Infectious Diseases

It’s been a decade since flu activity levels were this high this early in the season.

For the week ending Nov. 30, outpatient visits for influenza-like illness reached 3.5% of all visits to health care providers, the Centers for Disease Control and Prevention reported Dec. 6. That is the highest pre-December rate since the pandemic of 2009-2010, when the rate peaked at 7.7% in mid-October, CDC data show.

For the last week of November, eight states and Puerto Rico reported activity levels at the high point of the CDC’s 1-10 scale, which is at least five more states than any of the past five flu seasons. Three of the last five seasons had no states at level 10 this early in the season.

Another 4 states at levels 8 and 9 put a total of 13 jurisdictions in the “high” range of flu activity, with another 14 states in the “moderate” range of levels 6 and 7. Geographically speaking, 24 jurisdictions are experiencing regional or widespread activity, which is up from the 15 reported last week, the CDC’s influenza division said.

The hospitalization rate to date for the 2019-2020 season – 2.7 per 100,000 population – is “similar to what has been seen at this time during other recent seasons,” the CDC said.

One influenza-related pediatric death was reported during the week ending Nov. 30, which brings the total for the season to six, according to the CDC report.

[email protected]

It’s been a decade since flu activity levels were this high this early in the season.

For the week ending Nov. 30, outpatient visits for influenza-like illness reached 3.5% of all visits to health care providers, the Centers for Disease Control and Prevention reported Dec. 6. That is the highest pre-December rate since the pandemic of 2009-2010, when the rate peaked at 7.7% in mid-October, CDC data show.

For the last week of November, eight states and Puerto Rico reported activity levels at the high point of the CDC’s 1-10 scale, which is at least five more states than any of the past five flu seasons. Three of the last five seasons had no states at level 10 this early in the season.

Another 4 states at levels 8 and 9 put a total of 13 jurisdictions in the “high” range of flu activity, with another 14 states in the “moderate” range of levels 6 and 7. Geographically speaking, 24 jurisdictions are experiencing regional or widespread activity, which is up from the 15 reported last week, the CDC’s influenza division said.

The hospitalization rate to date for the 2019-2020 season – 2.7 per 100,000 population – is “similar to what has been seen at this time during other recent seasons,” the CDC said.

One influenza-related pediatric death was reported during the week ending Nov. 30, which brings the total for the season to six, according to the CDC report.

[email protected]

It’s been a decade since flu activity levels were this high this early in the season.

For the week ending Nov. 30, outpatient visits for influenza-like illness reached 3.5% of all visits to health care providers, the Centers for Disease Control and Prevention reported Dec. 6. That is the highest pre-December rate since the pandemic of 2009-2010, when the rate peaked at 7.7% in mid-October, CDC data show.

For the last week of November, eight states and Puerto Rico reported activity levels at the high point of the CDC’s 1-10 scale, which is at least five more states than any of the past five flu seasons. Three of the last five seasons had no states at level 10 this early in the season.

Another 4 states at levels 8 and 9 put a total of 13 jurisdictions in the “high” range of flu activity, with another 14 states in the “moderate” range of levels 6 and 7. Geographically speaking, 24 jurisdictions are experiencing regional or widespread activity, which is up from the 15 reported last week, the CDC’s influenza division said.

The hospitalization rate to date for the 2019-2020 season – 2.7 per 100,000 population – is “similar to what has been seen at this time during other recent seasons,” the CDC said.

One influenza-related pediatric death was reported during the week ending Nov. 30, which brings the total for the season to six, according to the CDC report.

[email protected]

From the University of Miami, Department of Pediatrics and Department of Medicine, Miami, FL.

Abstract

• Objective: Pediatric fungemia is associated with a low risk of fungal endocarditis and renal infections. The majority of current guidelines do not recommend routine abdominal imaging/echocardiograms in the evaluation of fungemia, but such imaging has been routinely ordered for patients on the pediatric gastroenterology service at our institution. Our goals were to assess the financial impact of this deviation from current clinical guidelines and redefine the standard work to reduce overutilization of abdominal ultrasounds and echocardiograms. Specifically, our goal was to reduce imaging by 50% by 18 months.
• Methods: Root cause analysis showed a lack of familiarity with current evidence. Using this data, countermeasures were implemented, including practitioner education of guidelines and creation of a readily accessible clinical pathway and an electronic order set for pediatric fungemia management. Balancing measures were missed episodes of fungal endocarditis and renal infection.
• Results: During the period January 1, 2016 to November 19, 2017, 18 of 21 episodes of fungemia in our pediatric institution occurred in patients admitted to the pediatric gastroenterology service. Abdominal imaging and echocardiograms were done 100% of the time, with no positive findings and an estimated cost of approximately $58,000. Post-intervention from November 20, 2017 to April 3, 2019, 7 of 13 episodes of fungemia occurred on this service. Frequency of abdominal imaging and echocardiograms decreased to 43% and 57%, respectively. No episodes of fungal endocarditis or renal infection were identified.
• Conclusion: Overutilization of abdominal imaging and echocardiograms in pediatric fungemia evaluation can be safely decreased.

Keywords: guidelines; cost; candidemia; endocarditis.

Practitioners may remain under the impression that routine abdominal ultrasounds (US) and echocardiograms (echo) are indicated in fungemia to evaluate for fungal endocarditis and renal infection, although these conditions are rare and limited to a subset of the population.^1-10 Risk factors include prematurity, immunosuppression, prior bacterial endocarditis, abnormal cardiac valves, and previous urogenital surgeries.¹¹

The 2016 Infectious Diseases Society of America (IDSA) guidelines do not recommend routine US or echo but rather provide scenarios in which Candida endocarditis should be suspected, and these include: persistently positive blood cultures, persistent fevers despite appropriate therapy, and clinical signs that may suggest endocarditis, such as a new heart murmur, heart failure, or embolic phenomena.¹¹ IDSA recommends abdominal imaging in neonates with persistently positive blood cultures to evaluate the urogenital system, in addition to the liver and spleen. They also recommend abdominal imaging in symptomatic ascending Candida pyelonephritis beyond the neonatal period and in chronic disseminated candidiasis; the latter is uncommon and seen almost exclusively in patients recovering from neutropenia with a hematologic malignancy.¹¹

We also reviewed guidelines on fungemia originating outside the United States. The 2010 Canadian clinical guidelines on invasive candidiasis do not explicitly recommend routine imaging, but rather state that various imaging studies, including US and echo among others, may be helpful.¹² The German Speaking Mycological Society and the Paul-Ehrlich-Society for Chemotherapy published a joint recommendation against routine US and echo in uncomplicated candidemia in 2011.¹³

The European Society for Clinical Microbiology and Infectious Diseases is the only society that recommends routine echo. Their 2012 guidelines on candidiasis recommend transesophageal echo in adults¹⁴ and echocardiography in children,¹⁵ as well as abdominal imaging in the diagnosis of chronic disseminated candidiasis in adults with hematological malignancies/hematopoietic stem cell transplantation.¹⁶

The 2013 Brazilian guidelines explicitly recommend against routine abdominal imaging and echo because of the low frequency of visceral lesions in adults with candidemia and recommend reserving imaging for those with persistently positive blood cultures or with clinical signs/symptoms suggestive of endocarditis/abdominal infection or clinical deterioration.¹⁷ The 2014 Japanese guidelines recommend ruling out chronic disseminated candidiasis in these patients with symptoms during the neutrophil recovery phase, but do not mention routinely imaging other patients. They do not address the role of echocardiography.¹⁸

Although physicians in the United Sates typically follow IDSA guidelines, abdominal US and echo were ordered routinely for patients with fungemia on the pediatric gastroenterology service at our institution, leading to higher medical costs and waste of medical resources. Our goals were to assess the current standard work for fungemia evaluation on this service, assess the impact of its deviation from current clinical guidelines, and redefine the standard work by (1) presenting current evidence to practitioners taking care of patients on this service, (2) providing a clinical pathway that allowed for variations where appropriate, and (3) providing a plan for pediatric fungemia management. Our SMART (Specific, Measurable, Attainable, Relevant and Timely) goal was to reduce overutilization of abdominal US and echo in pediatric patients with fungemia on the pediatric gastroenterology service by 50%.

Methods

Study, Setting, and Participants

We executed this quality improvement project at a quaternary care pediatric hospital affiliated with a school of medicine. The project scope consisted of inpatient pediatric patients with fungemia on the pediatric gastroenterology service admitted to the wards or pediatric critical care unit at this institution, along with the practitioners caring for these patients. The project was part of an institutional quality improvement initiative program. The quality improvement team included quality improvement experts from the departments of medicine and pediatrics, a pediatric resident and student, and physicians from the divisions of pediatric infectious disease, pediatric critical care, and pediatric gastroenterology. This study qualified for Institutional Review Board (IRB) exemption based on the University’s IRB stipulations.

Current Condition

Root cause analysis was performed by creating a process map of the current standard work and a fishbone diagram (Figure 1). We incorporated feedback from voice of the customer in the root cause analysis. In this analysis, the voice of the customer came from the bedside floor nurses, ultrasound clerk and sonographer, echo technician, cardiology fellow, and microbiology medical technician. We got their feedback on our process map, its accuracy and ways to expand, their thoughts on the problem and why we have this problem, and any solutions they could offer to help improve the problem. Some of the key points obtained were: echos were not routinely done on the floors and were not considered urgent as they often did not change management; the sonographer and those from the cardiology department felt imaging was often overutilized because of misconceptions and lack of available hospital guidelines. Suggested solutions included provider education with reference to Duke’s criteria and establishing a clinical pathway approved by all concerned departments.

Prior to education, we surveyed current practices of practitioners on teams caring for these patients, which included physicians of all levels (attendings, fellows, residents) as well as nurse practitioners and medical students from the department of pediatrics and divisions of pediatric gastroenterology, pediatric infectious disease, and pediatric critical care medicine.

Practitioner Education. In October 2017 practitioners were given a 20-minute presentation on the latest international guidelines on fungemia. Fifty-nine practitioners completed pre- and post-test surveys. Eight respondents were excluded due to incomplete surveys. We compared self-reported frequencies of ordering abdominal imaging and echo before the presentation with intention to order post education. Intention to change clinical practice after the presentation was also surveyed.

Clinical Pathway. Education alone may not result in sustainability, and thus we provided a readily accessible clinical pathway and an electronic order set for pediatric fungemia management. Inter-department buy-in was also necessary for success. It was important to get the input from the various teams (infectious disease, cardiology, gastroenterology, and critical care), which was done by incorporating members from those divisions in the project or getting their feedback through voice of the customer analysis.

We redefined standard work based on current evidence and created a clinical pathway during March 2018 that included variations when appropriate (Figure 2). We presented the clinical pathway to practitioners and distributed it via email. We also made it available to pediatric residents and fellows on their mobile institutional work resource application.

Electronic Order Set. We created an electronic order set for pediatric fungemia management and made it available in the electronic health record May 2018.

Measurement

Cases of fungemia were identified through the electronic health record pre-intervention (January 1, 2016 through November 19, 2017) and post-intervention (November 20, 2019 through April 3, 2019). An episode of fungemia was defined as an encounter with 1 or more positive blood culture(s) for Candida species or Cryptococcus species. We manually identified patients belonging to the pediatric gastroenterology service and reviewed these charts to determine the presenting complaint, organism isolated, transplant status, central lines status, risk factors, if abdominal imaging or echocardiography were done for the episode of fungemia, and their corresponding results. We calculated overall and per patient medical charges by using the average charges at our institution of US and echocardiography with a cardiology consult. These average charges were provided by patient financial services and the pediatric cardiology department, respectively. To address non-technical expenditures, we calculated the average time taken for transport to and from radiology and the echo suite for each identified patient. We identified missed fungal endocarditis and fungal balls as balancing measures.

Survey

Among the 51 practitioners surveyed, 36% were performing routine echo and 22% self-reported performing routine abdominal imaging. After education, no respondents planned to routinely do echo or abdominal imaging. All but 1 respondent planned to change their practice for evaluation of fungemia patients based on the presentation (eFigure 1).

Baseline Data

Over the 23-month period from January 1, 2016 to November 19, 2017, there were 21 episodes of fungemia, 18 of which occurred in patients on the pediatric gastroenterology service (2 of the 18 were transplant recipients). For the 18 episodes on this service, abdominal imaging and echo were done 100% of the time, with 0 positive findings (eFigure 2).

Of those 18 episodes, the average age was 4.6 years, with two-thirds of the population being male. There were 3 patients with multiple episodes that accounted for 8 of the episodes (3, 3, and 2 episodes each). Fever was the most common presenting complaint. The most common organism was Candida parapsilosis (6 of the 18 episodes). All episodes but one involved a central line, and all central lines were removed when present except for one case. Of the risk factors, 3 episodes occurred in neutropenic patients, and for 1 episode the patient had a questionable history of fungal endocarditis (and was on fungal prophylaxis). There were no patients with recent cardiac/urogenital surgery or prior fungal balls. No episodes had clinical symptoms suggestive of fungal endocarditis or fungal balls.

Post-Intervention Data

Over the subsequent 17-month period (November 11, 2017 to April 3, 2019), there were 13 episodes of candidemia. There were no episodes of Cryptococcus fungemia. Seven episodes occurred in patients on the pediatric gastroenterology service (2 of the 7 occurred in transplant recipients). Abdominal imaging was done in 3 of these episodes (43%), and in 2 of these 3 episodes, imaging was done at an outside institution prior to arrival, with no positive results (eFigure 2).

Echocardiography was done 57% of the time (n = 4), with echo being done at an outside institution prior to arrival half of the time (n = 2), with no endocarditis identified. The cases of abdominal imaging and echo done at outside institutions prior to arrival were not impacted by the countermeasures. Excluding those 2 patients who had both abdominal imaging and echocardiography done prior to arrival, the overall rate of imaging (both abdominal imaging and echo) done after countermeasures were instituted was 30% (Figure 3).

Of those 7 episodes, the average age was 6.8 years (57% female). There were no patients with multiple episodes. The most common presenting complaint was fever. The most common organism was Candida albicans (3 of the 7 episodes). All episodes involved a central line, which was removed in all cases except for one. Of the risk factors, 2 episodes were in neutropenic patients, and 1 episode had a history of bacterial endocarditis (not related to fungemia). No episodes occurred in patients with prior fungal renal infection, urogenital malformations, or recent cardiac/urogenital surgery. No episodes had clinical symptoms suggestive of fungal endocarditis or renal infection. No episodes of fungal endocarditis or renal infection were identified.

On average, a patient at our institution undergoing abdominal US and echo with a cardiology consult results in medical waste of approximately $3200 per patient. This cost does not take into account other miscellaneous charges possibly incurred, such as the radiologist interpreting the findings and transportation. Baseline data calculations show that patients waste on average 55 minutes in physical transport, and this does not take into account wait times.

Discussion

Candidemia contributes to 10% of central-line associated blood stream infections (CLABSI).¹⁹ Increased usage of indwelling central catheters for administration of parenteral nutrition will inevitably result in practitioners encountering cases of candidemia when caring for this population. As seen from our results, the majority of episodes of candidemia at our institution occurred on the pediatric gastroenterology service, and thus redefining standard work on this service will be impactful.

Candida parapsilosis and Candida albicans were the most common causative agents before and after intervention, respectively, but overall the most common organism was Candida albicans, which is in keeping with that of CLABSI in the literature.¹⁹ Growth of Candida parapsilosis has been particularly linked to CLABSI.¹⁹ The third most common organism in our study was Candida glabrata, which is the second most common cause of candidemia in CLABSI.¹⁹

The cases of positive abdominal imaging in fungemia in the literature are limited to the neonatal population^1-4 and chronic disseminated candidiasis in patients with hematologic malignancies/neutropenia/immunosuppression.^5,6 In fungal endocarditis, the reported cases were generally in neonates,^1,3,7 critically ill patients,⁸ patients with hematologic malignancies/neutropenia/immunosuppression,^6,9 or those with a cardiac history.^9,10 This population differs from the patient population on the pediatric gastroenterology service. Patients on this service may not need US or echo. Performing abdominal US and echo in fungemia patients in whom such imaging is not indicated may result in medical waste of approximately $3200 per patient. There is also a waste of medical resources and time.

We found almost all practitioners are willing to change clinical practice once provided with current guidelines. Face-to-face oral presentations allowed for questions and interaction, making this form of information dissemination better than e-mails or handouts.

Though the numbers were small over the short study period, we were able to decrease overutilization of abdominal imaging and echo after implementing countermeasures. Frequency decreased from 100% to 43% and 57% for abdominal imaging and echo, respectively. Imaging that was done after the countermeasures were implemented was mainly attributed to imaging patients underwent prior to presenting to our institution. This reinforces the need for education at other institutions as well. Of the balancing measures assessed, there were no missed cases of fungal balls or fungal endocarditis. Additionally, of the total 34 episodes of fungemia assessed (21 before and 13 after), even among those with risk factors, there were no cases of fungal endocarditis or renal infection.

The findings from this quality improvement project underscore current recommendations that, despite common misconceptions, routine abdominal US and echo are not indicated in all cases of fungemia. Case-by-case assessment based on the clinical scenario remains key to management of fungemia to avoid unnecessary medical interventions.

Corresponding author: Donna Cheung, MBBS, 200 Hawkins Drive, BT 1120-G, Iowa City, IA 52242; [email protected].

Financial support: None.

From the University of Miami, Department of Pediatrics and Department of Medicine, Miami, FL.

Abstract

• Objective: Pediatric fungemia is associated with a low risk of fungal endocarditis and renal infections. The majority of current guidelines do not recommend routine abdominal imaging/echocardiograms in the evaluation of fungemia, but such imaging has been routinely ordered for patients on the pediatric gastroenterology service at our institution. Our goals were to assess the financial impact of this deviation from current clinical guidelines and redefine the standard work to reduce overutilization of abdominal ultrasounds and echocardiograms. Specifically, our goal was to reduce imaging by 50% by 18 months.
• Methods: Root cause analysis showed a lack of familiarity with current evidence. Using this data, countermeasures were implemented, including practitioner education of guidelines and creation of a readily accessible clinical pathway and an electronic order set for pediatric fungemia management. Balancing measures were missed episodes of fungal endocarditis and renal infection.
• Results: During the period January 1, 2016 to November 19, 2017, 18 of 21 episodes of fungemia in our pediatric institution occurred in patients admitted to the pediatric gastroenterology service. Abdominal imaging and echocardiograms were done 100% of the time, with no positive findings and an estimated cost of approximately $58,000. Post-intervention from November 20, 2017 to April 3, 2019, 7 of 13 episodes of fungemia occurred on this service. Frequency of abdominal imaging and echocardiograms decreased to 43% and 57%, respectively. No episodes of fungal endocarditis or renal infection were identified.
• Conclusion: Overutilization of abdominal imaging and echocardiograms in pediatric fungemia evaluation can be safely decreased.

Keywords: guidelines; cost; candidemia; endocarditis.

Practitioners may remain under the impression that routine abdominal ultrasounds (US) and echocardiograms (echo) are indicated in fungemia to evaluate for fungal endocarditis and renal infection, although these conditions are rare and limited to a subset of the population.^1-10 Risk factors include prematurity, immunosuppression, prior bacterial endocarditis, abnormal cardiac valves, and previous urogenital surgeries.¹¹

The 2016 Infectious Diseases Society of America (IDSA) guidelines do not recommend routine US or echo but rather provide scenarios in which Candida endocarditis should be suspected, and these include: persistently positive blood cultures, persistent fevers despite appropriate therapy, and clinical signs that may suggest endocarditis, such as a new heart murmur, heart failure, or embolic phenomena.¹¹ IDSA recommends abdominal imaging in neonates with persistently positive blood cultures to evaluate the urogenital system, in addition to the liver and spleen. They also recommend abdominal imaging in symptomatic ascending Candida pyelonephritis beyond the neonatal period and in chronic disseminated candidiasis; the latter is uncommon and seen almost exclusively in patients recovering from neutropenia with a hematologic malignancy.¹¹

We also reviewed guidelines on fungemia originating outside the United States. The 2010 Canadian clinical guidelines on invasive candidiasis do not explicitly recommend routine imaging, but rather state that various imaging studies, including US and echo among others, may be helpful.¹² The German Speaking Mycological Society and the Paul-Ehrlich-Society for Chemotherapy published a joint recommendation against routine US and echo in uncomplicated candidemia in 2011.¹³

The European Society for Clinical Microbiology and Infectious Diseases is the only society that recommends routine echo. Their 2012 guidelines on candidiasis recommend transesophageal echo in adults¹⁴ and echocardiography in children,¹⁵ as well as abdominal imaging in the diagnosis of chronic disseminated candidiasis in adults with hematological malignancies/hematopoietic stem cell transplantation.¹⁶

The 2013 Brazilian guidelines explicitly recommend against routine abdominal imaging and echo because of the low frequency of visceral lesions in adults with candidemia and recommend reserving imaging for those with persistently positive blood cultures or with clinical signs/symptoms suggestive of endocarditis/abdominal infection or clinical deterioration.¹⁷ The 2014 Japanese guidelines recommend ruling out chronic disseminated candidiasis in these patients with symptoms during the neutrophil recovery phase, but do not mention routinely imaging other patients. They do not address the role of echocardiography.¹⁸

Although physicians in the United Sates typically follow IDSA guidelines, abdominal US and echo were ordered routinely for patients with fungemia on the pediatric gastroenterology service at our institution, leading to higher medical costs and waste of medical resources. Our goals were to assess the current standard work for fungemia evaluation on this service, assess the impact of its deviation from current clinical guidelines, and redefine the standard work by (1) presenting current evidence to practitioners taking care of patients on this service, (2) providing a clinical pathway that allowed for variations where appropriate, and (3) providing a plan for pediatric fungemia management. Our SMART (Specific, Measurable, Attainable, Relevant and Timely) goal was to reduce overutilization of abdominal US and echo in pediatric patients with fungemia on the pediatric gastroenterology service by 50%.

Methods

Study, Setting, and Participants

We executed this quality improvement project at a quaternary care pediatric hospital affiliated with a school of medicine. The project scope consisted of inpatient pediatric patients with fungemia on the pediatric gastroenterology service admitted to the wards or pediatric critical care unit at this institution, along with the practitioners caring for these patients. The project was part of an institutional quality improvement initiative program. The quality improvement team included quality improvement experts from the departments of medicine and pediatrics, a pediatric resident and student, and physicians from the divisions of pediatric infectious disease, pediatric critical care, and pediatric gastroenterology. This study qualified for Institutional Review Board (IRB) exemption based on the University’s IRB stipulations.

Current Condition

Root cause analysis was performed by creating a process map of the current standard work and a fishbone diagram (Figure 1). We incorporated feedback from voice of the customer in the root cause analysis. In this analysis, the voice of the customer came from the bedside floor nurses, ultrasound clerk and sonographer, echo technician, cardiology fellow, and microbiology medical technician. We got their feedback on our process map, its accuracy and ways to expand, their thoughts on the problem and why we have this problem, and any solutions they could offer to help improve the problem. Some of the key points obtained were: echos were not routinely done on the floors and were not considered urgent as they often did not change management; the sonographer and those from the cardiology department felt imaging was often overutilized because of misconceptions and lack of available hospital guidelines. Suggested solutions included provider education with reference to Duke’s criteria and establishing a clinical pathway approved by all concerned departments.

Prior to education, we surveyed current practices of practitioners on teams caring for these patients, which included physicians of all levels (attendings, fellows, residents) as well as nurse practitioners and medical students from the department of pediatrics and divisions of pediatric gastroenterology, pediatric infectious disease, and pediatric critical care medicine.

Practitioner Education. In October 2017 practitioners were given a 20-minute presentation on the latest international guidelines on fungemia. Fifty-nine practitioners completed pre- and post-test surveys. Eight respondents were excluded due to incomplete surveys. We compared self-reported frequencies of ordering abdominal imaging and echo before the presentation with intention to order post education. Intention to change clinical practice after the presentation was also surveyed.

Clinical Pathway. Education alone may not result in sustainability, and thus we provided a readily accessible clinical pathway and an electronic order set for pediatric fungemia management. Inter-department buy-in was also necessary for success. It was important to get the input from the various teams (infectious disease, cardiology, gastroenterology, and critical care), which was done by incorporating members from those divisions in the project or getting their feedback through voice of the customer analysis.

We redefined standard work based on current evidence and created a clinical pathway during March 2018 that included variations when appropriate (Figure 2). We presented the clinical pathway to practitioners and distributed it via email. We also made it available to pediatric residents and fellows on their mobile institutional work resource application.

Electronic Order Set. We created an electronic order set for pediatric fungemia management and made it available in the electronic health record May 2018.

Measurement

Cases of fungemia were identified through the electronic health record pre-intervention (January 1, 2016 through November 19, 2017) and post-intervention (November 20, 2019 through April 3, 2019). An episode of fungemia was defined as an encounter with 1 or more positive blood culture(s) for Candida species or Cryptococcus species. We manually identified patients belonging to the pediatric gastroenterology service and reviewed these charts to determine the presenting complaint, organism isolated, transplant status, central lines status, risk factors, if abdominal imaging or echocardiography were done for the episode of fungemia, and their corresponding results. We calculated overall and per patient medical charges by using the average charges at our institution of US and echocardiography with a cardiology consult. These average charges were provided by patient financial services and the pediatric cardiology department, respectively. To address non-technical expenditures, we calculated the average time taken for transport to and from radiology and the echo suite for each identified patient. We identified missed fungal endocarditis and fungal balls as balancing measures.

Survey

Among the 51 practitioners surveyed, 36% were performing routine echo and 22% self-reported performing routine abdominal imaging. After education, no respondents planned to routinely do echo or abdominal imaging. All but 1 respondent planned to change their practice for evaluation of fungemia patients based on the presentation (eFigure 1).

Baseline Data

Over the 23-month period from January 1, 2016 to November 19, 2017, there were 21 episodes of fungemia, 18 of which occurred in patients on the pediatric gastroenterology service (2 of the 18 were transplant recipients). For the 18 episodes on this service, abdominal imaging and echo were done 100% of the time, with 0 positive findings (eFigure 2).

Of those 18 episodes, the average age was 4.6 years, with two-thirds of the population being male. There were 3 patients with multiple episodes that accounted for 8 of the episodes (3, 3, and 2 episodes each). Fever was the most common presenting complaint. The most common organism was Candida parapsilosis (6 of the 18 episodes). All episodes but one involved a central line, and all central lines were removed when present except for one case. Of the risk factors, 3 episodes occurred in neutropenic patients, and for 1 episode the patient had a questionable history of fungal endocarditis (and was on fungal prophylaxis). There were no patients with recent cardiac/urogenital surgery or prior fungal balls. No episodes had clinical symptoms suggestive of fungal endocarditis or fungal balls.

Post-Intervention Data

Over the subsequent 17-month period (November 11, 2017 to April 3, 2019), there were 13 episodes of candidemia. There were no episodes of Cryptococcus fungemia. Seven episodes occurred in patients on the pediatric gastroenterology service (2 of the 7 occurred in transplant recipients). Abdominal imaging was done in 3 of these episodes (43%), and in 2 of these 3 episodes, imaging was done at an outside institution prior to arrival, with no positive results (eFigure 2).

Echocardiography was done 57% of the time (n = 4), with echo being done at an outside institution prior to arrival half of the time (n = 2), with no endocarditis identified. The cases of abdominal imaging and echo done at outside institutions prior to arrival were not impacted by the countermeasures. Excluding those 2 patients who had both abdominal imaging and echocardiography done prior to arrival, the overall rate of imaging (both abdominal imaging and echo) done after countermeasures were instituted was 30% (Figure 3).

Of those 7 episodes, the average age was 6.8 years (57% female). There were no patients with multiple episodes. The most common presenting complaint was fever. The most common organism was Candida albicans (3 of the 7 episodes). All episodes involved a central line, which was removed in all cases except for one. Of the risk factors, 2 episodes were in neutropenic patients, and 1 episode had a history of bacterial endocarditis (not related to fungemia). No episodes occurred in patients with prior fungal renal infection, urogenital malformations, or recent cardiac/urogenital surgery. No episodes had clinical symptoms suggestive of fungal endocarditis or renal infection. No episodes of fungal endocarditis or renal infection were identified.

On average, a patient at our institution undergoing abdominal US and echo with a cardiology consult results in medical waste of approximately $3200 per patient. This cost does not take into account other miscellaneous charges possibly incurred, such as the radiologist interpreting the findings and transportation. Baseline data calculations show that patients waste on average 55 minutes in physical transport, and this does not take into account wait times.

Discussion

Candidemia contributes to 10% of central-line associated blood stream infections (CLABSI).¹⁹ Increased usage of indwelling central catheters for administration of parenteral nutrition will inevitably result in practitioners encountering cases of candidemia when caring for this population. As seen from our results, the majority of episodes of candidemia at our institution occurred on the pediatric gastroenterology service, and thus redefining standard work on this service will be impactful.

Candida parapsilosis and Candida albicans were the most common causative agents before and after intervention, respectively, but overall the most common organism was Candida albicans, which is in keeping with that of CLABSI in the literature.¹⁹ Growth of Candida parapsilosis has been particularly linked to CLABSI.¹⁹ The third most common organism in our study was Candida glabrata, which is the second most common cause of candidemia in CLABSI.¹⁹

The cases of positive abdominal imaging in fungemia in the literature are limited to the neonatal population^1-4 and chronic disseminated candidiasis in patients with hematologic malignancies/neutropenia/immunosuppression.^5,6 In fungal endocarditis, the reported cases were generally in neonates,^1,3,7 critically ill patients,⁸ patients with hematologic malignancies/neutropenia/immunosuppression,^6,9 or those with a cardiac history.^9,10 This population differs from the patient population on the pediatric gastroenterology service. Patients on this service may not need US or echo. Performing abdominal US and echo in fungemia patients in whom such imaging is not indicated may result in medical waste of approximately $3200 per patient. There is also a waste of medical resources and time.

We found almost all practitioners are willing to change clinical practice once provided with current guidelines. Face-to-face oral presentations allowed for questions and interaction, making this form of information dissemination better than e-mails or handouts.

Though the numbers were small over the short study period, we were able to decrease overutilization of abdominal imaging and echo after implementing countermeasures. Frequency decreased from 100% to 43% and 57% for abdominal imaging and echo, respectively. Imaging that was done after the countermeasures were implemented was mainly attributed to imaging patients underwent prior to presenting to our institution. This reinforces the need for education at other institutions as well. Of the balancing measures assessed, there were no missed cases of fungal balls or fungal endocarditis. Additionally, of the total 34 episodes of fungemia assessed (21 before and 13 after), even among those with risk factors, there were no cases of fungal endocarditis or renal infection.

The findings from this quality improvement project underscore current recommendations that, despite common misconceptions, routine abdominal US and echo are not indicated in all cases of fungemia. Case-by-case assessment based on the clinical scenario remains key to management of fungemia to avoid unnecessary medical interventions.

Corresponding author: Donna Cheung, MBBS, 200 Hawkins Drive, BT 1120-G, Iowa City, IA 52242; [email protected].

Financial support: None.

From the University of Miami, Department of Pediatrics and Department of Medicine, Miami, FL.

Abstract

• Objective: Pediatric fungemia is associated with a low risk of fungal endocarditis and renal infections. The majority of current guidelines do not recommend routine abdominal imaging/echocardiograms in the evaluation of fungemia, but such imaging has been routinely ordered for patients on the pediatric gastroenterology service at our institution. Our goals were to assess the financial impact of this deviation from current clinical guidelines and redefine the standard work to reduce overutilization of abdominal ultrasounds and echocardiograms. Specifically, our goal was to reduce imaging by 50% by 18 months.
• Methods: Root cause analysis showed a lack of familiarity with current evidence. Using this data, countermeasures were implemented, including practitioner education of guidelines and creation of a readily accessible clinical pathway and an electronic order set for pediatric fungemia management. Balancing measures were missed episodes of fungal endocarditis and renal infection.
• Results: During the period January 1, 2016 to November 19, 2017, 18 of 21 episodes of fungemia in our pediatric institution occurred in patients admitted to the pediatric gastroenterology service. Abdominal imaging and echocardiograms were done 100% of the time, with no positive findings and an estimated cost of approximately $58,000. Post-intervention from November 20, 2017 to April 3, 2019, 7 of 13 episodes of fungemia occurred on this service. Frequency of abdominal imaging and echocardiograms decreased to 43% and 57%, respectively. No episodes of fungal endocarditis or renal infection were identified.
• Conclusion: Overutilization of abdominal imaging and echocardiograms in pediatric fungemia evaluation can be safely decreased.

Keywords: guidelines; cost; candidemia; endocarditis.

Practitioners may remain under the impression that routine abdominal ultrasounds (US) and echocardiograms (echo) are indicated in fungemia to evaluate for fungal endocarditis and renal infection, although these conditions are rare and limited to a subset of the population.^1-10 Risk factors include prematurity, immunosuppression, prior bacterial endocarditis, abnormal cardiac valves, and previous urogenital surgeries.¹¹

The 2016 Infectious Diseases Society of America (IDSA) guidelines do not recommend routine US or echo but rather provide scenarios in which Candida endocarditis should be suspected, and these include: persistently positive blood cultures, persistent fevers despite appropriate therapy, and clinical signs that may suggest endocarditis, such as a new heart murmur, heart failure, or embolic phenomena.¹¹ IDSA recommends abdominal imaging in neonates with persistently positive blood cultures to evaluate the urogenital system, in addition to the liver and spleen. They also recommend abdominal imaging in symptomatic ascending Candida pyelonephritis beyond the neonatal period and in chronic disseminated candidiasis; the latter is uncommon and seen almost exclusively in patients recovering from neutropenia with a hematologic malignancy.¹¹

We also reviewed guidelines on fungemia originating outside the United States. The 2010 Canadian clinical guidelines on invasive candidiasis do not explicitly recommend routine imaging, but rather state that various imaging studies, including US and echo among others, may be helpful.¹² The German Speaking Mycological Society and the Paul-Ehrlich-Society for Chemotherapy published a joint recommendation against routine US and echo in uncomplicated candidemia in 2011.¹³

The European Society for Clinical Microbiology and Infectious Diseases is the only society that recommends routine echo. Their 2012 guidelines on candidiasis recommend transesophageal echo in adults¹⁴ and echocardiography in children,¹⁵ as well as abdominal imaging in the diagnosis of chronic disseminated candidiasis in adults with hematological malignancies/hematopoietic stem cell transplantation.¹⁶

The 2013 Brazilian guidelines explicitly recommend against routine abdominal imaging and echo because of the low frequency of visceral lesions in adults with candidemia and recommend reserving imaging for those with persistently positive blood cultures or with clinical signs/symptoms suggestive of endocarditis/abdominal infection or clinical deterioration.¹⁷ The 2014 Japanese guidelines recommend ruling out chronic disseminated candidiasis in these patients with symptoms during the neutrophil recovery phase, but do not mention routinely imaging other patients. They do not address the role of echocardiography.¹⁸

Although physicians in the United Sates typically follow IDSA guidelines, abdominal US and echo were ordered routinely for patients with fungemia on the pediatric gastroenterology service at our institution, leading to higher medical costs and waste of medical resources. Our goals were to assess the current standard work for fungemia evaluation on this service, assess the impact of its deviation from current clinical guidelines, and redefine the standard work by (1) presenting current evidence to practitioners taking care of patients on this service, (2) providing a clinical pathway that allowed for variations where appropriate, and (3) providing a plan for pediatric fungemia management. Our SMART (Specific, Measurable, Attainable, Relevant and Timely) goal was to reduce overutilization of abdominal US and echo in pediatric patients with fungemia on the pediatric gastroenterology service by 50%.

Methods

Study, Setting, and Participants

We executed this quality improvement project at a quaternary care pediatric hospital affiliated with a school of medicine. The project scope consisted of inpatient pediatric patients with fungemia on the pediatric gastroenterology service admitted to the wards or pediatric critical care unit at this institution, along with the practitioners caring for these patients. The project was part of an institutional quality improvement initiative program. The quality improvement team included quality improvement experts from the departments of medicine and pediatrics, a pediatric resident and student, and physicians from the divisions of pediatric infectious disease, pediatric critical care, and pediatric gastroenterology. This study qualified for Institutional Review Board (IRB) exemption based on the University’s IRB stipulations.

Current Condition

Root cause analysis was performed by creating a process map of the current standard work and a fishbone diagram (Figure 1). We incorporated feedback from voice of the customer in the root cause analysis. In this analysis, the voice of the customer came from the bedside floor nurses, ultrasound clerk and sonographer, echo technician, cardiology fellow, and microbiology medical technician. We got their feedback on our process map, its accuracy and ways to expand, their thoughts on the problem and why we have this problem, and any solutions they could offer to help improve the problem. Some of the key points obtained were: echos were not routinely done on the floors and were not considered urgent as they often did not change management; the sonographer and those from the cardiology department felt imaging was often overutilized because of misconceptions and lack of available hospital guidelines. Suggested solutions included provider education with reference to Duke’s criteria and establishing a clinical pathway approved by all concerned departments.

Prior to education, we surveyed current practices of practitioners on teams caring for these patients, which included physicians of all levels (attendings, fellows, residents) as well as nurse practitioners and medical students from the department of pediatrics and divisions of pediatric gastroenterology, pediatric infectious disease, and pediatric critical care medicine.

Practitioner Education. In October 2017 practitioners were given a 20-minute presentation on the latest international guidelines on fungemia. Fifty-nine practitioners completed pre- and post-test surveys. Eight respondents were excluded due to incomplete surveys. We compared self-reported frequencies of ordering abdominal imaging and echo before the presentation with intention to order post education. Intention to change clinical practice after the presentation was also surveyed.

Clinical Pathway. Education alone may not result in sustainability, and thus we provided a readily accessible clinical pathway and an electronic order set for pediatric fungemia management. Inter-department buy-in was also necessary for success. It was important to get the input from the various teams (infectious disease, cardiology, gastroenterology, and critical care), which was done by incorporating members from those divisions in the project or getting their feedback through voice of the customer analysis.

We redefined standard work based on current evidence and created a clinical pathway during March 2018 that included variations when appropriate (Figure 2). We presented the clinical pathway to practitioners and distributed it via email. We also made it available to pediatric residents and fellows on their mobile institutional work resource application.

Electronic Order Set. We created an electronic order set for pediatric fungemia management and made it available in the electronic health record May 2018.

Measurement

Cases of fungemia were identified through the electronic health record pre-intervention (January 1, 2016 through November 19, 2017) and post-intervention (November 20, 2019 through April 3, 2019). An episode of fungemia was defined as an encounter with 1 or more positive blood culture(s) for Candida species or Cryptococcus species. We manually identified patients belonging to the pediatric gastroenterology service and reviewed these charts to determine the presenting complaint, organism isolated, transplant status, central lines status, risk factors, if abdominal imaging or echocardiography were done for the episode of fungemia, and their corresponding results. We calculated overall and per patient medical charges by using the average charges at our institution of US and echocardiography with a cardiology consult. These average charges were provided by patient financial services and the pediatric cardiology department, respectively. To address non-technical expenditures, we calculated the average time taken for transport to and from radiology and the echo suite for each identified patient. We identified missed fungal endocarditis and fungal balls as balancing measures.

Survey

Among the 51 practitioners surveyed, 36% were performing routine echo and 22% self-reported performing routine abdominal imaging. After education, no respondents planned to routinely do echo or abdominal imaging. All but 1 respondent planned to change their practice for evaluation of fungemia patients based on the presentation (eFigure 1).

Baseline Data

Over the 23-month period from January 1, 2016 to November 19, 2017, there were 21 episodes of fungemia, 18 of which occurred in patients on the pediatric gastroenterology service (2 of the 18 were transplant recipients). For the 18 episodes on this service, abdominal imaging and echo were done 100% of the time, with 0 positive findings (eFigure 2).

Of those 18 episodes, the average age was 4.6 years, with two-thirds of the population being male. There were 3 patients with multiple episodes that accounted for 8 of the episodes (3, 3, and 2 episodes each). Fever was the most common presenting complaint. The most common organism was Candida parapsilosis (6 of the 18 episodes). All episodes but one involved a central line, and all central lines were removed when present except for one case. Of the risk factors, 3 episodes occurred in neutropenic patients, and for 1 episode the patient had a questionable history of fungal endocarditis (and was on fungal prophylaxis). There were no patients with recent cardiac/urogenital surgery or prior fungal balls. No episodes had clinical symptoms suggestive of fungal endocarditis or fungal balls.

Post-Intervention Data

Over the subsequent 17-month period (November 11, 2017 to April 3, 2019), there were 13 episodes of candidemia. There were no episodes of Cryptococcus fungemia. Seven episodes occurred in patients on the pediatric gastroenterology service (2 of the 7 occurred in transplant recipients). Abdominal imaging was done in 3 of these episodes (43%), and in 2 of these 3 episodes, imaging was done at an outside institution prior to arrival, with no positive results (eFigure 2).

Echocardiography was done 57% of the time (n = 4), with echo being done at an outside institution prior to arrival half of the time (n = 2), with no endocarditis identified. The cases of abdominal imaging and echo done at outside institutions prior to arrival were not impacted by the countermeasures. Excluding those 2 patients who had both abdominal imaging and echocardiography done prior to arrival, the overall rate of imaging (both abdominal imaging and echo) done after countermeasures were instituted was 30% (Figure 3).

Of those 7 episodes, the average age was 6.8 years (57% female). There were no patients with multiple episodes. The most common presenting complaint was fever. The most common organism was Candida albicans (3 of the 7 episodes). All episodes involved a central line, which was removed in all cases except for one. Of the risk factors, 2 episodes were in neutropenic patients, and 1 episode had a history of bacterial endocarditis (not related to fungemia). No episodes occurred in patients with prior fungal renal infection, urogenital malformations, or recent cardiac/urogenital surgery. No episodes had clinical symptoms suggestive of fungal endocarditis or renal infection. No episodes of fungal endocarditis or renal infection were identified.

On average, a patient at our institution undergoing abdominal US and echo with a cardiology consult results in medical waste of approximately $3200 per patient. This cost does not take into account other miscellaneous charges possibly incurred, such as the radiologist interpreting the findings and transportation. Baseline data calculations show that patients waste on average 55 minutes in physical transport, and this does not take into account wait times.

Discussion

Candidemia contributes to 10% of central-line associated blood stream infections (CLABSI).¹⁹ Increased usage of indwelling central catheters for administration of parenteral nutrition will inevitably result in practitioners encountering cases of candidemia when caring for this population. As seen from our results, the majority of episodes of candidemia at our institution occurred on the pediatric gastroenterology service, and thus redefining standard work on this service will be impactful.

Candida parapsilosis and Candida albicans were the most common causative agents before and after intervention, respectively, but overall the most common organism was Candida albicans, which is in keeping with that of CLABSI in the literature.¹⁹ Growth of Candida parapsilosis has been particularly linked to CLABSI.¹⁹ The third most common organism in our study was Candida glabrata, which is the second most common cause of candidemia in CLABSI.¹⁹

The cases of positive abdominal imaging in fungemia in the literature are limited to the neonatal population^1-4 and chronic disseminated candidiasis in patients with hematologic malignancies/neutropenia/immunosuppression.^5,6 In fungal endocarditis, the reported cases were generally in neonates,^1,3,7 critically ill patients,⁸ patients with hematologic malignancies/neutropenia/immunosuppression,^6,9 or those with a cardiac history.^9,10 This population differs from the patient population on the pediatric gastroenterology service. Patients on this service may not need US or echo. Performing abdominal US and echo in fungemia patients in whom such imaging is not indicated may result in medical waste of approximately $3200 per patient. There is also a waste of medical resources and time.

We found almost all practitioners are willing to change clinical practice once provided with current guidelines. Face-to-face oral presentations allowed for questions and interaction, making this form of information dissemination better than e-mails or handouts.

Though the numbers were small over the short study period, we were able to decrease overutilization of abdominal imaging and echo after implementing countermeasures. Frequency decreased from 100% to 43% and 57% for abdominal imaging and echo, respectively. Imaging that was done after the countermeasures were implemented was mainly attributed to imaging patients underwent prior to presenting to our institution. This reinforces the need for education at other institutions as well. Of the balancing measures assessed, there were no missed cases of fungal balls or fungal endocarditis. Additionally, of the total 34 episodes of fungemia assessed (21 before and 13 after), even among those with risk factors, there were no cases of fungal endocarditis or renal infection.

The findings from this quality improvement project underscore current recommendations that, despite common misconceptions, routine abdominal US and echo are not indicated in all cases of fungemia. Case-by-case assessment based on the clinical scenario remains key to management of fungemia to avoid unnecessary medical interventions.

Corresponding author: Donna Cheung, MBBS, 200 Hawkins Drive, BT 1120-G, Iowa City, IA 52242; [email protected].

Financial support: None.

Progress in reducing the number of new HIV infections has stalled, according to a Vital Signs report published by the Centers for Disease Control and Prevention based upon a simultaneous MMWR Early Release. The report indicates that many Americans with HIV are not aware of their status or are not receiving effective treatment. Furthermore, the data suggest that few Americans who could benefit from preexposure prophylaxis (PrEP), a daily pill that prevents HIV, are receiving it.

CDC Vital Signs. Dec 3, 2019

The report “shows that HIV testing, treatment, and prevention have not reached enough Americans, and it emphasizes the continued urgent need to increase these interventions,” said Jay C. Butler, MD, deputy director for infectious diseases at the CDC, at a press conference. “We made a lot of progress in the late ’90s and into the early part of the 21st century in reducing the number of new cases of HIV. But HIV prevention progress has stalled in America since 2013. This stalling underscores the need to increase resources, deploy new technologies, and build expertise, particularly in areas where they’re needed most.”

To achieve these objectives, the CDC has proposed a federal initiative called Ending the HIV Epidemic: A Plan for America. The goal of the initiative is to reduce new HIV infections by 90% by 2030, in part by expanding access to PrEP medications.

Data suggest shortcomings in diagnosis, treatment, and prevention

In its review of data on HIV testing and treatment in 2017, the Vital Signs report found that approximately 154,000 people with HIV (that is, 14% of the total population with HIV) were unaware that they had the virus. These patients consequently could not take advantage of HIV treatment to maintain health, control the virus, and prevent HIV transmission. Young people aged 13-24 years were less likely to know their HIV status than did those aged 25 years and older, according to the report.

Furthermore, approximately two-thirds (63%) of patients who knew that they had HIV had the virus under control through effective treatment. Young people and African Americans were least likely to have the virus under control, according to the report.

The report also examines data about treatment with PrEP in 2018. About 1.2 million Americans could benefit from PrEP, but only 219,700 (18%) of them had received a prescription for the drug. The eligible groups with the lowest rates of coverage were young people, African Americans, and Latinos.

The report presents a conservative estimate of PrEP coverage, however. Researchers examined data from 92% of prescriptions from retail pharmacies in the United States but did not include prescriptions from closed health care systems such as managed care organizations and military health plans. PrEP coverage in 2018 likely was higher than these estimates indicate, according to the CDC.

“There has been a rapid increase in the number of people taking PrEP over the past 3 years, but there is no doubt that PrEP uptake is too low,” said Eugene McCray, MD, director of CDC’s division of HIV/AIDS prevention. “We are working hard to increase access to PrEP, especially among gay and bisexual men, women, transgender people, young people, African Americans, and Latinos.”

The rate of new HIV infections has not decreased, but remained stable, according to the report. The CDC estimates that there were about 38,000 new infections per year from 2013 to 2017.

Proposed initiative focuses on areas of greatest need

The proposed Ending the HIV Epidemic initiative, if it is funded, will target the locations of greatest need throughout the country. Its initial focus will be on 50 areas that account for more than half of new HIV diagnoses, including 48 counties; San Juan, Puerto Rico; and Washington, D.C. It also will direct resources to seven states with high rates of infection in rural areas. In a second phase, the initiative will expand nationwide, provided that additional resources are made available.

The proposed initiative relies on four science-based strategies. First, it will aim to diagnose all Americans with HIV (at least 95% of HIV infections) as early as possible. Second, the initiative will enable people with HIV to receive treatment rapidly and effectively. The CDC’s target is to achieve viral suppression in at least 95% of people with diagnosed HIV. Third, the initiative will use proven interventions such as PrEP and syringe services programs to prevent new HIV transmissions. One related goal is for at least 50% of people who could benefit from PrEP to receive a prescription. Finally, the initiative is intended to respond quickly to potential HIV outbreaks and provide prevention and treatment to those who need them.

The U.S. Department of Health & Human Services already has taken steps to enable the initiative to be implemented quickly if it is funded in 2020. The department has provided funding to Baltimore City, Md.; DeKalb County, Ga.; and East Baton Rouge Parish, La. to begin pursuing parts of the initiative. These communities are encouraged to share the lessons of their experiences with other communities. HHS also has supported local efforts to develop plans under the initiative in all priority geographic areas. These plans draw upon recommendations from the community, HIV-planning bodies, and health care providers.

“Ending the HIV epidemic would be one of the greatest public health triumphs in our nation’s history,” said Dr. McCray.

[email protected]

SOURCES: Centers for Disease Control and Prevention. CDC Vital Signs. 2019 Dec 3. and Harris NS et al. MMWR Morb Mortal Wkly Rep. 2019 Dec 3.

Progress in reducing the number of new HIV infections has stalled, according to a Vital Signs report published by the Centers for Disease Control and Prevention based upon a simultaneous MMWR Early Release. The report indicates that many Americans with HIV are not aware of their status or are not receiving effective treatment. Furthermore, the data suggest that few Americans who could benefit from preexposure prophylaxis (PrEP), a daily pill that prevents HIV, are receiving it.

CDC Vital Signs. Dec 3, 2019

The report “shows that HIV testing, treatment, and prevention have not reached enough Americans, and it emphasizes the continued urgent need to increase these interventions,” said Jay C. Butler, MD, deputy director for infectious diseases at the CDC, at a press conference. “We made a lot of progress in the late ’90s and into the early part of the 21st century in reducing the number of new cases of HIV. But HIV prevention progress has stalled in America since 2013. This stalling underscores the need to increase resources, deploy new technologies, and build expertise, particularly in areas where they’re needed most.”

To achieve these objectives, the CDC has proposed a federal initiative called Ending the HIV Epidemic: A Plan for America. The goal of the initiative is to reduce new HIV infections by 90% by 2030, in part by expanding access to PrEP medications.

Data suggest shortcomings in diagnosis, treatment, and prevention

In its review of data on HIV testing and treatment in 2017, the Vital Signs report found that approximately 154,000 people with HIV (that is, 14% of the total population with HIV) were unaware that they had the virus. These patients consequently could not take advantage of HIV treatment to maintain health, control the virus, and prevent HIV transmission. Young people aged 13-24 years were less likely to know their HIV status than did those aged 25 years and older, according to the report.

Furthermore, approximately two-thirds (63%) of patients who knew that they had HIV had the virus under control through effective treatment. Young people and African Americans were least likely to have the virus under control, according to the report.

The report also examines data about treatment with PrEP in 2018. About 1.2 million Americans could benefit from PrEP, but only 219,700 (18%) of them had received a prescription for the drug. The eligible groups with the lowest rates of coverage were young people, African Americans, and Latinos.

The report presents a conservative estimate of PrEP coverage, however. Researchers examined data from 92% of prescriptions from retail pharmacies in the United States but did not include prescriptions from closed health care systems such as managed care organizations and military health plans. PrEP coverage in 2018 likely was higher than these estimates indicate, according to the CDC.

“There has been a rapid increase in the number of people taking PrEP over the past 3 years, but there is no doubt that PrEP uptake is too low,” said Eugene McCray, MD, director of CDC’s division of HIV/AIDS prevention. “We are working hard to increase access to PrEP, especially among gay and bisexual men, women, transgender people, young people, African Americans, and Latinos.”

The rate of new HIV infections has not decreased, but remained stable, according to the report. The CDC estimates that there were about 38,000 new infections per year from 2013 to 2017.

Proposed initiative focuses on areas of greatest need

The proposed Ending the HIV Epidemic initiative, if it is funded, will target the locations of greatest need throughout the country. Its initial focus will be on 50 areas that account for more than half of new HIV diagnoses, including 48 counties; San Juan, Puerto Rico; and Washington, D.C. It also will direct resources to seven states with high rates of infection in rural areas. In a second phase, the initiative will expand nationwide, provided that additional resources are made available.

The proposed initiative relies on four science-based strategies. First, it will aim to diagnose all Americans with HIV (at least 95% of HIV infections) as early as possible. Second, the initiative will enable people with HIV to receive treatment rapidly and effectively. The CDC’s target is to achieve viral suppression in at least 95% of people with diagnosed HIV. Third, the initiative will use proven interventions such as PrEP and syringe services programs to prevent new HIV transmissions. One related goal is for at least 50% of people who could benefit from PrEP to receive a prescription. Finally, the initiative is intended to respond quickly to potential HIV outbreaks and provide prevention and treatment to those who need them.

The U.S. Department of Health & Human Services already has taken steps to enable the initiative to be implemented quickly if it is funded in 2020. The department has provided funding to Baltimore City, Md.; DeKalb County, Ga.; and East Baton Rouge Parish, La. to begin pursuing parts of the initiative. These communities are encouraged to share the lessons of their experiences with other communities. HHS also has supported local efforts to develop plans under the initiative in all priority geographic areas. These plans draw upon recommendations from the community, HIV-planning bodies, and health care providers.

“Ending the HIV epidemic would be one of the greatest public health triumphs in our nation’s history,” said Dr. McCray.

[email protected]

SOURCES: Centers for Disease Control and Prevention. CDC Vital Signs. 2019 Dec 3. and Harris NS et al. MMWR Morb Mortal Wkly Rep. 2019 Dec 3.

Progress in reducing the number of new HIV infections has stalled, according to a Vital Signs report published by the Centers for Disease Control and Prevention based upon a simultaneous MMWR Early Release. The report indicates that many Americans with HIV are not aware of their status or are not receiving effective treatment. Furthermore, the data suggest that few Americans who could benefit from preexposure prophylaxis (PrEP), a daily pill that prevents HIV, are receiving it.

CDC Vital Signs. Dec 3, 2019

The report “shows that HIV testing, treatment, and prevention have not reached enough Americans, and it emphasizes the continued urgent need to increase these interventions,” said Jay C. Butler, MD, deputy director for infectious diseases at the CDC, at a press conference. “We made a lot of progress in the late ’90s and into the early part of the 21st century in reducing the number of new cases of HIV. But HIV prevention progress has stalled in America since 2013. This stalling underscores the need to increase resources, deploy new technologies, and build expertise, particularly in areas where they’re needed most.”

To achieve these objectives, the CDC has proposed a federal initiative called Ending the HIV Epidemic: A Plan for America. The goal of the initiative is to reduce new HIV infections by 90% by 2030, in part by expanding access to PrEP medications.

Data suggest shortcomings in diagnosis, treatment, and prevention

In its review of data on HIV testing and treatment in 2017, the Vital Signs report found that approximately 154,000 people with HIV (that is, 14% of the total population with HIV) were unaware that they had the virus. These patients consequently could not take advantage of HIV treatment to maintain health, control the virus, and prevent HIV transmission. Young people aged 13-24 years were less likely to know their HIV status than did those aged 25 years and older, according to the report.

Furthermore, approximately two-thirds (63%) of patients who knew that they had HIV had the virus under control through effective treatment. Young people and African Americans were least likely to have the virus under control, according to the report.

The report also examines data about treatment with PrEP in 2018. About 1.2 million Americans could benefit from PrEP, but only 219,700 (18%) of them had received a prescription for the drug. The eligible groups with the lowest rates of coverage were young people, African Americans, and Latinos.

The report presents a conservative estimate of PrEP coverage, however. Researchers examined data from 92% of prescriptions from retail pharmacies in the United States but did not include prescriptions from closed health care systems such as managed care organizations and military health plans. PrEP coverage in 2018 likely was higher than these estimates indicate, according to the CDC.

“There has been a rapid increase in the number of people taking PrEP over the past 3 years, but there is no doubt that PrEP uptake is too low,” said Eugene McCray, MD, director of CDC’s division of HIV/AIDS prevention. “We are working hard to increase access to PrEP, especially among gay and bisexual men, women, transgender people, young people, African Americans, and Latinos.”

The rate of new HIV infections has not decreased, but remained stable, according to the report. The CDC estimates that there were about 38,000 new infections per year from 2013 to 2017.

Proposed initiative focuses on areas of greatest need

The proposed Ending the HIV Epidemic initiative, if it is funded, will target the locations of greatest need throughout the country. Its initial focus will be on 50 areas that account for more than half of new HIV diagnoses, including 48 counties; San Juan, Puerto Rico; and Washington, D.C. It also will direct resources to seven states with high rates of infection in rural areas. In a second phase, the initiative will expand nationwide, provided that additional resources are made available.

The proposed initiative relies on four science-based strategies. First, it will aim to diagnose all Americans with HIV (at least 95% of HIV infections) as early as possible. Second, the initiative will enable people with HIV to receive treatment rapidly and effectively. The CDC’s target is to achieve viral suppression in at least 95% of people with diagnosed HIV. Third, the initiative will use proven interventions such as PrEP and syringe services programs to prevent new HIV transmissions. One related goal is for at least 50% of people who could benefit from PrEP to receive a prescription. Finally, the initiative is intended to respond quickly to potential HIV outbreaks and provide prevention and treatment to those who need them.

The U.S. Department of Health & Human Services already has taken steps to enable the initiative to be implemented quickly if it is funded in 2020. The department has provided funding to Baltimore City, Md.; DeKalb County, Ga.; and East Baton Rouge Parish, La. to begin pursuing parts of the initiative. These communities are encouraged to share the lessons of their experiences with other communities. HHS also has supported local efforts to develop plans under the initiative in all priority geographic areas. These plans draw upon recommendations from the community, HIV-planning bodies, and health care providers.

“Ending the HIV epidemic would be one of the greatest public health triumphs in our nation’s history,” said Dr. McCray.

[email protected]

SOURCES: Centers for Disease Control and Prevention. CDC Vital Signs. 2019 Dec 3. and Harris NS et al. MMWR Morb Mortal Wkly Rep. 2019 Dec 3.

Certain types of oral antibiotics seem to be associated with an elevated risk of Parkinson’s disease with a delay that is consistent with the proposed duration of a prodromal period, according to a report published in Movement Disorders. Associations were found for broad-spectrum antibiotics and those that act against anaerobic bacteria and fungi. The timing of antibiotic exposure also seemed to matter.

In a nationwide case-control study, Finnish researchers compared data on antibiotic use in 13,976 individuals diagnosed with Parkinson’s disease between 1998 and 2014 with antibiotic-use data from 40,697 controls. The strongest connection with Parkinson’s disease risk was found for oral exposure to macrolides and lincosamides (adjusted odds ratio up to 1.416). After correction for multiple comparisons, exposure to antianaerobics and tetracyclines 10-15 years before the index date, and antifungal medications 1-5 years before the index date were positively associated with Parkinson’s disease risk. In post hoc analyses, further positive associations were found for broad-spectrum antibiotics.

Tuomas H. Mertsalmi, MD, from the Helsinki University Hospital and coauthors reported that this was the first study to explore a possible connection between antimicrobial use and Parkinson’s disease.

“In Parkinson’s disease, several studies have described alterations of gut microbiota composition, and changes in fecal microbiota abundance have been found to be associated with gastrointestinal and motor symptoms,” they wrote.

Commenting on the delay between the exposure and diagnosis for the most strongly associated antimicrobials, the authors noted that this 10-15 year lag was comparable with what has been found between the peripheral initiation of Parkinson’s disease and its motor manifestation.

“This would also explain the lack of association between antibiotic exposure 1-5 years before index date – if antibiotic exposure could induce or contribute to the pathogenesis of Parkinson’s disease in the gastrointestinal tract, it would probably take several years before the clinical manifestation of Parkinson’s disease,” they wrote.

With regards to the association seen for sulfonamides and trimethoprim – which was 1-5 years before the index date – they speculated this could reflect treatment for urinary tract infections, which individuals with Parkinson’s disease might be more susceptible to in the prodromal phase of the disease.

The authors noted that infectious disease has also been associated with Parkinson’s disease, and that their analysis did not include information about why the antimicrobial agents were prescribed. However, they pointed out that the associations were only for certain antibiotic classes, which makes it unlikely that the association was related to greater burden of infectious disease among individuals with Parkinson’s disease.

The pattern of associations supports the hypothesis that effects on gut microbiota could link antibiotics to Parkinson’s disease. “The link between antibiotic exposure and Parkinson’s disease fits the current view that in a significant proportion of patients the pathology of Parkinson’s disease may originate in the gut, possibly related to microbial changes, years before the onset of typical Parkinson’s disease motor symptoms such as slowness, muscle stiffness, and shaking of the extremities. It was known that bacterial composition of the intestine in patients with Parkinson’s disease is abnormal, but the cause is unclear. Our results suggest that some commonly used antibiotics, which are known to strongly influence the gut microbiota, could be a predisposing factor,” said lead investigator Filip Scheperjans, MD, PhD, from the department of neurology at Helsinki University Hospital.

The findings may have implications for antibiotic prescribing practices in the future, said Dr. Scheperjans. “In addition to the problem of antibiotic resistance, antimicrobial prescribing should also take into account their potentially long-lasting effects on the gut microbiome and the development of certain diseases.”

The study was funded by the Finnish Parkinson Foundation, the Finnish Medical Foundation, the Maire Taponen Foundation, and the Academy of Finland. One author declared relevant patents and his position as founder and chief executive of a private company. No other conflicts of interest were declared.

SOURCE: Mertsalmi TH et al. Mov Disord. 2019 Nov 18. doi: 10.1002/mds.27924.

Certain types of oral antibiotics seem to be associated with an elevated risk of Parkinson’s disease with a delay that is consistent with the proposed duration of a prodromal period, according to a report published in Movement Disorders. Associations were found for broad-spectrum antibiotics and those that act against anaerobic bacteria and fungi. The timing of antibiotic exposure also seemed to matter.

In a nationwide case-control study, Finnish researchers compared data on antibiotic use in 13,976 individuals diagnosed with Parkinson’s disease between 1998 and 2014 with antibiotic-use data from 40,697 controls. The strongest connection with Parkinson’s disease risk was found for oral exposure to macrolides and lincosamides (adjusted odds ratio up to 1.416). After correction for multiple comparisons, exposure to antianaerobics and tetracyclines 10-15 years before the index date, and antifungal medications 1-5 years before the index date were positively associated with Parkinson’s disease risk. In post hoc analyses, further positive associations were found for broad-spectrum antibiotics.

Tuomas H. Mertsalmi, MD, from the Helsinki University Hospital and coauthors reported that this was the first study to explore a possible connection between antimicrobial use and Parkinson’s disease.

“In Parkinson’s disease, several studies have described alterations of gut microbiota composition, and changes in fecal microbiota abundance have been found to be associated with gastrointestinal and motor symptoms,” they wrote.

Commenting on the delay between the exposure and diagnosis for the most strongly associated antimicrobials, the authors noted that this 10-15 year lag was comparable with what has been found between the peripheral initiation of Parkinson’s disease and its motor manifestation.

“This would also explain the lack of association between antibiotic exposure 1-5 years before index date – if antibiotic exposure could induce or contribute to the pathogenesis of Parkinson’s disease in the gastrointestinal tract, it would probably take several years before the clinical manifestation of Parkinson’s disease,” they wrote.

With regards to the association seen for sulfonamides and trimethoprim – which was 1-5 years before the index date – they speculated this could reflect treatment for urinary tract infections, which individuals with Parkinson’s disease might be more susceptible to in the prodromal phase of the disease.

The authors noted that infectious disease has also been associated with Parkinson’s disease, and that their analysis did not include information about why the antimicrobial agents were prescribed. However, they pointed out that the associations were only for certain antibiotic classes, which makes it unlikely that the association was related to greater burden of infectious disease among individuals with Parkinson’s disease.

The pattern of associations supports the hypothesis that effects on gut microbiota could link antibiotics to Parkinson’s disease. “The link between antibiotic exposure and Parkinson’s disease fits the current view that in a significant proportion of patients the pathology of Parkinson’s disease may originate in the gut, possibly related to microbial changes, years before the onset of typical Parkinson’s disease motor symptoms such as slowness, muscle stiffness, and shaking of the extremities. It was known that bacterial composition of the intestine in patients with Parkinson’s disease is abnormal, but the cause is unclear. Our results suggest that some commonly used antibiotics, which are known to strongly influence the gut microbiota, could be a predisposing factor,” said lead investigator Filip Scheperjans, MD, PhD, from the department of neurology at Helsinki University Hospital.

The findings may have implications for antibiotic prescribing practices in the future, said Dr. Scheperjans. “In addition to the problem of antibiotic resistance, antimicrobial prescribing should also take into account their potentially long-lasting effects on the gut microbiome and the development of certain diseases.”

The study was funded by the Finnish Parkinson Foundation, the Finnish Medical Foundation, the Maire Taponen Foundation, and the Academy of Finland. One author declared relevant patents and his position as founder and chief executive of a private company. No other conflicts of interest were declared.

SOURCE: Mertsalmi TH et al. Mov Disord. 2019 Nov 18. doi: 10.1002/mds.27924.

Certain types of oral antibiotics seem to be associated with an elevated risk of Parkinson’s disease with a delay that is consistent with the proposed duration of a prodromal period, according to a report published in Movement Disorders. Associations were found for broad-spectrum antibiotics and those that act against anaerobic bacteria and fungi. The timing of antibiotic exposure also seemed to matter.

In a nationwide case-control study, Finnish researchers compared data on antibiotic use in 13,976 individuals diagnosed with Parkinson’s disease between 1998 and 2014 with antibiotic-use data from 40,697 controls. The strongest connection with Parkinson’s disease risk was found for oral exposure to macrolides and lincosamides (adjusted odds ratio up to 1.416). After correction for multiple comparisons, exposure to antianaerobics and tetracyclines 10-15 years before the index date, and antifungal medications 1-5 years before the index date were positively associated with Parkinson’s disease risk. In post hoc analyses, further positive associations were found for broad-spectrum antibiotics.

Tuomas H. Mertsalmi, MD, from the Helsinki University Hospital and coauthors reported that this was the first study to explore a possible connection between antimicrobial use and Parkinson’s disease.

“In Parkinson’s disease, several studies have described alterations of gut microbiota composition, and changes in fecal microbiota abundance have been found to be associated with gastrointestinal and motor symptoms,” they wrote.

Commenting on the delay between the exposure and diagnosis for the most strongly associated antimicrobials, the authors noted that this 10-15 year lag was comparable with what has been found between the peripheral initiation of Parkinson’s disease and its motor manifestation.

“This would also explain the lack of association between antibiotic exposure 1-5 years before index date – if antibiotic exposure could induce or contribute to the pathogenesis of Parkinson’s disease in the gastrointestinal tract, it would probably take several years before the clinical manifestation of Parkinson’s disease,” they wrote.

With regards to the association seen for sulfonamides and trimethoprim – which was 1-5 years before the index date – they speculated this could reflect treatment for urinary tract infections, which individuals with Parkinson’s disease might be more susceptible to in the prodromal phase of the disease.

The authors noted that infectious disease has also been associated with Parkinson’s disease, and that their analysis did not include information about why the antimicrobial agents were prescribed. However, they pointed out that the associations were only for certain antibiotic classes, which makes it unlikely that the association was related to greater burden of infectious disease among individuals with Parkinson’s disease.

The pattern of associations supports the hypothesis that effects on gut microbiota could link antibiotics to Parkinson’s disease. “The link between antibiotic exposure and Parkinson’s disease fits the current view that in a significant proportion of patients the pathology of Parkinson’s disease may originate in the gut, possibly related to microbial changes, years before the onset of typical Parkinson’s disease motor symptoms such as slowness, muscle stiffness, and shaking of the extremities. It was known that bacterial composition of the intestine in patients with Parkinson’s disease is abnormal, but the cause is unclear. Our results suggest that some commonly used antibiotics, which are known to strongly influence the gut microbiota, could be a predisposing factor,” said lead investigator Filip Scheperjans, MD, PhD, from the department of neurology at Helsinki University Hospital.

The findings may have implications for antibiotic prescribing practices in the future, said Dr. Scheperjans. “In addition to the problem of antibiotic resistance, antimicrobial prescribing should also take into account their potentially long-lasting effects on the gut microbiome and the development of certain diseases.”

The study was funded by the Finnish Parkinson Foundation, the Finnish Medical Foundation, the Maire Taponen Foundation, and the Academy of Finland. One author declared relevant patents and his position as founder and chief executive of a private company. No other conflicts of interest were declared.

SOURCE: Mertsalmi TH et al. Mov Disord. 2019 Nov 18. doi: 10.1002/mds.27924.

After only 8 weeks, the 2019-2020 influenza season already has made itself noteworthy.

For the week ending Nov. 23, there were five states, along with Puerto Rico, at the highest level of the Centers for Disease Control and Prevention’s 1-10 scale of flu activity. That’s more than any year since 2012, including the pandemic season of 2017-2018, according to CDC data, and may suggest either an early peak or the beginning of a particularly bad winter.

“Nationally, ILI [influenza-like illness] activity has been at or above baseline for 3 weeks; however, the amount of influenza activity across the country varies with the south and parts of the west seeing elevated activity while other parts of the country are still seeing low activity,” the CDC’s influenza division said in its weekly FluView report.

The five highest-activity states – Alabama, Georgia, Louisiana, Mississippi, and Texas – are all at level 10, and they join two others – South Carolina and Tennessee, which are at level 8 – in the “high” range from 8-10 on the ILI activity scale; Puerto Rico also is at level 10. ILI is defined as “fever (temperature of 100° F [37.8° C] or greater) and a cough and/or a sore throat without a known cause other than influenza,” the CDC said.

The activity scale is based on the percentage of outpatient visits for ILI in each state, which is reported to the CDC’s Outpatient Influenza-like Illness Surveillance Network (ILINet) each week. The national rate for the week ending Nov. 23 was 2.9%, which is above the new-for-this-season baseline rate of 2.4%. For the three previous flu seasons, the national baseline was 2.2%, having been raised from its previous level of 2.1% in 2015-2016, CDC data show.

The peak month of flu activity occurs most often in February – 15 times from 1982-1983 to 2017-2018 – but there were seven peaks in December and six each in January and March over that time period, along with one peak each in October and November, the CDC said. The October peak occurred during the H1N1 pandemic year of 2009, when the national outpatient ILI rate climbed to just over 7.7%.
 

[email protected]

After only 8 weeks, the 2019-2020 influenza season already has made itself noteworthy.

For the week ending Nov. 23, there were five states, along with Puerto Rico, at the highest level of the Centers for Disease Control and Prevention’s 1-10 scale of flu activity. That’s more than any year since 2012, including the pandemic season of 2017-2018, according to CDC data, and may suggest either an early peak or the beginning of a particularly bad winter.

“Nationally, ILI [influenza-like illness] activity has been at or above baseline for 3 weeks; however, the amount of influenza activity across the country varies with the south and parts of the west seeing elevated activity while other parts of the country are still seeing low activity,” the CDC’s influenza division said in its weekly FluView report.

The five highest-activity states – Alabama, Georgia, Louisiana, Mississippi, and Texas – are all at level 10, and they join two others – South Carolina and Tennessee, which are at level 8 – in the “high” range from 8-10 on the ILI activity scale; Puerto Rico also is at level 10. ILI is defined as “fever (temperature of 100° F [37.8° C] or greater) and a cough and/or a sore throat without a known cause other than influenza,” the CDC said.

The activity scale is based on the percentage of outpatient visits for ILI in each state, which is reported to the CDC’s Outpatient Influenza-like Illness Surveillance Network (ILINet) each week. The national rate for the week ending Nov. 23 was 2.9%, which is above the new-for-this-season baseline rate of 2.4%. For the three previous flu seasons, the national baseline was 2.2%, having been raised from its previous level of 2.1% in 2015-2016, CDC data show.

The peak month of flu activity occurs most often in February – 15 times from 1982-1983 to 2017-2018 – but there were seven peaks in December and six each in January and March over that time period, along with one peak each in October and November, the CDC said. The October peak occurred during the H1N1 pandemic year of 2009, when the national outpatient ILI rate climbed to just over 7.7%.
 

[email protected]

After only 8 weeks, the 2019-2020 influenza season already has made itself noteworthy.

For the week ending Nov. 23, there were five states, along with Puerto Rico, at the highest level of the Centers for Disease Control and Prevention’s 1-10 scale of flu activity. That’s more than any year since 2012, including the pandemic season of 2017-2018, according to CDC data, and may suggest either an early peak or the beginning of a particularly bad winter.

“Nationally, ILI [influenza-like illness] activity has been at or above baseline for 3 weeks; however, the amount of influenza activity across the country varies with the south and parts of the west seeing elevated activity while other parts of the country are still seeing low activity,” the CDC’s influenza division said in its weekly FluView report.

The five highest-activity states – Alabama, Georgia, Louisiana, Mississippi, and Texas – are all at level 10, and they join two others – South Carolina and Tennessee, which are at level 8 – in the “high” range from 8-10 on the ILI activity scale; Puerto Rico also is at level 10. ILI is defined as “fever (temperature of 100° F [37.8° C] or greater) and a cough and/or a sore throat without a known cause other than influenza,” the CDC said.

The activity scale is based on the percentage of outpatient visits for ILI in each state, which is reported to the CDC’s Outpatient Influenza-like Illness Surveillance Network (ILINet) each week. The national rate for the week ending Nov. 23 was 2.9%, which is above the new-for-this-season baseline rate of 2.4%. For the three previous flu seasons, the national baseline was 2.2%, having been raised from its previous level of 2.1% in 2015-2016, CDC data show.

The peak month of flu activity occurs most often in February – 15 times from 1982-1983 to 2017-2018 – but there were seven peaks in December and six each in January and March over that time period, along with one peak each in October and November, the CDC said. The October peak occurred during the H1N1 pandemic year of 2009, when the national outpatient ILI rate climbed to just over 7.7%.
 

[email protected]

The benefits of influenza vaccination are clear to those in the medical community. Yet misinformation and unfounded fears continue to discourage some people from getting a flu shot. During the 2018–2019 influenza season, only 45% of US adults and 63% of children were vaccinated.¹

‘IT DOESN’T WORK FOR MANY PEOPLE’

Multiple studies have shown that the flu vaccine prevents millions of flu cases and flu-related doctor’s visits each year. During the 2016–2017 flu season, flu vaccine prevented an estimated 5.3 million influenza cases, 2.6 million influenza-associated medical visits, and 85,000 influenza-associated hospitalizations.²

Several viral and host factors affect vaccine effectiveness. In seasons when the vaccine viruses have matched circulating strains, flu vaccine has been shown to reduce the following:

• The risk of having to go to the doctor with flu by 40% to 60%
• Children’s risk of flu-related death and intensive care unit (ICU) admission by 74%
• The risk in adults of flu-associated hospitalizations by 40% and ICU admission by 82%
• The rate of cardiac events in people with heart disease
• Hospitalizations in people with diabetes or underlying chronic lung disease.³

In people hospitalized with influenza despite receiving the flu vaccine for the season, studies have shown that receiving the flu vaccine shortens the average duration of hospitalization, reduces the chance of ICU admission by 59%, shortens the duration of ICU stay by 4 days, and reduces deaths.³

‘IT TARGETS THE WRONG VIRUS’

Selecting an effective influenza vaccine is a challenge. Every year, the World Health Organization and the CDC decide on the influenza strains expected to circulate in the upcoming flu season in the Northern Hemisphere, based on data for circulating strains in the Southern Hemisphere. This decision takes place about 7 months before the expected onset of the flu season. Flu viruses may mutate between the time the decision is made and the time the vaccine is administered (as well as after the flu season starts). Also, vaccine production in eggs needs time, which is why this decision must be made several months ahead of the flu season.

Vaccine effectiveness varies by virus serotype. Vaccines are typically less effective against influenza A H3N2 viruses than against influenza A H1N1 and influenza B viruses. Effectiveness also varies from season to season depending on how close the vaccine serotypes match the circulating serotypes, but some effectiveness is retained even in seasons when some of the serotypes don’t match circulating viruses. For example, in the 2017–2018 season, when the influenza A H3N2 vaccine serotype did not match the circulating serotype, the overall effectiveness in preventing medically attended, laboratory-confirmed influenza virus infection was 36%.⁵

A universal flu vaccine that does not need to be updated annually is the ultimate solution, but according to the National Institute of Allergy and Infectious Diseases, such a vaccine is likely several years away.⁶

‘IT MAKES PEOPLE SICK’

Pain at the injection site of a flu shot occurs in 10% to 65% of people, lasts less than 2 days, and does not usually interfere with daily activities.⁷

Systemic symptoms such as fever, malaise, and myalgia may occur in people who have had no previous exposure to the influenza virus antigens in the vaccine, particularly in children. In adults, the frequency of systemic symptoms after the flu shot is similar to that with placebo.

The Vaccine Adverse Event Reporting System, which has been capturing data since 1990, shows that the influenza vaccine accounted for 5.7% of people who developed malaise after receiving any vaccine.⁸

The injectable inactivated influenza vaccine cannot biologically cause an influenza virus-related illness, since the inactivated vaccine viruses can elicit a protective immune response but cannot replicate. The nasal live-attenuated flu vaccine can in theory cause acute illness in the person receiving it, but because it is cold-adapted, it multiplies only in the colder environment of the nasal epithelium, not in the lower airways where the temperature is higher. Consequently, the vaccine virus triggers immunity by multiplying in the nose, but doesn’t infect the lungs.

From 10% to 50% of people who receive the nasal live-attenuated vaccine develop runny nose, wheezing, headache, vomiting, muscle aches, fever, sore throat, or cough shortly after receiving the vaccine, but these symptoms are usually mild and short-lived.

The most common reactions people have to flu vaccines are considerably less severe than the symptoms caused by actual flu illness.

While influenza illness results in natural immunity to the specific viral serotype causing it, this illness results in hospitalization in 2% and is fatal in 0.16% of people. Influenza vaccine results in immunity to the serotypes included in the vaccine, and multiple studies have not found a causal relationship between vaccination and death.⁹

In the United States, 3,000 to 6,000 people per year develop Guillain-Barré syndrome, or 1 to 2 of every 100,000, which translates to 80 to 160 cases per week.¹⁰ While the exact cause of Guillain-Barré syndrome is unknown, about two-thirds of people have an acute diarrheal or respiratory illness within 3 months before the onset of symptoms. In 1976, the estimated attributable risk of influenza vaccine-related Guillain-Barré syndrome in the US adult population was 1 case per 100,000 in the 6 weeks after vaccination.¹¹ Studies in subsequent influenza seasons have not shown similar findings.¹² In fact, one study showed that the risk of developing Guillain-Barré syndrome was 15 times higher after influenza illness than after influenza vaccination.¹³

Since 5% to 15% of the US population develop symptomatic influenza annually,¹⁴ the decision to vaccinate with respect to the risk of Guillain-Barré syndrome should be obvious: vaccinate. The correct question to ask before influenza vaccination should be, “Have you previously developed Guillain-Barré syndrome within 6 weeks after receiving the flu vaccine?” If the answer is yes, the CDC considers this a caution, not a contraindication against receiving the influenza vaccine, since the benefit may still outweigh the risk.

‘I GOT THE FLU SHOT AND STILL GOT SICK’

The flu vaccine does not prevent illnesses caused by other viruses or bacteria that can make people sick during flu season. Influenza, the common cold, and streptococcal pharyngitis can have similar symptoms that make it difficult for patients—and, frequently, even healthcare providers—to distinguish between these illnesses with certainty.

One study suggested that influenza vaccine recipients had an increased risk of virologically confirmed noninfluenza respiratory viral infections,¹⁵ citing the phenomenon of virus interference that was described in the 1940s¹⁶ as a potential explanation. In essence, people protected against influenza by the vaccine may lack temporary nonspecific immunity against other respiratory viruses. However, these findings have not been replicated in subsequent studies.¹⁷

Viral gastroenteritis, mistakenly called “stomach flu,” is also not prevented by influenza vaccination.

‘I’M ALLERGIC TO EGGS’

The prevalence of egg allergy in US children is 0.5% to 2.5%.¹⁸ Most outgrow it by school age, but in one-third, the allergy persists into adulthood.

In general, people who can eat lightly cooked eggs (eg, scrambled eggs) without a reaction are unlikely to be allergic. On the other hand, the fact that egg-allergic people may tolerate egg included in baked products does not exclude the possibility of egg allergy. Egg allergy can be confirmed by a consistent medical history of adverse reaction to eggs and egg-containing foods, in addition to skin or blood testing for immunoglobulin E directed against egg proteins.¹⁹

Most currently available influenza vaccines are prepared by propagation of virus in embryonated eggs and so may contain trace amounts of egg proteins such as ovalbumin, with the exception of the inactivated quadri­valent recombinant influenza vaccine (Flublok) and the inactivated quadrivalent cell culture-based vaccine (Flucelvax).

The ACIP recommends that persons with a history of urticaria (hives) after exposure to eggs should receive any licensed, recommended influenza vaccine that is otherwise appropriate for their age and health status. Persons who report having angioedema, respiratory distress, lightheadedness, or recurrent vomiting, or who required epinephrine or another emergency medical intervention after exposure to eggs, should receive the influenza vaccine in an inpatient or outpatient medical setting under the supervision of a healthcare provider who is able to recognize and manage severe allergic reactions.

A history of severe allergic reaction such as anaphylaxis to a previous dose of any influenza vaccine, regardless of the vaccine component (including eggs) suspected of being responsible for the reaction, is a contraindication to influenza vaccination. The ACIP recommends that vaccine providers consider observing patients for 15 minutes after administration of any vaccine (regardless of history of egg allergy) to decrease the risk of injury should syncope occur.²⁰

‘I DON’T WANT TO PUT POISONOUS MERCURY IN MY BODY’

A process of biomagnification of methylmercury occurs when humans eat large fish that have eaten smaller fish. Thus, larger fish such as shark can be hazardous for women who are or may become pregnant, for nursing mothers, and for young children, while smaller fish such as herring are relatively safe.

As a precautionary measure, thimerosal was taken out of childhood vaccines in the United States in 2001. Thimerosal-free influenza vaccine formulations include the nasal live-attenuated flu vaccine, the inactivated quadrivalent recombinant influenza vaccine, and the inactivated quadrivalent cell culture-based vaccine.

‘I DON’T LIKE NEEDLES’

At least 10% of US adults have aichmophobia, the fear of sharp objects including needles.²² Vasovagal syncope is the most common manifestation. Behavioral therapy, topical anesthetics, and systemic anxiolytics have variable efficacy in treating needle phobia. For those who are absolutely averse to needles, the nasal flu vaccine is an appropriate alternative.

‘I DON’T WANT TO TAKE ANYTHING THAT CAN MESS WITH MY OTHER MEDICATIONS’

Some immunosuppressive medications may decrease influenza vaccine immunogenicity. Concomitant administration of the inactivated influenza vaccine with other vaccines is safe and does not alter immunogenicity of other vaccines.¹ The live-attenuated influenza vaccine is contraindicated in children and adolescents taking aspirin or other salicylates due to the risk of Reye syndrome.

A recent systematic review and meta-analysis showed that the inactivated influenza vaccine is not associated with asthma exacerbation.²³ However, the nasal live-attenuated influenza vaccine is contraindicated in children 2 to 4 years old who have asthma and should be used with caution in persons with asthma 5 years old and older. In the systematic review, influenza vaccine prevented 59% to 78% of asthma attacks leading to emergency visits or hospitalization.²³ In other immune-mediated diseases such as rheumatoid arthritis, influenza vaccine does not precipitate exacerbations.²⁴

‘I HAD AN ORGAN TRANSPLANT, AND I’M AFRAID THE FLU SHOT WILL CAUSE ORGAN REJECTION’

A study of 51,730 kidney transplant recipients found that receipt of the inactivated influenza vaccine in the first year after transplant was associated with a lower risk of subsequent allograft loss (adjusted hazard ratio 0.77; 95% confidence interval 0.69–0.85; P < .001) and death (adjusted hazard ratio 0.82; 95% confidence interval 0.76–0.89; P < .001).²⁵ In the same study, although acute rejection in the first year was not associated with influenza vaccination, influenza infection in the first year was associated with rejection (odds ratio 1.58; 95% confidence interval 1.10–2.26; P < 0.001), but not with graft loss or death. Solid organ transplant recipients should receive the inactivated influenza vaccine starting 3 months after transplant.²⁶

Influenza vaccination has not been shown to precipitate graft-vs-host disease in hematopoietic stem cell transplant recipients. These patients should also receive the inactivated influenza vaccine starting 3 to 6 months after transplant.²⁷

The nasal live-attenuated influenza vaccine is contraindicated in these immunocompromised patients.

‘I’M PREGNANT, AND I DON’T WANT TO EXPOSE MY UNBORN BABY TO ANYTHING POTENTIALLY HARMFUL’

The morbidity and mortality risk from influenza is high in children under 2 years old because of low immunogenicity to flu vaccine. This is particularly true in children younger than 6 months, but the vaccine is not recommended in this population. The best way to protect infants is for all household members to be vaccinated against the flu.

Equally important, morbidity and mortality risk from influenza is much higher in pregnant women than in the general population. Many studies have shown the value of influenza vaccination during pregnancy for both mothers and their infants. A recently published study showed that 18% of infants who developed influenza required hospitalization.²⁸ In that study, prenatal and postpartum maternal influenza vaccination decreased the odds of influenza in infants by 61% and 53%, respectively. Another study showed that vaccine effectiveness did not vary by gestational age at vaccination.²⁹ A post hoc analysis of an influenza vaccination study in pregnant women suggested that the vaccine was also associated with decreased rates of pertussis in these women.³⁰

Healthcare providers should try to understand the public’s misconceptions³¹ about seasonal influenza and influenza vaccines in order to best address them.

The benefits of influenza vaccination are clear to those in the medical community. Yet misinformation and unfounded fears continue to discourage some people from getting a flu shot. During the 2018–2019 influenza season, only 45% of US adults and 63% of children were vaccinated.¹

‘IT DOESN’T WORK FOR MANY PEOPLE’

Multiple studies have shown that the flu vaccine prevents millions of flu cases and flu-related doctor’s visits each year. During the 2016–2017 flu season, flu vaccine prevented an estimated 5.3 million influenza cases, 2.6 million influenza-associated medical visits, and 85,000 influenza-associated hospitalizations.²

Several viral and host factors affect vaccine effectiveness. In seasons when the vaccine viruses have matched circulating strains, flu vaccine has been shown to reduce the following:

• The risk of having to go to the doctor with flu by 40% to 60%
• Children’s risk of flu-related death and intensive care unit (ICU) admission by 74%
• The risk in adults of flu-associated hospitalizations by 40% and ICU admission by 82%
• The rate of cardiac events in people with heart disease
• Hospitalizations in people with diabetes or underlying chronic lung disease.³

In people hospitalized with influenza despite receiving the flu vaccine for the season, studies have shown that receiving the flu vaccine shortens the average duration of hospitalization, reduces the chance of ICU admission by 59%, shortens the duration of ICU stay by 4 days, and reduces deaths.³

‘IT TARGETS THE WRONG VIRUS’

Selecting an effective influenza vaccine is a challenge. Every year, the World Health Organization and the CDC decide on the influenza strains expected to circulate in the upcoming flu season in the Northern Hemisphere, based on data for circulating strains in the Southern Hemisphere. This decision takes place about 7 months before the expected onset of the flu season. Flu viruses may mutate between the time the decision is made and the time the vaccine is administered (as well as after the flu season starts). Also, vaccine production in eggs needs time, which is why this decision must be made several months ahead of the flu season.

Vaccine effectiveness varies by virus serotype. Vaccines are typically less effective against influenza A H3N2 viruses than against influenza A H1N1 and influenza B viruses. Effectiveness also varies from season to season depending on how close the vaccine serotypes match the circulating serotypes, but some effectiveness is retained even in seasons when some of the serotypes don’t match circulating viruses. For example, in the 2017–2018 season, when the influenza A H3N2 vaccine serotype did not match the circulating serotype, the overall effectiveness in preventing medically attended, laboratory-confirmed influenza virus infection was 36%.⁵

A universal flu vaccine that does not need to be updated annually is the ultimate solution, but according to the National Institute of Allergy and Infectious Diseases, such a vaccine is likely several years away.⁶

‘IT MAKES PEOPLE SICK’

Pain at the injection site of a flu shot occurs in 10% to 65% of people, lasts less than 2 days, and does not usually interfere with daily activities.⁷

Systemic symptoms such as fever, malaise, and myalgia may occur in people who have had no previous exposure to the influenza virus antigens in the vaccine, particularly in children. In adults, the frequency of systemic symptoms after the flu shot is similar to that with placebo.

The Vaccine Adverse Event Reporting System, which has been capturing data since 1990, shows that the influenza vaccine accounted for 5.7% of people who developed malaise after receiving any vaccine.⁸

The injectable inactivated influenza vaccine cannot biologically cause an influenza virus-related illness, since the inactivated vaccine viruses can elicit a protective immune response but cannot replicate. The nasal live-attenuated flu vaccine can in theory cause acute illness in the person receiving it, but because it is cold-adapted, it multiplies only in the colder environment of the nasal epithelium, not in the lower airways where the temperature is higher. Consequently, the vaccine virus triggers immunity by multiplying in the nose, but doesn’t infect the lungs.

From 10% to 50% of people who receive the nasal live-attenuated vaccine develop runny nose, wheezing, headache, vomiting, muscle aches, fever, sore throat, or cough shortly after receiving the vaccine, but these symptoms are usually mild and short-lived.

The most common reactions people have to flu vaccines are considerably less severe than the symptoms caused by actual flu illness.

While influenza illness results in natural immunity to the specific viral serotype causing it, this illness results in hospitalization in 2% and is fatal in 0.16% of people. Influenza vaccine results in immunity to the serotypes included in the vaccine, and multiple studies have not found a causal relationship between vaccination and death.⁹

In the United States, 3,000 to 6,000 people per year develop Guillain-Barré syndrome, or 1 to 2 of every 100,000, which translates to 80 to 160 cases per week.¹⁰ While the exact cause of Guillain-Barré syndrome is unknown, about two-thirds of people have an acute diarrheal or respiratory illness within 3 months before the onset of symptoms. In 1976, the estimated attributable risk of influenza vaccine-related Guillain-Barré syndrome in the US adult population was 1 case per 100,000 in the 6 weeks after vaccination.¹¹ Studies in subsequent influenza seasons have not shown similar findings.¹² In fact, one study showed that the risk of developing Guillain-Barré syndrome was 15 times higher after influenza illness than after influenza vaccination.¹³

Since 5% to 15% of the US population develop symptomatic influenza annually,¹⁴ the decision to vaccinate with respect to the risk of Guillain-Barré syndrome should be obvious: vaccinate. The correct question to ask before influenza vaccination should be, “Have you previously developed Guillain-Barré syndrome within 6 weeks after receiving the flu vaccine?” If the answer is yes, the CDC considers this a caution, not a contraindication against receiving the influenza vaccine, since the benefit may still outweigh the risk.

‘I GOT THE FLU SHOT AND STILL GOT SICK’

The flu vaccine does not prevent illnesses caused by other viruses or bacteria that can make people sick during flu season. Influenza, the common cold, and streptococcal pharyngitis can have similar symptoms that make it difficult for patients—and, frequently, even healthcare providers—to distinguish between these illnesses with certainty.

One study suggested that influenza vaccine recipients had an increased risk of virologically confirmed noninfluenza respiratory viral infections,¹⁵ citing the phenomenon of virus interference that was described in the 1940s¹⁶ as a potential explanation. In essence, people protected against influenza by the vaccine may lack temporary nonspecific immunity against other respiratory viruses. However, these findings have not been replicated in subsequent studies.¹⁷

Viral gastroenteritis, mistakenly called “stomach flu,” is also not prevented by influenza vaccination.

‘I’M ALLERGIC TO EGGS’

The prevalence of egg allergy in US children is 0.5% to 2.5%.¹⁸ Most outgrow it by school age, but in one-third, the allergy persists into adulthood.

In general, people who can eat lightly cooked eggs (eg, scrambled eggs) without a reaction are unlikely to be allergic. On the other hand, the fact that egg-allergic people may tolerate egg included in baked products does not exclude the possibility of egg allergy. Egg allergy can be confirmed by a consistent medical history of adverse reaction to eggs and egg-containing foods, in addition to skin or blood testing for immunoglobulin E directed against egg proteins.¹⁹

Most currently available influenza vaccines are prepared by propagation of virus in embryonated eggs and so may contain trace amounts of egg proteins such as ovalbumin, with the exception of the inactivated quadri­valent recombinant influenza vaccine (Flublok) and the inactivated quadrivalent cell culture-based vaccine (Flucelvax).

The ACIP recommends that persons with a history of urticaria (hives) after exposure to eggs should receive any licensed, recommended influenza vaccine that is otherwise appropriate for their age and health status. Persons who report having angioedema, respiratory distress, lightheadedness, or recurrent vomiting, or who required epinephrine or another emergency medical intervention after exposure to eggs, should receive the influenza vaccine in an inpatient or outpatient medical setting under the supervision of a healthcare provider who is able to recognize and manage severe allergic reactions.

A history of severe allergic reaction such as anaphylaxis to a previous dose of any influenza vaccine, regardless of the vaccine component (including eggs) suspected of being responsible for the reaction, is a contraindication to influenza vaccination. The ACIP recommends that vaccine providers consider observing patients for 15 minutes after administration of any vaccine (regardless of history of egg allergy) to decrease the risk of injury should syncope occur.²⁰

‘I DON’T WANT TO PUT POISONOUS MERCURY IN MY BODY’

A process of biomagnification of methylmercury occurs when humans eat large fish that have eaten smaller fish. Thus, larger fish such as shark can be hazardous for women who are or may become pregnant, for nursing mothers, and for young children, while smaller fish such as herring are relatively safe.

As a precautionary measure, thimerosal was taken out of childhood vaccines in the United States in 2001. Thimerosal-free influenza vaccine formulations include the nasal live-attenuated flu vaccine, the inactivated quadrivalent recombinant influenza vaccine, and the inactivated quadrivalent cell culture-based vaccine.

‘I DON’T LIKE NEEDLES’

At least 10% of US adults have aichmophobia, the fear of sharp objects including needles.²² Vasovagal syncope is the most common manifestation. Behavioral therapy, topical anesthetics, and systemic anxiolytics have variable efficacy in treating needle phobia. For those who are absolutely averse to needles, the nasal flu vaccine is an appropriate alternative.

‘I DON’T WANT TO TAKE ANYTHING THAT CAN MESS WITH MY OTHER MEDICATIONS’

Some immunosuppressive medications may decrease influenza vaccine immunogenicity. Concomitant administration of the inactivated influenza vaccine with other vaccines is safe and does not alter immunogenicity of other vaccines.¹ The live-attenuated influenza vaccine is contraindicated in children and adolescents taking aspirin or other salicylates due to the risk of Reye syndrome.

A recent systematic review and meta-analysis showed that the inactivated influenza vaccine is not associated with asthma exacerbation.²³ However, the nasal live-attenuated influenza vaccine is contraindicated in children 2 to 4 years old who have asthma and should be used with caution in persons with asthma 5 years old and older. In the systematic review, influenza vaccine prevented 59% to 78% of asthma attacks leading to emergency visits or hospitalization.²³ In other immune-mediated diseases such as rheumatoid arthritis, influenza vaccine does not precipitate exacerbations.²⁴

‘I HAD AN ORGAN TRANSPLANT, AND I’M AFRAID THE FLU SHOT WILL CAUSE ORGAN REJECTION’

A study of 51,730 kidney transplant recipients found that receipt of the inactivated influenza vaccine in the first year after transplant was associated with a lower risk of subsequent allograft loss (adjusted hazard ratio 0.77; 95% confidence interval 0.69–0.85; P < .001) and death (adjusted hazard ratio 0.82; 95% confidence interval 0.76–0.89; P < .001).²⁵ In the same study, although acute rejection in the first year was not associated with influenza vaccination, influenza infection in the first year was associated with rejection (odds ratio 1.58; 95% confidence interval 1.10–2.26; P < 0.001), but not with graft loss or death. Solid organ transplant recipients should receive the inactivated influenza vaccine starting 3 months after transplant.²⁶

Influenza vaccination has not been shown to precipitate graft-vs-host disease in hematopoietic stem cell transplant recipients. These patients should also receive the inactivated influenza vaccine starting 3 to 6 months after transplant.²⁷

The nasal live-attenuated influenza vaccine is contraindicated in these immunocompromised patients.

‘I’M PREGNANT, AND I DON’T WANT TO EXPOSE MY UNBORN BABY TO ANYTHING POTENTIALLY HARMFUL’

The morbidity and mortality risk from influenza is high in children under 2 years old because of low immunogenicity to flu vaccine. This is particularly true in children younger than 6 months, but the vaccine is not recommended in this population. The best way to protect infants is for all household members to be vaccinated against the flu.

Equally important, morbidity and mortality risk from influenza is much higher in pregnant women than in the general population. Many studies have shown the value of influenza vaccination during pregnancy for both mothers and their infants. A recently published study showed that 18% of infants who developed influenza required hospitalization.²⁸ In that study, prenatal and postpartum maternal influenza vaccination decreased the odds of influenza in infants by 61% and 53%, respectively. Another study showed that vaccine effectiveness did not vary by gestational age at vaccination.²⁹ A post hoc analysis of an influenza vaccination study in pregnant women suggested that the vaccine was also associated with decreased rates of pertussis in these women.³⁰

Healthcare providers should try to understand the public’s misconceptions³¹ about seasonal influenza and influenza vaccines in order to best address them.

The benefits of influenza vaccination are clear to those in the medical community. Yet misinformation and unfounded fears continue to discourage some people from getting a flu shot. During the 2018–2019 influenza season, only 45% of US adults and 63% of children were vaccinated.¹

‘IT DOESN’T WORK FOR MANY PEOPLE’

Multiple studies have shown that the flu vaccine prevents millions of flu cases and flu-related doctor’s visits each year. During the 2016–2017 flu season, flu vaccine prevented an estimated 5.3 million influenza cases, 2.6 million influenza-associated medical visits, and 85,000 influenza-associated hospitalizations.²

Several viral and host factors affect vaccine effectiveness. In seasons when the vaccine viruses have matched circulating strains, flu vaccine has been shown to reduce the following:

• The risk of having to go to the doctor with flu by 40% to 60%
• Children’s risk of flu-related death and intensive care unit (ICU) admission by 74%
• The risk in adults of flu-associated hospitalizations by 40% and ICU admission by 82%
• The rate of cardiac events in people with heart disease
• Hospitalizations in people with diabetes or underlying chronic lung disease.³

In people hospitalized with influenza despite receiving the flu vaccine for the season, studies have shown that receiving the flu vaccine shortens the average duration of hospitalization, reduces the chance of ICU admission by 59%, shortens the duration of ICU stay by 4 days, and reduces deaths.³

‘IT TARGETS THE WRONG VIRUS’

Selecting an effective influenza vaccine is a challenge. Every year, the World Health Organization and the CDC decide on the influenza strains expected to circulate in the upcoming flu season in the Northern Hemisphere, based on data for circulating strains in the Southern Hemisphere. This decision takes place about 7 months before the expected onset of the flu season. Flu viruses may mutate between the time the decision is made and the time the vaccine is administered (as well as after the flu season starts). Also, vaccine production in eggs needs time, which is why this decision must be made several months ahead of the flu season.

Vaccine effectiveness varies by virus serotype. Vaccines are typically less effective against influenza A H3N2 viruses than against influenza A H1N1 and influenza B viruses. Effectiveness also varies from season to season depending on how close the vaccine serotypes match the circulating serotypes, but some effectiveness is retained even in seasons when some of the serotypes don’t match circulating viruses. For example, in the 2017–2018 season, when the influenza A H3N2 vaccine serotype did not match the circulating serotype, the overall effectiveness in preventing medically attended, laboratory-confirmed influenza virus infection was 36%.⁵

A universal flu vaccine that does not need to be updated annually is the ultimate solution, but according to the National Institute of Allergy and Infectious Diseases, such a vaccine is likely several years away.⁶

‘IT MAKES PEOPLE SICK’

Pain at the injection site of a flu shot occurs in 10% to 65% of people, lasts less than 2 days, and does not usually interfere with daily activities.⁷

Systemic symptoms such as fever, malaise, and myalgia may occur in people who have had no previous exposure to the influenza virus antigens in the vaccine, particularly in children. In adults, the frequency of systemic symptoms after the flu shot is similar to that with placebo.

The Vaccine Adverse Event Reporting System, which has been capturing data since 1990, shows that the influenza vaccine accounted for 5.7% of people who developed malaise after receiving any vaccine.⁸

The injectable inactivated influenza vaccine cannot biologically cause an influenza virus-related illness, since the inactivated vaccine viruses can elicit a protective immune response but cannot replicate. The nasal live-attenuated flu vaccine can in theory cause acute illness in the person receiving it, but because it is cold-adapted, it multiplies only in the colder environment of the nasal epithelium, not in the lower airways where the temperature is higher. Consequently, the vaccine virus triggers immunity by multiplying in the nose, but doesn’t infect the lungs.

From 10% to 50% of people who receive the nasal live-attenuated vaccine develop runny nose, wheezing, headache, vomiting, muscle aches, fever, sore throat, or cough shortly after receiving the vaccine, but these symptoms are usually mild and short-lived.

The most common reactions people have to flu vaccines are considerably less severe than the symptoms caused by actual flu illness.

While influenza illness results in natural immunity to the specific viral serotype causing it, this illness results in hospitalization in 2% and is fatal in 0.16% of people. Influenza vaccine results in immunity to the serotypes included in the vaccine, and multiple studies have not found a causal relationship between vaccination and death.⁹

In the United States, 3,000 to 6,000 people per year develop Guillain-Barré syndrome, or 1 to 2 of every 100,000, which translates to 80 to 160 cases per week.¹⁰ While the exact cause of Guillain-Barré syndrome is unknown, about two-thirds of people have an acute diarrheal or respiratory illness within 3 months before the onset of symptoms. In 1976, the estimated attributable risk of influenza vaccine-related Guillain-Barré syndrome in the US adult population was 1 case per 100,000 in the 6 weeks after vaccination.¹¹ Studies in subsequent influenza seasons have not shown similar findings.¹² In fact, one study showed that the risk of developing Guillain-Barré syndrome was 15 times higher after influenza illness than after influenza vaccination.¹³

Since 5% to 15% of the US population develop symptomatic influenza annually,¹⁴ the decision to vaccinate with respect to the risk of Guillain-Barré syndrome should be obvious: vaccinate. The correct question to ask before influenza vaccination should be, “Have you previously developed Guillain-Barré syndrome within 6 weeks after receiving the flu vaccine?” If the answer is yes, the CDC considers this a caution, not a contraindication against receiving the influenza vaccine, since the benefit may still outweigh the risk.

‘I GOT THE FLU SHOT AND STILL GOT SICK’

The flu vaccine does not prevent illnesses caused by other viruses or bacteria that can make people sick during flu season. Influenza, the common cold, and streptococcal pharyngitis can have similar symptoms that make it difficult for patients—and, frequently, even healthcare providers—to distinguish between these illnesses with certainty.

One study suggested that influenza vaccine recipients had an increased risk of virologically confirmed noninfluenza respiratory viral infections,¹⁵ citing the phenomenon of virus interference that was described in the 1940s¹⁶ as a potential explanation. In essence, people protected against influenza by the vaccine may lack temporary nonspecific immunity against other respiratory viruses. However, these findings have not been replicated in subsequent studies.¹⁷

Viral gastroenteritis, mistakenly called “stomach flu,” is also not prevented by influenza vaccination.

‘I’M ALLERGIC TO EGGS’

The prevalence of egg allergy in US children is 0.5% to 2.5%.¹⁸ Most outgrow it by school age, but in one-third, the allergy persists into adulthood.

In general, people who can eat lightly cooked eggs (eg, scrambled eggs) without a reaction are unlikely to be allergic. On the other hand, the fact that egg-allergic people may tolerate egg included in baked products does not exclude the possibility of egg allergy. Egg allergy can be confirmed by a consistent medical history of adverse reaction to eggs and egg-containing foods, in addition to skin or blood testing for immunoglobulin E directed against egg proteins.¹⁹

Most currently available influenza vaccines are prepared by propagation of virus in embryonated eggs and so may contain trace amounts of egg proteins such as ovalbumin, with the exception of the inactivated quadri­valent recombinant influenza vaccine (Flublok) and the inactivated quadrivalent cell culture-based vaccine (Flucelvax).

The ACIP recommends that persons with a history of urticaria (hives) after exposure to eggs should receive any licensed, recommended influenza vaccine that is otherwise appropriate for their age and health status. Persons who report having angioedema, respiratory distress, lightheadedness, or recurrent vomiting, or who required epinephrine or another emergency medical intervention after exposure to eggs, should receive the influenza vaccine in an inpatient or outpatient medical setting under the supervision of a healthcare provider who is able to recognize and manage severe allergic reactions.

A history of severe allergic reaction such as anaphylaxis to a previous dose of any influenza vaccine, regardless of the vaccine component (including eggs) suspected of being responsible for the reaction, is a contraindication to influenza vaccination. The ACIP recommends that vaccine providers consider observing patients for 15 minutes after administration of any vaccine (regardless of history of egg allergy) to decrease the risk of injury should syncope occur.²⁰

‘I DON’T WANT TO PUT POISONOUS MERCURY IN MY BODY’

A process of biomagnification of methylmercury occurs when humans eat large fish that have eaten smaller fish. Thus, larger fish such as shark can be hazardous for women who are or may become pregnant, for nursing mothers, and for young children, while smaller fish such as herring are relatively safe.

As a precautionary measure, thimerosal was taken out of childhood vaccines in the United States in 2001. Thimerosal-free influenza vaccine formulations include the nasal live-attenuated flu vaccine, the inactivated quadrivalent recombinant influenza vaccine, and the inactivated quadrivalent cell culture-based vaccine.

‘I DON’T LIKE NEEDLES’

At least 10% of US adults have aichmophobia, the fear of sharp objects including needles.²² Vasovagal syncope is the most common manifestation. Behavioral therapy, topical anesthetics, and systemic anxiolytics have variable efficacy in treating needle phobia. For those who are absolutely averse to needles, the nasal flu vaccine is an appropriate alternative.

‘I DON’T WANT TO TAKE ANYTHING THAT CAN MESS WITH MY OTHER MEDICATIONS’

Some immunosuppressive medications may decrease influenza vaccine immunogenicity. Concomitant administration of the inactivated influenza vaccine with other vaccines is safe and does not alter immunogenicity of other vaccines.¹ The live-attenuated influenza vaccine is contraindicated in children and adolescents taking aspirin or other salicylates due to the risk of Reye syndrome.

A recent systematic review and meta-analysis showed that the inactivated influenza vaccine is not associated with asthma exacerbation.²³ However, the nasal live-attenuated influenza vaccine is contraindicated in children 2 to 4 years old who have asthma and should be used with caution in persons with asthma 5 years old and older. In the systematic review, influenza vaccine prevented 59% to 78% of asthma attacks leading to emergency visits or hospitalization.²³ In other immune-mediated diseases such as rheumatoid arthritis, influenza vaccine does not precipitate exacerbations.²⁴

‘I HAD AN ORGAN TRANSPLANT, AND I’M AFRAID THE FLU SHOT WILL CAUSE ORGAN REJECTION’

A study of 51,730 kidney transplant recipients found that receipt of the inactivated influenza vaccine in the first year after transplant was associated with a lower risk of subsequent allograft loss (adjusted hazard ratio 0.77; 95% confidence interval 0.69–0.85; P < .001) and death (adjusted hazard ratio 0.82; 95% confidence interval 0.76–0.89; P < .001).²⁵ In the same study, although acute rejection in the first year was not associated with influenza vaccination, influenza infection in the first year was associated with rejection (odds ratio 1.58; 95% confidence interval 1.10–2.26; P < 0.001), but not with graft loss or death. Solid organ transplant recipients should receive the inactivated influenza vaccine starting 3 months after transplant.²⁶

Influenza vaccination has not been shown to precipitate graft-vs-host disease in hematopoietic stem cell transplant recipients. These patients should also receive the inactivated influenza vaccine starting 3 to 6 months after transplant.²⁷

The nasal live-attenuated influenza vaccine is contraindicated in these immunocompromised patients.

‘I’M PREGNANT, AND I DON’T WANT TO EXPOSE MY UNBORN BABY TO ANYTHING POTENTIALLY HARMFUL’

The morbidity and mortality risk from influenza is high in children under 2 years old because of low immunogenicity to flu vaccine. This is particularly true in children younger than 6 months, but the vaccine is not recommended in this population. The best way to protect infants is for all household members to be vaccinated against the flu.

Equally important, morbidity and mortality risk from influenza is much higher in pregnant women than in the general population. Many studies have shown the value of influenza vaccination during pregnancy for both mothers and their infants. A recently published study showed that 18% of infants who developed influenza required hospitalization.²⁸ In that study, prenatal and postpartum maternal influenza vaccination decreased the odds of influenza in infants by 61% and 53%, respectively. Another study showed that vaccine effectiveness did not vary by gestational age at vaccination.²⁹ A post hoc analysis of an influenza vaccination study in pregnant women suggested that the vaccine was also associated with decreased rates of pertussis in these women.³⁰

Healthcare providers should try to understand the public’s misconceptions³¹ about seasonal influenza and influenza vaccines in order to best address them.

Here are 5 articles from the December issue of Clinician Reviews (individual articles are valid for one year from date of publication—expiration dates below):

1. Sustainable weight loss seen 5 years after endoscopic sleeve gastroplasty

To take the posttest, go to: https://bit.ly/37lteRX
Expires May 16, 2020

2. PT beats steroid injections for knee OA

To take the posttest, go to: https://bit.ly/2KIWKY6
Expires May 17, 2020

3. Better screening needed to reduce pregnancy-related overdose, death

To take the posttest, go to: https://bit.ly/2XEZyuG
Expires May 17, 2020

4. Meta-analysis finds no link between PPI use and risk of dementia

To take the posttest, go to: https://bit.ly/2Xzs7JM
Expires June 3, 2020

5. Study: Cardiac biomarkers predicted CV events in CAP

To take the posttest, go to: https://bit.ly/33bAH2u
Expires August 13, 2020

Here are 5 articles from the December issue of Clinician Reviews (individual articles are valid for one year from date of publication—expiration dates below):

1. Sustainable weight loss seen 5 years after endoscopic sleeve gastroplasty

To take the posttest, go to: https://bit.ly/37lteRX
Expires May 16, 2020

2. PT beats steroid injections for knee OA

To take the posttest, go to: https://bit.ly/2KIWKY6
Expires May 17, 2020

3. Better screening needed to reduce pregnancy-related overdose, death

To take the posttest, go to: https://bit.ly/2XEZyuG
Expires May 17, 2020

4. Meta-analysis finds no link between PPI use and risk of dementia

To take the posttest, go to: https://bit.ly/2Xzs7JM
Expires June 3, 2020

5. Study: Cardiac biomarkers predicted CV events in CAP

To take the posttest, go to: https://bit.ly/33bAH2u
Expires August 13, 2020

Here are 5 articles from the December issue of Clinician Reviews (individual articles are valid for one year from date of publication—expiration dates below):

1. Sustainable weight loss seen 5 years after endoscopic sleeve gastroplasty

To take the posttest, go to: https://bit.ly/37lteRX
Expires May 16, 2020

2. PT beats steroid injections for knee OA

To take the posttest, go to: https://bit.ly/2KIWKY6
Expires May 17, 2020

3. Better screening needed to reduce pregnancy-related overdose, death

To take the posttest, go to: https://bit.ly/2XEZyuG
Expires May 17, 2020

4. Meta-analysis finds no link between PPI use and risk of dementia

To take the posttest, go to: https://bit.ly/2Xzs7JM
Expires June 3, 2020

5. Study: Cardiac biomarkers predicted CV events in CAP

To take the posttest, go to: https://bit.ly/33bAH2u
Expires August 13, 2020

Initiating antiretroviral therapy within an hour after birth, rather than waiting a few weeks, lowers the reservoir of HIV virus and improves immune response, early results from an ongoing study in Botswana, Africa, showed.

Comstock/Thinkstock

Despite advances in treatment programs during pregnancy that prevent mother to child HIV transmission, 300-500 pediatric HIV infections occur each day in sub-Saharan Africa, Roger Shapiro, MD, MPH, said during a media teleconference organized by the American Association for the Advancement of Science. “Most pediatric HIV diagnosis programs currently test children at 4-6 weeks of age to identify infections that occur either in pregnancy or during delivery,” said Dr. Shapiro, associate professor of immunology and infectious diseases at the Harvard T.H. Chan School of Public Health, Boston. “However, these programs miss the opportunity to begin immediate antiretroviral treatment for children who can be identified earlier. There are benefits to starting treatment and arresting HIV replication in the first week of life. These include limiting the viral reservoir or the population of infected cells, limiting potentially harmful immune responses to the virus, and preventing the rapid decline in health that can occur in the early weeks of HIV infection in infants. Without treatment, 50% of HIV-infected children regress to death by 2 years. Starting treatment in the first weeks or months of life has been shown to improve survival.”

With these benefits in mind, he and his associates initiated the Early Infant Treatment (EIT) study in 2015 to diagnose and treat HIV infected infants in Botswana in the first week of life or as early as possible after infection. They screened more than 10,000 children and identified 40 that were HIV infected. “This low transmission rate is a testament to the fact that most HIV-positive women in Botswana receive three-drug treatment in pregnancy, which is highly successful in blocking transmission,” Dr. Shapiro said. “When we identified an HIV-infected infant, we consented mothers to allow us to start treatment right away. We used a series of regimens because there are limited options. The available options include older drugs, some of which are no longer used for adults but which were the only options for children.”

The researchers initiated three initial drugs approved for newborns: nevirapine, zidovudine, and lamivudine, and then changed the regimen slightly after a few weeks, when they used ritonavir-boosted lopinavir, plus the lamivudine and zidovudine. “We followed the children weekly at first, then at monthly refill visits, and kept close track of how they were taking the medicines and the level of virus in each child’s blood,” Dr. Shapiro said.

In a manuscript published online in Science Translational Medicine on Nov. 27, 2019, he and his associates reported results of the first 10 children enrolled in the EIT study who reached about 96 weeks on treatment. For comparison, they also enrolled a group of children as controls, who started treatment later in the first year of life, after being identified at a more standard time of 4-6 weeks. Tests performed included droplet digital polymerase chain reaction, HIV near-full-genome sequencing, whole-genome amplification, and flow cytometry.

“What we wanted to focus on are the HIV reservoir cells that are persisting in the setting of antiretroviral treatment,” study coauthor Mathias Lichterfeld, MD, PhD, explained during the teleconference. “Those are the cells that would cause viral rebound if treatment were to be interrupted. We used complex technology to look at these cells, using next-generation sequencing, which allows us to identify those cells that harbor HIV that has the ability to initiate new viral replication.”

He and his colleagues observed that the number of reservoir cells was significantly smaller than in adults who were on ART for a median of 16 years. It also was smaller than in infected infants who started ART treatment weeks after birth.

In addition, immune activation was reduced in the cohort of infants who were treated immediately after birth.

“We are seeing a distinct advantage of early treatment initiation,” said Dr. Lichterfeld of the infectious disease division at Brigham and Women’s Hospital, Boston. “By doing these assays we see both virological benefits in terms of a very-low reservoir size, and we see immune system characteristics that are also associated with better abilities for antimicrobial immune defense and a lower level of immune activation.”

Another study coauthor, Daniel R. Kuritzkes, MD, chief of the infectious disease division at Brigham and Women’s Hospital, said the findings show “how critically important” it is to extend studies of HIV cure or long-term remission to infants and children. “Very-early intervention in neonates limits the size of the reservoir and offers us the best opportunity for future interventions aimed at cure and long-term drug-free remission of HIV infection,” he said. “We don’t think the current intervention is itself curative, but it sets the stage for the capacity to offer additional innovative interventions in the future. Beyond the importance of this work for cure research per se, this very early intervention in neonates also has the potential of conferring important clinical benefits to the children who participated in this study. Finally, our study demonstrates the feasibility and importance of doing this type of research in neonates in resource-limited settings, given the appropriate infrastructure.”

EIT is supported by the National Institutes of Health. Dr. Lichterfeld disclosed having received speaking and consulting honoraria from Merck and Gilead. Dr. Kuritzkes disclosed having received consulting honoraria and/or research support from Gilead, Merck, and ViiV.

[email protected]

SOURCE: Garcia-Broncano P et al. Sci Transl Med. 2019 Nov 27. eaax7350.

Initiating antiretroviral therapy within an hour after birth, rather than waiting a few weeks, lowers the reservoir of HIV virus and improves immune response, early results from an ongoing study in Botswana, Africa, showed.

Comstock/Thinkstock

Despite advances in treatment programs during pregnancy that prevent mother to child HIV transmission, 300-500 pediatric HIV infections occur each day in sub-Saharan Africa, Roger Shapiro, MD, MPH, said during a media teleconference organized by the American Association for the Advancement of Science. “Most pediatric HIV diagnosis programs currently test children at 4-6 weeks of age to identify infections that occur either in pregnancy or during delivery,” said Dr. Shapiro, associate professor of immunology and infectious diseases at the Harvard T.H. Chan School of Public Health, Boston. “However, these programs miss the opportunity to begin immediate antiretroviral treatment for children who can be identified earlier. There are benefits to starting treatment and arresting HIV replication in the first week of life. These include limiting the viral reservoir or the population of infected cells, limiting potentially harmful immune responses to the virus, and preventing the rapid decline in health that can occur in the early weeks of HIV infection in infants. Without treatment, 50% of HIV-infected children regress to death by 2 years. Starting treatment in the first weeks or months of life has been shown to improve survival.”

With these benefits in mind, he and his associates initiated the Early Infant Treatment (EIT) study in 2015 to diagnose and treat HIV infected infants in Botswana in the first week of life or as early as possible after infection. They screened more than 10,000 children and identified 40 that were HIV infected. “This low transmission rate is a testament to the fact that most HIV-positive women in Botswana receive three-drug treatment in pregnancy, which is highly successful in blocking transmission,” Dr. Shapiro said. “When we identified an HIV-infected infant, we consented mothers to allow us to start treatment right away. We used a series of regimens because there are limited options. The available options include older drugs, some of which are no longer used for adults but which were the only options for children.”

The researchers initiated three initial drugs approved for newborns: nevirapine, zidovudine, and lamivudine, and then changed the regimen slightly after a few weeks, when they used ritonavir-boosted lopinavir, plus the lamivudine and zidovudine. “We followed the children weekly at first, then at monthly refill visits, and kept close track of how they were taking the medicines and the level of virus in each child’s blood,” Dr. Shapiro said.

In a manuscript published online in Science Translational Medicine on Nov. 27, 2019, he and his associates reported results of the first 10 children enrolled in the EIT study who reached about 96 weeks on treatment. For comparison, they also enrolled a group of children as controls, who started treatment later in the first year of life, after being identified at a more standard time of 4-6 weeks. Tests performed included droplet digital polymerase chain reaction, HIV near-full-genome sequencing, whole-genome amplification, and flow cytometry.

“What we wanted to focus on are the HIV reservoir cells that are persisting in the setting of antiretroviral treatment,” study coauthor Mathias Lichterfeld, MD, PhD, explained during the teleconference. “Those are the cells that would cause viral rebound if treatment were to be interrupted. We used complex technology to look at these cells, using next-generation sequencing, which allows us to identify those cells that harbor HIV that has the ability to initiate new viral replication.”

He and his colleagues observed that the number of reservoir cells was significantly smaller than in adults who were on ART for a median of 16 years. It also was smaller than in infected infants who started ART treatment weeks after birth.

In addition, immune activation was reduced in the cohort of infants who were treated immediately after birth.

“We are seeing a distinct advantage of early treatment initiation,” said Dr. Lichterfeld of the infectious disease division at Brigham and Women’s Hospital, Boston. “By doing these assays we see both virological benefits in terms of a very-low reservoir size, and we see immune system characteristics that are also associated with better abilities for antimicrobial immune defense and a lower level of immune activation.”

Another study coauthor, Daniel R. Kuritzkes, MD, chief of the infectious disease division at Brigham and Women’s Hospital, said the findings show “how critically important” it is to extend studies of HIV cure or long-term remission to infants and children. “Very-early intervention in neonates limits the size of the reservoir and offers us the best opportunity for future interventions aimed at cure and long-term drug-free remission of HIV infection,” he said. “We don’t think the current intervention is itself curative, but it sets the stage for the capacity to offer additional innovative interventions in the future. Beyond the importance of this work for cure research per se, this very early intervention in neonates also has the potential of conferring important clinical benefits to the children who participated in this study. Finally, our study demonstrates the feasibility and importance of doing this type of research in neonates in resource-limited settings, given the appropriate infrastructure.”

EIT is supported by the National Institutes of Health. Dr. Lichterfeld disclosed having received speaking and consulting honoraria from Merck and Gilead. Dr. Kuritzkes disclosed having received consulting honoraria and/or research support from Gilead, Merck, and ViiV.

[email protected]

SOURCE: Garcia-Broncano P et al. Sci Transl Med. 2019 Nov 27. eaax7350.

Initiating antiretroviral therapy within an hour after birth, rather than waiting a few weeks, lowers the reservoir of HIV virus and improves immune response, early results from an ongoing study in Botswana, Africa, showed.

Comstock/Thinkstock

Despite advances in treatment programs during pregnancy that prevent mother to child HIV transmission, 300-500 pediatric HIV infections occur each day in sub-Saharan Africa, Roger Shapiro, MD, MPH, said during a media teleconference organized by the American Association for the Advancement of Science. “Most pediatric HIV diagnosis programs currently test children at 4-6 weeks of age to identify infections that occur either in pregnancy or during delivery,” said Dr. Shapiro, associate professor of immunology and infectious diseases at the Harvard T.H. Chan School of Public Health, Boston. “However, these programs miss the opportunity to begin immediate antiretroviral treatment for children who can be identified earlier. There are benefits to starting treatment and arresting HIV replication in the first week of life. These include limiting the viral reservoir or the population of infected cells, limiting potentially harmful immune responses to the virus, and preventing the rapid decline in health that can occur in the early weeks of HIV infection in infants. Without treatment, 50% of HIV-infected children regress to death by 2 years. Starting treatment in the first weeks or months of life has been shown to improve survival.”

With these benefits in mind, he and his associates initiated the Early Infant Treatment (EIT) study in 2015 to diagnose and treat HIV infected infants in Botswana in the first week of life or as early as possible after infection. They screened more than 10,000 children and identified 40 that were HIV infected. “This low transmission rate is a testament to the fact that most HIV-positive women in Botswana receive three-drug treatment in pregnancy, which is highly successful in blocking transmission,” Dr. Shapiro said. “When we identified an HIV-infected infant, we consented mothers to allow us to start treatment right away. We used a series of regimens because there are limited options. The available options include older drugs, some of which are no longer used for adults but which were the only options for children.”

The researchers initiated three initial drugs approved for newborns: nevirapine, zidovudine, and lamivudine, and then changed the regimen slightly after a few weeks, when they used ritonavir-boosted lopinavir, plus the lamivudine and zidovudine. “We followed the children weekly at first, then at monthly refill visits, and kept close track of how they were taking the medicines and the level of virus in each child’s blood,” Dr. Shapiro said.

In a manuscript published online in Science Translational Medicine on Nov. 27, 2019, he and his associates reported results of the first 10 children enrolled in the EIT study who reached about 96 weeks on treatment. For comparison, they also enrolled a group of children as controls, who started treatment later in the first year of life, after being identified at a more standard time of 4-6 weeks. Tests performed included droplet digital polymerase chain reaction, HIV near-full-genome sequencing, whole-genome amplification, and flow cytometry.

“What we wanted to focus on are the HIV reservoir cells that are persisting in the setting of antiretroviral treatment,” study coauthor Mathias Lichterfeld, MD, PhD, explained during the teleconference. “Those are the cells that would cause viral rebound if treatment were to be interrupted. We used complex technology to look at these cells, using next-generation sequencing, which allows us to identify those cells that harbor HIV that has the ability to initiate new viral replication.”

He and his colleagues observed that the number of reservoir cells was significantly smaller than in adults who were on ART for a median of 16 years. It also was smaller than in infected infants who started ART treatment weeks after birth.

In addition, immune activation was reduced in the cohort of infants who were treated immediately after birth.

“We are seeing a distinct advantage of early treatment initiation,” said Dr. Lichterfeld of the infectious disease division at Brigham and Women’s Hospital, Boston. “By doing these assays we see both virological benefits in terms of a very-low reservoir size, and we see immune system characteristics that are also associated with better abilities for antimicrobial immune defense and a lower level of immune activation.”

Another study coauthor, Daniel R. Kuritzkes, MD, chief of the infectious disease division at Brigham and Women’s Hospital, said the findings show “how critically important” it is to extend studies of HIV cure or long-term remission to infants and children. “Very-early intervention in neonates limits the size of the reservoir and offers us the best opportunity for future interventions aimed at cure and long-term drug-free remission of HIV infection,” he said. “We don’t think the current intervention is itself curative, but it sets the stage for the capacity to offer additional innovative interventions in the future. Beyond the importance of this work for cure research per se, this very early intervention in neonates also has the potential of conferring important clinical benefits to the children who participated in this study. Finally, our study demonstrates the feasibility and importance of doing this type of research in neonates in resource-limited settings, given the appropriate infrastructure.”

EIT is supported by the National Institutes of Health. Dr. Lichterfeld disclosed having received speaking and consulting honoraria from Merck and Gilead. Dr. Kuritzkes disclosed having received consulting honoraria and/or research support from Gilead, Merck, and ViiV.

[email protected]

SOURCE: Garcia-Broncano P et al. Sci Transl Med. 2019 Nov 27. eaax7350.

The Food and Drug Administration has approved the Tubes Under Local Anesthesia (Tula) System for treatment of recurrent ear infections (otitis media) via tympanostomy in young children, according to a release from the agency.

Olivier Le Moal/Getty Images

Consisting of Tymbion anesthetic, tympanostomy tubes developed by Tusker Medical, and several devices that deliver them into the ear drum, the system can be used in an office setting under local anesthesia rather than in hospital settings with general anesthesia.

“This approval has the potential to expand patient access to a treatment that can be administered in a physician’s office with local anesthesia and minimal discomfort,” said Jeff Shuren, MD, director of the FDA’s Center for Devices and Radiological Health.

The approval was based on data from 222 children treated with the device, with a procedural success rate of 86% in children under 5 years and 89% in children aged 5-12 years. The most common adverse event was insufficient anesthetic.

The system should not be used in children with allergies to some local anesthetics or those younger than 6 months. It also is not intended for patients with preexisting issues with their eardrums, such as perforated ear drums, according to the press release.

The Tula system was granted a Breakthrough Device designation, which means the FDA provided intensive engagement and guidance during its development. The full release can be found on the FDA website.

[email protected]

The Food and Drug Administration has approved the Tubes Under Local Anesthesia (Tula) System for treatment of recurrent ear infections (otitis media) via tympanostomy in young children, according to a release from the agency.

Olivier Le Moal/Getty Images

Consisting of Tymbion anesthetic, tympanostomy tubes developed by Tusker Medical, and several devices that deliver them into the ear drum, the system can be used in an office setting under local anesthesia rather than in hospital settings with general anesthesia.

“This approval has the potential to expand patient access to a treatment that can be administered in a physician’s office with local anesthesia and minimal discomfort,” said Jeff Shuren, MD, director of the FDA’s Center for Devices and Radiological Health.

The approval was based on data from 222 children treated with the device, with a procedural success rate of 86% in children under 5 years and 89% in children aged 5-12 years. The most common adverse event was insufficient anesthetic.

The system should not be used in children with allergies to some local anesthetics or those younger than 6 months. It also is not intended for patients with preexisting issues with their eardrums, such as perforated ear drums, according to the press release.

The Tula system was granted a Breakthrough Device designation, which means the FDA provided intensive engagement and guidance during its development. The full release can be found on the FDA website.

[email protected]

The Food and Drug Administration has approved the Tubes Under Local Anesthesia (Tula) System for treatment of recurrent ear infections (otitis media) via tympanostomy in young children, according to a release from the agency.

Olivier Le Moal/Getty Images

Consisting of Tymbion anesthetic, tympanostomy tubes developed by Tusker Medical, and several devices that deliver them into the ear drum, the system can be used in an office setting under local anesthesia rather than in hospital settings with general anesthesia.

“This approval has the potential to expand patient access to a treatment that can be administered in a physician’s office with local anesthesia and minimal discomfort,” said Jeff Shuren, MD, director of the FDA’s Center for Devices and Radiological Health.

The approval was based on data from 222 children treated with the device, with a procedural success rate of 86% in children under 5 years and 89% in children aged 5-12 years. The most common adverse event was insufficient anesthetic.

The system should not be used in children with allergies to some local anesthetics or those younger than 6 months. It also is not intended for patients with preexisting issues with their eardrums, such as perforated ear drums, according to the press release.

The Tula system was granted a Breakthrough Device designation, which means the FDA provided intensive engagement and guidance during its development. The full release can be found on the FDA website.

[email protected]

Kaposi sarcoma (KS) is a low-grade vascular tumor that is rare among the general US population, with an incidence rate of less than 1 per 100,000.¹ The tumor is more common among certain groups of individuals due to geographic differences in the prevalence of KS-associated herpesvirus (also referred to as human herpesvirus 8) as well as host immune factors.² Kaposi sarcoma often is defined by the patient's predisposing characteristics yielding the following distinct epidemiologic subtypes: (1) classic KS is a rare disease affecting older men of Mediterranean descent; (2) African KS is an endemic cancer with male predominance in sub-Saharan Africa; (3) AIDS-associated KS is an often aggressive AIDS-defining illness; and (4) iatrogenic KS occurs in patients on immunosuppressive therapy.³ When evaluating a patient without any of these risk factors, the clinical suspicion for KS may be low. We report a patient with postpolio syndrome (PPS) who presented with KS of the right leg, ankle, and foot. 

A 77-year-old man with a distant history of paralytic poliomyelitis presented for an annual skin examination with concern for a new lesion on the right ankle. The patient had a history of PPS primarily affecting the right leg. Physical examination revealed residual weakness in an atrophic right lower extremity with a mottled appearance and mild pitting edema to the knee. Two red, dome-shaped, vascular papules were appreciated on the medial aspect of the right ankle (Figure 1), and a shave biopsy of the larger papule was performed. Microscopic examination of the biopsy specimen was consistent with KS (Figure 2). This patient had no history of human immunodeficiency virus or immunosuppressive therapy and was not of Mediterranean descent. 

Because KS is a radiosensitive vascular neoplasm and radiation therapy (RT) alone can achieve local control,⁴ the patient was treated with 6 megaelectron-volt electron-beam RT. He received 30 Gy in 10 fractions to the affected area of the medial ankle. The patient tolerated RT well. Three weeks after completing treatment, he was found to have mild lichenification on the right medial ankle with no clinical evidence of disease. Four months later, he presented with multiple additional vascular papules on the right third toe and in the interdigital web space (Figure 3). Shave biopsy of one of these lesions was consistent with KS. Contrast computed tomography of the chest, abdomen, and pelvis was performed, revealing no evidence of metastatic disease. The patient was treated with 30 Gy in 15 fractions using opposed lateral 6 megaelectron-volt photon fields to the entire right lower extremity below the knee to treat all of the skin affected by the PPS. His posttreatment course was complicated by edema in the affected leg that resolved after daily pneumatic compression. He had no evidence of residual or recurrent disease 6 months after completing RT (Figure 4). 

Cutaneous KS is a human herpesvirus 8-positive tumor of endothelial origin typically seen in older men of Mediterranean or African descent and among immunosuppressed patients.⁴ Our patient did not have any classic risk factors for KS, but his disease did arise in the setting of a right lower extremity that was notably affected by PPS. Postpolio syndrome is characterized by muscle atrophy due to denervation of the motor unit.⁵ Bruno et al⁶ found that such deficits in motor innervation could lead to impairments in venous outflow causing cutaneous venous congestion. Acroangiodermatitis clinically resembles KS but is a benign reactive vasoproliferative disorder and is well known to occur in the lower extremities as a sequela of chronic venous insufficiency.⁷ A case of bilateral lower extremity pseudo-KS was reported in a patient with notable PPS.⁸ A report of 2 patients describes KS arising in the setting of chronic venous insufficiency without any classic risk factors.⁹ Therefore, patients with PPS characterized by venous insufficiency may represent a population at increased risk for KS. 
 

Kaposi sarcoma (KS) is a low-grade vascular tumor that is rare among the general US population, with an incidence rate of less than 1 per 100,000.¹ The tumor is more common among certain groups of individuals due to geographic differences in the prevalence of KS-associated herpesvirus (also referred to as human herpesvirus 8) as well as host immune factors.² Kaposi sarcoma often is defined by the patient's predisposing characteristics yielding the following distinct epidemiologic subtypes: (1) classic KS is a rare disease affecting older men of Mediterranean descent; (2) African KS is an endemic cancer with male predominance in sub-Saharan Africa; (3) AIDS-associated KS is an often aggressive AIDS-defining illness; and (4) iatrogenic KS occurs in patients on immunosuppressive therapy.³ When evaluating a patient without any of these risk factors, the clinical suspicion for KS may be low. We report a patient with postpolio syndrome (PPS) who presented with KS of the right leg, ankle, and foot. 

A 77-year-old man with a distant history of paralytic poliomyelitis presented for an annual skin examination with concern for a new lesion on the right ankle. The patient had a history of PPS primarily affecting the right leg. Physical examination revealed residual weakness in an atrophic right lower extremity with a mottled appearance and mild pitting edema to the knee. Two red, dome-shaped, vascular papules were appreciated on the medial aspect of the right ankle (Figure 1), and a shave biopsy of the larger papule was performed. Microscopic examination of the biopsy specimen was consistent with KS (Figure 2). This patient had no history of human immunodeficiency virus or immunosuppressive therapy and was not of Mediterranean descent. 

Because KS is a radiosensitive vascular neoplasm and radiation therapy (RT) alone can achieve local control,⁴ the patient was treated with 6 megaelectron-volt electron-beam RT. He received 30 Gy in 10 fractions to the affected area of the medial ankle. The patient tolerated RT well. Three weeks after completing treatment, he was found to have mild lichenification on the right medial ankle with no clinical evidence of disease. Four months later, he presented with multiple additional vascular papules on the right third toe and in the interdigital web space (Figure 3). Shave biopsy of one of these lesions was consistent with KS. Contrast computed tomography of the chest, abdomen, and pelvis was performed, revealing no evidence of metastatic disease. The patient was treated with 30 Gy in 15 fractions using opposed lateral 6 megaelectron-volt photon fields to the entire right lower extremity below the knee to treat all of the skin affected by the PPS. His posttreatment course was complicated by edema in the affected leg that resolved after daily pneumatic compression. He had no evidence of residual or recurrent disease 6 months after completing RT (Figure 4). 

Cutaneous KS is a human herpesvirus 8-positive tumor of endothelial origin typically seen in older men of Mediterranean or African descent and among immunosuppressed patients.⁴ Our patient did not have any classic risk factors for KS, but his disease did arise in the setting of a right lower extremity that was notably affected by PPS. Postpolio syndrome is characterized by muscle atrophy due to denervation of the motor unit.⁵ Bruno et al⁶ found that such deficits in motor innervation could lead to impairments in venous outflow causing cutaneous venous congestion. Acroangiodermatitis clinically resembles KS but is a benign reactive vasoproliferative disorder and is well known to occur in the lower extremities as a sequela of chronic venous insufficiency.⁷ A case of bilateral lower extremity pseudo-KS was reported in a patient with notable PPS.⁸ A report of 2 patients describes KS arising in the setting of chronic venous insufficiency without any classic risk factors.⁹ Therefore, patients with PPS characterized by venous insufficiency may represent a population at increased risk for KS. 
 

Kaposi sarcoma (KS) is a low-grade vascular tumor that is rare among the general US population, with an incidence rate of less than 1 per 100,000.¹ The tumor is more common among certain groups of individuals due to geographic differences in the prevalence of KS-associated herpesvirus (also referred to as human herpesvirus 8) as well as host immune factors.² Kaposi sarcoma often is defined by the patient's predisposing characteristics yielding the following distinct epidemiologic subtypes: (1) classic KS is a rare disease affecting older men of Mediterranean descent; (2) African KS is an endemic cancer with male predominance in sub-Saharan Africa; (3) AIDS-associated KS is an often aggressive AIDS-defining illness; and (4) iatrogenic KS occurs in patients on immunosuppressive therapy.³ When evaluating a patient without any of these risk factors, the clinical suspicion for KS may be low. We report a patient with postpolio syndrome (PPS) who presented with KS of the right leg, ankle, and foot. 

A 77-year-old man with a distant history of paralytic poliomyelitis presented for an annual skin examination with concern for a new lesion on the right ankle. The patient had a history of PPS primarily affecting the right leg. Physical examination revealed residual weakness in an atrophic right lower extremity with a mottled appearance and mild pitting edema to the knee. Two red, dome-shaped, vascular papules were appreciated on the medial aspect of the right ankle (Figure 1), and a shave biopsy of the larger papule was performed. Microscopic examination of the biopsy specimen was consistent with KS (Figure 2). This patient had no history of human immunodeficiency virus or immunosuppressive therapy and was not of Mediterranean descent. 

Because KS is a radiosensitive vascular neoplasm and radiation therapy (RT) alone can achieve local control,⁴ the patient was treated with 6 megaelectron-volt electron-beam RT. He received 30 Gy in 10 fractions to the affected area of the medial ankle. The patient tolerated RT well. Three weeks after completing treatment, he was found to have mild lichenification on the right medial ankle with no clinical evidence of disease. Four months later, he presented with multiple additional vascular papules on the right third toe and in the interdigital web space (Figure 3). Shave biopsy of one of these lesions was consistent with KS. Contrast computed tomography of the chest, abdomen, and pelvis was performed, revealing no evidence of metastatic disease. The patient was treated with 30 Gy in 15 fractions using opposed lateral 6 megaelectron-volt photon fields to the entire right lower extremity below the knee to treat all of the skin affected by the PPS. His posttreatment course was complicated by edema in the affected leg that resolved after daily pneumatic compression. He had no evidence of residual or recurrent disease 6 months after completing RT (Figure 4). 

Cutaneous KS is a human herpesvirus 8-positive tumor of endothelial origin typically seen in older men of Mediterranean or African descent and among immunosuppressed patients.⁴ Our patient did not have any classic risk factors for KS, but his disease did arise in the setting of a right lower extremity that was notably affected by PPS. Postpolio syndrome is characterized by muscle atrophy due to denervation of the motor unit.⁵ Bruno et al⁶ found that such deficits in motor innervation could lead to impairments in venous outflow causing cutaneous venous congestion. Acroangiodermatitis clinically resembles KS but is a benign reactive vasoproliferative disorder and is well known to occur in the lower extremities as a sequela of chronic venous insufficiency.⁷ A case of bilateral lower extremity pseudo-KS was reported in a patient with notable PPS.⁸ A report of 2 patients describes KS arising in the setting of chronic venous insufficiency without any classic risk factors.⁹ Therefore, patients with PPS characterized by venous insufficiency may represent a population at increased risk for KS.