number of interventions. Additionally, we were able to significantly decrease the number of days that immunizations were delayed compared to the routine infant vaccination schedule.”

There was no external funding for the study. One of the coauthors is on safety committees of vaccine studies for Merck. The other authors have no relevant financial disclosures.

[email protected]

SOURCE: Stetson R et al. Pediatr. 2019. doi: 10.1542/peds.2019-0337.

Up-to-date vaccination rates rose significantly in a neonatal ICU after implementation of five interventions targeting root causes of low immunization, according to a study in Pediatrics.

MarianVejcik/Getty Images

Investigators led by Raymond C. Stetson, MD, of the Mayo Clinic in Rochester, Minn., identified three root causes of underimmunization in a NICU at Mayo Clinic: providers’ lack of knowledge about recommended immunization schedules; immunizations not being ordered when they were due; and parental hesitancy toward vaccination. They addressed these causes with the following five phases of intervention: an intranet resource educating providers about vaccine schedules and dosing intervals; a spreadsheet-based checklist to track and flag immunization status; an intranet resource aimed at discussion with vaccine-hesitant parents; education about safety in providing immunization and review of material from the first three interventions; and education about documentation, including parental consent.

Over the project period, 1,242 infants were discharged or transferred from the NICU. The study included a 6-month “improve phase,” during which interventions were implemented, and a “control phase,” during which the ongoing effects after implementation were observed. At baseline, the rate of fully immunized infants in the NICU was only 56% by time of discharge or transfer, but during the combined improve and control phases, it was 93% with a P value of less than .001.

One of the limitations of the study is that the first three interventions were introduced simultaneously, which makes it hard to determine how much effect each might have had.

“Infants treated in NICUs represent a vulnerable population with the potential for high morbidity and mortality from vaccine-preventable infections,” the investigators wrote. “Our [quality improvement] effort, and others, demonstrate that this population is at risk for underimmunization and that immunization rates can be improved with a small number of interventions. Additionally, we were able to significantly decrease the number of days that immunizations were delayed compared to the routine infant vaccination schedule.”

There was no external funding for the study. One of the coauthors is on safety committees of vaccine studies for Merck. The other authors have no relevant financial disclosures.

[email protected]

SOURCE: Stetson R et al. Pediatr. 2019. doi: 10.1542/peds.2019-0337.

Up-to-date vaccination rates rose significantly in a neonatal ICU after implementation of five interventions targeting root causes of low immunization, according to a study in Pediatrics.

MarianVejcik/Getty Images

Investigators led by Raymond C. Stetson, MD, of the Mayo Clinic in Rochester, Minn., identified three root causes of underimmunization in a NICU at Mayo Clinic: providers’ lack of knowledge about recommended immunization schedules; immunizations not being ordered when they were due; and parental hesitancy toward vaccination. They addressed these causes with the following five phases of intervention: an intranet resource educating providers about vaccine schedules and dosing intervals; a spreadsheet-based checklist to track and flag immunization status; an intranet resource aimed at discussion with vaccine-hesitant parents; education about safety in providing immunization and review of material from the first three interventions; and education about documentation, including parental consent.

Over the project period, 1,242 infants were discharged or transferred from the NICU. The study included a 6-month “improve phase,” during which interventions were implemented, and a “control phase,” during which the ongoing effects after implementation were observed. At baseline, the rate of fully immunized infants in the NICU was only 56% by time of discharge or transfer, but during the combined improve and control phases, it was 93% with a P value of less than .001.

One of the limitations of the study is that the first three interventions were introduced simultaneously, which makes it hard to determine how much effect each might have had.

“Infants treated in NICUs represent a vulnerable population with the potential for high morbidity and mortality from vaccine-preventable infections,” the investigators wrote. “Our [quality improvement] effort, and others, demonstrate that this population is at risk for underimmunization and that immunization rates can be improved with a small number of interventions. Additionally, we were able to significantly decrease the number of days that immunizations were delayed compared to the routine infant vaccination schedule.”

There was no external funding for the study. One of the coauthors is on safety committees of vaccine studies for Merck. The other authors have no relevant financial disclosures.

[email protected]

SOURCE: Stetson R et al. Pediatr. 2019. doi: 10.1542/peds.2019-0337.

New York State has reported the end of all active measles cases related to the initial outbreak in 2018, but the state is now responding to new, unrelated cases in four counties, according to the Centers for Disease Control and Prevention.

The new cases – two in Nassau County and one each in Monroe, Putnam, and Rockland counties – are “related to measles exposures from international travel but not affiliated with the 2018 outbreak,” the New York State Department of Health said in a written statement. Officials in Rockland County had declared its 2018 measles outbreak, which involved 312 cases in 2018 and 2019, over on Sept. 25.

Nationally, there have been 1,250 cases of measles reported in 31 states during 2019, the CDC reported on Oct. 7. Of those cases, 1,163 (93%) were associated with 22 outbreaks, with the two largest occurring in New York City and Rockland County. “These two almost year-long outbreaks placed the United States at risk for losing measles elimination status,” the CDC said in a separate report, but “robust responses … ended transmission before the 1-year mark.”

[email protected]

New York State has reported the end of all active measles cases related to the initial outbreak in 2018, but the state is now responding to new, unrelated cases in four counties, according to the Centers for Disease Control and Prevention.

The new cases – two in Nassau County and one each in Monroe, Putnam, and Rockland counties – are “related to measles exposures from international travel but not affiliated with the 2018 outbreak,” the New York State Department of Health said in a written statement. Officials in Rockland County had declared its 2018 measles outbreak, which involved 312 cases in 2018 and 2019, over on Sept. 25.

Nationally, there have been 1,250 cases of measles reported in 31 states during 2019, the CDC reported on Oct. 7. Of those cases, 1,163 (93%) were associated with 22 outbreaks, with the two largest occurring in New York City and Rockland County. “These two almost year-long outbreaks placed the United States at risk for losing measles elimination status,” the CDC said in a separate report, but “robust responses … ended transmission before the 1-year mark.”

[email protected]

New York State has reported the end of all active measles cases related to the initial outbreak in 2018, but the state is now responding to new, unrelated cases in four counties, according to the Centers for Disease Control and Prevention.

The new cases – two in Nassau County and one each in Monroe, Putnam, and Rockland counties – are “related to measles exposures from international travel but not affiliated with the 2018 outbreak,” the New York State Department of Health said in a written statement. Officials in Rockland County had declared its 2018 measles outbreak, which involved 312 cases in 2018 and 2019, over on Sept. 25.

Nationally, there have been 1,250 cases of measles reported in 31 states during 2019, the CDC reported on Oct. 7. Of those cases, 1,163 (93%) were associated with 22 outbreaks, with the two largest occurring in New York City and Rockland County. “These two almost year-long outbreaks placed the United States at risk for losing measles elimination status,” the CDC said in a separate report, but “robust responses … ended transmission before the 1-year mark.”

[email protected]

A 29-year-old man with no prior history of mouth sores abruptly developed many 1- to 1.5-mm blisters on the gingiva (FIGURE 1A),tongue (FIGURE 1B), and buccal mucosa ­(FIGURE 1C), which evolved into small erosions accompanied by a low-grade fever 5 days prior to presentation. The patient had no history of any dermatologic conditions or systemic illnesses and was taking no medication.

IMAGES COURTESY OF ROBERT T. BRODELL, MD

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

Herpes simplex virus (HSV) is the causative agent for acute primary herpetic gingivostomatitis.¹ HSV-1 is primarily responsible for oral mucosal infections, while HSV-2 is implicated in most genital and cutaneous lower body lesions.¹ Herpetic gingivostomatitis often presents as a sudden vesiculoulcerative eruption anywhere in the mouth, including the perioral skin, vermillion border, gingiva, tongue, or buccal mucosa.² Associated symptoms include malaise, headache, fever, and cervical lymphadenopathy; however, most ­occurrences are subclinical or asymptomatic.²

A diagnosis that’s more common in children. Primary HSV occurs in people who have not previously been exposed to the virus. While it is an infection that classically presents in childhood, it is not limited to this group. Manifestations often are more severe in adults.¹

Utilize PCR for the diagnosis of herpetic gingivostomatitis because of its sensitivity, specificity, and rapid turnaround time.

Following an incubation period of a few days to 3 weeks, the primary infection typically lasts 10 to 14 days.^1,2 Recurrence is highly variable and generally less severe than primary infection, with grouped vesicles often recurring in the same spot with each recurrence on the vermillion border of the lip. Triggers for reactivation include immunosuppression, pregnancy, fever, UV radiation, or trauma.^1,2

Differential includes other conditions with mucosal lesions

Acute herpetic gingivostomatitis must be distinguished from other disease processes that cause ulcerative mucosal lesions.

Aphthous stomatitis (canker sores) is the most common ulcerative disease of the oral mucosa.³ It presents as painful, punched-out, shallow ulcers with a yellowish gray pseudomembranous center and surrounding erythema.³ No definitive etiology has been established; however, aphthae often occur after trauma.

Continue to: Herpangina...

Herpangina is caused by coxsackie A virus and primarily is seen in infants and children younger than 5.⁴ The papulovesicular lesions primarily affect the posterior oral cavity, including the soft palate, anterior tonsillar pillars, and uvula.⁴

Allergic contact dermatitis is precipitated by contact with an allergen and presents with pain or pruritus. Lesions are erythematous with vesicles, erosions, ulcers, or hyperkeratosis that gradually resolve after withdrawal of the causative allergen.⁵

Pemphigus vulgaris. Oral ulcerations of the buccal mucosa and gingiva are the first manifestation of pemphigus vulgaris in the majority of patients, with skin blisters occurring months to years later over areas exposed to frictional stress.⁶ Skin sloughs may be seen in response to frictional stress (Nikolsky sign).⁶

The new Dx gold standard is PCR

Acute herpetic gingivostomatitis usually is diagnosed by history and hallmark clinical signs and symptoms.¹ In this case, our patient presented with a sudden eruption of painful blisters on multiple areas of the oral mucosa associated with fever. The diagnosis can be confirmed by viral culture, serology with anti-HSV IgM and IgG, Tzanck preparation, immunofluorescence, and polymerase chain reaction (PCR).¹ Viral culture has been the gold standard for mucosal HSV diagnosis; however, PCR is emerging as the new gold standard because of its unrivaled sensitivity, specificity, and rapid turnaround time.^7,8 Specimens for PCR are submitted using a swab of infected cells placed in the same viral transport ­medium used for HSV cultures.

Our patient’s culture was positive for HSV-1.

Continue to: Prompt use of antivirals is key

Treatment of acute HSV gingivostomatitis involves symptomatic management with topical anesthetics, oral analgesics, and normal saline rinses.¹ Acyclovir is an established therapy; however, it has poor bioavailability and gastrointestinal absorption.¹ Valacyclovir has improved bioavailability and is well tolerated.¹ For primary herpes gingivostomatitis, we favor 1 g twice daily for 7 days.¹ Our patient responded well to this valacyclovir regimen and healed completely in 1 week.

CORRESPONDENCE
Robert T. Brodell, MD, 2500 N State St, Jackson, MS 39216; [email protected]

A 29-year-old man with no prior history of mouth sores abruptly developed many 1- to 1.5-mm blisters on the gingiva (FIGURE 1A),tongue (FIGURE 1B), and buccal mucosa ­(FIGURE 1C), which evolved into small erosions accompanied by a low-grade fever 5 days prior to presentation. The patient had no history of any dermatologic conditions or systemic illnesses and was taking no medication.

IMAGES COURTESY OF ROBERT T. BRODELL, MD

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

Herpes simplex virus (HSV) is the causative agent for acute primary herpetic gingivostomatitis.¹ HSV-1 is primarily responsible for oral mucosal infections, while HSV-2 is implicated in most genital and cutaneous lower body lesions.¹ Herpetic gingivostomatitis often presents as a sudden vesiculoulcerative eruption anywhere in the mouth, including the perioral skin, vermillion border, gingiva, tongue, or buccal mucosa.² Associated symptoms include malaise, headache, fever, and cervical lymphadenopathy; however, most ­occurrences are subclinical or asymptomatic.²

A diagnosis that’s more common in children. Primary HSV occurs in people who have not previously been exposed to the virus. While it is an infection that classically presents in childhood, it is not limited to this group. Manifestations often are more severe in adults.¹

Utilize PCR for the diagnosis of herpetic gingivostomatitis because of its sensitivity, specificity, and rapid turnaround time.

Following an incubation period of a few days to 3 weeks, the primary infection typically lasts 10 to 14 days.^1,2 Recurrence is highly variable and generally less severe than primary infection, with grouped vesicles often recurring in the same spot with each recurrence on the vermillion border of the lip. Triggers for reactivation include immunosuppression, pregnancy, fever, UV radiation, or trauma.^1,2

Differential includes other conditions with mucosal lesions

Acute herpetic gingivostomatitis must be distinguished from other disease processes that cause ulcerative mucosal lesions.

Aphthous stomatitis (canker sores) is the most common ulcerative disease of the oral mucosa.³ It presents as painful, punched-out, shallow ulcers with a yellowish gray pseudomembranous center and surrounding erythema.³ No definitive etiology has been established; however, aphthae often occur after trauma.

Continue to: Herpangina...

Herpangina is caused by coxsackie A virus and primarily is seen in infants and children younger than 5.⁴ The papulovesicular lesions primarily affect the posterior oral cavity, including the soft palate, anterior tonsillar pillars, and uvula.⁴

Allergic contact dermatitis is precipitated by contact with an allergen and presents with pain or pruritus. Lesions are erythematous with vesicles, erosions, ulcers, or hyperkeratosis that gradually resolve after withdrawal of the causative allergen.⁵

Pemphigus vulgaris. Oral ulcerations of the buccal mucosa and gingiva are the first manifestation of pemphigus vulgaris in the majority of patients, with skin blisters occurring months to years later over areas exposed to frictional stress.⁶ Skin sloughs may be seen in response to frictional stress (Nikolsky sign).⁶

The new Dx gold standard is PCR

Acute herpetic gingivostomatitis usually is diagnosed by history and hallmark clinical signs and symptoms.¹ In this case, our patient presented with a sudden eruption of painful blisters on multiple areas of the oral mucosa associated with fever. The diagnosis can be confirmed by viral culture, serology with anti-HSV IgM and IgG, Tzanck preparation, immunofluorescence, and polymerase chain reaction (PCR).¹ Viral culture has been the gold standard for mucosal HSV diagnosis; however, PCR is emerging as the new gold standard because of its unrivaled sensitivity, specificity, and rapid turnaround time.^7,8 Specimens for PCR are submitted using a swab of infected cells placed in the same viral transport ­medium used for HSV cultures.

Our patient’s culture was positive for HSV-1.

Continue to: Prompt use of antivirals is key

Treatment of acute HSV gingivostomatitis involves symptomatic management with topical anesthetics, oral analgesics, and normal saline rinses.¹ Acyclovir is an established therapy; however, it has poor bioavailability and gastrointestinal absorption.¹ Valacyclovir has improved bioavailability and is well tolerated.¹ For primary herpes gingivostomatitis, we favor 1 g twice daily for 7 days.¹ Our patient responded well to this valacyclovir regimen and healed completely in 1 week.

CORRESPONDENCE
Robert T. Brodell, MD, 2500 N State St, Jackson, MS 39216; [email protected]

A 29-year-old man with no prior history of mouth sores abruptly developed many 1- to 1.5-mm blisters on the gingiva (FIGURE 1A),tongue (FIGURE 1B), and buccal mucosa ­(FIGURE 1C), which evolved into small erosions accompanied by a low-grade fever 5 days prior to presentation. The patient had no history of any dermatologic conditions or systemic illnesses and was taking no medication.

IMAGES COURTESY OF ROBERT T. BRODELL, MD

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

Herpes simplex virus (HSV) is the causative agent for acute primary herpetic gingivostomatitis.¹ HSV-1 is primarily responsible for oral mucosal infections, while HSV-2 is implicated in most genital and cutaneous lower body lesions.¹ Herpetic gingivostomatitis often presents as a sudden vesiculoulcerative eruption anywhere in the mouth, including the perioral skin, vermillion border, gingiva, tongue, or buccal mucosa.² Associated symptoms include malaise, headache, fever, and cervical lymphadenopathy; however, most ­occurrences are subclinical or asymptomatic.²

A diagnosis that’s more common in children. Primary HSV occurs in people who have not previously been exposed to the virus. While it is an infection that classically presents in childhood, it is not limited to this group. Manifestations often are more severe in adults.¹

Utilize PCR for the diagnosis of herpetic gingivostomatitis because of its sensitivity, specificity, and rapid turnaround time.

Following an incubation period of a few days to 3 weeks, the primary infection typically lasts 10 to 14 days.^1,2 Recurrence is highly variable and generally less severe than primary infection, with grouped vesicles often recurring in the same spot with each recurrence on the vermillion border of the lip. Triggers for reactivation include immunosuppression, pregnancy, fever, UV radiation, or trauma.^1,2

Differential includes other conditions with mucosal lesions

Acute herpetic gingivostomatitis must be distinguished from other disease processes that cause ulcerative mucosal lesions.

Aphthous stomatitis (canker sores) is the most common ulcerative disease of the oral mucosa.³ It presents as painful, punched-out, shallow ulcers with a yellowish gray pseudomembranous center and surrounding erythema.³ No definitive etiology has been established; however, aphthae often occur after trauma.

Continue to: Herpangina...

Herpangina is caused by coxsackie A virus and primarily is seen in infants and children younger than 5.⁴ The papulovesicular lesions primarily affect the posterior oral cavity, including the soft palate, anterior tonsillar pillars, and uvula.⁴

Allergic contact dermatitis is precipitated by contact with an allergen and presents with pain or pruritus. Lesions are erythematous with vesicles, erosions, ulcers, or hyperkeratosis that gradually resolve after withdrawal of the causative allergen.⁵

Pemphigus vulgaris. Oral ulcerations of the buccal mucosa and gingiva are the first manifestation of pemphigus vulgaris in the majority of patients, with skin blisters occurring months to years later over areas exposed to frictional stress.⁶ Skin sloughs may be seen in response to frictional stress (Nikolsky sign).⁶

The new Dx gold standard is PCR

Acute herpetic gingivostomatitis usually is diagnosed by history and hallmark clinical signs and symptoms.¹ In this case, our patient presented with a sudden eruption of painful blisters on multiple areas of the oral mucosa associated with fever. The diagnosis can be confirmed by viral culture, serology with anti-HSV IgM and IgG, Tzanck preparation, immunofluorescence, and polymerase chain reaction (PCR).¹ Viral culture has been the gold standard for mucosal HSV diagnosis; however, PCR is emerging as the new gold standard because of its unrivaled sensitivity, specificity, and rapid turnaround time.^7,8 Specimens for PCR are submitted using a swab of infected cells placed in the same viral transport ­medium used for HSV cultures.

Our patient’s culture was positive for HSV-1.

Continue to: Prompt use of antivirals is key

Treatment of acute HSV gingivostomatitis involves symptomatic management with topical anesthetics, oral analgesics, and normal saline rinses.¹ Acyclovir is an established therapy; however, it has poor bioavailability and gastrointestinal absorption.¹ Valacyclovir has improved bioavailability and is well tolerated.¹ For primary herpes gingivostomatitis, we favor 1 g twice daily for 7 days.¹ Our patient responded well to this valacyclovir regimen and healed completely in 1 week.

CORRESPONDENCE
Robert T. Brodell, MD, 2500 N State St, Jackson, MS 39216; [email protected]

2018-2019 season retrospective

Last year’s influenza season was longer than usual. Infections, as measured by the percentage of outpatient visits due to influenza-like illness, increased in early November 2018, peaked in early February to mid-March of 2019, and remained above baseline levels through mid-May.^1,2 Ninety six percent of influenza-positive samples were influenza A,¹ and 57% of those were H1N1.² In the second half of the season, H3N2 became the predominant circulating virus and there was a genetic shift in this strain that caused a decrease in the effectiveness of influenza vaccines ­(FIGURE).¹ The influenza-confirmed hospitalization rate was 65.3/100,000, with the highest rate (221.7/100,000) occurring among those 65 years of age and older.² Of those hospitalized with influenza, 93% of adults and 55% of children had an underlying medical condition and 29% of women of childbearing age were pregnant.²

Morbidity and mortality from influenza during the 2018-2019 influenza season were moderate compared with previous years. Pneumonia and influenza mortality reached close to 8% of all deaths during the peak of the season (considered a modest peak), but stayed above the epidemic threshold for 10 weeks.² There were 119 pediatric deaths.¹ Overall, in the United States, there were an estimated 37 to 43 million influenza-related illnesses, 17 to 20 million flu-related medical visits, 531,000 to 647,000 flu-related hospitalizations, and 36,400 to 61,200 deaths.¹

Influenza viral resistance to oseltamivir remained very low throughout the season for both A and B viruses.²

Vaccine effectiveness was subpar

The effectiveness of influenza vaccine last season was disappointing. When assessed using laboratory-confirmed medically attended influenza, the vaccine was 29% effective; when assessed by age group, the confidence intervals included 0 in ages 9 to 17 years and 50 years and older.³ In the age group 6 months to 8 years, the vaccine was 49% effective.³ The vaccine was not effective against the predominant H3N2 strain circulating. It was 25% effective in preventing hospitalization, with a lack of benefit seen in individuals ages 18 to 49 years and those 65 and older.³

Vaccination was associated with increased rates of hospitalizations from infections cause by H3N2. It is not known if this finding was due to chance, unstable results from small numbers, an unknown bias, or some biological cause not yet understood. This is a topic of ongoing research.

Effectiveness in preventing pediatric hospitalizations was estimated at 31%, again with no effectiveness against H3N2.³ The estimate of vaccine effectiveness in the United States was similar to that in Canada.²

While these results are much lower than desired, influenza vaccine did prevent an estimated 40,000 to 90,000 hospitalizations and decreased influenza-like illnesses by 44%.³

Continue to: A look at vaccine safety

Numerous studies of influenza vaccine safety were presented at the June 2019 meeting of the Advisory Committee on Immunization Practices (ACIP).⁴ These studies included assessments using the Vaccine Adverse Events Reporting System; the Vaccine Safety Datalink (VSD), which conducts ongoing rapid analysis of adverse events throughout the influenza season; and Food and Drug Administration (FDA)-sponsored studies of Medicare patients. These vaccine safety monitoring systems have been described in a prior Practice Alert.⁵

The effectiveness of the influenza vaccine last season was disappointing. When assessed using laboratory-confirmed medically attended influenza, the vaccine was 29% effective.

Possible vaccine reactions studied included Guillain-Barre Syndrome (GBS), anaphylaxis, encephalitis, Bell’s palsy, febrile seizures, and pregnancy-related adverse events such as miscarriage and congenital anomalies. While preliminary safety signals were detected for anaphylaxis, Bell’s palsy, febrile seizures, and GBS, a more in-depth investigation found no association of any adverse events with vaccination except for febrile seizures, with an attributable risk of 4.24/100,000 doses in children ages 6 to 23 months and 1.8/100,000 in those ages 24 to 59 months.⁴ The incidence of febrile seizures was similar to that of previous seasons and primarily occurred when the vaccine was administered in conjunction with another vaccine. A preliminary FDA analysis found a small elevated risk of GBS with high-dose trivalent inactivated vaccine, with an attributable risk of 0.98 per million doses, but this was not confirmed by the VSD analysis.⁴

What you need to know about the upcoming season

ACIP recommendations on influenza vaccines for 2019 to 2020 are essentially unchanged from last year.⁶ All individuals ages 6 months and older, who do not have a contraindication, should receive a flu vaccine in the fall of 2019. The composition of this season’s vaccine contains new H1N1 and H3N2 variants to more closely match the circulating strains. ACIP has updated or clarified 4 logistical issues in this year’s recommendations:

1. Four inactivated-influenza vaccines are now available for children ages 6 to 35 months. Dose volumes are not the same for all 4 (TABLE).⁷
2. Vaccination is now encouraged for September or later for those requiring only 1 dose of vaccine. Earlier administration can result in waning immunity by the end of the flu season, especially in older adults.⁷
3. Children ages 6 months to 8 years may require 2 doses if they haven’t received any previous influenza vaccine, and the second dose should be given even if the child turns 9 between doses 1 and 2.⁷
4. One adjuvanted influenza vaccine containing MF59—the trivalent inactivated influenza vaccine, Fluad—is approved for those ages 65 years and older. One note of caution is that licensed vaccines for other conditions also contain new nonaluminum adjuvants and there are few data on the safety and effectiveness of simultaneous or sequential administration of Fluad with the 2 novel nonaluminum adjuvant-containing vaccines. These vaccines are the recombinant zoster subunit vaccine (Shingrix), which contains the liposome-based adjuvant ASO1, and the recombinant hepatitis B surface antigen vaccine (Heplisav-B), which contains cytosine phosphoguanine oligodeoxynucleotide. Given the lack of data and the availability of other influenza vaccine options, ACIP advises that selecting a nonadjuvanted influenza vaccine may be the best option when an older adult needs both an influenza vaccine and either Shingrix or Heplisav-B. However, do not delay giving any vaccine if a specific alternate product is unavailable.⁷

All recommendations concerning the use of influenza vaccine for the 2019-2020 influenza season and a listing of all available influenza vaccine products can be found on the ACIP Web site (cdc.gov/vaccines/acip/index.html) or in the Morbidity and Mortality Weekly Report.⁸

2018-2019 season retrospective

Last year’s influenza season was longer than usual. Infections, as measured by the percentage of outpatient visits due to influenza-like illness, increased in early November 2018, peaked in early February to mid-March of 2019, and remained above baseline levels through mid-May.^1,2 Ninety six percent of influenza-positive samples were influenza A,¹ and 57% of those were H1N1.² In the second half of the season, H3N2 became the predominant circulating virus and there was a genetic shift in this strain that caused a decrease in the effectiveness of influenza vaccines ­(FIGURE).¹ The influenza-confirmed hospitalization rate was 65.3/100,000, with the highest rate (221.7/100,000) occurring among those 65 years of age and older.² Of those hospitalized with influenza, 93% of adults and 55% of children had an underlying medical condition and 29% of women of childbearing age were pregnant.²

Morbidity and mortality from influenza during the 2018-2019 influenza season were moderate compared with previous years. Pneumonia and influenza mortality reached close to 8% of all deaths during the peak of the season (considered a modest peak), but stayed above the epidemic threshold for 10 weeks.² There were 119 pediatric deaths.¹ Overall, in the United States, there were an estimated 37 to 43 million influenza-related illnesses, 17 to 20 million flu-related medical visits, 531,000 to 647,000 flu-related hospitalizations, and 36,400 to 61,200 deaths.¹

Influenza viral resistance to oseltamivir remained very low throughout the season for both A and B viruses.²

Vaccine effectiveness was subpar

The effectiveness of influenza vaccine last season was disappointing. When assessed using laboratory-confirmed medically attended influenza, the vaccine was 29% effective; when assessed by age group, the confidence intervals included 0 in ages 9 to 17 years and 50 years and older.³ In the age group 6 months to 8 years, the vaccine was 49% effective.³ The vaccine was not effective against the predominant H3N2 strain circulating. It was 25% effective in preventing hospitalization, with a lack of benefit seen in individuals ages 18 to 49 years and those 65 and older.³

Vaccination was associated with increased rates of hospitalizations from infections cause by H3N2. It is not known if this finding was due to chance, unstable results from small numbers, an unknown bias, or some biological cause not yet understood. This is a topic of ongoing research.

Effectiveness in preventing pediatric hospitalizations was estimated at 31%, again with no effectiveness against H3N2.³ The estimate of vaccine effectiveness in the United States was similar to that in Canada.²

While these results are much lower than desired, influenza vaccine did prevent an estimated 40,000 to 90,000 hospitalizations and decreased influenza-like illnesses by 44%.³

Continue to: A look at vaccine safety

Numerous studies of influenza vaccine safety were presented at the June 2019 meeting of the Advisory Committee on Immunization Practices (ACIP).⁴ These studies included assessments using the Vaccine Adverse Events Reporting System; the Vaccine Safety Datalink (VSD), which conducts ongoing rapid analysis of adverse events throughout the influenza season; and Food and Drug Administration (FDA)-sponsored studies of Medicare patients. These vaccine safety monitoring systems have been described in a prior Practice Alert.⁵

The effectiveness of the influenza vaccine last season was disappointing. When assessed using laboratory-confirmed medically attended influenza, the vaccine was 29% effective.

Possible vaccine reactions studied included Guillain-Barre Syndrome (GBS), anaphylaxis, encephalitis, Bell’s palsy, febrile seizures, and pregnancy-related adverse events such as miscarriage and congenital anomalies. While preliminary safety signals were detected for anaphylaxis, Bell’s palsy, febrile seizures, and GBS, a more in-depth investigation found no association of any adverse events with vaccination except for febrile seizures, with an attributable risk of 4.24/100,000 doses in children ages 6 to 23 months and 1.8/100,000 in those ages 24 to 59 months.⁴ The incidence of febrile seizures was similar to that of previous seasons and primarily occurred when the vaccine was administered in conjunction with another vaccine. A preliminary FDA analysis found a small elevated risk of GBS with high-dose trivalent inactivated vaccine, with an attributable risk of 0.98 per million doses, but this was not confirmed by the VSD analysis.⁴

What you need to know about the upcoming season

ACIP recommendations on influenza vaccines for 2019 to 2020 are essentially unchanged from last year.⁶ All individuals ages 6 months and older, who do not have a contraindication, should receive a flu vaccine in the fall of 2019. The composition of this season’s vaccine contains new H1N1 and H3N2 variants to more closely match the circulating strains. ACIP has updated or clarified 4 logistical issues in this year’s recommendations:

1. Four inactivated-influenza vaccines are now available for children ages 6 to 35 months. Dose volumes are not the same for all 4 (TABLE).⁷
2. Vaccination is now encouraged for September or later for those requiring only 1 dose of vaccine. Earlier administration can result in waning immunity by the end of the flu season, especially in older adults.⁷
3. Children ages 6 months to 8 years may require 2 doses if they haven’t received any previous influenza vaccine, and the second dose should be given even if the child turns 9 between doses 1 and 2.⁷
4. One adjuvanted influenza vaccine containing MF59—the trivalent inactivated influenza vaccine, Fluad—is approved for those ages 65 years and older. One note of caution is that licensed vaccines for other conditions also contain new nonaluminum adjuvants and there are few data on the safety and effectiveness of simultaneous or sequential administration of Fluad with the 2 novel nonaluminum adjuvant-containing vaccines. These vaccines are the recombinant zoster subunit vaccine (Shingrix), which contains the liposome-based adjuvant ASO1, and the recombinant hepatitis B surface antigen vaccine (Heplisav-B), which contains cytosine phosphoguanine oligodeoxynucleotide. Given the lack of data and the availability of other influenza vaccine options, ACIP advises that selecting a nonadjuvanted influenza vaccine may be the best option when an older adult needs both an influenza vaccine and either Shingrix or Heplisav-B. However, do not delay giving any vaccine if a specific alternate product is unavailable.⁷

All recommendations concerning the use of influenza vaccine for the 2019-2020 influenza season and a listing of all available influenza vaccine products can be found on the ACIP Web site (cdc.gov/vaccines/acip/index.html) or in the Morbidity and Mortality Weekly Report.⁸

2018-2019 season retrospective

Last year’s influenza season was longer than usual. Infections, as measured by the percentage of outpatient visits due to influenza-like illness, increased in early November 2018, peaked in early February to mid-March of 2019, and remained above baseline levels through mid-May.^1,2 Ninety six percent of influenza-positive samples were influenza A,¹ and 57% of those were H1N1.² In the second half of the season, H3N2 became the predominant circulating virus and there was a genetic shift in this strain that caused a decrease in the effectiveness of influenza vaccines ­(FIGURE).¹ The influenza-confirmed hospitalization rate was 65.3/100,000, with the highest rate (221.7/100,000) occurring among those 65 years of age and older.² Of those hospitalized with influenza, 93% of adults and 55% of children had an underlying medical condition and 29% of women of childbearing age were pregnant.²

Morbidity and mortality from influenza during the 2018-2019 influenza season were moderate compared with previous years. Pneumonia and influenza mortality reached close to 8% of all deaths during the peak of the season (considered a modest peak), but stayed above the epidemic threshold for 10 weeks.² There were 119 pediatric deaths.¹ Overall, in the United States, there were an estimated 37 to 43 million influenza-related illnesses, 17 to 20 million flu-related medical visits, 531,000 to 647,000 flu-related hospitalizations, and 36,400 to 61,200 deaths.¹

Influenza viral resistance to oseltamivir remained very low throughout the season for both A and B viruses.²

Vaccine effectiveness was subpar

The effectiveness of influenza vaccine last season was disappointing. When assessed using laboratory-confirmed medically attended influenza, the vaccine was 29% effective; when assessed by age group, the confidence intervals included 0 in ages 9 to 17 years and 50 years and older.³ In the age group 6 months to 8 years, the vaccine was 49% effective.³ The vaccine was not effective against the predominant H3N2 strain circulating. It was 25% effective in preventing hospitalization, with a lack of benefit seen in individuals ages 18 to 49 years and those 65 and older.³

Vaccination was associated with increased rates of hospitalizations from infections cause by H3N2. It is not known if this finding was due to chance, unstable results from small numbers, an unknown bias, or some biological cause not yet understood. This is a topic of ongoing research.

Effectiveness in preventing pediatric hospitalizations was estimated at 31%, again with no effectiveness against H3N2.³ The estimate of vaccine effectiveness in the United States was similar to that in Canada.²

While these results are much lower than desired, influenza vaccine did prevent an estimated 40,000 to 90,000 hospitalizations and decreased influenza-like illnesses by 44%.³

Continue to: A look at vaccine safety

Numerous studies of influenza vaccine safety were presented at the June 2019 meeting of the Advisory Committee on Immunization Practices (ACIP).⁴ These studies included assessments using the Vaccine Adverse Events Reporting System; the Vaccine Safety Datalink (VSD), which conducts ongoing rapid analysis of adverse events throughout the influenza season; and Food and Drug Administration (FDA)-sponsored studies of Medicare patients. These vaccine safety monitoring systems have been described in a prior Practice Alert.⁵

The effectiveness of the influenza vaccine last season was disappointing. When assessed using laboratory-confirmed medically attended influenza, the vaccine was 29% effective.

Possible vaccine reactions studied included Guillain-Barre Syndrome (GBS), anaphylaxis, encephalitis, Bell’s palsy, febrile seizures, and pregnancy-related adverse events such as miscarriage and congenital anomalies. While preliminary safety signals were detected for anaphylaxis, Bell’s palsy, febrile seizures, and GBS, a more in-depth investigation found no association of any adverse events with vaccination except for febrile seizures, with an attributable risk of 4.24/100,000 doses in children ages 6 to 23 months and 1.8/100,000 in those ages 24 to 59 months.⁴ The incidence of febrile seizures was similar to that of previous seasons and primarily occurred when the vaccine was administered in conjunction with another vaccine. A preliminary FDA analysis found a small elevated risk of GBS with high-dose trivalent inactivated vaccine, with an attributable risk of 0.98 per million doses, but this was not confirmed by the VSD analysis.⁴

What you need to know about the upcoming season

ACIP recommendations on influenza vaccines for 2019 to 2020 are essentially unchanged from last year.⁶ All individuals ages 6 months and older, who do not have a contraindication, should receive a flu vaccine in the fall of 2019. The composition of this season’s vaccine contains new H1N1 and H3N2 variants to more closely match the circulating strains. ACIP has updated or clarified 4 logistical issues in this year’s recommendations:

1. Four inactivated-influenza vaccines are now available for children ages 6 to 35 months. Dose volumes are not the same for all 4 (TABLE).⁷
2. Vaccination is now encouraged for September or later for those requiring only 1 dose of vaccine. Earlier administration can result in waning immunity by the end of the flu season, especially in older adults.⁷
3. Children ages 6 months to 8 years may require 2 doses if they haven’t received any previous influenza vaccine, and the second dose should be given even if the child turns 9 between doses 1 and 2.⁷
4. One adjuvanted influenza vaccine containing MF59—the trivalent inactivated influenza vaccine, Fluad—is approved for those ages 65 years and older. One note of caution is that licensed vaccines for other conditions also contain new nonaluminum adjuvants and there are few data on the safety and effectiveness of simultaneous or sequential administration of Fluad with the 2 novel nonaluminum adjuvant-containing vaccines. These vaccines are the recombinant zoster subunit vaccine (Shingrix), which contains the liposome-based adjuvant ASO1, and the recombinant hepatitis B surface antigen vaccine (Heplisav-B), which contains cytosine phosphoguanine oligodeoxynucleotide. Given the lack of data and the availability of other influenza vaccine options, ACIP advises that selecting a nonadjuvanted influenza vaccine may be the best option when an older adult needs both an influenza vaccine and either Shingrix or Heplisav-B. However, do not delay giving any vaccine if a specific alternate product is unavailable.⁷

All recommendations concerning the use of influenza vaccine for the 2019-2020 influenza season and a listing of all available influenza vaccine products can be found on the ACIP Web site (cdc.gov/vaccines/acip/index.html) or in the Morbidity and Mortality Weekly Report.⁸

The Diagnosis: Fracture Blisters 

The shave biopsy pathology demonstrated a subepidermal bulla with re-epithelialization that was clinically consistent with fracture blisters (also known as fracture bullae)(Figure). Fracture blisters are a complication of bone fractures, usually occurring 24 to 48 hours after the trauma but possibly up to 3 weeks later. The skin usually is edematous with tense bullae overlying the fracture (in this case it was distal to the fracture); most blisters contain clear fluid, but older blisters tend to be more flaccid with hemorrhagic fluid.¹ The cause is thought to be the result of skin strain during fracture formation.² Edema and hypoxia from injured vessels and lymphatics contribute to the formation of bullae, which are seen as a dermoepidermal junction split on histology.¹ 

The bullae are histologically indistinguishable from edema blisters. A clinical history can help to differentiate. Edema blisters occur in the setting of an acute exacerbation of chronic edema, usually on the lower extremities in the setting of fluid overload.³ Bullous cellulitis is associated with skin erythema, warmth, and systemic symptoms. Bullous pemphigoid can be localized to the lower legs at times; however, biopsy would show a subepidermal bulla with eosinophils along the dermoepidermal junction. Linear IgA bullous dermatosis can be drug induced from vancomycin; however, pathology would show a subepidermal blister with a neutrophil predominant infiltrate. Nonsteroidal anti-inflammatory medications such as naproxen are a common culprit for bullous drug eruptions, which can be localized or generalized and include diagnoses such as fixed drug eruption, toxic epidermal necrolysis, and drug-induced pseudoporphyria. Naproxen-induced pseudoporphyria more commonly presents with blisters, erosions, and scarring with a predilection for the dorsal hands. Histology also will demonstrate subepidermal bullae. Clues to differentiate pseudoporphyria from fracture blisters include festooning of the dermal papilla and caterpillar bodies consisting of basement membrane material and colloid bodies in the basal layer of the epidermis, though they are not always present.⁴ 

Fracture blisters can be localized to the injury site or extend beyond the fracture site. They usually are found where there is minimal subcutaneous tissue, such as the tibia, ankles, and elbows. Fractures treated within 24 hours are much less likely to have bullae formation.¹ The bullae are sterile but may lead to wound healing complications, such as infections or delay in surgical management. However, there are no major adverse effects of postoperative fracture blisters.¹ Fracture blisters are self-healing, though silver sulfadiazine has been shown to minimize soft-tissue complications by promoting re-epithelialization.⁵ 
 

The Diagnosis: Fracture Blisters 

The shave biopsy pathology demonstrated a subepidermal bulla with re-epithelialization that was clinically consistent with fracture blisters (also known as fracture bullae)(Figure). Fracture blisters are a complication of bone fractures, usually occurring 24 to 48 hours after the trauma but possibly up to 3 weeks later. The skin usually is edematous with tense bullae overlying the fracture (in this case it was distal to the fracture); most blisters contain clear fluid, but older blisters tend to be more flaccid with hemorrhagic fluid.¹ The cause is thought to be the result of skin strain during fracture formation.² Edema and hypoxia from injured vessels and lymphatics contribute to the formation of bullae, which are seen as a dermoepidermal junction split on histology.¹ 

The bullae are histologically indistinguishable from edema blisters. A clinical history can help to differentiate. Edema blisters occur in the setting of an acute exacerbation of chronic edema, usually on the lower extremities in the setting of fluid overload.³ Bullous cellulitis is associated with skin erythema, warmth, and systemic symptoms. Bullous pemphigoid can be localized to the lower legs at times; however, biopsy would show a subepidermal bulla with eosinophils along the dermoepidermal junction. Linear IgA bullous dermatosis can be drug induced from vancomycin; however, pathology would show a subepidermal blister with a neutrophil predominant infiltrate. Nonsteroidal anti-inflammatory medications such as naproxen are a common culprit for bullous drug eruptions, which can be localized or generalized and include diagnoses such as fixed drug eruption, toxic epidermal necrolysis, and drug-induced pseudoporphyria. Naproxen-induced pseudoporphyria more commonly presents with blisters, erosions, and scarring with a predilection for the dorsal hands. Histology also will demonstrate subepidermal bullae. Clues to differentiate pseudoporphyria from fracture blisters include festooning of the dermal papilla and caterpillar bodies consisting of basement membrane material and colloid bodies in the basal layer of the epidermis, though they are not always present.⁴ 

Fracture blisters can be localized to the injury site or extend beyond the fracture site. They usually are found where there is minimal subcutaneous tissue, such as the tibia, ankles, and elbows. Fractures treated within 24 hours are much less likely to have bullae formation.¹ The bullae are sterile but may lead to wound healing complications, such as infections or delay in surgical management. However, there are no major adverse effects of postoperative fracture blisters.¹ Fracture blisters are self-healing, though silver sulfadiazine has been shown to minimize soft-tissue complications by promoting re-epithelialization.⁵ 
 

The Diagnosis: Fracture Blisters 

The shave biopsy pathology demonstrated a subepidermal bulla with re-epithelialization that was clinically consistent with fracture blisters (also known as fracture bullae)(Figure). Fracture blisters are a complication of bone fractures, usually occurring 24 to 48 hours after the trauma but possibly up to 3 weeks later. The skin usually is edematous with tense bullae overlying the fracture (in this case it was distal to the fracture); most blisters contain clear fluid, but older blisters tend to be more flaccid with hemorrhagic fluid.¹ The cause is thought to be the result of skin strain during fracture formation.² Edema and hypoxia from injured vessels and lymphatics contribute to the formation of bullae, which are seen as a dermoepidermal junction split on histology.¹ 

The bullae are histologically indistinguishable from edema blisters. A clinical history can help to differentiate. Edema blisters occur in the setting of an acute exacerbation of chronic edema, usually on the lower extremities in the setting of fluid overload.³ Bullous cellulitis is associated with skin erythema, warmth, and systemic symptoms. Bullous pemphigoid can be localized to the lower legs at times; however, biopsy would show a subepidermal bulla with eosinophils along the dermoepidermal junction. Linear IgA bullous dermatosis can be drug induced from vancomycin; however, pathology would show a subepidermal blister with a neutrophil predominant infiltrate. Nonsteroidal anti-inflammatory medications such as naproxen are a common culprit for bullous drug eruptions, which can be localized or generalized and include diagnoses such as fixed drug eruption, toxic epidermal necrolysis, and drug-induced pseudoporphyria. Naproxen-induced pseudoporphyria more commonly presents with blisters, erosions, and scarring with a predilection for the dorsal hands. Histology also will demonstrate subepidermal bullae. Clues to differentiate pseudoporphyria from fracture blisters include festooning of the dermal papilla and caterpillar bodies consisting of basement membrane material and colloid bodies in the basal layer of the epidermis, though they are not always present.⁴ 

Fracture blisters can be localized to the injury site or extend beyond the fracture site. They usually are found where there is minimal subcutaneous tissue, such as the tibia, ankles, and elbows. Fractures treated within 24 hours are much less likely to have bullae formation.¹ The bullae are sterile but may lead to wound healing complications, such as infections or delay in surgical management. However, there are no major adverse effects of postoperative fracture blisters.¹ Fracture blisters are self-healing, though silver sulfadiazine has been shown to minimize soft-tissue complications by promoting re-epithelialization.⁵ 
 

A study of 305 cases of acute flaccid myelitis has found further evidence of a viral etiology but is yet to identify a single pathogen as the primary cause.

Writing in Pediatrics, researchers published an analysis of patients presenting with acute flaccid limb weakness from January 2015 to December 2017 across 43 states.

A total of 25 cases were judged as probable for acute flaccid myelitis (AFM) because they met clinical criteria and had a white blood cell count above 5 cells per mm³ in cerebrospinal fluid, while 193 were judged as confirmed cases based on the additional presence of spinal cord gray matter lesions on MRI.

Overall, 83% of patients had experienced fever, cough, runny nose, vomiting, and/or diarrhea for a median of 5 days before limb weakness began. Two-thirds of patients had experienced a respiratory illness, 62% had experienced a fever, and 29% had experienced gastrointestinal illness.

Overall, 47% of the 193 patients who had specimens tested at a Centers for Disease Control and Prevention or non-CDC laboratory had a pathogen found at any site, 10% had a pathogen detected from a sterile site such as cerebrospinal fluid or sera, and 42% had a pathogen detected from a nonsterile site.

Among 72 patients who had serum specimens tested at the CDC, 2 were positive for enteroviruses. Among the 90 patients who had upper respiratory specimens tested, 36% were positive for either enteroviruses or rhinoviruses.

A number of stool specimens were also tested; 15% were positive for enteroviruses or rhinoviruses and one was positive for parechovirus.

Cerebrospinal fluid was tested in 170 patients, of which 4 were positive for enteroviruses. The testing also found adenovirus, Epstein-Barr virus, human herpesvirus 6, and mycoplasma in six patients. Sera testing of 123 patients found 9 were positive for enteroviruses, West Nile virus, mycoplasma, and coxsackievirus B.

“In our summary of national AFM surveillance from 2015 to 2017, we demonstrate that cases were widely distributed across the United States, the majority of cases occurred in late summer or fall, children were predominantly affected, there is a spectrum of clinical severity, and no single pathogen was identified as the primary cause of AFM,” wrote Tracy Ayers, PhD, from the National Center for Immunization and Respiratory Diseases, and coauthors. “We conclude that symptoms of a viral syndrome within the week before limb weakness, detection of viral pathogens from sterile and nonsterile sites from almost half of patients, and seasonality of AFM incidence, particularly during the 2016 peak year, strongly suggest a viral etiology, including [enteroviruses].”

The authors of an accompanying editorial noted that the clinical syndrome of acute flaccid paralysis caused by myelitis in the gray matter of the spinal cord has previously been associated with a range of viruses, including poliovirus, enteroviruses, and flaviviruses, so a single etiology to explain all cases would not be expected.

“The central question remains: What is driving seasonal biennial nationwide outbreaks of AFM since 2014?” wrote Kevin Messaca, MD, and colleagues from the University of Colorado at Denver, Aurora.

Two authors declared consultancies, grants, and research contracts with the pharmaceutical sector. No other conflicts of interest were declared. One editorial author declared funding from the National Institute of Allergy and Infectious Diseases.

SOURCE: Ayers T et al. Pediatrics. 2019 Oct 7. doi: 10.1542/peds.2019-1619.

*Updated 10/14/2019.

A study of 305 cases of acute flaccid myelitis has found further evidence of a viral etiology but is yet to identify a single pathogen as the primary cause.

Writing in Pediatrics, researchers published an analysis of patients presenting with acute flaccid limb weakness from January 2015 to December 2017 across 43 states.

A total of 25 cases were judged as probable for acute flaccid myelitis (AFM) because they met clinical criteria and had a white blood cell count above 5 cells per mm³ in cerebrospinal fluid, while 193 were judged as confirmed cases based on the additional presence of spinal cord gray matter lesions on MRI.

Overall, 83% of patients had experienced fever, cough, runny nose, vomiting, and/or diarrhea for a median of 5 days before limb weakness began. Two-thirds of patients had experienced a respiratory illness, 62% had experienced a fever, and 29% had experienced gastrointestinal illness.

Overall, 47% of the 193 patients who had specimens tested at a Centers for Disease Control and Prevention or non-CDC laboratory had a pathogen found at any site, 10% had a pathogen detected from a sterile site such as cerebrospinal fluid or sera, and 42% had a pathogen detected from a nonsterile site.

Among 72 patients who had serum specimens tested at the CDC, 2 were positive for enteroviruses. Among the 90 patients who had upper respiratory specimens tested, 36% were positive for either enteroviruses or rhinoviruses.

A number of stool specimens were also tested; 15% were positive for enteroviruses or rhinoviruses and one was positive for parechovirus.

Cerebrospinal fluid was tested in 170 patients, of which 4 were positive for enteroviruses. The testing also found adenovirus, Epstein-Barr virus, human herpesvirus 6, and mycoplasma in six patients. Sera testing of 123 patients found 9 were positive for enteroviruses, West Nile virus, mycoplasma, and coxsackievirus B.

“In our summary of national AFM surveillance from 2015 to 2017, we demonstrate that cases were widely distributed across the United States, the majority of cases occurred in late summer or fall, children were predominantly affected, there is a spectrum of clinical severity, and no single pathogen was identified as the primary cause of AFM,” wrote Tracy Ayers, PhD, from the National Center for Immunization and Respiratory Diseases, and coauthors. “We conclude that symptoms of a viral syndrome within the week before limb weakness, detection of viral pathogens from sterile and nonsterile sites from almost half of patients, and seasonality of AFM incidence, particularly during the 2016 peak year, strongly suggest a viral etiology, including [enteroviruses].”

The authors of an accompanying editorial noted that the clinical syndrome of acute flaccid paralysis caused by myelitis in the gray matter of the spinal cord has previously been associated with a range of viruses, including poliovirus, enteroviruses, and flaviviruses, so a single etiology to explain all cases would not be expected.

“The central question remains: What is driving seasonal biennial nationwide outbreaks of AFM since 2014?” wrote Kevin Messaca, MD, and colleagues from the University of Colorado at Denver, Aurora.

Two authors declared consultancies, grants, and research contracts with the pharmaceutical sector. No other conflicts of interest were declared. One editorial author declared funding from the National Institute of Allergy and Infectious Diseases.

SOURCE: Ayers T et al. Pediatrics. 2019 Oct 7. doi: 10.1542/peds.2019-1619.

*Updated 10/14/2019.

A study of 305 cases of acute flaccid myelitis has found further evidence of a viral etiology but is yet to identify a single pathogen as the primary cause.

Writing in Pediatrics, researchers published an analysis of patients presenting with acute flaccid limb weakness from January 2015 to December 2017 across 43 states.

A total of 25 cases were judged as probable for acute flaccid myelitis (AFM) because they met clinical criteria and had a white blood cell count above 5 cells per mm³ in cerebrospinal fluid, while 193 were judged as confirmed cases based on the additional presence of spinal cord gray matter lesions on MRI.

Overall, 83% of patients had experienced fever, cough, runny nose, vomiting, and/or diarrhea for a median of 5 days before limb weakness began. Two-thirds of patients had experienced a respiratory illness, 62% had experienced a fever, and 29% had experienced gastrointestinal illness.

Overall, 47% of the 193 patients who had specimens tested at a Centers for Disease Control and Prevention or non-CDC laboratory had a pathogen found at any site, 10% had a pathogen detected from a sterile site such as cerebrospinal fluid or sera, and 42% had a pathogen detected from a nonsterile site.

Among 72 patients who had serum specimens tested at the CDC, 2 were positive for enteroviruses. Among the 90 patients who had upper respiratory specimens tested, 36% were positive for either enteroviruses or rhinoviruses.

A number of stool specimens were also tested; 15% were positive for enteroviruses or rhinoviruses and one was positive for parechovirus.

Cerebrospinal fluid was tested in 170 patients, of which 4 were positive for enteroviruses. The testing also found adenovirus, Epstein-Barr virus, human herpesvirus 6, and mycoplasma in six patients. Sera testing of 123 patients found 9 were positive for enteroviruses, West Nile virus, mycoplasma, and coxsackievirus B.

“In our summary of national AFM surveillance from 2015 to 2017, we demonstrate that cases were widely distributed across the United States, the majority of cases occurred in late summer or fall, children were predominantly affected, there is a spectrum of clinical severity, and no single pathogen was identified as the primary cause of AFM,” wrote Tracy Ayers, PhD, from the National Center for Immunization and Respiratory Diseases, and coauthors. “We conclude that symptoms of a viral syndrome within the week before limb weakness, detection of viral pathogens from sterile and nonsterile sites from almost half of patients, and seasonality of AFM incidence, particularly during the 2016 peak year, strongly suggest a viral etiology, including [enteroviruses].”

The authors of an accompanying editorial noted that the clinical syndrome of acute flaccid paralysis caused by myelitis in the gray matter of the spinal cord has previously been associated with a range of viruses, including poliovirus, enteroviruses, and flaviviruses, so a single etiology to explain all cases would not be expected.

“The central question remains: What is driving seasonal biennial nationwide outbreaks of AFM since 2014?” wrote Kevin Messaca, MD, and colleagues from the University of Colorado at Denver, Aurora.

Two authors declared consultancies, grants, and research contracts with the pharmaceutical sector. No other conflicts of interest were declared. One editorial author declared funding from the National Institute of Allergy and Infectious Diseases.

SOURCE: Ayers T et al. Pediatrics. 2019 Oct 7. doi: 10.1542/peds.2019-1619.

*Updated 10/14/2019.

WASHINGTON – The top existential threats to health today are climate change and overpopulation, but third in this list is antimicrobial resistance, according to Helen Boucher, MD, of Tufts Medical Center, Boston. In her talk at an annual scientific meeting on infectious diseases, however, she focused on the last, presenting the hottest developments in the clinical science of treating and identifying disease-causing agents.

In particular, she discussed two of the most important developments in the area of rapid diagnostics: cell-free microbial DNA in plasma and the use of next-generation gene sequencing for determining disease etiology.

Using a meta-genomics test, cell-free microbial DNA can be identified in plasma from more than 1,000 relevant bacteria, DNA viruses, fungi, and parasites. Though importantly, RNA viruses are not detectable using this technology, she added. Although current sampling is of plasma, this might expand to the ability to use urine in the future. She discussed its particular use in sepsis, as outlined in a paper in Nature Microbiology (2019;4[4]:663-74). The researchers examined 350 suspected sepsis patients and they found a 93% sensitivity, compared with reference standards, using this new test. The main issue with the test was a high incidence of false positives.

Another test Dr. Boucher discussed was the use of meta-genomic next-generation sequencing. She referred to a 2019 paper in the New England Journal of Medicine, which discussed the use of clinical meta-genomic next-generation sequencing of cerebrospinal fluid for the diagnosis of meningitis and encephalitis (2019;380[27]:2327-40). Next-generation sequencing identified 13% of patients positive who were missed using standard screening. However, a number of patients were not diagnosed using the new test, showing that this technique was an improvement over current methods, but not 100% successful.

Dr. Boucher stressed the need for “diagnostic stewardship” to identify the correct microbial agent causing disease, allowing for the use of appropriate treatment rather than shotgun approaches to prevent the development of antibiotic resistance. This practice requires collaboration between the clinical laboratory, pharmacists, and infectious disease specialists.

Dr. Boucher then switched to the area of therapeutics, focusing on the introduction of new antibiotics and other innovations in disease treatment methodologies, especially in the field of transplant ID.

“We have new drugs. That is the good news,” with the goals of the 10 x ’20 initiative to develop 10 new systemic antibiotics by 2020, having “been met and then some,” said Dr. Boucher.

“We now have 13 new drugs, systemically available antibiotics, available by August 2019,” she added, discussing several of the new drugs.

In addition, she pointed out several studies that have indicated that shorter courses of antibiotics are better than longer, and that, in many cases, oral therapy is better than intravenous.

In the burgeoning area of transplant ID studies, Dr. Boucher discussed new research showing that vaccinations in transplanted patients can be advised in several instances, though may require higher dosing, and how the use of hepatitis C virus–positive organs for transplant is showing good results and increasing the availability of organs for transplant.

Dr. Boucher has served on data review committees for Actelion and Medtronix and has served as a consultant/advisor for Cerexa, Durata Therapeutics, Merck (adjudication committee), Rib-X, and Wyeth/Pfizer (data safety monitoring committee).

[email protected]

WASHINGTON – The top existential threats to health today are climate change and overpopulation, but third in this list is antimicrobial resistance, according to Helen Boucher, MD, of Tufts Medical Center, Boston. In her talk at an annual scientific meeting on infectious diseases, however, she focused on the last, presenting the hottest developments in the clinical science of treating and identifying disease-causing agents.

In particular, she discussed two of the most important developments in the area of rapid diagnostics: cell-free microbial DNA in plasma and the use of next-generation gene sequencing for determining disease etiology.

Using a meta-genomics test, cell-free microbial DNA can be identified in plasma from more than 1,000 relevant bacteria, DNA viruses, fungi, and parasites. Though importantly, RNA viruses are not detectable using this technology, she added. Although current sampling is of plasma, this might expand to the ability to use urine in the future. She discussed its particular use in sepsis, as outlined in a paper in Nature Microbiology (2019;4[4]:663-74). The researchers examined 350 suspected sepsis patients and they found a 93% sensitivity, compared with reference standards, using this new test. The main issue with the test was a high incidence of false positives.

Another test Dr. Boucher discussed was the use of meta-genomic next-generation sequencing. She referred to a 2019 paper in the New England Journal of Medicine, which discussed the use of clinical meta-genomic next-generation sequencing of cerebrospinal fluid for the diagnosis of meningitis and encephalitis (2019;380[27]:2327-40). Next-generation sequencing identified 13% of patients positive who were missed using standard screening. However, a number of patients were not diagnosed using the new test, showing that this technique was an improvement over current methods, but not 100% successful.

Dr. Boucher stressed the need for “diagnostic stewardship” to identify the correct microbial agent causing disease, allowing for the use of appropriate treatment rather than shotgun approaches to prevent the development of antibiotic resistance. This practice requires collaboration between the clinical laboratory, pharmacists, and infectious disease specialists.

Dr. Boucher then switched to the area of therapeutics, focusing on the introduction of new antibiotics and other innovations in disease treatment methodologies, especially in the field of transplant ID.

“We have new drugs. That is the good news,” with the goals of the 10 x ’20 initiative to develop 10 new systemic antibiotics by 2020, having “been met and then some,” said Dr. Boucher.

“We now have 13 new drugs, systemically available antibiotics, available by August 2019,” she added, discussing several of the new drugs.

In addition, she pointed out several studies that have indicated that shorter courses of antibiotics are better than longer, and that, in many cases, oral therapy is better than intravenous.

In the burgeoning area of transplant ID studies, Dr. Boucher discussed new research showing that vaccinations in transplanted patients can be advised in several instances, though may require higher dosing, and how the use of hepatitis C virus–positive organs for transplant is showing good results and increasing the availability of organs for transplant.

Dr. Boucher has served on data review committees for Actelion and Medtronix and has served as a consultant/advisor for Cerexa, Durata Therapeutics, Merck (adjudication committee), Rib-X, and Wyeth/Pfizer (data safety monitoring committee).

[email protected]

WASHINGTON – The top existential threats to health today are climate change and overpopulation, but third in this list is antimicrobial resistance, according to Helen Boucher, MD, of Tufts Medical Center, Boston. In her talk at an annual scientific meeting on infectious diseases, however, she focused on the last, presenting the hottest developments in the clinical science of treating and identifying disease-causing agents.

In particular, she discussed two of the most important developments in the area of rapid diagnostics: cell-free microbial DNA in plasma and the use of next-generation gene sequencing for determining disease etiology.

Using a meta-genomics test, cell-free microbial DNA can be identified in plasma from more than 1,000 relevant bacteria, DNA viruses, fungi, and parasites. Though importantly, RNA viruses are not detectable using this technology, she added. Although current sampling is of plasma, this might expand to the ability to use urine in the future. She discussed its particular use in sepsis, as outlined in a paper in Nature Microbiology (2019;4[4]:663-74). The researchers examined 350 suspected sepsis patients and they found a 93% sensitivity, compared with reference standards, using this new test. The main issue with the test was a high incidence of false positives.

Another test Dr. Boucher discussed was the use of meta-genomic next-generation sequencing. She referred to a 2019 paper in the New England Journal of Medicine, which discussed the use of clinical meta-genomic next-generation sequencing of cerebrospinal fluid for the diagnosis of meningitis and encephalitis (2019;380[27]:2327-40). Next-generation sequencing identified 13% of patients positive who were missed using standard screening. However, a number of patients were not diagnosed using the new test, showing that this technique was an improvement over current methods, but not 100% successful.

Dr. Boucher stressed the need for “diagnostic stewardship” to identify the correct microbial agent causing disease, allowing for the use of appropriate treatment rather than shotgun approaches to prevent the development of antibiotic resistance. This practice requires collaboration between the clinical laboratory, pharmacists, and infectious disease specialists.

Dr. Boucher then switched to the area of therapeutics, focusing on the introduction of new antibiotics and other innovations in disease treatment methodologies, especially in the field of transplant ID.

“We have new drugs. That is the good news,” with the goals of the 10 x ’20 initiative to develop 10 new systemic antibiotics by 2020, having “been met and then some,” said Dr. Boucher.

“We now have 13 new drugs, systemically available antibiotics, available by August 2019,” she added, discussing several of the new drugs.

In addition, she pointed out several studies that have indicated that shorter courses of antibiotics are better than longer, and that, in many cases, oral therapy is better than intravenous.

In the burgeoning area of transplant ID studies, Dr. Boucher discussed new research showing that vaccinations in transplanted patients can be advised in several instances, though may require higher dosing, and how the use of hepatitis C virus–positive organs for transplant is showing good results and increasing the availability of organs for transplant.

Dr. Boucher has served on data review committees for Actelion and Medtronix and has served as a consultant/advisor for Cerexa, Durata Therapeutics, Merck (adjudication committee), Rib-X, and Wyeth/Pfizer (data safety monitoring committee).

[email protected]

WASHINGTON – Patients hospitalized for pyelonephritis and discharged after receiving intravenous antibiotic treatment who then received step-down treatment with an oral beta-lactam had 30-day outcomes that were noninferior to patients who received an oral fluoroquinolone or trimethoprim-sulfamethoxazole as their discharge regimen, in a retrospective study of 211 patients managed at either of two U.S. hospitals.

This was the largest comparison reported on oral beta-lactam drugs for postdischarge treatment of pyelonephritis relative to the standard oral agents, fluoroquinolones and trimethoprim-sulfamethoxazole (Bactrim), Athena Hobbs, PharmD, said at an annual scientific meeting on infectious diseases. The superiority of an oral fluoroquinolone or trimethoprim-sulfamethoxazole and inferiority of oral beta-lactam drugs were cited in 2010 guidelines for managing pyelonephritis from the Infectious Diseases Society of America (Clin Infect Dis. 2011 March 1;52 [5]: e103-20).

Although limited as a nonrandomized, retrospective comparison, the finding of at least similar efficacy by beta-lactam agents “opens new treatment options” that avoid issues with drug resistance and adverse effects from treatment with fluoroquinolones or trimethoprim-sulfamethoxazole, Dr. Hobbs said in a video interview. Beta-lactams have already been embraced for this indication by some hospitalists, demonstrated by their use of beta-lactam antibiotics for 122 (58%) of the 211 patients included in the study. Among the 89 patients discharged on a non–beta-lactam, 69 (78%) had fluoroquinolone treatment and the remaining 20 patients went home taking trimethoprim-sulfamethoxazole. The new finding “confirms that we are not doing harm to patients,” with this existing practice of mostly prescribing an oral beta-lactam drug, noted Dr. Hobbs, an infectious diseases pharmacy specialist at Baptist Memorial Hospital in Memphis.

The study included patients aged 18-89 years hospitalized during 2014-2017 for a primary diagnosis of pyelonephritis at Baptist or at a second Hospital in Austin, Tex. The study excluded patients in intensive care, with a urologic abnormality, pregnant women, and patients treated with an intravenous antibiotic other than a beta-lactam for more than 24 hours. The most commonly used intravenous drugs were cefazolin and ceftriaxone. The enrolled patients averaged just over 40 years old, and more than 90% were women.

The study’s primary outcome was the 30-day rate of either hospital readmission or an ED visit for pyelonephritis or a urinary tract infection. This occurred in 4.9% of the patients discharged on an oral course of a beta-lactam drug, and in 5.6% of those discharged on either a fluoroquinolone or trimethoprim-sulfamethoxazole, a difference that was not statistically significant and that met the prespecified criteria for noninferiority, Dr. Hobbs reported. The most commonly prescribed oral beta-lactam was cefuroxime in about half the patients, followed by cephalexin or cefadroxil in about a quarter of patients, and amoxicillin with clavulanate in 19%. The two arms of the study also showed no significant difference in infection recurrences during 90-day follow-up.

The study received no commercial funding. Dr. Hobbs had no relevant disclosures.

[email protected]

WASHINGTON – Patients hospitalized for pyelonephritis and discharged after receiving intravenous antibiotic treatment who then received step-down treatment with an oral beta-lactam had 30-day outcomes that were noninferior to patients who received an oral fluoroquinolone or trimethoprim-sulfamethoxazole as their discharge regimen, in a retrospective study of 211 patients managed at either of two U.S. hospitals.

This was the largest comparison reported on oral beta-lactam drugs for postdischarge treatment of pyelonephritis relative to the standard oral agents, fluoroquinolones and trimethoprim-sulfamethoxazole (Bactrim), Athena Hobbs, PharmD, said at an annual scientific meeting on infectious diseases. The superiority of an oral fluoroquinolone or trimethoprim-sulfamethoxazole and inferiority of oral beta-lactam drugs were cited in 2010 guidelines for managing pyelonephritis from the Infectious Diseases Society of America (Clin Infect Dis. 2011 March 1;52 [5]: e103-20).

Although limited as a nonrandomized, retrospective comparison, the finding of at least similar efficacy by beta-lactam agents “opens new treatment options” that avoid issues with drug resistance and adverse effects from treatment with fluoroquinolones or trimethoprim-sulfamethoxazole, Dr. Hobbs said in a video interview. Beta-lactams have already been embraced for this indication by some hospitalists, demonstrated by their use of beta-lactam antibiotics for 122 (58%) of the 211 patients included in the study. Among the 89 patients discharged on a non–beta-lactam, 69 (78%) had fluoroquinolone treatment and the remaining 20 patients went home taking trimethoprim-sulfamethoxazole. The new finding “confirms that we are not doing harm to patients,” with this existing practice of mostly prescribing an oral beta-lactam drug, noted Dr. Hobbs, an infectious diseases pharmacy specialist at Baptist Memorial Hospital in Memphis.

The study included patients aged 18-89 years hospitalized during 2014-2017 for a primary diagnosis of pyelonephritis at Baptist or at a second Hospital in Austin, Tex. The study excluded patients in intensive care, with a urologic abnormality, pregnant women, and patients treated with an intravenous antibiotic other than a beta-lactam for more than 24 hours. The most commonly used intravenous drugs were cefazolin and ceftriaxone. The enrolled patients averaged just over 40 years old, and more than 90% were women.

The study’s primary outcome was the 30-day rate of either hospital readmission or an ED visit for pyelonephritis or a urinary tract infection. This occurred in 4.9% of the patients discharged on an oral course of a beta-lactam drug, and in 5.6% of those discharged on either a fluoroquinolone or trimethoprim-sulfamethoxazole, a difference that was not statistically significant and that met the prespecified criteria for noninferiority, Dr. Hobbs reported. The most commonly prescribed oral beta-lactam was cefuroxime in about half the patients, followed by cephalexin or cefadroxil in about a quarter of patients, and amoxicillin with clavulanate in 19%. The two arms of the study also showed no significant difference in infection recurrences during 90-day follow-up.

The study received no commercial funding. Dr. Hobbs had no relevant disclosures.

[email protected]

WASHINGTON – Patients hospitalized for pyelonephritis and discharged after receiving intravenous antibiotic treatment who then received step-down treatment with an oral beta-lactam had 30-day outcomes that were noninferior to patients who received an oral fluoroquinolone or trimethoprim-sulfamethoxazole as their discharge regimen, in a retrospective study of 211 patients managed at either of two U.S. hospitals.

This was the largest comparison reported on oral beta-lactam drugs for postdischarge treatment of pyelonephritis relative to the standard oral agents, fluoroquinolones and trimethoprim-sulfamethoxazole (Bactrim), Athena Hobbs, PharmD, said at an annual scientific meeting on infectious diseases. The superiority of an oral fluoroquinolone or trimethoprim-sulfamethoxazole and inferiority of oral beta-lactam drugs were cited in 2010 guidelines for managing pyelonephritis from the Infectious Diseases Society of America (Clin Infect Dis. 2011 March 1;52 [5]: e103-20).

Although limited as a nonrandomized, retrospective comparison, the finding of at least similar efficacy by beta-lactam agents “opens new treatment options” that avoid issues with drug resistance and adverse effects from treatment with fluoroquinolones or trimethoprim-sulfamethoxazole, Dr. Hobbs said in a video interview. Beta-lactams have already been embraced for this indication by some hospitalists, demonstrated by their use of beta-lactam antibiotics for 122 (58%) of the 211 patients included in the study. Among the 89 patients discharged on a non–beta-lactam, 69 (78%) had fluoroquinolone treatment and the remaining 20 patients went home taking trimethoprim-sulfamethoxazole. The new finding “confirms that we are not doing harm to patients,” with this existing practice of mostly prescribing an oral beta-lactam drug, noted Dr. Hobbs, an infectious diseases pharmacy specialist at Baptist Memorial Hospital in Memphis.

The study included patients aged 18-89 years hospitalized during 2014-2017 for a primary diagnosis of pyelonephritis at Baptist or at a second Hospital in Austin, Tex. The study excluded patients in intensive care, with a urologic abnormality, pregnant women, and patients treated with an intravenous antibiotic other than a beta-lactam for more than 24 hours. The most commonly used intravenous drugs were cefazolin and ceftriaxone. The enrolled patients averaged just over 40 years old, and more than 90% were women.

The study’s primary outcome was the 30-day rate of either hospital readmission or an ED visit for pyelonephritis or a urinary tract infection. This occurred in 4.9% of the patients discharged on an oral course of a beta-lactam drug, and in 5.6% of those discharged on either a fluoroquinolone or trimethoprim-sulfamethoxazole, a difference that was not statistically significant and that met the prespecified criteria for noninferiority, Dr. Hobbs reported. The most commonly prescribed oral beta-lactam was cefuroxime in about half the patients, followed by cephalexin or cefadroxil in about a quarter of patients, and amoxicillin with clavulanate in 19%. The two arms of the study also showed no significant difference in infection recurrences during 90-day follow-up.

The study received no commercial funding. Dr. Hobbs had no relevant disclosures.

[email protected]

A total of 1,249 measles cases were reported in the United States during Jan. 1–Oct.1, 2019, making it the most active year for the disease since 1992, according to investigators from the Centers for Disease Control and Prevention.

CDC/ Cynthia S. Goldsmith; William Bellini, Ph.D.

While 22 outbreaks were reported in 17 states during 2019, the majority of measles cases occurred in a pair of outbreaks that started in late 2018, one in New York City and the other in New York state. Theses two outbreaks, which occurred in underimmunized, close-knit communities, accounted for 934 (75%) of the 2019 total. An additional six outbreaks in similar communities accounted for nearly half of the remaining reported cases.

The overall median patient age was 6 years, with 31% being children aged 1-4 years, 27% being school-age children aged 5-17 years, and 29% were adults aged at least 18 years. However, when excluding the New York City (NYC) and New York state outbreaks, the median patient age was 19 years. Outbreak length also differed significantly between the NYC and New York state outbreaks, compared with all other outbreaks; the NYC outbreak lasted for 9.5 months, involving 702 patients from start to finish, the New York state outbreak lasted for 10.5 months and involved 412 cases.

The rate of patients who were either unvaccinated or had unknown vaccination status was similar in the New York outbreaks and in the other U.S. outbreaks, ranging from 87% to 91%. A total of 119 patients were hospitalized, 20% of whom were younger than 1 year; no deaths were reported. A total of 81 cases were internationally imported; the rate of patients who were unvaccinated or had unknown status in this group was 90%.

While most outbreaks in 2019 were similar to those previously seen, the outbreaks in NYC and New York state were more sustained for three reasons, the CDC investigators said: pockets of low vaccination coverage and variable vaccine acceptance, relatively high population density and closed social nature of the community, and repeated importations of measles cases among unvaccinated persons traveling internationally and returning to or visiting the affected communities.

“Public health authorities need to identify pockets of undervaccinated persons to prevent these outbreaks, which require substantial resources to control. A preventive strategy to build vaccine confidence is important, especially one that uses culturally appropriate communication strategies to offset misinformation and disseminate accurate information about the safety and importance of vaccination in advance of outbreaks,” the CDC investigators concluded.

The CDC investigators reported that they had no conflicts of interest.
 

[email protected]

SOURCE: Patel M et al. MMWR Morb Mortal Wkly Rep. 2019 Oct 4. doi: 10.15585/mmwr.mm6840e2.

A total of 1,249 measles cases were reported in the United States during Jan. 1–Oct.1, 2019, making it the most active year for the disease since 1992, according to investigators from the Centers for Disease Control and Prevention.

CDC/ Cynthia S. Goldsmith; William Bellini, Ph.D.

While 22 outbreaks were reported in 17 states during 2019, the majority of measles cases occurred in a pair of outbreaks that started in late 2018, one in New York City and the other in New York state. Theses two outbreaks, which occurred in underimmunized, close-knit communities, accounted for 934 (75%) of the 2019 total. An additional six outbreaks in similar communities accounted for nearly half of the remaining reported cases.

The overall median patient age was 6 years, with 31% being children aged 1-4 years, 27% being school-age children aged 5-17 years, and 29% were adults aged at least 18 years. However, when excluding the New York City (NYC) and New York state outbreaks, the median patient age was 19 years. Outbreak length also differed significantly between the NYC and New York state outbreaks, compared with all other outbreaks; the NYC outbreak lasted for 9.5 months, involving 702 patients from start to finish, the New York state outbreak lasted for 10.5 months and involved 412 cases.

The rate of patients who were either unvaccinated or had unknown vaccination status was similar in the New York outbreaks and in the other U.S. outbreaks, ranging from 87% to 91%. A total of 119 patients were hospitalized, 20% of whom were younger than 1 year; no deaths were reported. A total of 81 cases were internationally imported; the rate of patients who were unvaccinated or had unknown status in this group was 90%.

While most outbreaks in 2019 were similar to those previously seen, the outbreaks in NYC and New York state were more sustained for three reasons, the CDC investigators said: pockets of low vaccination coverage and variable vaccine acceptance, relatively high population density and closed social nature of the community, and repeated importations of measles cases among unvaccinated persons traveling internationally and returning to or visiting the affected communities.

“Public health authorities need to identify pockets of undervaccinated persons to prevent these outbreaks, which require substantial resources to control. A preventive strategy to build vaccine confidence is important, especially one that uses culturally appropriate communication strategies to offset misinformation and disseminate accurate information about the safety and importance of vaccination in advance of outbreaks,” the CDC investigators concluded.

The CDC investigators reported that they had no conflicts of interest.
 

[email protected]

SOURCE: Patel M et al. MMWR Morb Mortal Wkly Rep. 2019 Oct 4. doi: 10.15585/mmwr.mm6840e2.

A total of 1,249 measles cases were reported in the United States during Jan. 1–Oct.1, 2019, making it the most active year for the disease since 1992, according to investigators from the Centers for Disease Control and Prevention.

CDC/ Cynthia S. Goldsmith; William Bellini, Ph.D.

While 22 outbreaks were reported in 17 states during 2019, the majority of measles cases occurred in a pair of outbreaks that started in late 2018, one in New York City and the other in New York state. Theses two outbreaks, which occurred in underimmunized, close-knit communities, accounted for 934 (75%) of the 2019 total. An additional six outbreaks in similar communities accounted for nearly half of the remaining reported cases.

The overall median patient age was 6 years, with 31% being children aged 1-4 years, 27% being school-age children aged 5-17 years, and 29% were adults aged at least 18 years. However, when excluding the New York City (NYC) and New York state outbreaks, the median patient age was 19 years. Outbreak length also differed significantly between the NYC and New York state outbreaks, compared with all other outbreaks; the NYC outbreak lasted for 9.5 months, involving 702 patients from start to finish, the New York state outbreak lasted for 10.5 months and involved 412 cases.

The rate of patients who were either unvaccinated or had unknown vaccination status was similar in the New York outbreaks and in the other U.S. outbreaks, ranging from 87% to 91%. A total of 119 patients were hospitalized, 20% of whom were younger than 1 year; no deaths were reported. A total of 81 cases were internationally imported; the rate of patients who were unvaccinated or had unknown status in this group was 90%.

While most outbreaks in 2019 were similar to those previously seen, the outbreaks in NYC and New York state were more sustained for three reasons, the CDC investigators said: pockets of low vaccination coverage and variable vaccine acceptance, relatively high population density and closed social nature of the community, and repeated importations of measles cases among unvaccinated persons traveling internationally and returning to or visiting the affected communities.

“Public health authorities need to identify pockets of undervaccinated persons to prevent these outbreaks, which require substantial resources to control. A preventive strategy to build vaccine confidence is important, especially one that uses culturally appropriate communication strategies to offset misinformation and disseminate accurate information about the safety and importance of vaccination in advance of outbreaks,” the CDC investigators concluded.

The CDC investigators reported that they had no conflicts of interest.
 

[email protected]

SOURCE: Patel M et al. MMWR Morb Mortal Wkly Rep. 2019 Oct 4. doi: 10.15585/mmwr.mm6840e2.

WASHINGTON – An investigational, oral, small molecule designed to boost innate antiviral immunity safely cut the incidence of various viral respiratory infections in elderly people during a winter season by nearly a third when administered once daily in a placebo-controlled, multicenter, phase 2 study of 952 patients. Based on these and other findings the drug, RTB101, is now undergoing testing in a phase 3 study, Joan Mannick, MD, said at an annual scientific meeting on infectious diseases.

Mitchel L. Zoler/MDedge News

At a dosage of 10 mg once daily, RTB101 was “well tolerated, upregulated innate antiviral gene expression, and reduced the incidence” of laboratory-confirmed respiratory tract infections caused by several different viruses, said Dr. Mannick, who disclosed that she is a cofounder and chief medical officer of resTORbio, a Boston-based company that’s developing the drug.

During 16 weeks of treatment during the winter virus season, once-daily dosing led to cuts in the rates of respiratory infections compared with placebo by rhinovirus and enterovirus, respiratory syncytial virus, coronavirus, influenza virus, metapneuomovirus, and parainfluenza virus, especially in patients whom the results identified as having the best drug responses: those who were at least 85 years old, and those who were at least 65 years old and also had asthma. Enrolled patients who were at least 65 years old and had other risk factors – current smoking, chronic obstructive pulmonary disease, or diabetes – had notably less robust responses to treatment, and the phase 3 study is not enrolling elderly people who currently smoke or have chronic obstructive pulmonary disease, Dr. Mannick said in an interview.

RTB101 inhibits the active site of the “mechanistic target of rapamycin” (mTOR) protein, the key player of the TORC1 protein complex that appears to downregulate innate antiviral immunity when active. Hence inhibiting mTOR and TORC1 activity should boost innate antiviral immunity. Once-daily dosing with 10 mg of RTB101 appears to mimic the normal daily cycle of high and low levels of TORC1 activity seen in younger adults but which is missing the elderly who generally have persistently elevated levels of TORC1 activity, Dr. Mannick explained.

The study she reported enrolled a total of 952 people at any of 10 sites in the Southern Hemisphere or 17 Northern Hemisphere study sites. The researchers randomized patients to receive either RTB101 or placebo at either of two once-daily dosages or either of two twice-daily regimens. The best drug performance was among the 356 patients treated with 10 mg once daily or placebo. Those who received the active drug at this level had a 19% incidence of any laboratory-confirmed respiratory tract infection, while those who received placebo had a 28% incidence, a 30.6% relative risk reduction with RTB101 treatment that was statistically significant.

The actively-treated patients showed upregulation for 19 of 20 “antiviral” genes assessed in the study compared with upregulation of just five of these genes in the those who received placebo. Two post hoc analyses showed that the people who received 10 mg once daily had about half the rate of all-cause hospitalizations compared with those on placebo, and among those who had respiratory infections treated patients had alleviation of their moderate or severe symptoms in about half the time compared with patients on placebo.

The 10-mg daily dosage of RTB101 is less than 1% of the maximum-tolerated dose in people, and the safety data collected in the current study showed adverse events occurring at similar rates in the patients who received the active drug and those who got placebo. Discontinuations because of adverse events occurred in 5% of people who received RTB101 and in 6% of those on placebo.

The researchers are planning to run a cost-effectiveness study to see whether the observed prevention of respiratory tract infections and their consequences can offset the cost of taking RTB101 daily for 16 weeks, Dr. Mannick said.

[email protected]

WASHINGTON – An investigational, oral, small molecule designed to boost innate antiviral immunity safely cut the incidence of various viral respiratory infections in elderly people during a winter season by nearly a third when administered once daily in a placebo-controlled, multicenter, phase 2 study of 952 patients. Based on these and other findings the drug, RTB101, is now undergoing testing in a phase 3 study, Joan Mannick, MD, said at an annual scientific meeting on infectious diseases.

Mitchel L. Zoler/MDedge News

At a dosage of 10 mg once daily, RTB101 was “well tolerated, upregulated innate antiviral gene expression, and reduced the incidence” of laboratory-confirmed respiratory tract infections caused by several different viruses, said Dr. Mannick, who disclosed that she is a cofounder and chief medical officer of resTORbio, a Boston-based company that’s developing the drug.

During 16 weeks of treatment during the winter virus season, once-daily dosing led to cuts in the rates of respiratory infections compared with placebo by rhinovirus and enterovirus, respiratory syncytial virus, coronavirus, influenza virus, metapneuomovirus, and parainfluenza virus, especially in patients whom the results identified as having the best drug responses: those who were at least 85 years old, and those who were at least 65 years old and also had asthma. Enrolled patients who were at least 65 years old and had other risk factors – current smoking, chronic obstructive pulmonary disease, or diabetes – had notably less robust responses to treatment, and the phase 3 study is not enrolling elderly people who currently smoke or have chronic obstructive pulmonary disease, Dr. Mannick said in an interview.

RTB101 inhibits the active site of the “mechanistic target of rapamycin” (mTOR) protein, the key player of the TORC1 protein complex that appears to downregulate innate antiviral immunity when active. Hence inhibiting mTOR and TORC1 activity should boost innate antiviral immunity. Once-daily dosing with 10 mg of RTB101 appears to mimic the normal daily cycle of high and low levels of TORC1 activity seen in younger adults but which is missing the elderly who generally have persistently elevated levels of TORC1 activity, Dr. Mannick explained.

The study she reported enrolled a total of 952 people at any of 10 sites in the Southern Hemisphere or 17 Northern Hemisphere study sites. The researchers randomized patients to receive either RTB101 or placebo at either of two once-daily dosages or either of two twice-daily regimens. The best drug performance was among the 356 patients treated with 10 mg once daily or placebo. Those who received the active drug at this level had a 19% incidence of any laboratory-confirmed respiratory tract infection, while those who received placebo had a 28% incidence, a 30.6% relative risk reduction with RTB101 treatment that was statistically significant.

The actively-treated patients showed upregulation for 19 of 20 “antiviral” genes assessed in the study compared with upregulation of just five of these genes in the those who received placebo. Two post hoc analyses showed that the people who received 10 mg once daily had about half the rate of all-cause hospitalizations compared with those on placebo, and among those who had respiratory infections treated patients had alleviation of their moderate or severe symptoms in about half the time compared with patients on placebo.

The 10-mg daily dosage of RTB101 is less than 1% of the maximum-tolerated dose in people, and the safety data collected in the current study showed adverse events occurring at similar rates in the patients who received the active drug and those who got placebo. Discontinuations because of adverse events occurred in 5% of people who received RTB101 and in 6% of those on placebo.

The researchers are planning to run a cost-effectiveness study to see whether the observed prevention of respiratory tract infections and their consequences can offset the cost of taking RTB101 daily for 16 weeks, Dr. Mannick said.

[email protected]

WASHINGTON – An investigational, oral, small molecule designed to boost innate antiviral immunity safely cut the incidence of various viral respiratory infections in elderly people during a winter season by nearly a third when administered once daily in a placebo-controlled, multicenter, phase 2 study of 952 patients. Based on these and other findings the drug, RTB101, is now undergoing testing in a phase 3 study, Joan Mannick, MD, said at an annual scientific meeting on infectious diseases.

Mitchel L. Zoler/MDedge News

At a dosage of 10 mg once daily, RTB101 was “well tolerated, upregulated innate antiviral gene expression, and reduced the incidence” of laboratory-confirmed respiratory tract infections caused by several different viruses, said Dr. Mannick, who disclosed that she is a cofounder and chief medical officer of resTORbio, a Boston-based company that’s developing the drug.

During 16 weeks of treatment during the winter virus season, once-daily dosing led to cuts in the rates of respiratory infections compared with placebo by rhinovirus and enterovirus, respiratory syncytial virus, coronavirus, influenza virus, metapneuomovirus, and parainfluenza virus, especially in patients whom the results identified as having the best drug responses: those who were at least 85 years old, and those who were at least 65 years old and also had asthma. Enrolled patients who were at least 65 years old and had other risk factors – current smoking, chronic obstructive pulmonary disease, or diabetes – had notably less robust responses to treatment, and the phase 3 study is not enrolling elderly people who currently smoke or have chronic obstructive pulmonary disease, Dr. Mannick said in an interview.

RTB101 inhibits the active site of the “mechanistic target of rapamycin” (mTOR) protein, the key player of the TORC1 protein complex that appears to downregulate innate antiviral immunity when active. Hence inhibiting mTOR and TORC1 activity should boost innate antiviral immunity. Once-daily dosing with 10 mg of RTB101 appears to mimic the normal daily cycle of high and low levels of TORC1 activity seen in younger adults but which is missing the elderly who generally have persistently elevated levels of TORC1 activity, Dr. Mannick explained.

The study she reported enrolled a total of 952 people at any of 10 sites in the Southern Hemisphere or 17 Northern Hemisphere study sites. The researchers randomized patients to receive either RTB101 or placebo at either of two once-daily dosages or either of two twice-daily regimens. The best drug performance was among the 356 patients treated with 10 mg once daily or placebo. Those who received the active drug at this level had a 19% incidence of any laboratory-confirmed respiratory tract infection, while those who received placebo had a 28% incidence, a 30.6% relative risk reduction with RTB101 treatment that was statistically significant.

The actively-treated patients showed upregulation for 19 of 20 “antiviral” genes assessed in the study compared with upregulation of just five of these genes in the those who received placebo. Two post hoc analyses showed that the people who received 10 mg once daily had about half the rate of all-cause hospitalizations compared with those on placebo, and among those who had respiratory infections treated patients had alleviation of their moderate or severe symptoms in about half the time compared with patients on placebo.

The 10-mg daily dosage of RTB101 is less than 1% of the maximum-tolerated dose in people, and the safety data collected in the current study showed adverse events occurring at similar rates in the patients who received the active drug and those who got placebo. Discontinuations because of adverse events occurred in 5% of people who received RTB101 and in 6% of those on placebo.

The researchers are planning to run a cost-effectiveness study to see whether the observed prevention of respiratory tract infections and their consequences can offset the cost of taking RTB101 daily for 16 weeks, Dr. Mannick said.

[email protected]