News

Measles: A Case of Déjà Vu All Over Again

Last January, I had the opportunity to share some thoughts on PIDS' role in combating vaccine-preventable diseases, focusing on vaccine advocacy, innovative studies of pathogenesis, high-quality epidemiologic studies, and rigorous clinical trials. Now, one year later, we are experiencing a measles outbreak in the US that has affected over 100 people in 14 states, most of which are linked to an exposure at a California amusement park. As the outbreak unfolds, we are reminded of the cardinal symptoms of measles, a disease that many practicing physicians have never seen; the efficient transmission of the virus to unvaccinated individuals; and the importance of PIDS' ongoing education and vaccine advocacy efforts.

As recently as the 1950s, measles was one of the most common childhood infections in the US. On average, about half a million cases, 50,000 hospitalizations, 1,000 cases of chronic disability, and 500 deaths were reported each year; however, due to underreporting, it is estimated that as many as 4 million cases occurred annually. In many ways, measles is a typical respiratory illness, leading to fever, cough, coryza, conjunctivitis, and malaise. Because of this, and because of the fleeting nature of pathognomonic Koplik spots, we must maintain a reasonably high index of suspicion, particularly in our unvaccinated patients, in order to identify measles cases promptly. When measles is suspected, providers should evaluate measles-specific serum IgM antibody and measles RNA by PCR from both the oropharynx and the urine.

The timely diagnosis of a case of measles is of critical importance, since a single measles patient will infect approximately 15 others in the absence of pre-existing immunity (R0~15), making measles the most easily transmitted virus on the planet (for comparison, smallpox R0~5, Influenza R0~3). Moreover, 90% of non-immune individuals will develop measles infection following close contact with an infected individual. Fortunately, the MMR vaccine is remarkably effective (~95% after one dose and 98-99% after 2 doses) in generating life-long, protective immunity. The MMR vaccine is also effective if administered within 72 hours of measles exposure and is recommended for infants as young as 6 months of age if exposure is likely (e.g., travel to an endemic area).

This effectiveness of the MMR vaccine in preventing measles infection is the foundation of measles eradication efforts, which have been highly successful in many parts of the globe. PIDS members continue to play key roles in this effort, leading clinical trials, conducting global epidemiology studies, and informing public policy decisions. It is now time, through our vaccine advocacy committee, training programs, and local media markets to redouble our efforts in reassuring parents and providers about the safety of MMR vaccine and the importance of vaccine coverage (>93% coverage is required in a community to disrupt transmission). For more information about the current outbreak and for general talking points about measles, please visit the PIDS website (www.pids.org).

The eradication of measles has been a daunting task; unfortunately, the eradication of misinformation and mistrust may be even more so. Allowing measles to resurface essentially turns back the pediatric clock by several decades, reintroducing morbidity and mortality that are a distant memory. Our job, as a society and as individual members, is to provide clear, trustworthy information to our trainees, our patients, and the general public in order to ensure these preventable outbreaks do not become the new epidemiologic norm. - by Buddy Creech, MD, MPH, FPIDS

Pediatric Infectious Disease Experts Urge Vaccination as Measles Outbreak Continues

As physicians, scientists, and other medical professionals dedicated to treating and preventing infections in children, the Pediatric Infectious Diseases Society (PIDS) remains extremely concerned about the current measles outbreak as it continues to unfold.

It has become clear that we are in the midst of a larger, very disturbing trend. Despite the fact that measles was eradicated from the United States 15 years ago, this country had 644 measles cases in 2014, more than in any year since 1994. 2015 is now on pace to well exceed that number.

The measles vaccine is a victim of its own success. Vaccination was so effective at eliminating this disease, and many other diseases, that younger generations do not appreciate or understand the severity of vaccine-preventable diseases. Instead, the focus now often lies on unfounded, disproven and discredited concerns regarding the safety of the vaccine. We know that parents want the very best for their children, and this includes keeping them safe from serious infections. It is a tragedy that some parents, often because of misinformation they may have received from friends, colleagues, or the Internet, are putting their children and others in harm's way by refusing to vaccinate.

The current measles outbreak, which has now affected more than 100 people and will likely continue to spread, was entirely preventable. As long as approximately 95 percent of a population is vaccinated, a potential outbreak from measles will be halted in its tracks. Most states exceed this level of coverage, in part due to school vaccination requirements, but an increasing number of states have regions where vaccination coverage falls well below this level. This is in large part due to personal belief exemptions or religious exemptions that allow parents, misled by false information, to avoid vaccinating their children.

States with areas where vaccination rates are lower can look to Mississippi, where strong immunization requirements have maintained high vaccine coverage levels among children. As PIDS President David W. Kimberlin, MD, FPIDS, told The New York Times this week, "That kind of strong approach is helpful for the health of children in America. I believe that that should be something we all work toward, that we all hold in the highest of value in terms of our prioritization."

Simply put: vaccines are safe, vaccines are effective, vaccines save lives. Children are being harmed by the growing trend of vaccine refusal. We strongly urge any parent who has a concern about the safety of a vaccine, including the MMR vaccine, to discuss these concerns with their child's medical provider as soon as possible. Similarly, we encourage all primary care providers to actively engage all parents in the discussion about vaccines, provide clear messaging about their safety and efficacy, and be transparent about the minimal risks. This outbreak can be stopped, and future outbreaks prevented, with adequate vaccine coverage.

Download the PDF

Pediatric Infectious Disease Experts Urge Vaccination as Measles Outbreak Continues (PDF)

Reflections on Spiraling Empiricism

Written by: Pui-Ying Iroh Tam, MD

Last month, I was asked to consult on antimicrobial management for a premature baby who had presumed necrotizing enterocolitis. The baby was transferred from an outside hospital after a suspected aspiration event, and on arrival was started empirically on clindamycin. Due to suspected sepsis in a premature infant, she was also started on ampicillin, gentamicin and fluconazole. When she developed respiratory distress and deteriorated, neonatologists broadened her ampicillin and gentamicin to vancomycin and cefotaxime. Despite this, she continued to be unstable and blood cultures became positive for MSSA. Gentamicin was added for synergy and after there was no clinical response or sterilization of blood cultures after 3 days, was then changed to rifampin.

Hence, when we first met this patient, she was on vancomycin, clindamycin, rifampin, cefotaxime and fluconazole.

Kim and Gallis first coined the phrase 'spiraling empiricism' back in 1989 with an article in the American Journal of Medicine titled 'Observations in spiraling empiricism: its causes, allures and perils, with special reference to antibiotic therapy [1].' Their term refers to the 'inappropriate treatment, or the unjustifiable escalation of treatment, of suspected but undocumented infectious diseases.'

Sound familiar? I faintly ridicule other specialties for committing this transgression, but whom of us in pediatric infectious diseases have not been seduced by the fallacies of antibiotic therapy? However, the implications of this practice – where over half of hospitalized patients receive antimicrobials [2], and where an estimated 50% of outpatient antimicrobial prescriptions are considered unnecessary [3] – is that we have also contributed to the growing problem of antimicrobial resistance. When the CDC published their first ever report in 2013 quantifying the extent of antimicrobial resistance, they estimated that at least 2 million people a year in the US become infected with antimicrobial resistant bacteria, and a minimum of 23,000 people die annually as a direct result of these infections [4].

These fallacies (I have bolded this word lest a reader skimming this should think I am detailing pearls of wisdom) are, as Kim and Gallis lists:

  1. Broader is better
  2. Failure to respond is failure to cover
  3. When in doubt, change drugs, or add another
  4. More disease(s), more drugs
  5. Sickness requires immediate treatment
  6. Response implies diagnosis
  7. Bigger disease, bigger drugs
  8. Bigger disease, newer drugs
  9. Antibiotics are non-toxic

Most illustrative is a recent case published in the New England Journal of Medicine [5]. A 14 year-old male with severe combined immunodeficiency status post two bone marrow transplants presented to a medical facility three times over a four month period with fever and headache. With an extensive negative infectious workup and low suspicion for bacterial meningitis, he was not given any empiric antimicrobials until his third presentation when he had interval development of status epilepticus and basilar leptomeningitis on MRI. Then he was given a series of empiric antimicrobials that physicians continued to add to and broaden when he did not respond. When next-generation sequencing analysis suggested neuroleptospirosis, his therapy was narrowed to penicillin, and the patient gradually recovered over the next seven days.

Of all the antimicrobials this patient needed, with all the technology that we could provide in the 21st century, the answer was the first antibiotic ever discovered. There is a beautiful simplicity to that which reminds one how much of clinical practice remains more of an art than a science.

And my premature baby on a veritable cocktail of antimicrobials? We optimized and simplified her therapy, cognizant of the perils of excessive and redundant antimicrobial use. After that I don't know, since I signed her out to the next attending. But I suspect all must have turned out well, since isn't ignorance bliss?

References

  1. Kim JH, Gallis HA. Observations on spiraling empiricism: its causes, allure, and perils, with particular reference to antibiotic therapy. Am J Med. 1989 Aug;87(2):201-6.
  2. CDC. Antimicrobial resistance – threat report 2013. http://www.cdc.gov/drugresistance/threat-report-2013/ Accessed 15 January, 2015.
  3. Fridkin S, Baggs J, Fagan R, Magill S, Pollack LA, Malpiedi P, Slayton R, Khader K, Rubin MA, Jones M, Samore MH, Dumyati G, Dodds-Ashley E, Meek J,Yousey-Hindes K, Jernigan J, Shehab N, Herrera R, McDonald CL, Schneider A, Srinivasan A; Centers for Disease Control and Prevention (CDC). Vital signs: improving antibiotic use among hospitalized patients. MMWR Morb Mortal Wkly Rep. 2014 Mar 7;63(9):194-200.
  4. Hicks LA, Taylor TH Jr, Hunkler RJ. U.S. outpatient antibiotic prescribing, 2010. N Engl J Med. 2013 Apr 11;368(15):1461-2. doi: 10.1056/NEJMc1212055.
  5. Wilson MR, Naccache SN, Samayoa E, Biagtan M, Bashir H, Yu G, Salamat SM, Somasekar S, Federman S, Miller S, Sokolic R, Garabedian E, Candotti F,Buckley RH, Reed KD, Meyer TL, Seroogy CM, Galloway R, Henderson SL, Gern JE, DeRisi JL, Chiu CY. Actionable diagnosis of neuroleptospirosis by next-generation sequencing. N Engl J Med. 2014 Jun 19;370(25):2408-17. doi: 10.1056/NEJMoa1401268. Epub 2014 Jun 4.

 

January 2015: JPIDS Article Review & Commentary

Written by: Matthew Kronman, MD, MSCE

Fisher BT, Sammons JS, Li Y, de Blank P, Seif AE, Huang Y, Kavcic M, Klieger S, Harris T, Torp K, Rheam D, Shah A, Aplenc R. Variation in Risk of Hospital-Onset Clostridium difficile Infection Across β-Lactam Antibiotics in Children With New-Onset Acute Lymphoblastic Leukemia. J Pediatric Infect Dis Soc. 2014;3(4):329-35.

Summary

In the December 2014 issue of the Journal of the Pediatric Infectious Diseases Society, Fisher, Sammons and colleagues report the findings of a large, multi-center retrospective cohort study of children with new-onset acute lymphoblastic leukemia (ALL) that aimed to determine the relative contributions of different β-lactam antibiotics to the risk of developing Clostridium difficile infection (CDI).

The authors employed the Pediatric Health Information System (PHIS) database, which includes pharmaceutical billing data and diagnoses for all children admitted to 43 freestanding children's hospitals. To decrease misclassification, the authors used previously well-validated definitions for both new-onset ALL cases (based on an ALL diagnosis and receipt of appropriate chemotherapy) and CDI outcomes (based on a CDI diagnosis and billing for C. difficile testing.)[1, 2] The PHIS data provided the authors with the ability to track antibiotic exposures to the day; the analyses were adjusted for age, race, gender, illness severity, days in the hospital, antibiotic receipt other than β-lactams, and admission hospital itself. The authors furthermore had the ability to adjust for other factors that could have been associated with CDI, such as use of proton pump inhibitors or use of an enteric feeding tube.

In their adjusted analyses, the authors found that the hazard for developing CDI increased by 5% (adjusted Hazard Ratio 1.05, 95% Confidence Interval 1.01-1.09) for each additional day subjects were exposed to anti-pseudomonal β-lactam antibiotics. This relationship held true for ceftazidime (5% increased hazard) and cefepime (7% increased hazard), but not for anti-pseudomonal penicillins such as piperacillin/tazobactam or carbapenems.

Commentary

There are three main reasons why we should take note of this study. First, this study backs up the antibiotic stewardship mantra "every dose counts" with hard data. Accounting for other confounding variables, every additional day of certain anti-pseudomonal β-lactam antibiotics added a 5% risk of developing CDI. This daily additional risk compounds rapidly: just 5 days of exposure to these antibiotics contributes an almost 30% increased risk of CDI. Remembering that these authors have previously demonstrated that hospital-onset CDI is associated with an almost 7-fold increase in mortality,[3] we can all use the present study to remind us not to put off until tomorrow stopping those antibiotics we could otherwise stop today.

Second, the present study should serve to remind us that what may appear to be routine practice changes in the Divisions we support may come with unintended consequences. The authors demonstrated that two cephalosporins – cefepime and ceftazidime – were associated with CDI in adjusted analyses while anti-pseudomonal penicillins were not. In the initial univariate analyses, the incidence rate ratio of CDI among those exposed to cefepime was more than twice that of those exposed to ceftazidime. We might consider ceftazidime, cefepime, and piperacillin/tazobactam as approximately equivalent selections for the empiric treatment of the febrile neutropenia so often seen in the ALL patients who were the subjects of this study. These data should remind us that even apparently small decisions such as deciding among these three agents should be weighed carefully, especially when institutional guidelines that might affect hundreds of patients are being developed and updated.

Lastly, we continue to learn slowly about our relationship with our gut microbiota. Large-scale epidemiologic studies such as this one can provide hints and clues as to the underlying biology of the diseases we examine. A meta-analysis demonstrated increased risks for community-onset CDI among those exposed to cephalosporins, monobactams, and carbapenems relative to those exposed to penicillins.[4] One might have supposed that agents with the largest breadth of anaerobic activity (such as piperacillin/tazobactam and carbapenems) were universally more likely to be associated with CDI, by substantially reducing the vast numbers of anaerobic commensal gut bacteria, allowing C. difficile the ecological space to grow logarithmically. Here, the authors demonstrate that piperacillin/tazobactam, despite its breadth of anaerobic activity, was not associated with CDI. Perhaps this finding can suggest testable hypotheses to further our understanding of how and why CDI develops in the first place.

In summary, Fisher, Sammons, and colleagues nicely demonstrated in this study the importance every additional day of antibiotics can hold. We have more to learn about CDI and how to prevent it, but in the meanwhile, we are better equipped to encourage our colleagues to stop unnecessary antibiotics as soon as possible.

References

  1. Fisher BT, Harris T, Torp K, et al. Establishment of an 11-year cohort of 8733 pediatric patients hospitalized at United States free-standing children's hospitals with de novo acute lymphoblastic leukemia from health care administrative data. Med Care 2014 Jan;52(1):e1-6.
  2. Shaklee J, Zerr DM, Elward A, et al. Improving surveillance for pediatric Clostridium difficile infection: derivation and validation of an accurate case-finding tool. Pediatr Infect Dis J 2011 Mar;30(3):e38-40.
  3. Sammons JS, Localio R, Xiao R, Coffin SE, Zaoutis T. Clostridium difficile infection is associated with increased risk of death and prolonged hospitalization in children. Clin Infect Dis 2013 Jul;57(1):1-8.
  4. Brown KA, Khanafer N, Daneman N, Fisman DN. Meta-analysis of antibiotics and the risk of community-associated Clostridium difficile infection. Antimicrob Agents Chemother 2013 May;57(5):2326-32.

JPIDS Article Review: The 100 Day Cough and the 50 day Positive PCR

Written by Chris Nyquist, MD, MSPH

"The lung is so irritated that every attempt to expel that which is causing the trouble...it neither admits the air or easily expels the air. For they are without this troublesome coughing for the space of 4 or 5 hours at a time, then this paroxysm of coughing returns, now so severe that blood is expelled with force through the nose and through the mouth."
1578 Pertussis Epidemic in Paris, Guillamaume de Baillou

The"100 day cough" described in the 1500's in England ultimately became known in 1679 as pertussis, "violent cough", courtesy of Sydenham (of Sydenham's chorea fame). In the 21st century we now have better diagnostic tools to identify pertussis, vaccines for pertussis and effective antimicrobials that should decrease the contagiousness of patients yet we continue to and increasingly have pertussis epidemics.

The CDC MMWR recently reported another pertussis epidemic in California. The number of reported cases in 2014 is surpassing the recent 2010 epidemic and represents the most cases reported in California in the last 70 years. The overall rate of pertussis in the population is 26 per 100,000 population with the highest incidence in infants younger than 1 year (174.6 cases per 100,000). This "new normal" makes the case for continued pertussis research rethinking what we know about pertussis epidemiology, testing and antibiotic use.

Stone et al describe a prospective cohort study conducted from July 2004 to August 2006 at Primary Children's Medical Center in Salt Lake City, Utah. The objective of the study was to better understand the length of time pertussis PCR (polymerase chain reaction) is positive in a patient with clinical pertussis. Children less than 18 years of age who were hospitalized with a positive B. pertussis PCR and met CDC laboratory confirmed definition of B. pertussis infection were defined as index cases. Associated cases were defined as close contacts with at least 7 days of unexplained cough illness. Subjects enrolled in the study had nasopharyngeal samples tested with pertussis PCR at baseline and then weekly for 3 weeks, then monthly or every other month, for 1 year from symptom onset until the samples yielded a negative result.

True B. pertussis cases were cases that had the first pertussis PCR positive or who met CDC clinical criteria for pertussis but had the initial sampling after 21 days of illness. Over half of the associated cases (close contacts) were PCR positive for pertussis. The final analysis included 31 PCR positive and 3 PCR negative subjects who were sampled after 21 days but met CDC clinical case criteria. Despite completing an appropriate course of antibiotics (14 days erythromycin or 5 days azithromycin) B. pertussis PCR results remained positive for a median of 58 days after symptom onset (range: 4 to 172 days). Half of the patients continued to have a positive pertussis PCR for greater than 50 days after the onset of symptoms, despite antibiotic treatment and clinical improvement.

What does this study mean for Pediatric Infectious Disease clinicians and Hospital Epidemiologists? How should we clinically use pertussis PCR? Does the prolonged presence of B. pertussis DNA beyond 21 days of illness or after completing recommended antibiotic treatment correlate with continued contagiousness of the patient and further transmission to susceptible hosts? How do we clinically use this information to improve patient care and public health?

Pertussis culture is the only 100% specific method for identification and is still the gold standard. PCR is now the preferred method of diagnosis in the clinical setting. Commercial serologic tests, although not yet standardized by the FDA, can be helpful for diagnosis later in illness or for epidemiologic studies although the interpretation of serology may be influenced by recent vaccination. A 2007 Cochrane review of antibiotic treatment for pertussis evaluated 10 trials published between 1969 and 2004 that described microbiologic eradication determined by pertussis culture. Meta-analysis of microbiologic eradication as an outcome in these trials was not possible because of the difference in type of antibiotics used.

For patients hospitalized with pertussis, the AAP Committee on Infectious Diseases Red Book ®, recommends standard and droplet precautions for 5 days after the initiation of effective therapy, or if appropriate antimicrobial therapy is not given, until 3 weeks after cough onset. In the early 1990s at Children's Hospital Colorado, we experienced healthcare associated transmission of pertussis from a hospitalized coughing patient who completed an appropriate course of antibiotics and was thus removed from droplet isolation. We subsequently tightened our restrictions and kept patients with pertussis in droplet isolation until the time of hospital discharge. Recently we relaxed our isolation policy and now allow hospitalized patients with pertussis who are hospitalized greater than 14 days and with two documented negative pertussis PCRs one week apart to be removed from droplet isolation. Further studies evaluating pertussis PCR may help provide an evidence basis for changes to recommendations regarding appropriate isolation practices.

Pertussis continues to be a 21st century problem. We need to clearly develop research to answer the old and new questions. Replication and expansion of this pilot study in the ambulatory setting may bring us closer to answering questions in the time of the pertussis "new normal."

Let's Set the Record Straight on the Influenza Vaccine

By: Rebecca Wallihan, MD

Between abundant vaccine myths and increasingly vocal anti-vaccine celebrities, it seems like an uphill battle each year to increase rates of influenza vaccination. This year we are faced with an additional challenge.

Read more: Let's Set the Record Straight on the Influenza Vaccine

The Value of a Pediatric Infectious Disease Physician

Written by Chris Nyquist, MD, MSPH

What is the value of Pediatric Infectious Disease fellowship training? Is the equation "Value equals Quality divided by Cost" valid? Is the Pediatrics journal article, "Does Fellowship Pay?" (Pediatrics 2011;127:254) describing a negative financial impact of over $800,000 associated with pursuing a career in Pediatric Infectious Diseases compared to a career in general pediatrics accurate?

As we look to creating our future and understanding where it may be progress, PIDS is sponsoring a qualitative research study to explore the value of Pediatric Infectious Disease Specialists. This important global look at perception of value, work force, and our role in healthcare of children will provide us with actionable measures but will also raise more questions for the future. Before the study is complete we must start the journey and individually recognize our own value as a Pediatric Infectious Disease Specialist. This is the first step to more effectively recruit and retain the best pediatricians to an infectious diseases fellowship and to assert the overall value of Pediatric Infectious Diseases.

Recruitment and Retention:

  • Relationships Matter. This year fellowship opportunities exceed the number of applicants for the positions. Think back to how you decided to pursue a career in Peds ID. Was it a passion for the topic? Was it the Peds ID Attending who you sought to emulate? My path was set when during my first rotation on the Pediatric Communicable Diseases ward as a third year medical student. I was involved in the care of an incredibly interesting patient who developed cutaneous coccidiomycosis in the arm after a glass cut at a cock fight in Texas. (PIDJ 1986;5:485-486. Read the article to find out the fascinating details). My attending, Dr. Janet Gilsdorf, taught me, inspired me, and became a lifetime mentor. This experience helped to cement my desire to become a pediatrician specializing in infectious diseases. The relationship I developed interviewing the patient and the family in addition to the research I did to better understand the etiology of the illness was the first bright spark of my interest in Pediatric Infectious Diseases. Relationships with patients and families and mentors can encourage us and drive us toward a career in Peds ID.
     
  • Mentorship is Important but Sponsorship is Critical. Mentors will help to guide you in your career but sponsors will give you opportunities that push you forward. In short, mentors advise; sponsors act. Hewlett states that, "Mentors act as a sounding board or a shoulder to cry on, offering advice as needed and support and guidance as requested; they expect very little in return. Sponsors, in contrast, are much more vested in their protégés, offering guidance and critical feedback because they believe in them." We need to continue to play both roles.
     
  • Jobs and Opportunities Abound. Basic research, clinical and translational research, patient care, hospital epidemiology, antimicrobial stewardship, public health and industry are all potential paths for a successful career in Pediatric Infectious Diseases. We need to continue to improve the diversity of our academy and encourage residents and fellows to pursue a fellowship in infectious disease.

The Value Equation:

  • Change is Constant. The health care system is continuing to change and the academy of Peds ID physicians must continue to adjust to meet these demands. The highest compliment is that you are often asked for a consult because your colleagues know that you will complete a comprehensive history, you will fully examine the patient and review the old records and lab results. The patient will thank you and the overall care will improve. We are a critical cog in the fulfillment of the IHI Triple Aim: improve the patient experience of care (including quality and satisfaction); improve the health of populations; and reduce the per capita cost of health care. We need to measure our outcomes and share this information with stakeholders.
     
  • Being Invisible is Not an Option. The hospital infrastructure is clearly supported by the work of Pediatric Infectious Diseases which ranges from antimicrobial stewardship, outpatient antimicrobial treatment, transplant and immunocompromised programs, the microbiology laboratory, infection prevention, vaccination programs to ultimately inpatient and outpatient care. Our scope is broad and the goal is to move from invisibility to clearly identifying and stating what we do to support the hospital infrastructure and academic enterprise.

JPIDS Article Review: November 2014

Written by: Buddy Creech, MD, MPH

On my shelf are two staphylococcal books from the 1960s - Proceedings from Staphylococcal Symposia held at the the NY Academy of Sciences and in Warsaw, Poland.

Read more: JPIDS Article Review: November 2014

Joint Statement: Opposing Quarantine for Asymptomatic Healthcare Personnel Traveling from West Africa

ARLINGTON, Va. (October 31) – The Society for Healthcare Epidemiology of America (SHEA), the Infectious Disease Society of America (IDSA), the Association for Professionals in Infection Control and Epidemiology (APIC), the Pediatric Infectious Disease Society (PIDS), the HIV Medicine Association (HIVMA) and the Center for Global Health Policy remain opposed to mandatory quarantines being imposed on asymptomatic healthcare workers returning from Ebola-stricken countries in West Africa.

Read more: Joint Statement: Opposing Quarantine for Asymptomatic Healthcare Personnel Traveling from West...

PIDS: Current Activities & Future Impact

Written by: David Kimberlin, MD

At the PIDS Business Meeting held on October 10 at the 2014 IDWeek meeting, I shared good news about the state of the society and its numerous activities. Let me start by prefacing that PIDS continues to be financially stable. Our investment accounts are weaker than last year, but investments are not tapped for operating expenses and therefore are not impacting our current budget. PIDS leaders continue to press forward using the roadmap from the 2013 strategic planning session. The roadmap consists of four focus areas: 1) the value of pediatric infectious diseases as a subspecialty; 2) education and training for pediatric infectious specialists the future job markets; 3) communication to members and among members; and 4) the visibility of PIDS in the crowded marketplace of expertise that exists in this decade. Below is a list of activities that PIDS currently is doing or will soon undertake in the coming months as we focus on each of these areas.

Value of Pediatric ID as a Subspecialty

  • We have undertaken three separate studies to define the value of what we do in terms that department chairs, hospital administrators, and others will appreciate. To coordinate this effort, we created a Work Group to develop, implement, and analyze the studies.
  • At the outset, two focus group sessions at the 2013 IDWeek meeting to solicit additional input.
  • The three studies are summarized as follows:
    • The first is a qualitative study that will identify how clinical stakeholders at different types of hospitals define the value of pediatric ID. To date, interviews have been conducted at The Children's Hospital of Philadelphia, Kaiser in Oakland and Sacramento, California, Hasbro Children's Hospital in Providence, Rhode Island, and Arkansas Children's Hospital in Little Rock, Arkansas. The final interview will take place at Beaumont Children's Hospital in Royal Oak, Michigan. Preliminary findings were presented at the October 9, 2014, PIDS Board of Directors meeting. Final results will follow the final interview at Beaumont Children's Hospital later this year.
    • The second study is a systematic review of pediatric antimicrobial stewardship programs (ASPs). A manuscript and accompanying editorial were submitted for publication in JPIDS in August.
    • The third study is a quantitative study addressing the impact of ID consultation on several common pediatric infectious diseases, collecting data of osteomyelitis and complicated pneumonia patients ~3,000 charts per disease from the PHIS database. These efforts will harmonize with those undertaken independent of this mechanism by Janet Gilsdorf at her home institution.

Education and Training for the PID Job Market of the 21st Century

  • The Research Affairs Committee and Pediatric Transplant ID working group consisting of Jan Englund, Betsy Herold, Elaine Tuomanen, Lara Danziger-Isakov, Michael Green, Bill Steinbach, Marian Michaels, Monica Ardura, and Tanvi Sharma continue to develop great programming for the annual St. Jude/PIDS Pediatric Infectious Diseases Research Conference and Pediatric Transplant ID Symposium. In addition, a survey to seek interest in participating in a formal Pediatric Transplant ID Working Group for the broader PIDS membership was sent this past spring. The Working Group met for the first time at the 2014 IDWeek meeting, with 50 participants present in person or via teleconference. The WG now will proceed toward the goal of establishing a more formal network to facilitate research initiatives in this developing field.
  • The Pediatric Transplant ID Curricula was published in the Journal of the Pediatric Infectious Diseases Society (JPIDS) online in Advance Access on December 6, 2013.
  • The 5th annual Pediatric Antimicrobial Stewardship Conference (co-sponsored with Children's Mercy Hospital) was successful with record attendance (n=100). The total number of attendees over all five renditions of the conference is 300. Plans for 2015 are underway.
  • The first inaugural Antimicrobial Stewardship Research Mentoring Award was announced at the PIDS Business Meeting during 2014 IDWeek meeting. This year's winners were Beatriz Larru, The Children's Hospital of Philadelphia, and Joseph B. Cantey, University of Texas Southwestern Medical Center. 
  • The 2015 recipient of the Journal of the Pediatric Infectious Diseases Society Ralph D. Feigin Apprenticeship Award is Pui-Ying Iroh Tam, University of Minnesota.
  • The PIDS Poster Presentation Program, immediately following the Business Meeting, recognized five top ranked abstracts presented by PIDS fellows for outstanding research. This year's awardees were Kalpana Manthiram, Vanderbilt University Medical Center; Liset Olarte, Baylor College of Medicine; Sabine Schyner, Boston Medical Center; Ilan Youngster, Boston Children's Hospital; and Karl Yu, University of Chicago.
  • The Education Committee continues to meet regularly to discuss additional initiatives.

Communication

  • The Communications Committee developed a communication plan that focuses on web updates and social media.
  • The committee already has revamped PIDSNews (monthly newsletter). A reader survey was included in the September issue. Click here to provide your feedback.
  • They also have initiated outreach efforts to increase awareness of the Society and JPIDS. Activities include:
    • Two press releases for JPIDS articles since October 2013
    • The Infectious Diseases in Children print and online publications develop news stories from JPIDS articles
    • Several posts on the PIDS Twitter and Facebook pages

Visibility of PIDS

  • To begin this important process, we changed the PIDS Council to the PIDS Board of Directors. This aligns us more directly with other professional societies.
    • The PIDS Bylaws were changed to include member descriptions and establishment of the Fellow of the Pediatric Infectious Diseases Society ("FPIDS") designation. The advancement to Fellow of Pediatric Infectious Diseases Society 2014 launch was successful. Eighty-seven PIDS members advanced to FPIDS. The next cycle for nomination of new FPIDS member will begin in January 2015.
  • The PIDS Executive Committee also approved the development of a Media/Rapid Communications List (starting with members of the Board and the Communications Committee. The first media training session was held during IDWeek 2013. Plans to hold media training utilizing webinar capabilities are underway.

A critical aspect of increasing PIDS' visibility is the continued enhancement of the visibility of the society's journal, the Journal of the Pediatric Infectious Diseases Society (JPIDS). I strongly encourage you, the esteemed experts in our field, to submit your research to our journal via http://mc.manuscriptcentral.com/jpids. I also ask that you encourage your colleagues to do the same. I promise that you will find the peer review and online publication of manuscripts to be very rapid, the feedback from reviewers to be thoughtful, and the editorial staff of the journal to be extremely responsive. In addition, the Society will feature key articles to our membership via the enhanced Communications efforts detailed above.

Other Society activities include outreach efforts to international sister societies, including SLIPE, ESPID, Australian/New Zealand Pediatric Infectious Diseases Society (ANZPID), and the India Academy of Pediatrics. This is an ongoing initiative being housed under the International Affairs Committee. The discussions with SLIPE have resulted in updates from Latin America as a regular featured article in JPIDS that began in the June 2014 issue (Volume 3 Number 2). If you have international colleagues interested in collaborative initiatives with PIDS, please contact me via email (This email address is being protected from spambots. You need JavaScript enabled to view it.) as I am happy to discuss additional ways to advance our international efforts.

In addition to the International Affairs Committee, PIDS has 12 other committees that are actively working toward advancing the Society's goals and bringing value to its members. This year, 61% of members offering to serve on committees were assigned to their 1st or 2nd committee preferences. There is still much to do, so please contact me if you are passionate about a particular issue that you think PIDS can help with (or that it can help with PIDS).

I encourage you to read this entire issue of PIDSNews. Meeting information such as the Call for Cases for the St. Jude/PIDS Transplant ID Symposium, Call for Abstracts for the St. Jude/PIDS Pediatric Infectious Diseases Research Conference, and other important information are provided. In addition, the Antibacterial Resistance (AR) Leadership Group is seeking pediatric proposals in their efforts to reduce the public health threat of AR. Please follow the link provided in this newsletter to learn more.

Finally, I want to update you on Ebola and PIDS' response to the recent Centers for Disease Control and Prevention (CDC) guidance and the implications for pediatricians. On October 28, PIDS publicly joined with IDSA to implore our political leaders to follow the science in the development of public policy relating to this unfolding human catastrophe. We must think strategically when faced with challenges of this magnitude, and PIDS members are uniquely suited to address those areas that affect children's health. To be certain, this is a dynamic and fluid situation. Our approach to it, therefore, must be flexible as well. We believe that by joining our voices with those of the CDC, American Academy of Pediatrics (AAP), and others, we can most favorably impact the care provided to children with documented or suspected Ebola virus infection. Many of these efforts will be behind the scenes – we all have seen the detrimental effects of too many voices adding to the confusion perceived by the public. But rest assured that we are doing the work, both as individuals and as a group. We – the Pediatric Infectious Diseases community – are making a difference.

In the coming months and years, I am excited about our Society's continuing growth as an organization, maintaining a focus on important issues related to pediatric infectious diseases and providing value to our members. On behalf of the PIDS leaders, thank you for all of your support, hard work, and commitment to the Society!

Lessons Learned from Ebola Preparations

Written by: David K. Hong, MD

The continuing Ebola crisis in West Africa has been unprecedented. As of October 22, 2014, there have been 9936 confirmed cases of Ebola, many more cases than any previous Ebola outbreak (1).

Read more: Lessons Learned from Ebola Preparations

CDC Activates Children's Task Force in Response to Ebola Outbreak

A Children's Task Force has been activated by the Centers for Disease Control and Prevention (CDC) Emergency Operations Center (EOC) as part of the 2014 Ebola outbreak response.

Read more: CDC Activates Children's Task Force in Response to Ebola Outbreak

PIDS Supports the IDSA Statement on Involuntary Quarantine of Healthcare Workers Returning From Ebola-Affected Countries

The Pediatric Infectious Diseases Society (PIDS) endorses Statement from the Infectious Diseases Society of America (IDSA) regarding involuntary quarantine of healthcare workers returning from Ebola-affected countries. PIDS is the world's largest organization of professionals dedicated to the treatment, control and eradication of infectious diseases affecting children. PIDS agrees that strategies to limit Ebola Virus disease transmission should be based on the best available medical, scientific, and epidemiological evidence, as stated by IDSA. Furthermore, PIDS supports the policies promoted by the Centers for Disease Control and Prevention and the National Institutes of Health to end the Ebola outbreak without further losses.

Articles Published Today on Ebola in Children

Drs. Georgina Peacock, Timothy Uyeki and Sonja Rasmussen published "Ebola Virus Disease and Children: What Pediatric Health Care Professionals Need to Know" in JAMA Pediatrics.

In AAP News, Dr. Carrie Byington authored the article, " Ebola and Children: Identifying and Meeting Their Needs."

Enterovirus D68 in the United States, 2014

The United States has been experiencing a nationwide outbreak of enterovirus D68 (EV-D68) associated with severe respiratory illness. The most recent version of key points on EV-D68 is now available.

On October 14, 2014 the Centers for Disease Control and Prevention (CDC) issued a press release sharing news about a new lab test developed by CDC for EV-D68 which will allow more rapid testing of specimens. Because of this new test, confirmed cases of EV-D68 will appear to rise rapidly over the next 7-10 days as specimen testing accelerates, however, changes in case counts won't represent a real-time influx of new cases.

Almost all of the CDC-confirmed cases this year of EV-D68 infection have been among children. Many of the children had asthma or a history of wheezing. Many parents continue to be worried about the outbreak and want information about what they can do to prevent illness and protect themselves and their families. CDC has developed information and resources for parents about EV-D68. Please help us to address parents' questions and concerns and make them aware that these resources are available.

Below are CDC resources about EV-D68 developed for parents:

JPIDS Article Review: September 2014

A Prospective, International Cohort Study of Invasive Mold Infections in Children
Written by: Pia S. Pannaraj, MD, MPH

Invasive mold infections (IMI) are life-threatening infections in immunocompromised children. Most of our current knowledge of the epidemiology, diagnosis, treatment, and outcomes of pediatric mold infections is extrapolated from studies in adults. Whereas amphotericin B formulations (polyenes) were once the mainstay of therapy of IMIs, new generation azoles and novel echinocandins have expanded the arsenal of antifungal agents and are being used in children despite limited pediatric pharmacokinetic and efficacy data. In addition, treatment with a combination of different classes of antifungal agents appears attractive despite a paucity of studies. In the Journal of the Pediatric Infectious Diseases Society Advance Access online on July 19, 2014, Wattier et al. and the International Pediatric Fungal Network (PFN) addressed these issues by characterizing the current epidemiology of IMIs in children with varied underlying conditions, describing the patterns of antifungal therapy, and reporting contemporary outcomes from their large, international, multicenter network.

Between 2007 and 2011, PFN enrolled 131 children diagnosed with proven or probable IMIs from 22 study sites (12 US, 10 international) of 42 sites in the network. Most children (75%) had invasive Aspergillosis (IA); 25% had other mold infections. Malignancy and hematopoietic stem cell transplantation were the most common underlying conditions, but the study also characterized IMIs in children with inherited immunodeficiencies, autoimmune diseases, and non-malignant hematologic conditions.

Three main points are emphasized from this study of IMI in children:

  1. Case-fatality rates (CFR) in children who develop IMI remain high at 30%. Active fungal disease was present at the time of death in 85% of children. Fortunately, we have seen a decrease from CFRs as high as 42-85% reported for IA in the early 2000s. One reason for this may be earlier diagnosis allowing for more timely treatment. Traditionally, IMI diagnosis relied on clinical signs, radiographic evidence and attempts to isolate the pathogen. These methods were nonspecific, lacked sensitivity or were invasive. Galactomannan enzyme immunoassay, licensed by the FDA in 2003, offers an adjunctive, non-invasive diagnostic test for guiding initiation of anti-Aspergillus therapy. Of 64 patients with probable invasive Aspergillus (IA) in this study, the diagnosis was established by a positive galactomannan assay in 66%. A second reason for improved outcomes may be the availability of more antifungal treatment options. Voriconazole was used in 82% of patients with IA and has replaced polyenes as the most frequently used agent to treat IA, likely based on evidence primarily in adults showing superiority of voriconazole to amphotericin B deoxycholate in outcome and tolerability. Polyenes were most commonly used for mucormycosis, and voriconazole and polyenes were used in equal frequency to treat other IMIs. Improved therapies in combination with good prospective treatment studies in children are necessary to decrease the CFR even further.
     
  2. The study describes but does not answer the question of which is better: monotherapy or combination antifungal therapy in the treatment of IMI. Given the high CFRs associated with IMI, using combination antifungal therapy is appealing to achieve potential synergistic effects by acting on different targets, inhibiting different steps in the same pathway, or possibly reducing acquired drug resistance. However, experimental animal studies, clinical series, and randomized trials have been performed with varying and sometimes contradicting results. In this PFN study, 53% of patients received combination therapy with 2 or more concurrent agents sometime within the 12 weeks after diagnosis. Median time to start combination therapy was 5 days. Importantly, combination therapy was significantly associated with almost 2 times increased risk of adverse events but did not change treatment outcome. The variation in combination regimens, timing, and duration of therapy, however, make it difficult to analyze this outcome. Well-designed randomized controlled trials are still necessary to adequately address whether combination antifungal therapy provides any additional benefit over monotherapy.
     
  3. Exposure to mold active antifungals was associated with higher risk for mucormycosis and other non-Aspergillus IMIs compared to IA. Children with mucormycosis and other non-Aspergillus IMIs did not have more severe underlying conditions or immunologic risk factors compared with those with IA. They differed only in exposure to voriconazole, posaconazole, or an echinocandin for at least 3 days during the 30-days preceding the IMI diagnosis. Unfortunately, the study sites were not required to report the doses, duration, or indication for use (i.e., prophylaxis vs. empiric therapy). Other studies have shown similar breakthrough IMI in patients receiving voriconazole, posaconazole, and caspofungin. The 12-week treatment success of IA, mucormycosis, and other IMIs was similar in this study.

This large study of IMI in children had some limitations. The majority of patients were enrolled from 6 sites, with 25% of the patients from one site alone. Twenty PHN sites did not enroll any patients. The study did not document if this was due to lack of cases or lack of time/resources for the investigators to enroll patients. The study did attempt to control for potential confounding by adjusting for clustering by site in the outcomes analysis. Study sites also may differ in their interpretation of underlying risk factors, approach to diagnostic evaluation, and reporting of adverse events. Furthermore, they may differ in aggressive treatment with surgical excision of localized infection known to improve outcome; this study did not collect data on surgical interventions. Despite these limitations, PHN's study provides us with additional understanding of the epidemiology, contemporary treatment, and outcomes of IMIs in children. More pediatric studies are needed.

Website developed by Katalyst Solutions, LLC